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Is osteoprotegerin a Better Serum Biomarker of Coronary Artery Calcification than Osteocalcin in Type 2 Diabetes? | Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes. We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores ≥10, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay. Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 ± 2.0 pmol/L vs. 4.2 ± 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R2 for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores. | Natural disasters expose entire communities to stress and trauma, leading to increased risk for psychiatric symptoms. Yet, the majority of exposed individuals are resilient, highlighting the importance of identifying underlying factors that contribute to outcomes. The current study was part of a larger prospective study of children in Long Island, New York (n = 260). At age 9, children viewed unpleasant and pleasant images while the late positive potential (LPP), an event-related potential component that reflects sustained attention toward salient information, was measured. Following the event-related potential assessment, Hurricane Sandy, the second costliest hurricane in United States history, hit the region. Eight weeks after the hurricane, mothers reported on exposure to hurricane-related stress and children's internalizing and externalizing symptoms. Symptoms were reassessed 8 months after the hurricane. The LPP predicted both internalizing and externalizing symptoms after accounting for prehurricane symptomatology and interacted with stress to predict externalizing symptoms. Among children exposed to higher levels of hurricane-related stress, enhanced neural reactivity to unpleasant images predicted greater externalizing symptoms 8 weeks after the disaster, while greater neural reactivity to pleasant images predicted lower externalizing symptoms. Moreover, interactions between the LPP and stress continued to predict externalizing symptoms 8 months after the hurricane. |
Does bRCA1 reflect Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy? | The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. | This study compared the movement demands of players competing in matches from the elite Australian and European rugby league competitions. Global positioning system devices were used to measure 192 performances of forwards, adjustables, and outside backs during National Rugby League (NRL; n = 88) and European Super League (SL; n = 104) matches. Total and relative distances covered overall and at low (0-3.5 m/s), moderate (3.6-5 m/s), and high (>5 m/s) speeds were measured alongside changes in movement variables across the early, middle, and late phases of the season. The relative distance covered in SL matches (95.8 ± 18.6 m/min) was significantly greater (P < .05) than in NRL matches (90.2 ± 8.3 m/min). Relative low-speed activity (70.3 ± 4.9 m/min vs 75.5 ± 18.9 m/min) and moderate-speed running (12.5 ± 3.3 m m/min vs 14.2 ± 3.8 m/min) were highest (P < .05) in the SL matches, and relative high-speed distance was greater (P < .05) during NRL matches (7.8 ± 2.1 m/min vs 6.1 ± 1.7 m/min). |
Does glutamine potently stimulate glucagon-like peptide-1 secretion from GLUTag cells? | Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to nutrient ingestion. As glutamine is an important metabolic fuel for the gut, the aim of this study was to investigate the effect of glutamine on the GLP-1-secreting cell line, GLUTag. GLP-1 release was measured following incubation of GLUTag cells under a range of conditions. Single cells were studied by electrophysiology, calcium imaging and cytosolic ATP measurement using recombinant luciferase. Glutamine was a more potent GLP-1 secretagogue than glucose or other amino acids, increasing GLP-1 release 7.1+/-0.7-fold ( n=19) at 10 mmol/l, with an estimated median effective concentration of between 0.1 and 1 mmol/l. Glutamine (10 mmol/l) induced a sodium-dependent inward current of 3.2+/-1.2 pA per cell ( n=9), which triggered membrane depolarisation and an increase in intracellular calcium. Asparagine and alanine produced electrophysiological and calcium changes that were at least as large as those caused by glutamine, but they were less effective GLP-1 secretagogues, suggesting that glutamine also potentiates secretion downstream of the calcium signal. This was confirmed by measuring secretion in the presence of 30 mmol/l KCl + diazoxide, or in alpha-haemolysin-permeabilised cells. Glutamine increased cytosolic ATP, but was less effective than glucose. | Patients with brain arteriovenous malformation (AVM) are at life-threatening risk of intracranial hemorrhage (ICH). Identification of genetic variants associated with increased new ICH risk would facilitate risk stratification and guide therapeutic intervention. Brain AVM patients evaluated at University of California, San Francisco or Kaiser Permanente Northern California were followed longitudinally. Primary outcome was new ICH after diagnosis; censoring events were any AVM treatment or last follow-up examination. The association of ApoE epsilon2 and epsilon4 genotype with new ICH was evaluated by Kaplan-Meier survival analysis and further characterized via a Cox proportional hazards model. We genotyped 284 brain AVM patients (50% women; 57% Caucasian; median follow-up time, 0.3 yr) including 18 patients with a history of new ICH). ApoE epsilon2, but not ApoE epsilon4 genotype, was associated with new ICH (P = 0.0052). ApoE epsilon2 carriers had fivefold increased risk of new ICH (hazard ratio, 5.09; 95% confidence interval, 1.46-17.7; P = 0.010; Cox proportional hazards model adjusting for race/ethnicity and clinical presentation). Subset analysis in the largest homogenous ethnic subcohort (Caucasians) confirmed the increased risk of new ICH in ApoE epsilon2 carriers (hazard ratio, 8.71; 95% confidence interval, 1.4-53.9; P = 0.020; multivariate model adjusting for clinical presentation). |
Do macrophages dictate the progression and manifestation of hypertensive heart disease? | Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). | To determine whether in-house patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) results predict Imaging and Radiation Oncology Core (IROC)-Houston phantom results. IROC Houston's IMRT head and neck phantoms have been irradiated by numerous institutions as part of clinical trial credentialing. We retrospectively compared these phantom results with those of in-house IMRT QA (following the institution's clinical process) for 855 irradiations performed between 2003 and 2013. The sensitivity and specificity of IMRT QA to detect unacceptable or acceptable plans were determined relative to the IROC Houston phantom results. Additional analyses evaluated specific IMRT QA dosimeters and analysis methods. IMRT QA universally showed poor sensitivity relative to the head and neck phantom, that is, poor ability to predict a failing IROC Houston phantom result. Depending on how the IMRT QA results were interpreted, overall sensitivity ranged from 2% to 18%. For different IMRT QA methods, sensitivity ranged from 3% to 54%. Although the observed sensitivity was particularly poor at clinical thresholds (eg 3% dose difference or 90% of pixels passing gamma), receiver operator characteristic analysis indicated that no threshold showed good sensitivity and specificity for the devices evaluated. |
Does brain-Derived Neurotrophic Factor contribute to Colonic Hypermotility in a Chronic Stress Rat Model? | Brain-derived neurotrophic factor (BDNF) has prokinetic effects on gut motility and is increased in the colonic mucosa of irritable bowel syndrome. We aimed to investigate the possible involvement of BDNF in stress-induced colonic hypermotility. Male Wistar rats were exposed to daily 1-h water avoidance stress (WAS) or sham WAS for 10 consecutive days. The presence of BDNF and substance P (SP) in the colonic mucosa was determined using enzyme immunoassay kits. Immunohistochemistry and western blotting were performed to assess the expression of BDNF and its receptor, TrkB. The contractions of muscle strips were studied in an organ bath system. Repeated WAS increased the fecal pellet expulsion and spontaneous contractile activities of the colonic muscle strips. Both BDNF and SP in the colonic mucosa were elevated following WAS. Immunohistochemistry revealed the presence of BDNF and TrkB in the mucosa and myenteric plexus. BDNF and TrkB were both up-regulated in colon devoid of mucosa and submucosa from the stressed rats compared with the control. BDNF pretreatment caused an enhancement of the SP-induced contraction of the circular muscle (CM) strips. TrkB antibody significantly inhibited the contraction of the colonic muscle strips and attenuated the excitatory effects of SP on contractions of the CM strips. Repeated WAS increased the contractile activities of the CM strips induced by SP after BDNF pretreatment, and this effect was reversed by TrkB antibody. | Cancer antigen-125 (CA-125) might be a useful biomarker to predict long-term mortality in patients with recent exacerbation of chronic obstructive pulmonary disease (COPD). A total of 87 consecutive patients with COPD were evaluated prospectively. Mean age of patients was 68 ± 10 years (55% males, 45% females) with a median follow-up period of 49 months. Optimal cut-off value of CA-125 to predict mortality was found as >93.34 U/ml, with 91% specificity and 40% sensitivity. After follow-up, 20 out of 87 (23%) experienced cardiovascular death. CA-125 levels were higher among those who died compared to those who survived [55 (12-264) versus 28 (5-245) U/ml, p = 0.013]. In multivariate Cox proportional-hazards model with forward stepwise method, only CA-125 > 93.34 U/ml on admission (HR = 3.713, 95% CI: 1.035-13.323, p = 0.044) remained associated with an increased risk of death. |
Does radiofrequency application to the posteroseptal region alter retrograde accessory pathway activation? | Radiofrequency applications to the posteroseptal region can ablate the atrioventricular accessory pathway residing in this area. In conjunction with the adjacent anatomic structures, however, ablative lesions which do not effectively ablate the accessory pathway could markedly alter retrograde atrial activation sequence and confound interpretation of further mapping of an accessory pathway. Electrophysiologic studies, endocardial activation mapping and radiofrequency catheter ablation were undertaken in three patients with recurrent supraventricular tachycardia. Patients were initially thought to have a single posteroseptal accessory pathway; earliest ventrioatrial activation during tachycardias and during ventricular pacing was at the coronary sinus ostium, but initial radiofrequency applications were unsuccessful to ablate the pathway. After initial radiofrequency applications to the posteroseptal region, the earliest retrograde atrial activation changed to the right atrial free wall in two patients. Additional radiofrequency application to the posteroseptal area was able to ablate the single posteroseptal accessory pathway in one patient. Radiofrequency application to the right atrial free wall was required to stop tachycardia initiation in other patient. The third patient was suspected of having a slow-slow atrioventricular nodal reentry tachycardia. Radiofrequency application to the posteroseptal area changed the earliest retrograde atrial activation to the distal coronary sinus recording site, mimicking an accessory pathway at the left atrial free wall. Radiofrequency application to the anteroseptum was able to ablate the concealed accessory pathway. | IL-2 deficient (IL-2(-/-)) mice mono-colonized with E. coli mpk develop colitis whereas IL-2(-/-)-mice mono-colonized with B. vulgatus mpk do not and are even protected from E. coli mpk induced colitis. We investigated if mono-colonization with E. coli mpk or B. vulgatus mpk differentially modulates distribution, activation and maturation of intestinal lamina propria (LP) dendritic cells (DC). LP DC in mice mono-colonized with protective B. vulgatus mpk or co-colonized with E. coli mpk/B. vulgatus mpk featured a semi-mature LP DC phenotype (CD40(lo)CD80(lo)MHC-II(hi)) whereas mono-colonization with colitogenic E. coli mpk induced LP DC activation and maturation prior to onset of colitis. Accordingly, chemokine receptor (CCR) 7 surface expression was more strikingly enhanced in mesenteric lymph node DC from E. coli mpk than B. vulgatus mpk mono- or co-colonized mice. Mature but not semi-mature LP DC promoted Th1 polarization. As B. vulgatus mpk promotes differentiation of semi-mature DC presumably by IL-6, mRNA and protein expression of IL-6 was investigated in LP DC. The data demonstrated that IL-6 mRNA and protein was increased in LP DC of B. vulgatus mpk as compared to E. coli mpk mono-colonized IL-2(-/-)-mice. The B. vulgatus mpk mediated suppression of CCR7 expression and DC migration was abolished in IL-6(-/-)-DC in vitro. |
Is reexploration for bleeding a risk factor for adverse outcomes after cardiac operations? | Although previous studies have included early reexploration for bleeding as a risk factor in analyzing adverse outcomes after cardiac operations, reexploration for bleeding has not been systematically examined as a multivariate risk factor for increased morbidity and mortality after cardiac surgery. Furthermore, multivariate predictors of the need for reexploration have not been identified. Accordingly, we performed a retrospective analysis of 6100 patients requiring cardiopulmonary bypass from January 1, 1986, to December 31, 1993. Eighty-five patients who had ventricular assist devices were excluded from further analysis because of the prevalence of bleeding and the significant morbidity and mortality associated with placement of a ventricular assist device, unrelated to reexploration. In the remaining 6015 patients, potential adverse outcomes analyzed included operative mortality, mediastinitis, stroke, renal failure, adult respiratory distress syndrome, prolonged mechanical ventilation, sepsis, atrial arrhythmias, and ventricular arrhythmias. To control for the confounding effects of other risk factors, we performed a multivariate logistic regression analysis. Potential covariates considered in the logistic model included age, sex, race, history of reoperation, urgency of the operation, congestive heart failure, prior myocardial infarction, renal failure, diabetes, hypertension, chronic obstructive pulmonary disease or stroke, and the bypass and crossclamp time. The overall incidence of reexploration was 4.2% (253/6015). Four independent risk factors--increased patient age (p < 0.001), preoperative renal insufficiency (p = 0.02), operation other than coronary bypass (p < 0.001), and prolonged bypass time (p = 0.0.3)--were identified as predictors of the need for reexploration. The preoperative use of aspirin, heparin, or thrombolytic agents and the bleeding time were not identified as predictors. Reexploration for bleeding was identified as a strong independent risk factor for operative mortality (p = 0.005), renal failure (p < 0.0001), prolonged mechanical ventilation (p < 0.0001), adult respiratory distress syndrome (p = 0.03), sepsis (p < 0.0001), and atrial arrhythmias (p = 0.006). | Ursolic acid (UA) is a pentacyclic triterpenoid found in most plant species, which has been shown anti-inflammatory and anti-oxidative activities. In this study, we examined the effects of UA on collagen-induced arthritis (CIA) in mice, and to identify the mechanisms underlying the effects. CIA was induced in mice. Two weeks later, the mice were treated with UA (150 mg/kg, ip, 3 times per week) for 4 weeks. The expression of cytokines and oxidative stress markers in joint tissues was measured with immunohistochemistry. The numbers of CD4+IL-17+, CD4+CD25+Foxp3+ and pSTAT3 cells in spleens were determined using confocal immunostaining or flowcytometric analyses. Serum antibody levels and B cell-associated marker mRNAs were analyzed with ELISAs and qRT-PCR, respectively. CD4+ T cells and CD19+ B cells were purified from mice spleens for in vitro studies. UA treatment significantly reduced the incidence and severity of CIA-induced arthritis, accompanied by decreased expression of proinflammatory cytokines (TNF-α, IL-1β, IL-6, IL-21 and IL-17) and oxidative stress markers (nitrotyrosine and iNOS) in arthritic joints. In CIA mice, UA treatment significantly decreased the number of Th17 cells, while increased the number of Treg cells in the spleens, which was consistent with decreased expression of pSTAT3, along with IL-17 and RORγt in the splenocytes. In addition, UA treatment significantly reduced the serum CII-specific IgG levels in CIA mice. The inhibitory effects of UA on Th17 cells were confirmed in an in vitro model of Th17 differentiation. Furthermore, UA dose-dependently suppressed the expression of B cell-associated markers Bcl-6, Blimp1 and AID mRNAs in purified CD19+ B cells pretreated with IL-21 or LPS in vitro. |
Does vP2118 have major roles in Vibrio parahaemolyticus response to oxidative stress? | Reactive oxygen species (ROS), including superoxide anion radical, induce chronic risk of oxidative damage to many cellular macromolecules resulting in damage to cells. Superoxide dismutases (SODs) catalyze the dismutation of superoxide to oxygen and hydrogen peroxide and are a primary defense against ROS. Vibrio parahaemolyticus, a marine bacterium that causes acute gastroenteritis following consumption of raw or undercooked seafood, can survive ROS generated by intestinal inflammatory cells. However, there is little information concerning SODs in V. parahaemolyticus. This study aims to clarify the role of V. parahaemolyticus SODs against ROS. V. parahaemolyticus SOD gene promoter activities were measured by a GFP reporter assay. Mutants of V. parahaemolyticus SOD genes were constructed and their SOD activity and resistance to oxidative stresses were measured. Bioinformatic analysis showed that V. parahaemolyticus SODs were distinguished by their metal cofactors, FeSOD (VP2118), MnSOD (VP2860), and CuZnSOD (VPA1514). VP2118 gene promoter activity was significantly higher than the other SOD genes. In a VP2118 gene deletion mutant, SOD activity was significantly decreased and could be recovered by VP2118 gene complementation. The absence of VP2118 resulted in significantly lowered resistance to ROS generated by hydrogen peroxide, hypoxanthine-xanthine oxidase, or Paraquat. Furthermore, both the N- and C-terminal SOD domains of VP2118 were necessary for ROS resistance. | Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes. Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol. Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. |
Does pacemaker stress echocardiography predict cardiac events in patients with permanent pacemaker? | Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied. We studied 136 patients (mean age 64+/-12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate). Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5+/-2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P=.01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P=.004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model. | Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. |
Does foam during reconstitution affect the potency of botulinum toxin type A? | Among factors that may affect the potency of botulinum toxin A (Botox), it is said that foam, together with bubbles, may cause surface denaturation of the toxin. To determine whether the muscle relaxation effect of Botox is preserved and has the same duration when it is reconstituted in the presence of foam. Six female volunteers, aged 42 to 56 years old, were treated for glabellar and periocular wrinkles. Each half of the face was treated with 16 U of Botox divided in four sites: three at the lateral orbital area and one at the medial brow, in the glabellar region. The right side received Botox gently reconstituted with saline to avoid foaming formation. The left side of the face was treated with Botox that was rapidly reconstituted in order to achieve as many bubbles as possible, even with shaking. Blinded observers compared pretreatment and posttreatment photographs and answered assessment-related questions. The results were analyzed clinically and statistically. There was no difference in muscle paralysis between treated sides in all patients, neither in early (15 days) nor late (4 months) follow-up evaluations. | Previous studies have demonstrated an association between polymorphisms in the regulatory regions of Cyclophilin A (CypA) and susceptibility to both HIV-1 infection and disease progression. Here we studied whether these polymorphisms are associated with susceptibility to HIV-1 infection and disease progression in the Amsterdam Cohort on HIV-1 infection and AIDS (ACS) in a group of men having sex with men (MSM) and drug users (DU). We screened participants of the ACS for the C1604G and A1650G polymorphisms in the regulatory regions of CypA. The prevalence of the 1650G allele was significantly higher in high risk seronegative MSM than in HIV-1 infected MSM. However, C1604G or A1650G were not associated with the clinical course of infection in MSM of the ACS. Interestingly, participants of the ACS-DU who carried the 1604G allele showed a significantly accelerated progression when viral RNA load above 10(4.5) copies per ml plasma was used as an endpoint in survival analysis. |
Does btk inhibition suppress agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants? | Bruton's tyrosine kinase (Btk) is required for B lymphocyte and myeloid cell contributions to pathology in murine models of arthritis. Here, we examined the potential contributions of synovial Btk expression and activation to inflammation in rheumatoid arthritis (RA). Btk was detected by immunohistochemistry and digital image analysis in synovial tissue from biologically naive RA (n=16) and psoriatic arthritis (PsA) (n=12) patients. Cell populations expressing Btk were identified by immunofluorescent double labelling confocal microscopy, quantitative (q-) PCR and immunoblotting. The effects of a Btk-specific inhibitor, RN486, on gene expression in human macrophages and RA synovial tissue explants (n=8) were assessed by qPCR, ELISA and single-plex assays. Btk was expressed at equivalent levels in RA and PsA synovial tissue, restricted to B lymphocytes, monocytes, macrophages and mast cells. RN486 significantly inhibited macrophage IL-6 production induced by Fc receptor and CD40 ligation. RN486 also reduced mRNA expression of overlapping gene sets induced by IgG, CD40 ligand (CD40L) and RA synovial fluid, and significantly suppressed macrophage production of CD40L-induced IL-8, TNF, MMP-1 and MMP-10, LPS-induced MMP-1, MMP-7 and MMP-10 production, and spontaneous production of IL-6, PDGF, CXCL-9 and MMP-1 by RA synovial explants. | Outcome after correction of atrioventricular septal defect depends to a great deal on the postoperative function of the left atrioventricular valve. The related role of the zone of apposition ('cleft') has been debated: should it be closed (bileaflet repair) or should it be left untouched (trileaflet repair)? This study aims to answer the question by comparing the outcome of patients treated according to these two approaches. We reviewed all our patients who underwent repair of complete atrioventricular septal defect from 1984 to 1997 and selected those in whom the closure of the zone of apposition in principle would have been possible. Two groups with similar characteristics were constituted: group I (n=63), where the zone of apposition was deliberately not closed as part of a trileaflet repair (postoperative open zone of apposition) and group II (n=96), where it was electively closed as part of a bileaflet AV valve repair (closed zone of apposition). Since we changed from a trileaflet to a bileaflet repair in 1987, the two groups differ in terms of size and length of follow-up. Outcome was compared with regard to survival and freedom from reoperation for left atrioventricular valve incompetence. Late atrioventricular valve function was evaluated by Echo-Doppler. For statistical analysis, we used Chi-square or Fisher's exact test, the Mann-Whitney test and the log-rank test for comparison of Kaplan-Meier curves. The difference was considered statistically significant with a P-value of 0.05 or less. Early mortality was 9.5% (6/63) in group I and 3.1% (3/96) in group II (P=0.16). Actuarial survival after 1, 4 and 8 years was 80.4, 68.4 and 64.8%, respectively, for group I. Actuarial survival for group II was 94.7, 92.1 and 92.1% (P=0.0002). Freedom from reoperation for left atrioventricular valve regurgitation was 90.2, 85.6 and 77.8% for group I at the same time interval. It was a constant 97.9% for group II (P=0.0016). At reoperation, left atrioventricular valve regurgitation was present through the open zone of apposition in 63% of group I cases. The follow-up is 96% (126/131) complete. An increase in degree of left atrioventricular valve incompetence was noted in 28% (11/39) of group I cases and in 9% (8/87) of group II cases (P=0.0131). |
Does mometasone furoate nasal spray relieve the ocular symptoms of seasonal allergic rhinoconjunctivitis? | Recent studies have examined the effects of intranasal corticosteroids (INSs) in relieving the ocular symptoms of seasonal allergic rhinoconjunctivitis (SAR) and perennial allergic rhinitis. However, because most of these studies were based on subjective assessments by patients, the associated factors and mechanism of action are unknown. A single-center, randomized, double-blind, parallel-group study was carried out in which patients with SAR were randomly assigned to an INS mometasone furoate nasal spray (MFNS) group or to a placebo group and treated once daily for 4 weeks. Substance P concentrations in tears were measured, ocular and nasal symptoms were recorded by patients in an allergy diary, and findings were recorded by an ophthalmologist. There was no significant difference between treatment groups in the mean change from baseline of substance P concentration in tears after 4 weeks of treatment, but the mean change tended to increase in the placebo group and tended to decrease in the MFNS group (P = 0.089). All ocular and nasal symptom scores, except eye tearing, were significantly lower in the MFNS group than in the placebo group. Furthermore, substance P concentrations were strongly correlated with ocular and nasal symptom scores. | Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis) or patients with proximal gastric cancer (P=0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis). |
Is methacholine responsiveness associated with O3-induced decreases in FEV1? | Controlled human exposure studies have suggested that the National Ambient Air Quality Standard for ozone (O3) may not provide a margin of safety to protect the most susceptible members of the population from adverse health effects. Although the subgroups of the population that are most susceptible to O3 have not been identified, recent work in our laboratory suggested that methacholine responsiveness might be an important determinant of susceptibility to O3. To test the hypothesis that methacholine responsiveness is correlated with FEV1 response after O3 exposure, we conducted methacholine challenge tests and O3 (0.20 ppm) and filtered air exposures for 4 h with moderate exercise on 66 healthy individuals. Repeated measures analysis of variance demonstrated significant changes in FEV1 (-0.82 +/- 0.63 L), FVC (-0.69 +/- 0.48 L), and specific airway resistance (SRaw) (+1.5 +/- 1.1 L x cm H2O/L/s) across the O3 exposure that persisted after adjusting for responses to air. Baseline PC100 (the concentration of methacholine that caused a doubling of the baseline SRaw) was weakly associated with O3-induced increases in SRaw (F1.54 = 2.85, p = 0.09), but not O3-induced declines in FEV1 or FVC. There was a weak association (r = -0.29) between O3-induced responses for SRaw and FEV1. The FEV1 responses for O3 were weakly associated with the symptoms of cough (r = -0.37), wheeze (r = -0.29), chest pain on deep inspiration (r = -0.31), and shortness of breath (r = -0.37), but not with chest discomfort or sputum production. | Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). |
Does loss of SFRP1 Expression be Associated with Poor Prognosis in Hepatocellular Carcinoma? | Secreted frizzled-related protein-1 (SFRP1) is a well-known inhibitor of the wingless type (WNT)-β-catenin signaling pathway and its inactivation plays an important role in the development and progression of various types of cancer. However, the clinical significance of SFRP1 expression in patients with hepatocellular carcinoma (HCC) remains unknown. A total of 63 patients with HCC who underwent hepatectomy at our Institution were enrolled in this study. A quantitative real-time polymerase chain reaction (RT-PCR) was performed to determine the SFRP1 mRNA expression level in both the tumorous and non-tumorous tissues of HCC. The patients were divided into low and high gene-expression groups based on the SFRP1 gene expression level in their tumor tissues. We analyzed the differences in clinicopathological characteristics between these two groups of patients. The expression level of SFRP1 was significantly lower in tumor tissue than in non-tumor tissue (p<0.0001). Significant correlations were observed between a high expression of SFRP1 in tumor tissue and older than 65 years (p=0.030), tumor size less than 5 cm (p=0.011); and no vascular invasion (p=0.004). Patients with high SFRP1 expression in tumor tissue had a significantly better overall survival rate (p=0.040). However, the SFRP1 expression level was not defined as an independent risk factor for patient survival based on results of multivariate analysis. | To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission. Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging ((1)H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm(3) volume of interest (VOI) with 3D multivoxel (1)H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation. The patients' mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls' 0.94 and 9.6 mM. In contrast, the patients' mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls' 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023). |
Does temporary malar augmentation help with preoperative planning for a permanent procedure? | Cheek augmentation improves the appearance of patients with flat malar eminences, creating a more youthful image. Autologous adipose tissue has been demonstrated to be a safe injectable filling material for malar augmentation. Before proceeding to fat transplantation, a rapidly absorbable substance such as normal saline is injected into the cheek with a fine needle to enhance the malar eminence. This method helps the surgeon to determine the location and amount of fat to be injected. Patients can also see a simulation of the final results. | CD73 is a membrane associated 5'-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course. Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray. Associations between CD73 expression and retrospectively obtained clinicopathological data were evaluated by contingency analysis. Survival analysis was performed to investigate the predictive value of CD73 within the subgroup of pTa and pT1 tumors in regard to progression-free survival (PFS). High CD73 expression was found in 46 (26.4%) patients and was significantly associated with lower stage, lower grade, less adjacent carcinoma in situ and with lower Ki-67 proliferation index. High CD73 immunoreactivity in the subgroup of pTa and pT1 tumors (n = 158) was significantly associated with longer PFS (HR: 0.228; p = 0.047) in univariable Cox regression analysis. |
Does nitric oxide mediate the blood pressure response to mental stress in humans? | Nitric oxide (NO) regulates arterial pressure by modulating peripheral vascular tone and sympathetic vasoconstrictor outflow. NO synthesis is impaired in several major cardiovascular disease states. Loss of NO-induced vasodilator tone and restraint on sympathetic outflow could result in exaggerated pressor responses to mental stress. We, therefore, compared the sympathetic (muscle sympathetic nerve activity) and haemodynamic responses to mental stress performed during saline infusion and systemic inhibition of NO-synthase by NG-monomethyl-L-arginine (L-NMMA) infusion. The major finding was that mental stress which during saline infusion increased sympathetic nerve activity by ~50 percent and mean arterial pressure by ~15 percent had no detectable sympathoexcitatory and pressor effect during L-NMMA infusion. These findings were not related to a generalised impairment of the haemodynamic and/or sympathetic responsiveness by L-NMMA, since the pressor and sympathetic nerve responses to immersion of the hand in ice water were preserved during L-NMMA infusion. | It has been shown that the p53 gene is mutated in 30-80% of ovarian carcinomas and that the genetic alterations most often manifest as an accumulation of mutant p53 protein in tumor tissue. The prognostic significance of these findings for patients with ovarian cancer, however, must be established clearly. Mutant p53 protein in 90 consecutive epithelial ovarian carcinomas was quantitatively analyzed using a time-resolved immunofluorometric procedure. In contrast to immunohistochemical techniques, this method uses two anti-p53 antibodies. The Cox model was used to evaluate the strength of the associations between the prognostic markers and disease relapse or death at univariate and multivariate levels. Kaplan-Meier survival curves were calculated for patients who were p53-positive or negative and for subgroups with a different clinical stage, histologic grade, or residual postsurgical tumor. The positivity rates for p53 included 1/21 (5%) with Stage I disease, 1/6 (17%) with Stage II, 29/51 (57%) with Stage III, and 8/12 (67%) with Stage IV (total = 39/90, 43%). Patients with p53-negative tumors had a significantly longer disease free survival than did patients with p53-positive tumors (P = 0.03); these results were similar for overall survival (P = 0.06). Multivariate analysis revealed that the presence of postsurgical residual tumor was the only predictor significantly associated with poor patient outcome. However, when patients were divided into groups based on histologic grade, patients with well (G1) and moderately (G2) differentiated tumors had a significantly higher risk of cancer relapse and death if mutant p53 protein was present in their tumors compared with patients who were negative for mutant p53 protein (< 0.01). |
Is mesoderm required for coordinated cell movements within zebrafish neural plate in vivo? | Morphogenesis of the zebrafish neural tube requires the coordinated movement of many cells in both time and space. A good example of this is the movement of the cells in the zebrafish neural plate as they converge towards the dorsal midline before internalizing to form a neural keel. How these cells are regulated to ensure that they move together as a coherent tissue is unknown. Previous work in other systems has suggested that the underlying mesoderm may play a role in this process but this has not been shown directly in vivo. Here we analyze the roles of subjacent mesoderm in the coordination of neural cell movements during convergence of the zebrafish neural plate and neural keel formation. Live imaging demonstrates that the normal highly coordinated movements of neural plate cells are lost in the absence of underlying mesoderm and the movements of internalization and neural tube formation are severely disrupted. Despite this, neuroepithelial polarity develops in the abnormal neural primordium but the resulting tissue architecture is very disorganized. | Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia. To determine effect of vitamin E supplementation on ribavirin-associated haemolysis in chronic hepatitis C treated with standard alpha-interferon and ribavirin. Fifty-one naive chronic hepatitis C patients were randomized to receive either alpha-interferon/ribavirin therapy (control) or therapy plus vitamin E 800 IU b.d. with 24-week follow-up. Alanine aminotransferase ALT, haemoglobin and reticulocyte percentage were monitored. Symptoms and health-related quality of life were also monitored at each visit. Forty-seven subjects were treated (27 vitamin E /20 controls). Thirteen withdrew because of adverse effects or non-compliance. Groups were similar in demographics, genotype and baseline lab indices. Comparison with baseline, treatment and follow-up values showed a significant haemoglobin and ALT reduction in both groups. There was no significant difference in haemoglobin and reticulocyte percentage between groups. Sustained viral response was not significantly different between vitamin E (11/18) and control (6/16) groups. Three patients required ribavirin dose-reduction in the vitamin E group compared with two controls. Health-related quality of life during and end-of-treatment was not different between groups. |
Is maternal second-hand smoke exposure in pregnancy associated with childhood asthma development? | Childhood asthma development has been associated with active maternal smoking during pregnancy, but its association with maternal second-hand smoke exposure in pregnancy needs to be evaluated. We investigated longitudinal associations between maternal smoke exposure in pregnancy and childhood asthma development. In a population-based cohort of 5619 seven-year-old Toronto children, parents reported age of physician-diagnosed asthma development, maternal smoking during pregnancy, home second-hand smoke exposure from pregnancy until 7 years, demographics, and family history of atopy. By using Cox proportional and discrete-time hazard survival analyses, we evaluated associations between asthma and maternal smoking or home second-hand smoke exposure in pregnancy. During pregnancy, 5.0% of mothers smoked and 6.2% were nonsmokers and exposed to home second-hand smoke; 15.5% of children developed asthma. Children whose mothers smoked or were exposed to home second-hand smoke during pregnancy were more likely to develop asthma (adjusted hazard ratio [HR] 1.30 [95% CI, 1.06-1.60]). The association persisted for children of nonsmoking mothers with home second-hand smoke exposure during pregnancy (adjusted HR 1.34 [95% CI, 1.01-1.76]), children with asthma symptoms in the past year (adjusted HR 1.36 [95% CI, 1.03-1.79]), and after adjusting for home second-hand smoke exposure from birth to age 7 years. | To assess any relationship between hyperglycemia and muscle protein catabolism associated with critical illness. Cohort analytic study. Clinical research center and intensive care unit of a university hospital. Six healthy volunteers and five patients with severe sepsis. Study subjects were given infusions of 6,6,d2 glucose and 15N lysine for 6 hours. After infusion of the stable isotopes for 2 hours (basal period), dichloroacetate, which accelerates pyruvate oxidation, was given (dichloroacetate period). Leg blood flow was measured by indocyanine green dye dilution, and femoral artery and vein substrate concentrations were quantitated. The metabolic rates of glucose production, oxidation, and clearance; the whole-body protein breakdown rate; and the net efflux of amino acids from the leg were determined. In comparison with the healthy volunteers, septic patients had significant elevations in glucose production, oxidation, and clearance, accelerated protein catabolism, and greater net peripheral efflux of amino acids. Dichloroacetate significantly decreased glucose production and increased the percentage of glucose directed toward oxidation in both healthy volunteers and septic patients. However, this dichloroacetate-induced perturbation of glucose utilization had no significant effect on whole-body protein breakdown or the efflux of specific amino acids from the leg except for alanine, whose net efflux doubled (P < or = .05). |
Does chronic administration of anabolic androgenic steroid alter murine thyroid function? | The administration of anabolic-androgenic steroids (AAS) to improve athletic performance has increased notably during the past three decades, even among nonathletes. Thyroid function is affected by AAS use in humans, although the mechanisms of the effects of AAS are unclear. We evaluated the effects on thyroid function of supraphysiologic doses of nandrolone decanoate (DECA), which is one of the most anabolic-androgenic steroids (AAS) used. Male Wistar rats were treated with vehicle or 1 mg.100 g(-1) body weight (b.w.) of DECA, once a week for 8 wk, intramuscularly. We analyzed thyroperoxidase (TPO) activity, type 1 iodothyronine deiodinase (D1) activities in liver, kidney, pituitary, and thyroid, and serum levels of total T3, total T4, free T4, and TSH. Parametric and nonparametric t-tests were employed for statistical analyses. Treated animals showed a significant increase in the weight of kidneys and heart, and a decrease in the relative testis weight. Retroperitoneal adipose tissue was only slightly decreased. DECA treatment induced a significant increase in the absolute and relative thyroid gland weight. The concentrations of total serum T3, free T4, and TSH decreased significantly with treatment, but total serum T4 levels were unchanged. Thyroperoxidase activity was unaltered, whereas liver and kidney D1 activities were significantly increased, but pituitary and thyroid D1 did not change. | The role of Helicobacter pylori in gastro-oesophageal reflux disease (GERD) is controversial. To compare the severity of GERD in infected vs. non-infected patients, as part of an ongoing randomized controlled trial that examines the impact of H. pylori eradication on GERD-related outcomes. Consecutive GERD patients underwent urea breath testing and completed validated GERD symptom severity, and quality of life questionnaires as well as, 24-h pH-metry. These parameters, as well as demographics and endoscopic findings were assessed in double-blinded fashion and compared between H. pylori-infected and non-infected subjects. Helicobacter pylori-infected GERD patients (n=50) were significantly older and less educated than non-infected patients (n=51). They also used proton pump inhibitors less often but had no difference in symptoms (as measured with both the Spechler's Activity Index and the Gastrointestinal Symptom Rating Scale), quality of life, endoscopic findings or 24-h pH-metry findings. |
Does variability of Automated Intraoperative ST Segment Values predict Postoperative Troponin Elevation? | Intraoperative electrocardiographic monitoring is considered a standard of care. However, there are no evidence-based algorithms for using intraoperative ST segment data to identify patients at high risk for adverse perioperative cardiac events. Therefore, we performed an exploratory study of statistical measures summarizing intraoperative ST segment values determine whether the variability of these measurements was associated with adverse postoperative events. We hypothesized that elevation, depression, and variability of ST segments captured in an anesthesia information management system are associated with postoperative serum troponin elevation. We conducted a single-institution, retrospective study of intraoperative automated ST segment measurements from leads I, II, and III, which were recorded in the electronic anesthesia record of adult patients undergoing noncardiac surgery. The maximum, minimum, mean, and SD of ST segment values were entered into logistic regression models to find independent associations with myocardial injury, defined as an elevated serum troponin concentration during the 7 days after surgery. Performance of these models was assessed by measuring the area under the receiver operator characteristic curve. The net reclassification improvement was calculated to quantify the amount of information that the ST segment values analysis added regarding the ability to predict postoperative troponin elevation. Of 81,011 subjects, 4504 (5.6%) had postoperative myocardial injury. After adjusting for patient characteristics, the ST segment maximal depression (e.g., lead I: odds ratio [OR], 1.66; 95% confidence interval [CI], 1.26-2.19; P = 0.0004), maximal elevation (e.g., lead I: OR, 1.70; 95% CI, 1.34-2.17; P < 0.0001), and SD (e.g., lead I: OR, 0.16; 95% CI, 0.06-0.42; P = 0.0002) were found to have statistically significant associations with myocardial injury. Increased SD was associated with decreased risk when accounting for the maximal amount of ST segment depression and elevation and for patient characteristics. The ST segment summary statistics model had fair discrimination, with an area under the receiver operator characteristic curve of 0.71 (95% CI, 0.68-0.73). Addition of ST segment data produced a net reclassification improvement of 0.0345 (95% CI, 0.00016-0.0591; P = 0.0474). | B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known. The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal transduction were explored. The influence of BAFF on the expression of related genes was also studied. Our data indicated that BAFF had a proliferative effect on human mesangial cells, as supported by the results of cell proliferation assays and the inhibited expression of the pro-apoptotic gene Bim. BAFF-R was expressed on the cell membrane of human mesangial cells and blockade of BAFF/BAFF-R binding abrogated the proliferative effect of BAFF on human mesangial cells. BAFF stimulation led to rapid phosphorylation of NF-κBp65, Akt and MAPK p38 kinase in human mesangial cells, whereas it had no effect on the expression of NF-κB p100 and phosphorylation of Erk. The phosphorylation of Akt was very sensitive to blockade of BAFF/BAFF-R ligation, although activation of MAPK p38 and NF-κBp65 was not. BAFF treatment resulted in decreased expression of BAFF-R, which implied negative feedback regulation after its binding. |
Do glucose fluctuations increase the incidence of atrial fibrillation in diabetic rats? | We investigated whether glucose fluctuations aggravate cardiac fibrosis and increase the occurrence of atrial fibrillation (AF) in rats with diabetes mellitus (DM). Streptozotocin-induced diabetic rats were randomly divided into three groups: uncontrolled DM (U-STZ) group, controlled DM (C-STZ) group, and DM with glucose fluctuations (STZ-GF) group. Glucose fluctuations were induced by fasting for 24 h and additional regular insulin injections (0.5 IU/kg) administered three times per week for three consecutive weeks. C-STZ rats were administered long acting insulin (20 IU/kg) twice a day to control blood glucose levels. Cardiac fibrosis evaluated by Masson trichrome staining and the expressions of collagen type 1, collagen type 3, and α-smooth muscle actin were increased in U-STZ rats compared with C-STZ rats, which were more pronounced in STZ-GF rats. The inducibility of AF was significantly larger in U-STZ rats than C-STZ rats and was greatest in STZ-GF rats. To explore the mechanism of cardiac fibrosis, we investigated the levels of reactive oxygen species (ROS) and apoptosis. The expression of malondialdehyde, an indicator of ROS levels, was significantly upregulated in STZ-GF rats compared with U-STZ rats, along with increased thioredoxin-interacting protein (Txnip) expression in STZ-GF rats. Furthermore, caspase-3 expression and the number of TUNEL-positive cells were significantly increased in STZ-GF rats compared with U-STZ and C-STZ rats. | Vaccines are very important to reduce morbidity and mortality by preventable infectious diseases, especially during childhood. Optimal coverage is not always achieved, for several reasons. Here we assessed vaccine coverage for the first 12 months of age in children between 12 and 59 months old, residing in the urban area of a small Amazonian city, and factors associated with incomplete vaccination. A census was performed in the urban area of Assis Brasil, in the Brazilian Amazon, in January 2010, with mothers of 282 children aged 12 to 59 months old, using structured interviews and data from vaccination cards. Mixed logistic regression was used to determine factors associated with incomplete vaccination schemes. Only 82.6% of all children had a completed the basic vaccine scheme for the first year of life. Vaccine coverage ranged from 52.7% coverage (oral rotavirus vaccine) to 99.7% coverage (for Bacille Calmette-Guérin). The major deficiencies occurred in doses administered after the first six months of life. Incomplete vaccination was associated with not having enough income to buy a house (aOR = 2.12, 95% CI 1.06-4.21), low maternal schooling (aOR = 2.60, 95% CI 1.28 - 5.29) , and time of residence of the child in the urban area of the city (aOR = 0.73, 95% CI 0.55 - 0.95). |
Do survival in major burn injuries is predicted by early response to Swan-Ganz-guided resuscitation? | Two years ago the authors began to use Swan-Ganz catheters to generate more complex hemodynamic data as a better guide to resuscitation of burns. This study uses the information to identify differences between survivors and nonsurvivors. Fifty-three consecutive patients with major burns were treated using Swan-Ganz-generated data. Additional information was collected, including demographics, intake and output, medications, and arterial blood gas (including calculated oxygen consumption). Statistical analysis incorporated adjustments for autocorrelation. The patients included 38 men and 15 women, averaged 43.7 years of age, and had a mean burn size of 40%. Thirteen patients suffered severe inhalation injury. Data collected hourly over 3 days were collapsed across 6-hour observation periods. Mean values, when plotted across time, discriminated the 37 survivors from the 16 nonsurvivors. Poor response to resuscitation as evidenced by increased use of colloid fluid and cardiotonic drugs plus failure to maximize oxygen consumption were associated with nonsurvival. | To conduct clinical and genetic studies in a European family with autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to investigate the functional consequences of a novel ELOVL4 mutation. Ophthalmic examination and mutation screening by direct sequencing of the ELOVL4 gene was performed in two affected individuals. Wild-type and mutant ELOVL4 genes were expressed as enhanced green fluorescent protein (EGFP) fusion proteins in transient transfection in NIH-3T3 and HEK293 cells. To determine the subcellular localization of ELOVL4, an endoplasmic-reticulum (ER)-specific marker for pDsRed2-ER was cotransfected with ELOVL4 constructs. Transfected cells were viewed by confocal microscopy. Western blot analysis was performed to assess protein expression using an anti-GFP antibody. Affected patients exhibited macular atrophy with surrounding flecks characteristic of adSTGD-like MD. A novel ELOVL4 p.Tyr270X mutation was detected in affected individuals. In cell-transfection studies, wild-type ELOVL4 localized preferentially to the ER. In contrast, the mutant protein appeared to be mislocalized within transfected cells. |
Does maternal separation alter serotonergic transporter densities and serotonergic 1A receptors in rat brain? | The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders. The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain. Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined. serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei. | Standard treatment for patients with multiple myeloma is debulking chemotherapy with non-alkylating agents followed by a regimen to mobilize peripheral blood stem cells (PBSC) and the transplantation of the mobilized, autologous PBSC. The aim of this study was to evaluate the efficacy of a new regimen and compare it with that of a previous regimen. In a large cohort of 106 patients (group I) we administered a new pre-transplant program which includes 2 courses of pulsed-VAD (vincristine, adriamycin, dexamethasone) followed by 2 courses of DCEP (dexamethasone, cyclophosphamide, etoposide and cis-platinum). We compared the efficacy of this new VAD-DCEP sequence, in terms of mobilizing capacity, toxicity and anti-myeloma activity in comparison with that of the previous VAD-high-dose cyclophosphamide program (group II, 40 patients). In group I 81/106 (76.4%) patients yielded >or= 4x10(6)/kg CD34+ cells, as did 30/40 (75%) in group II but with a significantly higher toxicity in this latter group. In detail, 9 patients in group I (8.5%) had WHO grade III neutropenia versus 35 in group II (87.5%), 5 patients of group I (4.7%) had grade III thrombocytopenia versus 12 patients in group II (30%), and 8 patients in group I (7.5%) experienced an infections fever versus 9 patients in group II (22.5%). Therefore, nearly all patients in group II had to be admitted to hospital (39/40, 97.5%). There was a higher percentage of responses (CR+VGPR+PR) in group I than in group II: 73% versus 50% (p=0.02). |
Does radiographic Stage Correlate With Symptom Severity in Thumb Basilar Joint Osteoarthritis? | We hypothesize that thumb basilar joint osteoarthritis (TBJA) radiographic stage does not correlate with patient-reported measures of symptom severity. Patients with unilateral TBJA who completed the 11-item QuickDASH (Disabilities of the Arm, Shoulder, and Hand), Short-Form 12 Health Survey (SF-12) Mental Component and SF-12 Physical Component surveys were prospectively enrolled in the study. The Eaton-Littler radiographic stage was assigned for each patient. The correlation between the radiographic score and disease stage was calculated. Sixty-two patients (15 men, 47 women; average age, 62.3 years) formed the basis of this study. The average QuickDASH score (and standard deviation) for patients with stage 1 TBJA was 31.5 (11.4); for those with stage 2, it was 37.9 (17.4); with stage 3, it was 30.1 (13.0), and with stage 4, it was 39.4 (12.5). Eaton-Littler stage did not correlate significantly with QuickDASH scores (rho = -0.014, P = 0.91). Neither SF-12 Mental Component scores (MCS-12: rho = 0.019, P = 0.89) nor the SF-12 Physical Component scores (PCS-12: rho = 0.145, P = 0.26) correlated with TBJA stage. | The role of nitric oxide (NO) in cardiac pathophysiology remains controversial. According to data from several studies using rat and rabbit isolated hearts, NO is an endogenous cardioprotectant against reperfusion-induced ventricular fibrillation (VF). Thus, if cardiac NO production is abolished by perfusion with L-N(G)-nitro-L-arginine methylester (L-NAME) (100 microM) there is a concomittant increase in the incidence of reperfusion-induced VF, with L-NAME's effects on NO and VF prevented by L- (but not D-) arginine co-perfusion. To make a better estimate of the clinical relevance of these findings, 100 microM L-NAME was tested in primate hearts under similar conditions. Marmoset (Callithrix jaccus) hearts, isolated and perfused, were subjected to 60 min left regional ischaemia followed by 10 min reperfusion in vitro. The ECG was recorded and NO in coronary effluent measured by chemiluminescence. L-NAME (100 micro M) decreased NO in coronary effluent throughout ischaemia and reperfusion (e.g. from 3720+/-777 pmol min(-1) g(-1) in controls to 699+/-98 pmol min(-1) g(-1) after 5 min of ischaemia) and, during ischaemia, lowered coronary flow and reduced heart rate, actions identical to those seen in rat and rabbit hearts. However, the incidence of reperfusion-induced VF was unchanged (20%, with or without L-NAME). |
Does global transcriptional analysis suggest Lasiodiplodia theobromae pathogenicity factors involved in modulation of grapevine defensive response? | Lasiodiplodia theobromae is a fungus of the Botryosphaeriaceae that causes grapevine vascular disease, especially in regions with hot climates. Fungi in this group often remain latent within their host and become virulent under abiotic stress. Transcriptional regulation analysis of L. theobromae exposed to heat stress (HS) was first carried out in vitro in the presence of grapevine wood (GW) to identify potential pathogenicity genes that were later evaluated for in planta expression. A total of 19,860 de novo assembled transcripts were obtained, forty-nine per cent of which showed homology to the Botryosphaeriaceae fungi, Neofusicoccum parvum or Macrophomina phaseolina. Three hundred ninety-nine have homology with genes involved in pathogenic processes and several belonged to expanded gene families in others fungal grapevine vascular pathogens. Gene expression analysis showed changes in fungal metabolism of phenolic compounds; where genes encoding for enzymes, with the ability to degrade salicylic acid (SA) and plant phenylpropanoid precursors, were up-regulated during in vitro HS response, in the presence of GW. These results suggest that the fungal L-tyrosine catabolism pathway could help the fungus to remove phenylpropanoid precursors thereby evading the host defense response. The in planta up-regulation of salicylate hydroxylase, intradiol ring cleavage dioxygenase and fumarylacetoacetase encoding genes, further supported this hypothesis. Those genes were even more up-regulated in HS-stressed plants, suggesting that fungus takes advantage of the increased phenylpropanoid precursors produced under stress. Pectate lyase was up-regulated while a putative amylase was down-regulated in planta, this could be associated with an intercellular growth strategy during the first stages of colonization. | In 2004, the American Association of Physicists in Medicine (AAPM) issued a report outlining recommended 125I and 103Pd datasets for consistency in calculating brachytherapy dose distributions. In 2005, to aid evaluating the clinical impact of implementing these datasets, the AAPM assessed the historical dependence of how prescribed doses differed from administered doses for 125I and 103Pd for permanent implantation of the prostate. Consequently, the American Brachytherapy Society (ABS) considered the nature of these changes towards issuing recommended dose prescriptions for 125I and 103Pd interstitial brachytherapy implants for monotherapy and standard boosts. An investigation was performed of the 2005 AAPM analysis to determine changes in administered dose while affixing prescribed dose using 2004 AAPM 125I and 103Pd brachytherapy dosimetry datasets for prostate implants. For 125I and 103Pd, administered dose would change by +1.4% and +4.2%, respectively. The biological and societal impact of changing prescribed dose was considered. Based on the need for clinical constancy and in recognition of overall uncertainties, the ABS recommends immediate implementation of the 2004 AAPM consensus brachytherapy dosimetry datasets and no changes to 125I and 103Pd dose prescriptions at this time. |
Does acute disruption of glucagon secretion or action improve glucose tolerance in an insulin-deficient mouse model of diabetes? | Normal glucose metabolism depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilisation, glucagon excess is the principal factor in diabetic glucose overproduction. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance. Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metabolism was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist. Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass. | The purpose of the present study is to investigate the trends in incidence of both usual (u) and differentiated (d) vulvar intraepithelial neoplasia (VIN) separately, their malignant potential and the relation with other HPV related anogenital lesions in the Netherlands during a 14-year-period. The incidences of both types of VIN and vulvar SCC were retrieved from the Nationwide Netherlands Database of Histo- and Cytopathology. Population data were retrieved from the Database of Statistics Netherlands. In the study period, the incidence of uVIN and dVIN increased, while the incidence of vulvar SCC remained stable. The overall percentage of uVIN patients that were later diagnosed with vulvar SCC was 5.7%, which was significantly lower than the percentage for dVIN patients (32.8%). In addition to this 5.6-fold increased conversion rate, the time of progression from dVIN to SCC development was significantly shorter than that of uVIN (p=0.005). Percentage of uVIN patients that were later diagnosed with SCC significantly increased with age (p=0.005), whereas the time to SCC significantly shortened with age (p=0.05). Forty-one percent of uVIN patients had a past, concomitant or future HPV-associated lesion of the lower genital tract, which is in contrast to the 3% for dVIN patients. |
Does inhibition of nitric oxide synthesis reduce infarct size by an adenosine-dependent mechanism? | Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart. We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 mumol/L NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% (P < .05 versus control). This effect was abolished by pretreatment with 75.5 mumol/L 8-p-sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 mumol/L per 100 g of heart (control) to a peak of 24.0 mumol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 mumol/g dry wt; L-NAME, 5.5 mumol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 mumol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 mumol/g dry wt. | Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. |
Is percutaneous intervention of circumflex chronic total occlusions associated with worse procedural outcomes : insights from a Multicentre US Registry? | We sought to determine whether outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) vary according to CTO target vessel: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). We evaluated the clinical and angiographic characteristics and procedural outcomes of 636 patients who underwent CTO PCI at 6 high-volume centres in the United States between January 2012 and March 2014. The CTO target vessel was the RCA in 387 cases (61%), LAD in 132 (21%), and LCX in 117 (18%). LCX lesions were more tortuous and RCA lesions had greater occlusion length and Japanese Chronic Total Occlusion (J-CTO) score, but were less likely to have a side branch at the proximal cap and had more developed collateral circulation. The rate of procedural success was lower in LCX CTOs (84.6%), followed by RCA (91.7%), and LAD (94.7%) CTOs (P = 0.016). Major complications tended to occur more frequently in LCX PCI (4.3% vs 1.0% for RCA vs 2.3% for LAD; P = 0.07). LCX and RCA CTO PCI required longer fluoroscopy times (45 [interquartile range (IQR), 30-74] minutes vs 45 [IQR, 21-69] minutes for RCA vs 34 [IQR, 20-60] minutes for LAD; P = 0.018) and LCX CTOs required more contrast administration (280 [IQR, 210-370] mL vs 250 [IQR, 184-350] mL for RCA and 280 [IQR, 200-400] mL for LAD). | There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively. |
Is buccal absorption of fentanyl pH-dependent in dogs? | Analgesia and sedation have been achieved noninvasively by fentanyl administration through the oral and nasal mucosa. In theory, the transmucosal bioavailability and absorption of fentanyl could be improved by converting more fentanyl to the unionized form by adjusting the surrounding pH. The authors tested this hypothesis in dogs. Under general anesthesia, each of six mongrel dogs was given fentanyl on repeated occasions, first intravenously (once), then by application to the buccal mucosa (six times). Buccal fentanyl administration was accomplished by placement of a pH-buffered solution of fentanyl into a specially constructed cell, which was clamped to the dog's buccal mucosa for 60 min. Fentanyl solutions with pHs of 6.6, 7.2, and 7.7 were studied to span a tenfold difference in the unionized fraction of fentanyl. Femoral arterial blood samples were sampled frequently and analyzed for fentanyl using a radioimmunoassay. Peak plasma concentration and the time of its occurrence for each buccal study were noted from the plasma concentration verses time profile. Terminal elimination half-life, bioavailability, and permeability coefficients were calculated using standard pharmacokinetic techniques. The variables peak plasma concentration, bioavailability, and permeability coefficient increased three- to fivefold as the pH of the fentanyl buccal solution increased and more fentanyl molecules became unionized. There was no difference in terminal elimination half-life after intravenous fentanyl (244 +/- 68 min) or buccal fentanyl administration (pH 7.7, 205 +/- 89 min; pH 7.2, 205 +/- 65 min; pH 6.6, 196 +/- 48 min). In all buccal studies regardless of pH, time to peak plasma concentration occurred within 10 min of removal of the fentanyl solutions from the buccal mucosa. | The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). |
Does absolute lymphocyte count with extreme hyperleukocytosis have a prognostic impact in chronic lymphocytic leukemia? | BACKGROUND/ AIM: The prognostic significance of hyperleukocytosis in chronic lymphocytic leukemia (CLL) remains uncertain. The aim of the present study was to evaluate the clinical characteristics and outcome of patients with CLL and white blood count (WBC) >150×10(6)/l at the time of diagnosis. Using the database of the Israeli CLL Study Group, which includes 1,507 cases, we identified 41 patients diagnosed with WBC >150×10(6)/l and analyzed the survival in the group that was 62 months compared to 174 months in patients without hyperleukocytosis (p<0.001). However, multivariate analysis demonstrated that the WBC count had no predictive value in relation to survival time. While in the entire patient cohort advanced age and Binet stage, presence of thrombocytopenia and ZAP-70 expression were independently associated with poor prognosis, these parameters lost their prognostic value in patients with hyperleukocytosis. | The present study aimed to investigate the intraplantar (ipl) and central (icv) effects of neuropeptide S (NPS) in the formalin test and to evaluate the role of adenosine receptors, mainly A1 and A2A, in mediating such effects. The ipl injection of formalin was used to assess the nociceptive activity. Moreover, by pretreating mice with non-selective and selective antagonists of adenosine receptors, the effects of icv NPS on formalin-induced ongoing nociception were assessed. Morphine-induced antinociceptive effects were observed during phases 1 and 2 of the test, while indomethacin was active only at the later nociceptive phase. The ipl injection of NPS (alone or combined with formalin) did not modify the nociceptive response. However, icv NPS significantly reduced formalin-induced nociception during both phases. Caffeine (3 mg/kg, ip), a non-selective adenosine receptor antagonist, prevented NPS-induced antinociceptive effects. Similar to caffeine, icv ZM241385 (0.01 nmol), an A2A receptor antagonist, prevented the antinociceptive effects of NPS. Moreover, icv DPCPX (0.001 nmol), an A1 receptor antagonist, blocked the effects of NPS only during phase 1. |
Does cognitive-behavioural therapy reduce unwanted thought intrusions in generalized anxiety disorder? | Voluntary attempts to suppress certain thoughts can paradoxically increase their intrusive return. Particular impairments in thought suppression are thought to be key mechanisms in the pathogenesis of mental disorders. To assess the role of this processing bias in the maintenance of generalized anxiety disorder (GAD), we investigated whether it is susceptible to cognitive-behavioural treatment (CBT). 22 GAD patients and 22 healthy controls (HC) were tested twice within 15 weeks, with patients receiving CBT in between. A subset of patients was additionally tested while waiting for treatment to control for retest effects. Using a mental control paradigm, we measured intrusion frequency during the voluntary suppression of thoughts related to (a) the individual main worry topic, (b) a negative non-worry topic, and (c) a neutral topic. Self-reported worry was measured before and after treatment, and at 6-months follow-up. Compared to HC, GAD showed specifically more worry-related intrusions. CBT reduced this bias to a healthy level, over and above mere test-retest effects. | To investigate serum levels of the advanced glycation end-products (AGEs) pentosidine and N epsilon-carboxymethyllysine (CML) in patients classified into different osteoporosis subgroups according to histomorphometric data. Serum samples were obtained from 116 osteoporotic patients (34 men, 82 women) classified by bone histomorphometry into subgroups with high turnover (HTO, n = 32), low turnover (LTO, n = 39), normal turnover (NTO, n = 9) and cellular uncoupled osteoporosis (CUO, n = 36). Pentosidine was measured by high-performance liquid chromatography, and CML by a competitive enzyme-linked immunoassay. The entire osteoporosis group had significantly higher pentosidine and CML serum concentrations than healthy subjects. In contrast to healthy subjects, no correlation between levels of AGEs and age could be found. In subgroups characterized by increased bone resorption (HTO, CUO), serum pentosidine correlated significantly with the histomorphometric marker reflecting osteoclast activity/bone resorption (eroded surface as a percentage of trabecular surface). Moreover, in CUO a strong correlation between pentosidine and the mineral apposition rate was found. Surprisingly, in HTO the levels of CML and percentage of eroded surface were significantly negatively correlated. |
Is [ A perioperative screening for metastatic disease indicated in patients with primary breast cancer and no clinical signs of tumor spread ]? | Is a perioperative metastatic screening programme indicated in patients presenting with primary operable breast cancer and no signs of distant metastases? The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analysed in 1 076 patients with an operable breast cancer and no clinical signs of metastases. Staging examinations revealed 30 (2.8 %) distant metastases, 130 (12.1 %) suspect findings and excluded metastases in 916 (85.1 %) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4 %) and excluded them in 123 (94.6 %) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing tumor size (pT < or = 2.0 cm: 1.6 %, pT 2.1-5.0 cm: 3.0 %, respectively pT > 5.0 cm: 15.1 %; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.4 %, pN1-3 +: 1.8 %, pN4-9 +: 4.0 %, pN > 10 +: 12.5 %; p < 0.001). Due to false positive findings 123 (11.4 %) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1 076 patients saves costs of at least euro 259,366.68. | Uromodulin is a kidney specific glycoprotein whose expression can modulate kidney homeostasis. However, the set of sequence specific transcription factors that regulate the uromodulin gene UMOD and their upstream binding locations are not well characterized. We built a high resolution map of its transcriptional regulation. We applied in silico phylogenetic footprinting on the upstream regulatory regions of a diverse set of human UMOD orthologs to identify conserved binding motifs and corresponding position specific weight matrices. We further analyzed the predicted binding motifs by motif comparison, which identified transcription factors likely to bind these discovered motifs. Predicted transcription factors were then integrated with experimentally known protein-protein interactions available from public databases and tissue specific expression resources to delineate important regulators controlling UMOD expression. Analysis allowed the identification of a reliable set of binding motifs in the upstream regulatory regions of UMOD to build a high confidence compendium of transcription factors that could bind these motifs, such as GATA3, HNF1B, SP1, SMAD3, RUNX2 and KLF4. ENCODE deoxyribonuclease I hypersensitivity sites in the UMOD upstream region of the mouse kidney confirmed that some of these binding motifs were open to binding by predicted transcription factors. The transcription factor-transcription factor network revealed several highly connected transcription factors, such as SP1, SP3, TP53, POU2F1, RARB, RARA and RXRA, as well as the likely protein complexes formed between them. Expression levels of these transcription factors in the kidney suggest their central role in controlling UMOD expression. |
Is the effect of Rho kinase inhibition on long-term keratinocyte proliferation rapid and conditional? | We previously demonstrated that the lifespan of primary human keratinocytes could be extended indefinitely by culture in the presence of the Rho kinase (ROCK) inhibitor Y-27632. This technique has proven to be very useful in diverse areas of basic and clinical research. In this follow-up study we determine whether the continual presence of Y-27632 is required for sustained proliferation. We also test whether different ROCK inhibitors can be used for this technique and whether it can also promote indefinite proliferation of animal keratinocytes. We measure keratinocyte gene expression, proliferation, behaviour and lifespan in the presence and absence of Y-27632. We demonstrate that the extension of lifespan observed by culture of keratinocytes in the presence of fibroblast feeders and a ROCK inhibitor is reversible and that cells senesce gradually when the inhibitor is removed from the medium. Conversely, keratinocytes that are close to the end of their replicative life span can be revived by ROCK inhibition. We demonstrate that different inhibitors of ROCK can also efficiently extend the lifespan of human keratinocytes and that ROCK inhibition extends the lifespan of animal keratinocytes derived from mouse and bovine epithelia. Gene expression analysis of human epidermal keratinocytes cells grown in the presence of Y-27632 demonstrates that ROCK inhibition primarily inhibits keratinocyte differentiation. Live-imaging of keratinocytes cultured with ROCK inhibitors show that the effect of ROCK inhibition on cellular proliferation is immediate and ROCK inhibited cells proliferate rapidly without differentiation or stratification. | To determine the reliability of Internet-based information on community-based weight-loss programs and grade their degree of concordance with 2013 American Heart Association, American College of Cardiology, and The Obesity Society weight-management guidelines. An online search was conducted for weight-loss programs in the Maryland-Washington, DC-Virginia corridor. Content analysis was performed to abstract program components from their websites, and then 80 programs were randomly selected for a telephone survey to verify this information. Reliability of Internet information was determined in comparison with telephone interview responses. Of the 191 programs, 1% were graded as high, 8% as moderate, and 91% as low with respect to guideline concordance based on website content. Fifty-two programs participated in the telephone survey (65% response rate). Program intensity, diet, physical activity, and use of behavioral strategies were underreported on websites as compared to description of these activities during the phone interview. Within the subsample, 6% of programs were graded as high based on website information, whereas 19% were graded as high after the telephone interview. |
Is hypoxia induced changes in lung fluid balance in humans associated with beta-2 adrenergic receptor density on lymphocytes? | Previous studies have demonstrated an important role for beta-2 adrenergic receptors (β(2)AR) in lung fluid clearance. The purpose of this investigation was to examine the relationship between β(2)AR density on lymphocytes and indices of lung water in healthy humans exposed to ≈ 17 h of hypoxia (FIO2 = 12.5% in a hypoxia tent). Thirteen adults (mean ± SEM; age=31 ± 3 years, BMI=24 ± 1 kg/m(2), VO2 Peak = 40 ± 2 ml/kg/min ) participated. Pulmonary function, CT derived lung tissue volume (V(tis)-tissue, blood and water), lung diffusing capacity for carbon monoxide (D(CO)) and nitric oxide (D(NO)), alveolar-capillary conductance (D(M)), pulmonary capillary blood volume (V(c)) and lung water (CT V(tis)-V(c)) were assessed before and after ≈ 17 h normobaric hypoxia (FIO2 = 12.5%). β(2)AR density on lymphocytes was measured via radioligand binding. Arterial oxygen saturation (SaO2), cardiac output (Q), right ventricular systolic pressure (RVSP) and blood pressure (BP) were also assessed. After 17 h hypoxia, SaO2 decreased from 97 ± 1 (normoxia) to 82 ± 4% and RVSP increased from 14 ± 3 (normoxia) to 29 ± 2 mmHg (p<0.05) with little change in Q or BP. V(c) and D(M) both increased with hypoxia with a small increase in D(M)/V(c) ratio (p>0.05). CT V(tis) decreased and lung water was estimated to decline 7 ± 13%, respectively. β(2)AR density averaged 1497 ± 187 receptors/lymphocyte and increased 21 ± 34% with hypoxia (range -31 to +86%). The post-hypoxia increase in β(2)AR density was significantly related to the reduction in lung water (r=-0.64, p<0.05), with the subjects with the greatest increase in density demonstrating the largest decline in lung water. | Matrix metalloproteinases (MMPs) are the major class of enzymes responsible for degradation of extracellular matrix components and participate in the pathogenesis of periapical inflammatory lesions. MMP expression may be regulated by DNA methylation. The purpose of the present investigation was to analyze the expression of MMP2 and MMP9 in periapical granulomas and radicular cysts and to test the hypothesis that, in these lesions, their transcription may be modulated by DNA methylation. Methylation-specific polymerase chain reaction was used to evaluate the DNA methylation pattern of the MMP2 gene in 13 fresh periapical granuloma samples and 10 fresh radicular cyst samples. Restriction enzyme digestion was used to assess methylation of the MMP9 gene in 12 fresh periapical granuloma samples and 10 fresh radicular cyst samples. MMP2 and MMP9 messenger RNA transcript levels were measured by quantitative real-time polymerase chain reaction. All periapical lesions and healthy mucosa samples showed partial methylation of the MMP2 gene; however, periapical granulomas showed higher MMP2 mRNA expression levels than healthy mucosa (P = .014). A higher unmethylated profile of the MMP9 gene was found in periapical granulomas and radicular cysts compared with healthy mucosa. In addition, higher MMP9 mRNA expression was observed in the periapical lesions compared with healthy tissues. |
Does regulator of the mucoid phenotype A gene increase the virulent ability of extended-spectrum beta-lactamase-producing serotype non-K1/K2 Klebsiella pneumonia? | To determine whether the presence of a capsule regulator gene [i.e., regulator of mucoid phenotype A (rmpA) gene] contributes to virulence on extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) with serotype non-K1/K2 strains. Twenty-eight ESBL-KP and non-ESBL-KP isolates were collected from the Tri-Service General Hospital (Taipei, Taiwan). The impact of the virulent rmpA gene in different capsular polysaccharide serotypes on ESBL-KP and non-ESBL-KP isolates was studied by a neutrophil phagocytosis reaction, a serum bactericidal assay, and an animal survival model. Resistance to broad spectrum antibiotics was more prevalent in ESBL-KP strains than in non-ESBL-KP strains (p < 0.01). The ESBL-KP strains had different molecular patterns from non-ESBL-KP strains, based on pulsed-field gel electrophoresis. The frequency of serum-resistant isolates was the highest among ESBL-KP strains with rmpA (i.e., rmpA(+)) [71.4% (5/7)] than among of non-ESBL-KP rmpA(+) strains [42.8% (6/14)], ESBL-KP strains without rmpA (rmpA(-)) [33.3% (7/21)], and non-ESBL-KP rmpA(-) strains [14.2% (2/14)]. The most significant increase in neutrophil resistance occurred in the ESBL-KP rmpA(+) strains in comparison to the non-ESBL-KP rmpA(+), ESBL-KP rmpA(-), and non-ESBL-KP rmpA(-) strains (p < 0.01). The results of the animal survival model were compatible with the neutrophil phagocytosis reaction and serum bactericidal assay. | Subthalamic nucleus deep brain stimulation (STN0 DBS) is a widely performed surgical treatment in PD. However, the relationship between motor results and cognitive/behavioural modifications is unclear. This study investigated the correlation patterns of the motor, cognitive and behavioural consequences of STN DBS with respect to positioning of the active contact. Fifty-eight consecutive PD patients having undergone STN DBS were assessed pre-operatively and 12 months after surgery. Motor, cognitive and behavioural results were neither correlated to each other nor linked to the position of the active contact. Three patients with a history of pre-operative, dopaminergic psychosis or post-surgical confusion became demented. Age and a distant history of depression were associated with the occurrence of post-surgical depression. |
Are anticancer effects of bishydroxycoumarin mediated through apoptosis induction , cell migration inhibition and cell cycle arrest in human glioma cells? | To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action. Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V-FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC. BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells. | pulmonary rehabilitation (PR) improves health status and exercise tolerance, but not respiratory function in patients with chronic obstructive pulmonary disease (COPD). Our objective was to identify predictors of improvement in the 6-min walked distance (6'WD) in elderly COPD patients after PR. this was a prospective observational study performed in an ambulatory rehabilitation setting. We enrolled 74 patients aged 65-83 years (mean: 74.2, SD: 4.4) with stable COPD in GOLD stage 3-4. About half (45.6%) of them had a basal O(2) saturation of 90% or less. After a baseline multi-dimensional assessment, patients underwent a 20-session rehabilitation cycle including training of the upper and lower extremities, and respiratory exercises, along with education sessions. The difference between final and basal 6'WD was expressed as a per cent of the basal value (6'WD gain). Patients were divided into two groups according to whether the 6'WD gain was above or under the 75th percentile, corresponding to 33% gain. patients whose 6'WD improved more had lower baseline forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) (46.0 versus 52.2%, P = 0.03) and baseline 6'WD, both as an absolute value (329.5 versus 408.9 m, P = 0.01) and as a per cent of the predicted (71.1 versus 93.5%, P = 0.002). After correction for potential confounders, baseline 6'WD was the only variable associated with the outcome (OR for 5% increments: 0.79; 95% CI 0.65-0.95). |
Is adequate enteral protein intake inversely associated with 60-d mortality in critically ill children : a multicenter , prospective , cohort study? | The impact of protein intake on outcomes in pediatric critical illness is unclear. We examined the association between protein intake and 60-d mortality in mechanically ventilated children. In a prospective, multicenter, cohort study that included 59 pediatric intensive care units (PICUs) from 15 countries, we enrolled consecutive children (age: 1 mo to 18 y) who were mechanically ventilated for ≥48 h. We recorded the daily and cumulative mean adequacies of energy and protein delivery as a percentage of the prescribed daily goal during the PICU stay ≤10 d. We examined the association of the adequacy of protein delivery with 60-d mortality and determined variables that predicted protein intake adequacy. We enrolled 1245 subjects (44% female) with a median age of 1.7 y (IQR: 0.4, 7.0 y). A total of 985 subjects received enteral nutrition, 354 (36%) of whom received enteral nutrition via the postpyloric route. Mean ± SD prescribed energy and protein goals were 69 ± 28 kcal/kg per day and 1.9 ± 0.7 g/kg per day, respectively. The mean delivery of enteral energy and protein was 36 ± 35% and 37 ± 38%, respectively, of the prescribed goal. The adequacy of enteral protein intake was significantly associated with 60-d mortality (P < 0.001) after adjustment for disease severity, site, PICU days, and energy intake. In relation to mean enteral protein intake <20%, intake ≥60% of the prescribed goal was associated with an OR of 0.14 (95% CI: 0.04, 0.52; P = 0.003) for 60-d mortality. Early initiation, postpyloric route, shorter interruptions, larger PICU size, and a dedicated dietitian in the PICU were associated with higher enteral protein delivery. | To examine the differentiation-related expression of cannabinoid receptor type 1 (CB1-R) messenger RNA (mRNA) and protein in endometrial tissue obtained from women with and without endometriosis and to determine the impact of acute 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on CB1-R gene expression in isolated endometrial stromal cells. Laboratory-based study. University-affiliated medical center. Women with and without endometriosis undergoing volunteer endometrial biopsies after informed consent. None. Analysis of in vivo CB1-R mRNA and protein expression in human endometrial tissues and mRNA expression in isolated stromal cells after exposure to TCDD or a progesterone receptor antagonist (onapristone). Expression of CB1-R mRNA and protein was highest during the progesterone-dominated secretory phase in control samples, but expression was minimal in the endometrial tissues acquired from women with endometriosis, regardless of the cycle phase. Although progesterone was found to induce CB1-R mRNA expression in endometrial stromal cells from control donors, steroid-induced expression of this gene was inhibited by cotreatment with either TCDD or onapristone. |
Is childhood maltreatment associated with depression but not with hypochondriasis in later life? | Previous studies demonstrated that a history of childhood trauma is linked to mental disorders in adulthood, particularly to depression. Adverse childhood experiences are also considered to contribute to the risk of hypochondriasis, but the results of previous studies have not been conclusive with respect to the strength and specificity of this association. Therefore, we compared the association of adverse childhood experiences with both hypochondriasis and depression. Fifty-eight patients with hypochondriasis, 52 patients with depression, and 52 healthy control participants completed the Childhood Trauma Questionnaire (CTQ) which assesses 5 varieties of abuse and neglect. A clinical interview (SCID-I) was used to establish DSM-IV diagnoses. Associations between childhood maltreatment, hypochondriasis and depression were estimated by means of analyses of variance and multiple linear regression analyses. In comparison to hypochondriacal and healthy participants, patients with a current depressive disorder reported more emotional abuse as well as more emotional and physical neglect during childhood. Patients with hypochondriasis reported more emotional neglect than healthy individuals. However, when predicting the CTQ trauma types by diagnostic category adjusting for sex and comorbid DSM-IV diagnoses, emotional abuse, emotional neglect, physical abuse, physical neglect, as well as the CTQ total score were significantly associated with depression, but none of the CTQ scores was significantly related to hypochondriasis. | Effective material exchange between blood and tissue depends on the heterogeneity of microvascular flow. The objective was to address inconsistencies between intravital studies regarding this dependency. We tested the hypothesis that heterogeneity of red blood cell velocity (VRBC) in capillary beds varies with the strength of metabolic stimulus and with capillary bed geometry. We used videomicroscopy to measure VRBC in a bed of 10-24 capillaries at the surface of extensor digitorum longus (EDL) muscle in anesthetized rats. The coefficient of variation (CV = standard deviation/mean; an index of spatial heterogeneity) was computed in the same bed before and after (i) 1, 2, 4, or 8 Hz supramaximal muscle contraction or (ii) adenosine superfusion (10(-7)-10(-3) M). Beds with or without arteriolar-venular capillary shunts were used. Although control VRBC differed between beds (shunt: 232 microns/s; no shunt: 130 microns/s), the percentage increases in postcontraction VRBC did not (range: 111-326%). In both beds, control CV varied greatly (overall range: 28-117%) and 2-8 Hz muscle contractions reduced CV significantly by 25%. Similar results were obtained for adenosine. In confirmatory experiments using the rat cremaster muscle, contractions (4 Hz) and adenosine (10(-4) M) also reduced CV. Based on all data, CV = 63-0.022 VRBC (r = 0.82, P < 0.001). |
Is phenylacetate an inhibitor of prostatic growth and development in organ culture? | Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men, and the obstructive uropathy it causes results in serious morbidity and financial cost. Phenylacetate (PA) is a small molecule that is a product of phenylalanine metabolism and is normally present in the mammalian circulation at very low levels. It has long been safely used in humans to treat the hyperammonemia resulting from urea synthesis disorders and liver failure. It has recently been investigated as an anticancer agent because it decreased growth and increased differentiation of a variety of human neoplasms, including prostate cancer in which a phase I trial has recently been completed. Because of PA's growth-inhibitory effects on a variety of cell lines and the idea that BPH is due to a reawakening of embryonic-like inductive activity in prostatic stromal cells, which then induce development of epithelial nodules, we examined the effect of PA on serum-free organ cultures of developing rat prostates. We found that PA markedly decreased rat prostatic growth and ductal morphogenesis at concentrations that have previously been well tolerated in patients. In ventral prostates grown for 7 days in organ culture, histodifferentiation was inhibited as measured by a marked decrease in ductal lumen formation and ductal branching morphogenesis. This inhibition of differentiation was confirmed by using cytokeratin antibodies specific for basal and luminal cells. Synthesis of DNA was also significantly decreased per organ with PA. The growth inhibitory effects of PA were reversible, and the mechanism did not appear to be due to glutamine or glycine deprivation, or androgen receptor inhibition. | Assessing acute myocardial infarction (MI) with respect to long-term survival is not easy. Authorities in the field suggest that inflammation predicts short-range (up to 17 months) coronary death. It is not known whether long-term survival is associated with the inflammatory response. In this study, we evaluate the relationships between survival for more than 8 years and inflammation, i.e., circulating interleukin-6 (IL-6) and neutrophil counts, in acute MI. Patients with ST-segment elevation MIs (STEMI; n=33) and non-ST-segment MIs (non-STEMI; n=39) in 1996 were included in the study. All STEMI patients received thrombolytic therapy. Acute coronary angiography was not an option. Determination of IL-6 and neutrophils was carried out within 24 h after commencement of pain. The subjects were followed for more than 8 years (until December 31, 2005) using the national death registry. Inflammatory markers at the time of MI were compared with long-term survival (n=35). At the time of acute MI, survivors for more than 8 years proved to have lower IL-6 (p<0.01) and decreased neutrophil counts (p<0.05). The differences remained (p<0.01 for both markers) when excluding deaths (n=11) occurring in 1996 and 1997. Subsequently, the subjects were divided into two equally sized groups, depending on their IL-6 values at the beginning of the study. As expected, a lower IL-6 was associated with a more favorable long-term prognosis (p<0.01). |
Does inhibition of p21-Activated Kinase 1 by IPA-3 promote Locomotor Recovery After Spinal Cord Injury in Mice? | Ninety-six male adult CD-1 mice were randomly divided into sham, spinal cord injury (SCI) + vehicle, and SCI + IPA-3 groups. Expression of matrix metalloproteinase (MMP)-2 and MMP-9, production of tumor necrosis factors (TNF)-α and interleukin (IL)-1β, tissue edema, blood-spinal cord barrier penetrability, neural cell apoptosis, and neurological function recovery were measured. The aim of the study was to evaluate the effect of specific inhibition of p21-activated kinase 1 (PAK1) by IPA-3 on SCI and the underlying mechanisms thereof. SCI is a devastating clinical condition that may result in long-lasting and deteriorating functional deficits. The major goal of SCI treatment is to limit the development of secondary injury. IPA-3, a PAK1 inhibitor, exhibited neuroprotection against secondary damage after traumatic brain injury and subarachnoid hemorrhage (SAH). MMP-2, MMP-9, and cleaved caspase-3 expression were assessed by Western blot. Inflammatory cytokines TNF-α and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The blood-spinal cord barrier disruption was measured by water content and Evans blue extravasation of the spinal cord. Neuronal apoptosis was evaluated by Nissl staining and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The locomotor behavior of hind limb was evaluated by Basso Mouse Scale (BMS) at 1, 3, 7, 14, and 28 days post-injury. Compared with SCI + vehicle mice, IPA-3 treatment showed decreased p-PAK1, MMP-2, MMP-9, cleaved caspase-3, TNF-α, and IL-1β expression. Moreover, inhibition of PAK1 by IPA-3 reduced spinal cord water content and Evans blue extravasation, increased neuronal survival, and reduced TUNEL-positive cells at 24 hours after SCI. Furthermore, IPA-3 improved spinal cord functional recovery 7 days after SCI. | The bioavailability of natural food folates is lower than that of synthetic folic acid, but no agreement exists as to the extent of the difference. In a 4-wk dietary intervention study, we determined the aggregate bioavailability of food folates from fruit, vegetables, and liver relative to that of folic acid. Seventy-two healthy adults were randomly divided into 4 treatment groups. Group A (n = 29) received a high-folate diet with 369 mug food folate/d and a placebo capsule; groups B, C, and D (n = 14 or 15) received a low-folate diet with 73 microg food folate/d and folic acid capsules. These capsules contained 92 microg folic acid/d for group B, 191 microg for group C, and 289 microg for group D. In addition, all 72 subjects daily ingested a capsule with 58 microg [(13)C(11)]-labeled folic acid. We measured the percentage of [(13)C(11)]-labeled folate in plasma folate at the end of the intervention and ascertained the changes in serum folate concentrations over the 4 wk of the intervention. Bioavailability of food folate relative to that of folic acid was 78% (95% CI: 48%, 108%) according to [(13)C(11)]-labeled folate and 85% (52%, 118%) according to changes in serum folate concentrations. |
Do impact of electrode design and surgical approach on scalar location and cochlear implant outcomes? | Three surgical approaches: cochleostomy (C), round window (RW), and extended round window (ERW); and two electrodes types: lateral wall (LW) and perimodiolar (PM), account for the vast majority of cochlear implantations. The goal of this study was to analyze the relationship between surgical approach and electrode type with final intracochlear position of the electrode array and subsequent hearing outcomes. Comparative longitudinal study. One hundred postlingually implanted adult patients were enrolled in the study. From the postoperative scan, intracochlear electrode location was determined and using rigid registration, transformed back to the preoperative computed tomography which had intracochlear anatomy (scala tympani and scala vestibuli) specified using a statistical shape model based on 10 microCT scans of human cadaveric cochleae. Likelihood ratio chi-square statistics were used to evaluate for differences in electrode placement with respect to surgical approach (C, RW, ERW) and type of electrode (LW, PM). Electrode placement completely within the scala tympani (ST) was more common for LW than were PM designs (89% vs. 58%; P < 0.001). RW and ERW approaches were associated with lower rates of electrode placement outside the ST than was the cochleostomy approach (9%, 16%, and 63%, respectively; P < 0.001). This pattern held true regardless of whether the implant was LW or PM. When examining electrode placement and hearing outcome, those with electrode residing completely within the ST had better consonant-nucleus-consonant word scores than did patients with any number of electrodes located outside the ST (P = 0.045). | Psoriasis appears to have increased cardiovascular morbidity. The underlying pathogenetic mechanisms remain unclear. Multiple factors, including systemic inflammation, oxidative stress, aberrant lipid profile, and concomitant established risk factors, have been discussed. However, previous studies consist of heterogeneous patient materials, including persons with highly varying disease duration and treatment. Two-hundred patients were investigated at the onset of psoriasis, comparing plasma concentrations of lipids, lipoproteins, and apolipoproteins with those of matched controls (N = 285). Psoriasis patients manifest significant lipid abnormalities. Specifically, patients had significantly higher cholesterol concentrations in the very-low-density lipoprotein and high-density-lipoprotein fractions. Adjustment for established environmental risk factors did not affect the results. |
Is combining ECT with pharmacological treatment of depressed inpatients in a naturalistic study associated with serum BDNF level increase? | BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls. Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group. There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00). | Progression from actinic keratosis (AK) to invasive squamous cell carcinoma (iSCC) of the skin is thought to occur after the development of full thickness epidermal neoplasia, as in the classic pathway of cervical cancer. Nevertheless, cutaneous iSCC may also directly arise from a proliferation of atypical basaloid cells limited mostly to the epidermal basal layer (AK I), akin to what happens in the 'differentiated pathway' of iSCC of the vulva, oral cavity and other locations. To evaluate the prevalence of classic and differentiated pathways in the development of cutaneous iSCC. The epidermis adjacent to and overlying iSCC, assumed to be representative of pre-existing lesions, was histologically studied in 196 skin biopsy specimens showing iSCC. AK I, AK II and AK III lesions overlying iSCC were present in 63.8%, 17.9% and 18.4% of cases respectively. The corresponding percentages in the epidermis adjacent to iSCC were 77.9%, 6.6% and 8.3% respectively (stage could not be assessed in 8.1% of cases). Focal epidermal ulceration overlying iSCC was seen in 32% of AK I, 28.6% of AK II and 33.3% of AK III instances. Adnexal involvement by atypical keratinocytes (proliferative AK) was present more frequently in cases with overlying AK I (39/125, 31.2%) than with AK II (8/35, 22.9%) and AKII I (5/36, 13.9%). |
Does peripheral group I metabotropic glutamate receptor activation lead to muscle mechanical hyperalgesia through TRPV1 phosphorylation in the rat? | Elevated glutamate levels within injured muscle play important roles in muscle pain and hyperalgesia. In this study, we hypothesized that protein kinase C (PKC)-dependent TRPV1 phosphorylation contributes to the muscle mechanical hyperalgesia following activation of Group I metabotropic glutamate receptors (mGlu1/5). Mechanical hyperalgesia induced by (R,S)-3,5-dihydroxyphenylglycine (DHPG), an mGlu1/5 agonist, in the masseter muscle was attenuated by AMG9810, a specific TRPV1 antagonist. AMG9810 also suppressed mechanical hyperalgesia evoked by pharmacologic activation of PKC. DHPG-induced mechanical hyperalgesia was suppressed by pretreatment with a decoy peptide that disrupted interactions between TRPV1 and A-kinase-anchoring protein (AKAP), which facilitates phosphorylation of TRPV1. In dissociated trigeminal ganglia, DHPG upregulated serine phosphorylation of TRPV1 (S800), during which DHPG-induced mechanical hyperalgesia was prominent. The TRPV1 phosphorylation at S800 was suppressed by a PKC inhibitor. Electrophysiologic measurements in trigeminal ganglion neurons demonstrated that TRPV1 sensitivity was enhanced by pretreatment with DHPG, and this was prevented by a PKC inhibitor, but not by a protein kinase A inhibitor. These results suggest that mGlu1/5 activation in masseter afferents invokes phosphorylation of TRPV1 serine residues including S800, and that phosphorylation-induced sensitization of TRPV1 is involved in masseter mechanical hyperalgesia. These data support a role of TRPV1 as an integrator of glutamate receptor signaling in muscle nociceptors. | Haplodiploidy, where females develop from diploid, fertilized eggs and males from haploid, unfertilized eggs, is abundant in some insect lineages. Some species in these lineages reproduce by thelytoky that is caused by infection with endosymbionts: infected females lay haploid eggs that undergo diploidization and develop into females, while males are very rare or absent. It is generally assumed that in thelytokous wasps, endosymbionts merely diploidize the unfertilized eggs, which would then trigger female development. We found that females in the parasitoid wasp Asobara japonica infected with thelytoky-inducing Wolbachia produce 0.7-1.2% male offspring. Seven to 39% of these males are diploid, indicating that diploidization and female development can be uncoupled in A. japonica. Wolbachia titer in adults was correlated with their ploidy and sex: diploids carried much higher Wolbachia titers than haploids, and diploid females carried more Wolbachia than diploid males. Data from introgression lines indicated that the development of diploid individuals into males instead of females is not caused by malfunction-mutations in the host genome but that diploid males are most likely produced when the endosymbiont fails to activate the female sex determination pathway. Our data therefore support a two-step mechanism by which endosymbionts induce thelytoky in A. japonica: diploidization of the unfertilized egg is followed by feminization, whereby each step correlates with a threshold of endosymbiont titer during wasp development. |
Does fluid resuscitation with deferoxamine hetastarch complex attenuate the lung and systemic response to smoke inhalation? | We determined the effect of infusing the iron chelator deferoxamine complexed to hetastarch on the degree of lung dysfunction and systemic abnormalities produced by a severe smoke exposure. Adult sheep were given a smoke exposure under anesthesia that produced a peak carboxyhemoglobin between 40% and 45%. Twenty-eight sheep were studied; eight were given smoke alone and resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. Seven sheep were given a bolus plus 1 ml/kg/hr of a 10% deferoxamine-hetastarch solution for resuscitation; five were given hetastarch alone. The response was compared with eight controls during a period of 24 hours. Smoke alone and smoke with hetastarch resulted in a shunt fraction of greater than 25% and a 50% decrease in compliance, severe airway inflammation, mucosal slough, atelectasis, and some alveolar edema. Increased lipid peroxides measured as malondialdehyde were present in airway fluid. In addition, oxygen consumption increased by 100% early after injury, net 24-hour positive fluid balance was almost 3 L, and a significant increase occurred in liver lipid peroxidation. The group given deferoxamine had a significantly attenuated lung response, with only modest airway damage lung dysfunction, and minimal systemic changes including a net positive fluid balance of just over 1L and no liver lipid peroxidation. | Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The aim of the present study was to investigate the role of CALPAIN-5 (CAPN5) gene in PCOS susceptibility. We analysed four intronic polymorphisms of the CAPN5 gene in 148 well-characterized women with PCOS and 606 unrelated controls. We performed a case-control study and an intracohort analysis of clinical characteristics associated with PCOS. Analysis of haplotypes distribution between PCOS population compared to controls showed a strong deviation (P = 0.00029). The haplotypes GGCA and GGTG were overrepresented in PCOS patients (P = 0.009 and P = 0.001, respectively). In addition, we identified several CAPN5 haplotypes associated with phenotypic differences observed between PCOS patients, such as the presence of obesity (P = 0.02), cardiovascular complications (P = 0.02), familial antecedents of obesity (P = 0.003) and of hypertension (P = 0.007) and type 2 diabetes mellitus aggregation (P = 0.04). |
Is cYP2C9 Genetic Polymorphism a Potential Predictive Marker for the Efficacy of Rosuvastatin Therapy? | There is well-known inter-individual variability in the cholesterol-lowering effect of statins. However, inter-individual variability in response to rosuvastatin treatment in subjects with hypercholesterolemia has not been clearly established. This study aimed to evaluate the associations of CYP2C9 genetic polymorphism with the efficacy and safety of rosuvastatin in Chinese patients with hyperlipidemia. A total of 218 patients with hyperlipidemia were selected and treated with 10 mg rosuvastatin per day for 12 weeks. Blood samples were collected prior to the treatment and after 4, 8, and 12 weeks of treatment. Clinical biochemistry analyses for serum lipid profiles were performed. Genotyping for CYP2C9 polymorphisms was performed using allele-specific real-time PCR. 197 out of 218 patients featured a wild-type CYP2C9*1/*1 genotype, and 21 patients featured a CYP2C9*1/*3 or CYP2C9*3/*3 mutation genotype. No patients with CYP2C9*2 alleles were identified. Sixteen patients discontinued the medication due to adverse effects. No serious adverse events (i.e., hepatotoxicity or myolysis) were observed. After the 12 weeks of treatment, we observed significant reductions in total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) levels compared to baseline (p < 0.05). Patients with the mutant genotype showed a higher TC-lowering and LDL-lowing effect compared to those with wild-type genotypes (TC: 45.05% vs. 38.96%, p = 0.041; LDL: 44.97% vs. 39.28%, p = 0.029). The frequency of adverse drug reactions in the studied patients did not differ by CYP2C9 genotypes (p > 0.05). | The theoretical effects on corneal transparency induced by changes in collagen fibril packing following phototherapeutic keratectomy were compared to changes in objective measurements of haze. Phototherapeutic keratectomy was performed on the right eyes of four young rabbits; left eyes were used as controls. Postoperative slit-lamp measurements of haze were taken at regular intervals up to 19 months. Wounded stromas were studied by synchrotron x-ray diffraction to calculate the average interfibrillar spacing of the collagen fibrils. These data were combined with transmission electron microscope measurements, and the summation of scattered fields method was used to predict the transmission of visible light. Objective measurements of haze were higher than the baseline control throughout the study. Electron micrographs of anterior stroma in 8-month-old wounds displayed irregularly spaced and poorly organized fibrils and x-ray diffraction indicated larger mean interfibrillar spacing compared to the controls. However, the predicted transmission of visible light through the anterior stromal scar tissue was not significantly different than normal. |
Is nOX2-generated oxidative stress associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease? | Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver. The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels. Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed. | Genetically modified T-lymphocytes are potential therapeutic agents for the treatment of various disorders. Successful retroviral infection of primary murine T-lymphocytes is a prerequisite to the study of adoptive cell therapies in a small animal model. The definition of factors controlling retroviral infection of T-lymphocytes would also be useful to better understand retroviral diseases. However, retroviral-mediated gene transfer into murine primary T-cells has remained elusive. In order to define the requirements for stable and efficient gene transfer in primary murine T-lymphocytes, we investigated factors capable of affecting retroviral infection. These include activation conditions (using mitogens or monoclonal antibodies), culture conditions (including media composition and cytokine addition), timing of viral exposure, retroviral receptor selection (ecotropic, amphotropic, or vesicular stomatitis virus G (VSV-G) glycoprotein receptor), and viral titer. We show that efficient gene transfer can be achieved in murine T-lymphocytes, provided that a number of favorable conditions are met, in particular optimized T-cell activation conditions, optimal timing of infection, adequate interleukin-2 concentration and T-cell density, and a high viral titer. On a particulate basis, we find that ecotropic particles are more effective than amphotropic or VSV-G-pseudotyped particles, and recommend the use of a specifically selected retroviral packaging cell line. CD4+ T-cells are equally or more infectible than CD8+ lymphocytes, depending on the activation conditions. The Th1 and Th2 subsets are comparably susceptible to retroviral infection, in contrast to what has been reported in some instances of human T-cell infection by human immunodeficiency virus (HIV). |
Are neither multiple tumors nor portal hypertension surgical contraindications for hepatocellular carcinoma? | The surgical indications for multiple hepatocellular carcinomas (HCCs) and for HCC with portal hypertension (PHT) remain controversial. We reviewed 434 patients who had undergone an initial resection for HCC and divided them into a multiple (n = 126) or single (n = 308) group according to the number of tumors. We also classified 386 of the patients into a PHT group (n = 136) and a no-PHT (n = 250) group according to whether they had PHT (defined by the presence of esophageal varices or a platelet count of <100,000/microL in association with splenomegaly). Among Child-Pugh class A patients, the overall survival rates in the multiple group were 58% at 5 years, and 56% in the PHT group, which were lower than those in the single group (68%, P = .035) and the no-PHT group (71%, P = .008). Among Child-Pugh class B patients with multiple HCCs, the 5-year overall survival rate was 19%. Multivariate analyses revealed that the presence of multiple tumors was an independent risk factor for postoperative recurrence (relative risk, 1.64; 95% confidence interval, 1.23-2.18; P = .001). A second resection resulted in satisfactory overall survival after the diagnosis of recurrence in the multiple (73% at 3 years) or PHT (73%) groups, as well as in the single (79%) or no PHT (81%) groups. | Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood-brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference. |
Is the protective dose of the potent GPIIb/IIIa antagonist SC-54701A reduced when used in combination with aspirin and heparin in a canine model of coronary artery thrombosis? | Fibrinogen receptor antagonists block the fibrinogen-platelet interaction at the GPIIb/IIIa receptors and inhibit thrombus formation. SC-54701 is the active metabolite of SC-54684A, an orally fibrinogen receptor antagonist. We compared the efficacy of SC-54701A (SCa, hydrochloride salt) with that of aspirin (ASA) or heparin and with combination therapy in a canine model of continuous current injury. Sixty-six dogs were used (6 per treatment). SCa (15-minute loading dose followed by [//] infusion [microgram/kg per minute]: (0.87//0.39=1 X SCa; 0.52//0.23=0.6 X SCa; and 0.425//0.20= 0.5 X SCa), ASA (2.8 mg/kg), heparin (200 U/kg plus 1000 U/h), or saline (0.1 mL/kg) was administered intravenously. Experimental time was 180 minutes of current. Time to occlusion was increased (P < .05) by SCa (T=incidence of thrombosis) (1 X SCa, >180 minutes [T=0]; 0.6 X SCa, 158 +/- 15 minutes [T=2]; 0.5 X SCa, 130 +/- 22 minutes [T=4]), heparin (114 +/- 16 minutes [T=5]), and ASA plus heparin (130 +/- 11 minutes [T=5]) relative to saline (58 +/- 7 minutes [T=6]). Time to occlusion for the SCa treatments was increased compared with ASA (64 +/- 7 minutes [T=6]). When 0.5 X SCa was administered with ASA plus heparin, time to occlusion was >180 minutes [T=0]. SCa provided complete protection at > or = 90% inhibition of ex vivo collagen-induced platelet aggregation. Cyclic flow variations were minimal with SCa or any treatment involving 0.5 X SCa and ASA. | Oral cancer is the 4th leading cause of cancer death for males and the top cancer in young adult males in Taiwan. Tongue squamous cell carcinoma (TSCC) is a common oral cancer and generally associated with poor prognosis. Global DNA hypomethylation at the 5 position of cytosine (5mC) is a well-known epigenetic feature of cancer. Therefore, the purpose of this study was to investigate the relationship of the global 5mC content with the tumorigenesis and prognosis of patients with TSCC. The levels of global 5mC were evaluated by immunohistochemistry using tissue microarray slides of 248 surgically resected TSCC and 202 corresponding tumor adjacent normal (TAN) tissues. We found that the level of 5mC in TSCC (P < 0.001) was significantly decreased as compared to TAN. Among TSCC tissues, decreased levels of 5mC were associated with female gender (P = 0.036). In addition, the global hypomethylation was associated with the poor disease-specific survival in TSCC patients (adjusted hazard ratio: 1.55, P = 0.043), especially for patients in older age group (> 50 years, P = 0.013), with moderate or poor cell differentiation (P = 0.044), early stage of disease (I-II, P = 0.046), small tumor size (T1-T2, P = 0.005), without lymph node involvement (P = 0.041), and ever received postoperative radiotherapy (P = 0.009). |
Is tea consumption inversely associated with weight status and other markers for metabolic syndrome in US adults? | Tea (Camellia sinensis) is a widely consumed beverage, and laboratory and some intervention studies have indicated the potential health benefits of hot tea. The present study examines the association between tea consumption (evaluating hot and iced tea independently) and markers for metabolic syndrome adults in a sample of 6,472 who participated in the 2003-2006 National Health and Nutrition Examination surveys. Tea consumption was evaluated using food frequency questionnaires and 24-h dietary recalls. Seventy percent of the sample reported any consumption of iced tea and 16 % were daily consumers, whereas approximately 56 % of this sample reported hot tea consumption and 9 % were daily consumers. Hot tea consumption was inversely associated with obesity: tea consumers had lower mean waist circumference and lower BMI (25 vs. 28 kg/m² in men; 26 vs. 29 kg/m² in women; both P < 0.01) than non-consumers after controlling for age, physical activity, total energy intake, and other confounders. For iced tea consumption, the association was reversed: increased iced tea consumption was associated with higher BMI, greater waist circumference, and greater subcutaneous skinfold thickness after controlling for age, physical activity, energy intake, sugar intake, and other confounders. Hot tea consumption was associated with beneficial biomarkers of cardiovascular disease risk and inflammation (increased high-density lipoprotein-associated cholesterol and decreased C-reactive protein in both sexes, and reduced triglycerides in women), whereas the association with iced tea consumption was again reversed. | The retroviral RNase H is essential for viral replication. This component has not yet been extensively studied for antiviral therapy. It can be activated by an oligodeoxynucleotide (ODN) resulting in self-destruction of the virions. To examine antiviral potential of ODN in clinical samples using plasma of HIV-1-infected patients. Plasma of 19 HIV-1-infected patients from Zurich and 10 HIV-1 isolates from Africa and drug-resistant strains were processed for ex-vivo treatment. Cell-free virions were treated with ODN in the plasma and HIV RNA was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, infectivity of the treated virions was tested on primary human peripheral blood mononuclear cells. Cell-free virions in plasma contained significantly less intact HIV RNA upon treatment with ODN (P = 0.0004), and their infectivity was decreased 52-fold (P = 0.0004). In 39% of the Zurich samples, infectivity was reduced more than 10-fold, in 33% more than 100-fold, and in 28% more than 1000-fold. Also, the isolates from Africa exhibited a 63-fold reduction in infectivity (P = 0.0069) with 80% of the isolates responding more than 10-fold, 40% more than 100-fold, and 10% more than 1000-fold. |
Is one of the rubber latex allergens a lysozyme? | Type I hypersensitivity reactions caused by latex products are ascribed to proteins eluted from them, but little is known about the properties of these allergenic proteins. The reason for the cross-reaction between rubber latex and fruits is also not known. We have speculated that a series of defense-related proteins in plants is a cause of latex allergy and the cross reaction. To verify our hypothesis, we selected a lysozyme as a representative defense-related protein and examined its relationship to latex allergy. Lysozymes eluted from latex gloves were detected with a cell-suspension clearing test. A chromatographically separated lysozyme was investigated for its physicochemical and enzymatic properties and allergenicity. Lysozyme activity was detected in extracts from ammoniated latex and latex gloves. We separated a lysozyme (27 kd; isoelectric point, 9.5) using cation-exchange and gel filtration chromatography. This lysozyme was enzymatically very similar to fruit lysozymes and was demonstrated to be an allergen. | Whether obesity affects surgical outcomes in patients with hepatocellular carcinoma (HCC) is controversial. Here we retrospectively evaluated the impact of obesity on outcomes in HCC patients after curative hepatectomy. Patients with Child-Pugh A liver function who underwent curative hepatectomy between 2006 and 2010 were categorized as obese (BMI ≥25 kg/m2, n = 68) and non-obese (<25 kg/m2, n = 242). To reduce interference from baseline differences between the two groups, propensity score-matched analysis was performed in the ratio 1:2 using a caliper width of 0.1. Surgical outcomes were compared for 61 obese and 115 non-obese patients. Obese patients had higher levels of albumin and aspartate aminotransferase, and more solitary tumors compared to the non-obese patients (all P<0.05). In the propensity-matched cohort, baseline characteristics did not differ between the two groups (all P>0.05). Obese and non-obese patients had comparable 30-day mortality (1.6% vs. 2.6%, P = 1.000), 90-day mortality (3.3% vs. 4.3%, P = 1.000), and incidence of postoperative complications (19.7% vs. 18.3%, P = 0.819). Overall survival at 1, 3, and 5 years was similar for obese patients (83.6%, 63.6%, 41.6%) as for non-obese patients (80.9%, 65.9%, 49.1%; P = 0.358). Disease-free survival at 1, 3, and 5 years was also similar for obese patients (71.5%, 36.3%, 24.3%) as for non-obese ones (60.2%, 43.7%, 27.7%; P = 0.969). |
Do three year follow up of a self certification system for the assessment of fitness to dive in Scotland? | The need for routine medical examinations of sport divers in the Scottish Sub-Aqua Club (Scot-SAC) was revised in March 2000, and a new system using a self administered screening questionnaire was developed to allow divers to be assessed when necessary by doctors with diving medicine experience. To assess the effect of the new medical system on medical referee workload, diver exclusion rates, and diving incident frequency. All divers were required to complete a questionnaire to screen for conditions that might affect fitness to dive. Divers answering "Yes" to any of the questions had their medical background assessed by a diving doctor, and, if necessary, received a clinical examination or investigation. The rate of diver exclusions based on the questionnaire response was recorded in conjunction with analysis of the incident reports. The number of forms requiring review by diving doctors increased from 1.2% to 5.7% (p<0.0001, 95% confidence interval (CI) -0.06 to -0.03) in the year after the introduction of the new medical system and gradually increased in subsequent years to 7.7% (p<0.0001, 95% CI -0.08 to -0.05). The number of divers failing to be certified fit to dive increased slightly from 0.7% to 1.0% after one year (p = 0.26, 95% CI -0.01 to 0.00) and subsequently to 2.0% (p = 0.0003, 95% CI 0.02 to -0.01) after three years. Most divers were certified fit to dive on the basis of the questionnaire alone, and only 0.9% required objective investigation (such as exercise testing or echocardiography). Analysis of the incidents during three years of follow up confirmed that no incident occurred because of an undetected pre-existing medical condition. Two incidents involved divers with hypertension, but both had received medical examinations and investigation based on their responses to the questionnaire. | We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known. We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo. RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of β-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/β-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE. |
Does oral zinc supplementation reduce the erythropoietin responsiveness index in patients on hemodialysis? | In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. | Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats. In the present study, 20-mo-old rats were administered GTS-21 or an equal volume of saline by intraperitoneal injection 30 min before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Spatial learning and memory of the rats were assessed at 2 wk after isoflurane exposure. The expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus and cerebral cortex were determined by enzyme-linked immunosorbent assay. Simultaneously, neuronal apoptosis in the hippocampus was also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and Nissl staining. We found that exposure to isoflurane induces learning and memory deficits of old rats. IL-1β in the hippocampus was increased at 4 h after isoflurane exposure. Isoflurane also increased neuroapoptosis in the hippocampus and decreased neuronal density in the CA1 region. And GTS-21 pretreatment effectively alleviated these changes. |
Is oral decontamination with aminoglycosides associated with lower risk of mortality and infections in high-risk patients colonized with colistin-resistant , KPC-producing Klebsiella pneumoniae? | Invasive infections caused by KPC-producing Klebsiella pneumoniae (KPCKP) are associated with very high mortality. Because infection is usually preceded by rectal colonization, we investigated if decolonization therapy (DT) with aminoglycosides had a protective effect in selected patients. Patients with rectal colonization by colistin-resistant KPCKP who were at high risk of developing infection (because of neutropenia, surgery, previous recurrent KPCKP infections or multiple comorbidities) were followed for 180 days. Cox regression analysis including a propensity score was used to investigate the impact of the use of two intestinal decolonization regimens with oral aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of KPCKP infections and microbiological success. The study was registered with ClinicalTrials.gov (NCT02604849). The study sample comprised 77 colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up, decolonization was associated with a lower risk of mortality in multivariate analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR 0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI 1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at 180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06-0.9). | The DAZ family genes boule, daz and dazl encode RNA binding proteins essential for fertility of diverse animals including human. dazl has bisexual expression in both mitotic and meiotic germ cells, whereas daz has male premeiotic expression, and boule is largely a unisexual meiotic regulator. Although boule has been proposed as the ancestor for dazl/daz by gene duplication, it has been identified only in invertebrates and mammals. It has, however, remained unclear when and how the DAZ family has evolved in vertebrates. This study was aimed at identifying and characterizing the DAZ family genes in fish as the basal vertebrate. We show that boule and dazl coexist in medaka and stickleback. Similar to the medaka dazl (Odazl), the medaka boule (Obol) is maternally supplied and segregates with primordial germ cells. Surprisingly, Obol is expressed in adult germ cells at pre-meiotic and meiotic stages of spermatogenesis and oogenesis. However, the maximal meiotic Obol expression in spermatocytes contrasts with the predominant pre-meiotic Odazl expression in spermatogonia, and the diffuse cytoplasmic Obol distribution in early oocytes contrasts with the Odazl concentration in the Balbinani's body. |
Does glucose modulate event-related potential components of recollection and familiarity in healthy adolescents? | 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). | Increased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated. The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms. Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS-/-) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS-/- mice with BLM-induced pulmonary fibrosis. The histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS-/- mice. Long-term treatment with the supplemental NO donor in n/i/eNOS-/- mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs. |
Is arterial Vasoreactivity Equally Affected by In Vivo Cross-Clamping with Increasing Loads in Young and Middle-Aged Mice Aortas? | To compensate for the lack of haptic feedback by surgical robots, limitation of exerted forces could be implemented. The limits should be based on the observed relationship between tissue load and induced damage. This study examines whether age-related changes influence this relationship. Descending thoracic aortas of male C57BL/6J mice of 10, 25 and 40 weeks were clamped in vivo (no clamp, 0.5N or 2.0N) for 2 min. Functional integrity was tested in vitro by studying endothelium-dependent and -independent vasoreactivity. Endothelium-dependent relaxation deteriorated with increased clamping force at all ages. Clamping did not influence endothelium-independent vasodilation. Age (10, 25 and 40 weeks) did not significantly impact on the effect of clamping on endothelium-dependent and independent vasoreactivity. | Several clinical observations suggest that there is a link between vitiligo and melanoma. We examined whether an immune response to similar antigens on pigment cells could account for this association. We tested 30 patients with melanoma, 29 patients with vitiligo, and 28 patients with unrelated conditions for antibodies to human melanocyte antigens using an immunoprecipitation sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis assay. Antibodies to melanocytes were present in 24 (80%) patients from the melanoma group, 24 (83%) patients from the vitiligo group, and in two (7%) patients from the control group. The antibodies in patients with melanoma or vitiligo were directed to similar antigens with molecular weights of approximately 40 to 45, 75, and 90 kd. The frequency of antibody responses to each of these antigens was similar in both diseases. By sequential immunodepletion, the antigens defined by antibodies in both diseases were similar. These antigens were also expressed on melanoma cells. |
Does change in adiposity minimally affect the lipid profile in youth with recent onset type 1 diabetes? | Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D. We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c). We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz. | Cisplatin is widely used as an antineoplastic agent since it is effective against a broad spectrum of different tumours. Nevertheless, it has several potential side effects affecting different organ systems and an overdose may lead to life-threatening complications and even death. We report on a 46-year old woman with non-small cell lung cancer who accidentally received 225 mg/m2 of cisplatin, which was threefold the dose as scheduled, within a 3-day period. Two days later, the patient presented with hearing loss, severe nausea and vomiting, acute renal failure as well as elevated liver enzymes. In addition, she developed a severe myelodepression. After plasmapheresis on two consecutive days and vigorous supportive treatment, the toxicity-related symptoms improved and the patient recovered without any sequelae. |
Is termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test Attributable to Endogenous Inhibitory Mechanisms , but not by Opioid Receptors Activation? | Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses; 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study. To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50µL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection. While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A; but had no effect on delayed termination of formalin test. | Microalgae provide an excellent platform for the production of high-value-products and are increasingly being recognised as a promising production system for biomass, animal feeds and renewable fuels. Here, we describe an automated screen, to enable high-throughput optimisation of 12 nutrients for microalgae production. Its miniaturised 1,728 multiwell format allows multiple microalgae strains to be simultaneously screened using a two-step process. Step 1 optimises the primary elements nitrogen and phosphorous. Step 2 uses Box-Behnken analysis to define the highest growth rates within the large multidimensional space tested (Ca, Mg, Fe, Mn, Zn, Cu, B, Se, V, Si) at three levels (-1, 0, 1). The highest specific growth rates and maximum OD750 values provide a measure for continuous and batch culture. |
Does mangiferin inhibit lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling? | Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms. The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits. We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-κB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment. | Multiple intercostal recordings were supposed to get a more comprehensive view of the depolarization vector of the outflow tract ventricular arrhythmia (OT-VA), which may help to identify the OT-VA more accurately. This study was undertaken to develop a more accurate electrocardiogram (ECG) criterion for differentiating between left and right OT-VA origins. We studied OT-VA with a left bundle branch block pattern and inferior axis QRS morphology in 47 patients with successful catheter ablation in the right ventricular OT (RVOT; n = 37) or aortic coronary cusp (ACC; n = 10). Superior and inferior precordial leads were taken together with the routine 12-lead ECG. The ECG during the OT-VA and during sinus beats were analyzed. Transition ratio, transition zone (TZ) index, R/S amplitude ratio, and R-wave duration ratio were measured in the regular, superior, and inferior precordial leads. The combined TZ index, TZ index inferior was significantly smaller, while the V2 inferior transition ratio was significantly larger for ACC origins than RVOT origins (P < 0.05). The area under the curve for the combined TZ index by a receiver operating characteristic analysis was 0.974, which was significantly larger than other parameters. A cutoff value ≤0.25 predicted an ACC origin with 94% sensitivity and 100% specificity. This advantage of the parameter over others also held true for a subanalysis of OT-VAs with a lead V3 precordial transition or TZ index = 0. |
Do tNF-α inhibitors impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment? | The aim of this study was to study the influence of active disease status and TNF-α antagonists on sperm quality in a group of AS patients. Twenty-three active AS patients and 42 controls were recruited. Patients' sperm samples were analysed at baseline (previous to) and at 3-6 months after TNF-α therapy (adalimumab, infliximab, etanercept) administration. Baseline assessment was made for only 20 patients, 2 of them proving to have normal fertility, 2 having a pregnant stable partner and the third having a 9-month-old child. Six patients were retested after 12 months of biologic therapy. Each patient acted as his own comparator. Results were further compared with sperm samples from age-matched controls. Sperm analysis was performed according to the World Health Organization (WHO) 1999 guidelines. Patients' baseline assessment showed normozoospermia in 91% and oligozoospermia in 9% of patients. No significant differences in sperm quality were noticed at follow-up visits compared with baseline. Comparison to controls showed no statistically significant differences in semen quality, with some exceptions: the control group presented a higher percentage of non-progressive and immobile sperm cells and higher numbers of head and tail atypias. | Gastric cancer is the third leading cause of cancer-related deaths in the world with high mortality rate due to the lack of markers in early detection and effective therapies. MicroRNAs (miRNAs), a critical part of epigenetic regulations in tumor, have been shown to be closely related to the initiation, development, invasion, metastasis and prognosis of gastric cancer. The present study aims to investigate the expression of miR-1290 in gastric tumor cells and to elucidate the target gene of miR-1290 in SGC-7901 gastric cancer cells. The fluorescence in situ hybridization, real time PCR and Western blot were used to investigate the expression of miR-1290 in gastric tumor cells and clinical gastric tumor samples. The effect of miR-1290 expression on gastric tumor cells was studied using Synthetic miR-1290 inhibitor transfection, in vitro wound healing assay and flow cytometry analysis. Bioinformatics and Luciferase reporter assay were used to predict and validate the target gene of miR-1290. Our results revealed that miR-1290 was highly expressed in SGC-7901 gastric cancer cells as well as in clinical gastric cancer samples, which was correlated with clinical stages, depth of invasion and lymph node metastasis. Synthetic miR-1290 inhibitor transfection significantly inhibited the proliferation and migration of SGC-7901 cells. Bioinformatics analysis and luciferase reporter assay suggested that miR-1290 functioned in gastric cancer cells by targeting FOXA1 gene. |
Is elevated plasma phospholipid transfer protein activity a determinant of carotid intima-media thickness in type 2 diabetes mellitus? | The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima-media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects. The IMT (mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity (phospholipid vesicle-HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects. In diabetic patients, carotid IMT (p=0.02), pulse pressure (p=0.003), plasma PLTP activity (p<0.001), triglycerides (p=0.01), C-reactive protein (p<0.01) and insulin (p<0.001) were higher, whereas HDL cholesterol was lower (p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age (p<0.001), sex (p=0.001), pulse pressure (p=0.003), plasma PLTP activity (p=0.03) and HDL cholesterol (p=0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin (all p>0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects. | To determine the efficacy and safety of botulinum toxin-B (BTX-B) in two groups of patients with urodynamically proven idiopathic detrusor overactivity (IDO) or neurogenic DO (NDO) refractory to conservative treatment. This was a nonrandomized, prospective study. We diluted 5000 U of BTX-B in 20 mL of normal saline and injected it at 20 sites around the bladder, avoiding the trigone. The data collected at recruitment and 10 and 26 weeks postoperatively included number of incontinent episodes, frequency, and nocturia, King's Health Questionnaire score, and the urodynamic parameters of volume at the first overactive contraction and maximal cystometric capacity. A total of 25 patients were recruited, 20 with IDO and 5 with NDO. Only 7 patients, all with IDO, reported symptomatic improvement at the 10-week assessment. The symptoms had returned in these 7 patients at a median of 136 days (range 106 to 151) after injection. Of the remaining 20 patients, 16 (13 with IDO and 3 with NDO) thought an initial improvement had occurred but it had worn off or was wearing off by the first assessment. Two patients (both with NDO) reported no improvement. |
Is serum REG4 level a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer? | Preoperative chemoradiotherapy is one of the key strategies for the improvement of survival in pancreatic cancer; however, no method to predict the response has yet been established. The aim of this study was to prospectively evaluate the predictive value of REG4, a new member of the regenerating (REG) islet-derived family of proteins. Stably REG4-expressing cells were established from a pancreatic cancer cell line and exposed in vitro to gamma-ray or gemcitabine to investigate the relevance of REG4 to the resistance to chemotherapy or radiotherapy. In 23 patients with resectable pancreatic cancer, the serum concentration of REG4 was measured before preoperative chemoradiotherapy, and the histologic response was evaluated after the surgery. A 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and fluorescence activated cell scanning (FACS) revealed that REG4-overexpressing cells were resistant to gamma-radiation but showed a modest resistance to gemcitabine. The patients with a higher REG4 level, but not carcinoembryonic antigen or CA-19-9, showed an unfavorable histologic response to chemoradiotherapy (Spearman, rho = 0.439, P = 0.039). The patients showing a higher REG4 level experienced local recurrence postoperatively. | To determine if an unselected group of rodeo athletes would report a more benign outcome to their motor vehicle whiplash injuries than a group of spectators at rodeo events. This survey compares the self-reported outcome of motor vehicle collision whiplash injuries (neck and/or back sprain) in rodeo athletes and spectators attending rodeo events. Subjects were asked to recall motor vehicle collision experiences, the type of vehicle they were in, the presence of symptoms as a result, and outcomes for those symptoms. Forty-seven percent of rodeo athletes and 59% of spectators recalled being in a motor vehicle collision. A total of 33% of rodeo athletes who had collisions recalled acute symptoms they associated with the collision compared to a recall of symptoms in 61% of spectators who had collisions. Vehicle types during collisions and occupation type at time of the survey were the same for both groups. Duration of symptoms, however, was 30 days (+/- 14 days) in rodeo athletes and 73 days (+/- 61 days) in spectators. None of the rodeo athletes recalled symptoms lasting for more than 60 days compared to 15% of spectators who had symptoms more than 60 days. Rodeo athletes took no more than 3 weeks off work, whereas among spectators, it was common to take more than 6 weeks off. |
Does clinician-delivered contingency management increase engagement and attendance in drug and alcohol treatment? | This study examined the impact of a low-cost contingency management (CM) delivered by program clinicians on treatment attendance and utilization for patients enrolled in outpatient psychosocial substance abuse treatment. The study used a pre-posttest design to compare substance abuse patients who received Reinforcement-Based Treatment (RBT) plus low cost CM (n=130; RBT+CM) to patients who received RBT only (n=132, RBT). RBT+CM participants received a $10 incentive for returning to treatment the day following intake assessment (day one), and a $15 incentive for attending treatment on day five following admission. RBT clients received standard care intervention without the addition of the CM procedures. Groups were compared on proportion of participants who returned to treatment on day one, mean days of treatment attendance, individual sessions attended, and treatment utilization during the first week and the first month following treatment admission. Both the RBT+CM and RBT group participants returned to the clinic on day one at high rates (95% versus 89%, respectively). However, the RBT group participants were more likely to attend the intake assessment only (i.e., never return to treatment) compared to the RBT+CM participants. Additionally, the RBT+CM participants attended significantly more treatment days, attended more individual counseling sessions, and had higher rates of overall treatment utilization compared to the RBT participants during the one week and one month following treatment admission. | There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE) patients. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls), inflammatory response (interleukin-6 and myeloperoxidase activity), and activation of the TLR-4-NF-kB pathway. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. |
Is vacuum-assisted biopsy a viable alternative to surgical biopsy in the investigation of breast lesions of uncertain malignant potential? | In patients presenting with a breast lesion, when initial core biopsy histology falls into the category of "uncertain malignant potential" (i.e. a B3 lesion), the next line of investigation has traditionally been a surgical biopsy (SBx). Vacuum-assisted biopsy (VAB) may be a viable minimally invasive alternative to SBx for B3 lesions. The primary aims of this study were to establish whether VAB reduces the need for surgical biopsy and determine VAB sensitivity for carcinoma following initial B3 histology. B3 lesion data was collected from 2004 to 2013 retrospectively, from a single institution that utilises both VAB and SBx. A total of 413 lesions were categorised B3 on initial biopsy. Mean age was 61 years (range: 24-91 years). Mean follow up was 52 months (range: 19-60 months). 156 patients (38%) underwent VAB. Only 20% of patients underwent VAB in 2004, with an increase to 95% by 2013. VAB histology revealed twelve carcinomas, all of which progressed to surgical excision. In six cases, a SBx was required following VAB in order to provide further diagnostic information. In one case, carcinoma was missed on VAB. | Type II diabetes in the Goto Kakizaki (GK) rats (derived from Wistar rats) is not associated with the development of obesity, hyperlipidemia, hypertension, or pronounced renal functional changes. The aim of this study was to investigate the effect of superimposed hypertension on renal function and morphology under conditions of hyper- and normoglycemia. The evolution of biochemical and morphologic renal changes was examined in GK and Wistar rats treated with deoxycorticosterone acetate (DOCA) salt over 24 weeks. Blood pressure was increased from 6 weeks on in GK and Wistar rats with no difference in blood pressure levels between both groups (week 24, 183 +/- 14 mm Hg vs. 191 +/- 13 mm Hg, P = NS, vs. 144 +/- 6 mm Hg in normal controls, P < 0.01). A progressive increase in proteinuria was observed in hypertensive GK rats from 12 weeks on (week 24, 168 +/- 62 mg/day vs. 41 +/- 30 mg/day in hypertensive Wistar rats, P = 0.002). Histologic analysis at weeks 15 and 24 showed progressive glomerulosclerosis in hypertensive GK and Wistar rats (week 24, 13 +/- 4% vs. 8 +/- 1%, P = NS) but not in nonhypertensive GK controls. This was associated with evidence of podocyte damage (de novo desmin expression) in hypertensive as compared to nonhypertensive GK rats (week 24, score 1.4 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.001) while no significant increase was observed in hypertensive vs. nonhypertensive Wistar rats. Tubulointerstitial damage was increased in hypertensive GK as compared to hypertensive Wistar rats (week 24, score 1.5 +/- 0.6 vs. 0.6 +/- 0.3, P = 0.01). By immunohistochemistry, this was associated with an up-regulation of tubulointerstitial type IV collagen as well as alpha-smooth muscle actin (alpha-SMA) expression, macrophage infiltration and cell proliferation in hypertensive GK rats. |
Does marine-derived oligosaccharide sulfate ( JG3 ) suppress heparanase-driven cell adhesion events in heparanase over-expressing CHO-K1 cells? | To elucidate the detailed mechanisms underlying the appreciable effects of JG3, a novel marine-derived oligosaccharide, on cell migration using a Chinese hamster ovary (CHO) cell line stably over-expressing heparanase. A retrovirus infection system was used to establish a CHO-K1 cell line stably transfected with heparanase. Immunocytochemistry was used to assess cell morphology. Flow cytometry was selected to analyze the activation of beta1-integrin, and Western blotting was used to analyze the downstream effects on the cell adhesion pathway. An affinity precipitation assay was used to determine activation of the small GTPases, Rac1, and RhoA. JG3 abolished heparanase-driven formation of focal adhesions and cell spreading. Although JG3 failed to block the heparanase-triggered activation of beta1-integrin or the phosphorylation of Src, the oligosaccharide caused a significant dephosphorylation of FAK and subsequent inactivation of Erk. Furthermore, JG3 was found to arrest the activation of Rac1. | Noninvasive blood pressure (NIBP) monitoring methods are widely used in critically ill patients despite poor evidence of their accuracy. The erroneous interpretations of blood pressure (BP) may lead to clinical errors. To test the accuracy and reliability of aneroid (ABP) and oscillometric (OBP) devices compared to the invasive BP (IBP) monitoring in an ICU population. Fifty adult patients (200 comparisons) were included in a randomized crossover trial. BP was recorded simultaneously by IBP and either by ABP or by OBP, taking IBP as gold standard. Compared with ABP, IBP systolic values were significantly higher (mean difference ± standard deviation 9.74 ± 13.8; P < 0.0001). Both diastolic (-5.13 ± 7.1; P < 0.0001) and mean (-2.14 ± 7.1; P=0.0033) IBP were instead lower. Compared with OBP, systolic (10.80 ± 14.9; P < 0.0001) and mean (5.36 ± 7.1; P < 0.0001) IBP were higher, while diastolic IBP (-3.62 ± 6.0; P < 0.0001) was lower. Bland-Altman plots showed wide limits of agreement in both NIBP-IBP comparisons. |
Does interleukin-32 increase human gastric cancer cell invasion associated with tumor progression and metastasis? | The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32-mediated migration and invasion. Gastric cancer cells with ectopic expression or silencing of IL-32 were examined to identify downstream molecules and establish their effects on cell motility, invasion, and lung metastasis in vivo. IL-32 was significantly upregulated in gastric cancer and positively correlated with aggressiveness of cancer and poor prognosis. Ectopic expression of IL-32 induced elongated morphology and increased cell migration and invasion via induction of IL-8, VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 expression via phosphor-AKT/phospho-glycogen synthase kinase 3β/active β-catenin as well as hypoxia-inducible factor 1α (HIF-1α) signaling pathways. Conversely, depletion of IL-32 in gastric cancer cells reversed these effects and decreased lung colonization in vivo. Examination of gene expression datasets in oncomine and staining of gastric cancer specimens demonstrated the clinical significance of IL-32 and its downstream molecules by providing information on their coexpression patterns. | Nocturnal polyuria has been well known in renal insufficiency. Recently, we found that as renal function deteriorated in chronic kidney disease (CKD), natriuresis was enhanced during the night with nocturnal blood pressure elevation. In the present study, we investigated whether nocturnal polyuria in CKD was due to the inability to concentrate urine, as previously proposed, or based on osmotic diuresis mainly by natriuresis. In 27 CKD patients, circadian rhythms of urinary sodium, potassium, urea and osmolar excretion rates (U(Na)V, U(K)V, U(urea)V, U(osm)V) as well as of urinary volume (V) and free-water clearance (C(H(2)O)) were estimated during both daytime (6:00 to 21:00) and nighttime (21:00 to 6:00). Then, the night/day ratios of these parameters were analysed in relation to creatinine clearance (C(cr)) as a marker of glomerular filtration rate. C(cr) had significantly negative relationships with night/day ratios of V (R = -0.69; P < 0.0001), U(osm)V (R = -0.54; P = 0.004) and U(Na)V (R = -0.63; P = 0.0005), but no correlation with night/day ratios of C(H(2)O) (R = -0.33; P = 0.1), U(K)V (R = -0.29; P = 0.1) or U(urea)V (R = -0.31; P = 0.1). Linear and multiple regression analysis identified nocturnal natriuresis rather than urea excretion as an independent determinant of nocturia. |
Is placental size associated with mental health in children and adolescents? | The role of the placenta in fetal programming has been recognized as a highly significant, yet often neglected area of study. We investigated placental size in relation to psychopathology, in particular attention deficit hyperactivity disorder (ADHD) symptoms, in children at 8 years of age, and later as adolescents at 16 years. Prospective data were obtained from The Northern Finland Birth Cohort (NFBC) 1986. Placental weight, surface area and birth weight were measured according to standard procedures, within 30 minutes after birth. ADHD symptoms, probable psychiatric disturbance, antisocial disorder and neurotic disorder were assessed at 8 years (n = 8101), and ADHD symptoms were assessed again at 16 years (n = 6607), by teachers and parents respectively. We used logistic regression analyses to investigate the association between placental size and mental health outcomes, and controlled for gestational age, birth weight, socio-demographic factors and medical factors, during gestation. There were significant positive associations between placental size (weight, surface area and placental-to-birth-weight ratio) and mental health problems in boys at 8 and 16 years of age. Increased placental weight was linked with overall probable psychiatric disturbance (at 8 y, OR= 1.14 [95% CI= 1.04-1.25]), antisocial behavior (at 8 y, OR = 1.14 [95% CI= 1.03-1.27]) and ADHD symptoms (inattention-hyperactivity at 16 y, OR= 1.19 [95% CI = 1.02-1.38]). No significant associations were detected among girls. | The proteasome degrades NF-kappaB blocking protein (I-kappaB) and activates NF-kappaB that plays as a key transcriptional factor to regulate inflammatory factors that are involved in the tissue reperfusion injury. This study was designed to assess whether the proteasome inhibitor can attenuate peripheral nerve ischemia/reperfusion (I/R) injury and consequently promote motor functional recovery after ischemic insult. Rat sciatic nerves were exposed to 2 hour of ischemia followed by various periods of reperfusion. Rats were administered either proteasome inhibitor (bortezomib) or phosphate-buffered saline 30 minutes before reperfusion start. Results were evaluated using a walking track test, and an isolated muscle contraction test, and by muscle weight, and histology. Bortezomib treatment induced an earlier improvement in sciatic functional index and a more rapid restoration of contractile force and wet weight of extensor digitorum longus muscle. Bortezomib reduced early axonal degeneration and promoted regeneration. |
Is voriconazole delivered from antifungal-loaded bone cement? | Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown. (1) Is voriconazole release dose-dependent? (2) Is released voriconazole active? (3) Is the loss of ALBC's compressive strength caused by voriconazole dose- and elution-dependent? Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance. Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively. | Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley. The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant. The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea. |
Do passive leg movements and passive cycling alter arterial leg blood flow in subjects with spinal cord injury? | Subjects with a spinal cord injury (SCI) are at increased risk for cardiovascular disease-related secondary complications, such as pressure ulcers and attenuated wound healing. It has been suggested that passive exercise enhances blood flow via mechanical pump effects or reflex activation. The purpose of this study was to assess the effects of passive leg movements and passive cycling on the arterial circulation in subjects with SCI. Eight men with motor complete SCI and 8 male control subjects participated. Echo Doppler measurements were obtained to measure leg blood flow at rest, during and after 10 minutes of standardized passive leg movements, and during and after 20 minutes of passive leg cycling. Blood pressure was measured continuously, and total vascular resistance and leg vascular resistance were calculated. In both groups, no changes in leg blood flow, vascular resistance, or blood pressure were observed during or after the 2 interventions. | BACKGROUND/AIMs: Pleiotrophin (PTN) have been demonstrated to play an important role in the development of human gastric cancer. However, the prognostic value remains unclear. The aim of this study was to investigate whether expression of PTN has prognostic relevance in human gastric cancer. Immunohistochemistry was used to investigate the expression of PTN proteins in 178 patients with gastric cancer. The level of PTN mRNA in gastric cancer tissues and paratumor tissues were evaluated in 52 paired cases by quantitative real-time polymerase chainreaction(qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. The expression level of PTN in gastric cancer tissues was significantly higher (P<0.001) than those in paratumor tissues according to the immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of PTN was significantly associated with the tumor site (P=0.001), Lauren’s classification (P<0.001),histologic differentiation(P=0.014),depth of invasion(P<0.001), TNM stage (P=0.003),and lymph node metastasis (P=0.002). Moreover, the Cox proportional- hazards regression analysis revealed that the increased expression of PTN was an independent prognostic factor for poor recurrence-free survival(RFS) and overall survival(OS)(both P<0.001). |
Does neonatal intensive care unit census influence discharge of moderately preterm infants? | The timely discharge of moderately premature infants has important economic implications. The decision to discharge should occur independent of unit census. We evaluated the impact of unit census on the decision to discharge moderately preterm infants. In a prospective multicenter cohort study, we enrolled 850 infants born between 30 and 34 weeks' gestation at 10 NICUs in Massachusetts and California. We divided the daily census from each hospital into quintiles and tested whether discharges were evenly distributed among them. Using logistic regression, we analyzed predictors of discharge within census quintiles associated with a greater- or less-than-expected likelihood of discharge. We then explored parental satisfaction and postdischarge resource consumption in relation to discharge during census periods that were associated with high proportions of discharge. There was a significant correlation between unit census and likelihood of discharge. When unit census was in the lowest quintile, patients were 20% less likely to be discharged when compared with all of the other quintiles of unit census. In the lowest quintile of unit census, patient/nurse ratio was the only variable associated with discharge. When census was in the highest quintile, patients were 32% more likely to be discharged when compared with all of the other quintiles of unit census. For patients in this quintile, a higher patient/nurse ratio increased the likelihood of discharge. Conversely, infants with prolonged lengths of stay, an increasing Score for Neonatal Acute Physiology II, and minor congenital anomalies were less likely to be discharged. Infants discharged at high unit census did not differ from their peers in terms of parental satisfaction, emergency department visits, home nurse visits, or rehospitalization rates. | Hepatocyte growth factor/scatter factor (HGF/SF) can sufficiently and independently induce pathophysiological angiogenesis. However, the treatment strategies have mostly been unsuccessful. The present study is the first to evaluate the possible targeting of downstream signals for the inhibition of HGF/SF-induced angiogenesis. In a multichannel scratch assay with human endothelial cells (ECs), HGF/SF induced a strong and prolonged activation of MAPK and cell proliferation that was inhibited by PD98059 and LY294002/wortmannin, selective inhibitors of MAPK and PI3K signaling modules, respectively. Western blotting demonstrated a temporal relation between the activation of the two pathways. Chemical inhibition of the PI3K and MAPK signals inhibited HGF/SF-induced chemoinvasion of ECs in vitro and blocked the HGF/SF-induced neovascularization into a polymer scaffold in vivo, as quantified by vessel counts and the clearance of radioactive 133Xe. |
Is expression of IL-8 during reperfusion of renal allografts dependent on ischemic time? | Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion. This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR. Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies. | Riboflavin deficiency is common in many parts of the world, particularly in developing countries. The use of riboflavin-producing strains in the production of dairy products such as fermented milk, yogurt, and cheese is feasible and economically attractive because it would decrease the costs involved during conventional vitamin fortification and satisfy consumer demands for healthier foods. The present study in a rat bioassay assessed the response of administration of yogurt containing a riboflavin-producing strain of Propionibacterium freudenreichii on the riboflavin status of deficient rats. Propionibacterium freudenreichii NIZO B2336 is a spontaneous roseoflavin-resistant mutant derived from P. freudenreichii B374 that produces larger amounts of riboflavin than the parental stain. Rats were fed a riboflavin-deficient diet for 21 d (depletion period), after which this same diet was supplemented with conventional yogurt, yogurt containing the riboflavin-producing strain (B2336), or the parental non-producing strain (B374) and fed to animals for 28 d (repletion period). As controls, rats were fed the same diet with different concentrations of commercial riboflavin. The novel fermented product containing P. freudenreichii B2336, with increased levels of riboflavin, eliminated most physiologic manifestations of ariboflavinosis such as stunted growth, high erythrocyte glutathione reductase activation coefficient values, and hepatomegaly that were observed when using a riboflavin depletion-repletion model, whereas the product fermented with the non-riboflavin-producing strain did not show this beneficial effect. |
Does chronic isolation of adult rats decrease gene expression of catecholamine biosynthetic enzymes in adrenal medulla? | Isolation of adult animals represents a form of psychsocial stress that produces sympatho-adrenomedullar activation. The aim of this work was to investigate the changes in gene expression and protein levels of catecholamine biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of naive control and chronically (12 weeks) socially isolated adult Wistar rat males and the response of these animals to additional immobilization stress (2 h). TH, DBH and PNMT mRNA levels were quantified by quantitative real-time RT-PCR (qRT-PCR). TH, DBH and PNMT immunoproteins were assayed by Western Blot. In chronically isolated rats, gene expression levels of catecholamine biosynthetic enzymes in the adrenal medulla were decreased, but only TH mRNA was significantly decreased. However, protein levels of TH, DBH and PNMT of these animals were elevated by 55%, 20% and 18%, respectively, in relation to the corresponding control. Naive control and chronically socially isolated rats exposed to additional 2-h-immobilization showed increased gene expression of the examined enzymes, the increase being greater in socially isolated rats as compared to the controls. Additional immobilization of naive controls did not affect TH, DBH and PNMT protein levels. In contrast, this stress produced increased TH, DBH and PNMT protein levels in long-term socially isolated rats. | Platelet monocyte aggregates (PMA) and monocyte chemoattractant protein-1 (MCP-1) play a significant role in atherosclerotic disease but the effect of aspirin and their role in peripheral arterial disease (PAD) requires further investigation. We have compared p-selectin, PMA and MCP-1 in patients with PAD treated with aspirin (75 mgs daily), with age matched controls not treated with aspirin. Using flow cytometry and ELISA, P-selectin, PMA and MCP-1 were compared in 3 populations; healthy controls (n=12), intermittent claudication (n=19) and critical limb ischaemia (CLI), (n=10). P-selectin was significantly higher in CLI patients (3.48% positive) compared to the claudicants (1. 36% positive) and the controls (1.76% positive). PMA levels were significantly higher for CLI population (44.5% positive) compared to the claudicants (20.48% positive) and the controls (28.33% positive). MCP-1 levels expression was significantly higher for the CLI patients (175.4 pg/mL) compared to the claudicants (76.1 pg/mL) and the controls (117.0 pg/mL). |
Does antibacterial therapy improve the effectiveness of prostate cancer detection using prostate-specific antigen in patients with asymptomatic prostatitis? | To improve prostate cancer (PC) detection accuracy among patients with a prostate-specific antigen (PSA) above 4.0 ng/ml and asymptomatic prostate inflammation. A total of 136 patients with PSA ranging from 4.0 to 50.0 ng/ml with asymptomatic prostatitis were included in the study cohort. All these patients underwent antibacterial therapy for 2 weeks followed by repeat PSA determination and transrectal ultrasound-guided needle prostate biopsy. The PSA, PSAD (PSA density), and f/t PSA (free/total PSA) before and after antibacterial therapy were compared using t-test. The receiver-operating characteristic (ROC) technique was used to evaluate the effectiveness of PSA, PSAD, f/t PSA, and their changes after antibacterial therapy (DeltaPSA, DeltaPSAD, and Deltaf/t PSA) on PC detection. Among the 136 patients, 33 had PC and the other 103 histologically confirmed benign prostatic disease. After antibacterial therapy for 2 weeks, the PSA (mean +/- standard deviation) decreased from 14.0 +/- 7.8 ng/ml to 10.4 +/- 7.7 ng/ml (P < 0.01). The DeltaPSA, DeltaPSAD, and Deltaf/tPSA were -3.60 +/- 4.3 ng/ml, -0.1 +/- 0.1 ng/ml/ml, and -0.1 +/- 0.1 respectively. The areas under ROC curve were 0.29 for PSA, 0.64 for PSAD, and 0.50 for f/t PSA. The areas under ROC curve were 0.91 for DeltaPSA, 0.96 for DeltaPSAD, and 0.98 for Deltaf/t PSA. These values were increased significantly when compared with those for the PSA-related parameters before antibacterial therapy (P value, DeltaPSA, DeltaPSAD, and Deltaf/t PSA were <0.01). | Cocaine administration to near-term pregnant sheep causes fetal hypoxemia, but oxygen delivery to the heart and brain are preserved because of increased blood flow. We hypothesized that cocaine administration during earlier fetal gestation impairs oxygen delivery to the heart and brain. Ten pregnant ewes and fetuses at 0.7 term gestation underwent surgical instrumentation. After 48 hours of recovery fetal blood pressure, heart rate, cerebral and myocardial blood flow, and arterial oxygen content were determined before and during cocaine administration to the ewe. Fetal hypoxemia was not noted in these animals. Fetal myocardial blood flow increased from 220 +/- 100 ml per 100 gm per minute to 349 +/- 183 ml per 100 gm per minute (p=0.03), and oxygen delivery increased from 16 +/- 5 ml of oxygen per 100 gm per minute to 22 +/- ml of oxygen per 100 gm per minute (p=0.02). Fetal cerebral blood flow and oxygen delivery remained unchanged. |
Does metabolomic analysis of CSF indicate brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey? | Iron deficiency (ID) anemia leads to long-term neurodevelopmental deficits by altering iron-dependent brain metabolism. The objective of the study was to determine if ID induces metabolomic abnormalities in the cerebrospinal fluid (CSF) in the pre-anemic stage and to ascertain the aspects of abnormal brain metabolism affected. Standard hematological parameters [hemoglobin (Hgb), mean corpuscular volume (MCV), transferrin (Tf) saturation, and zinc protoporphyrin/heme (ZnPP/H)] were compared at 2, 4, 6, 8, and 12 months in iron-sufficient (IS; n = 7) and iron-deficient (ID; n = 7) infant rhesus monkeys. Five CSF metabolite ratios were determined at 4, 8, and 12 months using ID infants developed ID (Tf saturation < 25%) by 4 months of age and all became anemic (Hgb < 110 g/L and MCV < 60 fL) at 6 months. Their heme indices normalized by 12 months. Pyruvate/glutamine and phosphocreatine/creatine (PCr/Cr) ratios in CSF were lower in the ID infants by 4 months (P < 0.05). The PCr/Cr ratio remained lower at 8 months (P = 0.02). ZnPP/H, an established blood marker of pre-anemic ID, was positively correlated with the CSF citrate/glutamine ratio (marginal correlation, 0.34; P < 0.001; family wise error rate = 0.001). | To study the role of peroperative transrectal ultrasonography (peTRUS) for the dissection of the bladder neck during robot-assisted laparoscopic prostatectomy (RALP). Integrated peTRUS in the da Vinci S system (Intuitive Surgical, Sunnyvale, CA, USA) was used for bladder neck identification and dissection in the initial 80 patients with clinically localized prostate cancer operated by two urologists. The clinical and pathological results were compared with the initial 80 patients who had RALP with no peTRUS. The location of positive margins was recorded. The operative duration, blood loss, hospital stay, catheter dependency, clinical and pathological T-stage and Gleason sum score were no different between the groups. The prostate-specific antigen level at time of diagnosis was slightly higher for patients in the peTRUS group. Basal surgical margins (bladder neck and basal areas of both prostate lobes) were positive for tumour in 9.1% and 2.3% of patients treated without and with peTRUS, respectively (P = 0.001). Although the use of peTRUS improved the basal margin rate in the initial 30 patients in each group, it did not in the last 30 in each group, when the urologist's experience apparently improved. In a multivariate analysis the use of peTRUS and pathological T-stage were the best predictors of basal margin status. Pad use at 6 months after surgery was similar for both groups. |
Is early activation of matrix metalloproteinase-9 associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats? | The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood-brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia. Male Sprague-Dawley rats weighing 250-300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay. The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury. | To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients. This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed. The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non-exempt patients. |
Does myocardial protection evoked by hyperoxic exposure involve signaling through nitric oxide and mitogen activated protein kinases? | Hyperoxic exposure in vivo (> 95% oxygen) attenuates ischemia-reperfusion injury, but the signaling mechanisms of this cardioprotection are not fully determined. We studied a possible role of nitric oxide (NO) and mitogen activated protein kinases (MAPK) in hyperoxic protection. Mice (n = 7-9 in each group) were kept in normoxic or hyperoxic environments for 15 min prior to harvesting the heart and Langendorff perfusion with global ischemia (45 min) and reperfusion (60 min). Endpoints were cardiac function and infarct size. Additional hearts were collected to evaluate MAPK phosphorylation (immunoblot). The nitric oxide synthase inhibitor L-NAME, the ERK1/2 inhibitor PD98059 and the p38 MAPK inhibitor FR167653 were injected intraperitoneally before hyperoxia or normoxia. Hyperoxia improved postischemic functional recovery and reduced infarct size (p < 0.05). Hyperoxic exposure caused cardiac phosphorylation of the MAPK family members p38 and ERK1/2, but not JNK. L-NAME, PD98059 and FR167653 all reduced the protection afforded by hyperoxic exposure, but did not influence performance or infarction in hearts of normoxic mice. The hyperoxia-induced phosphorylation of ERK1/2 and p38 was reduced by L-NAME and both MAPK inhibitors. | To determine the clinical significance of IgG antibodies to type II collagen (CII) and to define any correlation of antibodies to CII with the inflammatory response in patients with rheumatoid arthritis (RA). IgG antibodies to native human type II collagen (IgG anti-CII) were measured in sera and synovial fluid (SF) from patients with RA, patients with osteoarthritis (OA), and healthy controls by an improved ELISA. Demographic, clinical, and laboratory data including tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also obtained at the time of sampling in patients with RA. The median level and positivity for circulating IgG anti-CII were higher in patients with RA (n = 297) than patients with OA (n = 34) and healthy controls (n = 50) (p < 0.001). The titers of IgG anti-CII in SF were also higher in RA (n = 45) than in OA (n = 16) (p < 0.001). In paired samples, the levels of IgG anti-CII were significantly higher in SF compared to the sera in patients with RA (n = 45) (p < 0.001), but levels were not different in patients with OA (n = 16). Circulating IgG anti-CII converted from positive to negative in 13 patients (10.7%) and from negative to positive in 18 patients (14.8%) among 122 patients with RA in whom IgG anti-CII were monitored sequentially at a mean interval of 12.2 months. IgG anti-CII positive patients (n = 98) had shorter disease duration (p = 0.04) and less frequent deformity (p = 0.013), and higher median erythrocyte sedimentation rate (ESR) (p = 0.001) and C-reactive protein (CRP) (p < 0.001) than IgG anti-CII negative patients (n = 120). The levels of IgG anti-CII correlated with CRP (r = 0.270) and ESR (r = 0.253). CRP decreased significantly in patients (n = 13) who converted from IgG anti-CII positive to negative (p = 0.013). IgG anti-CII positive patients (n = 40) had higher levels of TNF-alpha and IL-6 than negative patients (n = 40) (p < 0.001). Levels of IgG anti-CII correlated well with TNF-alpha (r = 0.617) and IL-6 (r = 0.347). |
Does targeting factor VIII expression to platelets for hemophilia A gene therapy induce an apparent thrombotic risk in mice? | Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. | The cost effectiveness of preoperative localization in cases of primary hyperpara-thyroidism has not been established. We analyzed the potential savings in operative time after localization with technetium 99m (99mTc) sestamibi scan. Thirty-three patients had localization of a solitary adenoma with 99mTc-sestamibi. Measurement was made of the time required for adenomectomy, unilateral neck exploration (UNE), unilateral neck exploration and confirmation of one contralateral parathyroid gland (UNEC), or bilateral neck exploration (BNE). The total operative time in minutes was 76.4 +/- 18.8 for adenomectomy; 87.5 +/- 20.4 for UNE; 105.6 +/- 25.0 for UNEC; and 117.9 +/- 26.7 for BNE. The time difference was significant between adenomectomy versus UNE, UNEC, and BNE. There were also significant time differences between UNE versus UNEC and BNE. |
Is it highly unlikely that the development of an abdominal wall hernia can be attributable to a single strenuous event? | There is a commonly held belief that the development of a hernia can be attributed to a single strenuous or traumatic event. Hence, many litigants are successful in compensation claims, causing mounting financial burdens on employers, the courts, insurance companies and the tax-payer. However, there is very little scientific evidence to support this assertion. The aim of this study was to ascertain whether there was any causal link in this process. A total of 133 new patients with 135 abdominal herniae of all varieties (115 inguinal, 3 femoral, 9 umbilical, 4 incisional, and 4 ventral or epigastric), of which 25 were recurrent received structured questionnaires on arrival in the surgical clinic. These questionnaires covered all possible aetiological factors for hernia development (type of work, COAD, smoking, pregnancy, obesity, chronic bladder outflow obstruction, previous surgery including appendicectomy), in addition to any possible attribution to a single strenuous or traumatic event. We then reviewed the GP records in the surgery of all patients who answered positively to the latter possible cause. In the study group, 119 (89%) reported a gradual onset of symptoms. Of the 15 (12 male, 3 female; 11%) who believed that their hernia might be related to a single strenuous or traumatic event, 5 had no other aetiological factors. However, not one of the 15 was found to have contemporaneous forensic medical evidence to support their possible claim. | To determine the antiviral activity of phosphorodiamidate morpholino oligomers (PMO) and peptide-conjugated PMO (PPMO) in AG129 mice infected with dengue 2 virus (DENV-2). Antisense PMO and PPMO were designed against the 5' terminal region (5'SL) or the 3'-cyclization sequence region (3'CS) of DENV genomic RNA and administered to AG129 mice before and/or after infection with DENV-2. In addition, cell culture evaluations designed to determine optimum PPMO length, and pharmacokinetic and toxicity analysis of PPMO were also carried out. Mock-treated AG129 mice lived for 9-17 days following intraperitoneal (ip) infection with 10(4)-10(6) pfu of DENV-2 (strain New Guinea C). Intraperitoneal administration of 5'SL or 3'CS PPMO before and after DENV infection produced an increase in the average survival time of up to 8 days. Animals receiving only post-infection PPMO treatment did not benefit significantly. Cell culture studies showed that PPMO of 22-24 bases long produced substantially higher DENV titre reductions than did PPMO that were either shorter or longer. Pharmacokinetic and toxicology analysis with non-infected animals showed that nine consecutive once-daily ip treatments of 10 mg/kg PPMO resulted in high concentrations of PPMO in the liver and caused little impact on overall health. |
Is pentraxin 3 reduced in bipolar disorder? | Immunologic abnormalities have been found in bipolar disorder but pentraxin 3, a marker of innate immunity, has not been studied in this population. Levels of pentraxin 3 were measured in individuals with bipolar disorder, schizophrenia, and non-psychiatric controls. Linear regression models were used to compare the pentraxin 3 levels in each of the psychiatric groups to that in the control group, adjusting for demographic and clinical variables. Logistic regression models were used to calculate the odds ratios associated with levels of pentraxin 3 which differed from specified levels of the control group. The sample consisted of 831 individuals: 256 with bipolar disorder, 309 with schizophrenia, and 266 without a psychiatric disorder. The levels of pentraxin 3 in the bipolar disorder, but not in the schizophrenia, group were significantly lower than those of controls, adjusting for age, gender, race, maternal education, smoking status, and body mass index (t = -3.78, p < 0.001). The individuals with bipolar disorder also had significantly increased odds of having low levels of pentraxin 3 relative to both the 10th and 25th percentile level of the controls and significantly decreased odds of having a level greater than the 75th and the 90th percentile level of the controls, adjusting for the same covariates. | Chlorophyll b is a major photosynthetic pigment in green plants that is synthesized by chlorophyllide a oxygenase (CAO). The regulation of chlorophyll b biosynthesis is an important determinant for the antenna size of photosystems. Chlorophyll b synthesis is partly regulated on a transcriptional level by the expression of the CAO gene. In addition, the synthesis of chlorophyll b is strictly regulated on a protein level by the stability of the CAO enzyme. CAO consists of three domains, which are sequentially named from the N terminus as the A, B and C domains. The A domain of CAO participates in the regulation of the CAO protein stability. In order to clarify the physiological function of the A domain, we constructed transgenic Arabidopsis (Arabidopsis thaliana) plants which either overexpressed the complete CAO or a truncated version of CAO lacking the A domain. The transgenic plants overexpressing the A-domain-deleted CAO accumulated an excess amount of chlorophyll b during greening. The transgenic plants which lacked the A domain either died or were obviously retarded when they were exposed to continuous light immediately after etiolation. In addition, the loss of the A domain in CAO impaired another step of chlorophyll biosynthesis, namely the conversion of divinyl-protochlorophyllide a to monovinyl protochlorophyllide a under dark conditions. |
Does global incomplete cerebral ischemia produce predominantly cortical neuronal injury? | We determined the neuropathologic damage in a canine model of global incomplete ischemia commonly used in a variety of physiological experiments. We induced 20 minutes of incomplete ischemia in dogs (n = 9) by increasing intracranial pressure via intraventricular infusion of artificial cerebrospinal fluid to maintain a cerebral perfusion pressure of 10 mm Hg while keeping body temperature at 38 degrees C during and immediately after ischemia. After a 7-day recovery period, animals were perfusion-fixed for neuropathology. In hematoxylin and eosin preparations, ischemic neuronal injury was assessed, neurons were counted, and percentage of cell damage was determined. No focal neurological deficits or overt seizures were observed during the 7-day recovery period. In superior temporal gyrus, 49 +/- 11% and 70 +/- 10% damage (mean +/- SEM) was observed in layer III pyramidal cells in the crown and sulcus, respectively. All neocortical regions examined showed neuronal damage in layers III and/or V. In hippocampus, 59 +/- 11% damage of pyramidal neurons occurred in CA1, with dorsal (septal) hippocampus showing more injury than ventral (temporal) portions. The caudate nucleus (head) exhibited 27 +/- 7% neuronal injury. In cerebellar cortex (anterior lobule), 70 +/- 7% damage of Purkinje cells occurred, but different folia of cerebellum showed varying degrees of injury. Brain stem and thalamus were minimally affected despite reduced blood flow. Inflammatory changes (leukocytic infiltration and neuronal incrustations) were observed, but only when neuronal degeneration was severe. Pancellular necrosis and infarction did not occur. | Colorectal cancer (CRC) is the third most common cancer in Canada. Screening guidelines recommend that first-time screening should occur at 50 years of age for average-risk individuals and at 40 years of age for those with a family history of CRC. To examine whether persons with a positive CRC family history were achieving screening at 40 years of age and whether average-risk persons were achieving screening at 50 years of age. The present study was a cross-sectional analysis of subjects who entered a colon cancer screening program and were undergoing CRC screening for the first time. A total of 778 individuals were enrolled in the present study: 340 (174 males) with no family history of CRC, and 438 (189 males) with a positive family history of CRC. For the group with a positive family history, the mean (± SD) age for primary screening was 54.4 ± 8.5 years, compared with 58.2 ± 6.4 years for the group with no family history. On average, those with a positive family history initiated screening 3.8 years (95% CI 2.8 to 4.8; P<0.05) earlier than those without. Adenoma polyp detection rate for the positive family history group was 20.8% (n=91) compared with 23.5 % (n=80) for the group with no family history. |
Is s-phase fraction a prognostic factor in stage I breast carcinoma? | The prognostic significance of cell proliferation, estimated as cytometric S-phase fraction (SPF), was investigated in node-negative breast cancer patients with small tumors (T1, NO). The 219 stage I patients originated from two series and were diagnosed either from 1978 to 1981 or from 1981 to 1985. The tumors were analyzed for estrogen receptors (ERs) by isoelectric focusing and for cellular DNA content by static cytofluorometry or flow cytometry. A high SPF correlated with the absence of ERs and abnormal DNA content, and was less often found in tumors smaller than 11 mm compared with those with a diameter between 11 and 20 mm. Among the variables age, tumor size, DNA ploidy, ER status, and SPF, only SPF showed a significant association with distant recurrence and breast cancer survival in systemically untreated patients. The relative recurrence rate for patients with an SPF of 10% or greater was three times that for patients with lower SPFs. Estimated 8-year breast cancer survival rates for the same groups were 72% and 91%, respectively. | Acute mountain sickness may be caused by cerebrovascular fluid leakage due to oxidative damage to the endothelium. This may be reduced by oral antioxidant supplementation. To assess the effectiveness of antioxidant supplementation for the prevention of acute mountain sickness (AMS). A parallel-group double blind, randomized placebo-controlled trial. The study was conducted in a university clinical research facility and a high altitude research laboratory. Eighty-three healthy lowland volunteers ascended to 5200 m on the Apex 2 high altitude research expedition. The treatment group received a daily dose of 1 g l-ascorbic acid, 400 IU of alpha-tocopherol acetate and 600 mg of alpha-lipoic acid (Cultech Ltd., Wales, UK) in four divided doses. Prevalence of AMS was measured using the Lake Louise Consensus score sheet (LLS). Secondary outcomes were AMS severity measured using a novel visual analogue scale, arterial oxygen saturation and pulmonary artery systolic pressure (PASP). Forty-one subjects were allocated to the antioxidant group, and 42 to the placebo group. There was no difference in AMS incidence or severity between the antioxidant and placebo groups using the LLS at any time at high altitude. At the pre-determined comparison point at Day 2 at 5200 m, 69% of the antioxidant group (25/36) and 66% of the placebo group (23/35) had AMS using the LLS criteria (P = 0.74). No differences were observed between the groups for PASP, oxygen saturation, presence of a pericardial effusion or AMS assessed by VAS. |
Does [ Programmed application of extracellular matrix promote neural differentiation of mouse embryonic stem cells ]? | To study the role of extracellular matrix (ECM) in neural differentiation of mouse embryonic stem cells (ESCs). Mouse ESCs were incubated in the ESC conditioned medium, and the formation of embryonic bodies (EBs) were induced in bacteriological dishes using high-concentration all-trans retinoic acid (RA). The EBs were seeded on different matrixes (gelatin, fibronectin, and laminin/poly-L-ornithine) to test their impact on neural differentiation of the ESCs using immunofluorescence assay. The effect of laminin/poly-L-ornithine on the growth of neurites was evaluated with fluorescence microscopy. High-concentration RA activated and accelerated the differentiation of ESCs toward nestin-positive neural progenitor cells. Fibronectin supplement in the matrix dose-dependently promoted ESC differentiation into neural progenitor cells, while laminin/poly-L-ornithine increased the growth of the neurites and induced the maturation of the differentiated neural cells. | Cytochrome P450 oxidoreductase (POR) is the only flavoprotein that donates electrons to all microsomal P450 enzymes (CYP), and several POR SNPs have been shown to be important contributors to altered CYP activity or CYP-mediated drug metabolism. In this study we examined the association between 6 POR SNPs and tacrolimus concentrations in Chinese renal transplant recipients. A total of 154 renal transplant recipients were enrolled. Genotyping of CYP3A5*3 and 6 POR SNPs was performed. All patients received a triple immunosuppressive regimen comprising tacrolimus, mycophenolate mofetil and prednisone. Dose-adjusted tacrolimus trough concentrations were obtained on d 7 (C0D7/D) after transplantation when steady-state concentration of tacrolimus was achieved (dosage had been unchanged for more than 3 d). Tacrolimus C0D7/D in CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype carriers was 1.62- and 2.72-fold higher than those in CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype non-carriers and CYP3A5*1 carriers (220.17±48.09 vs 135.69±6.86 and 80.84±5.27 ng/mL/mg/kg, respectively, P<0.0001). Of CYP3A5*3/*3/ POR rs1057868-rs2868177GC-GT diplotype carriers, 85.71% exceeded the upper limit of the target range (8 ng/mL), which was also significantly higher compared with the latter two groups (14.29% and 0.00%, respectively, P<0.0001). The CYP3A5*3 and POR rs1057868-rs2868177 GC-GT diplotype explained 31.7% and 5.7%, respectively, of the inter-individual variability of tacrolimus C0D7/D, whereas the POR rs1057868-rs2868177 GC-GT diplotype could explain 10.9% of the inter-individual variability of tacrolimus C0D7/D in CYP3A5 non-expressers. |
Do heated jackets and dryland-based activation exercises used as additional warm-ups during transition enhance sprint swimming performance? | The lengthy competition transition phases commonly experienced by competitive swimmers may mitigate the benefits of the pool warm-up. To combat this, we examined the impact of additional passive and active warm-up strategies on sprint swimming performance. Counterbalanced, repeated-measures cross-over study. Sixteen junior competitive swimmers completed a standardised pool warm-up followed by a 30min transition and 100m freestyle time-trial. Swimmers completed four different warm-up strategies during transition: remained seated wearing a conventional tracksuit top and pants (Control), wore an insulated top with integrated heating elements (Passive), performed a 5min dryland-based exercise circuit (Dryland), or a combination of Passive and Dryland (Combo). Swimming time-trial performance, core and skin temperature and perceptual variables were monitored. Time variables were normalised relative to Control. Both Combo (-1.05±0.26%; mean±90% confidence limits, p=0.00) and Dryland (-0.68±0.34%; p=0.02) yielded faster overall time-trial performances, with start times also faster for Combo (-0.37±0.07%; p=0.00) compared to Control. Core temperature declined less during transition with Combo (-0.13±0.25°C; p=0.01) and possibly with Dryland (-0.24±0.13°C; p=0.09) compared to Control (-0.64±0.16°C), with a smaller reduction in core temperature related to better time-trial performance (R(2)=0.91; p=0.04). | The aim of this study was to assess serum levels of presurgical α-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) as prognostic markers in patients with hepatic carcinoma after liver transplantation (LT). A total of 226 patients were recruited for the analysis of serum AFP and CA19-9 levels, on the basis of which the tumor marker type (TMT) was defined and evaluated for prognostic prediction. Overall survival (OS) and relapse-free survival (RFS) were analyzed using Kaplan-Meier curves, and univariate and multivariate Cox models. One-year and 5-year OS were 79.0 and 58.0%, respectively, whereas RFS were 70.3 and 62.2%, respectively, in this cohort of patients. There were six variables predicting both OS and RFS, including TMT, tumor size, number of tumor lesions, extrahepatic or vascular invasion, and histopathological grade. Among these, TMT, tumor size, and extrahepatic invasion were all independent predictors of OS and RFS among these patients. Further, on the basis of TMT, novel LT selection criteria for patients with hepatic carcinoma, which supplemented the Milan criteria, were adopted, because the patients within the Milan criteria (n=107) and those exceeding Milan but fulfilling the proposed criteria (n=30) had similar 5-year OS (77.8 vs. 79.3%, P=0.862) and RFS (85.5 vs. 75.1%, P=0.210) rates. |
Is tRPC1 required for survival and proliferation of cochlear spiral ganglion stem/progenitor cells? | The present studies were designed to test the hypothesis that canonical transient receptor potential channel 1 (TRPC1) is required for the proliferation of cochlear spiral ganglion stem/progenitor cells (SPCs). TRPC1 were detected and evaluated in postnatal day 1 CBA/CaJ mice pups derived-cochlear spiral ganglion SPCs by reverse transcription-polymerase chain reaction, Western blot, immunocytochemistry, and calcium imaging. The cell viability and proliferation of the spiral ganglion SPCs following si-RNA mediated knockdown of TRPC1 or addition of TRPC channel blocker SKF9635 were compared to controls. In spiral ganglion SPCs, TRPC1 was found to be the most abundantly expressed TRPC subunit and shown to contribute to store-operated calcium entry. Silencing of TRPC1 or addition of TRPC channel blockers significantly decreased the rate of cell proliferation. | To determine the frequency of pulmonary embolism (PE) diagnosis when different alternative diagnoses were considered most likely before testing, because the relationship between specific alternative diagnoses and the diagnosis of PE has not been explored. This study was a preplanned secondary analysis of a prospective study of the diagnosis of pulmonary embolism conducted in the emergency department (ED) of an urban university hospital. Physicians were queried as to their most likely pretest diagnosis when they ordered any of the following tests to evaluate possible PE: D-dimer, contrast-enhanced computed tomography of the chest, ventilation-perfusion lung scan, or pulmonary angiogram. To compare the frequency of PE diagnosis across alternative diagnoses, risk ratios, 95% confidence intervals (CI), and p-values using Fisher's exact test were calculated. Six hundred seven patients were enrolled, and 61 had PE. Physicians thought PE was the most likely pretest diagnosis in 162 (26.7%) patients, and 20.4% (95% CI = 14.4% to 27.4%) of these patients had PE. For four alternative diagnoses, PE was diagnosed less frequently than when PE was considered most likely: musculoskeletal pain (2.2%, 95% CI = 0.4% to 6.2%), anxiety (1.7%, 95% CI = 0.0 to 9.2%), asthma or chronic obstructive pulmonary disease (0, 95% CI = 0.0 to 10.9%), and viral syndrome (0, 95% CI = 0.0 to 14.3%). |
Do several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge? | On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms. We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation. A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2. A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (K(D) value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality). | Peripheral arterial disease (PAD) is common among patients on chronic dialysis. Despite severe clinical manifestations, the indication for bypass surgery is controversial, because of the high morbidity and mortality rate of these patients. The less invasive percutaneous transluminal angioplasty (PTA) is a possible alternative, but data about PTA in dialysis patients are scarce. We followed 107 dialysis patients (mean age 67+/-10, 75 males) with 132 ischaemic limbs (97% with critical limb ischaemia and ischaemic foot lesions or rest pain) consecutively treated by PTA. PTA was successful in 97% of cases. Median follow-up was 22 months. Cumulative limb salvage rates at 12, 24, 36 and 48 months were 86, 84, 84 and 62%, respectively. Log-rank test showed an association between major amputation and baseline presence of foot lesions (P=0.04). This association was confirmed by a Cox survival multivariate analysis [hazard ratio (HR)=7.03, 95% confidence interval (CI)=1.1-43.0, P=0.035]. Limb salvage without any new intervention on the same leg was achieved in 70% of the cases, and was associated with the absence of diabetes mellitus (P=0.01), lower number of treated lesions (P=0.04) and proximal level (iliac and/or femoro-popliteal) of PTA (P<0.001). Independent predictors were diabetes mellitus (HR=3.47, 95% CI=1.31-9.17, P=0.01) and proximal PTA (HR=0.28, 95% CI=0.08-0.94, P=0.04). Fifty-three (49%) patients died during follow-up. Patients older than 67 years (the median value in our sample) had a 2.4-fold increase in mortality risk (95% CI=1.4-4.1, P<0.001). |
Does cisplatin enhance apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand? | Cancer cells frequently exhibit resistance to the cytotoxic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Pretreatment of TRAIL-resistant cells with cisplatin sensitizes them to this ligand. Cisplatin also has been shown to enhance adenoviral transgene expression. This study aims to evaluate the ability of cisplatin to enhance the expression and the cytotoxic effect of the tumor-specific adenoviral vector Ad/gTRAIL, which expresses a green fluorescent protein-TRAIL fusion protein. Cultured cancer cells and normal human cells were infected with Ad/gTRAIL with or without cisplatin pretreatment. Adenoviral transgene expression was determined by using flow cytometry to measure green fluorescent protein fluorescence. Cytotoxicity was measured by using thiazolyl blue tetrazolium bromide assays and an apoptosis enzyme-linked immunosorbent assay kit. Green fluorescent protein-TRAIL fusion protein expression was significantly enhanced by cisplatin pretreatment in cancer cells. Cisplatin treatment before Ad/gTRAIL infection resulted in a 2- to 12-fold increase in green fluorescent protein fluorescence intensity across cancer lines. Although Ad/gTRAIL induced mild cytotoxicity in all cancer lines (inhibitory concentration of 50% values of >500 pfu/cell), pretreatment with cisplatin resulted in a dose-dependent enhancement of Ad/gTRAIL-mediated cytotoxicity, as indicated by the drastic reduction of inhibitory concentration of 50% values to 4 to 42 pfu/cell in all cell lines. There was no cytotoxicity noted in normal cells treated with both cisplatin and Ad/gTRAIL. | To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants. A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks' postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks' PMA. Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 ± 0.66 at birth to -1.89 ± 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 ± 0.64 at 36 weeks' PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks. |
Do prevalence of psychiatric and substance use disorders among single mothers nearing lifetime welfare eligibility limits? | In the 1990s, US welfare reform legislation imposed a 5-year lifetime limit on financial support for low-income families with young children (younger than 18 years). With increasing numbers of single mothers and their children reaching the end of their welfare eligibility, there is concern about potentially high rates of untreated psychiatric and substance use disorders in this population. To determine the prevalence, correlates, and likelihood of treatment for mental and substance use disorders in a population of urban single mothers receiving Temporary Assistance for Needy Families (TANF). In-person diagnostic assessments were conducted from November 1, 2003, to October 31, 2004. Cook County, Illinois. Female TANF recipients and residents of Cook County (N = 333) who were randomly sampled during the final 24 months of their eligibility for TANF. Prevalence rates of DSM-IV mental and substance use disorders using the World Health Organization's Composite International Diagnostic Interview. Lifetime prevalence of Composite International Diagnostic Interview disorders was 61.0% (95% confidence interval [CI], 55.7%-66.3%); 12-month prevalence was 46.8% (41.5%-52.2%). Lifetime prevalence of mental disorders was 53.2% (95% CI, 47.8%-58.5%); 12-month prevalence was 44.1% (38.8%-49.5%). Lifetime prevalence of substance use disorders was 29.1% (95% CI, 23.9%-33.8%); 12-month prevalence was 9.0% (6.8%-12.0%). Lifetime prevalence of comorbid mental/substance use disorders was 21.3% (95% CI, 16.9%-25.7%); 12-month prevalence was 6.3% (3.7%-8.9%). Only 21.7% (95% CI, 14.8%-28.5%) of participants with 12-month mental disorders received treatment for mental disorders; 41.4% (22.3%-60.4%) of participants with 12-month substance abuse disorders received treatment for substance use disorders. | Angiostatin is a potent angiogenesis inhibitor that has been identified as a cryptic fragment of plasminogen molecule containing the first four kringle domain. Angiogenin, a 14-kDa monomeric protein, a potent blood vessel inducer, is expressed in tumors and present in mammalian plasma. The purpose of this study was to determine whether recombinant kringle 1-3 (rKI-3) of human plasminogen could interfere with angiogenesis induced by angiogenin and to evaluate the role of angiogenin in corneal angiogenesis in rabbit. A Hydron polymer pellet containing 2.0 microg of angiogenin was implanted intrastromally into the superior cornea of each of 44 rabbit eyes. All eyes received an intrastromal pellet and were randomized into either one group treated with 12.5 microg of rKI-3 (n = 25) or the other group treated with phosphate-buffered saline (PBS; n = 19). Both pellets were positioned in parallel at the site 1.2 mm from the superior limbus. Two masked observers kept the angiogenesis score daily, based on the number and the length of new vessels. The corneas with induced angiogenesis also were examined histologically. On the third day of the angiogenin pellets implantation, the eye treated with rKI-3 had less angiogenesis (mean score, 4.2 +/- 6.6) than eye treated with PBS (mean score, 16.1 +/- 17.1; p < 0.05, Mann-Whitney U test). The cornea treated with PBS also showed much more leukocyte adhesion than the cornea treated with rKI-3. |
Are progranulin protein levels differently regulated in plasma and CSF? | We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels. Plasma and CSF PGRN were measured in a cohort of 345 subjects from the Mayo Clinic Study of Aging by ELISA. Single nucleotide polymorphism genotyping was performed using TaqMan assays. Associations between PGRN and sex, age at sample collection, diagnosis, single nucleotide polymorphism genotypes (GRN, SORT1, and APOE), and Pittsburgh compound B score were explored separately in CSF and plasma using single variable linear regression models. Pearson partial correlation coefficient was used to estimate the correlation of PGRN in CSF and plasma. Plasma (p = 0.0031) and CSF (p = 0.0044) PGRN significantly increased with age, whereas plasma PGRN levels were 7% lower (p = 0.0025) and CSF PGRN levels 5% higher (p = 0.0024) in male compared with female participants. Correcting for age and sex, higher plasma PGRN was associated with higher CSF PGRN (partial r = 0.17, p = 0.004). In plasma, both rs5848 (GRN; p = 0.002) and rs646776 (SORT1; p = 3.56E-7) were associated with PGRN, while only rs5848 showed highly significant association in CSF (p = 5.59E-14). Age, sex, rs5848 genotype, and plasma PGRN together accounted for only 18% of the variability observed in CSF PGRN. | To define the ability of a virtual reality (VR) simulator to reflect clinical skill in surgical residents, we compared clinical laparoscopic performance and contemporary lab performance during curricular VR skills training. Nine postgraduate year (PGY) 1 and 2 surgical residents were assessed during laparoscopic cholecystectomies and appendectomies using a web-based interactive database (OpRate)over a 6-mo period. Operative performance data were collected at the conclusion of procedures (mean responses of attending surgeons in nine areas pertaining to resident preparedness and technical skill). During this period, all residents undertook iterative laparoscopic training using a new VR trainer (SEP: SimSurgery AS, Oslo, Norway; METI, Sarasota FL). OpRate performance over 4-wk blocks and closest VR performance data (mean time, path length, and errors for three iterations of six basic skills tasks) were tested for correlation by linear (Pearson) correlation method. Residents performed 1 to 6 operative cases each (median = 3) during time blocks used for comparisons (median separation operative and SEP performance data 18 d). Significant correlation of operative and VR scores was found for time to task completion in 5 of 6 VR tasks. Results were most significant for a gallbladder dissection task (P = 0.0066, correlation coefficient = -0.6671). No significant correlation of path length or error data and operative performance was observed for any VR task. |
Does dietary alpha-linolenic acid inhibit proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects? | Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects. The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets. A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured. IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-alpha was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by PBMCs (r = -0.423, P < 0.05). | Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear. We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined. PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone. |
Does taurolidine specifically inhibit growth of neuroblastoma cell lines in vitro? | Neuroblastoma is a common pediatric solid tumor with poor outcome for metastatic disease. Thus, novel therapeutic options are of main interest. The anti-neoplastic properties of taurolidine have been demonstrated on a variety of human cancer cells. However, data on neuroblastoma is lacking. Therefore, our aim was to evaluate the effect of taurolidine on growth of neuroblastoma cell lines. Neuroblastoma SK-N-BE(2)-M17 and SK-N-SH cells and nonmalignant human umbilical vein endothelial cells as controls were incubated with increasing concentrations of taurolidine (100, 250, 500 µM). Cell growth was examined after 12, 24, and 48 hours of exposure. Inhibition of cell growth by taurolidine was seen in both malignant cell lines. When compared with human umbilical vein endothelial cells, the neuroblastoma cell lines were significantly more responsive to taurolidine. | Several studies have shown that the rotation of the femoral component is an essential factor in total knee replacement. Consequently, different intra-operative landmarks for femoral implantation were established but most of them are either hard to define or have a high variance, so reducing their utility value. The aim of this randomised, prospective study was to prove that a preoperative CT scan is a usable help for femoral orientation. In 2006, 57 consecutive patients designated for implantation of a knee arthroplasty were split up in two groups (a and b) corresponding to a randomisation scheme. The implantation of the femoral component in group a) was done with a posterior condylar angle of three degrees of external rotation as invariable determined by the resection guide. In addition the surgeon could correct the rotation following any other landmarks (surgeon's own method). In group b) the posterior condylar angle was measured preoperatively with the help of a CT scan and transferred on a resection guide allowing variation of the posterior condylar angle in single degree steps. In this case variation of femoral rotation (surgeon's own method) was not possible. The rotation of all knee replacements (groups a and b) was measured postoperatively with a CT scan following the technique of Berger et al. The implantation with the femoral component lying parallel to the transepicondylar axis was regarded as correct. Differences were measured in degrees. Regarding the degree of femoral malrotation without consideration of the direction (external/internal rotation) the difference between group a) and group b) was highly statistically significant (p < 0.000001). The highest range of malrotation in group b) was two degrees versus six degrees in group a). In group b) 19 of 30 (= 63.3 %) femoral components showed no malrotation at all, in group a) only 5 of 27 (= 18.5 %) components were implanted completely correctly. |
Does metabolic efficiency promote protection from pressure overload in hearts expressing slow skeletal troponin I? | The failing heart displays increased glycolytic flux that is not matched by a commensurate increase in glucose oxidation. This mismatch induces increased anaplerotic flux and inefficient glucose metabolism. We previously found adult transgenic mouse hearts expressing the fetal troponin I isoform, (ssTnI) to be protected from ischemia by increased glycolysis. In this study, we investigated the metabolic response of adult mouse hearts expressing ssTnI to chronic pressure overload. At 2 to 3 months of age, ssTnI mice or their nontransgenic littermates underwent aortic constriction (TAC). TAC induced a 25% increase in nontransgenic heart size but only a 7% increase in ssTnI hearts (P<0.05). Nontransgenic TAC developed diastolic dysfunction (65% increase in E/A ratio), whereas the E/A ratio actually decreased in ssTnI TAC. Isolated perfused hearts from nontransgenic TAC mice showed reduced cardiac function and reduced creatine phosphate:ATP (16% reduction), but ssTnI TAC hearts maintained cardiac function and energy charge. Contrasting nontransgenic TAC, ssTnI TAC significantly increased glucose oxidation at the expense of palmitate oxidation, preventing the increase in anaplerosis observed in nontransgenic TAC hearts. Elevated glucose oxidation was mediated by a reduction in pyruvate dehydrogenase kinase 4 expression, enabling pyruvate dehydrogenase to compete against anaplerotic enzymes for pyruvate carboxylation. | To evaluate the rate of discordance between patients and physicians on adherence to highly active antiretroviral therapy (HAART) and identify factors related to discordance in these two assessments. Prospective, multicenter, cohort study (AdICONA) nested within the Italian Cohort Naive Antiretrovirals (ICONA) study. Tertiary clinical centers. The patients filled out a 16-item self-administered questionnaire on adherence to HAART. At the same time, physicians estimated the current HAART adherence of their patient. Discordance between patient and physician on adherence to antiretroviral therapy. From May 1999 to March 2000, 320 paired patient-physician assessments were obtained. Patients had a mean plasma HIV RNA of 315 copies/ml (64% had undetectable HIV RNA) and a mean CD4+ cell count of 577 cells x 10(6)/L. Nonadherence was reported by 30.9% of patients and estimated by physicians in 45.0% cases. In 111 cases (34.7%), patients and physicians were discordant on adherence to HAART. Kappa statistics was 0.27. Using patient-assessed adherence as reference, sensitivity, specificity, positive predictive value, and negative predictive value of physician-estimated adherence were 64.7%, 66.6%, 81.2%, and 45.8%, respectively. On multivariable analysis, low education level, unemployment, absence of a social worker in the clinical center, and unavailability of afternoon visits were significantly correlated with patient-physician discordance on adherence to antiretrovirals. |
Does gaAlAs laser-induced pulp mineralization involve dentin matrix protein 1 and osteopontin expression? | GaAlAs lasers induce pulp mineralization by promoting reparative dentinogenesis. This study analyzed the expression of dentin matrix protein 1 (DMP1) and osteopontin in GaAlAs laser-irradiated rat molars, to examine the hypothesis that these proteins play a role in the laser-induced reparative dentinogenic process. The mesial surfaces of the upper first molars of 8-week-old Wistar rats were irradiated with a pulsed GaAlAs laser. After 1-14 days, mRNA expression of DMP1 and osteopontin in the coronal pulp was analyzed using real-time PCR. DMP1, osteopontin, and heat shock protein 25 (HSP25) were immunolocalized at 1-21 days. The pulp exhibited a degenerative zone in its mesial portion on days 1-3, and progressive formation of reparative dentin lined with HSP25-immunoreactive odontoblast-like cells, from day 7 onwards. DMP1 and osteopontin mRNA expression were significantly upregulated on days 1-7 and 3-7, respectively. From day 7 onwards, DMP1 and osteopontin immunoreactivity colocalized along the boundary between the primary and reparative dentin. | Measurement of sputum or blood eosinophils may allow identification of a severe eosinophilic asthma population responsive to mepolizumab. The primary objective was assessment of a single blood eosinophil measurement to predict future eosinophil measurements in the following year versus using multiple blood eosinophil measurements. In addition, we examined whether a single sputum or blood eosinophil measurement was a useful biomarker for predicting treatment response to mepolizumab. Based on data from placebo subjects (n = 155), we determined whether a blood eosinophil count of 150/μl or greater at screening remained on average above this level during the following year. The rate of exacerbation reduction in the sputum substudy population based on the screening blood eosinophil count and sputum eosinophils was evaluated. Of 115 patients with eosinophils 150/μl or greater at screening, 98 (85%) remained above this level in their post-screening average. Using the average of two, three or four measurements 150/μl or greater, 97 (85%), 103 (90%), and 105 (92%) have postscreening averages above 150/μl. Mepolizumab reduced exacerbations by 69% (95% confidence interval [CI] = 41-83%) in subjects with baseline sputum eosinophils of 3% or greater compared with 66% (95% CI = 7-87%) in subjects with baseline sputum eosinophils under 3%. The reduction was 72% (95% CI = 41-83%) in subjects with blood eosinophils of 150/μl or greater compared with 30% (95% CI = -134 to 79%) in subjects with blood eosinophils under 150/μl. |
Does the incorporation of prior genomic information necessarily improve the performance of Bayesian linkage methods : an example involving sex-specific recombination and the two-point PPL? | We continue statistical development of the posterior probability of linkage (PPL). We present a two-point PPL allowing for unequal male and female recombination fractions, thetaM and thetaF, and consider alternative priors on thetaM, thetaF. We compare the sex-averaged PPL (PPLSA), assuming thetaM = thetaF, to the sex-specific PPL (PPLSS) in (thetaM, thetaF), in a series of simulations; we also compute the PPLSS using alternative priors on (thetaM, thetaF). The PPLSS based on a prior that ignores prior genomic information on sex specific recombination rates performs essentially identically to the PPLSA, even in the presence of large thetaM, thetaF differences. Moreover, adaptively skewing the prior, to incorporate (correct) genomic information on thetaM, thetaF differences, actually worsens performance of the PPLSS. We demonstrate that this has little to do with the PPLSS per se, but is rather due to extremely high levels of variability in the location of the maximum likelihood estimates of (thetaM, thetaF) in realistic data sets. | The soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4. hlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage-independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array. Our data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell-cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC-CM incubation of H28 cells completely eliminated the drug-resistant sphere-forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin. |
Does x-shaped DNA potentiate therapeutic efficacy in colitis-associated colon cancer through dual activation of TLR9 and inflammasomes? | Immunotherapy has been extensively pursed as a promising strategy for the treatment of cancer. Pattern-recognition receptors (PRRs) play important roles in triggering activation of innate and adaptive immunity. Therefore, agents that stimulate PRRs could be useful for cancer immunotherapy. We developed two kinds of X-shaped double-stranded oligodeoxynucleotides (X-DNA), a single unit of X-DNA (XS-DNA) composed of four strands of DNA and a ligated X-DNA complex (XL-DNA) formed by crosslinking each XS-DNA to the other, and investigated if they had immunostimulatory activity and could be applied to anti-cancer immunotherapy. Activation of MAPKs and NF-κB was determined by immunoblotting in bone marrow-derived primary dendritic cells (BMDCs). Immune cytokines and co-stimulatory molecules were measured by ELISA and flow cytometry analysis. Anti-cancer efficacy was examined in an azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer mouse model. Association of X-DNA and TLR9 was determined by co-immunoprecipitation followed by immunoblotting. The involvement of TLR9 and inflammasomes was determined using TLR9- or caspase-1-deficient BMDCs. Inflammasome activation was examined by degradation of pro-caspase-1 to caspase-1 and cleavage of pro-IL-1β to IL-1β in BMDCs. XL-DNA and XS-DNA induced activation of MAPKs and NF-κB and production of immune cytokines and co-stimulatory molecules in BMDCs. BMDCs stimulated by XL-DNA induced differentiation of naïve CD4(+) T cells to TH1 cells. Intravenous injection of XL-DNA into mice resulted in increased serum IFN-γ and IL-12 levels, showing in vivo efficacy of XL-DNA to activate TH1 cells and dendritic cells. XL-DNA greatly enhanced the therapeutic efficacy of doxorubicin, an anti-cancer drug, in colitis-associated colon cancer. XL-DNA directly associated with TLR9. In addition, immunostimulatory activities of X-DNA were abolished in TLR9-deficient dendritic cells. Furthermore, X-DNA induced caspase-1 degradation and IL-1β secretion in BMDCs, which were abolished in caspase-1-deficient cells. | Serum uric acid (SUA) has been associated to incident hypertension and increased risk of cardiovascular diseases. Among the 2191 subjects enrolled during the last population survey of the Brisighella Heart Study, we identified 146 new cases of arterial hypertension and 394 treated but uncontrolled hypertensive patients with different levels of SUA. Their hemodynamic characteristics have been compared with those of age- and sex-matched normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by logistic regression analysis, we evaluated which factors were associated with a worse BP control under pharmacological treatment. SUA levels were significantly higher in untreated hypertensive and uncontrolled hypertensive patients when compared to normotensives and controlled hypertensive patients. Pulse wave velocity (PWV) was significantly higher (p<0.001) in undiagnosed and uncontrolled hypertensive patients, while controlled hypertensive patients had PWV values comparable to normotensive controls. A similar trend has been observed for the augmentation index (AI). A worse BP control was associated with SUA levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass index, nor estimated glomerular filtration rate. |
Do volatile compounds of Salvadora persica inhibit the growth of oral Candida species? | The antibacterial effect of Salvadora persica has been demonstrated both in vitro and in vivo. However, data on its possible antifungal effect is scarce. Therefore, the aim of the present study was to investigate the antifungal effect of solid or pulverized S. persica on clinically important oral Candida species in vitro. The antifungal activity of S. persica was examined against reference strains and clinical isolates of oral Candida species by two different methods. In an agar diffusion test, solid as well as pulverized pieces of S. persica were tested. Mounting the S. persica test specimens inside the lid tested growth inhibition by volatile compounds. S. persica exhibited antifungal activity against all Candida species tested. In particular, the volatile compounds of solid test specimens demonstrated strong growth inhibition, whereas pulverized S. persica revealed no antifungal activity. Parameters such as storage and incubation time as well as the diameter of the sticks influenced the growth inhibition. | In essential hypertensive patients, blunted renal plasma flow responsiveness to angiotensin II suggests a pathologic increase in angiotensin II in the kidneys. This blunting has been associated with the angiotensinogen 235TT genotype. As several measures of renal function decline with age, we sought to determine the interaction of age and genotype on this intermediate phenotype. Three hundred fifteen participants had renal plasma flow response to subpressor doses of angiotensin II (3 ng/kg/min) measured by para-aminohippuric acid clearance in high-sodium balance. Individuals were divided by median age into young (<45 years) and older (> or =45 years) sets. A subset of participants was also studied after administration of captopril. Age, baseline renal plasma flow, BMI and angiotensinogen 235 genotype independently predicted renal plasma flow responsiveness to angiotensin II. Renal plasma flow responses were lower in older individuals than younger (P = 0.03, hypertensive patients; P = 0.004, normotensive individuals). Both hypertensive patients and normotensive individuals carrying either angiotensinogen 235MM or MT genotypes showed this inverse association (P = 0.005, hypertensive patients; P = 0.05, normotensive individuals). However, among angiotensinogen 235TT homozygotes the pattern differed: normotensive individuals had a fall in renal vascular responsiveness with age (P = 0.01) but hypertensive patients did not (P = 0.72). Young hypertensive patients already showed blunted responses. Of all genotype subsets, only angiotensinogen 235TT hypertensive patients showed enhancement (P = 0.03) of the renal vascular responsiveness to angiotensin II after captopril. |
Is the Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response Modified by Maternal Atopy? | Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. | This study was undertaken to determine the survival benefit of extending resections to obtain microscopically negative margins after positive intraoperative frozen sections. The impact of residual microscopic disease after pancreaticoduodenectomy is currently a point of controversy. It is, however, generally believed that microscopically positive margins negatively impact survival and this may be improved by ultimately achieving negative margins. Since 1995, patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma have been prospectively followed. Margin status has been codified as macro/microscopically negative (R0) or macroscopically negative/microscopically positive (R1). The impact of margin status on survival was evaluated utilizing survival curve analysis. Data are presented as median, mean +/- SD where appropriate. For pancreatic adenocarcinoma, 202 patients underwent pancreaticoduodenectomy. R0 resections were achieved in 158 patients, 17 of whom required extended resections to achieve complete tumor extirpation after an initially positive intraoperative frozen section (R1 --> R0). R1 resections were undertaken in 44 patients. Median survival for patients undergoing R0 resections was 21 months, 26 +/- 23.4 months versus 13 months, 17 +/- 21.0 months for patients undergoing R1 resections (P = 0.02). Median survival for patients undergoing R1 --> R0 resections was 11 months, 16 +/- 17.3, (P = 0.001). Margin status had a significant correlation with "N" stage and AJCC stage but not "T" stage. |
Does prevalence and trigger of allergic rhinitis in the United Arab Emirates? | Allergic rhinitis is a morbid condition that is frequently overlooked by patients and physicians. This type of atopy has not been adequately investigated in the United Arab Emirates. This cross-sectional, population-based observational study was conducted in the seven Emirates (Abu Dhabi, Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah). It used the European Community Respiratory Health Survey (ECRHS II) to screen for allergic rhinitis in people living in this region. Symptoms of allergic rhinitis were present in 85 (7%) of the 1,229 study population. Only 33 (39%) patients received treatment. Seventy-six (89%) patients had asthma. Thirty-seven (44%) patients were poly-sensitized. Symptoms were aggravated by dust (59%), grass/pollens (44%) and proximity to animals (21%). Winter was the peak season (37%), followed by spring (30%), autumn (18%) and summer (15%). Grass/pollen allergies were clustered in the winter, spring and summer (p ≤ 0.001). Dust was non-seasonal (p ≥ 0.121) and animal allergy was worse in the winter (p = 0.024) and spring (p = 0.044). Spring symptoms were less common in people living in the inner city (p = 0.003). | Heart failure (HF) patients are at risk for structural brain changes due to cerebral hypoperfusion. Past work shows obesity is linked with reduced cerebral blood flow and associated with brain atrophy in healthy individuals, although its effects on the brain in HF are unclear. This study examined the association among body mass index (BMI), cerebral perfusion, and brain volume in HF patients. Eighty HF patients underwent transcranial Doppler sonography to quantify cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA) and brain magnetic resonance imaging (MRI) to quantify total brain, total and subcortical gray matter, white matter volume, and white matter hyperintensities. Body mass index (BMI) operationalized weight status. Nearly 45% of HF patients exhibited a BMI consistent with obesity. Regression analyses adjusting for medical variables, demographic characteristics, and CBF-V of the MCA, showed increased BMI was associated with reduced white matter volume ( |
Does fusobacterium nucleatum enter normal human oral fibroblasts in vitro? | Fusobacterium nucleatum, a commensal opportunistic oral bacterium, is capable of invading gingival epithelial cells, but the entrance into human primary oral fibroblast cells has not been documented. This study evaluated the ability of three strains of F. nucleatum (F. nucleatum ssp. nucleatum, F. nucleatum ssp. polymorphum, and F. nucleatum ssp. vincentii) to enter gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PLFs). GFs and PLFs were cocultured for various periods of time with different strains of F. nucleatum. Scanning and transmission electron microscopy, together with confocal laser scanning microscopy, were used to visualize the entrance and presence of bacteria in host cells. Flow cytometry was performed to compare the load of internalized bacteria in GFs and PLFs exposed for 3 and 5 hours to live F. nucleatum labeled with fluorescein isothiocyanate. All three strains of F. nucleatum were found entering and located in the cytoplasm of GFs and PLFs after 1 hour of exposure. Flow cytometry tests revealed a significant increase in the fluorescent signal, compared to baseline, derived from bacteria internalized in fibroblasts exposed for 3 hours (P <0.001); a further increase was found at 5 hours. The greatest bacterial mass in exposed fibroblasts of both types was of F. nucleatum ssp. polymorphum; the smallest was of F. nucleatum ssp. vincentii. Although not statistically significant, PLFs had a higher bacterial load than corresponding GFs. | To investigate the effect of multiple-dose paroxetine intake on the stereoselective pharmacokinetics and the pharmacodynamics of metoprolol. We conducted an open trial with two sessions in eight healthy male volunteers. Racemic metoprolol (100 mg single oral dose) was administered before and after paroxetine treatment (20 mg/day for 6 days). The (R)- and (S)-metoprolol pharmacokinetics, metoprolol metabolic ratio (MR), exercise heart rate and blood pressure were assessed for 12 (pharmacodynamic data) to 24 (pharmacokinetic data) hours after each metoprolol intake. Paroxetine treatment increased the mean area under the plasma concentration-time curve extrapolated to infinity (AUC) of (R)- and (S)-metoprolol significantly (169 to 1,340 ng x h/mL [P < .001] and 279 to 1,418 ng x h/mL [P < .001], respectively), with an approximately twofold increase in both maximum plasma concentration and terminal elimination half-life. Furthermore, the (S)/(R) AUC ratio was significantly decreased, from 1.72 to 1.07 (P < .001). The mean metoprolol MR was significantly increased, from 0.17 to 5.69 (P < .05). The AUC of the metoprolol-induced decrease in exercise heart rate versus time curve was increased, with 46% (P < .01) after multiple-dose paroxetine intake, reaching significance from 6 hours after metoprolol intake, illustrating a more sustained beta-blockade. Similar results were obtained for the effect on exercise systolic blood pressure. Multiple-dose metoprolol administration combined with paroxetine can lead to an accumulation of the beta-blocking (S)-enantiomer of metoprolol, possibly resulting in unacceptable bradycardia, loss of cardioselectivity, or both. |
Does pRMT5 enhance generation of induced pluripotent stem cells from dairy goat embryonic fibroblasts via down-regulation of p53? | Protein arginine methyltransferase 5 (PRMT5), is thought to play a role in epigenetic reprogramming of mouse germ cells. However, up to now there has been little information concerning its expression profile and effects on generation of induced pluripotent stem cells (iPSCs) from somatic cells, in livestock. Here, we have explored PRMT5 expression profiles in dairy goats and its consequences to derivation of iPSCs from dairy goat embryonic fibroblasts (GEFs). We investigated effects of PRMT5 on iPS-like cells production in vitro. alkaline phosphatase (AP) staining, QRT-PCR and western blotting analysis of expression of related markers were used to evaluate efficiency of generation of iPSCs derived from GEFs. These showed PRMT5 to be a conservative gene widely expressed in various tissues and different-aged testes. PRMT5 overexpression in combination with OCT3/4, SOX2, KLF4 and C-MYC (POSKM) significantly increased number of AP positive iPS-like colony-derived GEFs compared to OSKM alone, in our dairy goats. Moreover, our results demonstrated that PRMT5 overexpression stimulated GEF proliferation and down-regulated p53, p21 (a target gene of p53) and the apoptotic marker caspase 3, to enhance somatic cell reprogramming. | Although chest radiography is quick and inexpensive, previous research suggests that it is often misleading in emergency department (ED) patients with decompensated heart failure, resulting in misdiagnosis and inappropriate treatment. This study determines the rate of negative chest radiography results in patients found to have disease and the potential contribution of negative findings to a diagnosis discordant with heart failure by an emergency physician. We used data from the Acute Decompensated Heart Failure National Registry (ADHERE), a registry of patients with a primary hospital discharge diagnosis of heart failure. We compared initial ED admitting diagnosis to the criterion standard of a hospital discharge diagnosis of heart failure and related these to radiographic findings of heart failure (interstitial edema, pulmonary edema, or vascular congestion, as determined by a staff radiologist) for patients first treated in the ED. The proportion of patients with a non-heart failure ED diagnosis and the diagnostic sensitivity of radiographic findings of heart failure are calculated. There were 85,376 patients with chest radiograph results and an ED admitting diagnosis. Overall, there were 15,937 patients with no signs of congestion on ED chest radiography, giving a negative rate of 18.7% (95% confidence interval [CI] 18.4% to 18.9%). The proportion of patients with an ED non-heart failure admitting diagnosis was higher in patients with a negative chest radiograph result (23.3%; 95% CI 22.6% to 23.9%) than in patients with a positive chest radiograph result (13.0%; 95% CI 12.7% to 13.2%). |
Does pancreatic intubation facilitated by methylene blue injection decrease the risk for postpapillectomy acute pancreatitis? | Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis. Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy. ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%). | Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that epsilon4 carriers may benefit from regular physical activity. We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE epsilon3 and APOE epsilon4 transgenic mice at 10-12 months of age. Sedentary epsilon4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in epsilon4 mice resulted in improvements on the RAWM to the level of epsilon3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in epsilon3 and epsilon4 mice, and after exercise BDNF was similarly increased in both epsilon3 and epsilon4 mice. In sedentary epsilon4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in epsilon4 mice to the level of epsilon3 mice, and in epsilon4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function. |
Do a new model for the standardization of experimental burn wounds? | Burns are common and recurrent events treated by physicians on a daily basis at most emergency rooms around the world. There is a constant need to understand the physiopathology of burns, so as to minimize their devastating results. The objective of the present report is to describe a burn apparatus in association with an innovative method of animal fixation, as to produce burns of varying sizes and depths. Rats were subjected to burns of 60 °C, 70 °C, and 80 °C for 10 s and after 3 days half of the rats in each group were killed and the resulting lesions were analyzed using histological techniques. In the other half of the rats the wound was measured weakly until complete re-epithelialization. All burns were easily visible and the histological feature for the 60 °C burn was a superficial second-degree burn (28% of the dermis), for 70 °C we observed a deep second-degree burn (72% of the dermis), and in the 80 °C group, a third degree-burn was present (100% of the dermis). | Characterizing young women's willingness to enter motherhood is critical to understanding the high rates of unintended pregnancy among women under 20 years. Our objectives were to discuss a measure called Positive Orientation towards Early Motherhood (POEM), and investigate its association with self-reported unintended pregnancy experience. We used data from 332 African-American women 13-19 years old recruited at public family planning and prenatal clinics in New Orleans. Using a series of ANOVAs and multinomial logistic regression, we assessed differences in POEM between four different outcome groups: women who were never pregnant and those who had only intended pregnancies, only unintended pregnancies and both unintended and intended pregnancies. The data suggested that young women perceive pregnancy as an opportunity to assert responsibility, become closer with their families and achieve greater intimacy with their boyfriends. Multiple regression analysis indicated that this positive orientation toward early motherhood independently raised the likelihood that young women experienced unintended pregnancies. In particular, the perception that a pregnancy makes a young woman feel more responsible was associated with an increased likelihood that a young woman had only unintended pregnancies compared to no pregnancies at all. Interestingly, this perception did not differentiate young women who had only intended pregnancies from those who were never pregnant. |
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