instruction
stringlengths 22
321
| context
stringlengths 75
3.6k
| context_neg
stringlengths 75
3.6k
|
|---|---|---|
Is liposarcomatous differentiation in malignant phyllodes tumours unassociated with MDM2 or CDK4 amplification?
|
Breast sarcomas are rare, usually occurring in the setting of malignant phyllodes tumour (MPT). Heterologous differentiation commonly resembles well-differentiated or pleomorphic liposarcoma. In extramammary sites, these subtypes have different biological behaviours and distinct genetic alterations: MDM2 and CDK4 amplification in well-differentiated liposarcoma, and polyploidy with complex structural rearrangements in pleomorphic liposarcoma. The aim of this study was to investigate foci resembling well-differentiated liposarcoma in MPT for MDM2 and CDK4 amplification. We evaluated the clinicopathological characteristics of MPTs received by the Vanderbilt Breast Consultation Service containing components resembling well-differentiated or pleomorphic liposarcoma. Cases with available tissue blocks were subjected to fluorescence in-situ hybridization with MDM2 and CDK4 probes. Thirty-eight MPTs with liposarcomatous components were available for review. The mean patient age was 49.8 years (range 26-84 years). In addition to well-differentiated liposarcoma, the following components were also present: high-grade undifferentiated sarcoma (n = 9; 23.7%), pleomorphic liposarcoma (n = 4; 10.5%), non-high-grade sarcoma not otherwise specified (n = 22; 57.9%), and malignant peripheral nerve sheath tumour-like (n = 2; 5.2%). Among 10 cases tested, none showed amplification of MDM2 or CDK4.
|
The adverse consequences of a non-dialysis-requiring acute kidney injury (AKI) are unclear. This study aimed to assess the long-term prognoses for critically ill patients experiencing a non-dialysis-requiring AKI. This retrospective observational cohort study investigated non-dialysis-requiring AKI survivors in surgical intensive care units between January 2002 and June 2010. All longitudinal post-discharge serum creatinine measurements and information regarding end-stage renal disease (ESRD) and death were collected. We assessed the long-term outcomes of chronic kidney disease (CKD), ESRD and all-cause mortality beyond discharge. Of the 922 identified critically ill patients with a non-dialysis-requiring AKI, 634 (68.8%) patients who survived to discharge were enrolled. A total of 207 patients died after a median follow-up of 700.5 days. The median intervals between the onset of the AKI and the composite endpoints "stage 3 CKD or death", "stage 4 CKD or death", "stage 5 CKD or death", and "ESRD or death" were 685, 1319, 1743, and 2048 days, respectively. This finding shows a steady long-term decline in kidney function after discharge. Using the multivariate Cox proportional hazard model, we found that every 1 mL/min/1.73 m2 decrease from baseline estimated glomerular filtration rate (eGFR) of individuals who progressed to stage 3, 4, and 5 CKD increased the risks of long-term mortality by 0.7%, 2.3%, and 4.1%, respectively (all p < 0.05). This result indicates that the mortality risk increased significantly in a graded manner as kidney function declined from the baseline eGFR to advanced stages of CKD during the follow-up period.
|
Does a family history of smoking predict heightened levels of stress-induced cigarette craving?
|
Individuals with histories of smoking in first-degree relatives are significantly more likely to be persistent smokers themselves. The mechanisms underlying this relationship are unknown. Considerable research has demonstrated that smokers display heightened levels of cigarette craving after being exposed to stressful situations, and the magnitude of these craving responses is thought to be predictive of later cessation failure. Based on this research, we tested experimentally the hypothesis that smokers with two or more first-degree relatives who smoked (FH+) would exhibit stronger craving reactions following stressful stimuli than smokers without such family histories (FH-). We recruited 83 smokers by advertisement (mean age = 41.2 years, 57% female, 41% completed some college, 59% African American). The study was conducted in an interview room in an urban medical center. Participants were exposed to a neutral situation (changing a lightbulb) and a stressful situation (dental work) using script-guided imagery. Participants completed background measures of demographics, distress and smoking behavior. In addition, participants completed cigarette craving and anxiety questionnaires immediately before and after each condition. Supporting the study hypothesis, FH+ smokers (n = 39) selectively displayed stronger craving reactions to dental imagery (P < 0.03) than did FH- smokers (n = 44).
|
Several aspects of renoprotection by angiotensin-converting enzyme inhibitors (ACEi) in IgA nephropathy (IgAN) are poorly defined: factors affecting responsiveness, role of proteinuria components and histological lesions, and criteria to identify patients who may benefit from ACEi. In an observational study of 140 IgAN patients (follow up 62 +/- 36 months), 73 untreated and 67 ACEitreated for 53 +/- 28 months, 9 baseline risk factors (RFs) (blood pressure, serum creatinine, proteinuria/day, fractional excretion of IgG [FEIgG] and alpha1-microglobulin, global and segmental [SS] glomerular sclerosis, tubulointerstitial damage and arteriolar hyalinosis [AH] score), each divided into 2 subgroups according to a cutoff with the highest sensitivity and specificity for progression, were evaluated for ability to predict renoprotection. Primary end point: end-stage renal disease (ESRD) and doubling of serum creatinine (sCr); secondary end point: increase >or=25% of sCr with last sCr >or=1.58 mg/dL; total progression: sum of end points. Patients with RFs below cutoffs did not benefit from ACEi. All clinical and proteinuric and 2 histological RFs (SS, AH score) with values above cutoffs showed significant reduction of progression in ACEitreated vs. untreated patients; FEIgG showed the highest prediction of renoprotection: ESRD/sCrx2: 20% vs. 62% (p=0.0004); total progression: 40% vs. 85% (p=0.0003). By multivariate analysis, independent predictors of progression were FEIgG, sCr and no ACEi treatment. Proteinuria reduction from -100% to -30%, spontaneous or after ACEi treatment, did not affect progression in treated vs. untreated patients (19% vs. 13%, p=0.85). Patients with proteinuria increased or reduced <30% showed a reduction of total progression if ACEi-treated (15% vs. 77%, p=0.0002). Presence of 1 clinical or proteinuric RF above the cutoff may be a criterion to identify patients who may benefit from ACEi.
|
Are rectal microRNAs perturbed in pediatric inflammatory bowel disease of the colon?
|
Changes in intestinal microRNAs have been reported in adult patients with ulcerative colitis or Crohn's disease. The goal of this study was to identify changes in microRNA expression associated with colitis in children with inflammatory bowel disease. Rectal mucosal biopsies (n = 50) and blood samples (n = 47) were collected from patients with known or suspected inflammatory bowel disease undergoing endoscopy. Rectal and serum microRNA levels were profiled using the nCounter platform and the TaqMan low-density array platform, respectively. Significantly altered microRNAs were validated in independent sample sets via quantitative RT-PCR. In vitro luciferase reporter assays were performed in the human colorectal Caco-2 cell line to determine the effect of miR-192 on NOD2 expression. Profiling of rectal RNA identified 21 microRNAs significantly altered between control, UC, and colonic CD sample groups. Nine of the ten microRNAs selected for validation were confirmed as significantly changed. Rectal miR-24 was increased 1.47-fold in UC compared to CD samples (p = 0.0052) and was the only microRNA altered between IBD subtypes. Three colitis-associated microRNAs were significantly altered in sera of disease patients and displayed diagnostic utility. However, no serum microRNAs were found to distinguish ulcerative colitis from Crohn's colitis. Finally, miR-192 inhibition did not affect luciferase reporter activity, suggesting that miR-192 does not regulate human NOD2.
|
Plasma volume expansion is frequently recommended to correct the low output state resulting from right ventricular (RV) infarction. However, any subsequent increase in pericardial and RV filling pressures from volume expansion could impair RV collateral blood flow. We examined whether volume expansion in dogs before right coronary ligation reduced collateral perfusion and worsened the extent of RV necrosis. Randomized experimental study. Animal research laboratory in university medical center. Forty anesthetized, closed-chest dogs were randomly assigned to normovolemic, pericardium opened (n = 10) or intact (n = 10) groups, and hypervolemic, pericardium opened (n = 10) or intact (n = 10) groups. Hypervolemic animals received 24 mL/kg of 6% hetastarch. All animals underwent 90 min right coronary ligation, followed by 120 min reperfusion. Collateral coronary blood flow (radioactive microspheres) and area of necrosis (An) were determined in the area at risk (Ar). Stroke volume decreased in all groups with ischemia but remained 25 to 40% greater in both hypervolemic groups than in normovolemic animals (p < 0.05). In hypervolemic animals with intact pericardium, RV end-diastolic pressure increased to 10.4 +/- 2.1 mm Hg (mean +/- SD), a value that significantly exceeded those of the other three groups. During RV ischemia, collateral perfusion in the Ar was similar in both normovolemic groups and in hypervolemic animals with opened pericardium (mean range, 12.9 +/- 8.8 to 13.8 +/- 7.6 mL/min/100 g; p = NS), and the An/Ar varied from 11.8 +/- 6.3 to 18.6 +/- 17.4% (p = NS). In contrast, in hypervolemic animals with intact pericardium, collateral perfusion decreased to 7.2 +/- 3.5 mL/min/100 g and the An/Ar was increased to 38.2 +/- 18.6% (p < 0.05 compared with other groups, respectively). Overall, An/Ar was inversely related to collateral blood flow in the Ar (r = -0.46; p < 0.05) and correlated positively with RV end-diastolic pressure (r = 0.61; p < 0.05).
|
Does cryptosporidium parvum rhomboid1 have an activity in microneme protein CpGP900 cleavage?
|
Apicomplexan parasites actively release transmembrane (TM) adhesive proteins involved in host cell attachment and invasion. Rhomboids, a family of intramembrane serine proteases, cleave these secreted adhesive proteins within their TM domains as an essential step in completing the invasion process. In Cryptosporidium parvum, the activity of rhomboids in cleaving microneme proteins (MICs) has not been reported. In the present study, the interaction between C. parvum rhomboids (CpROM1 and CpROM4) and C. parvum microneme proteins (CpGP900 and CpTRAP-C1) was investigated using yeast two-hybrid assay and co-immunoprecipitation assays. Our study demonstrated that CpROM1 protein could interact with CpGP900 protein in co-transformed AH109 yeasts. Analysis of these proteins in co-transfected mammalian cells showed that the cleavage product of the CpGP900 protein was detected in the co-transfected cells. As control, CpGP900 only was transfected into cells and no cleavage was observed. The results suggested that CpGP900 protein was the substrate of CpROM1. Moreover, CpROM1 and CpROM4 could not cleave CpTRAP-C1 protein, which is the substrate of T. gondii rhomboid 2.
|
To examine whether anemia is associated with a higher incidence of recurrent falls. Prospective cohort study. Community-dwelling sample in The Netherlands. Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam. Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men. Falls were prospectively determined using fall calendars that participants filled out weekly for 3 years. Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up. Of the 394 persons, 11.9% (18 women and 29 men) had anemia. The incidence of recurrent falls was 38.3% of anemic persons versus 19.6% of nonanemic persons (P=.004). After adjustment for sex, age, body mass index, and diseases, anemia was significantly associated with a 1.91 times greater risk for recurrent falls (95% confidence interval=1.09-3.36). Poor physical function (indicated by muscle strength, physical performance, and limitations) partly mediated the association between anemia and incidence of recurrent falls.
|
Do dopamine transporters in striatum correlate with deactivation in the default mode network during visuospatial attention?
|
Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [(11)C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.
|
Histiocytoid Sweet syndrome (HSS) is a rare variant of Sweet syndrome (SS). The nature of histiocytoid cells is still uncertain. We sought to offer a comprehensive overview on clinical features of HSS and further information on immunohistochemical phenotype of the infiltrate. The clinical, histologic, and immunohistochemical features of 12 of our patients with HSS and all cases retrieved through a PubMed search were analyzed. Lesions consisted of erythematous-violaceous papules and plaques, randomly distributed mostly on the trunk and the limbs. Three patients had myelodysplastic syndrome and 1 had a monoclonal gammopathy. The infiltrate was mainly composed of CD68(+)CD163(+)myeloperoxidase(+)myeloid cell nuclear differentiation antigen(+)CD117(-)CD15(-)CD34(-), a phenotype suggestive of M2-like macrophages. A few mature neutrophils and lymphocytes were also present. Review of all HSS cases showed no sex predominance and no extracutaneous infiltrates; inconstant presence of fever and blood neutrophilia; association with hematologic or solid neoplasms (26%), autoimmune conditions (12%), and infectious diseases (10%); and good response to steroid treatment, with rare relapses or recurrences.
|
Does intracerebroventricular administration of neuropeptide Y induce hepatic insulin resistance via sympathetic innervation?
|
We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The downstream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY administration modulates the suppressive action of insulin on EGP via hepatic sympathetic or parasympathetic innervation. The effects of a continuous intracerebroventricular infusion of NPY on glucose turnover were determined in rats during a hyperinsulinemic-euglycemic clamp. Either rats were sham operated, or the liver was sympathetically (hepatic sympathectomy) or parasympathetically (hepatic parasympathectomy) denervated. Sympathectomy or parasympathectomy did not affect the capacity of insulin to suppress EGP in intracerebroventricular vehicle-infused animals (50 +/- 8 vs. 49 +/- 6 vs. 55 +/- 6%, in hepatic sympathectomy vs. hepatic parasympathectomy vs. sham, respectively). Intracerebroventricular infusion of NPY significantly hampered the suppression of EGP by insulin in sham-denervated animals (29 +/- 9 vs. 55 +/- 6% for NPY/sham vs. vehicle/sham, respectively, P = 0.038). Selective sympathetic denervation of the liver completely blocked the effect of intracerebroventricular NPY administration on insulin action to suppress EGP (NPY/hepatic sympathectomy, 57 +/- 7%), whereas selective parasympathetic denervation had no effect (NPY/hepatic parasympathectomy, 29 +/- 7%).
|
Lung cancer is the most important cause of cancer mortality worldwide, but the underlying mechanisms of this disease are not fully understood. Copy number variations (CNVs) are promising genetic variations to study because of their potential effects on cancer. Here we conducted a pilot study in which we systematically analyzed the association of CNVs in two lung cancer datasets: the Environment And Genetics in Lung cancer Etiology (EAGLE) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial datasets. We used a preestablished association method to test the datasets separately and conducted a combined analysis to test the association accordance between the two datasets. Finally, we identified 167 risk SNP loci and 22 CNVs associated with lung cancer and linked them with recombination hotspots. Functional annotation and biological relevance analyses implied that some of our predicted risk loci were supported by other studies and might be potential candidate loci for lung cancer studies.
|
Does anatomic location of penetrating lower-extremity trauma predict compartment syndrome development?
|
Compartment syndrome of the lower extremity can be a difficult diagnosis to make with serious consequences if diagnosis and intervention is delayed. Identifying patients who are more likely to develop this syndrome can help prevent the associated complications. The purpose of this study was to evaluate whether the anatomic location of the penetrating lower-extremity injuries can predict development of compartment syndrome. A retrospective chart review was performed of all patients admitted for a minimum of 23 hours to the University of South Alabama trauma center for penetrating lower-extremity trauma during the 8-year period from July 1998 through June 2006. Patients were entered in the study if wound trajectory was confined to the lower extremity between the inguinal ligament and the ankle. Injuries were categorized as above knee (AK) or below knee (BK), and whether the injury was in the proximal or distal half of the extremity segment. Clinical examination or compartmental pressures were used to diagnose BK compartment syndrome. A total of 321 patients sustained 393 lower-extremity injuries during the study period, of which 255 (65%) were AK and 138 (35%) were BK. Thirty-one (8%) lower extremities developed BK compartment syndrome with 29 (94%) secondary to penetrating injuries of the BK segment. All BK injuries that developed compartment syndrome were located in the proximal half of the BK segment. Eighteen (7%) AK injuries underwent BK 4-compartment fasciotomy, 16 (6%) of which were prophylactic after surgical intervention for AK vascular injury. Two patients (1%) developed postoperative BK compartment syndrome after superficial femoral vein ligation. All AK injuries that underwent fasciotomy sustained vascular injuries requiring surgical intervention. No BK compartment syndromes occurred in any patients with expectantly managed AK or distal BK injuries.
|
It is well-known that chronic administration of β2AR agonists can induce β2AR desensitization. Our previous study showed that Rho guanine nucleotide dissociation inhibitor 2 (RhoGDI2) overexpression induced beta-2 adrenergic receptor (β2AR) desensitization in airway smooth muscle cells. The purpose of this study was to further study the function of RhoGDI2 in β2AR desensitization by β2AR desensitization mouse model. Studies were performed using a β2AR desensitization mice model induced by salbutamol. The mice were randomly divided into five groups (n=45): RhoGDI2 overexpression group (n=10); RhoGDI2 siRNA group (n=10); empty viral vector group (n=10); experimental control group (n=10); blank control group-without any drug treatment (n=5). The first four groups were used the same methods and the same dose to establish β2AR desensitization mice model by salbutamol. The first three groups that salbutamol-treated were used for intratracheal delivery of lentiviral vectors. Airway hyperreactivity was measured through a whole-body plethysmograph system. RhoGDI2, β2AR, GRK2 mRNA and protein expression levels were then detected by RT-PCR and western blot analyses in fresh lung tissues. As well as the activity of GRK was assessed by light-dependent phosphorylation of rhodopsin. We successfully constructed β2AR desensitization mouse model. As expected, airway responsiveness after inhaling acetylcholine chloride (Ach) was markedly increased in the RhoGDI2 overexpression group compared to experimental control group and blank control group when concentrations of Ach was 45 mg/mL (all P<0.05), while, it was markedly decreased in the RhoGDI2 siRNA group compared to experimental control group (P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly increased in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly decreased in RhoGDI2 siRNA group compared to experimental control group and blank control group (all P<0.05). Conversely, β2AR expression were significantly lower in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05), exhibiting an inverse correlation with RhoGDI2 expression.
|
Are the status of rheumatoid factor and anti-cyclic citrullinated peptide antibody associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis : a meta-analysis?
|
This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody are associated with the clinical response to anti-tumor necrosis factor (TNF) alpha treatment in rheumatoid arthritis (RA). A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54) and 0.88 (95% CI: 0.76-1.03, p=0.11), respectively, with I(2) values of 43% (p=0.05) and 67% (p<0.01), respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab), response criteria (DAS28 vs. ACR20 vs. EULAR response), follow-up period (≥ 6 vs. <6 months), and ethnic group did not reveal a significant association for the status of RF and anti-CCP.
|
Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT). Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S), carbon monoxide and nitric oxide (NO), belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate) to study its lung protective potential in vitro and in vivo. In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation.
|
Does left ventricular reconstruction bring benefit for patients with ischemic cardiomyopathy?
|
Optimal treatment strategies for some patients with ischemic cardiomyopathy can be unclear. We compared the outcome for patients treated with revascularization only or with additional ventricular reconstruction. We compared 74 consecutive patients with an ejection fraction <35% and a left end-systolic volume index >80 mL/m(2). All patients underwent revasularization but some received only revascularization (group 1) and some were randomized into a group that received additional ventricular reconstruction (group 2). Preoperative and postoperative ejection fraction, end-systolic volume, mitral regurgitation, mortality, heart failure (HF) symptoms, and recurrence were compared between groups. There was 1 postoperative death in group 2 (P =. 58). Preoperative ejection fraction between the groups was similar (P =. 19) but it differed significantly postoperatively (P < .001). HF class (New York Heart Association) decreased more in group 2 (group 2, 2.3 +/- 0.4 versus group 1, 1.4 +/- 0.4; P < .001). Incidence of HF recurrence and rehospitalization was significantly less in group 2 (P = .028). The postoperative development of higher-grade mitral regurgitation was greater in group 1 (147 +/- 32 mL/m(2) versus 119 +/- 25 mL/m(2), P = .024).
|
Long non-coding RNAs (LncRNAs) are an important class of widespread molecules involved in diverse biological functions, which are exceptionally expressed in numerous types of diseases. Currently, limited study on LncRNA in rheumatoid arthritis (RA) is available. In this study, we aimed to identify the specifically expressed LncRNA that are relevant to adjuvant-induced arthritis (AA) in rats, and to explore the possible molecular mechanisms of RA pathogenesis. To identify LncRNAs specifically expressed in rheumatoid arthritis, the expression of LncRNAs in synoviums of rats from the model group (n=3) was compared with that in the control group (n=3) using Arraystar Rat LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR). Up to 260 LncRNAs were found to be differentially expressed (≥1.5-fold-change) in the synoviums between AA model and the normal rats (170 up-regulated and 90 down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs, XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected to analyze the relationship between LncRNAs and RA via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the AA rats.
|
Is promoter variation in the DC-SIGN-encoding gene CD209 associated with tuberculosis?
|
Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (-871G and -336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations.
|
We quantitatively evaluated the collagen-to-smooth muscle tissue matrix ratio in ureteropelvic junction obstruction, and compared the ratio with the degree of obstruction, patient age and postoperative renal recovery. We analyzed histological sections from 65 patients with ureteropelvic junction obstruction and 6 normal controls. Morphological and functional grading systems were adapted to determine the degree of renal obstruction. To examine smooth muscle and collagen tissue, sections were stained using Masson's trichrome. Two distinct populations of collagen versus smooth muscle were identified and the tissue matrix ratio was calculated by color image analysis. The mean tissue matrix ratio plus or minus standard deviation was 1.32+/-0.79 in all patients with ureteropelvic junction obstruction but only 0.30+/-0.10 in normal controls (p <0.0001). It appeared that the lower the tissue matrix ratio, the better the improvement in postoperative hydronephrosis (r = -0.50, p = 0.0001). Better recovery of renal function after pyeloplasty was observed with a decrease in the tissue matrix ratio (r = -0.43, p = 0.0004). We divided patients according to the tissue matrix ratio into groups 1--ratio 1 or less, 2--greater than 1 to 1.5 and 3--greater than 1.5 to determine a more detailed and clinically applicable correlation of tissue matrix ratio with postoperative renal functional changes. Better improvement in postoperative renal function was observed in group 1 than in group 3 (p = 0.002). Also, the tissue matrix ratio increased with patient age (r = 0.33, p = 0.007).
|
Does lactobacillus reuteri DSM 17938 shorten acute infectious diarrhea in a pediatric outpatient setting?
|
Two randomized controlled clinical trials have shown that Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea. This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1×10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded. The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15h, 60.4±24.5h [95% CI: 51.0-69.7h] vs. 74.3±15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted.
|
Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro. Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with ephrin-B2/Fc (2 μg/mL) for 14 days, and the neointima/media ratio was measured in matched veins. Primary human umbilical vein endothelial cells were treated with ephrin-B2/Fc (2 μg/mL) and examined with quantitative polymerase chain reaction, Western blot, immunoassays, and for release of NO. Ephrin-B2/Fc (2 μg/mL) was placed on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence. The baseline intima/media ratio in saphenous vein rings was 0.456 ± 0.097, which increased to 0.726 ± 0.142 in untreated veins after 14 days in organ culture but only to 0.630 ± 0.132 in veins treated with ephrin-B2/Fc (n = 19, P = .017). Ephrin-B2/Fc stimulated Akt, endothelial NO synthase and caveolin-1 phosphorylation, and NO release (P = .007) from human umbilical vein endothelial cells (n = 6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n = 3).
|
Does secretory immunoglobulin a blunt gut-mediated priming of neutrophils in vitro?
|
Gut ischemia may prime neutrophils to produce an exaggerated inflammatory response when challenged with bacterial pathogens. Secretory immunoglobulin A (sIgA) is the first line of defense against potential pathogens, but may also exert its anti-inflammatory effects on potentially destructive neutrophil functions. We hypothesized that sIgA would blunt the gut-mediated priming events that lead to neutrophil hypersensitivity to bacterial challenge. Confluent Caco2 cell monolayers were grown in a two-chamber culture system under normoxic or hypoxic conditions for 90 minutes followed by a 90-minute reoxygenation period. sIgA was placed in apical chamber media in experimental groups before reoxygenation period. Supernatants were then collected and incubated with neutrophils. Lipopolysaccharide was then used to activate neutrophils. Measurements of CD11b expression, elastase and superoxide anion production, and chemotaxis were undertaken. Polymorphonuclear neutrophils (PMNs) treated with Caco2 cells undergoing hypox-reoxygenation followed by activation with lipopolysaccharide show a dramatic increase in inflammatory potential when compared with naïve neutrophils (n = 4, *p < 0.001). The addition of sIgA in this same group before the activation step showed a blunting of the inflammatory response, but never to the level of naïve PMN.
|
To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients. An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance. The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment.
|
Does the nitric oxide donor glyceryl trinitrate increase subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy?
|
To examine the effect of glyceryl trinitrate (GTN), a nitric oxide (NO) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (OA). Bilateral lateral meniscectomy (MX) was performed on 12 ewes to induce OA. Six were treated with topical GTN (0.7mg/kg twice weekly) (MX+GTN). Six other sheep formed non-operated controls (NOC). After sacrifice at six months, the subchondral bone density (BMD) of the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP) was assessed by DEXA. Dynamic biomechanical testing was performed across the MTP and LTP. Histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (SCB) was determined by image analysis. MX+GTN displayed significantly greater SCB thickness relative to MX in the LFC (mean increase +88% and +42%, respectively) and the MFC. SCB BMD was 10-12% greater in MX+GTN relative to MX in the LFC, LTP and MTP. MX+GTN sheep also showed greater increases in some histopathology variables, greater central erosion of the LTP, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the LTP.
|
Recognising colorectal cancer (CRC) patients with Lynch syndrome (LS) can increase life expectancy of these patients and their close relatives. To improve identification of this under-diagnosed disease, experts suggested raising the age limit for CRC tumour genetic testing from 50 to 70 years. The present study evaluates the efficacy and cost-effectiveness of this strategy. Probabilistic efficacy and cost-effectiveness analyses were carried out comparing tumour genetic testing of CRC diagnosed at age 70 or below (experimental strategy) versus CRC diagnosed at age 50 or below (current practice). The proportions of LS patients identified and cost-effectiveness including cascade screening of relatives, were calculated by decision analytic models based on real-life data. Using the experimental strategy, four times more LS patients can be identified among CRC patients when compared with current practice. Both the costs to detect one LS patient (€9437/carrier versus €4837/carrier), and the number needed to test for detecting one LS patient (42 versus 19) doubled. When family cascade screening was included, the experimental strategy was found to be highly cost-effective according to Dutch standards, resulting in an overall ratio of €2703 per extra life-year gained in additionally tested patients.
|
Does development of ICF Core set for patients with chronic conditions?
|
The objective of the ICF Core Sets project is the development of internationally agreed Brief ICF Core Sets and Comprehensive ICF Core Sets. The methods to develop both ICF Core Sets, the Comprehensive ICF Core Set and the Brief ICF Core Set, involved a formal decision-making and consensus process integrating evidence gathered from preliminary studies and expert opinion. The results regarding the development of the ICF Core Sets for 12 health conditions (chronic widespread pain, low back pain, osteoarthritis, osteoporosis, rheumatoid arthritis, chronic ischemic heart disease, diabetes mellitus, obesity, obstructive pulmonary diseases, breast cancer, depression, and stroke) are presented in this supplement.
|
Many factors gave been reported to be of prognostic importance for thyroid cancer. Biologic aggressiveness may influence postoperative recurrences and the prognosis of thyroid cancer. Immunohistochemical staining for the p53 protein and DNA content are novel factors that suggest biologic aggressiveness. Retrospective study of the survival rate after operation of differentiated thyroid cancer was undertaken at Osaka Police Hospital. Age, gender operative method, extent of lymph node dissection, use of radioiodine, primary or recurrent tumor, tumor size and invasion, lymph node involvement, presence of distant metastases, DNA ploidy, percentage of S phase and G2M phase fractions, positive staining for the p53 protein, and histologic type and subtype were evaluated as possible prognostic factors by univariate and multivariate analyses of survival. Positive staining for the p53 protein was related to postoperative local recurrence, and DNA ploidy was related to distant metastatic recurrence. Univariate analysis suggested that age, tumor size and invasion, lymph node involvement, presence of distant metastases, percentage of S phase fraction, histologic subtype, DNA ploidy, and positive staining for the p53 protein were significant prognostic factors. Multivariate analysis suggested that positive staining of the protein and DNA ploidy were independent prognostic factors for overall survival.
|
Does pulsatile pulmonary perfusion during cardiopulmonary bypass reduce the pulmonary inflammatory response?
|
Pulmonary dysfunction presumably linked to an inflammatory response is frequent after cardiac operations using cardiopulmonary bypass (CPB) and pulmonary hypoperfusion. We previously demonstrated that active perfusion of the lungs during CPB reduces ischemic lung injury. We now hypothesized that avoiding ischemia of the lungs during CPB by active pulmonary perfusion would decrease pulmonary inflammatory response. Pigs were randomized to a control group with CPB for 120 minutes, followed by 120 minutes of postbypass reperfusion, or to the study groups where animals underwent active pulmonary perfusion with pulsatile or nonpulsatile perfusion during CPB (n = 7 in each group). Activation of transcription factor activity (nuclear factor [NF]-kappaB and activating protein [AP]-1) was determined by electrophoretic mobility shift assay. Levels of proinflammatory protein expression (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) were quantified by enzyme-linked immunoabsorbent assay. Caspase-3 activity was measured using a fluorogenic assay. The activation of transcription factor AP-1 and NF-kappaB was reduced in the pulsatile pulmonary perfusion group. The caspase-3 activity and the expression of IL-1, IL-6, and TNF-alpha revealed a significant decrease in the pulsatile and nonpulsatile pulmonary perfusion groups. Animals of the pulsatile pulmonary perfusion group showed significantly reduced IL-6 expression and caspase-3 activity compared with the nonpulsatile pulmonary perfusion group.
|
Vitamin D insufficiency in children may have long-term skeletal consequences as vitamin D affects calcium absorption, bone mineralization and bone mass attainment. This school-based study investigated vitamin D status and its association with vitamin D intake and bone health in 195 Finnish children and adolescents (age range 7-19 years). Clinical characteristics, physical activity and dietary vitamin D intake were evaluated. Blood and urine samples were collected for serum 25-hydroxyvitamin D (25-OHD) and other parameters of calcium homeostasis. Bone mineral density (BMD) and body composition were measured with dual-energy X-ray absorptiometry (DXA). Altogether 71% of the subjects were vitamin D insufficient (25-OHD <50 nmol/L). The median 25-OHD was 41 nmol/L for girls and 45 nmol/L for boys, and the respective median vitamin D intakes 9.1 µg/day and 10 µg/day. In regression analysis, after adjusting for relevant factors, 25-OHD concentration explained 5.6% of the variance in lumbar BMD; 25-OHD and exercise together explained 7.6% of the variance in total hip BMD and 17% of the variance in whole body BMD. S-25-OHD was an independent determinant of lumbar spine and whole body BMD and in magnitude surpassed the effects of physical activity.
|
Does gabapentin reduce post-thoracotomy shoulder pain : a randomized , double-blind placebo-controlled study?
|
Despite adequate epidural analgesia, up to 97% of patients undergoing thoracotomy experience ipsilateral shoulder pain. In this setting, this study evaluated the safety and the efficacy of pre-emptive gabapentin. A double-blind, placebo-controlled study was undertaken in 51 patients randomized into two groups. Two hours before surgery, 23 patients received gabapentin 1200 mg po (Group G), and 28 patients received placebo (Group P). Shoulder pain and postoperative pain, at the surgical site, were monitored every four hours for 24 hr, using a numerical rating scale. Subcutaneous hydromorphone was administered for rescue analgesia against shoulder pain. Forty-four patients complained of shoulder pain (prevalence of 86%). Demographic and surgical data were similar between the two groups. There were no significant differences in the total cumulative doses of hydromorphone administered at eight, 16, and 24 hr, nor were there differences in individual numerical rating scale scores for shoulder pain. The groups were similar with respect to the degree of pain at the surgical site. The frequency of side effects between groups at corresponding time intervals was also similar, with the exception of sedation. At four hours, the incidence of sedation scores > 1 was greater in Group G (21/23 patients), compared to Group P (18/28 patients; P = 0.025). In contrast, by 24 hr, 5/18 patients in Group P had sedation scores > 1, compared to 0/28 patients in Group G (P = 0.05).
|
Cycle-dependent fluctuations in natural killer (NK) cell populations in endometrium and circulation may differ, contributing to unexplained infertility. NK cell phenotypes were determined by flow cytometry in endometrial biopsies and matched blood samples. While circulating and endometrial T cell populations remained constant throughout the menstrual cycle in fertile and infertile women, circulating NK cells in infertile women increased during the secretory phase. However, increased expression of CD94, CD158b (secretory phase), and CD158a (proliferative phase) by endometrial NK cells from infertile women was observed. These changes were not reflected in the circulation.
|
Does lenalidomide reduce microglial activation and behavioral deficits in a transgenic model of Parkinson 's disease?
|
Parkinson's disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and neuroinflammation. Currently, there are no disease modifying alternatives for PD; however, targeting neuroinflammation might be a viable option for reducing motor deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed for reduced toxicity and increased immunomodulatory properties. Lenalidomide has shown protective effects in an animal model of amyotrophic lateral sclerosis, and its mechanism of action involves modulation of cytokine production and inhibition of NF-κB signaling. In order to assess the effect of lenalidomide in an animal model of PD, mThy1-α-syn transgenic mice were treated with lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks. Lenalidomide reduced motor behavioral deficits and ameliorated dopaminergic fiber loss in the striatum. This protective action was accompanied by a reduction in microgliosis both in striatum and hippocampus. Central expression of pro-inflammatory cytokines was diminished in lenalidomide-treated transgenic animals, together with reduction in NF-κB activation.
|
To evaluate the effectiveness and safety of hydroxyethyl starch (HES 130/ 0.4, 60 g/L) in resuscitation during shock stage of burns. Sixty-six burn patients who were admitted to hospital within 2 hours after burn injury requiring fluid resuscitation were enrolled into this study, and they were randomized into HES( n = 33, with HES as a component of fluid resuscitation) and plasma (P, n = 33, with plasma as a component of fluid resuscitation) groups. HES or plasma was given as colloid within 48 postburn hours (PBH), and only albumin [( 111 +/- 4) , ( 105 +/- 5 ) g for each group] were given to the patients during 3 to 7 postburn days (PBD). Heart rate, blood pressure, central venous pressure (CVP) , urine output per hour were measured, gain/loss of body fluid during the first and second 24 PBH were recorded, serum total protein, albumin, hemoglobin( Hb) , prothrombin time (PT) , fibrinogen; platelet ( PLT) , as well as liver and renal function, allergy and bleeding tendency were determined and observed at corresponding time-points. There were no obvious differences in heart rate, blood pressure, CVP and urine output per hour within 24 PBH between the two groups (P > 0.05). Also there was no difference in gain/loss of body fluid during the first and second 24 PBH. The content of hemoglobin on 1 ,3, 7,14 PBD ,and the PT, the content of fibrinogen, the number of PLT on 1,3,14 PBD also exhibited no difference between the two groups (P > 0.05). The serum contents of total protein and albumin in HES group were [(31 +/- 3) g/L, (30 +/- 3)g/L ] on 1 PBD, and [(20.4 +/- 3.6) g/L, (18.4 +/-2.3) g/L] on 3 PBD, which were obviously lower than those in P group [(45 +/- 4) g/L, (39 +/- 3) g/L on 1 PBD, and 1 (24.5 +/- 4.3) g/L, (21.3 +/- 3.9) g/L) on 3 PBD, (P <0. 01). Though the serum content of albumin on 7 PBD was similar in the two groups (P > 0.05), the serum total protein in HES group (40 +/- 4) g/L was markedly lower than that in P group [(45 +/- 4) g/L, P < 0.01] . Within 7 PBD, no abnormal bleeding was found in the two groups, and the liver function and renal function were similar. There were 4 cases showing allergic reaction in plasma group while none in HES group.
|
Does overexpression of pyruvate dehydrogenase kinase support dichloroacetate as a candidate for cutaneous melanoma therapy?
|
We aimed to verify if there is evidence to consider dichloroacetate (DCA), which inhibits the pyruvate dehydrogenase kinase (PDK) and reverts the metabolic shift of cancer cells from glycolysis to oxidative phosphorylation, as a promising drug for therapy of cutaneous melanoma (CM) patients. We assessed the expression profile of PDK 1, 2 and 3 in a series of melanoma samples, to verify if melanoma tumors express the DCA targets, if this expression correlates with the activation of important signaling cascades for melanomagenesis and also with the prognosis of melanoma patients. We also established the sensitivity of melanoma cell lines to DCA treatment, by assessing their metabolic alterations, proliferation and survival. We observed that both PDK 1 and 2 isoforms are overexpressed in CM compared to nevi, this expression being associated with the expression of the mTOR pathway effectors and independent of the BRAF mutational status. Melanoma cell lines treated with DCA showed a shift in metabolism, that is, a decrease in glucose consumption and lactate production, downregulation of proliferation, an increase of apoptosis and a decrease in mTOR pathway activation.
|
Application of antibodies against cardiac troponin I (cTnI-Ab) can induce dilation and dysfunction of the heart in mice. Recently, we demonstrated that immunization with cTnI induces inflammation and fibrosis in myocardium of mice. Others have shown that auto-antibodies to cTnI are present in patients with acute coronary syndrome, but little is known about the clinical relevance of detected cTnI-Ab. First, anti-cTnI and anti-cTnT antibody titres were measured in sera from 272 patients with dilated- (DCM) and 185 with ischaemic- (ICM) cardiomyopathy. Secondly, 108 patients with acute myocardial infarction (AMI) were included for a follow-up study. Heart characteristics were determined by magnetic resonance imaging 4 days and 6-9 months after AMI. Altogether in 7.0% of patients with DCM and in 9.2% with ICM, an anti-cTnI IgG antibody titre >/=1:160 was measured. In contrast, only in 1.7% of patients with DCM and in 0.5% with ICM, an anti-cTnT IgG antibody titre >/=1:160 was detected. Ten out of 108 patients included in the follow-up study were tested positive for cTnI-Ab with IgG Ab titres >/=1:160. TnI-Ab negative patients showed a significant increase in left ventricular ejection fraction (LVEF) and stroke volume 6-9 months after AMI. In contrast, there was no significant increase in LVEF and stroke volume in TnI-Ab positive patients.
|
Does c-Peptide be a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico?
|
Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS.
|
Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. We set to determine the role of toll-like receptor 3 and the binding of double-stranded RNA in the pathogenesis of sterile injury following lung contusion. Toll-like receptor 3 expression was analyzed in postmortem lung samples from patients with lung contusion. Unilateral lung contusion was induced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-β (-/-), and wild-type mice. Subsequently, lung injury and inflammation were evaluated. Apoptotic indices, phagocytic activity, and phenotypic characterization of the macrophages were determined. Double-stranded RNA in bronchoalveolar lavage and serum samples following lung contusion was measured. A toll-like receptor 3/double-stranded RNA ligand inhibitor was injected into wild-type mice prior to lung contusion. Toll-like receptor 3 expression was higher in patients and wild-type mice with lung contusion. The degree of lung injury, inflammation, and macrophage apoptosis was reduced in toll-like receptor 3 (-/-), TIR-domain-containing adapter-inducing interferon-β (-/-), and wild-type mice with toll-like receptor 3 antibody neutralization. Alveolar macrophages from toll-like receptor 3 (-/-) mice had a lower early apoptotic index, a predominant M2 phenotype and increased surface translocation of toll-like receptor 3 from the endosome to the surface. When compared with viral activation pathways, lung injury in lung contusion demonstrated increased p38 mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 phosphorylation with inflammasome activation without a corresponding increase in nuclear factor-κB or type-1 interferon production. Additionally, pretreatment with toll-like receptor 3/double-stranded RNA ligand inhibitor led to a reduction in injury, inflammation, and macrophage apoptosis.
|
Are circulating levels of IL-1beta , a prothrombotic cytokine , elevated in unstable angina versus stable angina?
|
Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina. We measured plasma levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls. Mean levels of IL-1beta were significantly higher in patients with unstable angina as compared to patients with stable angina (p =.009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p =.031 and.006, respectively). No significant differences were found in the levels of TNF-alpha.
|
This study was carried out to evaluate the impact of the presence of teratomatous component in orchiectomy specimen on complete response rates to primary chemotherapy in a large series of patients with stage II nonseminomatous germ cell tumors (NSGCT). Chemotherapy was administered to 113 patients with stage II testicular NSGCT. Resection of retroperitoneal residual tumor masses was performed in all patients with partial response to chemotherapy. Patients were categorized into 2 groups according to presence or absence of teratomatous component in the primary orchiectomy specimen. Of patients with teratomatous component in the orchiectomy specimen, 32.1% (17/53) had complete response to primary chemotherapy and of those without teratomatous component 55% (33/60) had complete response (P = 0.022). Stage IIC patients had lower response rate 28.8% (23/80) compared with IIA and IIB patients (P = 0.0001). Teratomatous elements were found in retroperitoneal mass in 70.6% of patients with teratomatous component in orchiectomy specimens compared to 36.8% of patients without teratomatous component (P = 0.022). After retroperitoneal surgery and additional treatments, complete response rate increased to 92.4% and 89.5% in patients with and without teratomatous component in primary pathology, respectively, (P > 0.05).
|
Do soluble Notch ligand and receptor peptides act antagonistically during angiogenesis?
|
Notch signalling is essential for blood vessel formation. During angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of the Notch ligands binds to the EGF-like repeats 11-13 of the Notch receptor. This study aimed to elucidate how soluble proteins containing these short domains interfere with Notch signalling during angiogenesis. Adenoviral vectors were generated to express the DSL domains of DLL1, DLL4, JAG1, and the Notch1 EGF-like repeats 11-13 fused to immunoglobulin-G heavy chain. These soluble ligand peptides inhibited Notch signalling in endothelial cells and this caused hyperbranching in cellular angiogenesis assays and in the neonatal mouse retina. The soluble Notch receptor peptides bound stronger to JAG1 than DLL4 ligands, resulting in increased signalling activity. This led to impaired tip cell formation and less vessel sprouting in the retina.
|
Serum prostate-specific antigen (PSA) level is a widely used serum marker for diagnosis and management of prostate cancer. Although not well-defined, liver appears to be the most likely site of PSA metabolism. However, general anaesthesia usually changes hepatic blood flow, therefore it may affect the metabolism of PSA. In this study we investigated the affect of general anaesthesia on the serum total PSA, free PSA and free to total PSA levels. 30 male patients who were hospitalised in the internal medicine clinic (non-surgery group) and 30 male patients who would undergo operation under general anaesthesia (15 for cholecystectomy and 15 for inguinal hernia repair) enrolled into the study. PSA measurement was done on the day of the hospitalisation (which was also the day of operation for surgery group), on the 24th hour following the first measurement and on the 21st day. Anaesthesia was standardized for all patients. There was no statistically significant difference in serum total PSA (p >0.05), free PSA levels (p >0.05) and free to total PSA ratio (p >0.05) between the surgery and non-surgery groups. There were statistically significant decreases in the 24th hour total PSA levels (13.8% in surgery group, p <0.05, and 13.1% in non-surgery group, p <0.05) and in the free PSA levels (4.0% in surgery group, p <0.05, and 8.2% in non-surgery group, p <0.05). There was no statistically significant difference in the free to total PSA ratios (p >0.05 and p >0.05, respectively).
|
Does tLR4 contribute to the host response to Klebsiella intraocular infection?
|
Klebsiella pneumoniae causes a blinding infection called endogenous endophthalmitis. The role of innate immune recognition of K. pneumoniae in the eye during infection is not known. We hypothesized that intraocular recognition of K. pneumoniae was mediated by Toll-like receptor (TLR)-4 and may be dependent on MagA-regulated hypermucoviscosity. Experimental endophthalmitis was induced in C57BL/6J or TLR4(-/-) mice by intravitreal injection of 100 CFU of wild type or ΔmagA K. pneumoniae. Infection and inflammation were quantified by determining viable K. pneumoniae per eye, retinal responses via electroretinography, myeloperoxidase activity of infiltrating neutrophils and the proinflammatory cytokine and chemokine response. C57BL/6J and TLR4(-/-) mice could not control intraocular wild-type K. pneumoniae growth. TLR4(-/-) mice were less able than C57BL/6J to control the intraocular growth of ΔmagA K. pneumoniae. Retinal function testing suggested that infection with ΔmagA K. pneumoniae resulted in less retinal function loss. There was a TLR4-dependent delay in initial neutrophil recruitment, regardless of the infecting organism. The proinflammatory cytokine/chemokine data supported these results. These findings were not due to an inability of TLR4(-/-) neutrophils to recognize or kill K. pneumoniae.
|
Recent evidence suggests that insulin resistance and hyperinsulinemia may account for many of the medical complications of obesity. This study was performed to determine whether a predominance of body fat in the abdominal region is associated with insulin resistance and hyperinsulinemia. Two groups of nine obese women were matched for age and total obesity but differed significantly in the pattern of fat distribution as defined by the waist-to-hip circumference ratio (WHR). The high-WHR group had a WHR of 0.87 (+/- 0.01), and the low-WHR group had WHR of 0.77 (+/- 0.02) (P < .05). Plasma levels of glucose, free fatty acids, and insulin, measured hourly for eight hours while the subjects consumed a diet of regular food, were higher in the high-WHR group.
|
Are circulating levels of MCP-1 and IL-8 elevated in human obese subjects and associated with obesity-related parameters?
|
Chemotactic cytokines, referred to as chemokines, play an important role in leukocyte trafficking. The circulating levels of chemokines have been shown to increase in inflammatory processes including obesity-related pathologies (e.g. atherosclerosis and diabetes). However, little is currently known about the relationship between chemokines and human obesity. In the present study, we investigated the circulating levels of selected chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), leukotactin-1, interleukin-8 (IL-8)) and the association between the chemokine levels and obesity-related parameters: body mass index (BMI), waist circumference, fasting glucose and insulin levels, lipids profile, and the level of C-reactive protein (CRP). A total of 100 subjects, 50 obese (BMI>or=25 kg/m2) and 50 who were not obese (BMI<25 kg/m2) participated in the present study. The levels of chemokines and CRP were measured in a fasting state serum by sandwich enzyme-linked immunosorbent assay. Total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, glucose, and insulin levels were measured by enzymatic analysis and immunoassay. The circulating levels of MCP-1 and IL-8 in the serum were significantly (P<0.05) higher in obese subjects (BMI>30 kg/m2) compared with those of nonobese controls (BMI<25 kg/m2). The levels of CRP were positively correlated with BMI (P<0.001) or waist circumference (P<0.0001). The levels of MCP-1 and IL-8 were positively related to BMI (MCP-1, P<0.02; IL-8, P<0.01) and/or waist circumference (MCP-1, P<0.009; IL-8, P<0.03). The levels of MCP-1 were positively related to the levels of CRP (P<0.007) or interleukin-6 (IL-6) (P<0.0001), and negatively related to the levels of HDL-cholesterol (P<0.01). Homeostasis model assessment (HOMA) score was positively related to the levels of MCP-1 (P<0.02) or IL-8 (P<0.03) in obese subject.
|
Droperidol is useful for postoperative sedation in infants and children after cardiac surgery because it provides sedation and akinesia with minimal respiratory depression. However, droperidol has been associated with QT prolongation and ventricular arrhythmias. We investigated, if neuroleptanalgesic doses of droperidol led to QT prolongation and cardiac arrhythmias in children undergoing cardiac surgery. We retrospectively analysed electrocardiogram rhythm strips that were obtained before and in time increments after a 100 microg x kg(-1) intravenous bolus of droperidol in 20 children undergoing cardiac surgery. The longest QT interval was determined in each ECG and corrected for heart rate (QTc). All arrhythmias were recorded. Droperidol led to a significant increase in QTc time that was still present at 15 min but had resolved within 30 min after the bolus. No associated arrhythmias were observed.
|
Is the Expression of CD9 and PIK3CD Associated with Prognosis of Follicular Lymphoma?
|
Follicular lymphoma (FL) frequently develops drug-resistance and transforms into more aggressive subtypes over time. It is urgent to find prognostic biomarkers and disclose signaling pathways that have potential to be drug targets. In this study, we investigated the association of FL prognosis with the expression of 2 proteins: PIK3CD, a PI3K pathway component, and CD9, a tetraspanin family member. The expression of PIK3CD and CD9 were examined on 76 FL tumor tissues and 15 normal tissues with Immunohistochemistry. Chi-square test, Cox proportional hazards model, and Kaplan-Meier estimates were used to analyze the relationships of CD9 and PIK3CD expression and major clinicopathological features. PIK3CD expression was significantly higher, whereas CD9 expression was significantly lower in the 76 FL specimens than normal tissues. Concomitantly, low CD9 or high PIK3CD expression is associated with high degrees of Ann Arbor stages. In agreement with this, PIK3CD is an unfavorable and CD9 is a favorable factor for progression-free survival (PFS). Interestingly, PIK3CD expression is negatively correlated with CD9 expression, and the PIK3CD-high/CD9-low was significantly associated with short PFS when the 2 factors were combined together. Lastly, CD9 expression was significant higher in patients with bone marrow infiltration (BMI) than those without BMI.
|
Minute ventilation (MV) has been proven to be very useful in rate responsive pacing. The aim of this study was to evaluate the feasibility of using implantable cardioverter-defibrillator (ICD) leads as part of the MV detection system. At implant in 10 patients, the transthoracic impedance was measured from tripolar ICD, tetrapolar ICD, and atrial lead vectors during normal, deep, and shallow voluntary respiration. MV and respiration rate (RespR) were simultaneously measured through a facemask with a pneumotachometer (Korr), and the correlations with impedance-based measurements were calculated. Air sensitivity was the change in impedance per change in respiratory tidal volume, ohms (Omega)/liter (L), and the signal-to-noise ratio (SNR) was the ratio of the respiratory and cardiac contraction components. The air sensitivity and SNR in tripolar ICD vector were 2.70 +/- 2.73 ohm/L and 2.19 +/- 1.31, respectively, and were not different from tetrapolar. The difference in RespR between tripolar ICD and Korr was 0.2 +/- 1.91 breaths/minute. The regressed correlation coefficient between impedance MV and Korr MV was 0.86 +/- 0.07 in tripolar ICD.
|
Do mental health service use among high school students exposed to interpersonal violence?
|
Violence-exposed youth rarely receive mental health services, even though exposure increases risk for academic and psychosocial problems. This study examines the association between violence exposure and mental health service contact. The 4 forms of violence exposure were peer, family, sexual, and witnessing. Data are from 1534 Boston public high school students who participated in a 2008 self-report survey of violence exposure and its correlates. Multivariate logistic regressions estimated associations between each form of violence with service contact, then examined whether associations persisted when controlling for suicidality and self-injurious behaviors. In unadjusted models, violence-exposed students more often reported service contact than their peers. However, in multivariate models, only exposure to family (odds ratio [OR] = 1.69, 95% confidence interval [CI] = 1.23-2.31) and sexual violence (OR = 2.34, 95% CI = 1.29-4.20) were associated with service contact. Associations attenuated when controlling for suicidality and self-injurious behaviors, indicating they were largely explained by self-harm. Sexual violence alone remained associated with mental health service contact in fully adjusted models, but only for girls (OR=3.32, 95% CI=1.30-8.45), suggesting sex-specific pathways.
|
To investigate the prognostic value of weight loss before diagnosis in patients with advanced stage non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. A total of 81 NSCLC patients with stages IIIB/IV were included in this retrospective cross-sectional study. Study variables were weight loss in the last 3 months before diagnosis, patient demographic, clinical and laboratory characteristics and histological features of the tumor before administering first-line chemotherapy. Then, the patients were stratified into 4 groups based on their weight loss before being diagnosed with NSCLC. The patients were predominantly male (68%), with a smoking history (62%), 5 to 10 kg weight loss in the last 3 months (31%), and had metastatic disease (64%) and adenocarcinoma (40%) at the time of diagnosis. On the other hand, most of the patients with 5 to 10 kg weight loss in the last 3 months before diagnosis had squamous cell carcinoma (44%), stage IV disease (56%), and the first disease progression was in the brain (64%). Pre-diagnosis weight loss had a negative impact on progression-free survival (PFS), independent from weight loss during first-line chemotherapy, but no such effect was noticed on overall survival (OS).
|
Do marginal and internal fit of two different zirconium copings fabricated on the implant abutment?
|
To evaluate the accuracy of marginal and internal fit of the zirconium copings manufactured by two different computer-aided design(CAD)/computer-aided manufacturing(CAM)system on the implant abutment. Using different scanning mode,five Procera(®) zirconium copings and five Lava zirconium copings were fabricated on the same implant abutment, and then compared with five precious metal copings fabricated by traditional method. Fifteen abutment replica were made with die-stone and the copings were randomly cemented on them, then they were sectioned and invested. The marginal, shoulder, occlusal, and axial fit of each sample was measured by scanning electron microscopy (SEM). There was no significant difference in marginal and axial fit among the three groups(P>0.05). Significant difference in occlusal fit was found among the three groups(P<0.05): Lava group showed better fit than the others(P<0.05)and Procera(®) group showed better fit than the control(P<0.05).
|
Adenylyl cyclase is a transmembrane signaling system involved in the inhibition of cellular responses. Recently, we showed that the activity of adenylyl cyclase may be potentiated by stimuli that induce an increase of cellular responses but that do not activate adenylyl cyclase. This is probably an important physiologic feedback mechanism that prevents cells from becoming "overstimulated." Because increased cellular activities are frequently observed in persons with asthma, we hypothesized that a defect in potentiation of adenylyl cyclase might be involved. Potentiation of isoprenaline-induced adenosine cyclic monophosphate (cAMP) production with the mitogen phytohemagglutin (PHA; 45 micrograms/ml) or the calcium ionophore A23187 (1 mumol/L) was studied in peripheral blood mononuclear cells taken from patients with asthma (n = 8) and healthy control subjects (n = 11). Isoprenaline-induced cAMP production was potentiated significantly in the healthy control subjects (PHA, 110% +/- 15%; A23187, 92% +/- 25%). In contrast, potentiation was not seen with PHA or A23187 in the total group of patients with asthma. However, some patients showed weak potentiation, whereas in others PHA decreased isoprenaline-induced cAMP production. Moreover, the effect of PHA on isoprenaline-induced cAMP production correlated significantly with the degree of bronchial hyperreactivity in patients with asthma (r = 0.96; p = 0.0001).
|
Is alcoholism associated with hepatitis C but not hepatitis B in an urban population?
|
Previous studies have suggested an association of viral hepatitis with alcoholism, although the role of confounding risk factors (e.g. i.v. drug use) has not been adequately excluded. We therefore compared the seroprevalences of hepatitis B and C in alcoholic patients to that of a nonalcoholic control group. Hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody, and hepatitis C virus antibody testing (second generation ELISA and a confirmatory recombinant immunoblot assay) was performed in 150 consecutive alcoholics admitted for detoxification and in 166 randomly selected patients attending a general medical clinic who were screened for alcoholism. Hepatitis B and C seropositivities in actively drinking alcoholics are 49.3 and 35.3%, respectively, and were significantly associated with a history of i.v. drug abuse. Out of 166 general medicine clinics patients, 93 were classified as nonalcoholic (by both self-report and collateral verification), 46 patients had a history of alcoholism , and 27 were indeterminate. In the subgroup of patients without known viral hepatitis risk factors, there was no significant difference in hepatitis B seropositivity among nonalcoholic general medicine clinic patients, alcoholic general medicine clinic patients, and alcoholic patients admitted for detoxification (22.1%, 30.3%, and 27.6%, respectively). In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcohol patients admitted for detoxification without risk factors was significantly greater than in nonalcoholic general medicine patients without risk factors (10 vs 0%, p >0.01). Stepwise logistic regression analysis revealed that alcoholism requiring detoxification was a significant risk factor for hepatitis C but not for hepatitis B seropositivity.
|
To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with Insulin-like growth factor-1 (IGF-1) and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 h after compression +/-IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24h compression suppressed this effect. Compression alone up-regulated expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 and transforming growth factor (TGF)-beta, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, tissue inhibitor of metalloproteinase (TIMP)-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated.
|
Do radiological findings support lateral residual tumour as a major cause of local recurrence of rectal cancer?
|
The aim of this study was to determine the sites of local recurrence following radical (R0) total mesorectal excision (TME) for rectal cancer in an effort to elucidate the reasons for recurrence. Thirty-seven patients with recurrence following curative resection for rectal cancer were identified from a population of 880 patients operated on by surgeons trained in the TME procedure. Two radiologists independently examined 33 available computed tomograms and magnetic resonance images taken when the recurrence was detected. Twenty-nine of the 33 recurrences were found in the lower two-thirds of the pelvis. Two recurrent tumours appeared to originate from lateral pelvic lymph nodes. Evidence of residual mesorectal fat was identified in 15 patients. Fourteen of the recurrent tumours originated from primary tumours in the upper rectum; all of these tumours recurred at the anastomosis and 12 of the 14 patients had evidence of residual mesorectal fat.
|
Asthma is an inflammatory disease of the airways and the current focus in managing asthma is the control of inflammation. In this study, we attempted to investigate the anti-asthmatic potential of a plant derived natural compound, luteolin. We used a murine model of airway hyperreactivity, which mimicked some of the characteristic features of asthma. Male BALB/c mice (8-9 weeks) were used for this study. Mice (n = 6) were sensitized by intraperitoneal (i. p.) injection of 10 mg of ovalbumin (OVA) on days 0, 7 and 14 followed by aerosol inhalation (5% OVA) treatments daily beginning from day 19 to day 23. To study its preventive effect, luteolin (0.1, 1.0, and 10 mg/kg body weight; daily) was administered orally during the entire period (0 to 23 day) of sensitization. To study its curative effect, mice were first sensitized and then luteolin (1.0 mg/kg body weight daily) was given orally from day 26 to 32. The airway hyperreactivity, immunoglobulin E (IgE) in the sera, and cytokines (IFN-gamma, IL-4 and IL-5) in the bronchoalveolar lavage fluid (BALF) were measured. Both during sensitization and after sensitization, luteolin, at a dose of 0.1 mg/kg body weight, significantly modulated OVA-induced airway bronchoconstriction and bronchial hyperreactivity (p < 0.05). Luteolin also reduced OVA-specific IgE levels in the sera, increased interferon gamma (IFN-gamma) levels and decreased the interleukin-4 (IL-4) and interleukin-5 (IL-5) levels in the BALF.
|
Do mRI features have a role in pre-surgical planning of colloid cyst removal?
|
Endoscopic resection is becoming a well-established treatment option for patients with colloid cysts of the third ventricle. A disadvantage of this approach is the decreased ability to resect cysts in their entirety. Correlations between magnetic resonance imaging (MRI) features and cyst content could potentially help surgeons decide on the extent of resection and approach. We attempted to identify a correlation between patients' MRI imaging patterns and difficult cyst removal, post-operative adverse outcomes and the need for cerebrospinal fluid (CSF) diversion, in order to detect markers that may affect pre-surgical planning. A retrospective examination of all patients' records that underwent a colloid cyst excision attempt at our institution between 2001 and 2014, and which had a minimum 1-year follow-up was compiled. Of the 25 patients fulfilling the criteria, we found cysts with a low T2 signal, specifically when combined with high T1 signal, to be significantly correlated with piecemeal, difficult removals. Correlation was also found between high T2 signal cysts and pre-operative hydrocephalus. Among patients that had pre-existing hydrocephalus, those that required a piecemeal removal possessed a strong trend towards a need for subsequent shunting.
|
Whole-grain cereals and diets with a low glycemic index may protect against the development of type 2 diabetes and heart disease, but the mechanisms are poorly understood. We studied the effect of carbohydrate modification on serum metabolic profiles, including lipids and branched chain amino acids, and dependencies between these and specific gene expression pathways in adipose tissue. Twenty subjects with metabolic syndrome were selected from the larger FUNGENUT study population, randomized either to a diet high in oat and wheat bread and potato (OWP) or rye bread and pasta (RP). Serum metabolomics analyses were performed using ultra-performance liquid chromatography coupled to electrospray ionization mass spectrometry (UPLC/MS), gas chromatography (GC) and UPLC. In the OWP group multiple proinflammatory lysophosphatidylcholines increased, while in the RP group docosahexaenoic acid (DHA 22:6n-3) increased and isoleucine decreased. mRNA expression of stress reactions- and adipose tissue differentiation-related genes were up-regulated in adipose tissue in the OWP group. In the RP group, however, pathways related to stress reactions and insulin signaling and energy metabolism were down-regulated. The lipid profiles had the strongest association with the changes in the adipose tissue differentiation pathway when using the elastic net regression model of the lipidomic profiles on selected pathways.
|
Is the prostatic utricle a Müllerian duct remnant : immunohistochemical evidence for a distinct urogenital sinus origin?
|
The embryological origin of the utricle is thought to be a remnant of the fused caudal ends of the müllerian ducts (MDs). Others propose that the urogenital sinus (UGS) contributes either partially or totally to the development of this structure. Using immunohistochemical probes, we provide strong evidence that the utricle is of UGS origin only. Human fetal prostates, gestational ages 9 to 24 weeks, were serially cross-sectioned. Representative sections were stained with antibodies to p63 (basal cell marker), vimentin (mesoderm marker), uroplakins (marker for urothelium) Pax-2 (expressed in ductal and mesenchyme of urogenital system including the MDs and wolffian ducts) and Ki67 (proliferation). Apoptosis was detected with the TUNEL assay. By 9 weeks there was weak expression of p63 in the basal layer of the UGS. At 11 weeks there was increased staining of p63 in the UGS and some p63 staining of the fused MDs, which expressed Pax-2 at this time. At 14 to 15 weeks as the MDs were undergoing apoptosis, there was an ingrowth of uroplakin-expressing UGS epithelium into the periurethral stroma, which formed a plate of p63 positive cells just beneath the UGS that was Ki67 positive. The remaining caudal MD epithelium was p63 negative and expressed vimentin and Pax-2. By 17 weeks the plate of p63 positive cells elongated forming the utricle that remained p63 positive but Pax-2 and vimentin negative.
|
Aerobic exercise can decrease postprandial triglyceride (TG) concentrations but the relationship between exercise-induced energy deficits and postprandial lipemia is still unclear. The aim of the present study was to examine the effect of a single bout of aerobic exercise, with and without energy replacement, on postprandial lipemia and on peripheral blood mononuclear cell (PBMC) mRNA expression of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) receptors and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Nine healthy male humans completed three two-day trials in a random order. On day 1, volunteers rested (CON), completed 60 minutes of treadmill walking at 50% of VO2peak (EX) or completed the same bout of walking but with the energy replaced afterwards with a glucose solution (EXG). On day 2, volunteers rested and consumed a high fat test meal in the morning. Total and incremental TG AUC were significantly lower on the EXG (P < 0.05) and EX (P < 0.05) trials than the CON trial with no difference between the two exercise trials. No significant difference was observed in VLDL or LDL receptor mRNA expression among the trials (P > 0.05).
|
Is hIV infection associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero : Multicenter AIDS Cohort Study ( MACS )?
|
HIV-infected individuals bear increased cardiovascular risk even in the absence of traditional cardiovascular risk factors. In the general population, coronary artery calcium (CAC) scanning is of value for cardiovascular risk stratification, but whether a CAC score of zero implies a low noncalcified coronary plaque burden in HIV-infected persons is unknown. We assessed the prevalence of noncalcified coronary plaque and compared noncalcified coronary plaque burden between HIV-infected and HIV-uninfected participants who had CAC scores of zero in the Multicenter AIDS Cohort Study (MACS) using coronary computed tomography (CT) angiography. HIV infection was associated with the presence of noncalcified coronary plaque among these men with CAC scores of zero. In a model adjusted only for age, race, centre, and pre- or post-2001 cohort, the prevalence ratio for the presence of noncalcified plaque was 1.27 (95% confidence interval 1.04-1.56; P = 0.02). After additionally adjusting for cardiovascular risk factors, HIV infection remained associated with the presence of noncalcified coronary plaque (prevalence ratio 1.31; 95% confidence interval 1.07-1.6; P = 0.01).
|
We previously found that Dual-specificity phosphatase 6 (Dusp6) over-expression enhanced the growth-promoting effect of estrogen in endometrial adenocarcinoma cells. The aim of this study was to explore the correlation of Dusp6 expression with progestin sensitivity in atypical endometrial hyperplasia (AEH) and earlier endometrial carcinomas (EC). Using immunohistochemistry study, we analyzed the expression of Dusp6 protein in AEH. We found that progestin treatment was effective in 89% of AEH and 50% of EC. Before treatment, Dusp6 expression was significantly higher in progestin-sensitive AEH groups compared with progestin-resistant groups. After treatment, Dusp6 expression was significantly upregulated in progestin-sensitive groups, but not in progestin-resistant groups. Moreover, a high-dose of Dusp6 transfection significantly enhanced progestin-induced growth-inhibition in Ishikawa cells.
|
Is cytologic atypia in the contralateral unaffected breast related to parity and estrogen-related genes?
|
The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1.
|
Nothing by mouth (NPO) is the standard treatment for small-bowel obstruction. Whether oral medications should be prohibited during treatment of adhesive, partial small-bowel obstruction is unclear. The goal of this study was to determine whether a combination of specific oral medications in adhesive, partial small-bowel obstruction will decrease the need for operative intervention. Of 266 consecutive adult patients with partial small-bowel obstruction admitted at a tertiary medical center, 236 were randomized into 2 groups. Group I patients were treated with intravenous hydration, nasogastric tube decompression, and NPO. Group II patients were placed on intravenous hydration, nasogastric tube decompression, and oral fluids incorporating an oral laxative, a digestant, and a defoaming agent. We compared differences between the groups in (1) the number of patients having a successful nonoperative treatment, (2) complications, and (3) recurrence of symptoms. A total of 116 and 120 patients comprised groups I and II, respectively. The number of patients treated successfully by a nonoperative approach was less in group I than in group II (77% vs 90%, P < .01). The complications and recurrence rate for groups I and II did not differ (4% vs 5% and 5% vs 4%, respectively).
|
Is perilipin-5 regulated by statins and controls triglyceride contents in the hepatocyte?
|
Perilipin-5 (PLIN5) is a member of the perilipin family of lipid droplet (LD)-associated proteins. PLIN5 is expressed in oxidative tissues including the liver, and is critical during LD biogenesis. Studies showed that statins reduce hepatic triglyceride contents in some patients with non-alcoholic fatty liver disease and in rodent models of diet-induced hepatosteatosis. Whether statins alter triglyceride synthesis, storage, and/or utilization within the hepatocyte is unknown, though. Here we tested the hypothesis that statins alter the metabolism of LD in the hepatocyte during physiological conditions, such as fasting-induced steatosis. Mice were gavaged with saline or atorvastatin, and the expression of LD-associated genes was determined in fed and fasted animals. The accumulation of triglycerides and LD was studied in mouse or human primary hepatocytes in response to statins, and following knock-down of SREBP2 or PLIN5. We show that statins decrease the levels of PLIN5, but not other LD-associated genes, in both mouse liver and mouse/human primary hepatocytes, which is paralleled by a significant reduction in both intracellular triglycerides and the number of LD. We identify an atypical negative sterol regulatory sequence in the proximal promoter of mouse/human PLIN5 that recruits the transcription factor SREBP2 and confers response to statins. Finally, we show that the statin-dependent reduction of hepatocyte triglyceride contents is mimicked by partial knock-down of PLIN5; conversely, ectopic overexpression of PLIN5 reverts the statin effect.
|
To investigate the possibility of using a modified reverse transfer function (RTF) measurement intraoperatively during surgery of a new transcutaneous bone conduction hearing implant to evaluate the status of the device. Tests were performed on a cadaver skull (preclinically) and two conductive hearing loss patients implanted with a new transcutaneous bone conduction implant. During intraoperative activation, the RTF was measured using a microphone attached perpendicularly and directly to the skin in the middle section of the forehead. The RTF could be measured for all frequencies from 500 to 6, 000 Hz.
|
Does docosahexaenoic acid pretreatment confer neuroprotection in a rat model of perinatal cerebral hypoxia-ischemia?
|
We hypothesized that pretreatment with docosahexaenoic acid (DHA), a potentially neuroprotective polyunsaturated fatty acid, would improve function and reduce brain damage in a rat model of perinatal hypoxia-ischemia. Seven-day-old rats were divided into 3 treatment groups that received intraperitoneal injections of DHA 1, 2.5, or 5 mg/kg as DHA-albumin complex and 3 controls that received 25% albumin, saline, or no injection. Subsequently, rats underwent right carotid ligation followed by 90 minutes of 8% oxygen. Rats underwent sensorimotor testing (vibrissae-stimulated forepaw placing) and morphometric assessment of right-sided tissue loss on postnatal day 14. DHA pretreatment improved forepaw placing response to near-normal levels (9.5 +/- 0.9 treatment vs 7.1 +/- 2.2 controls; normal = 10; P < .0001). DHA attenuated hemisphere damage compared with controls (P = .0155), with particular benefit in the hippocampus with 1 mg/kg (38% protection vs albumin controls).
|
Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis. We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification. The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).
|
Is timing n't everything : an analysis of when to start salvage chemotherapy in ovarian cancer?
|
Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third line agents and to compare these finding to results of GOG 178. We conducted a retrospective parallel study to GOG 178 using identical criteria for PFS definitions. Patients (pts) with stage III-IV cancer achieving a CR following surgery and five to eight cycles of platinum-based CT were identified. Patients not obtaining a CR and those with a CR who underwent second look surgery were excluded. Rather than immediately beginning consolidation CT after CR, second line agents were started at recurrence and were followed by a third line when pts progressed. Clinical-pathologic characteristics were abstracted, and time intervals including time to recurrence, time to use of second line CT, time to use of third line (3rd line) CT, and survival were recorded. Time intervals were studied by Kaplan-Meier method. Of 217 reviewed pts (1991-2001), 59 eligible pts were identified. Forty-nine patients had stage III disease and ten had stage IV. At completion of surgery, 44 were optimally debulked. With a median follow-up of 51 months, the median PFS (from CR) of all patients was 20 months. At 5 years, 36% of pts remain disease-free, and 66% of pts are alive. Twenty-three pts have not received second line agents, and thirty-six have received them. For all pts, the median time from CR to start of second line chemotherapy was 21 months, and the median time to start of third line agents was 43 months. Recurrences occurred after 6 months from completion of first line (1st line) therapy in 87% of cases and after 12 months in 50%.
|
The purpose of this study was to examine how variation in the beta-2 adrenergic receptor gene (ADRB2), in combination with the moderating influences of race, body mass index (BMI), and anger expression style (anger-in, anger-out), affects blood pressure (BP) at rest and in response to acute laboratory stress. Four hundred fifty adolescents (mean age = 18.5 +/- 2.7 years; 228 [124 males] whites and 222 [110 males] blacks completed two stressors (video game challenge, forehead cold pressor). Hemodynamic measures were taken before, during, and after each stressor. Stressors were separated by a 20-minute rest period. Frequency of detrimental haplotype (Gly16/Glu27) carrier status was greater among whites than blacks (p < .05). A significant three-way interaction among haplotype, BMI, and race for resting systolic blood pressure (SBP) found the highest BP level to be among high BMI carriers, but only for whites. A separate three-way interaction was found to be significant for haplotype, anger-in and race such that high anger-in carriers showed the highest level of resting SBP (p < .05) and total peripheral resistance (TPR) (p < .05) and the greatest TPR reactivity to the cold pressor task (p < .01). Post hoc analyses revealed these interactions with anger-in were only present among blacks. No significant interactions with anger-out for either ethnic group were observed.
|
Does intratympanic Iodine Contrast Injection diffuse Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging?
|
Whether the round window membrane (RWM) is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the RWM, enhancing the perilymphatic space. Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately postexposure, and at 1-, 6-, and 24-hour intervals. Postprocessing was accomplished using color ramping and subtraction imaging. After the third method, positive RWM and perilymphatic enhancement were observed with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared with precontrast imaging. The cochlea was measured for attenuation differences compared with pure water, revealing a preinjection average of -1,103 HU and a postinjection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid.
|
To characterize metabolic features of women with polycystic ovary syndrome (PCOS) by exercise behavior and determine relative health benefits of different exercise intensities. Cross-sectional study. Tertiary academic institution. Three hundred and twenty-six women aged 14-52 years-old with PCOS by Rotterdam criteria examined between 2006 and 2013. International Physical Activity Questionnaire (IPAQ) administered to classify patients into three groups based on Department of Health and Human Services (DHHS) Guidelines of vigorous, moderate, and inactive, along with physical examination and serum testing. Blood pressure, body mass index (BMI), waist circumference, fasting lipids, fasting glucose and insulin, 2-hour 75-gram oral glucose tolerance, homeostatic model assessment of insulin resistance (HOMA-IR). The DHHS guidelines for adequate physical activity were met by 182 (56%) women. Compared with moderate exercisers and inactive women, the vigorous exercisers had lower BMI and lower HOMA-IR; higher levels of high-density lipoprotein cholesterol and sex hormone-binding globulin; and a reduced prevalence of the metabolic syndrome. In a multivariate logistic regression analysis controlling for age, BMI, and total energy expenditure, every hour of vigorous exercise reduced a patient's odds of metabolic syndrome by 22% (odds ratio 0.78; 95% confidence interval, 0.62, 0.99).
|
Does clinical trial demonstrate exercise following bariatric surgery improves insulin sensitivity?
|
Roux-en-Y gastric bypass (RYGB) surgery causes profound weight loss and improves insulin sensitivity (S(I)) in obese patients. Regular exercise can also improve S(I) in obese individuals; however, it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I) and other cardiometabolic factors. We conducted a single-blind, prospective, randomized trial with 128 men and women who recently underwent RYGB surgery (within 1-3 months). Participants were randomized to either a 6-month semi-supervised moderate exercise protocol (EX, n = 66) or a health education control (CON; n = 62) intervention. Main outcomes measured included S(I) and glucose effectiveness (S(G)), which were determined from an intravenous glucose tolerance test and minimal modeling. Secondary outcomes measured were cardiorespiratory fitness (VO2 peak) and body composition. Data were analyzed using an intention-to-treat (ITT) and per-protocol (PP) approach to assess the efficacy of the exercise intervention (>120 min of exercise/week). 119 (93%) participants completed the interventions, 95% for CON and 91% for EX. There was a significant decrease in body weight and fat mass for both groups (P < 0.001 for time effect). S(I) improved in both groups following the intervention (ITT: CON vs. EX; +1.64 vs. +2.24 min⁻¹/μU/ml, P = 0.18 for Δ, P < 0.001 for time effect). A PP analysis revealed that exercise produced an additive S(I) improvement (PP: CON vs. EX; +1.57 vs. +2.69 min⁻¹/μU/ml, P = 0.019) above that of surgery. Exercise also improved S(G) (ITT: CON vs. EX; +0.0023 vs. +0.0063 min⁻¹, P = 0.009) compared with the CON group. Exercise improved cardiorespiratory fitness (VO2 peak) compared with the CON group.
|
Clonal typing of neurogenic clones. To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease. Michigan State University; VA Medical Center, Minneapolis, MN, USA. Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR. Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones.
|
Does tamoxifen inhibit transforming growth factor-alpha gene expression in human breast carcinoma samples treated with triiodothyronine?
|
To examine the effects of triiodothyronine (T3), 17beta-estradiol (E2), and tamoxifen (TAM) on transforming growth factor (TGF)-alpha gene expression in primary breast cancer cell cultures and interactions between the different treatments. Patients included in the study (no.=12) had been newly diagnosed with breast cancer. Fresh human breast carcinoma tissue was cut into 0.3- mm slices. These slices were placed in six 35-mm dishes on 2-ml organ culture medium. Dishes received the following treatments: dish 1: ethanol; dish 2: T3; dish 3: T3+TAM; dish 4: TAM; dish 5: E2; dish 6: E2+TAM. TGF-alpha mRNA content was normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. All tissues included in this study were positive for estrogen receptor (ER) and thyroid hormone receptor expression. Treatment with T3 for 48 h significantly increased TGF-alpha mRNA levels compared to controls (15-fold), and concomitant treatment with TAM reduced expression to 3.4-fold compared to controls. When only TAM was added to the culture medium, TGF-alpha mRNA expression increased 5.3-fold, significantly higher than with all other treatment modalities.
|
Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4(+) T cells.
|
Does hSV-1 Infection modulate the Radioresponse of a HPV16-positive Head and Neck Cancer Cell Line?
|
The combined effects of Human papillomavirus (HPV) and Herpes simplex type 1 (HSV-1) infections and their effects on cancer cell radioresistance are unexplored. An HPV16-positive hypopharyngeal carcinoma cell line (UD-SCC-2) was infected with wt-HSV-1 at low multiplicity of infection (MOI) and irradiated with 2 Gy at 24 h postinfection. Viability assays and quantitative reverse-transcriptase PCR for HPV16 E6, E7, nuclear factor kappa B1, B-cell CLL/lymphoma 2 (BCL2), and caspases 3, 8 and 9 at 24, and 72 h, as well as immunocytochemistry for BCL2, caspase 3, cyclin E, mouse double minute 2 homolog (MDM2), HSV-1 and Ki-67 were performed at 144 h postirradiation. At 144 h, cell viability was significantly lowered by irradiation only in uninfected cells. Infection combined with irradiation resulted in increased expression of E6, E7, BCL2 and NF-κB1 at 144 h. Simultaneously, E6 and E7 were down-regulated in non-irradiated infected cells. Irradiation and infection with 0.00001 MOI separately up-regulated caspase 3 but infection with 0.0001 MOI halved its expression in irradiated cells.
|
An association between anthropometric measurements, including waist circumference (WC), and alanine aminotransferase (ALT) levels has been reported among adults. However, studies conducted among population-based elementary schoolchildren to date have been limited, especially in Japan, where the measurement of WC and blood collection are not usually performed in the annual health examination at elementary schools. The present study investigated the association between anthropometric measurements and ALT levels among population-based elementary schoolchildren in Japan. Subjects were fourth-grade schoolchildren (aged 9 or 10) from the town of Ina in Saitama Prefecture, Japan during 2004-2009. The height, weight, and WC of each subject were measured, and blood samples were drawn to measure ALT levels. Childhood overweight or obesity was defined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman's correlation coefficients between anthropometric measurements (body mass index (BMI), WC, and waist-to-height ratio (WHtR)) and ALT levels were calculated. Data from 2499 subjects (1293 boys and 1206 girls) were analyzed. BMI, WC, and WHtR were significantly positively correlated with ALT levels; the correlation coefficient of ALT levels with WHtR was higher than that with BMI and WC in boys and girls. In the analysis stratified by physique (non-overweight/obesity, overweight, or obesity), all anthropometric measurements were significantly positively correlated with ALT levels among boys, while only WHtR was significantly positively correlated with ALT levels among girls. Moreover, the correlation coefficient of ALT levels with WHtR was more pronounced than that with BMI and WC in the non-overweight/obesity group, in the overweight group, and in the obesity group for each sex.
|
Does stat3 signaling activation crosslinking of TGF-β1 in hepatic stellate cell exacerbate liver injury and fibrosis?
|
The role of signal transducer and activator of transcription 3 (Stat3) in liver fibrosis is still controversial. Since hepatic stellate cells (HSCs) and transforming growth factor-β1 (TGF-β1) are central to the fibrogenesis, our goal was to clarify the mechanism of Stat3 crosslinking of TGF-β1 signaling. Stat3, TGF-β1 mRNA and protein expressions were examined in liver tissues of chronic hepatitis B (CHB) patients and diethylinitrosamine (DEN)-induced rat fibrosis model. The effect of Stat3 activation or suppression on TGF-β1 signaling in HSCs was tested in vitro and in vivo. Stat3 expression as well as TGF-β1 was increased in CHB patients and DEN-induced fibrosis rat model. This was strongly correlated with increase in fibrosis staging. TGF-β1, a mediator of fibrosis, was enhanced by Stat3, but suppressed by siRNA-mediated RNA knockdown of Stat3 (siStat3) or Janus kinase 2 inhibitor (AG490) both in vivo and in vitro. Stat3 crosslinking TGF-β1 signaling plays an important role in HSC activation and increasing fibrosis related products. TGF-β1 could not achieve profibrogenic cytokine and anti-apoptosis characteristics without Stat3 activation in HSCs.
|
Behavioural evidence supports the notion that oral glucose ingestion enhances recognition memory judgements based on recollection, but not familiarity. The present study sought to clarify and extend upon these behavioural findings by investigating the influence of glucose administration on event-related potential (ERP) components that are thought to be differentially mediated by recollection and familiarity processes in healthy adolescents. In a within-subjects design, participants performed a recognition memory task, during which time electroencephalogram (EEG) was recorded, subsequent to ingestion of either (a) glucose or (b) placebo in a counterbalanced order. Response times during the recognition memory task were observed to be faster for the glucose condition, relative to a placebo control. Further, glucose ingestion was associated with an enhanced left parietal old/new ERP effect (a marker of recollection) and an enhanced mid-frontal old/new ERP effect (known to be mediated by familiarity).
|
Do [ Endothelial cells promote islet survival and function ]?
|
To investigate islet graft survival and function after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. We isolated ECs, and assessed the viability of isolated islets in a group of standard culture and a group of co-culture with ECs. Then we put the diabetic rats in 4 groups: an islet transplantation group, an islet graft with EC transplantation group, an EC transplantation group, and a PBS control group. Blood glucose and insulin concentrations were measured daily. Cell morphology and cell markers were investigated by immunohistochemical staining and electron microscope. Normal morphology was shown in more than 90% of AO/PI staining positive islets while co-cultured with ECs for 7 days. Insulin release assays showed a significantly higher simulation index co-culture except for the first day (P<0.05). There was a significant difference in concentrations of blood glucose and insulin among the 4 groups after 3 days after the transplantation (P<0.05).
|
Airway hyperresponsiveness (AHR) is associated with persistent air flow limitation and accelerated FEV(1) decline. AHR can influence diagnosis, treatment, and prognosis. We assessed the value of pulmonary function variables, symptoms, and history as selection criteria for methacholine bronchoprovocation testing to detect AHR in symptomatic subjects. Over a 4-year period we conducted a prospective study of consecutive subjects who underwent methacholine bronchoprovocation testing. Baseline pulmonary function testing (PFT) and a questionnaire were obtained prior to methacholine bronchoprovocation testing. PFT and symptom and history variables were assessed as AHR predictors in univariate and multiple logistic regression analyses for the whole group and for 4 different age groups. There were 530 subjects, with ages ranging from 5 to 87 years, and 232 (44%) were positive for methacholine AHR. AHR was more prevalent among subjects < or = 25 years old (59%) and > 65 years old (47%) than among the other age groups. PFT values, symptom, and history variables had different AHR predictive values among the different age groups. Symptom and history variables had no AHR predictive value among subjects < or = 25 or > 65 years old.
|
Does pentoxifylline prevent a decrease in arterial oxygen tension in oleic acid-induced lung injury?
|
a) To determine whether pentoxifylline has a preventive effect on the decrease in PaO2 that is caused by oleic acid, and whether pentoxifylline facilitates normalization of PaO2 from the decreased state. b) To examine whether pentoxifylline can attenuate an increase in pulmonary vascular permeability that is induced by oleic acid. Prospective trial. University laboratory. a) A total of 48 guinea pigs (700 to 1100 g) for blood gas analysis. b) A total of 28 guinea pigs (390 to 670 g) for measurement of pulmonary vascular permeability. a) For blood gas analysis, the guinea pigs were mechanically ventilated. Oleic acid (15 microL/kg) was injected into the guinea pigs to decrease PaO2. Pentoxifylline (5 or 20 mg/kg) was administered 40 or 3 mins before oleic acid injection or 13 mins after oleic acid injection. b) For measurement of pulmonary vascular permeability, the guinea pigs were anesthetized with pentobarbital and catheterized via the external jugular vein for drug administration. Pentoxifylline (20 mg/kg) plus Evans blue (30 mg/kg) or theophylline (20 mg/kg) plus Evans blue (30 mg/kg) were administered at 40- and 1-min intervals before oleic acid (15 microL/kg) injection, respectively. Perfusion with saline was performed through the aorta 90 mins after the oleic acid injection. The airways were removed and separated into the trachea, the main bronchus, the proximal bronchus, and the distal bronchus. Evans blue was extracted from the airways with formamide for 18 hrs and measured. a) We measured PaO2, PaCO2, and pH, and recorded airway pressure and systemic blood pressure at 15, 10, and 5 mins before oleic acid injection and at 6, 10, 15, 35, 55, and 75 mins after oleic acid injection. Compared with the control groups, a decrease in PaO2 by oleic acid was significantly prevented when pentoxifylline (5 or 20 mg/kg) was administered 40 mins before oleic acid injection. However, a decrease in PaO2 by oleic acid was not significantly reduced when pentoxifylline was administered 3 mins before oleic acid injection. Pentoxifylline administered 13 mins after oleic acid injection did not affect the recovering course of PaO2 significantly. b) An increase in pulmonary vascular permeability by oleic acid was significantly attenuated by both pentoxifylline and theophylline. The effect of theophylline was significantly stronger than the effect of pentoxifylline in the main bronchi. The effect of theophylline was not significantly different from the effect of pentoxifylline in other areas.
|
Low back pain (LBP) and sciatica are usually caused by degenerative disc disease (DDD). Although they are common, the etiology of these conditions is poorly understood. A large population case-control study in the Southern Chinese was performed to study genetic risk factors to DDD. To gain a better understanding of the etiology of DDD in relation to structural defects of the intervertebral disc. A Finnish study found an association between LBP and sciatica with two variants of the alpha-chains of collagen IX, encoded by the Trp2 and Trp3 alleles, representing Gln326Trp and Arg103Trp amino acid substitutions in the COL9A2 and COL9A3 genes, respectively. Trp2 was found only in affected individuals (4%), whereas Trp3 was present in both affected (24%) and unaffected (9%) individuals. Because of the low frequency of the Trp2 allele in whites, the significance and contribution of this allele to DDD are not known. Using more objective criteria to define the disease by magnetic resonance imaging (MRI), we tested these alleles for association with DDD in a large population study. Lumbar DDD, the presence of anular tears, and disc and endplate herniations were defined by MRI in 804 Southern Chinese volunteers 18 to 55 years of age. These were correlated with the frequencies of the Trp2 and Trp3 alleles. The Trp2 allele was present in 20% of the population and was associated with a fourfold increase in the risk of developing anular tears at 30 to 39 years and a 2.4-fold increase in the risk of developing DDD and endplate herniations at 40 to 49 years. Affected Trp2 individuals had more severe degeneration. The Trp3 allele was absent from the Southern Chinese population.
|
Does maslinic acid activate mitochondria-dependent apoptotic pathway in cardiac carcinoma?
|
Cardiac carcinoma is the most common subtype of gastric cancer and its incidence has increased in recent years. The current chemotherapeutic drugs exhibit limited effectiveness and significant side effects in patients. Maslinic acid (MA) exerts an anti-tumor activity on a wide range of cancers and has no significant side effect; however, the anti-tumor effect of MA on cardiac carcinoma has not yet been explored. MTT assays, tumor xenograft animal model, immunoblotting, MMP assessment and flow cytometry were performed in this study. MA was able to suppress the viability of cardiac carcinoma cells in both a time- and dose-dependent manner. This natural compound exhibited no cytotoxicity in normal cells. Its inhibitory effect on tumor growth was further confirmed in a mouse model. Mechanistically, MA induced the activation of p38 MAPK in cardiac carcinoma cells and, in turn, changed their mitochondrial membrane potential (MMP). Finally, caspase cascades were activated by a series of cleavages, leading to apoptosis in cardiac cancer cells. Inhibition of p38 MAPK signaling was able to rescue the effect of MA on cardiac carcinoma cells.
|
Various surgical techniques to treat posterolateral knee instability have been described. To date, the recommended treatment is an anatomic form of reconstruction in which the 3 key structures of the posterolateral corner (PLC) are addressed: the popliteofibular ligament, the popliteus tendon, and the lateral collateral ligament. The purpose of this study was to identify the role of each key structure of the PLC in kinematics of the knee and to biomechanically analyze a single-graft, fibular-based reconstruction that replicates the femoral insertions of the lateral collateral ligament and popliteus to repair the PLC. The hypothesis was that knee kinematics can be reasonably restored using a single graft with a 2-strand "modified Larson" technique. Descriptive laboratory study. Eight fresh-frozen cadaveric knees were used in this study. We conducted sequential sectioning of the popliteofibular ligament (PFL) and then subsequently the popliteal tendon (PT), the lateral collateral ligament (LCL), and the anterior cruciate ligament (ACL). We then reconstructed the ACL first and then the posterolateral corner using the modified Larson technique. A surgical navigation system was used to measure varus laxity and external rotation at 0°, 30°, 60°, and 90° with a 9.8-N·m varus stress and 5-N·m external rotation force applied to the tibia. In extension, varus laxity increased only after the sectioning of the lateral collateral ligament. At 30° of flexion, external rotation in varus and translation of the lateral tibial plateau increased after the isolated popliteofibular ligament section. From 60° to 90° of flexion, translation and mobility of the lateral plateau section increased after sectioning of the PFL. After reconstruction, we observed a restoration of external varus rotation in extension and translation of the lateral tibial plateau at 90° of flexion. This technique provided kinematics similar to the normal knee.
|
Does hypoxia-conditioned media allow species-specific attraction of bone marrow stromal cells without need for recombinant proteins?
|
In vivo tissue regeneration depends on migration of stem cells into injured areas, their differentiation into specific cell types, and their interaction with other cells that are necessary to generate new tissue. Human mesenchymal stem cells, a subset of bone marrow stromal cells (BMSCs), can migrate and differentiate into osteoblasts in bone tissue. This can be facilitated by recombinant growth factors and cytokines. In many animal species, the availability of genomic sequences, recombinant proteins, and/or antibodies is limited so that new approaches are needed to generate resources that facilitate migration of stem cells into tissue defect areas. Here we used bone marrow stromal cells of human, ovine, equine, and canine origin to generate hypoxia-conditioned media (HCM) in order to attract BMSCs of the respective species in migration assays. We show that HCM contain attractors even more potent than vascular endothelial growth factor and can therefore be used in many animal species without the need for purified proteins.
|
Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI. We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks. When reflux symptoms occurred less than once per week, the dose of lansoprazole was decreased to 15 mg/day, but if symptoms then occurred more than once per week, it was restored to 30 mg/day. CYP2C19 genotypes were classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). In 18 of 54 RMs, 28 of 56 IMs, and 8 of 14 PMs, the maintenance dose of lansoprazole was decreased to 15 mg/day, but in 16 (88.9%), 22 (78.6%), and 4 (50%), respectively, there was symptomatic recurrence of GERD and the dose was restored to 30 mg/day. The hazard ratios of symptomatic recurrence of GERD in IMs and PMs compared with RMs were 0.40 (95%CI: 0.19-0.87, P = 0.021) and 0.19 (95%CI: 0.05-0.69, P = 0.011).
|
Does monocyte chemoattractant protein-1 secreted by adipose tissue induce direct lipid accumulation in hepatocytes?
|
For many years, adipose tissue has been mainly considered as an inert reservoir for storing triglycerides. Since the discovery that adipocytes may secrete a variety of bioactive molecules (hormones, chemokines, and cytokines), an endocrine and paracrine role for white adipose tissue (WAT) in the regulation of energy balance and other physiological processes has been established, particularly with regard to brain and muscle. In contrast, little is known about the interactions of WAT with liver. Hence, we examined the effect of the secretory products of WAT on hepatocytes. Conditioned medium of human WAT explants induced significant steatosis in hepatocyte cell lines. Factor(s) responsible for the conditioned medium-induced steatosis were screened by a battery of blocking antibodies against different cytokines/chemokines shown to be secreted by WAT. In contrast to interleukin-8 and interleukin-6, the monocyte chemoattractant protein-1 was capable of inducing steatosis in hepatocytes in a time-dependent manner at concentrations similar to those found in conditioned medium. Incubation of conditioned medium with antimonocyte chemoattractant protein-1 antibodies prevented triglyceride accumulation. Investigation of the mechanism leading to the triglyceride accumulation showed that both a diminution of apolipoprotein B secretion and an increase in phosphoenolpyruvate carboxykinase messenger RNA may be involved.
|
A previous systematic review showed that atraumatic restorative treatment (ART) can be an option to restore the occlusoproximal cavities in primary teeth; however, few studies fulfilled the criteria of inclusion to generate a high level of evidence. To update the existing systematic review and address questions regarding survival rate of ART restorations compared to the conventional approach in occlusoproximal cavities in primary molars. The search was extended beyond the original search through the PubMed/MEDLINE database up to February 2016. Furthermore, Web of Science and EMBASE were searched. The inclusion criteria were subjects related to the scope of the systematic review. After selection by title and abstract, potentially eligible articles were read in full and included in accordance with exclusion criteria. Meta-analysis was carried out with the outcome being the survival rate of restorations. The search strategy identified 560 potentially relevant studies, in addition to 127 from the original systematic review. A total of four articles were included in the qualitative and quantitative analyses. Meta-analysis showed no statistically significant difference between ART and conventional approaches in survival rate of occlusoproximal cavities (OR = 0.887, 95% CI: 0.574-1.371).
|
Does electroporation-mediated transfer of plasmid DNA encoding IL-10 attenuate orthotopic tracheal allograft stenosis in rats?
|
Electroporation has been shown to increase the efficacy of intramuscular injection of plasmid DNA, resulting in a higher level of foreign gene expression. Using this technique, we examined the effect of viral IL-10 gene transfer on the prevention of tracheal allograft stenosis in an animal model. On the day of tracheal transplantation, recipient Lewis rats were intramuscularly injected with either plasmid pCAGGS-LacZ or plasmid pCAGGS-viral IL-10, followed immediately by electroporation. Tracheas from Brown Norway donors were transplanted into the backs of Lewis recipients, and the histology of the grafts were assessed 2 and 4 weeks after transplantation. The serum level of IL-10 peaked at 2000 pg/ml one day after injection; the level then slowly decreased, but was maintained above 1000 pg/ml until 8 days after injection. At Day 28, the airway lumina of the tracheal allografts were almost completely obliterated by fibroproliferative tissue in the control pCAGGS-LacZ-treated rats. In rats injected once with pCAGGS-viral IL-10, luminal obliteration was significantly decreased compared with the control pCAGGS-LacZ-treated rats (mean luminal opening 46.8% vs 0% p<0.05). The loss of epithelial cells lining the airway was also decreased in the IL-10-treated group (mean epithelial coverage 42% vs 5% p<0.05). Multiple injections with pCAGGS-viral IL-10 did not further improve the histological changes.
|
Both the FRAX and Garvan calculators are used to estimate absolute risk of fracture, but they sometimes produce different estimates. We sought to determine which patient characteristics contribute to these discrepancies. Ten-year hip fracture risk was estimated for 122 women, using both FRAX and Garvan with bone mineral density (BMD). Differences in estimates of hip fracture were assessed, both in absolute terms and with respect to a treatment threshold of 3%. Garvan estimates were higher than FRAX estimates across the range of ages and BMDs studied. A history of falls or of multiple fractures increased risk calculated by Garvan 3-6-fold, but did not account for all differences between calculators. Discrepancies around a 3% treatment threshold occurred in 31/122 (25%). Women aged 70-74 years, and women with osteopenia were most likely to have discordant estimates. Most discordant estimates (29/31) had a Garvan estimate ≥ 3% and FRAX <3%. Falls, multiple fractures, ethnicity and a history of parental hip fracture contributed to some discordant estimates.
|
Does music reduce patient anxiety during interfacility ground critical care transport?
|
Interfacility ground critical care transport (CCT) of patients by ambulance may be stressful. This study evaluated whether playing music during CCT reduces patient anxiety and whether objective evidence is manifested by a change in vital signs. Urban teaching hospital. In this prospective cohort study, music was played for eligible adult patients during CCT while recording vital signs. A questionnaire was subsequently mailed to patients to rate whether the ambulance transport was stressful, the impact music had on transport, whether music changed their anxiety, whether music made them comfortable and relaxed, and whether they would prefer music to be played on future transports. Vital signs were compared between respondents who perceived transport as stressful and those who did not. One hundred two patients were enrolled; 23 respondents (22.5%) constituted the study group. Four patients (17.4%) reported CCT as stressful (average response, 4.75). Nineteen (82.6%) rated CCT as not stressful (average response, 1.63). Subjectively, patients reported a positive impact of music on transport, with improved comfort and relaxation but only a minimal decrease in anxiety. No statistically significant change in vital signs was observed between cohorts; too few patients were enrolled to generate power to detect any difference.
|
Insulin- and insulin growth factor-1 stimulated signaling through the insulin receptor substrate-1 (IRS-1) promotes hepatocellular proliferation and survival. IRS-1 over-expression in transgenic (Tg) mouse livers caused constitutive activation of Erk mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) resulting in significantly increased levels of DNA synthesis and larger hepatic masses relative to non-transgenic (non-Tg) littermates. However, the livers eventually ceased to grow but remained approximately 25% larger than non-Tg livers. We hypothesized that this growth homeostasis was achieved by parallel activation of pro-apoptosis pathways. Since Fas-mediated apoptosis is a common mechanism of hepatocyte destruction, we investigated the potential role of Fas receptor as a regulator of hepatic mass in IRS-1 transgenic mice. Significantly increased Fas-receptor levels were detected in the livers of IRS-1 Tg compared to non-Tg mice by Western blot analysis. Functional activation of Fas-receptor in IRS-1 Tg livers was demonstrated by increased hepatocellular apoptosis caused by intravenous injection of anti-Fas (Jo-2).
|
Does [ Indirubin inhibit the proliferation of prostate cancer PC-3 cells ]?
|
To explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms. We measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot. The viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.
|
To determine whether nonoperative management of splenic and hepatic injury in the multiply injured pediatric and adolescent patient is both safe and efficacious. Retrospective case series. Level 1 trauma center. All patients younger than 19 years old who suffered trauma to the spleen or liver between February 1978 and December 1991 (n = 103) were retrospectively identified by a trauma registry. These patients were divided into three groups: the group as a whole, those suffering multiple injuries, and those suffering either head injury or injury remote from the abdomen that required operative repair. Injury severity and outcome within each group of patients were compared based on whether the splenic or hepatic injury was managed operatively or nonoperatively. Mean Injury Severity Scores among the multiply injured patients were not different depending on whether the splenic or hepatic injury was managed nonoperatively or operatively. Except for a higher incidence of transfusion requirement among patients who were treated operatively, measures of morbidity among the multiply injured patients did not differ based on treatment. The success rates of nonoperative treatment among all patients, those with multiple injuries, and those with either head injury or remote injury that required surgery were 94%, 90%, and 86%, respectively.
|
Are serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities related to overweight and cardiovascular risk factors in adolescents?
|
The objective of this study was to describe the relation of serum fatty acids and desaturase activity (DA) to overweight, insulin sensitivity and cardiovascular disease (CVD) risk factors in adolescents. The relations of % serum phospholipid (PL) and cholesteryl ester (CE) fatty acids and estimated DA with CVD risk factors were examined in 264 adolescents (average age 15 years). Fatty acids were determined by gas liquid chromotography. Surrogate measures of DA were expressed as ratios of serum fatty acids: Delta9 DA=16:0/16:1; Delta6 DA=20:3,n6/18:2,n6 (PL) or 18:3,n6/18:2,n6 (CE); and Delta5 DA=20:4,n6/20:3,n6. Spearman partial correlations of fatty acids (%) and DA ratios with CVD risk factors were reported, adjusting for age, sex, race, Tanner stage, energy intake and physical activity. Overweight adolescents compared to normal weight had more adverse levels of CVD risk factors, composition of PL and CE fatty acids in serum, and Delta6 DA and Delta5 DA ratios. Linoleic acid was inversely related to body mass index (BMI), waist circumference and triglycerides (P<or=0.01). Dihomo-gamma-linolenic acid was positively related to BMI, waist, insulin, and triglycerides, and inversely related to high-density lipoprotein-cholesterol levels (P<or=0.01). Delta6 DA was adversely associated with most of the risk factors (P<or=0.01), whereas triglycerides and fasting insulin were beneficially related to Delta5 DA (P<or=0.01).
|
We have demonstrated that in some human cancer cells both chronic mild heat and ionizing radiation exposures induce a transient block in S and G2 phases of the cell cycle. During this delay, cyclin B1 protein accumulates to supranormal levels, cyclin B1-dependent kinase is activated, and abrogation of the G2/M checkpoint control occurs resulting in mitotic catastrophe (MC). Using syngenic mouse embryonic fibroblasts (MEF) with wild-type or mutant p53, we now show that, while both cell lines exhibit delays in S/G2 phase post-irradiation, the mutant p53 cells show elevated levels of cyclin B1 followed by MC, while the wild-type p53 cells present both a lower accumulation of cyclin B1 and a lower frequency of MC.
|
Do pilot study of glaucoma drainage implant surgery supplemented with reticulated hyaluronic acid gel in severe glaucoma?
|
This pilot study, the first of its type, was conducted to determine the clinical outcome of glaucoma drainage implant (GDI) surgery supplemented with injectable crosslinked hyaluronic acid (HA) in patients with severe glaucoma. This was a retrospective chart study involving 10 eyes of 10 patients with severe glaucoma (glaucomatous visual field loss worse than -20 dB) who had previously undergone GDI surgery supplemented with crosslinked HA with a 2-year follow-up. Surgical success was defined as intraocular pressure (IOP) <21 mm Hg with a reduction of ≥40% (definition A) or ≥50% (definition B) from baseline IOP on 2 consecutive follow-up visits, IOP >5 mm Hg on 2 consecutive follow-up visits, and neither reoperation of glaucoma nor loss of light perception vision. The mean ± SD baseline IOP before GDI was 38.5 ± 10.7 mm Hg, and the mean IOP at the last follow-up visit was 13.0 ± 5.0 mm Hg, with a mean pressure drop of 24.4 ± 10.9 mm Hg (62%; p = 0.005). According to definition A, life-table analysis showed an overall success rate of 80%, while according to definition B, the success rate was 50% after 24 months of follow-up. Complications were infrequent and not serious. No complications resulting from the reticulated HA therapy itself were observed.
|
Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles.
|
Does incentive spirometry enhance recovery after thoracic surgery?
|
To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. Randomized controlled trial. University hospital, intensive care unit, and surgical department. Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay.
|
Alzheimer's disease (AD) is characterized by neurodegeneration and changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Owing to varying APP processing, several beta-amyloid peptides (Abeta) are generated. In contrast to the form with 40 amino acids (Abeta40), the variant with 42 amino acids (Abeta42) is thought to be the pathogenic form triggering the pathological cascade in AD. While total-Abeta effects have been studied extensively, little is known about specific genome-wide effects triggered by Abeta42 or Abeta40 derived from their direct precursor C99. A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated Abeta peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference. Here we studied the transcriptomic and proteomic responses to increased or decreased Abeta42 and Abeta40 levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed Abeta42- and Abeta40-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased Abeta42/Abeta40 ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the Abeta42/Abeta40 ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.
|
Does the indole derivative NecroX-7 improve nonalcoholic steatohepatitis in ob/ob mice through suppression of mitochondrial ROS/RNS and inflammation?
|
Nonalcoholic steatohepatitis (NASH) is associated with cirrhosis and hepatocellular carcinoma. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play key roles in the development of the disease. However, the therapeutic target of NASH has not been fully defined and new treatments are needed. We investigated the protective effects of the antioxidant indole-derived NecroX-7 in a NASH mouse model using leptin-deficient ob/ob and methionine- and choline-deficient (MCD) diet-fed ob/ob mice. Six-week-old male mice were divided into three groups: ob/+ mice, ob/ob mice treated with vehicle and ob/ob mice treated daily with NecroX-7 (20 mg/kg) for 4 weeks. To study the effects of NecroX-7 in a fibrosis model, NASH was induced by feeding ob/ob mice an MCD diet. The effects of NecroX-7 on NASH progression were evaluated using biochemical, histological and molecular markers. NecroX-7-treated ob/ob mice had a marked decrease in serum aspartate aminotransferase and alanine transaminase compared with vehicle-treated controls. Interestingly, hepatic steatosis and lipid peroxidation were significantly improved by NecroX-7 treatment. NecroX-7 inhibited tert-butylhydroperoxide- and H2 O2 -induced mitochondrial ROS/RNS in primary hepatocytes and attenuated mitochondrial dysfunction in vitro and in vivo. Furthermore, NecroX-7-treated mice exhibited fewer infiltrating macrophages and reduced hepatic tumour necrosis factor-alpha expression. Hepatic fibrosis in MCD-fed ob/ob mice was significantly decreased by NecroX-7 treatment.
|
Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs. To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses. In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7).
|
Does the Microcuff tube allow a longer time interval until unsafe cuff pressures are reached in children?
|
To compare cuff pressures during nitrous oxide exposure in the new Microcuff pediatric tracheal tube (MPT) with ultrathin high volume - low pressure polyurethane cuff to a tube with a standard polyvinyl chloride (PVC) cuff. With approval of the local Ethics Committee, 30 pediatric patients requiring tracheal intubation [tube size internal diameter (ID) 4.0 mm, or ID 7.0 mm) were included. Patients were randomly divided in three groups: A) MPT, baseline cuff pressure 20 cm H(2)O; B) PVC, baseline cuff pressure 20 cm H(2)O; and C) MPT, baseline cuff pressure set to sealing pressure. Anesthesia technique and ventilator settings were standardized. The time required for cuff pressure to increase to 25 cm H(2)O was recorded and pressure reduced to baseline. The number of gas removals required during the first hour was noted. Data are median (range). Groups were compared by the Kruskal-Wallis test (P < 0.05). There were no differences between groups in patient characteristics. PVC and MPT cuffs inflated to a baseline pressure of 20 cm H(2)O were similar regarding the time to first removal of gas [A: nine minutes (4-24), B: eight minutes (4-46)], and number of removals required [A: four (2-6), B: three (1-5)]. In MPT with baseline pressure set to sealing pressure [10 cm H(2)O (8-14)] time to first gas removal and number of removals were significantly less (P < 0.05).
|
The purpose of the study is to evaluate the associations between polymorphisms of the human SA (SAH) gene, an acyl-CoA synthetase gene, with dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal women. One hundred and forty-two postmenopausal women were recruited for the study. Each subject received anthropometric and blood pressure measurements, fasting sampling for lipids, and a 75-g oral glucose tolerance test for insulin resistance. Genotypes of two polymorphisms in the promoter region (c.-962ins/del, c.-451G>A), one missense variant (c.1077G>C, p.K359N) in exon 8, and one in intron 12 (A>G) of the SAH gene, were determined. There were significant differences in genetic distribution of the SAH gene promoter I/D polymorphism between the two groups of subjects by non-high-density lipoprotein cholesterol (non-HDL-C) levels (p=0.004). The subjects with the DD genotype was associated with high levels of non-HDL-C (>160 mg/dL) as compared with the ID or II genotypes (p=0.002). Furthermore, three haplotypes were constructed based on the promoter I/D and the exon 8 G/C polymorphisms. Homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the post menopausal women. The subjects with haplotype 3 had double the risk to have higher non-HDL-C levels than those with haplotype 1.
|
Does above 5 cm , size matter anymore in patients with hepatocellular carcinoma?
|
Solitary hepatocellular carcinoma (HCC) is a good candidate for surgical resection. However, the significance of the size of the tumor in solitary HCC remains unclear. The aim of this study was to evaluate the impact of tumor size on overall and recurrence-free survival of patients with solitary HCC. We retrospectively reviewed 616 patients with histologically confirmed solitary HCC who underwent curative surgical resection between 1994 and 2010. The characteristics and prognosis of patients with HCC were analyzed stratified by tumor size. A total of 403 patients (65 %) had tumors <5 cm, 172 (28 %) had tumors between 5 and 10 cm, and 41 (7 %) had tumors >10 cm. The incidence of microvascular invasion, satellite nodules, and advanced tumor grade significantly increased with tumor size. The 5-year overall and recurrence-free survival rates of HCC <5 cm were 69.6 % and 32 %, respectively, which were significantly better than those of HCC between 5 and 10 cm (58 % and 26 %, respectively) and HCC >10 cm (53 % and 24 %, respectively). On multivariate analysis, cirrhosis (p = 0.0307), Child-Pugh B (p = 0.0159), indocyanine green retention rate at 15 min >10 % (p = 0.0071), microvascular invasion (p < 0.0001), and satellite nodules (p = 0.0009) were independent predictors of poor survival, whereas tumor size >5 cm was not.
|
In the absence of humidity receptors in human skin, the perception of skin wetness is considered a somatosensory experience resulting from the integration of temperature (particularly cold) and mechanical inputs. However, limited data are available on the role of the temperature sense. Wet and dry stimuli at 4°C and 8°C above local skin temperature were applied on the back of seven participants (age 21 ± 2 years) while skin temperature and conductance, thermal and wetness perceptions were recorded. Resting local skin temperature was always increased by the application of the stimuli (+0.5-+1.4°C). No effect of stimulus wetness was found on wetness perceptions (P > 0.05). The threshold (point '-2 slightly wet' on the wetness scale) to identify a clearly perceived wetness was never reached during any stimulations and participants did not perceive that some of the stimuli were wet. Overall, warm temperature stimuli suppressed the perception of skin wetness.
|
Does prevalence and correlate of Myocardial Scar in a US Cohort?
|
Myocardial scarring leads to cardiac dysfunction and poor prognosis. The prevalence of and factors associated with unrecognized myocardial infarction and scar have not been previously defined using contemporary methods in a multiethnic US population. To determine prevalence of and factors associated with myocardial scar in middle- and older-aged individuals in the United States. The Multi-Ethnic Study of Atherosclerosis (MESA) study is a population-based cohort in the United States. Participants were aged 45 through 84 years and free of clinical cardiovascular disease (CVD) at baseline in 2000-2002. In the 10th year examination (2010-2012), 1840 participants underwent cardiac magnetic resonance (CMR) imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at baseline and year 10. Logistic regression models were used to estimate adjusted odds ratios (ORs) for myocardial scar. Cardiovascular risk factors, CAC scores, left ventricle size and function, and carotid intima-media thickness. Myocardial scar detected by CMR imaging. Of 1840 participants (mean [SD] age, 68 [9] years, 52% men), 146 (7.9%) had myocardial scars, of which 114 (78%) were undetected by electrocardiogram or by clinical adjudication. In adjusted models, age, male sex, body mass index, hypertension, and current smoking at baseline were associated with myocardial scar at year 10. The OR per 8.9-year increment was 1.61 (95% CI, 1.36-1.91; P < .001); for men vs women: OR, 5.76 (95% CI, 3.61-9.17; P < .001); per 4.8-SD body mass index: OR, 1.32 (95% CI, 1.09-1.61, P = .005); for hypertension: OR, 1.61 (95% CI, 1.12-2.30; P = .009); and for current vs never smokers: 2.00 (95% CI, 1.22-3.28; P = .006). Age-, sex-, and ethnicity-adjusted CAC scores at baseline were also associated with myocardial scar at year 10. Compared with a CAC score of 0, the OR for scores from 1 through 99 was 2.4 (95% CI, 1.5-3.9); from 100 through 399, 3.0 (95% CI, 1.7-5.1), and 400 or higher, 3.3 (95% CI, 1.7-6.1) (P ≤ .001). The CAC score significantly added to the association of myocardial scar with age, sex, race/ethnicity, and traditional CVD risk factors (C statistic, 0.81 with CAC vs 0.79 without CAC, P = .01).
|
Ephrin ligands and Eph receptors play important roles for cell behavior and movement by transducing bidirectional signaling into interacting cells. Since we found that the expression of ephrinB2 in the hematopoietic progenitor cell line was changed by coculture with stromal cells, we tried to examine the function of ephrinB2 in the hematopoietic microenvironment. Expression of ephrinB2 was measured by flow cytometry and reverse transcriptase polymerase chain reaction in the bone marrow (BM) hematopoietic cells and the stroma-dependent hematopoietic cell line (DFC-28) cocultured with stromal cells. Effect of ephrinB2 on the cells' behavior was monitored by overexpression of ephrinB2 cDNA in mouse pre-B-cell line (70z/3). EphrinB2 expression in DFC-28 cells was modulated by two different stromal cells; ephrinB2 expression was high in DFC-28 cells when cocultured with MSS62 cells, whereas it was low when they were cocultured with TBR31-1 cells. Expression of EphB4, a receptor for ephrinB2, was detected in MSS62 cells but not in TBR31-1 cells. Similarly, BM hematopoietic cells did not express ephrinB2, but most of the BM cells expressed ephrinB2 after coculture with stromal cells. Ectopic expression of ephrinB2 in 70z/3 cells acquires specific binding to EphB4 and leads to significant decline in the locomotive activity underneath stromal cells.
|
Is long-chain fatty acid uptake upregulated in omental adipocytes from patients undergoing bariatric surgery for obesity?
|
To determine the impact of obesity on adipocyte cell size and long-chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic abdominal surgery. A total of 10 obese patients (BMI 49.8+/-11.9 (s.d.) kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI 24.2+/-2.3 kg/m(2)) undergoing other clinically indicated laparoscopic abdominal surgical procedures. Cell size distribution and [(3)H]oleic acid uptake kinetics were studied in adipocytes isolated from omental fat biopsies obtained during surgery. Adipocyte surface area (SA) was calculated from the measured cell diameters. Plasma leptin and insulin concentrations were measured by RIA in fasting blood samples obtained on the morning of surgery. The mean SA of obese adipocytes (41 508+/-5381 mu(2)/cell) was increased 2.4-fold compared to that of nonobese adipocytes (16 928+/-6529 mu(2)/cell; P<0.01). LCFA uptake in each group was the sum of saturable and nonsaturable components. Both the V(max) of the saturable component (21.3+/-6.3 vs 5.1+/-1.9 pmol/s/50,000 cells) and the rate constant k of the nonsaturable component (0.015+/-0.002 vs 0.0066+/-0.0023 ml/s/50 000 cells) were increased (P<0.001) in obese adipocytes compared with nonobese controls. When expressed relative to cell size, V(max)/mu(2) SA was greater in obese than nonobese adipocytes (P<0.05), whereas k/mu(2) SA did not differ between the groups.
|
More and more experiments have shown that transcription and mRNA processing are not two independent events but are tightly coupled to each other. Both promoter and transcription rate were found to influence alternative splicing. More than half of human genes have alternative promoters, but it is still not clear why there are so many alternative promoters and what their biological roles are. In this study, we explored whether there is a functional correlation between alternative promoters and alternative splicing by a genome-wide analysis of human and mouse genes. We constructed a large data set of genes with alternative promoter and alternative splicing annotations. By analyzing these genes, we showed that genes with alternative promoters tended to demonstrate alternative splicing compare to genes with single promoter, and, genes with more alternative promoters tend to have more alternative splicing variants. Furthermore, transcripts from different alternative promoters tended to splice differently.
|
Are anticytomegalovirus antibody titres associated with caregiving burden in younger caregivers?
|
This analysis examines whether or not younger caregivers, parents of children with developmental disabilities, differed from controls in terms of cytomegalovirus (CMV) seropositivity and CMV-specific antibody titre. Secondly, it examined whether any particular socio-demographics, health behaviours, or psychological/caregiving variables were associated with a higher CMV antibody titre among caregivers. Young caregivers and age- and sex-matched controls were compared with respect to their reported health behaviour and psychosocial status as well as latent virus control. One hundred and seventeen parents of children with developmental disabilities and 52 control parents completed standard measures of health behaviours, socio-demographics, perceived stress, depression and anxiety, caregiver burden, child problem behaviours. They also provided a blood sample assayed for the presence of CMV-specific antibody. Caregivers were no more likely to be CMV positive than controls and did not have higher antibody titres against CMV. In addition, there was no association between CMV antibody titre in seropositive caregivers and any of the psychological/caregiving variables. However, higher CMV antibody titres were significantly associated with a higher BMI, lower exercise levels, smoking, and lower fruit and vegetable and fat intake among seropositive caregivers.
|
Metastatic bone disease is one of the major causes of morbidity and mortality in prostate cancer patients. Bisphosphonates are currently used to inhibit bone resorption and reduce tumor-induced skeletal complications. More effective bisphosphonates would enhance their clinical value. We tested several bisphosphonates in a green fluorescent protein (GFP)-expressing human prostate cancer nude mouse model. The in vivo effects of four bisphosphonates, including pamidronate, etidronic acid, and olpadronate, on bone tumor burden in mice intratibially inoculated with PC-3-GFP human prostate cancer cells were visualized by whole-body fluorescence imaging and X-ray. The PC-3-GFP cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC-3-GFP cell growth was monitored by GFP fluorescence and the bone destruction was evaluated by X-ray. We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography. The GFP tumor area and X-ray score significantly correlated. Reduced tumor growth in the bone was accompanied by reduced serum calcium, parathyroid hormone-related protein, and osteoprotegerin.
|
Does intratumoral coadministration of hyaluronidase enzyme and oncolytic adenoviruses enhance virus potency in metastatic tumor models?
|
Evaluate the codelivery of hyaluronidase enzyme with oncolytic adenoviruses to determine whether it improves the spread of the virus throughout tumors, thereby leading to a greater overall antitumor efficacy in tumor models. The optimal dose of hyaluronidase that provided best transduction efficiency and spread of a green fluorescent protein (GFP)-expressing adenovirus within tumors was combined with oncolytic viruses in tumor models to determine whether the combination treatment results in an improvement of antitumor efficacy. In mice injected with the adenovirus Ad5/35GFP and an optimal dose of hyaluronidase (50 U), a significant increase in the number of GFP-expressing cells was observed when compared with animals injected with virus only (P < 0.0001). When the oncolytic adenoviruses Ad5OV or Ad5/35 OV (OV-5 or OV5T35H) were codelivered with 50 U of hyaluronidase, a significant delay in tumor progression was observed, which translated into a significant increase in the mean survival time of tumor-bearing mice compared with either of the monotherapy-treated groups (P < 0.0001). Furthermore, the mice that received the combination of Ad5/35 OV and hyaluronidase showed the best antitumor efficacy. Importantly, the combination treatment did not increase the metastatic potential of the tumors. Lastly, the increase in virus potency observed in animals injected with both enzyme and virus correlated with enhanced virus spread throughout tumors.
|
To understand whether the relationship between young children's autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS reactivity at 3.5-5 years of age, and whether zBMI predicts later ANS reactivity or whether early ANS reactivity predicts later zBMI, was studied. Low-income, primarily Latino children (n=112) were part of a larger cohort study of mothers recruited during early pregnancy. Study measures included maternal prenatal weight, children's health behaviors (i.e., time watching television, fast food consumption, and time playing outdoors), children's height and weight at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS measures of sympathetic nervous system (i.e., pre-ejection period) and parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were monitored during rest and four challenges. Reactivity was calculated as the difference between mean challenge response and rest. Structural equation models analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors, and changes in height. There was no association between zBMI and ANS cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI increases from 2 to 3.5 years of age had decreased sympathetic activity at 5 years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted later zBMI.
|
Is resistive heating more effective than metallic-foil insulation in an experimental model of accidental hypothermia : A randomized controlled trial?
|
We study a resistive-heating blanket in a volunteer model of severe accidental hypothermia to evaluate differences in rates of rewarming, core temperature afterdrop, and body heat content and distribution during active and passive rewarming. Eight volunteers participated in a crossover design on 2 days. The volunteers were anesthetized and cooled to 33 degrees C (91.4 degrees F); anesthesia was subsequently discontinued, and shivering was prevented with meperidine. On one randomly assigned day, the volunteers were rewarmed passively with reflective foil (passive insulation), whereas on the other they were covered with a carbon fiber-resistive heating blanket set to 42 degrees C (107.6 degrees F; active rewarming). Trunk and head temperature and heat content were calculated from core (tympanic membrane) temperature. Peripheral (arm and leg) tissue temperature and heat content were estimated by using fourth-order regressions and integration over volume from 30 tissue and skin temperatures. Core heat content increased 73+/-14 kcal (mean+/-SD) during 3 hours of active warming, but only 31+/-24 kcal with passive insulation, a difference of 41+/-20 kcal (95% confidence interval [CI] 27 to 55 kcal; P <. 001). Peripheral tissue heat content increased linearly by 111+/-16 kcal during active warming but only by 38+/-31 kcal during passive warming, a difference of 74+/-34 kcal (95% CI 50 to 97; P <.001). Consequently, total body heat increased 183+/-22 kcal during active warming but only 68+/-54 kcal with passive insulation, a difference of 115+/-42 kcal (95% CI 86 to 144 kcal; P <.001). Core temperature increased from 32.9 degrees C+/-0.2 degrees C to 35.2 degrees C+/-0. 4 degrees C during 3 hours of active warming, a difference of 2.3 degrees C+/-0.4 degrees C. In contrast, core temperature with foil insulation only increased from 32.9 degrees C+/-0.2 degrees C to 33. 8 degrees C+/-0.5 degrees C, a difference of only 0.8 degrees C+/-0. 4 degrees C. The difference in the core temperature increase between the two treatments was thus 1.5 degrees C+/-0.4 degrees C (95% CI 1. 2 degrees C to 1.7 degrees C; P <.001 between treatments). Active warming was not associated with an afterdrop, whereas the afterdrop was 0.2 degrees C+/-0.2 degrees C and lasted a median of 45 minutes (interquartile range, 41 to 64 minutes) with passive insulation.
|
The biogenesis of autophagosomes, the hallmark of autophagy, depends on the function of the autophagy-related (Atg) proteins and the generation of phosphatidylinositol-3-phosphate (PtdIns3P) at the phagophore assembly site (PAS), the location where autophagosomes arise. The current model is that PtdIns3P is involved primarily in the recruitment of Atg proteins to the PAS and that once an autophagosome is complete, the Atg machinery is released from its surface back into the cytoplasm and reused for the formation of new vesicles. We have identified a PtdIns3P phosphatase, Ymr1, that is essential for the normal progression of both bulk and selective types of autophagy. This protein is recruited to the PAS at an early stage of formation of this structure through a process that requires both its GRAM domain and its catalytic activity. In the absence of Ymr1, Atg proteins fail to dissociate from the limiting membrane of autophagosomes, and these vesicles accumulate in the cytoplasm.
|
Does clinical and treatment correlate of access to Section 8 certificates for homeless mentally ill persons?
|
The study assessed how clients' housing preference and other variables were related to the acquisition of Section 8 certificates, facilitating independent living, for homeless persons with severe mental illness who were being served by an experimental assertive community treatment team. For 77 clients, demographic and clinical differences between receivers and nonreceivers of certificates were examined, and correlates of time from referral to the team to completion of the Section 8 application were analyzed. Reasons clients did not receive certificates and housing outcomes were summarized in relation to client preference. The 34 clients who received certificates (44 percent) had significantly less psychopathology after three months than did nonreceivers and tended to have affective disorders rather than schizophrenia. Of the 43 nonreceivers, the two largest groups were 19 clients who did not want certificates and ten clients who wanted certificates but whom staff considered unable to live safely in an unsupervised apartment. The mean +/- SD length of time for application for a certificate was 5.7 +/- 5.8 months. Longer time to apply was significantly associated with having schizophrenia, having the team as a representative payee, and showing increased psychotic symptoms at referral and at three months.
|
7-Ketocholesterol, a major oxysterol in oxidized low-density lipoproteins in advanced atherosclerotic plaques, induces vascular smooth muscle cell (SMC) death. We investigated whether cytochrome c release participated in SMC death induced by 7-ketocholesterol and whether the processes were reversible. SMC cultures derived from the rabbit aorta were exposed to 25 microM 7-ketocholesterol. Cytochrome c and Bax were studied by means of immunofluorescence and immunoblotting, apoptosis by the TUNEL technique and mitochondrial structure by transmission electron microscopy. 7-Ketocholesterol induced rapid upregulation of the proapoptotic protein Bax and its translocation from cytosol into the mitochondria (4 h). This was followed by mitochondrial cytochrome c release (65% at 8 h) into the cytosol, which was almost complete at 16 h. The mitochondria became spherical and ultracondensed, without showing signs of lysis. They clustered around the nucleus and were wrapped by wide cisternae of the rough endoplasmic reticulum. Cytochrome c release was not blocked by the pan-caspase inhibitor zVAD-fmk, in contrast to DNA fragmentation and SMC loss. Interestingly, upon removal of 7-ketocholesterol after 16 h and re-exposure to serum for 24 h, the mitochondrial cytochrome c content, their transmembrane potential and TUNEL labelling normalised and SMC loss decreased. However, none of these cell death markers was rescued when the SMCs had been exposed to the oxysterol for 24 h.
|
Does a novel biomechanical device improve gait pattern in patient with chronic nonspecific low back pain?
|
A retrospective study on patients with chronic nonspecific low back pain (NSLBP). To describe the gait stride characteristics of patients with chronic NSLBP, and to examine the effect of a novel biomechanical device on the gait stride characteristics of these patients. Patient with NSLBP alters their gait patterns. This is considered a protective mechanism as patients try to avoid extensive hip and spine ranges of motion and minimize forces and moments acting on the body. In addition, there are changes in the neuromuscular control system in patients with LBP that could possibly be attributed to the effects of pain on motor control. Nineteen patients underwent a gait test, using an electronic walkway, at baseline and after 12 weeks of treatment. Spatiotemporal parameters were used to identify changes in gait pattern. A novel biomechanical device comprised of 4 modular elements attached to foot-worn platforms was used in the study. The modules are 2 convex shaped biomechanical elements attached to each foot, one is located under the hindfoot region and the other is located under the forefoot region. The device was individually calibrated to each patient. The patients were instructed to walk with the calibrated biomechanical device on a daily basis for a period of 12 weeks. Significant differences were found at baseline and after 12 weeks in normalized velocity (P = 0.03), cadence (P < 0.01), left normalized step length (P = 0.02), right normalized step length (P = 0.02), right swing (P < 0.01), right stance (P < 0.01), left single limb support (P = 0.01), left double limb support (P = 0.02), and right double limb support (P = 0.02).
|
We used a murine model of orthotopic corneal transplantation to determine whether host deficiency in ICAM-1 promotes survival of corneal grafts with different degrees of allodisparity. ICAM-1-/- and wild-type C57BL/6 (ICAM-1+/+) received corneal grafts from the following strains of mice: BALB/c (fully mismatched), BALB.b (mismatched at multiple minor H only), or B10.D2 [including major histocompatibility complex (MHC) mismatch]. Graft rejection, induction of allospecific delayed-type hypersensitivity (DTH) responses, and leukocytic infiltration of grafts were measured. There were no differences in long-term survival of allografts that were either fully mismatched or had only minor H disparity in ICAM-1+/+ vs. ICAM-1-/-hosts. However, whereas B10.D2 grafts were accepted in only 58% of the ICAM-1+/+ hosts, graft survival in ICAM-1-/- recipients was 100% (P=0.006). Moreover, none of the ICAM-1-/- mice receiving B10.D2 grafts developed allospecific DTH.
|
Does geographical disparity in breast reconstruction following mastectomy have reduced over time?
|
Breast reconstruction (BR) following mastectomy for breast cancer has been shown to improve quality of life and body image; however, there is significant geographic variation in BR rates. We explored factors associated with BR following mastectomy. This is a population-based data linkage study consisting of cancer registry records linked to hospital inpatient episodes for 4104 women aged 20 years and over-diagnosed with a first primary invasive localized stage breast cancer between 1997 and 2012 in Queensland, Australia, who underwent a mastectomy. Multivariate logistic regression was used to model predictors of BR. Overall, 481 women (11.7%) underwent reconstruction. Proportions increased over time and were higher for younger women. Younger age, more recent diagnosis, living in high or very high accessibility areas or less disadvantaged areas, smaller tumours and attending a private or high-volume hospital independently increased the odds of reconstruction. The geographical disparity reduced significantly over time.
|
Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin.
|
Do periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis?
|
Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD). To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD. An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed. Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD.
|
We sought to evaluate whether improvement in ejection fraction (EF) with carvedilol therapy is accompanied by improvement in neurohumoral factors. Forty-two patients with dilated cardiomyopathy were given carvedilol for 3 to 5 months. Changes in EF, plasma atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and norepinephrine levels were determined. Iodine-123 metaiodobenzylguanidine (MIBG) images were also obtained before and after carvedilol therapy. Myocardial uptake of MIBG was calculated as the heart to mediastinal activity ratio (H/M). Storage and release of MIBG was calculated as percent myocardial MIBG washout rate (WR). We divided patients into 2 groups: 27 responders whose EF increased by more than 5% and 15 nonresponders whose EF increased by 5% or less. EF of responders increased by 15 +/- 5% and that of nonresponders by 1 +/- 4%. Although MIBG image-derived indexes of nonresponders remained unchanged, the delayed H/M (1.91 +/- 0.34 v 2.24 +/- 0.53, P < .01) and WR (49 +/- 11 v 39 +/- 9%, P < .01) of responders improved, respectively. The plasma ANP (51 +/- 50 v 27 +/- 24 pg/mL, P < .01) and BNP (194 +/- 197 v 49 +/- 62 pg/mL, P < .01) levels of responders decreased. The degree of changes in the plasma BNP level correlated with changes in EF (r = -.698, P < .01).
|
Do morbidity of early spine surgery in the multiply injured patient?
|
The optimal timing of surgery for multiply injured patients with operative spinal injuries remains unknown. The purported benefits of early intervention must be weighed against the morbidity of surgery in the early post-injury period. The performance of spine surgery in the Afghanistan theater permits analysis of the morbidity of early surgery on military casualties. The objective is to compare surgical morbidity of early spinal surgery in multiply injured patients versus stable patients. Patients were retrospectively categorized as stable or borderline unstable depending on the presence of at least one of the following: ISS >40, ISS >20 and chest injury, exploratory laparotomy or thoracotomy, lactate >2.5 mEq/L, platelet <110,000/mm(3), or >10 U PRBCs transfused pre-operatively. Surgical morbidity, complications, and neurologic improvement between the two groups were compared retrospectively. 30 casualties underwent 31 spine surgeries during a 12-month period. 16 of 30 patients met criteria indicating a borderline unstable patient. Although there were no significant differences in the procedures performed for stable and borderline unstable patients as measured by the Surgical Invasiveness Index (7.5 vs. 6.9, p = 0.8), borderline unstable patients had significantly higher operative time (4.3 vs. 3.0 h, p = 0.01), blood loss (1,372 vs. 366 mL, p = 0.001), PRBCs transfused intra-op (3.88 vs. 0.14 U, p < 0.001), and total PRBCs transfused in theater (10.18 vs. 0.31 U, p < 0.001).
|
To describe the clinical and genetic characteristics of the second family with a recently described recessive syndrome characterized by posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen. Observational case report. Three affected subjects and one healthy sibling from a consanguineous marriage from Spain were studied. Complete ophthalmologic examinations including A- and B-mode ultrasonography (US), electroretinography (ERG), fluorescein retinal angiography (FA), and optical coherence tomography (OCT) were performed in each individual. Genetic analysis included polymerase chain reaction amplification and direct nucleotide sequencing of the complete MFRP gene. All three affected siblings had bilateral shortening of the posterior ocular segment associated with high hyperopia and normal anterior segment dimensions. Best-corrected visual acuity ranged from 20/200 to 20/60. Funduscopy, ERG, and FA were compatible with retinitis pigmentosa, and B-mode ultrasound showed optic disk drusen. OCT analysis revealed outer retinal layer schisis with absence of foveal pit. Inheritance of this syndrome followed an autosomal recessive pattern. Molecular analysis revealed a novel homozygous 1-bp deletion (c.498delC) in exon 5 of MFRP, predicting a prematurely truncated protein (P166fsX190). A healthy sister demonstrated to be a carrier of the mutation.
|
Does morus alba leaf extract stimulate 5'-AMP-activated protein kinase in isolated rat skeletal muscle?
|
Morus alba (mulberry) leaf is a natural therapeutic agent that has been shown to have an antidiabetic effect. We explored the possibility that 5'-AMP-activated protein kinase (AMPK) is involved in metabolic enhancement by the Morus alba leaf. Isolated rat epitrochlearis muscle was incubated in a buffer containing Morus alba leaf hot water extract (MLE) and the AMPK activation and related events were examined. In response to MLE treatment, the Thr(172) phosphorylation of the catalytic alpha subunit of AMPK, an essential step for full kinase activation increased in a dose- and time-dependent manner. Ser(79) phosphorylation of acetyl CoA carboxylase, an intracellular substrate of AMPK, increased similarly. Analysis of isoform-specific AMPK activity revealed that MLE activated both the alpha1 and alpha2 isoforms of the catalytic subunit. This increase in enzyme activity was associated with an increased rate of 3-O-methyl-D-glucose transport in the absence of insulin and with phosphorylation of AS160, a signaling intermediary leading to glucose transporter 4 translocation. The intracellular energy status, estimated from the ATP and phosphocreatine concentrations, was not affected by MLE.
|
In our previous study, we found that the ability of supragingival plaque to induce Toll-like receptor (TLR)4-mediated stimulation was positively associated with plaque score and bleeding on probing (BOP) at the sampled sites and that the ability to induce TLR2-mediated stimulation was negatively associated with probing depth (PD) and clinical attachment level (CAL). Because signaling from TLR leads to the induction of pro- and anti-inflammatory cytokines, we further analyzed the influence of the ability of supragingival plaque to induce TLR2-/TLR4-mediated stimulation of cytokine production by peripheral blood mononuclear cells (PBMCs). The abilities of 125 plaque samples to induce TLR2- or TLR4-mediated stimulation were determined using genetically engineered Chinese hamster ovary reporter cells that express a reporter molecule upon activation of nuclear factor-kappa B through TLR2 or TLR4. PBMCs were stimulated with each plaque sample, and the production of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin [IL]-6 and -8) and an anti-inflammatory cytokine (IL-10) was analyzed by enzyme-linked immunosorbent assay. The levels of the cytokines produced by PBMCs all correlated with the ability of supragingival plaque to induce TLR4-mediated stimulation but not with its ability to induce TLR2-mediated stimulation. Cytokine production was inhibited by an anti-TLR4 monoclonal antibody and a TLR4 antagonist, compound 406. The levels of cytokines were associated with plaque index, BOP, PD, and CAL at the sampled sites.
|
Does mST1 coordinately regulate autophagy and apoptosis in diabetic cardiomyopathy in mice?
|
Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM. Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated diabetes to probe mechanisms. Mst1 knockout alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes. Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced protein aggregation. In contrast, typical autophagosomes were observed in diabetic Mst1-knockout mice with increased LC3 expression and reduced protein aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by increased LC3-II and decreased p62 expression in the presence of bafilomycin A1. Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased, cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2 (Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely, Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction between Bcl-2 and Bax.
|
The author addresses whether the face bow is irrelevant for all types of prosthetic work and for planning orthognathic surgery. The author searched electronic databases to find studies whose investigators used the strongest clinical evidence (that is, randomized clinical trials) and studies whose investigators incorporated the use of cinefluorography. The author found 13 studies and 1 Internet video that provided strong evidence to support the irrelevancy of the face bow transfer. Evidence indicates that the face bow has nothing to do with speech, the fit and comfort of the prostheses, ridge morphology, facial contours, the color of the teeth and denture bases, the arrangement of the artificial teeth, chewing efficiency stability, and the psychological aspects of prosthodontic treatment. The cinefluorographic example showed that there was no condylar axis of rotation during functional activity, a sawing action of the mandibular incisors during the incising of toast and the mandible moving in a back and forth, rocking chair-like movement during functional activity.
|
Are heat shock proteins therapeutic targets in autoimmune diseases and other chronic inflammatory conditions?
|
Exploitation of antigen-specific regulatory T cells (Tregs) as critical regulators in the control of chronic inflammatory diseases is hampered by the obscure nature of most disease-relevant autoantigens. Heat shock proteins (Hsp) are possible targets for Tregs due to their enhanced expression in inflamed (stressed) tissues and there is evidence that Hsp can induce anti-inflammatory immunoregulatory T-cell responses. Recent publications showing that exogenous administration of stress proteins has induced immunoregulation in various models of inflammatory disease have also been shown to be effective in first clinical trials in humans. Now, in the light of a growing interest in T-cell regulation, it is of interest to further explore the mechanisms through which Hsp can be utilized to trigger immunoregulatory pathways, capable of suppressing such a wide and diversified spectrum of inflammatory diseases.
|
Parkinsonian signs, especially gait impairment, are common and associated with morbidity and mortality in older persons. Our objective was to test the hypothesis that substantia nigra neurofibrillary tangles (NFTs) are related to parkinsonian signs in older persons with and without dementia. We studied 86 deceased older Catholic clergy without idiopathic Parkinson's disease from the Religious Order Study, a longitudinal clinical-pathological study. Mean age at death was 85.3 years. Signs of gait disturbance, bradykinesia, rigidity, and tremor were assessed proximate to death using a modified Unified Parkinson's Disease Rating Scale. Forty-micrometer paraffin-embedded sections of substantia nigra were bleached before tau immunohistochemistry and the optical disector was used to count NFTs. We used multivariable linear regression to examine parkinsonian signs as a function of nigra NFTs, controlling for age, sex, education, and cortical NFTs. Substantia nigra NFTs were present in 67 of 86 persons (77.9%). After controlling for age, sex, education, and cortical NFTs, nigra NFTs were related to gait impairment (p < 0.001), but not bradykinesia, rigidity, or tremor. Results were not confounded by dementia, Braak score, neuroleptic medication, cerebral infarcts, or Lewy bodies.
|
Are [ Parathyroid glands differentiated from lymph node by activated-carbon particles ]?
|
To probe into an new methods preserving parathyroid gland of patients with thyroid carcinoma. Thirty-six patients with thyroid carcinoma that primary treated were random divided into two groups: trial group and control group. Emulsion of activated-carbon particles was injected into the thyroid gland of trial group patients. After thirty minutes, central compartment dissection was performed in the all patients. The black stained tissue in the dissection specimen of trial group was separated. Total lymph node, metastasis lymph node and parathyroid gland in the black stained tissue, and non-black stained tissue in the central compartment dissection specimen of trial group and central compartment dissection specimen of control group were counted respectively. Nineteen and twenty central compartment dissection was performed in trial group and control group respectively. There are 177 lymph nodes included 83 metastasis lymph nodes in the black-stained tissue of central compartment dissection specimen of trial group. No parathyroid gland was found in the black-stained tissue. Nine lymph nodes included 2 metastasis lymph nodes and 7 parathyroid glands were found in the non-black stained tissue of central compartment dissection specimen of trial group. There were 124 lymph nodes included 80 metastasis lymph nodes and 8 parathyroid glands in central compartment dissection specimen of control group. There are statistic difference between the amount of lymph node in black stain tissue and that of control group (t = 0.340, P = 0.003). Rate of staining lymph node were 95.2 percent.
|
Fatigue contributes directly to anterior cruciate ligament (ACL) injury via promotion of high risk biomechanics. The potential for central fatigue to dominate this process, however, remains unclear. With centrally mediated movement behaviors being trainable, establishing this link seems critical for improved injury prevention. We thus determined whether fatigue-induced landing biomechanics were governed by a centrally fatiguing mechanism. Twenty female NCAA athletes had initial contact (IC) and peak stance (PS) three-dimensional hip and knee biomechanics quantified during anticipated and unanticipated single-leg landings, before and during unilateral fatigue accumulation. To induce fatigue, subjects performed repetitive (n = 3) single-leg squats and randomly ordered landings, until squats were no longer possible. Subject-based dependent factors were calculated across prefatigue trials and for those denoting 100%, 75%, 50%, and 25% fatigue and were submitted to three-way mixed-design analyses of covariance to test for decision, fatigue time, and limb effects. Fatigue produced significant (P < 0.01) decreases in IC knee flexion angle and PS knee flexion moment and increases in PS hip internal rotation and knee abduction angles and moments, with differences maintained from 50% fatigue through to maximum. Fatigue-induced increases in PS hip internal rotation angles and PS knee abduction angles and loads were also significantly (P < 0.01) greater during unanticipated landings. Apart from PS hip moments, significant limb differences in fatigued landing biomechanics were not observed.
|
Does aCTH-cortisol activity during the 17beta-estradiol and LH preovulatory surge of the menstrual cycle?
|
A strong positive coupling has been already documented between the adrenocortical axis and the gonadal axis at the time of the initiation of the preovulatory LH surge of the menstrual cycle in the human. The LH preovulatory surge starts in the morning at the time of the acrophase (maximal plasma cortisol values) of the cortisol circadian rhythm. Also, it was shown that morning maximal plasma cortisol values were higher during the follicular phase than during the luteal phase. The objective of the present study was designed to determine the exact day of the fall of morning maximal plasma cortisol values and the functional correlates which could exist between plasma 17beta-Estradiol, LH, ACTH and Cortisol at the time of the preovulatory LH surge. We performed a detailed analysis of variations of plasma ACTH and cortisol concentrations during the various phases of the LH surge: 1) the day before the ascending phase, 2) the day of the ascending phase, 3) the day of the LH peak, 4) the day of the descending phase, 5) the day after the descending phase. 17beta-Estradiol, LH and FSH were determined by microparticle enzyme immunoassays kits and Progesterone determination was made using a radioimmunoassay kit. ACTH determination was made using a RIA kit and Cortisol was assayed by a RIA method. Plasma ACTH concentrations were at their highest the day before the day of the ascending phase of the LH surge and significantly higher than the day of the descending phase and the day after the day of the descending phase (p < 0.02). Plasma cortisol concentrations were at their highest, with almost similar values, the day before the day of the ascending phase, the day of the ascending phase and the day of the LH peak; then, plasma cortisol concentrations were significantly lower than those of the preceding days, the day of the descending phase (p = 0.0001) and the day after the day of the descending phase (p = 0.02), when plasma 17beta-Estradiol starts to decrease.
|
Ginsenoside Rd (GSRd), one of the main active ingredients in traditional Chinese herbal Panax ginseng, has been found to have therapeutic effects on ischemic stroke. However, the molecular mechanisms of GSRd's neuroprotective function remain unclear. Ischemic stroke-induced oxidative stress results in DNA damage, which triggers cell death and contributes to poor prognosis. Oxidative DNA damage is primarily processed by the base excision repair (BER) pathway. Three of the five major DNA glycosylases that initiate the BER pathway in the event of DNA damage from oxidation are the endonuclease VIII-like (NEIL) proteins. This study aimed to investigate the effect of GSRd on the expression of DNA glycosylases NEILs in a rat model of focal cerebral ischemia. NEIL expression patterns were evaluated by quantitative real-time polymerase chain reaction in both normal and middle cerebral artery occlusion (MCAO) rat models. Survival rate and Zea-Longa neurological scores were used to assess the effect of GSRd administration on MCAO rats. Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damages were evaluated by the way of real-time analysis of mutation frequency. NEIL expressions were measured in both messenger RNA (mRNA) and protein levels by quantitative polymerase chain reaction and Western blotting analysis. Apoptosis level was quantitated by the expression of cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay. We found that GSRd administration reduced mtDNA and nDNA damages, which contributed to an improvement in survival rate and neurological function; significantly up-regulated NEIL1 and NEIL3 expressions in both mRNA and protein levels of MCAO rats; and reduced cell apoptosis and the expression of cleaved caspase-3 in rats at 7 days after MCAO.
|
Does morbidity and mortality of colorectal carcinoma surgery differ by insurance status?
|
Uninsured and underinsured patients are reported to be at an increased risk for impaired access to healthcare, delayed medical treatment, and the receipt of substandard care. These differences in care may result in disparities in surgical outcomes among patients with different types of insurance. In the current study, the authors examined associations between the insurance provider and short-term surgical outcomes after surgery for colorectal carcinoma and evaluated the extent to which two risk factors (comorbid disease and admission type) might explain any observed association. The authors conducted a nationally representative retrospective cohort study of 13,415 adults ages 40-64 years who were admitted for surgery for colorectal carcinoma to hospitals that participated in the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project National Inpatient Sample, releases 6 and 7, in 1997 and 1998. Multivariate logistic regression models were developed to describe the correlations between insurance status and the risks of a postoperative complication or postoperative death after adjustment for socioeconomic factors, comorbid conditions, and admission type. Uninsured and Medicaid patients were found to have more emergent admissions and more comorbid disease compared with patients with private health insurance. Patients without private health insurance had higher rates of postoperative complications and in-hospital death compared with those patients with private insurance. After adjusting for patient and hospital characteristics, patients with Medicaid were found to be 22% more likely to develop a complication during their hospital admission (odds ratio [OR] of 1.22; 95% confidence interval [95%CI], 1.06-1.40) and 57% more likely to die postoperatively (OR of 1.57; 95% CI, 1.01-2.42) compared with patients with private insurance.
|
We examined the impact of an acute bout of resistance-type exercise on mixed muscle protein synthesis in the fed state. After a standardized breakfast, 10 untrained males completed a single, unilateral lower-limb resistance-type exercise session. A primed, continuous infusion of l-[ring-C6]phenylalanine was combined with muscle biopsy collection from both the exercised (Ex) and the nonexercised (NEx) leg to assess the impact of local muscle contractions on muscle protein synthesis rates after food intake. Western blotting with phosphospecific and pan antibodies was used to determine the phosphorylation status of AMP-activated kinase (AMPK), 4E-binding protein (4E-BP1), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase (S6K1). Muscle protein synthesis rates were approximately 20% higher in Ex compared with NEx (0.098% +/- 0.005% vs 0.083% +/- 0.002%.h, respectively, P < 0.01). In the fed state, resistance-type exercise did not elevate AMPK phosphorylation. However, the phosphorylation status of 4E-BP1 was approximately 20% lower after cessation of exercise in Ex compared with NEx (P < 0.05). Conversely, 4E-BP1 phosphorylation was significantly higher in Ex compared with NEx after 6 h of recovery (P < 0.05) with no changes in mTOR phosphorylation. S6 phosphorylation was greater in Ex versus NEx after cessation of exercise (P < 0.05), although S6K1 phosphorylation at T was not up-regulated (P > 0.05).
|
Is sumo E2 enzyme UBC9 required for efficient protein quality control in cardiomyocytes?
|
Impairment of proteasomal function is pathogenic in several cardiac proteinopathies and can eventually lead to heart failure. Loss of proteasomal activity often results in the accumulation of large protein aggregates. The ubiquitin proteasome system (UPS) is primarily responsible for cellular protein degradation, and although the role of ubiquitination in this process is well studied, the function of an ancillary post-translational modification, SUMOylation, in protein quality control is not fully understood. To determine the role of ubiquitin-conjugating enzyme 9 (UBC9), a small ubiquitin-like modifier-conjugating enzyme, in cardiomyocyte protein quality control. Gain- and loss-of-function approaches were used to determine the importance of UBC9. Overexpression of UBC9 enhanced UPS function in cardiomyocytes, whereas knockdown of UBC9 by small interfering RNA caused significant accumulations of aggregated protein. UPS function and relative activity was analyzed using a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluorescent protein (GFPu). Subsequently, the effects of UBC9 on UPS function were tested in a proteotoxic model of desmin-related cardiomyopathy, caused by cardiomyocyte-specific expression of a mutated αB crystallin, CryAB(R120G). CryAB(R120G) expression leads to aggregate formation and decreased proteasomal function. Coinfection of UBC9-adenovirus with CryAB(R120G) virus reduced the proteotoxic sequelae, decreasing overall aggregate concentrations. Conversely, knockdown of UBC9 significantly decreased UPS function in the model and resulted in increased aggregate levels.
|
We describe the epidemiology of smoking behaviors in a national young adult sample and identify common and unique demographic, social, and psychological correlates of daily smoking and lifetime and current nicotine dependence by race/ethnicity. Data are from the National Longitudinal Survey of Adolescent Health, wave III. Dependence was measured by the Revised Fagerström Test for Nicotine Dependence. Logistic regressions were estimated. Hispanic ethnicity, low education, parental and peer smoking, novelty seeking, early age of smoking onset, and pleasurable initial smoking experiences are significantly correlated with daily smoking and lifetime nicotine dependence. Depressive symptoms are uniquely associated with lifetime and current dependence. Few factors are highly associated with current dependence. Initial sensitivity to smoking has a significantly greater impact on daily smoking than on dependence. Correlates of smoking behaviors are mostly common across racial/ethnic groups, although parental and peer smoking are significant for Whites and Hispanics but not for African Americans.
|
Do clinical experience with 3-dimensional surface matching-based deep inspiration breath hold for left-sided breast cancer radiation therapy?
|
Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system. The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system. Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique.
|
To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2.
|
Does sodium nitroprusside iontophoresis on the finger pad consistently increase skin blood flow in healthy controls and patients with systemic sclerosis?
|
Sodium nitroprusside (SNP) iontophoresis is a commonly used technique to assess non endothelium-dependent skin microvascular function in the forearm. However, the lack of data on the finger pad is a limitation when studying diseases affecting the digits (e.g. systemic sclerosis, SSc). We thus aimed to validate this technique in the finger pad compared to the forearm in SSc patients and healthy controls. Six SSc patients and six controls were recruited. SNP and NaCl iontophoresis were performed on the finger pad and the forearm, with and without lidocaine/prilocaine. Cutaneous blood flow was simultaneously monitored using laser Doppler flowmetry. In all subjects, iontophoresis of SNP induced hyperemia in the forearm, which was not affected by pretreatment with lidocaine/prilocaine. In contrast, no increase in cutaneous vascular conductance was observed in the finger pad in any subject (apart from one patient with SSc).
|
Observational studies suggest that dietary isoflavones reduce breast cancer risk, and this may be caused in part by effects on endogenous hormone concentrations. Because intestinal bacteria metabolize isoflavones, it was hypothesized that consumption of probiotic bacteria would enhance the biologic effects of isoflavones, including effects on endogenous hormones. Twenty (20) postmenopausal breast cancer survivors and 20 healthy postmenopausal women completed four 42-day diet periods in a randomized, crossover design. They received one of the following: isolated soy protein; isolated milk protein; soy + probiotic capsules; or milk + probiotic capsules. Each protein supplement provided 0.38 g protein/(kg body weight/day) (26.6 +/- 4.5 g protein/day) and soy protein provided 0.64 mg isoflavones/(kg body weight/day) (44.4 +/- 7.5 mg isoflavones/day). Probiotic capsules provided 10(9) colony-forming units Lactobacillus acidophilus (strain DDS-1), Bifidobacterium longum, and 15-20 mg fructo-oligosaccharide. Plasma samples were collected at baseline and after each diet for analysis of estrogens, follicle-stimulating hormone (FSH), androgens, and sex hormone?binding globulin (SHBG). Hormone levels were not affected by soy, probiotic supplements, or equol producer status, and neither cancer status nor equol producer status altered the effects of soy or probiotics. Furthermore probiotics did not alter the effects of soy consumption. Soy protein tended to decrease SHBG compared to milk protein diets (p = 0.05), although both proteins significantly decreased SHBG relative to baseline (p = 0.0001 and p = 0.03).
|
Do early post operative visual outcome in microsurgically treated suprasellar meningiomas predict long-term visual outcome?
|
Different data exist regarding long-term visual prognosis associated with suprasellar meningiomas. The aim of this study was to determine the outcome of suprasellar meningiomas with respect to short and long-term visual outcomes. During the period of 1997 to 2006, 45 patients were operated either through a pterional (30) or bifrontal (15) approach. Visual parameters were evaluated early and late post-operatively. 5 patients died post-operatively and 2 cases failed to attend follow up. During the early post-operative period, 15 (39.5%) showed improvement and 9 (23.7%) worsening of vision among 38 patients. Patients were followed-up for 1 to 8 years with mean of 4.1 years. Follow-up data revealed that 26 (68.4%) patients had visual improvement in at least one eye (10 of them in both eyes) while 10 (26.3%) patients had visual deterioration in one or both eyes. Data showed no significant correlation between visual outcome and extent of tumor removal or surgical approach. Visual outcome was better in patients with preoperative vision > 1mfc (p-value=0.001). Data also showed that early post-op vision significantly correlates with long term visual outcome (p-value =0.003).
|
Adipose inflammation is a crucial link between obesity and its metabolic complications. Human experimental endotoxemia is a controlled model for the study of inflammatory cardiometabolic responses in vivo. We hypothesized that adipose genes down-regulated during endotoxemia would approximate changes observed with obesity-related inflammation and reveal novel candidates in cardiometabolic disease. Healthy volunteers (n = 14) underwent a 3 ng/kg endotoxin challenge; adipose biopsies were taken at 0, 4, 12, and 24 h for mRNA microarray. A priority list of highly down-regulated and biologically relevant genes was validated by RT-PCR in an independent sample of adipose from healthy subjects (n = 7) undergoing a subclinical 0.6 ng/kg endotoxemia protocol. Expression of validated genes was screened in adipose of lean and severely obese individuals (n = 11 per group), and cellular source was probed in cultured adipocytes and macrophages. Endotoxemia (3 ng/kg) suppressed expression of 353 genes (to <67% of baseline; P < 1 × 10(-5)) of which 68 candidates were prioritized for validation. In low-dose (0.6 ng/kg) endotoxin validation, 22 (32%) of these 68 genes were confirmed. Functional classification revealed that many of these genes are involved in cell development and differentiation. Of validated genes, 59% (13 of 22) were down-regulated more than 1.5-fold in primary human adipocytes after treatment with endotoxin. In human macrophages, 59% (13 of 22) were up-regulated during differentiation to inflammatory M1 macrophages whereas 64% (14 of 22) were down-regulated during transition to homeostatic M2 macrophages. Finally, in obese vs. lean adipose, 91% (20 of 22) tended to have reduced expression (χ(2) = 10.72, P < 0.01) with 50% (11 of 22) reaching P < 0.05 (χ(2) = 9.28, P < 0.01).
|
Does acute metformin preconditioning confer neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagy?
|
Recent clinical trials report that metformin, an activator of AMP-activated protein kinase (AMPK) used to treat type 2 diabetes, significantly reduces the risk of stroke by actions that are independent of its glucose-lowering effects. However, the underlying molecular mechanisms are not known. Here, we tested the possibility that acute metformin preconditioning confers neuroprotection by pre-activation of AMPK-dependent autophagy in a rat model of permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats were pretreated with either vehicle, an AMPK inhibitor, Compound C, or an autophagy inhibitor, 3-methyladenine, and were injected with a single dose of metformin (10 mg kg(-1), i.p.). Then, AMPK activity and autophagy biomarkers in the brain were assessed. At 24 h after metformin treatment, rats were subjected to pMCAO; infarct volume, neurological deficits and cell apoptosis were evaluated 24 and 96 h later. A single dose of metformin significantly activated AMPK and induced autophagy in the brain. The enhanced autophagic activity was inhibited by Compound C pretreatment. Furthermore, acute metformin preconditioning significantly reduced infarct volume, neurological deficits and cell apoptosis during a subsequent focal cerebral ischaemia. The neuroprotection mediated by metformin preconditioning was fully abolished by Compound C and partially inhibited by 3-methyladenine.
|
We investigated whether serum markers and clinical factors could be used to preoperatively predict lymph node (LN) metastasis in colorectal cancer (CRC). The present study enrolled 157 curative CRC patients for whom preoperative serum carcinoembryonic antigen (CEA), systemic inflammatory markers (C-reactive protein (CRP) and angiopoietin-like protein 2 (ANGPTL2)) and objective preoperative clinical factors were available as indicators of pathological LN status. Specific clinical factors, including gender, tumor size, histopathology of biopsy sample and tumor morphology, were significantly correlated with LN metastases. Additionally, CEA, CRP and ANGPTL2 levels were also predictive factors for LN status. Multivariate analysis revealed that clinical factors, including gender, histopathology, tumor morphology and ANGPTL2, were identified as independent predictive factors for LN metastases. A combination of clinical factors reached high predictive accuracy of LN metastases and, combined with clinical factors, ANGPTL2 further improved the accuracy.
|
Is early resuscitation with low-volume PolyDCLHb effective in the treatment of shock induced by penetrating vascular injury?
|
To study the efficacy of an oxygen-carrying solution in early resuscitation of hemorrhagic shock induced by penetrating vascular injury. Experimental study with anesthetized rats. Severe hemorrhagic shock was induced by a 25-gauge needle puncture to the infrarenal aorta. Forty animals were resuscitated 10 minutes after injury with either lactated Ringer's solution (LR; 60 mL/kg), 7.5% hypertonic saline (HTS; 5 mL/kg), or modified diaspirin cross-linked hemoglobin (PolyDCLHb; 5 or 20 mL/kg) or were not resuscitated (NR) and followed for 6 hours. Total blood loss was similar in all treatment groups. Mean arterial pressure was restored to baseline values, base deficit was corrected to base excess, and venous oxygen saturation improved with PolyDCLHb and more slowly with LR but persisted below baseline values with HTS and NR. The 6-hour mortality rates were zero of eight (low-dose PolyDCLHb), three of eight (high-dose PolyDCLHb), two of eight (LR), six of eight (HTS), and six of eight (NR).
|
To investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia. The ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41). In all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42].
|
Is vEGF important for early liver regeneration after partial hepatectomy?
|
The aim of the study was to determine the role of Vascular Endothelial Growth Factor (VEGF) on the microvasculature and on angiogenetic gene expression after partial hepatectomy (PH) in the rat model. To determine the effect of exogenous and endogenous VEGF after PH, rats were subjected to 70% PH and treated either with VEGF, anti-VEGF or NaCl. Postoperatively (3-168 h), vessel density (VD), vessel diameter (VDi), and intersinusoidal space, liver body weight ratio (LBR), hepatic proliferation and biochemical markers were assessed. To further elucidate the underlying molecular mechanisms hepatic gene expression was determined by customized cDNA arrays and quantitative RT-PCR. In the VEGF group, VD, VDi, and LBR were significantly increased compared with anti-VEGF or controls. Blockage of endogenous VEGF led to a marked increase of biochemical markers. Anti-VEGF almost completely suppressed and VEGF markedly enhanced hepatic proliferation in the first 24 h after surgery. This was associated with a modulation of cell cycle control genes (PC4, Gadd45a, Tis21/BTG2), v-jun, and CD14 by VEGF.
|
Apathy has recently been recognized as a distinct clinical syndrome although it is difficult to differentiate from late life depression. In old age, apathy as a syndrome in itself and depression may have different etiologies. Inflammatory markers have been associated with depression in the elderly, but the relation with apathy is unknown. To assess the relation between C-reactive protein (CRP) and apathy as a syndrome in itself, apart from depression, in subjects aged 85 and older. All data come from the Leiden 85-Plus Study, a prospective, population-based study of 599 elderly subjects. CRP was measured at baseline. In all subjects with a Mini Mental State Examination (MMSE) > or = 19 points (n = 500), apathy and depression were assessed annually from age 85 to 90 using the three apathy and twelve depression questions of the 15-item Geriatric Depression Scale (GDS-15). The association between CRP and apathy or depressive symptoms was assessed both at baseline and longitudinally. At baseline, no association was found between CRP-concentration and apathy or depression. In subjects free of apathy and depression at baseline, subjects in the highest CRP-tertile at baseline had significantly more increase in depressive symptoms but not in apathy symptoms during follow-up.
|
Is locomotive syndrome associated not only with physical capacity but also degree of depression?
|
Reports of locomotive syndrome (LS) have recently been increasing. Although physical performance measures for LS have been well investigated to date, studies including psychiatric assessment are still scarce. Hence, the aim of this study was to investigate both physical and mental parameters in relation to presence and severity of LS using a 25-question geriatric locomotive function scale (GLFS-25) questionnaire. 150 elderly people aged over 60 years who were members of our physical-fitness center and displayed well-being were enrolled in this study. Firstly, using the previously determined GLFS-25 cutoff value (=16 points), subjects were divided into two groups accordingly: an LS and non-LS group in order to compare each parameter (age, grip strength, timed-up-and-go test (TUG), one-leg standing with eye open, back muscle and leg muscle strength, degree of depression and cognitive impairment) between the groups using the Mann-Whitney U-test followed by multiple logistic regression analysis. Secondly, a multiple linear regression was conducted to determine which variables showed the strongest correlation with severity of LS. We confirmed 110 people for non-LS (73%) and 40 people for LS using the GLFS-25 cutoff value. Comparative analysis between LS and non-LS revealed significant differences in parameters in age, grip strength, TUG, one-leg standing, back muscle strength and degree of depression (p < 0.006, after Bonferroni correction). Multiple logistic regression revealed that functional decline in grip strength, TUG and one-leg standing and degree of depression were significantly associated with LS. On the other hand, we observed that the significant contributors towards the GLFS-25 score were TUG and degree of depression in multiple linear regression analysis.
|
Tongue squamous cell carcinoma (TSCC) is the most common malignant cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be novel indicators for tumor metastasis. The aim of the present study was to investigate the expression and function of ANGPTL4 in TSCC and the relationship between ANGPTL4 and MVD. The expression levels of ANGPTL4 and MVD (CD34) were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using immunohistochemistry (IHC). siRNA was delivered into TSCCA cells to downregulate ANGPTL4 expression. Subsequently, validation with real-time RT-PCR and western blot analyses was performed to analyze ANGPTL4 expression levels. In addition, a proliferation assay, migration and invasion assays were carried out. ANGPTL4 expression was associated with tumor stage, lymph node metastasis and MVD expression. Cox regression analysis showed that high levels of ANGPTL4 expression were closely associated with poor survival time. In vitro analyses using qRT-PCR and western blot confirmed that ANGPTL4 was successfully inhibited in TSCCA cells. Suppressing ANGPTL4 resulted in the inhibition of cell proliferation and migration, but neither invasion nor cisplatin resistance was significantly affected.
|
Does tissue factor predict response to chemotherapy in esophageal cancer?
|
Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer. In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy. TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P = 0.0431). TF expression was also independently associated with poor progression-free survival (P = 0.0353).
|
We evaluated the relationship between antenatal depressive symptoms and preterm birth. Patients completed the Edinburgh Postnatal Depression Scale between 24-28 weeks of gestation. A score ≥ 12 (or thoughts of self-harm) indicated an at-risk woman. Symptomatic women were compared to risk-negative patients for relevant demography, historical variables, and pregnancy outcome. After screening 14,175 women we found a screen positive rate of 9.1% (n = 1298). At-risk women had a significant increase in preterm birth at <37, <34, <32, and <28 weeks of gestation. Multivariable analysis adjusting for maternal age, race/ethnicity, prior preterm delivery, and insurance status revealed a persistent association between antenatal depressive symptoms and preterm birth (adjusted odds ratio, 1.3; 95% confidence interval, 1.09-1.35), which was also observed after multiple gestations were excluded from the analysis (odds ratio, 1.7; 95% confidence interval, 1.38-1.99).
|
Does chronic kidney disease predict long-term mortality after major lower extremity amputation?
|
Despite low peri-operative mortality after major lower extremity amputation, long-term mortality remains substantial. Metabolic syndrome is increasing in incidence and prevalence at an alarming rate in the USA. This study was to determine whether metabolic syndrome predicts outcome after major lower extremity amputation. A retrospective review of charts between July 2005 and June 2010. Fifty-four patients underwent a total of 60 major lower extremity amputations. Sixty percent underwent below-knee amputation and 40% underwent above-knee amputation. The 30-day mortality was 7% with no difference in level (below-knee amputation, 8%; above-knee amputation, 4%; P = 0.53). The mean follow-up time was 39.7 months. The 5-year survival was 54% in the whole group, and was independent of level of amputation (P = 0.24) or urgency of the procedure (P = 0.51). Survival was significantly decreased by the presence of underlying chronic kidney disease (P = 0.04) but not by other comorbidities (history of myocardial infarction, P = 0.79; metabolic syndrome, P = 0.64; diabetes mellitus, P = 0.56).
|
Interleukin 4 (IL-4) is a key regulator of the immune system and an important factor in the development of allergic hypersensitivity. Together with interleukin 13 (IL-13), IL-4 plays an important role in exacerbating allergic and asthmatic symptoms. For signal transduction, both cytokines can utilise the same receptor, consisting of the IL-4Ralpha and the IL-13Ralpha1 chain, offering an explanation for their overlapping biological functions. Since both cytokine ligands share only moderate similarity on the amino acid sequence level, molecular recognition of the ligands by both receptor subunits is of great interest. IL-4 and IL-13 are interesting targets for allergy and asthma therapies. Knowledge of the binding mechanism will be important for the generation of either IL-4 or IL-13 specific drugs. We present a structure/function analysis of the IL-4 ligand-receptor interaction. Structural determination of a number of IL-4 variants together with in vitro binding studies show that IL-4 and its high-affinity receptor subunit IL-4Ralpha interact via a modular protein-protein interface consisting of three independently-acting interaction clusters. For high-affinity binding of wild-type IL-4 to its receptor IL-4Ralpha, only two of these clusters (i.e. cluster 1 centered around Glu9 and cluster 2 around Arg88) contribute significantly to the free binding energy. Mutating residues Thr13 or Phe82 located in cluster 3 to aspartate results in super-agonistic IL-4 variants. All three clusters are fully engaged in these variants, generating a three-fold higher binding affinity for IL-4Ralpha. Mutagenesis studies reveal that IL-13 utilizes the same main binding determinants, i.e. Glu11 (cluster 1) and Arg64 (cluster 2), suggesting that IL-13 also uses this modular protein interface architecture.
|
Is cognitive impairment in late-life bipolar disorder associated with Alzheimer 's disease pathological signature in the cerebrospinal fluid?
|
Cognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (Aβ1-42 ) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature. Seventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n = 16) and the comparison groups comprised patients with dementia due to AD (n = 17), patients with amnestic MCI (aMCI; n = 14), and cognitively healthy older adults (control group; n = 25). CSF samples were obtained by lumbar puncture and concentrations of Aβ1-42 , T-tau and P-tau were determined. CSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF Aβ1-42 compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD.
|
Venous grafts are commonly used to treat drug-resistant coronary artery disease, although long-term functionality is limited because of proliferation and migration of smooth muscle cells (SMC). As proliferating SMC are particularly susceptible for the stimulating effects of cytomegalovirus (CMV), we hypothesized that CMV infection may enhance cell proliferation and graft failure. Furthermore, we evaluated the potential of FK778 to prevent intimal hyperplasia. Apart from its antiviral properties, FK778 is a new immunosuppressive agent which may also affect SMC proliferation, making it an interesting drug to prevent (CMV-enhanced) venous graft intimal hyperplasia. Epigastric vein-to-common femoral artery interposition grafts were placed in four groups of 10 rats each. Rats received either FK778 (oral treatment, 15 mg/kg), were infected with CMV (1.25 x 10(6) plaque-forming units) or were both treated and infected. CMV infection resulted in a significant increase in intimal and medial cross-sectional area and medial wall thickness of the vein grafts. This effect was diminished by administration of FK778. Moreover, FK778 treatment alone resulted in a significant decrease in neointimal area and percentage of stenosis versus the control group.
|
Does two-stage portal vein ligation facilitate liver regeneration in rats?
|
Recent reports have demonstrated that some patients are unable to undergo scheduled liver resection after preoperative portal vein embolization due to insufficient hypertrophy of the future remnant liver. The present study examined whether two-stage portal vein ligation (PVL) increases hypertrophy of the future remnant liver compared to conventional PVL in rats. Rats were divided into 3 groups: group A, ligation of left primary branch; group B, ligation of right and left primary branches; group C, ligation of the left primary branch, followed by 2-stage PVL 7 days postoperatively. To evaluate liver regeneration, the proliferating cell nuclear antigen labeling index (LI), mitotic index (MI) in the caudate lobe and weight ratio of caudate lobe to body weight were measured. The weight ratio of caudate lobe to body weight was significantly higher in group C than in groups A or B 14 days postoperatively. In groups A and B, LI and MI in the caudate lobe peaked 2 days postoperatively, then decreased to preoperative levels by 7-8 days postoperatively, but remained significantly elevated until 10-14 days postoperatively in group C.
|
Sleep disorders are common in patients with HIV/AIDS, and can lead to poor quality of life. Although many studies have investigated the aetiology of these disorders, it is still unclear whether impaired sleep quality is associated with HIV itself, social problems, or side effects of antiretroviral therapy (ART). Moreover, despite its known neurological associations, little is known about the role of the trans-activator of transcription (Tat) protein in sleep disorders in patients with HIV/AIDS. The purpose of this study was to test the hypothesis that the sleep quality of patients with HIV/AIDS affected by an altered circadian rhythm correlates with cerebrospinal HIV Tat protein concentration. Ninety-six patients with HIV/AIDS between 20 and 69 years old completed the Pittsburgh Sleep Quality Index. Their circadian rhythm parameters of blood pressure, Tat concentration in cerebrospinal fluid, melatonin concentration, CD4 cell count and HIV RNA viral load in serum were measured. The circadian amplitude of systolic blood pressure and the score for sleep quality (Pittsburgh Sleep Quality Index) were negatively correlated with HIV Tat protein concentration, while the melatonin value was positively correlated with Tat protein concentration.
|
Does automated auditory mismatch negativity paradigm improve coma prognostic accuracy after cardiac arrest and therapeutic hypothermia?
|
EEG and somatosensory evoked potential are highly predictive of poor outcome after cardiac arrest; their accuracy for good recovery is however low. We evaluated whether addition of an automated mismatch negativity-based auditory discrimination paradigm (ADP) to EEG and somatosensory evoked potential improves prediction of awakening. EEG and ADP were prospectively recorded in 30 adults during therapeutic hypothermia and in normothermia. We studied the progression of auditory discrimination on single-trial multivariate analyses from therapeutic hypothermia to normothermia, and its correlation to outcome at 3 months, assessed with cerebral performance categories. At 3 months, 18 of 30 patients (60%) survived; 5 had severe neurologic impairment (cerebral performance categories = 3) and 13 had good recovery (cerebral performance categories = 1-2). All 10 subjects showing improvements of auditory discrimination from therapeutic hypothermia to normothermia regained consciousness: ADP was 100% predictive for awakening. The addition of ADP significantly improved mortality prediction (area under the curve, 0.77 for standard model including clinical examination, EEG, somatosensory evoked potential, versus 0.86 after adding ADP, P = 0.02).
|
Intraflagellar transport (IFT) is a motility process operating between the ciliary/flagellar (interchangeable terms) membrane and the microtubular axoneme of motile and sensory cilia. Multipolypeptide IFT particles, composed of complexes A and B, carry flagellar precursors to their assembly site at the flagellar tip (anterograde) powered by kinesin, and turnover products from the tip back to the cytoplasm (retrograde) driven by cytoplasmic dynein. IFT is essential for the assembly and maintenance of almost all eukaryotic cilia and flagella, and mutations affecting either the IFT motors or the IFT particle polypeptides result in the inability to assemble normal flagella or in defects in the sensory functions of cilia. We found that the IFT complex B polypeptide, IFT27, is a Rab-like small G protein. Reduction of the level of IFT27 by RNA interference reduces the levels of other complex A and B proteins, suggesting that this protein is instrumental in maintaining the stability of both IFT complexes. Furthermore, in addition to its role in flagellar assembly, IFT27 is unique among IFT polypeptides in that its partial knockdown results in defects in cytokinesis and elongation of the cell cycle and a more complete knockdown is lethal.
|
Is midluteal buserelin superior to early follicular phase buserelin in combined gonadotropin-releasing hormone analog and gonadotropin stimulation in in vitro fertilization?
|
To establish whether time to down-regulation and pregnancy and live birth rates were different when buserelin acetate was started in the midluteal phase or early follicular phase in IVF-ET patients. Prospective, controlled, randomized, parallel-group multicenter clinical study. Women attending seven infertility clinics. One hundred twenty-four women with tubal or unexplained infertility with normal menstruation and fertile partners. Intranasal buserelin acetate started in the midluteal or early follicular phase combined with standard hMG and hCG stimulation after achievement of down-regulation. Established IVF-ET methods. Duration of down-regulation; clinical pregnancy and live birth rates. Kaplan-Meier estimations of the duration of down-regulation were 15.5 days when buserelin acetate was started in the early follicular phase (127 cycles) and 14.6 days when it was started in the midluteal phase (96 cycles). This difference was statistically significant. The pregnancy rates per first treatment cycle, treatment cycle, oocyte retrieval, and ET were significantly higher when buserelin acetate was started in the midluteal phase. The live birth rates were also higher, but only significantly so for the rate per first treatment cycle.
|
Burns cause thermal injury to local tissue and trigger systemic acute inflammatory processes, which may lead to multiple distant organ dysfunction. We investigated the protective effect of dietary whey supplementation on distant organs in a rat model. Forty-eight rats were divided into six groups of eight: groups 1 and 2 were the controls, fed a standard diet and a whey-supplemented diet, respectively; groups 3 and 4 were fed a standard diet and subjected to burn injury; and groups 5 and 6 were fed a whey-supplemented diet and subjected to burn injury. We measured the oxidative stress variables, as well as glutathione in the liver and kidney, and histologically examined skin samples obtained 4 h (groups 3 and 5) and 72 h (groups 4 and 6) after burn injury. Glutathione (GSH) levels remained the same in the liver but were slightly elevated in the kidneys after burn injury in the rats fed a standard diet. Whey supplementation caused a significant increase in hepatic GSH levels 4 h after burn injury. Moreover, there was a significant rebound effect in the liver and kidney GSH levels after 72 h and whey supplementation potentiated this effect. Hepatic and renal lipid peroxide levels were also increased 4 h after burn injury in the rats fed a standard diet. Whey supplementation significantly suppressed the burn-induced increase in hepatic and renal lipid peroxide levels. Histological examination revealed that although whey supplementation resulted in decreased subepidermal inflammation, the indicators of wound healing and collagen deposition were not improved.
|
Do prior hematologic conditions carry a high morbidity and mortality in patients supported with continuous-flow left ventricular assist devices?
|
Mechanical support leads to an increased risk of both bleeding and thrombotic events, but little is known about the risk of device support in patients with a baseline predisposition to these events. The aim of this study was to examine outcomes among patients with baseline hematologic conditions who underwent continuous-flow LVAD implantation (CF-LVAD). We retrospectively reviewed records of 286 patients who underwent CF-LVAD implantation at the Columbia University Medical Center between April 2008 and December 2013. Patients diagnosed with the following hematologic conditions were enrolled: idiopathic thrombocytopenic purpura (ITP); Factor V Leiden; elevated Factor VIII; heparin-induced thrombocytopenia (HIT); or undefined hypercoagulable state. Of the 286 CF-LVAD patients implanted during the study period, 12 were considered to have a significant hematologic condition predisposing them to either bleeding or thrombotic events. The study included 5 patients with ITP, 1 with Factor V Leiden, 1 with elevated Factor VIII, 2 with HIT and 3 patients with undefined hypercoagulable state. Patients were supported for a total of 168.46 months, with a median of 10.76 months (IQR 4.78 to 21.36 months). There was a high frequency of thrombotic (0.57 event per patient-year), neurologic (0.36 event per patient-year) and bleeding (0.64 event per patient-year). Actuarial survival rates at 6 and 12 months were 81.8%, but fell to 49% at 2 years.
|
Melatonin, the neurohormone for darkness, mediates photoperiod dependent changes in physiology and behavior by targeting specific membrane bound receptors (MT1 and MT2). In the present study, we investigated the impact of MT1 receptor-deficiency on feeding behavior, locomotor activity and mRNA expression levels encoding for the polypeptide Pomc and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the adenohypophysis (pars distalis, PD and pars intermedia, PI) in a comparison between wild-type (WT) and MT1-deficient (MT1-/-) mice. The MT1-/- mice spent significantly more time in feeding than the WT-mice, while the general locomotor behavior, body weight and the total amount of food consumed did not differ between both genotypes. The nocturnal expression levels of Pomc in ARC and PD were significantly higher in WT as compared to MT1-/- mice and exogenous melatonin administered during the light phase stimulated Pomc expression in WT mice only. No differences were found between WT and MT1-/- mice with regard to Pomc expression levels in the PI.
|
Does depletion of pulmonary intravascular macrophages prevent hyperacute pulmonary xenograft dysfunction?
|
Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been rapid with kidney and heart xenografts, progress with pulmonary xenografts has lagged behind. Recent findings have suggested that donor pulmonary intravascular macrophages may play a critical role in the hyperacute dysfunction of pulmonary xenografts. The function of pulmonary xenografts from pigs depleted of pulmonary intravascular macrophages was compared with the function of xenografts from normal pigs. Pulmonary xenografts from pigs from which pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours) about five times longer than normal (macrophage sufficient) xenografts (4.4+/-1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular macrophages, whereas all normal xenografts had failed.
|
Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3). Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway. Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 μg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death.
|
Does altered endosome biogenesis in prostate cancer have biomarker potential?
|
Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70 years. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and nonmalignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signaling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function are altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumors and concentrated staining within tumor masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer.
|
Primary hemifacial spasm (HFS) is characterized by irregular and involuntary contraction of the muscles innervated by the ipsilateral facial nerve. Treatment controls symptoms and improves quality of life (QoL). Evaluate the initial diagnosis and treatment of HFS prior to referral to a tertiary center. We interviewed through a standard questionnaire 66 patients currently followed in our center. Mean age: 64.19±11.6 years, mean age of symptoms onset: 51.9±12.5 years, male/female ratio of 1:3. None of the patients had a correct diagnosis in their primary care evaluation. Medication was prescribed to 56.8%. Mean time from symptom onset to botulinum toxin treatment: 4.34 ±7.1 years, with a 95% satisfaction. Thirty percent presented social embarrassment due to HFS.
|
Is triglyceride/HDL-cholesterol ratio an independent predictor for coronary heart disease in a population of Iranian men?
|
To determine whether triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), which has been shown to be an indicator of the metabolic syndrome (MetS) and insulin resistance, can predict coronary heart disease (CHD) independently of total cholesterol (TC) and other risk factors in an Iranian population with a high prevalence of MetS and low HDL-C. Between February 1999 and August 2001, 1824 men > or =40 years old, free of clinical cardiovascular diseases at baseline, were followed. Baseline measurements included serum level of TC, HDL-C, TG and risk factors for CHD including age, systolic and diastolic blood pressure, body mass index, waist circumference, diabetes, smoking and a family history of premature cardiovascular diseases. During a median follow up of 6.5 years until March 2007 (11,316 person-years at risk), a total of 163 new CHD events (27 fatal and 136 nonfatal) occurred. The prevalence of MetS in subjects with TG/HDL-C > or =6.9 (top quartile) reached 63.6% versus 3.0% in those with TG/HDL-C <2.8 (low quartile). According to a stepwise Cox proportional hazard model, including TG and TG/HDL-C quartiles, with TC and other risk factors, men in the top quartile of TG/HDL-C relative to the first quartile had a significant hazard ratio (HR) of 1.75 (95% CI, 1.02-3.00), while TG did not remain in the model.
|
H(2)S is pro-inflammatory in inflammatory models, thus we investigated whether H(2)S plays a role in haemorrhagic shock (HS)-associated inflammation. Male, Sprague-Dawley rats were given an inhibitor of H(2)S biosynthesis, DL-propargylglycine (PAG, 50 mg/kg, i. v.) or saline (1 ml/kg) 30 min before blood withdrawal and subjected to HS (mean arterial pressure (MAP) of 40 mM Hg for 90 min) followed by reinfusion of shed blood. Animals were killed at 5, 90, 270 and 630 min after reinfusion. Pre-treatment of animals with PAG 1) increased the HR recovery rate (n = 6 - 12, P < 0.05); 2) attenuated the increase in plasma levels of TNF-alpha and IL-6 and reduced lung iNOS expression levels (n =5 P, < 0.05); and 3) attenuated the increase in plasma levels of ALT and reduced HS-induced increase in liver and lung myeloperoxidase (MPO) activity (n = 5, P < 0.05).
|
Does selenium status in pregnancy influence children 's cognitive function at 1.5 years of age?
|
Selenium deficiency has been shown to affect the neurological development in animals, but human research in this area is scarce. We aimed to assess the impact of selenium status during pregnancy on child development at 1.5 years of age. This prospective cohort study was nested into a food and micronutrient supplementation trial (MINIMat) conducted in rural Bangladesh. Using inductively coupled plasma mass spectrometry, we measured selenium concentrations in erythrocyte fraction of blood collected from 750 mothers at gestational week 30, and calculated μg per g hemoglobin. A revised version of Bayley Scales of Infant Development was used to assess children's mental and psychomotor development. A Bangladeshi version of MacArthur's Communicative Development Inventory was used to assess language comprehension and expression. Linear regression analyses adjusted for multiple covariates were used to assess the associations. Maternal erythrocyte selenium concentrations varied considerably, from 0.19 to 0.87 μg/g hemoglobin (median 0.46 μg/g hemoglobin), and were associated with developmental measures. An increase in erythrocyte selenium by 0.50 μg/g hemoglobin was associated with an increase in children's language comprehension by 3.7 points (0.5 standard deviations; 95% confidence interval: 0.40, 7.1; p = 0.028). The same increase in erythrocyte selenium corresponded to an increase in the girls' psychomotor development by 12 points (0.9 standard deviation; 95% confidence interval: 4.3, 19; p = 0.002), but much less in boys.
|
Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system. The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system. Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique.
|
Is less advanced disease at initiation of salvage androgen deprivation therapy associated with decreased mortality following biochemical failure post-salvage radiation therapy?
|
The optimal clinical context for initiation of salvage androgen deprivation therapy (SADT) following the biochemical recurrence of localized prostate cancer remains controversial. We chose to investigate if disease burden at time of SADT initiation is associated with clinical outcomes following biochemical failure (BF) post-salvage radiation therapy (SRT). Medical records of 575 patients receiving SRT at a single institution from 1986-2010 were retrospectively reviewed. Of 250 patients experiencing BF post-SRT, 172 had a calculable prostate-specific antigen doubling time (PSADT) prior to SADT initiation. These patients comprise the analyzed cohort and were divided into four groups based on characteristics at SADT initiation: those with PSADTs >3 months without distant metastasis (DM) (group 1 [less advanced disease], n=62), those with PSADTs <3 months without DM (group 2 [more advanced disease], n=28), those with DM (group 3 [more advanced disease], n=32), and those not receiving SADT during follow-up (group 4, n=50). Endpoints included prostate cancer-specific mortality (PCSM) and overall mortality (OM). Kaplan-Meier methods were used to estimate survival, and Cox proportional hazards models were used for multivariate analysis. Median follow-up post-SRT was 7.9 years. Patients starting SADT with more advanced disease were at significantly increased risk for PCSM (hazard ratio [HR]:2.8, 95% confidence interval [CI]: 1.4-5.6, p=0.005) and OM (HR:1.9, 95% CI: 1.0-3.5, p=0.04) compared to those receiving SADT with less advanced disease. PCSM and OM did not significantly differ between groups 1 and 4 or groups 2 and 3. Of note, patients in group 4 had very long PSADTs (median = 27.0 months) that were significantly longer than those of group 1 (median = 6.0 months) (p<0.001). Multivariate analysis including groups 1-3 found a pre-SADT PSADT <3 months to be the most significant predictor of PCSM (HR:4.2, 95% CI: 1.6-11.1, p=0.004) and the only significant predictor of OM (HR:2.9, 95% CI: 1.3-6.7, p=0.01).
|
The worldwide outbreak of influenza A (H5N1) viruses among poultry species and humans highlighted the need to develop efficacious and safe vaccines based on efficient and scaleable production. White spot syndrome virus (WSSV) immediate-early promoter one (ie1) was shown to be a stronger promoter for gene expression in insect cells compared with Cytomegalovirus immediate-early (CMV) promoter in luciferase assays. In an attempt to improve expression efficiency, a recombinant baculovirus was constructed expressing hemagglutinin (HA) of H5N1 influenza virus under the control of WSSV ie1 promoter. HA expression in SF9 cells increased significantly with baculovirus under WSSV ie1 promoter, compared with CMV promoter based on HA contents and hemagglutination activity. Further, immunization with baculovirus under WSSV ie1 promoter in chickens elicited higher level anti-HA antibodies compared to CMV promoter, as indicated in hemagglutination inhibition, virus neutralization and enzyme-linked immunosorbent assays. By immunohistochemistry, strong HA antigen expression was observed in different chicken organs with vaccination of WSSV ie1 promoter controlled baculovirus, confirming higher efficiency in HA expression by WSSV ie1 promoter.
|
Does transcutaneous oxygen tension measurements following peripheral transluminal angioplasty procedure have more specificity and sensitivity than ankle brachial index?
|
To evaluate the superiority of transcutaneous oxygen pressure (TcPO2) before, during and after peripheral transluminal angioplasty (PTA) in comparison with ankle brachial index (ABI) in patients with diabetes. 40 consecutive patients with diabetes treated by PTA where included. This study shows results before, during and after PTA and their progression for 8 weeks. The TcPO2 increased from 28.11 ± 8.1 to 48.03 ± 8.4 mmHg, 8 weeks after PTA (p < 0.001). The ABI increased from 0.48 ± 0.38 to 0.77 ± 0.39 after PTA (p < 0.001). After PTA, the stenosis of the vessel decreased from 58.33 ± 20.07% to 21.87 ± 13.57% (p < 0.001). TcPO2 was determined in all the patients, but ABI could not be determined in all patients. Furthermore, we determined patients with "false negatives" with an improvement in ABI and "false positives" in 12.5% of patients. Additionally, in this study, we monitored TcPO2 while performing PTA, revealing variations in each phase of the radiological procedure.
|
Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate. By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the alpha3 domain, but our results suggest that homogenisation also concerns certain residues of the alpha1-alpha2 codomain that lie outside the antigen recognition site.
|
Do metabolite signatures of exercise training in human skeletal muscle relate to mitochondrial remodelling and cardiometabolic fitness?
|
Targeted metabolomic and transcriptomic approaches were used to evaluate the relationship between skeletal muscle metabolite signatures, gene expression profiles and clinical outcomes in response to various exercise training interventions. We hypothesised that changes in mitochondrial metabolic intermediates would predict improvements in clinical risk factors, thereby offering novel insights into potential mechanisms. Subjects at risk of metabolic disease were randomised to 6 months of inactivity or one of five aerobic and/or resistance training programmes (n = 112). Pre/post-intervention assessments included cardiorespiratory fitness ([Formula: see text]), serum triacylglycerols (TGs) and insulin sensitivity (SI). In this secondary analysis, muscle biopsy specimens were used for targeted mass spectrometry-based analysis of metabolic intermediates and measurement of mRNA expression of genes involved in metabolism. Exercise regimens with the largest energy expenditure produced robust increases in muscle concentrations of even-chain acylcarnitines (median 37-488%), which correlated positively with increased expression of genes involved in muscle uptake and oxidation of fatty acids. Along with free carnitine, the aforementioned acylcarnitine metabolites were related to improvements in [Formula: see text], TGs and SI (R = 0.20-0.31, p < 0.05). Muscle concentrations of the tricarboxylic acid cycle intermediates succinate and succinylcarnitine (R = 0.39 and 0.24, p < 0.05) emerged as the strongest correlates of SI.
|
To clarify the reason for the linear pattern of West Nile virus (WNV)-associated chorioretinitis. The study included 12 patients (24 eyes) with WNV-associated chorioretinitis. All the patients underwent a complete ophthalmic evaluation, including dilated fundus examination, fundus photography, fluorescein angiography, and indocyanine green angiography. Characteristics of linear streaks, particularly their relationship to the course of retinal and choroidal vessels, and pattern of retinal nerve fibres, were analysed. All patients had bilateral multifocal chorioretinitis with linear clustering of chorioretinal lesions associated with a variable number of scattered lesions. Linear streaks, variable in number and length, originated from the optic disc or its vicinity in most cases. Their course in all cases appeared to closely follow the course of retinal nerve fibres, rather than that of retinal or choroidal vessels.
|
Does calmodulin kinase II inhibition limit the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors?
|
A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under β-adrenergic receptor (β-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors. Excitation-contraction coupling was investigated in isolated adult rat ventricular myocytes loaded with Fura-2 and paced at 1 Hz allowing coincident measurement of intracellular Ca(2+) and sarcomere shortening. The PDE4 inhibitor Ro 20-1724 (Ro) promoted the inotropic effects of the non-selective β-AR agonist isoprenaline (Iso) and also spontaneous diastolic Ca(2+) waves (SCWs). PDE4 inhibition potentiated RyR2 and PLB phosphorylation at specific PKA and CaMKII sites increasing sarcoplasmic reticulum (SR) Ca(2+) load and SR Ca(2+) leak measured in a 0Na(+)/0Ca(2+) solution ± tetracaine. PKA inhibition suppressed all the effects of Iso ± Ro, whereas CaMKII inhibition prevented SR Ca(2+) leak and diminished SCW incidence without affecting the inotropic effects of Ro. Inhibition of Epac2 but not Epac1 diminished the occurrence of SCWs. PDE3 inhibition with cilostamide induced an SR Ca(2+) leak, which was also blocked by CaMKII inhibition.
|
Private umbilical cord blood (UCB) banking after delivery has increased over the last decade. For adult/somatic stem cell research UCB is an essential source of stem cells and researchers question if the number of UCB samples for research might be reduced by private banking. A survey among seven private blood banks in Germany and analysis and comparison of the number of UCB samples donated for research within the STEMMAT project with private blood banking were performed from 03/2003 to 06/2005 at the Frauenklinik (OB/GYN), Technical University Munich, Germany. Within 27.5 months 1,551 UCB samples were collected for research purposes; the effective recruitment rate was higher than expectations at an effective 66.2 %. Private UCB banking [n = 24] was distributed among three cord blood banks [n = 16, 6 and 4]. The rate of private blood banking was 0.99 % for all deliveries, thus reducing the effective rate for research purpose by only 1.5 %.
|
Is a high body mass index in esophageal cancer patients associated with adverse outcomes following esophagectomy?
|
There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients. From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models. The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors.
|
Floral development can help to shed light on puzzling features across flowering plants. The enigmatic Amazonian monospecific genus Petaladenium of the legume family (Leguminosae) had rarely been collected and only recently became available for ontogenetic studies. The fimbriate-glandular wing petals of P. urceoliferum are unique among the more than 19000 legume species. Ontogenetic data illuminate the systematic position of the genus and foster our understanding on floral evolution during the early diversification of the papilionoid legumes. Flower buds were collected in the field, fixed in 70% ethanol, and investigated using scanning electron microscopy (SEM). Results were compared with existing material from early-diverging papilionoid legumes. Formation of sepals and petals shows bidirectional tendencies. Stamens arise in two whorls, and the single carpel arises concomitantly with the outer stamen whorl. Gland formation starts early on the edges of the wing petals. The carpel reopens for a short time when the initiation of ovules is visible. Stomata at the base of the hypanthium indicate that the flower functions like other standard flag blossoms.
|
Is interleukin-6 production by rat hepatocellular carcinoma cells associated with metastatic potential but not with tumorigenicity?
|
The phenotypic characteristics that allow some tumor cells to metastasize have not been fully identified. The production and/or response of tumor cells to various growth factors have been shown to distinguish cells of differing metastatic potentials. To determine (1) whether rat hepatocellular carcinoma cell lines produce interleukin-6 (IL-6) and (2) whether production of IL-6 correlates with either metastatic potential or tumorigenicity. The clonal cell lines 1682.C.2.9.L0 (poorly metastatic) and 1682.C.2.9.L10 (highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet and adapted to growth in vitro. Both cell lines resulted in primary tumors with equal frequency and developed a 40-mm nodule in a similar period time, when an inoculum of 5 X 10(6) cells was injected subcutaneously; however, only L10 cells metastasized to the lung. These cell lines did not demonstrate differential expression of several antigens noted to correlate with metastatic potential, including CD44 variant glycoprotein, p53, transferrin receptor, and E-cadherin. In contrast, L0 cells produced less than 10 U of IL-6 per milliliter in culture (as determined by bioassay using 7TD1 cells), whereas L10 cells released more than 95 U of this cytokine per milliliter under identical culture conditions (P<.01, Student's t test). In addition, serum concentrations of IL-6 were elevated in animals bearing L10-induced primary tumors but not in those with L0-induced tumors of comparable mass. Exogenous addition of IL-6 to both tumor cell lines had no effect on the rate of growth in vitro, supporting the similar the tumorigenic potentials observed in vivo.
|
High pulse wave velocity (PWV) is related to cardiovascular risk in essential hypertension (EHT). It is reported that short-term treatment with an angiotensin II receptor blocker (ARB) decreases PWV, as well as blood pressure (BP), and increases the serum adiponectin, known as an adipocytokine, which has an anti-atherosclerotic effect. However, it is not known whether long-term treatment with ARB prevents the increase in PWV independently of the reduction of BP, and whether adiponectin is related to the chronic effect of ARB on PWV. In order to examine the short-term effect of ARB on PWV, 9 subjects with EHT had PWV measured before and after treatment with an ARB for 1 month. The treatment significantly reduced PWV and BP. For evaluation of the long-term effect of ARB therapy, 56 consecutive subjects with EHT who were already taking anti-hypertensive drugs other than an angiotensin-converting enzyme inhibitor had their PWV measured. We divided the EHT subjects into 2 groups: (1) the ARB group (EHT treated with an ARB for at least 6 months) and (2) the control group (EHT treated with anti-hypertensive drugs other than an ARB). Although there was no significant difference between the 2 groups in BP, age or body mass index, the PWV value in the ARB group was significantly lower than that in the control group. Moreover, the serum adiponectin concentration in the ARB group was significantly higher than that in the control group.
|
Are serum endostatin concentrations higher in men with symptoms of intermittent claudication?
|
A cleavage fragment of collagen XVIII, endostatin, is released into the circulation and has been demonstrated to have antiangiogenic effects in animal models. We hypothesized that circulating endostatin would be increased in patients with symptoms of lower limb peripheral artery disease. Cross-sectional study. Community dwelling older men. Intermittent claudication was defined using the Edinburgh Claudication Questionnaire (ECQ). Serum endostatin was measured by a commercial ELISA. The association of serum endostatin with intermittent claudication was examined using logistic regression adjusting for age, diabetes, hypertension, dyslipidemia, coronary heart disease, and stroke. Serum endostatin was measured in 1114 men who completed the ECQ. 106 men had intermittent claudication, 291 had atypical pain, and 717 had no lower limb pain. Mean (± standard deviation) serum endostatin concentrations (ng/mL) were 145.22 ± 106.93 for men with intermittent claudication, 129.11 ± 79.80 for men with atypical pain, and 116.34 ± 66.57 for men with no lower limb pain; P < 0.001. A 70 ng/mL increase in endostatin was associated with a 1.17-fold rise in the adjusted odds of having intermittent claudication (OR 1.17, 95% confidence interval 1.00-1.37, and P = 0.050).
|
Esophageal squamous cell carcinoma (ESCC) is one of the most malignant diseases and the five year survival rate remains less than 10%. RASSF10 is a newly identified member of the Ras-association family, but the regulation and the function of RASSF10 in ESCC remain unclear. Research methodologies such as methylation specific PCR (MSP), semi-quantitative RT-PCR, immunohistochemistry, Sodium bisulfite sequencing, and colony formation assay were utilized in this investigation. Loss of RASSF10 expression was found in KYSE150 cells and reduced expression was found in KYSE70 and KYSE180 cells. Expression of RASSF10 was found in KYSE140, KYSE450, KYSE510, TE1, TE3, and TE8 cell lines. Complete methylation was found in KYSE30 and KYSE150 cells, partial methylation was found in KYSE70, KYSE180, KYSE510, and TE1, and unmethylation was found in KYSE140, KYSE450, TE3, and TE8. Re-expression or increased expression was induced by 5-Aza-dC treatment. RASSF10 was methylated in 44.3% primary esophageal squamous cell carcinoma. RASSF10 inhibits cell proliferation and induces G2/M phase arrest in esophageal cancer cells.
|
Does o-012 The Intestinal Wound Regeneration modulate Mucosal Microenvironment to Stimulate Expansion of a Local Pro-restitutive Microbiota?
|
Ulcerative colitis and Crohn's disease frequently cause epithelial damage in the intestine, leading to gut inflammation accompanied by areas of ulceration. The regeneration of damaged mucosa as well as the restoration of intestinal homeostasis involve induced and coordinated proliferation and migration of intestinal epithelial cells. Commensal bacterial colonization of the intestine is essential for normal intestinal development, renewal, and repair. N-formyl peptide receptors (FPRs) are widely expressed pattern recognition receptors that can specifically bind and induce responses to host-derived and bacterial peptides and small molecules during repair of mucosal injury in a redox dependent manner. However, little is known about the host-microbiota crosstalk mediated by FPRs during repair of gut mucosal injuries. Herein, purpose of this study is to exploit the mechanism of mucosal healing promoted by a consortium of gut microbiota that preferentially colonizes ulcerated mucosa undergoing resealing. The regeneration of injured epithelial was studied using defined mechanical wounds inflicted in the mouse distal colon by employing a miniature endoscope and forceps. Microbiota studies were performed by high throughput sequencing of the V4 region of 16s rRNA gene of the bacteria harvested from mucosal wounds undergoing different stages of regenerative events. The high throughput sequencing analysis of bacterial 16s rDNA determined rapid, reversible spatiotemporal alterations in the composition and diversity of microbiota in the wound microenvironment. Our data demonstrated that these ecological changes are dependent on FPR1/NOX2-mediated local tissue hypoxia, depletion of muc2 mucin, and compensatory effect of the over expression of HIF1-regulated MUC3 mucin. Our data show that these events of mucosal regeneration enrich a dominant member of this wound-associated consortium, Akkermansia muciniphila, which is associated with the pro-restitutive function. A. muciniphila, an anaerobic, mucinophilic commensal bacterium, enhanced proliferation and migration of enterocytes adjacent to the colonic wound beds in a process involving FPR1/NOX1 dependent redox signaling.
|
We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups.
|
Do serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer 's disease?
|
Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation. Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control. Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.
|
The poor survival rate of surgically treated patients with oesophageal cancer has not improved substantially over the last 25 years, but combined modality therapy has shown early promising results. A prospective study was undertaken to determine the effect of pre-operative synchronous chemoradiotherapy followed by oesophagectomy in 53 patients with squamous cell carcinoma (SCC) of the oesophagus. The patient group was unselected, other than by fitness for surgery. In 25% of patients, complete pathological regression of the tumour was achieved. All but one of the patients in this subgroup had T2 tumours on pre-operative clinical staging and two had evidence of lymph node involvement, but postoperative pathological examination revealed that pre-operative chemoradiotherapy had downstaged their disease to T0N0. There was no hospital mortality in this subgroup and the actuarial 7 year survival was 69%.
|
Does postoperative PTH monitoring of hypocalcemia expedite discharge after thyroidectomy?
|
Hypocalcemia is the most common complication after total thyroidectomy. Some patients need to stay in the hospital for monitoring of hypocalcemic symptoms and serum calcium levels for several days. We investigated the efficacy and safety of using early postoperative parathyroid hormone (PTH) results for early discharge after thyroidectomy. A retrospective cohort study of 2 sequential groups of patients undergoing total thyroidectomy between January 2010 and March 2013 was undertaken. Patients were divided into 2 groups. In Group 1 (before June 2011), patients had daily monitoring of serum calcium level and hypocalcemic symptoms. They were discharged when calcium level was static and asymptomatic. Postoperative PTH was not utilized for discharge plan. In Group 2 (after June 2011), postoperative PTH and calcium level on day 1 were utilized to dictate subsequent management and discharge plan. Of the 107 patients reviewed, 54 (50.5%) were in Group 1 and 53 (49.5%) were in Group 2. A total of 51 (47.7%) patients developed hypocalcemia. The two groups were comparable in demographic data, early postoperative PTH value, rate of hypocalcemia, the need for oral calcium and vitamin D supplements and rate of permanent hypoparathyroidism. Fewer patients in Group 2 experienced hypocalcemic symptoms, p=0.005. None of the patients in Group 2 needed intravenous calcium supplement (p=0.003). The median postoperative hospital stay for Group 1 was 4 days and for Group 2 was 1 day (p<0.0001).
|
Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII.
|
Is habitual abortion accompanied by low serum levels of placental protein 14 in the luteal phase of the fertile cycle?
|
To study serum levels of placental protein 14 (PP14) in relation to endometrial function in women with a history of habitual abortion. Prospective study. Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. Fifty patients (26 primary and 24 secondary habitual aborters) and 38 controls without a history of abortion studied during a regular cycle. Habitual aborters as a whole or when subgrouped into those with normal cycles (n = 40) or with a luteal phase defect (LPD; n = 10) and control women demonstrated a distinct increase in PP14 levels from late follicular to late luteal phases. In the luteal phase, serum PP14 levels were lower in the patients than in the controls (27.2 +/- 3.1 versus 48.5 +/- 10.1 micrograms/L), but the differences in PP14 levels between habitual aborters with or without LPD was not significant (16.3 +/- 4.3 versus 29.9 +/- 3.7 micrograms/L).
|
To analyze the correlation factors affecting the incidence of burn shock, so as to provide guidance for the clinical treatment of shock after burns. Retrospective analysis of clinical data of 15 624 patients hospitalized in our department from 1973 to 2005 was undertaken . The incidence of shock during every 10 years, as well as the relationship between shock incidence and age, burn area, interval between injury and hospitalization, and complications were analyzed statistically. The incidence of shock during 1973-1980, 1981-1990, 1991-2000 and 2001-2005 periods was 14.69%, 13.50%, 9.38% and 7.88%, respectively, and there was significant difference of shock incidence between each 10 years and its succeeding period (P < 0.01). The occurrence of shock was closely related to age, length of time between injury and hospitalization, and burn area. The shock incidence of children under 7 years old or elderly more than 60 years old was obviously higher than other age groups, and there was positive relationship between burn area and shock incidence. Moreover, the shock incidence of the patients hospitalized later than 4 to 12 hours after burn shock was also markedly higher than those hospitalized earlier (P < 0.01). In addition, the incidence of sepsis, alimentary tract hemorrhage, acute renal failure, pulmonary failure, and cardiac failure in patients with shock was obviously higher than those without shock (P < 0.01).
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.