text
stringlengths 1.03k
99.1k
|
|---|
['The objective of the study was to assess the role of uterine activity on fetal outcome.', "Intrauterine pressure (IUP) recordings from consecutive term singleton, vaginal deliveries collected between June 1, 1993, and July 1, 2004, were analyzed. One thousand four hundred thirty-three recordings were included. IUP data were obtained using HP 8040A and HP M1350 cardiotocographs. For each recording the uterine contraction curve was analyzed, and the following contraction parameters were determined: relaxation time; contraction duration, frequency, amplitude, and surface; Montevideo units; and active planimeter units and contraction frequency. IUP recordings and contraction parameters from deliveries ending with an umbilical artery pH of 7.11 or less were compared with those ending with an umbilical artery pH of 7.12 or greater. Statistical analyses were performed using Student's t test and logistic regression.", 'An umbilical artery pH 7.11 or less at birth is associated with significant more uterine activity during the first and second stage of labor.'] |
['Recently described, aggressive B-cell lymphomas with genetic abnormalities involving MYC and BCL2 have been shown to have a poor prognosis when treated with regimens for diffuse large B-cell lymphomas. Similar data on cases with concurrent MYC and BCL6 translocation are still scant. Moreover, little is known regarding the morphologic and immunophenotypic characteristics of these cases, which further complicates their identification. This study describes six cases of aggressive B-cell lymphoma with translocations involving MYC and BCL6.', 'Six cases of large B-cell lymphoma with translocation involving MYC and BCL6 confirmed by fluorescence in situ were identified. The morphologic, immunophenotypic, and clinical features of the cases were examined.', 'All the patients were older women, and in 50% of cases, the presentation was extranodal. In two cases, the liver was involved at presentation. A starry-sky pattern was a constant feature of the cases in which the morphology could be reliably assessed. Five of six cases had an immunophenotype corresponding to the germinal center B cells, and only one was positive for BCL2, an immunophenotype reminiscent of that of Burkitt lymphoma.'] |
["In hemodialysis (HD) patients, the plasma brain natriuretic peptide (BNP) level is associated with left ventricular dysfunction and patients' survival. Malnutrition is common in HD patients, it is associated with inflammation and contributes to the high incidence of cardiovascular (CV) disease in this setting (malnutrition-inflammation-atherosclerosis syndrome). In a cross-sectional study, we assessed the relationship between predialysis plasma BNP level and nutritional markers in chronic HD patients.", "Of 210 patients receiving HD treatment in our unit, 51 patients who were treated with three times weekly long-hour HD (5-8 h/session) for at least 6 months (mean age 65.8 +/- 15.0 years; F/M ratio 23/28; vintage 71.3 +/- 71.9 months; BMI 24.9 +/- 5.9; session time 6.9 +/- 1.3 h; percentage of diabetic patients 31%) were studied before a mid-week HD session for nutritional markers (plasma albumin 35.3 +/- 3.7 g/l; prealbumin 0.36 +/- 0.09 g/l; CRP 15.3 +/- 14.7 mg/l; nPNA 1.29 +/- 0.29 g/kg/day) and plasma BNP (246.9 +/- 252.2 ng/l, normal <100 ng/l, Bayer(R) kit). The interdialytic weight gain was 2.1 +/- 1.0 kg. In the last 3 months prior to the commencement of the study, the patients' dry weight varied by +0.17 +/- 1.9 kg.", 'Predialysis plasma BNP levels did not differ according to gender and the presence of diabetes. It was not correlated with age and vintage but was found to be negatively associated with the session time (r = -0.34, p = 0.018). Several nutritional markers were negatively correlated with BNP levels: prealbumin (r = -0.46, p = 0.001), BMI (r = -0.33, p = 0.018), nPNA (r = -0.46, p = 0.002). The plasma albumin relationship with the BNP level was close to significance (p = -0.26, p = 0.070). The 3-month dry weight variation was also negatively correlated with BNP levels (r = -0.34, p = 0.018). With multiple stepwise regression analysis, prealbumin and session time remained significant (respectively p = 0.004 and 0.01). BNP levels were higher in a subgroup of malnourished patients (n = 12) (400 +/- 405 vs. 202 +/- 166 ng/l, p = 0.03) than in patients who did not meet the malnutrition criteria (34 patients). They were not correlated with CRP levels, interdialytic weight gain, or predialysis MAP.'] |
['Men are more susceptible to gastric cancer (GC) than women. However, the genetic factors associated with the sex difference are not well understood. Chemokines have been shown to modulate tumor behavior, and the sex-specific effect of the chemokine polymorphisms on the host susceptibility to several diseases has been reported. We aimed to determine the role of chemokine polymorphisms on host susceptibility to GC, with special interest on their sex-specific effect.', 'A hospital-based case-control study, including 177 patients with GC and 217 age-matched unaffected healthy controls, was performed in three major tertiary care hospitals. Genotyping for regulated upon activation, normal T-cell expressed and secreted (RANTES) -403 A/G and -28 C/G, CC chemokine receptor 5 (CCR5) deletion, and CCR2-V64I was performed using peripheral blood DNA.', 'The RANTES -403 GA and AA genotypes were independently associated with a 2.3-fold reduced risk of developing GC (OR=0.44, 95% CI 0.22-0.90, P=0.025) compared with GG genotype in women, but not in men. The RANTES -28C/G and CCR2-V64I polymorphisms were not associated with different risk of developing GC. The tumor stage, histological features, and survival rate were not different when stratified by RANTES -403 and -28 and CCR2-V64I genotypes.'] |
['The equilibrium between endothelial apoptosis and endothelial renewal is altered in acute coronary syndromes and may be related to differences in the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers).', 'We evaluated the effect of treatment on endothelial function in post-myocardial infarction (MI) patients treated with perindopril (group 2, n\u2009=\u200916) or valsartan (group 3, n\u2009=\u200917) at baseline and after 7, 15, and 30 days and in normal controls (group 1, n\u2009=\u200920). Endothelial apoptosis was determined by cultivating serum samples in vitro with human umbilical vein endothelial cells (HUVECs), while endothelial renewal was assessed by mobilization of CD34+ bone marrow cells.', 'At baseline, post-MI patients had significantly elevated rates of apoptosis (16.6\u2009±\u20095.0% and 16.5\u2009±\u20098.4% in groups 2 and 3, respectively [both p\u2009=\u20090.01] vs 1.6\u2009±\u20090.7% in group 1), which declined in group 2 (10.5\u2009±\u20094.4% at 30 days, p\u2009=\u20090.04), but not in group 3. Similar results and trends were found for the Bax/Bcl-2 ratio. CD34+ mobilization was significantly increased in group 2 (3.0\u2009±\u20091.0 at baseline to 6.2\u2009±\u20091.6 at 15 days, p\u2009=\u20090.03), whereas in group 3 CD34+ mobilization did not change significantly. The findings in group 2 were accompanied by an increase in vascular endothelial growth factor at 15 days, and a reduction in tumor necrosis factor-α and its soluble receptors, versus no change in group 3. Similar findings were observed for angiotensin II and bradykinin.'] |
['The aim of the study was to assess if QT dispersion and RR interval on the standard 12-lead electrocardiogram (ECG) predict cardiac death and late arrhythmic events in postinfarction patients with low left ventricular ejection fraction (LVEF). QT dispersion on a standard electrocardiogram (ECG) is a measure of repolarization inhomogeneity, but its prognostic meaning in myocardial infarction (MI) survivors is unclear, especially in patients with left ventricular dysfunction. RR interval has been shown to predict mortality in post-MI patients, but its prognostic power has not been compared with other noninvasive risk factors.', 'Retrospective cohort study. Ninety patients were identified, from a series of 547 consecutive postinfarction patients admitted to our institution for phase II cardiac rehabilitation, as having a LVEF of <0.40 at two-dimensional echocardiography (mean LVEF 0.35+/-0.04; range 0.20-0.39). QT dispersion and RR interval were analyzed on the admission 12-lead electrocardiogram, 20+/-10 (range 8-45) days after MI, using specially designed software. Additional risk markers were collected from clinical variables, signal-averaged ECG and Holter recording.', 'During 24+/-18 (range 1-63) months of follow-up, 10 of 90 patients (11%) died, all from cardiac causes, and there were 18 late arrhythmic events, defined as sudden death or the occurrence of a sustained ventricular arrhythmia > or =5 days after the index MI. QT interval and dispersion were not significantly prolonged in patients who died compared to survivors and not significantly different between patients with and without arrhythmic events. Mean RR interval from standard ECG was significantly shorter in patients with both cardiac death (682+/-99 vs. 811+/-134 ms; P=0.004) and arrhythmic events (720+/-100 vs. 818+/-139 ms; P=0.006). A Cox proportional hazards model identified RR interval from standard ECG (P<0.001) and a history of more than one MI (P=0.002) as significant predictors of cardiac death independent of thrombolytic therapy, LVEF, filtered QRS complex duration at signal-averaged ECG, mean RR and its standard deviation at 24-h Holter monitoring.'] |
['More than 90% of house dust mite-allergic patients are sensitized to the major Dermatophagoides pteronyssinus allergen, Der p 2. The aim of this study was to develop and characterize an allergy vaccine based on carrier-bound Der p 2 peptides, which should allow reducing IgE- and T-cell-mediated side-effects during specific immunotherapy (SIT).', 'Five Der p 2 peptides (P1-P5) were synthesized and analyzed regarding IgE reactivity and allergenic activity. Lymphoproliferative and cytokine responses induced with Der p 2 and Der p 2 peptides were determined in peripheral blood mononuclear cells from mite-allergic patients. Der p 2-specific IgG antibodies induced with carrier-bound Der p 2 peptides in mice and rabbits were tested for their capacity to inhibit IgE binding and basophil activation in allergic patients.', "Of five overlapping peptides (P1-P5) covering the Der p 2 sequence, two peptides (P2 and P4) were identified, which showed no relevant IgE reactivity, allergenic activity, and induced lower Der p 2-specific T-cell activation than Der p 2. However, when coupled to a carrier, P2 and P4 induced Der p 2-specific IgG antibodies in animals, which inhibited allergic patients' IgE binding to the allergen and allergen-induced basophil activation similar as antibodies induced with Der p 2."] |
['Histopathologic evidence of fibrosis on surgical lung biopsy has been associated with reduced survival in patients with hypersensitivity pneumonitis (HP). Changes of pulmonary fibrosis detected on CT may also correlate with prognosis in patients with HP.', 'We identified 69 consecutive patients with HP diagnosed between January 1997 and December 2002 at Mayo Clinic, Rochester, MN. Patients were stratified into fibrotic and nonfibrotic groups based on the CT findings. Fibrosis was defined by the presence of irregular linear opacities, traction bronchiectasis, or honeycombing.', 'Of 69 patients, 26 were classified as fibrotic and 43 as nonfibrotic. Patients in the fibrotic group were older, had longer symptom duration, were more likely to have crackles on auscultation, more likely to be exposed to avian antigen, and had greater restrictive lung impairment (p<0.05 for all comparisons). There were 11 deaths in the fibrotic group and 1 death in the nonfibrotic group (p<0.0001). In the regression analysis, CT evidence of fibrosis, more severe pulmonary function abnormalities, and the presence of crackles on auscultation were predictive of reduced survival (p<0.05 for all). The presence as well as the extent of fibrosis on CT was associated with increased mortality. The age-adjusted hazard ratio for mortality in patients with fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p<0.0001).'] |
['Resistance to conventional antiestrogens is a major cause of treatment failure and, ultimately, death in breast cancer.', 'The objective of the study was to identify small-molecule estrogen receptor (ER)-α antagonists that work differently from tamoxifen and other selective estrogen receptor modulators.', 'Based on in silico screening of a pharmacophore database using a computed model of the BRCA1-ER-α complex (with ER-α liganded to 17β-estradiol), we identified a candidate group of small-molecule compounds predicted to bind to a BRCA1-binding interface separate from the ligand-binding pocket and the coactivator binding site of ER-α. Among 40 candidate compounds, six inhibited estradiol-stimulated ER-α activity by at least 50% in breast carcinoma cells, with IC50 values ranging between 3 and 50 μM. These ER-α inhibitory compounds were further studied by molecular and cell biological techniques.', 'The compounds strongly inhibited ER-α activity at concentrations that yielded little or no nonspecific toxicity, but they produced only a modest inhibition of progesterone receptor activity. Importantly, the compounds blocked proliferation and inhibited ER-α activity about equally well in antiestrogen-sensitive and antiestrogen-resistant breast cancer cells. Representative compounds disrupted the interaction of BRCA1 and ER-α in the cultured cells and blocked the interaction of ER-α with the estrogen response element. However, the compounds had no effect on the total cellular ER-α levels.'] |
['The structure and function of chromatin can be altered by modifications to histone. Histone acetylation in vivo is a dynamic reversible process governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC6 is a unique isoform among the HDACs, and a gene expression pattern study, with cDNA microarray in MCF-7 cells, showed the HDAC6 gene to be late responsive, estrogen induced, and up-regulated. This led us to hypothesize that there was a link between levels of HDAC6 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients.', 'In the present study, the level of HDAC6 mRNA expression was analyzed with quantitative real-time reverse transcription-PCR, in 135 female patients with invasive breast cancer. HDAC6 protein expression was also determined by immunohistochemistry. An association was sought between HDAC6 expression and various clinicopathologic factors.', 'HDAC6 mRNA was expressed at significantly higher levels in breast cancer patients with small tumors measuring less than 2 cm, with low histologic grade, and in estrogen receptor alpha- and progesterone receptor-positive tumors. By contrast, no relationship was found between HDAC6 mRNA expression and any of the other clinicopathologic factors, namely, age, menopausal status, and axillary lymph node involvement. Patients expressing high levels of HDAC6 mRNA and protein had a better prognosis than those expressing low levels, in terms of disease-free survival. However, multivariate analysis failed to show that HDAC6 mRNA and protein are an independent prognostic factors for disease-free survival and overall survival. Furthermore, the patients with high levels of HDAC6 mRNA tended to be more responsive to endocrine treatment than those with low levels. Specific HDAC6 staining was found in the nucleus of some normal epithelial cells and in the cytoplasm of the majority of cancer cells. Although postmenopausal patients showed higher HDAC6 protein expression, there were no relationship between protein expression and any other clinicopathologic factors.'] |
['Pre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis.', 'Case-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results.', 'Some of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling.'] |
['The link between reproductive life history and incidence of ovarian tumors is well known. Periods of reduced ovulations may confer protection against ovarian cancer. Using phenotypic data available for mouse, a possible association between the ovarian transcriptome, reproductive records and spontaneous ovarian tumor rates was investigated in four mouse inbred strains. NIA15k-DNA microarrays were employed to obtain expression profiles of BalbC, C57BL6, FVB and SWR adult ovaries.', 'Linear regression analysis with multiple-test control (adjusted p ≤ 0.05) resulted in ovarian tumor frequency (OTF) and number of litters (NL) as the top-correlated among five tested phenotypes. Moreover, nearly one-hundred genes were coincident between these two traits and were decomposed in 76 OTF(-) NL(+) and 20 OTF(+) NL(-) genes, where the plus/minus signs indicate the direction of correlation. Enriched functional categories were RNA-binding/mRNA-processing and protein folding in the OTF(-) NL(+) and the OTF(+) NL(-) subsets, respectively. In contrast, no associations were detected between OTF and litter size (LS), the latter a measure of ovulation events in a single estrous cycle.'] |
['Stress-related glucocorticoid and glutamate release have been implicated in hippocampal atrophy evident in patients with post-traumatic stress disorder (PTSD). Glutamatergic mechanisms activate nitric oxide synthase (NOS), while gamma-amino-butyric acid (GABA) may inhibit both glutamatergic and nitrergic transmission. Animal studies support a role for NOS in stress.', 'We have studied the role of NOS and glucocorticoids, as well as inhibitory and excitatory transmitters, in a putative animal model of PTSD that emphasizes repeated trauma.', 'Hippocampal NOS activity, N-methyl-D-aspartate (NMDA) receptor binding characteristics and GABA levels were studied in Sprague-Dawley rats 21 days after exposure to a stress-restress paradigm, using radiometric analysis, radioligand studies and high-performance liquid chromatography (HPLC) analysis with electrochemical detection, respectively. The NOS isoform involved, and the role of stress-mediated corticosterone release in NOS activation, was verified with the administration of selective iNOS and nNOS inhibitors, aminoguanidine (50 mg/kg/day i.p.) and 7-nitroindazole (12.5 mg/kg/day i.p.), and the steroid synthesis inhibitor, ketoconazole (24 mg/kg/day i.p.), administered for 21 days prior to and during the stress procedure.', 'Stress evoked a sustained increase in NOS activity, but reduced NMDA receptor density and total GABA levels. Aminoguanidine or ketoconazole, but not 7-nitroindazole or saline, blocked stress-induced NOS activation.'] |
['Leptin is involved in the regulation of bodyweight and metabolism in man and might also be involved in the pathophysiology of the insulin resistance syndrome, which is associated with the development of cardiovascular diseases. We tested whether leptin is a risk factor for acute myocardial infarction (AMI) in a nested case-referent study.', 'Sixty-two men with first-ever AMI were identified who, prior to AMI, had participated in population-based health surveys in Northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographical region. Blood pressure, body mass index (BMI) and the presence of smoking, diabetes and hypertension were recorded. Total cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B), plasminogen activator inhibitor (PAI-1), insulin, and leptin were analysed in stored samples. Their influences on first-ever AMI were analysed by conditional logistic regression analysis.', 'Men with first-ever AMI had higher BMI, plasma insulin and leptin, and diastolic blood pressure than the referents. Furthermore, they had lower plasma apo A-1 and were more often smokers. Smoking, high leptin, PAI-1 and cholesterol, and low apo A-1 levels were significant risk factors for first-ever AMI in univariate analysis. High leptin (OR 8.97; 95% CI: 1.73-46.5) and cholesterol (OR 5.18; 95% CI: 1.34-20.0) levels remained significant risk factors for AMI in a multivariate model. High apo A-1 was protective (OR = 0.13; 95% CI: 0.03-0.55). The combination of high leptin and low apo A-1 was associated with a particularly pronounced increased risk for AMI.'] |
['Voltage-dependent Na+ currents are important determinants of excitability. We hypothesized that gastric inflammation alters Na+ current properties in primary sensory neurons.', "The stomach was surgically exposed in rats to inject the retrograde tracer 1.1'-dioctadecyl-3,3,3,'3-tetramethylindocarbocyanine methanesulfonate and saline (control) or 20% acetic acid (ulcer group) into the gastric wall. Nodose or thoracic dorsal root ganglia (DRG) were harvested after 7 days to culture neurons and record Na+ currents using patch clamp techniques.", 'There were no lesions in the control and 3 +/- 1 ulcers in the ulcer group. Na+ currents recovered significantly more rapidly from inactivation in nodose and DRG neurons obtained from animals in the ulcer group compared with controls. This was partially a result of an increase in the relative contribution of the tetrodotoxin-resistant to the peak sodium current. In addition, the recovery kinetics of the tetrodotoxin-sensitive current were faster. In DRG neurons, gastric inflammation shifted the voltage-dependence of activation of the tetrodotoxin-resistant current to more hyperpolarized potentials.'] |
['To investigate the action of palmitate on insulin receptor (IR) signaling pathway in rat pancreatic islets. The following proteins were studied: IR substrate-1 and -2 (IRS1 and IRS2), phosphatidylinositol 3-kinase, extracellular signal-regulated protein kinase-1 and -2 (ERK1/2), and signal transducer and activator of transcription 3 (STAT3).', 'Immunoblotting and immunoprecipitation assays were used to evaluate the phosphorylation states of IRS1 and IRS2 (tyrosine [Tyr]), ERK1/2 (threonine 202 [Thr202]/Tyr204), and STAT3 (serine [Ser727]).', 'The exposure of rat pancreatic islets to 0.1-mmol/L palmitate for up to 30 minutes produced a significant increase of Tyr phosphorylation in IRS2 but not in IRS1. The association of phosphatidylinositol 3-kinase with IRS2 was also upregulated by palmitate. Exposure to 5.6-mmol/L glucose caused a gradual decrease in ERK1/2 (Thr202/Tyr204) and STAT3 (serine [Ser727]) phosphorylations after 30-minute incubation. The addition of palmitate (0.1 mmol/L), associated with 5.6-mmol/L glucose, abolished these latter effects of glucose after 15-minute incubation.'] |
['Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established.', 'To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development.', 'Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival.', 'A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan-Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups.'] |
['To determine whether an active intervention is beneficial for the survival of elderly patients with hepatocellular carcinoma (HCC).', 'The survival of 740 patients who received various treatments for HCC between 1983 and 2011 was compared among different age groups using Cox regression analysis. Therapeutic options were principally selected according to the clinical practice guidelines for HCC from the Japanese Society of Hepatology. The treatment most likely to achieve regional control capability was chosen, as far as possible, in the following order: resection, radiofrequency ablation, percutaneous ethanol injection, transcatheter arterial chemoembolization, transarterial oily chemoembolization, hepatic arterial infusion chemotherapy, systemic chemotherapy including molecular targeting, or best supportive care. Each treatment was used alone, or in combination, with a clinical goal of striking the best balance between functional hepatic reserve and the volume of the targeted area, irrespective of their age. The percent survival to life expectancy was calculated based on a Japanese national population survey.', 'The median ages of the subjects during each 5-year period from 1986 were 61, 64, 67, 68 and 71 years and increased significantly with time (P < 0.0001). The Child-Pugh score was comparable among younger (59 years of age or younger), middle-aged (60-79 years of age), and older (80 years of age or older) groups (P = 0.34), whereas the tumor-node-metastasis stage tended to be more advanced in the younger group (P = 0.060). Advanced disease was significantly more frequent in the younger group compared with the middle-aged group (P = 0.010), whereas there was no difference between the middle-aged and elderly groups (P = 0.75). The median survival times were 2593, 2011, 1643, 1278 and 1195 d for 49 years of age or younger, 50-59 years of age, 60-69 years of age, 70-79 years of age, or 80 years of age or older age groups, respectively, whereas the median percent survival to life expectancy were 13.9%, 21.9%, 24.7%, 25.7% and 37.6% for each group, respectively. The impact of age on actual survival time was significant (P = 0.020) with a hazard ratio of 1.021, suggesting that a 10-year-older patient has a 1.23-fold higher risk for death, and the overall survival was the worst in the oldest group. On the other hand, when the survival benefit was evaluated on the basis of percent survival to life expectancy, age was again found to be a significant explanatory factor (P = 0.022); however, the oldest group showed the best survival among the five different age groups. The youngest group revealed the worst outcomes in this analysis, and the hazard ratio of the oldest against the youngest was 0.35 for death. The survival trends did not differ substantially between the survival time and percent survival to life expectancy, when survival was compared overall or among various therapeutic interventions.'] |
['The goal of this study was to determine the impact of an oral hygiene education programme for caregivers on the oral health of institutionalised elderly and to examine the effect of disability and low muscle strength on programme outcomes.', 'The subjects of this study were geriatric patients (n = 80) from a nursing home. Katz Index for activities of daily living, handgrip strength and mucosal-plaque score (MPS) was evaluated at baseline and 1 year after intervention. The intervention consisted of an educational programme and specific guidelines for caregivers (to perform oral hygiene for dependent elderly and to supervise the independent elderly during oral hygiene practices). Differences on MPS were evaluated using a paired-sample t-test. A stratified analysis was carried out to identify differences in response to the programme according to the Katz Index and handgrip strength of elderly.', 'The MPS was significantly reduced (p = 0.001) at follow-up; however, a separate analysis showed that only the independent elderly (p = 0.002) and those with normal muscle strength (p = 0.006) showed a reduction in MPS during the follow-up examination.'] |
['Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor impairments. The aim of this study was to assess whether WMA were predictive of all levels of motor impairments in very preterm children.', 'Two hundred and twenty-seven very preterm infants (< 30 wks gestational age or birthweight < 1250 g) had brain magnetic resonance imaging at term-equivalent age to assess for WMA, which were categorized as nil, mild, or moderate to severe. At 5 years of age children were classified as having a moderate to severe motor impairment if they were below the 5th centile or mild to severe motor impairment if their score placed them no higher than the 15th centile on the Movement Assessment Battery for Children (MABC). WMA (nil vs mild and nil vs moderate-severe) were explored as predictors of motor impairment using logistic regression. Analyses were repeated adjusting for the effects of other perinatal variables and excluding children with CP.', 'Of the 193 very preterm children (97 males, 96 females) assessed with the MABC, 53 (27%) were classified as having a moderate to severe motor impairment and 96 (50%) a mild to severe motor impairment. WMA were predictive of motor impairment in very preterm children, with mild versus no WMA increasing the odds of moderate to severe motor impairment by over fivefold (odds ratio [OR] 5.6; 95% confidence interval [CI] 1.9-16.1; p=0.002) and mild to severe impairment by twofold (OR 2.2; 95% CI 1.1-4.2; p=0.02). Compared with no WMA, moderate to severe WMA increased the odds for moderate to severe impairment 19-fold (OR 19.4; 95% CI 5.6-66.7; p<0.001) and for mild to severe motor impairment ninefold (OR 9.4; 95% CI 3.2-28.1; p<0.001). Results remained similar after controlling for several potential confounders and after excluding 14 children who had CP at age 2 years.'] |
['Patients with severe cerebral ischemia may lose autoregulation to increase cerebral blood flow following neural activity. Although the steal phenomenon under conventional cerebral blood flow study has been known as a high-risk factor for stroke, the cerebral oxygen hemodynamics in ischemic patients during functional activation has not been thoroughly investigated. In this study, we present rare cases with intracortical steal phenomenon during motor tasks detected by multichannel functional near-infrared spectroscopy before and after surgery.', 'The relative concentration change of oxygenated, deoxygenated and total hemoglobin in and around the primary sensorimotor cortex during contralateral hand grasping was investigated in 11 patients with severe internal carotid artery stenosis.', 'In 3 patients, the concentration of total hemoglobin around the primary sensorimotor cortex significantly decreased in response to motor stimulation and returned to baseline soon after termination of the motor task. This phenomenon partially disappeared postoperatively in all patients who underwent surgery. The remaining 8 patients showed no signs of total hemoglobin decrease in and around the sensorimotor cortex. In 9 patients, lack of decrease in deoxygenated hemoglobin in the center of the primary motor cortex during the motor task was observed and 3 of them showed significant increase in deoxygenated hemoglobin.'] |
['Provoked vestibulodynia is a poorly understood disease that affects 8-15% of women in their lifetime. There is significant inflammation and nerve growth in vestibular biopsies from affected women treated by vestibulectomy compared with matched female population controls without vestibulodynia. The triggers leading to this neurogenic inflammation are unknown, but they are likely multifactorial.', 'Our objective was to determine whether vestibulodynia is more common in close and distantly related female relatives of women diagnosed with the disease and those specifically treated by vestibulectomy. Excess familial clustering would support a potential genetic predisposition for vestibulodynia and warrant further studies to isolate risk alleles.', 'Using population-based genealogy linked to University of Utah Hospital CPT coded data, we estimated the relative risk of vestibulectomy in female relatives of affected women. We also compared the average pairwise relatedness of cases to the expected relatedness of the population and identified high-disease-burden pedigrees.', 'A total of 183 potential vestibulectomy probands were identified using CPT codes. The relative risk of vestibulectomy was elevated in first-degree (20 [6.6-47], P < .00001), second-degree (4.5 [0.5-16], P\xa0= .07), and third-degree female relatives (3.4 [1.2-8.8], P\xa0= .03). Seventy of these 183 CPT-based probands had available clinical history to confirm a diagnosis of moderate to severe vestibulodynia. Notably, this smaller group of confirmed probands (n\xa0= 70) revealed a similar familiality in first-degree (54 [17.5-126], P < .00001), second-degree (19.7 [2.4-71], P\xa0= .005), and third-degree relatives (12\xa0[3.3-31], P\xa0= .0004), despite less statistical power for analysis. Overall, the average pairwise relatedness of affected women was significantly higher than expected (P < .001) and a number of high-disease-burden Utah families were identified.'] |
['Magnesium (Mg(2+)) is essential for cellular growth and the maintenance of normal cellular processes. However, little is known about how maternal hypomagnesemia during pregnancy affects fetal growth and development. This study investigated the effects of maternal hypomagnesemia on the late gestation placenta and fetus, and postnatal outcomes until weaning.', 'Female CD1 mice consumed a control (0.2%\xa0w/w\xa0Mg(2+)), moderately Mg(2+) deficient (MMD; 0.02%\xa0w/w\xa0Mg(2+)) or severely Mg(2+) deficient (SMD; 0.005%\xa0w/w\xa0Mg(2+)) diet for 4 weeks prior to mating and throughout pregnancy. Dams were killed at E18.5 for embryonic studies or allowed to litter naturally and the offspring studied up to postnatal day 21.', 'At E18.5, both Mg(2+) deficient diets decreased maternal plasma and bone Mg(2+) but only the SMD diet decreased fetal plasma Mg(2+). Maternal hypomagnesemia led to fetal loss and fetal growth restriction. Maternal Mg(2+) deficiency increased placental glycogen cell area and decreased spongiotrophoblast cell area while upregulating mRNA expression of the MagT1 Mg(2+) transporter in spongiotrophoblast cells. The SMD animals also displayed instances of gross placental abnormalities. After birth, pups in the SMD group had increased early postnatal mortality and failed to thrive. Pups in the MMD group underwent catch-up growth but remained shorter than controls at PN21 and were hypomagnesemic and hypoglycemic.'] |
['Maternal glucocorticoid (GC) treatment is widely used to prevent lung immaturity in preterm infants. There is growing evidence that GCs may be detrimental to the Central Nervous System (CNS). We investigated whether antenatal GC administration affects CNS function in a dose-dependent manner by measuring urine concentrations of a well-established brain damage marker, S100B.', 'We conducted a case-control-study in 70 preterm infants (1 GC vs 1 control) whose mothers received a complete GC-course (GC2, n=16), half-course (GC1, n=19), and controls (n=35). At four predetermined time-points, in the first 72 h from birth, we assessed S100B urine concentrations, using a commercially available immunoluminometric assay (Lia-mat Sangtec 100, AB Sangtec Medical, Bromma, Sweden). Data were correlated with primary neonatal outcomes (incidence of respiratory distress syndrome, length of ventilatory support and hospital stay, incidence of intraventricular hemorrhage, adverse 7th day neurological follow-up and neonatal death).', 'S100B in GC2 group at all monitoring time-points was significantly lower (P<0.01) than controls and GC1 group, while no differences (P>0.05) were evident between controls and GC1 group. No significant differences (P>0.05) were shown in primary outcomes between half or complete GC-course treated groups.'] |
['Transplant arteriosclerosis is characterized by intraluminal obstructive proliferation occurring in response to immune-mediated arterial wall injury. Cell therapy with vascular progenitor cells have been suggested to repair intimal lesions following endothelial injury. The aim of the current study was to assess the effects of autologous bone marrow cell direct transfer and of Fucan-mobilization bone marrow-derived progenitor cells on intimal thickening in vascular grafts.', 'Aortic allografts were performed in Brown Norway (BN) and Lewis (LEW) rats. Cell therapy was performed by injection of two doses of 10 million LEW bone marrow mononuclear cells to recipient LEW following aortic grafting. Fucan, a low molecular weight sulfated polysaccharide (LMWF) was used to mobilize bone marrow-derived progenitor cells. Five groups of 10 rats included: untreated isografts (BN to BN), untreated allografts, and three allografted groups, respectively, treated by fucan therapy, cell therapy, or cell and fucan therapy. Aorta were studied by morphometric analysis at 30 d.', 'In the absence of treatment, intimal thickening was greater in allograft than in isograft groups (299±50 versus 3.5±1.7 μm, P<0.001). Cell therapy alone, fucan therapy alone, and the combined treatment were shown to prevent intimal thickening in allografts (5.1±1.7, 6.1±2.3, 4.1±2.5, versus 299±50 μm respectively, P<0.001). In the three treated groups, the intimal lining was a single layer of endothelial cells expressing CD34 positive, endothelial nitric oxide synthase (eNOS) positive, and Ox3 specific-recipient monoclonal antibody positive.'] |
['Mitosis is regulated by MPF (maturation promoting factor), the active form of Cdc2/28-cyclin B complexes. Increasing levels of cyclin B abundance and the loss of inhibitory phosphates from Cdc2/28 drives cells into mitosis, whereas cyclin B destruction inactivates MPF and drives cells out of mitosis. Cells with defective spindles are arrested in mitosis by the spindle-assembly checkpoint, which prevents the destruction of mitotic cyclins and the inactivation of MPF. We have investigated the relationship between the spindle-assembly checkpoint, cyclin destruction, inhibitory phosphorylation of Cdc2/28, and exit from mitosis.', 'The previously characterized budding yeast mad mutants lack the spindle-assembly checkpoint. Spindle depolymerization does not arrest them in mitosis because they cannot stabilize cyclin B. In contrast, a newly isolated mutant in the budding yeast CDC55 gene, which encodes a protein phosphatase 2A (PP2A) regulatory subunit, shows a different checkpoint defect. In the presence of a defective spindle, these cells separate their sister chromatids and leave mitosis without inducing cyclin B destruction. Despite the persistence of B-type cyclins, cdc55 mutant cells inactivate MPF. Two experiments show that this inactivation is due to inhibitory phosphorylation on Cdc28: phosphotyrosine accumulates on Cdc28 in cdc55 delta cells whose spindles have been depolymerized, and a cdc28 mutant that lacks inhibitory phosphorylation sites on Cdc28 allows spindle defects to arrest cdc55 mutants in mitosis with active MPF and unseparated sister chromatids.'] |
['Patients with myocardial ischemia after noncardiac surgery have a three- to ninefold increased risk of adverse cardiac events. In this study we tested the hypothesis that altered preoperative heart rate variability (HRV) predicts postoperative prolonged myocardial ischemia (>10 min) in elderly surgical patients. Thirty-two patients, age 60 yr or older, admitted to hospital for surgical repair of a traumatic hip fracture with preoperative night and daytime Holter recordings were included. Holter monitoring was initiated at arrival at hospital and continued until the third postoperative morning. Conventional HRV measures along with analysis of short-term fractal scaling exponent (alpha(1)) of RR intervals were assessed for night (from 2 AM to 5 AM) and day (7 AM to 12 AM) periods in each patient. Preoperative alpha(1) was significantly lower (i.e., increased randomness in HRV) during the nighttime compared with daytime (mean +/- SEM; 0.92 +/- 0.08 versus 1.03 +/- 0.06; P = 0.002) in patients with postoperative myocardial ischemia. Patients without ischemia had no such difference. In stepwise multivariate logistic regression analysis, increased preoperative night-day difference of alpha(1) was the only independent predictor of postoperative prolonged ischemia. The odds ratio for an increase of 0.16 U in night-day difference of alpha(1) (corresponding to interquartile range) was 7.7 (95% confidence interval, 1.9-51.4; P = 0.0018). Breakdown of fractal-like heart rate dynamics is predictive for postoperative prolonged myocardial ischemia in elderly patients having emergency surgery for traumatic hip fracture.'] |
["To report a qualitative study which explores registered nurses' views on the issue of time in the workplace.", "There is a worldwide shortage of healthcare workers, subsequently time as a healthcare resource is both finite and scarce. As a result, increased attention is being paid to the restructuring of nursing work. However, the experience of time passing is a subjective one and there exists little research which, over a prolonged period of time, describes nurses' experiences of working in time-pressurized environments.", 'A narrative inquiry.', 'Five registered nurses were individually interviewed a total of three times over a period of 12\xa0months, amounting to a total of 15 interviews and 30\xa0hours of data. Data were collected and analysed following a narrative enquiry approach during the period 2008-2010.', "Participants describe how attempts to work more effectively sometimes resulted in unintended negative consequences for patient care and how time pressure encourages collegiality amongst nurses. Furthermore, the registered nurses' account of how they opportunistically create time for communication with patients compels us to re-evaluate the nature of communication during procedural nursing care."] |
['A whole-genome association study of 4631 progeny-tested Nordic Red dairy cattle bulls using imputed next-generation sequencing data revealed a major quantitative trait locus (QTL) that affects birth index (BI) on Bos taurus autosome (BTA) 23. We analyzed this QTL to identify which of the component traits of BI are affected and understand its molecular basis.', "A genome-wide scan of BI in Nordic Red dairy cattle detected major QTL on BTA6, 14 and 23. The strongest associated single nucleotide polymorphism (SNP) on BTA23 was located at 13,313,896 bp with [Formula: see text]. Analyses of component traits showed that the QTL had a large effect on stillbirth. Based on the 10 most strongly associated SNPs with stillbirth, we constructed a haplotype. Among this haplotype's alleles, HAPQTL had a large negative effect on stillbirth. No animals were found to be homozygous for HAPQTL. Analysis of stillbirth records that were categorized by carrier status for HAPQTL of the sire and maternal grandsire suggested that this haplotype had a recessive mode of inheritance. Illumina BovineHD BeadChip genotypes and genotype intensity data indicated a chromosomal deletion between 12.28 and 12.81 Mbp on BTA23. An independent set of Illumina Bovine50k BeadChip genotypes identified a recessive lethal haplotype that spanned the deleted region."] |
['Recent researches have shown that myeloperoxidase (MPO) is a potential inflammatory risk factor for coronary heart disease (CHD). In the present study, the possible associations of MPO with acute coronary syndrome (ACS), low density lipoprotein cholesterol (LDL-C) and other risk factors in CHD patients were investigated.', 'Five hundred thirty-six CHD patients [363 ACS and 173 stable angina pectoris (SAP)] and 181 non-CHD patients confirmed by coronary angiography were enrolled in this study. The association study was performed by logistic regression analysis.', 'ACS patients had significantly higher MPO activities than SAP and non-CHD patients (p < 0.001). The area under the receiver operating characteristic (ROC) curve of MPO for diagnosing ACS was 0.84 (95% CI: 0.80-0.88, p < 0.001). The optimal cut-off value (sensitivity; specificity) of MPO was 164.77 ng/mL (79.1% and 82.1%). LDL-C (III versus I tertile, OR: 3.24, 95% CI: 1.67-6.29, p = 0.001) and ACS (yes versus no, OR 2.74, 95% CI: 1.71-4.39, p < 0.001) were significantly associated with elevated serum MPO activities, which had the highest odds ratio in quantitative and qualitative variables, respectively. There were significant increase trends in the prevalence of ACS and high LDL-C levels from I to III MPO tertile, which were 46.4% and 8.9% for I, 68.0% and 31.5% for II, 88.8% and 59.8% for III tertile, respectively (p < 0.001).'] |
['Non-alcoholic fatty liver disease (NAFLD) appears to be a new risk factor for the development of coronary artery disease (CAD). Members of a class of non-coding RNAs, termed microRNAs (miRNAs), have been identified as post-transcriptional regulators of cholesterol homoeostasis and can contribute to the development of NAFLD. The aims of this study were to (i) to assess the relationship between NAFLD and sudden cardiac death (SCD) from severe CAD in forensic autopsies and (ii) to quantify several hepatic miRNAs previously associated with lipid metabolism and NAFLD to correlate their expression with the presence of NAFLD, CAD, obesity parameters and postmortem lipid profile.', 'A total of 133 cases of autopsies with SCD and established CAD (patient group, CAD-SCD) and 106 cases of non-CAD sudden death (control group, non-CAD-SD) were included. miRNAs were quantified in frozen liver tissues.', 'Males predominated in both groups. Patients more frequently exhibited NAFLD and necroinflammatory steatohepatitis (NASH) than controls (62% vs 26%, P = 0.001 and 42% vs 26%, P = 0.001 respectively). In both groups, the presence of NAFLD correlated with body mass index and abdominal circumference (P < 0.05). An increase in miR-34a-5p and a decrease in miR-122-5p and -29c-3p in patients with NASH vs controls without NAFLD were observed (P < 0.05). Finally, significant correlations between miR-122-5p and unfavourable lipid profile and also hs-CRP and miR-34a-5p were noted.'] |
['To analyze the total grip force and load distribution of the hand with midcarpal fusion (MCF) and total wrist fusion (TWF).', 'Twelve patients with unilateral TWF and 12 patients with unilateral MCF were assessed at an average 64 months (range, 19-100 months) postoperatively. The total grip force and load distribution of both hands were measured by the Manugraphy system using 3 cylinder sizes. The load applied to 7 anatomical areas of the hand during cylinder grip was analyzed, comparing the operated and the nonsurgical hands.', 'For the 100 mm and 150 mm cylinders, a significantly lower total grip force was found in hands operated with either TWF or MCF. For the 200 mm cylinder, there was a significant difference between nonsurgical hands and those with MCF but not between nonsurgical hands and those with TWF. For the 100 mm cylinder, the difference between nonsurgical and operated hands was greater in hands with TWF than those with MCF. For the load distribution of the hand, no differences between the operated and the nonsurgical hand were found for either MCF or TWF.'] |
['To evaluate the impact of different prognostic factors that has been suggested to be useful in predicting the survival of patients with multiple myeloma (MM).', 'A longitudinal prospective study was conducted on 24 adult Mexican patients diagnosed with primary MM. The levels of expression of CD38, CD138 and cyclin D1 were analyzed in plasma cells (PCs) from patients and mononuclear cells from healthy donors. Serum levels of lactate dehydrogenase, creatinine, calcium, beta2 microglobulin and interleukin-6 (IL-6) as well as hemoglobin and platelet count were taken into consideration. RESULTS; CD138 and cyclin D1 levels in absolute numbers were significantly overexpressed in malignant PCs. A positive correlation was noted between cyclin D1 and CD38 expression levels in malignant PCs. IL-6 and serum calcium were also positively correlated in MM patients. Cyclin D1 overexpression was not associated with better overall survival (OS). Normal calcium levels were associated with better overall survival (OS). Serum calcium was the only variable correlating with better OS in Cox regression analysis.'] |
['According to the ISO, the radiopacity of luting cements should be equal to or greater than that of aluminum. The aim of this in vitro study was to determine the radiopacity of 13 commercially available dental luting cements and compare them with human enamel and dentin.', "Five classes of luting cements were evaluated: zinc phosphate (Cegal N and Harvard Zinc Phosphate), zinc polycarboxylate (Harvard Polycarboxylate and Hoffmann's Carboxylate), glass ionomers (Ketac Cem Easymix, Ketac Cem Radiopaque, and Fuji I), resin-modified glass ionomer (Rely X Luting), and resin cements (Multilink Automix, Variolink II, Speed CEM, Rely X Unicem Automix, and three shades of Variolink Veneer). Tooth slices served as controls. Five specimens of each material measuring 8 mm in diameter and 1 mm thick were prepared and radiographed alongside tooth slices and an aluminum stepwedge using a Trophy RVG sensor. The radiopacity values were expressed in mm Al and analyzed by the ANOVA and Tukey tests (P < .05).", 'All the cements examined except Variolink Veneer had significantly higher radiopacities than that of dentin. Rely X Unicem Automix, glass ionomer, and resin-modified glass-ionomer cements demonstrated radiopacities that were not significantly different with respect to enamel. Zinc phosphate, zinc polycarboxylate, and three of the resin cements presented radiopacity values that were significantly greater than that of enamel.'] |
['Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.', 'Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73\u2009998), eGFR using cystatin C (eGFRcys: n=22\u2009937), and urinary albumin to creatinine ratio (n=31\u2009580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease.', 'Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02).'] |
['Intraperitoneal administration of paclitaxel (PTX) can elicit a marked clinical response in peritoneal metastases of gastric cancer.', 'In this study, we retrospectively analyzed the clinical outcome of 17 patients who underwent R0 resection with D2 dissection for advanced gastric cancer with macroscopic serosal exposure and received intraperitoneal PTX as adjuvant therapy.', 'A pathological study revealed that the depth of invasion of the primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14 cases, all of which were positive for carcinoembryonic antigen mRNA. In these patients, PTX was intraperitoneally administered at 20-60 mg/m(2) with oral S-1 for 3-36 months after surgery. In a median follow-up period of 66 months, recurrence occurred in the liver and peritoneum in 2 (11.7%) and 1 (5.9%) patients, respectively, and no nodal recurrence was observed. Five-year overall survival and disease-free survival were 88.2 and 82.3%, respectively.'] |
['The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis.', 'Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR.', 'The present study showed that PG suppressed the migration, invasion, and EMT of breast cancer cells MDA-MB-231 in a dose-dependent manner. The results also revealed that impairment of the metastatic potential caused by PG was associated with the activation of AMPK and downregulation of both DNMT1 and Sp1. Moreover, the data from the in vivo model also supported the in vitro findings, which showed that inhibition of metastasis by PG was associated with the downregulation of DNMT1 and Sp1 as well as increased level of phosphorylated AMPK.'] |
['Alcohol-related driving accidents and fatalities occur most frequently at nighttime and at dawn, that is, a mesopic lighting condition in which visual processing depends on both rod and cone photoreceptors. The temporal functions of the rod and cone pathways are critical for driving in this lighting condition. However, how alcohol influences the temporal functions in the rod and cone pathways at mesopic light levels is inconclusive. To address this, this study investigated whether an acute intoxicating dose of alcohol impairs rod- and/or cone-mediated critical fusion frequency (CFF; the lowest frequency of which an intermittent or flickering light stimulus is perceived as steady).', "In Experiment I, we measured the CFFs for 3 types of visual stimuli (rod stimulus alone, cone stimulus alone, and the mixture of both stimuli types), under 3 illuminant light levels (dim illuminance: 2 Td; low illuminance: 20 Td; and medium illuminance: 80 Td) in moderate-heavy social drinkers before and after they consumed an intoxicating dose of alcohol (0.8 g/kg) compared with a placebo beverage. In Experiment II, we examined whether the illuminance level (dark vs. light) of the visual area surrounding the test stimuli alters alcohol's effect on the temporal processing of rods and cones.", 'The results showed that compared with placebo, alcohol significantly reduced CFFs of all stimulus types at all illuminance levels. Furthermore, alcohol intoxication produced a larger impairment on rod-pathway-mediated CFFs under light versus dark surround.'] |
['Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP.', 'arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed.', 'We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes.'] |
['Increased carotid artery intima-media thickness (IMT) is a noninvasive marker of systemic arterial disease, associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. In the elderly, clinically elevated IMT is related to diminished attention-executive function. In this context, previous work involving paper-and-pencil measures of cognition has demonstrated that a threshold of pathology (i.e., IMT>or=0.9 mm) is needed before IMT consistently relates to poor neuropsychological test performance. Given the critical role of arterial health in the development of cognitive dysfunction, the goal of this study was to investigate early markers of brain vulnerability by examining subclinical levels of IMT in relation to a sensitive marker of neuronal integrity, cerebral N-acetyl-aspartate/creatine (NAA/Cr) ratio, in midlife.', 'A total of 40 participants aged 50+/-6 years, underwent neuropsychological assessment, proton magnetic resonance spectroscopy ((1)H MRS) examination of occipitoparietal grey matter and B-mode ultrasound of the common carotid artery. IMT was defined as the distance between the luminal-endothelial interface and the junction between the media and the adventitia. The relation between IMT and cerebral metabolite ratios was modeled using a single multivariate multiple regression analysis adjusted for age and current systolic blood pressure.', 'Increased IMT was associated with significantly lower NAA/Cr ratios (IMT beta=-0.62, p=0.001), independent of age and systolic blood pressure (F(3,36)=4.928, p=0.006).'] |
['To identify risk factors for reoperation following surgery for spontaneous pneumothorax.', 'This is a retrospective clinical study conducted on 240 consecutive patients operated on for spontaneous pneumothorax in Lund University Hospital between January 1996 and December 2003. Patient information was gained from medical charts and operation reports. Logistic regression analysis was used to evaluate risk factors. Median follow-up was 54 months.', 'Video-assisted thoracoscopic surgery (VATS) was used in 93% of the patients, where bullectomy with or without pleurodesis/pleurectomy was performed in most cases. Conversion to anterolateral thoracotomy was required in 6 cases (2.3%). Operative mortality (<30 days) was 0.8% (0% after VATS). Altogether 35 patients (13.7%) required a reoperation. Twenty patients were reoperated on within one month from surgery, most often due to prolonged air leakage (n=13, 5.1%) and bleeding (n=6, 2.3%). Fifteen patients (5.8%) were reoperated on because of recurrent pneumothorax, on average 17 months (range 1-39 months) after the primary operation. Significant independent risk factors for reoperation were; young age, operations performed for secondary pneumothorax due to emphysema and recurrent pneumothorax. The risk was also increased in patients where wedge resection was not performed. However, the type of pleurodesis or pleurectomy was not related to increased risk.'] |
['Sera of patients with IgA nephropathy (IgAN) contain circulating immune complexes (CIC) composed of galactose-deficient IgA1 complexed with antiglycan antibodies. The role of these CIC in the pathogenesis of IgAN is not known.', 'We studied how proliferation of cultured mesangial cells (MC) is affected by CIC prepared from sera of IgAN patients and healthy control subjects using size-exclusion chromatography. CIC-containing fractions were added to serum-starved MC in culture, and cell proliferation was measured using (3)H-thymidine incorporation. The results were confirmed by staining MC using an antibody against proliferating cell nuclear antigen.', 'The incubation of starved MC with serum fractions with M(r) 800 to 900 kD, rich with galactose-deficient IgA1, stimulated proliferation, while fractions with smaller complexes were inhibitory. Furthermore, CIC-containing larger molecular mass fractions isolated from serum of an IgAN patient collected during an episode of macroscopic hematuria stimulated MC proliferation more than CIC obtained during a subsequent quiescent phase. To examine the role of IgA, we removed IgA1 from serum before fractionation. The resultant IgA1-depleted fractions were devoid of stimulatory IgA-CIC. Sera of IgAN patients were also fractionated after addition of desialylated galactose-deficient polymeric IgA1 to form additional immune complexes. Supplementation with a small quantity of this IgA1 increased cellular proliferation in assays using serum fractions of M(r)>/=800 to 900 kD; uncomplexed IgA1 did not affect MC proliferation significantly. In contrast, supplementation with a larger quantity of this IgA1 inhibited cellular proliferation in assays using serum fractions of M(r) 700 to 800 kD.'] |
['Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low-flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low-flow ischemia.', 'Isolated perfused rat hearts underwent 60 minutes of low-flow ischemia induced by reducing perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was induced by 2 x 5 minutes episodes of zero-flow ischemia. In yet other groups, preconditioned or non-preconditioned hearts were treated either with bradykinin (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L).', 'IPC reduced the number of ventricular premature beats, as well as the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. In addition, this protection was abolished by HOE 140 given during low-flow ischemia. Pharmacological preconditioning using short bradykinin perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin administered during low-flow ischemia and reperfusion reduced the number of ventricular premature beats and the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia.'] |
['Bile acids (BAs) play a crucial role in dietary fat digestion and in the regulation of lipid, glucose, and energy metabolism. Thyroid-stimulating hormone (TSH) is a hormone produced by the anterior pituitary gland that directly regulates several metabolic pathways. However, the impact of TSH on BA homeostasis remains largely unknown.', 'We analyzed serum BA and TSH levels in healthy volunteers under strict control of caloric intake. Thyroidectomized rats were administered thyroxine and injected with different doses of TSH. Tshr(-/-) mice were supplemented with thyroxine, and C57BL/6 mice were injected with Tshr-siRNA via the tail vein. The serum BA levels, BA pool size, and fecal BA excretion rate were measured. The regulation of SREBP-2, HNF-4α, and CYP7A1 by TSH were analyzed using luciferase reporter, RNAi, EMSA, and CHIP assays.', 'A negative correlation was observed between the serum levels of TSH and the serum BA levels in healthy volunteers. TSH administration led to a decrease in BA content and CYP7A1 activity in thyroidectomized rats supplemented with thyroxine. When Tshr was silenced in mice, the BA pool size, fecal BA excretion rate, and serum BA levels all increased. Additionally, we found that HNF-4α acts as a critical molecule through which TSH represses CYP7A1 activity. We further confirmed that the accumulation of mature SREBP-2 protein could impair the capacity of nuclear HNF-4α to bind to the CYP7A1 promoter, a mechanism that appears to mediate the effects of TSH.'] |
['Non-Fc-binding anti-CD3-specific antibodies represent a promising therapy for preserving C-peptide production in subjects with recent-onset type 1 diabetes. However, the mechanisms by which anti-CD3 exerts its beneficial effect are still poorly understood, and it is questionable whether this therapeutic approach will prove durable with regard to its ability to impart metabolic preservation without additional actions designed to maintain immunological tolerance. We used the NOD mouse model to test whether rapamycin, a compound well-known for its immunomodulatory activity in mice and humans, could increase the therapeutic effectiveness of anti-CD3 treatment in type 1 diabetes.', 'Rapamycin was administered to diabetic NOD mice simultaneously with anti-CD3 or to NOD mice cured by anti-CD3 therapy. The ability of this combined therapy to revert type 1 diabetes and maintain a state of long-term tolerance was monitored and compared with that of anti-CD3 therapy alone.', 'Rapamycin inhibited the ability of anti-CD3 to revert disease without affecting the frequency/phenotype of T-cells. Rapamycin also reinstated diabetes in mice whose disease was previously reversed by anti-CD3. Withdrawal of rapamycin in these latter animals promptly restored a normoglycemic state.'] |
['To assess the association between demographic and lifestyle parameters and perceived severity of the climacteric syndrome in perimenopausal women.', 'A cross-sectional study of 151 healthy women aged 45-55 years who attended the University Medical Center affiliated menopause clinics. The analysis was based on self completion of the Greene climacteric score, consisting of psychological, somatic/physical, sexual and vasomotor subscores. The Greene total score and subscores were the main outcomes of the study.', 'Of all demographic, anthropometric and lifestyle parameters recorded, the correlates with reduced total Greene score were high-order maternity and regular physical exercise. Mothers of 3 or more children reported significantly lower total Greene score (18±12.8 vs. 22.1±8.1) (p=0.01) as well as lower psychological subscore (8.7±6.8 vs. 11.5±5.4) (p=0.01). Regular physical activity was also associated with significantly lower total Greene score (17.0±11.0 vs. 22.6±11.3) (p=0.01) and specifically lower psychological subscore (9.5±6.6 vs. 12.8±7.7) (p=0.03) and sexual subscore (1.1±0.99 vs. 1.61±1.05) (p=0.03). Linear regression models showed that regular exercise was the lifestyle parameter most significantly correlated with a lower total Greene score (p=0.006) independent of menopausal status. Of particular note, regular exercise was significantly correlated with lower psychological (p=0.006) and physical subscores (p=0.06). Moreover, the higher the frequency of exercise (both aerobic and non aerobic), the lower the severity of the climacteric symptoms reported, yet the vasomotor and sexual subscores remained unchanged.'] |
['Test-retest reliability of an asthma paper diary versus an electronic diary (e-diary) with an integrated peak flow meter was investigated. The equivalence of the two modes was also evaluated.', 'Prospective, randomized crossover study design in adolescents (12-17 years) and adults (≥18 years). Key inclusion criteria were persistent asthma, Asthma Control Test (ACT) scores ≥16, use of inhaled corticosteroid with or without long-acting beta-agonist for ≥12 weeks, nocturnal awakenings <2 times in the past week, and activity limitations <1 per week. Participants were randomized to either paper then e-diary or e-diary then paper, to be completed for 14 days each.', 'Forty-seven participants completed all study visits. Weekly percentage of symptom-free days (SFDs) and rescue-free days (RFDs) were calculated. Intraclass correlation coefficients (ICCs) of Week 1 mean SFD and RFD (test) and Week 2 mean SFD and RFD (retest), respectively, were estimated in three groups defined as stable: (i) minimal changes in asthma symptoms, as measured by the global patient reported symptom change question, (ii) less than 15% change (absolute value) in 1 second FEV(1) at adjacent study visits, and (iii) changes in ACT scores less than three points for each mode. SFD demonstrated acceptable ICC (≥0.70) using all three definitions of asthma stability for both modes.'] |
['Infection rates for breast surgery are 3 to 15 percent, higher than average for a clean surgical procedure. Preoperative and postoperative antibiotics have lowered infection rates in other surgical groups, yet there is no consensus on postoperative prophylactic antibiotic use in microsurgical breast reconstruction.', 'A retrospective review of consecutive patients who underwent autologous breast reconstruction between 2006 and 2009 was performed. Specific risk factors for autologous reconstruction were reviewed, including medical comorbidities, irradiation, and chemotherapy history. Data were collected on type and duration of prophylactic antibiotics. A prospective cohort of patients who received only 24 hours of postoperative antibiotics was identified. The incidence of surgical-site infections was measured using Centers for Disease Control and Prevention criteria.', 'A total of 256 patients with 360 microvascular breast reconstructions who received both preoperative and postoperative prophylactic antibiotics were analyzed. The overall surgical-site infection rate was 17.2 percent (44 of 256 patients). Surgical-site infection was correlated with increased age, tobacco use, and prior radiation. Duration of postoperative antibiotic use did not differ in those patients who developed surgical-site infections (6.2 versus 7.7 days; p = 0.19). Eighty-two patients (32 percent) received only 24 hours of postoperative antibiotics, while 174 (68 percent) received more than 24 hours of antibiotics for a median duration of 10 days. There was no difference in the overall surgical-site infection rate in those who received more than 24 hours of antibiotics (19.5 versus 15.5 percent; p = 0.47).'] |
['The sphincter of Oddi (SO) manometry via the transpapillary route is performed usually for a period of several minutes. To investigate whether there is a considerable variation in the manometric measurements of SO over a longer period of time, we have performed long-term manometry of SO via the transpapillary (n = 5) as well as the percutaneous (n = 7) routes.', 'Transpapillary manometry of SO was carried out by a conventional low-compliant continuously perfused technique. The location of the manometric catheter was maintained at the same level by observing the video monitor. SO manometry and the duodenal migrating motor complex (MMC) was simultaneously measured with a specially designed catheter via the percutaneous route.', 'The mean recording time was 41 min (range 11-72 min). The frequency of phasic contractions of SO varied from 0 to 12/min. Throughout the entire recording period, high-frequency contractions (over 8/min) were noted 14.9% of the time. In the cases of percutaneous transductal SO manometry, the periods of high-frequency contractions coincided with phase III of duodenal MMC. The interval between the first high-frequency contractions and the second was 47 min. The mean duration of high-frequency contractions was 6 min and 42 s. There was no significant change in the amplitude, basal pressure, and contraction sequence among the various periods of frequencies.'] |
['Following an acute burn injury, higher distress is consistently observed among individuals exhibiting a conflict between approach coping (e.g., processing) and avoidance coping (e.g., suppression) relative to those individuals who use only one of these methods. Study objectives were to determine if contradictory coping messages would lead to such approach-avoidance coping conflict and to determine if experiment-induced coping conflict is also associated with higher distress.', 'Participants (n=59 adults hospitalized with acute burn injuries) were assigned randomly to experimental conditions differing in the order in which training was provided in two ways of coping with posttrauma re-experiencing symptoms (i.e., process-then-suppress versus suppress-then-process). The primary dependent variable was coping behavior during the 24-hr posttraining period. Coping behavior was categorized as approach coping (processing), avoidance coping (suppressing), or approach-avoidance coping conflict (both) on the basis of median splits on subscales assessing these behaviors. Secondary analyses examined the relationship between this experiment-induced coping conflict and re-experiencing symptoms.', 'Results indicated that participants in the process-then-suppress condition, relative to the suppress-then-process condition, were significantly more likely to exhibit approach-avoidance coping conflict (i.e., above median split on both processing and suppressing) during the next 24 hr. Furthermore, approach-avoidance coping conflict was associated with greater re-experiencing symptoms assessed via self-report and by blinded coding of recorded speech.'] |
['A homozygous line of transgenic mice that expresses the human elastin promoter/CAT (chloramphenicol acetyltransferase) reporter gene construct in a tissue-specific and developmentally regulated manner is presented. Previous studies have shown that subcutaneous injections of various glucocorticosteroids up-regulate the human transgene in the mouse skin potentially through their interaction with three putative glucocorticosteroid-responsive elements contained within the human elastin promoter. In this study, we propose the use of these transgenic mice as a model system for assaying the potency of various topical glucocorticosteroid preparations.', 'In the first set of experiments, three different commercially available topical glucocorticosteroid creams, 2.5% Hytone (2.5% hydrocortisone) (Dermik Laboratories, Fort Washington, Pa), Cutivate (0.05% fluticasone propionate) (Glaxo Inc, Research Triangle Park, NC), and Temovate (0.05% clobetasol propionate) (Glaxo Inc) (being classified into class VII, V, and I steroids, respectively) were applied to the skin of transgenic mice, with Eucerin (Beiersdorf Inc, Lindenhurst, NY) as the control cream. In a series of six experiments, Hytone 2.5% cream caused a 3.1-fold increase on the average, with Cutivate and Temovate creams resulting in 2.2-fold and 12.4-fold increases in CAT activity over control, respectively. Next, two different preparations of diflorasone diacetate 0.05% cream (Florone [class III] and Psorcon [class II], both from Dermik Laboratories), formulated with different vehicles, were compared. Psorcon caused a 22.8-fold increase in CAT activity over the control compared with a 4.4-fold increase for Florone. However, an assay comparing Psorcon ointment (class I) and Psorcon cream (class II) showed no statistically significant difference in their potencies.'] |
['To investigate the pathways by which cyclic AMP (cAMP) stimulates glucagon-like peptide-1 (GLP-1) secretion, using the GLUTag enteroendocrine cell line.', 'GLP-1 release from GLUTag cells was measured in response to agents that increase cAMP, and single cells were studied by fluorescence calcium imaging and electrophysiology to evaluate the underlying pathways.', 'Pituitary adenylate cyclase-activating polypeptide increased cAMP levels and stimulated GLP-1 release from GLUTag cells. Agents that increase cAMP levels, including forskolin plus 3-isobutyl-1-methylxanthine (fsk/IBMX), triggered a rise in the intracellular calcium concentration and enhanced the response to glucose by increasing both the number of cells responding to glucose and the magnitude of calcium responses in individual cells. Importantly, fsk/IBMX also stimulated GLP-1 release and intracellular calcium elevation even in the absence of nutrients. fsk/IBMX triggered membrane depolarisation and the firing of action potentials, associated with a +14 mV shift in the voltage-dependence of activation of hyperpolarisation-activated currents and the closure of a background potassium conductance.'] |
['The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been associated with adverse clinical outcome. Calpain-9 was thought to be exclusively expressed in the digestive tract; however recent studies have shown that this protein is also expressed in breast tissue.', 'We investigated the expression of calpain-9 in a large cohort of early stage breast cancer patients (n\u2009=\u2009783) using immunohistochemistry on a tissue microarray. Patients had long-term follow-up information available for analysis.', 'Low expression of calpain-9 was associated with patients over 40\xa0years of age (P\u2009=\u20090.025), smaller tumour size (P\u2009=\u20090.001), lower tumour stage (P\u2009=\u20090.009), a more favourable Nottingham Prognostic Index value (P\u2009=\u20090.002) and positive oestrogen receptor status (P\u2009=\u20090.014). Calpain-9 expression was not associated with survival in the total patient cohort, however low calpain-9 expression was associated with adverse survival in patients who received endocrine therapy (P\u2009=\u20090.033), which remained significant in multivariate Cox regression analysis accounting for potential confounding factors (hazard ratio (HR)\u2009=\u20090.56, 95% confidence interval (95% CI)\u2009=\u20090.36-0.89, P\u2009=\u20090.013). Low calpain-9 expression was also associated with adverse survival in patients with an intermediate Nottingham Prognostic Index value (P\u2009=\u20090.009), and remained so in multivariate analysis (HR\u2009=\u20090.54, 95% CI\u2009=\u20090.36-0.82, P\u2009=\u20090.003).'] |
['The expression of gax, an anti-proliferative homeobox gene, is rapidly downregulated in vascular smooth muscle cells (VSMCs) following arterial injury. Here we performed percutaneous adenovirus-mediated gene transfer into the iliac arteries of normal rabbits using a channel balloon catheter to assess the effects of gax overexpression on neointima formation, lumen diameter, reendothelialization and functional vasomotion.', 'A channel balloon catheter was used to perform both the arterial injury and local gene delivery. In each animal both iliac arteries were randomly assigned to receive either an adenovirus expressing the gax gene (Ad-Gax) or the beta-galactosidase gene (Ad-beta gal). In a second group of animals arteries were randomly assigned to receive either Ad-beta gal or saline.', 'At one month, angiography revealed 36% less luminal narrowing in the Ad-Gax-treated arteries relative to the Ad-beta gal-treated control arteries. Histological analysis revealed that the intimal/medial ratio (I/M) was reduced by 56% in the Ad-Gax group. Endothelium-dependent vasomotion was not affected by the gax gene transfer. In the second group, no statistically significant differences were found between the saline and the Ad-beta gal-treated vessels for any of these parameters.'] |
['Oxidative stress pathways are activated in diabetes, particularly when dialysis is required (DD). NF-kB is activated in this clinical condition. Since N-Acetyl-cysteine (NAC) is an anti-oxidant, we aimed at investigating its effect in modulating NF-kB activation in lymphomonocytes (PBMC) of DD patients.', 'Twenty-five DD patients were enrolled in a cross-over designed study. Tests were performed at T0 and after one month (T1) of treatment with NAC and three months after NAC withdrawal. We assessed NF-kB activation by EMSA, levels of advanced oxidation protein products (AOPP) by spectral analysis, total antioxidant capacity (TAC) by colorimetry, and apoptosis by FACS.', 'At T0 a statistically significant increased activation of the subunits of NF-kB, p50/p65, was detected in PBMC of DD patients in comparison to controls (both P<.0001). After one month of NAC both p50-p50/p50-p65 dimers were significantly reduced (P<.004 and .006). Three months after drug withdrawal NF-kB increased again to basal levels (P<.002 and P<.001 vs. end of treatment with NAC). AOPP and TAC levels and the percentage of apoptotic PBMC revealed modifications in accordance with NFkB activation. In a multivariate linear regression model using delta AOPP as the dependent variable and delta p50-p50, delta TAC, and delta APO as independent variables, we found that all three dependent parameters all retained an independent correlation with delta AOPP.'] |
['We report the results of a prospective study of 1,381 Mentor Alpha I penile prostheses implanted to treat impotence, and compare original and enhanced penile prosthesis mechanical reliability.', 'The study consisted of 410 original models manufactured before November 1992 and 971 enhanced models manufactured since December 1992. Implants were further stratified as first time (virgin) or replacements of a previous implant. Mechanical failure-free survival rates for the original prosthetic and enhanced models were compared.', 'The 5-year survival rate increased from 75.3% for the original to 92.6% for the enhanced model overall (log rank p<0.0001), and from 75.3 to 93.6%, respectively, for the virgin implants only (log rank p<0.0001). The estimated failure rate of approximately 5.6% for the original model was fairly consistent during followup, while the significantly lower failure rate of 1.3% for the enhanced model was not. The failure rate of the enhanced model implants was about 0.8% per year during the first 3.5 years and increased to approximately 3.1% per year thereafter.'] |
['Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.', 'Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.', 'Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.'] |
['To determine whether immunization with pneumolysin (PLY) protects against pneumococcal endophthalmitis.', 'New Zealand white rabbits were immunized with a mutant form of PLY that retains only 1% of its cytolytic activity until serum IgG titers were ≥51,200. For a negative control, rabbits were immunized with phosphate-buffered saline (mock). Each vitreous was injected with 10(2) colony-forming units of a clinical endophthalmitis isolate of Streptococcus pneumoniae. Severity of endophthalmitis was graded by slit lamp examination at 24 and 48\u2009h postinfection (PI). Serial dilutions of vitreous were plated for bacterial colony-forming units quantitation, eyes were extracted for histology, and a whole blood survival assay was performed.', 'Immunized rabbits had a significantly lower mean slit lamp examination score at 24 and 48\u2009h PI when compared to mock immunized rabbits (P\u2009≤\u20090.002). There was not a significant difference in bacterial load in the vitreous at 24 or 48\u2009h PI. Histological sections showed that retinas of mock immunized rabbits appeared to be destroyed, whereas those of PLY immunized rabbits remained largely intact. Damage spread to the aqueous humor, stroma, and conjunctiva of mock immunized rabbits by 48\u2009h PI. Minimal damage was observed in the vitreous of PLY immunized rabbits and did not spread to other parts of the eye. Whole blood from immunized rabbits inhibited the growth of bacteria better than whole blood from mock immunized rabbits.'] |
['To investigate the reliable markers reflecting treatment response better than the traditional inflammatory indices in patients with rheumatoid arthritis (RA) receiving tocilizumab therapy.', 'A total of 58 RA patients treated with tocilizumab for more than six months from January 2013 to December 2014 were initially included. Flares were defined as events that required steroid dose escalation, intra-articular steroid injections, or switching tocilizumab to other biologic agents. The clinical and laboratory data were retrospectively collected from electronic medical records.', 'Of the 52 patients except for six patients who were excluded, 16 experienced flares, and 36 were stable during tocilizumab therapy. The C-reactive protein (CRP) level did not significantly differ between a stable state before flares and at flares. Compared with those at the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels (n\u2009=\u20099) were within the normal limit or decreased (n\u2009=\u20094) at flares. Interestingly, NLR increased at flares in all but one patient in the flare group.'] |
['Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients.', 'To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma were measured in a subset of patients.', 'The results indicate that patients treated with doxorubicin showed sustained elevations in oxidative byproducts in plasma. At the RNA level, women who exhibited low EFs after chemotherapy had 260 transcripts that differed >2-fold (p<0.05) compared to women who received chemo but maintained normal EFs. Most of these transcripts (201) were not altered in non-chemotherapy patients with low EFs. Pathway analysis of the differentially expressed genes indicated enrichment in apoptosis-related transcripts. Notably, women with chemo-induced low EFs had a 4.8-fold decrease in T-cell leukemia/lymphoma 1A (TCL1A) transcripts. TCL1A is expressed in both cardiac and skeletal muscle, and is a known co-activator for AKT, one of the major pro-survival factors for cardiomyocytes. Further, women who developed low EFs had a 2-fold lower level of ABCB1 transcript, encoding the multidrug resistance protein 1 (MDR1), which is an efflux pump for doxorubicin, potentially leading to higher cardiac levels of drug. In vitro studies confirmed that inhibition of MDR1 by verapamil in rat H9C2 cardiomyocytes increased their susceptibility to doxorubicin-induced toxicity.'] |
['Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro-inflammatory cytokines typically released by activated monocytes. The E4 variant of apolipoprotein E is a recognized risk factor for atherosclerosis. It has recently been shown that apolipoprotein E affects monocyte functions in vitro and leads to higher levels of median lipoprotein (a) in humans. The aim of the study is to investigate if the E4 genetic variant of apolipoprotein E affects cytokine release after CPB surgery.', '22 patients were operated on with standard coronary artery bypass grafting. Concentrations of interleukin 8 (IL-8) and tumor necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at regular intervals within 48 h after surgery. Total apparent cytokine outputs were calculated as area under the curve. Results are expressed as mean+/-standard deviation and compared by unpaired t-test.', 'In the presented patient population 6 (27%) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean cross clamp time (CCT) was 56.2+/-13.5 min versus 55.7+/-12.1 min and CPB time was 91.8+/-17.5 versus 93.5+/-15.7 min. No statistical difference between E4-carriers and E4 non-carriers regarding CCT and CPB was observed. The total amount of IL-8 and TNF-alpha was higher in patients carrying the E4 genetic variant of apolipoprotein E in comparison to E4 non-carriers (P<0.08, P<0.039).'] |
['To study the inhibition of the expression of bcl-xL gene induced by RNA interference in CNE-2Z cell line in addition to the inhibition of its proliferation and apoptotic induction.', 'Small interfering RNAs targeting bcl-xL gene were synthesized by using web design software provided by Amnion and the silencer short interfering RNA (siRNA) construction kit; fluorescein-labeled siRNAs were done by FAM-silencer siRNA labeling kit; siRNAs were transfected into CNE-2Z cells by using lipofectamine 2000 reagent; siRNA transfection efficiencies were analyzed by fluorescent microscopy; down-regulation of bcl-xL was detected by RT-PCR; thiazolyl blue (MTT) assay was used to assess the cell growth; apoptosis of CNE-2Z cells was analyzed by flow cytometry.', 'Green fluorescence in the cells was seen clearly in FAM-labeled siRNA transfected group under the fluorescent microscope while none in the untransfected group. Different down-regulations of bcl-xL mRNA expression were found in the transfected groups. The expression of bcl-xL mRNA decreased by 10% - 70% in the siRNAs transfected CNE-2Z by RT-PCR scan analysis. The inhibitory rate of cell proliferation depended on time and concentrations to some extent. Different cell apoptosis could be induced by different concentrations of siRNA4.'] |
['Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats.', 'Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring.', 'During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered.'] |
['While hospital mortality after the Norwood operation for hypoplastic left heart syndrome (HLHS) has decreased steadily, interstage mortality until the superior cavopulmonary anastomosis (SCPA) remains a major concern. Our aim was to institute a home surveillance programme to decrease interstage mortality.', 'We enrolled 45 HLHS patients surviving the Norwood operation into our home surveillance programme and compared them with 97 patients treated before the initiation of the programme and with a third group of 20 patients not discharged between the first- and the second-stage operation. While still in hospital, parents were taught to record weight and fluid intake as well as oxygen saturations with the help of a vital sign monitor. During the last week of the hospital stay, the following criteria had to be met: oxygen saturation >75%, weight gain of at least 20-30 g in 3 days and a maximum weight loss of 30 g in a day. After discharge, these criteria had to be maintained at all times or the parents were supposed to call our hospital. Additionally, an experienced paediatric cardiologist from our centre called the parents at home once a week.', 'Interstage mortality was reduced significantly from 12.4% (12/97) to 2.2% (1/45) (P = 0.042). The number of patients, who were not discharged before the SCPA, was significantly higher after the start of the home surveillance programme (12/57 vs. 8/105, P = 0.022). After discharge, 14 (31%) infants breached the surveillance criteria. Of these, one patient died and eight patients were operated earlier (SCPA, n = 6; shunt replacement, n = 2). The remaining five patients could be discharged home after observation. Children in the home surveillance programme were younger [102 (67-299) vs. 152 (77-1372) days, P = 0.001] and weighed less (5.09 ± 0.79 vs. 5.75 ± 1.22 kg, P = 0.001) at the SCPA compared with the remainder. Early survival after SCPA was not different.'] |
['The impact of coagulopathy on survival of patients with myeloma has not been studied in detail. We aimed to assess the correlation between activated partial thromboplastin time/prothrombin time at diagnosis and overall survival in myeloma patients.', 'Data including activated partial thromboplastin time and prothrombin time obtained before treatment and at the time of diagnosis of multiple myeloma (excluding monoclonal gammopathy of undetermined significance, POEMS syndrome, IgM myeloma and myeloma with amyloidosis) collected from 222 patients were analyzed.', 'Twenty-one patients (9.5%) had prolonged activated partial thromboplastin time (nine with prolonged a activated partial thromboplastin time alone, 12 with both prolonged activated partial thromboplastin time and prothrombin time) and 10 (4.5%) had prolonged prothrombin time alone. Coagulopathy occurred only in patients with IgA and IgG myeloma but not light-chain disease. Prolonged activated partial thromboplastin time was an independent prognostic factor in IgA and IgG myeloma (median survival = 12.7 months, P = 0.004), while prolonged prothrombin time alone had no impact on survival. Subgroup analysis revealed that prolonged activated partial thromboplastin time indicated less favorable survival in IgA myeloma (P = 0.001), but not the IgG myeloma (P = 0.341). This observation still holds true in IgA myeloma with Durie-Salmon stage II or III (P = 0.002).'] |
['Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Epothilone B (EpoB), Taxol and vinblastine are anti-neoplastic agents that interfere with microtubules and arrest the cell cycle in the G2/M phase. EpoB is being evaluated in phase III clinical trials, and its analogs are currently being used in the treatment of taxane-resistant metastatic breast cancer. Little is known about the effect of these drugs on the immune response to tumors. Cancer cells evade immune recognition by down-regulating HLA Class I expression, allowing escape from immune surveillance and destruction. Our data illustrates the effect of microtubule-interacting agents on HLA Class I and HLA-A2 expression as well as the modulation of cytokine expression in ovarian cancer cells.', 'Ovarian cancer cells were treated with different concentrations of drugs. Cell surface expression and mRNA transcription of HLA Class I molecules and HLA-A2 was examined. IFNα, IL1β, IL12 and IL6 mRNA expression was also evaluated upon EpoB treatment.', 'Low-dose EpoB, Taxol and vinblastine greatly increased expression of HLA Class I and HLA-A2 molecules in Hey ovarian cancer cells. EpoB does not modulate HLA expression in drug-resistant ovarian cancer cells. The expression of IFNα, IL1β, IL12 and IL6 is also markedly increased upon EpoB treatment.'] |
['Nonenzymatic reactions between sugars or lipids and protein and formation of advanced glycation and lipoxidation end products (AGE/ALEs) contribute to the chemical modification and cross-linking of tissue proteins with age. Accelerated formation of AGE/ALEs during hyperglycemia is implicated in the development of diabetic complications. In this study, we examined the effect of the AGE/ALE inhibitor pyridoxamine on chemical modification and cross-linking of collagen and development of renal disease in the streptozotocin-diabetic rat.', 'Diabetic rats were treated with pyridoxamine; parallel experiments were conducted with aminoguanidine, the prototype AGE inhibitor. Progression of renal disease was evaluated by measurements of albuminuria and plasma creatinine concentration. Plasma triglycerides, cholesterol, lactate and pyruvate were measured by enzymatic assays, and AGE/ALEs in skin collagen by HPLC and GC-MS assays.', 'Pyridoxamine significantly inhibited the increase in albuminuria, plasma creatinine, hyperlipidemia and plasma lactate/pyruvate ratio in diabetic rats, without an effect on blood glucose or glycated hemoglobin. AGE/ALEs, fluorescence and cross-linking of skin collagen increased approximately twofold in diabetic versus control rats after seven months of diabetes. Pyridoxamine caused a significant (25 to 50%) decrease the AGE/ALEs, carboxymethyllysine and carboxyethyllysine, cross-linking and fluorescence in skin collagen of diabetic rats, but did not affect pentosidine.'] |
['Children with severe/difficult-to-treat asthma experience high morbidity including frequent severe exacerbations. More knowledge is required to identify predictors of these exacerbations to reduce their occurrence.', 'To investigate the risk of future severe exacerbations (FSEs) in children with severe/difficult-to-treat asthma and recent severe exacerbations (RSEs).', 'We analyzed the occurrence and association of RSE (defined as 1 or more corticosteroid bursts during the 3 months before each of 3 annual visits) and FSE (defined as 1 or more corticosteroid bursts 6 or 12 months later) in children age 6 to 11 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study. Repeated measures logistic regression analysis assessed the risk of FSE adjusted for demographics and clinical variables.', 'In a multivariable model, FSE at 6 months was most strongly predicted by RSE (odds ratio [OR], 3.08; 95% CI, 2.21-4.28) and having 3 to 4 allergic triggers (OR, 2.05; 95% CI, 1.31-3.20). Race (OR, 1.77; 95% CI, 1.25-2.51) and being very poorly controlled according to the impairment component of the National Heart, Lung, and Blood Institute guidelines (OR, 1.59; 95% CI, 1.14-2.23) also significantly predicted FSE.'] |
['Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown.', 'We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (>18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared.', 'One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008).'] |
['To determine the association between prophylactic plasma transfusion and periprocedural red blood cell (RBC) transfusion rates in patients with elevated international normalized ratio (INR) values undergoing interventional radiology procedures.', 'In this retrospective cohort study, adult patients undergoing interventional radiology procedures with a preprocedural INR available within 30 days of the procedure during a study period of January 1, 2009, to December 31, 2013, were eligible for inclusion. Baseline characteristics, coagulation parameters, transfusion requirements, and procedural details were extracted. Univariate and multivariable propensity-matched analyses were used to assess the relationships between prophylactic plasma transfusion and the outcomes of interest, with a primary outcome assessed a priori of RBC transfusion occurring during the procedure or within the first 24 hours postprocedurally.', 'A total of 18,204 study participants met inclusion criteria for this study, and 1803 (9.9%) had an INR of 1.5 or greater before their procedure. Of these 1803 patients, 196 patients (10.9%) received prophylactic plasma transfusion with a median time of 1.9 hours (interquartile range [IQR], 1.1-3.2 hours) between plasma transfusion initiation and procedure initiation. In multivariable propensity-matched analysis, plasma administration was associated with increased periprocedural RBC transfusions (odds ratio, 2.20; 95% CI, 1.38-3.50; P<.001) and postprocedural intensive care unit admission rates (odds\xa0ratio, 2.11; 95% CI, 1.41-3.14; P<.001) as compared with those who were not transfused preprocedurally. Similar relationships were seen at higher INR thresholds for plasma transfusion.'] |
['We aimed to assess the impact of an automated dispensing system on the incidence of medication errors related to picking, preparation, and administration of drugs in a medical intensive care unit. We also evaluated the clinical significance of such errors and user satisfaction.', 'Preintervention and postintervention study involving a control and an intervention medical intensive care unit.', 'Two medical intensive care units in the same department of a 2,000-bed university hospital.', 'Adult medical intensive care patients.', 'After a 2-month observation period, we implemented an automated dispensing system in one of the units (study unit) chosen randomly, with the other unit being the control.', 'The overall error rate was expressed as a percentage of total opportunities for error. The severity of errors was classified according to National Coordinating Council for Medication Error Reporting and Prevention categories by an expert committee. User satisfaction was assessed through self-administered questionnaires completed by nurses. A total of 1,476 medications for 115 patients were observed. After automated dispensing system implementation, we observed a reduced percentage of total opportunities for error in the study compared to the control unit (13.5% and 18.6%, respectively; p<.05); however, no significant difference was observed before automated dispensing system implementation (20.4% and 19.3%, respectively; not significant). Before-and-after comparisons in the study unit also showed a significantly reduced percentage of total opportunities for error (20.4% and 13.5%; p<.01). An analysis of detailed opportunities for error showed a significant impact of the automated dispensing system in reducing preparation errors (p<.05). Most errors caused no harm (National Coordinating Council for Medication Error Reporting and Prevention category C). The automated dispensing system did not reduce errors causing harm. Finally, the mean for working conditions improved from 1.0±0.8 to 2.5±0.8 on the four-point Likert scale.'] |
['To assess whether socioeconomic inequalities were already present in preschool children.', "We used data from 2954 Dutch children participating in a longitudinal birth cohort study. Indicators of socioeconomic status were mother's educational level and household income. Body mass index (BMI)-for-age standard deviation scores were derived from a national reference. Overweight was defined at 24 and 36 months according to age- and sex-specific cut-off points for BMI. Multivariable regression analyses were performed.", 'Relative to children from mothers with the highest educational level, mean BMI standard deviation scores was lower at age 24 months in children from mothers with the low, mid-low, and mid-high educational level, and in the mid-low group at 36 months (P < .001). Prevalence of overweight was lower in children from mothers with the mid-low educational level at age 24 and 36 months (adjusted odds ratio at 24 months: 0.61; 95% confidence interval: 0.43-0.87 and at 36 months: 0.65; 95% confidence interval: 0.44-0.96) but was not significantly different for the other educational levels. There were no significant differences in childhood overweight by income level.'] |
['It is challenging to identify malnutrition, which is a risk factor for poor outcome in patients with liver cirrhosis. In the present study, we aimed to investigate the prevalence of malnutrition among patients listed for liver transplantation, as assessed by different methods, and also to relate dual-energy X-ray absorptiometry (DXA) to short-term post-transplant outcomes.', 'In this retrospective cohort study, we reviewed the medical records of 106 patients who underwent liver transplantation in 2009-2012. Body composition was assessed by the fat-free mass index (FFMI) and fat mass index (FMI) obtained using DXA. Severe infections within 1 month, length of stay in intensive care unit and length of hospital stay were endpoints of primary interest.', 'The prevalence of malnutrition was 2-20% depending on sex and the assessment method. Thirty-nine (37%) patients developed severe infections within 1 month after liver transplantation. In multivariate analysis with logistic regression, body composition was significantly associated with post-operative infection when measured with FFMI (P = 0.043) but not with FMI (P = 0.087). Post-operative dialysis (P = 0.004) and post-operative infections (P < 0.001) were significantly associated with length of stay in hospital. Post-operative bleeding (P = 0.015), duration of mechanical ventilation (P < 0.001) and the need for dialysis (P < 0.001), but not body composition, were significant predictors of the length of stay in the intensive care unit.'] |
['In osteosarcoma patients the development of metastases, often to the lungs, is the most frequent cause of death. The aim of this study was to elucidate the molecular mechanisms governing osteosarcoma development and dissemination and, thereby, to identify possible novel drug targets for improved treatment.', 'Osteosarcoma samples were characterized using genome-wide microarrays: increased expression of the EphA2 receptor and its ligand EFNA1 was detected. In addition, increased expression of EFNB1, EFNB3 and EphA3 was suggested. Immunohistochemistry revealed an absence of EphA2 in normal bone, and de novo expression in osteosarcomas. EFNA1 was expressed in normal bone, but was significantly elevated in tumours. Further in vitro investigations on the functional role of EphA2 and EFNA1 showed that EFNA1 ligand binding induced increased tyrosine phosphorylation, receptor degradation and downstream mitogen-activated protein kinase (MAPK) activation. Interference with the MAPK pathway unravelled a potential autoregulatory loop governing mainly EFNA1 expression via the same pathway.'] |
['Evidence suggests that the aging process tends to lead to sarcopenia and osteoporosis which reduce the quality of life in older women. Resistance training (RT) is widely supported as a means of delaying or offsetting the decline in muscle strength and loss of bone mineral content in older women. The purpose of this investigation was to analyze the effects of a 12-wk RT program (3 times a week) with dietary intake maintenance on muscle strength and body composition of healthy, sedentary older women.', 'Forty-four older women were randomly assigned to a RT program (n = 22, 66.3 ± 4.8 years, 60.7 ± 9.1 kg, 153.1 ± 0.90 cm, 24.9 ± 3.3 kg/m² ) or a control group (n = 22, 66.4 ± 4.0 years, 63.3 ± 7.5 kg, 155.5 ± 5.8 cm, 26.2 ± 2.6 kg/m²) performing stretching exercises during the same period. One-repetition maximum test on chest press and leg extension were used to assess muscle strength. Body composition was measured by dual energy x-ray absorptiometry to determine fat mass, fat-free mass, and bone mineral content. Dietary intake was recorded using a 3-day food records. All subjects maintained their normal diet during the investigation.', 'No significant differences were found for the body composition components within and between groups. A significant time by group interaction indicated that the RT group made greater improvements in upper and lower limb muscle strength (chest press ~12%, p = 0.0001; leg extension ~13%, p <0.0001).'] |
['Thyroglobulin (Tg) is a marker of tumor recurrence during thyroid cancer follow-up. While helpful in the postoperative setting, the clinical significance of preoperative Tg measurements remains unclear. The aim of the study was to determine if preoperative Tg levels are indicative of underlying malignancy or burden of metastatic disease.', 'A retrospective review of a prospectively collected database at an academic medical center of all thyroidectomy patients with a measured preoperative Tg level was conducted. Patients were grouped by Tg level into quartiles for initial univariate analysis, followed by multivariable analysis of variance.', "Between 2007 and 2012, 611 patients met criteria. Quartile breakdown was as follows: ≤19\xa0ng/mL, 19.1-54\xa0ng/mL, 54.1-151\xa0ng/mL, and >151\xa0ng/mL. Patients' age and gender were equivalent. Hashimoto's thyroiditis was most common in the lowest Tg group (24% versus 11%-12%, P\xa0<\xa00.01). While cancer was more common in the low Tg, metastatic disease was most common in the high Tg group. Specimen weight increased with increasing Tg levels (P\xa0<\xa00.01). Body mass index, gland weight, cancer, and Hashimoto's and metastatic disease were entered into a multivariable analysis. Only gland weight and metastatic disease correlated with Tg levels (both P\xa0<\xa00.001). All patients with Tg\xa0>\xa05000\xa0ng/mL had metastatic disease (n\xa0=\xa06)."] |
['Elucidation of the mechanisms by which plants adapt to elevated CO2 is needed; however, most studies of the mechanisms investigated the response of plants adapted to current atmospheric CO2. The rapid respiration rate of cotton (Gossypium hirsutum) fruits (bolls) produces a concentrated CO2 microenvironment around the bolls and bracts. It has been observed that the intercellular CO2 concentration of a whole fruit (bract and boll) ranges from 500 to 1300 µmol mol(-1) depending on the irradiance, even in ambient air. Arguably, this CO2 microenvironment has existed for at least 1·1 million years since the appearance of tetraploid cotton. Therefore, it was hypothesized that the mechanisms by which cotton bracts have adapted to elevated CO2 will indicate how plants will adapt to future increased atmospheric CO2 concentration. Specifically, it is hypothesized that with elevated CO2 the capacity to regenerate ribulose-1,5-bisphosphate (RuBP) will increase relative to RuBP carboxylation.', 'To test this hypothesis, the morphological and physiological traits of bracts and leaves of cotton were measured, including stomatal density, gas exchange and protein contents.', 'Compared with leaves, bracts showed significantly lower stomatal conductance which resulted in a significantly higher water use efficiency. Both gas exchange and protein content showed a significantly greater RuBP regeneration/RuBP carboxylation capacity ratio (Jmax/Vcmax) in bracts than in leaves.'] |
['We explored whether the opiate, morphine, affects the actions of maraviroc, as well as a recently synthesized bivalent derivative of maraviroc linked to an opioid antagonist, naltrexone, on HIV-1 entry in primary human glia.', 'HIV-1 entry was monitored in glia transiently transfected with an LTR construct containing a luciferase reporter gene under control of a promoter for the HIV-1 transactivator protein Tat. The effect of maraviroc and the bivalent ligand with or without morphine on CCR5 surface expression and cytokine release was also explored.', 'Maraviroc inhibits HIV-1 entry into glial cells, whereas morphine negates the effects of maraviroc leading to a significant increase in viral entry. We also demonstrate that the maraviroc-containing bivalent ligand better inhibits R5-tropic viral entry in astrocytes than microglia compared to maraviroc when coadministered with morphine. Importantly, the inhibitory effects of the bivalent compound in astrocytes were not compromised by morphine. Exposure to maraviroc decreased the release of pro-inflammatory cytokines and restricted HIV-1-dependent increases in CCR5 expression in both astrocytes and microglia, whereas exposure to the bivalent had a similar effect in astrocytes but not in microglia. The CCR5-μ-opioid receptor (MOR) stoichiometric ratio varied among the two cell types with CCR5 expressed at much higher levels than MOR in microglia, which could explain the effectiveness of the bivalent ligand in astrocytes compared to microglia.'] |
['Sclerosing hemangiomas (SH) are lung tumors characterized by surface cuboidal cells and round stromal cells. The cell of origin remains controversial, though immunohistochemical and ultrastructural studies suggest primitive respiratory epithelium. Napsin A, a human aspartic proteinase found primarily in type II pneumocytes and alveolar macrophages, is emerging as a helpful immunohistochemical marker in characterizing the origin of lung neoplasms, and may be of use in evaluating SH.', 'To evaluate napsin A immunohistochemical staining in SH to further characterize the cell of origin.', 'Six cases of SH were stained for napsin A, as well as thyroid transcription factor 1 and cytokeratin in selected cases.', 'Surface and round cells were positive for thyroid transcription factor 1 in all cases stained with this marker. Cytokeratins were positive in surface cells in all cases stained with this marker; 2 cases had focal cytokeratin staining in round cells. Round cells had focal napsin A staining in 1 case (17%); surface cells were napsin positive in all cases.'] |
['Nutritionally essential polyunsaturated fatty acids (PUFAs) have been implicated as potentially important factors in mood disorders. For instance, n-3 PUFA supplementation is reported to improve outcomes in major depressive disorder and bipolar disorder. However, the role of PUFAs in acute mania has been minimally investigated. We performed a pilot study to compare plasma levels of free (non-esterified) and esterified PUFAs between patients in an acute manic episode and healthy volunteers, and to explore associations between symptom severity and levels of fatty acids and of the arachidonic acid metabolite, prostaglandin E2 (PGE2).', 'Patients (n=10) who were medication-free for at least two weeks and seeking inpatient admission for an acute manic episode were compared with healthy volunteers (n=10). Symptom severity was assessed at admission and after six weeks of naturalistic treatment. Fasting baseline free and esterified plasma levels of docosahexaneoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3), arachidonic acid (AA,20:4n-6) and the AA metabolite PGE2 were determined, and PGE2 levels were tested again at six weeks.', 'No between-group differences were found in levels of individual or total fatty acids, or of PGE2. Among subjects, manic symptom severity correlated negatively with levels of free AA and free EPA, and positively with the free AA:EPA ratio. PGE2 levels did not differ between groups or in subjects pre- and post-treatment.'] |
['Idiopathic dilated cardiomyopathy (DCM) is typically diagnosed in adulthood, yet familial cases exhibit variable age-dependent penetrance and a subset of patients develop sporadic DCM in childhood. We sought to discover the molecular basis of sporadic DCM in an 11-year-old female with severe heart failure necessitating cardiac transplantation.', 'Parental echocardiograms excluded asymptomatic DCM. Whole exome sequencing was performed on the family trio and filtered for rare, deleterious, recessive, and de novo variants. Of the 8 candidate genes identified, only 2 had a role in cardiac physiology. A de novo missense mutation in TNNT2 was identified, previously reported and functionally validated in familial DCM with markedly variable penetrance. Additionally, recessive compound heterozygous truncating mutations were identified in XIRP2, a member of the ancient Xin gene family, which governs intercalated disc (ICD) maturation. Histomorphological analysis of explanted heart tissue revealed misregistration, mislocalization, and shortening of ICDs, findings similar to Xirp2(-/-) mice.'] |
['Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients.', 'This study included 10 patients (83.7 +/- 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation.', 'DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594).'] |
['This study sought to determine whether tissue oxygenation (StO(2)) could be used as a surrogate for central venous oxygenation (ScVO(2)) in early goal-directed therapy (EGDT).', 'The study enrolled a prospective convenience sample of patients aged > or =18 years with sepsis and systolic blood pressure <90 mm Hg after 2 L of normal saline or lactate >4 mmol, who received a continuous central venous oximetry catheter. StO(2) and ScVO(2) were measured at 15-minute intervals. Data were analyzed using a random coefficients model, correlations, and Bland-Altman plots.', 'There were 284 measurements in 40 patients. While a statistically significant relationship existed between StO(2) and ScVO(2) (F(1,37) = 10.23, p = 0.002), StO(2) appears to systematically overestimate at lower ScVO(2) and underestimate at higher ScVO(2). This was reflected in the fixed effect slope of 0.49 (95% confidence interval [CI] = 0.266 to 0.720) and intercept of 34 (95% CI = 14.681 to 50.830), which were significantly different from 1 and 0, respectively. The initial point correlation (r = 0.5) was fair, but there was poor overall agreement (bias = 4.3, limits of agreement = -20.8 to 29.4).'] |
['To investigate the prognostic significance of endocan, compared with procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC), neutrophils (N), and clinical severity scores in patients with ARDS.', 'A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II) was calculated on day 1 after the patient met the defining criteria of ARDS.', 'Endocan levels significantly correlated with the APACHE II score in the ARDS group (r = 0.676, P = 0.000, n = 42). Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR) 5.01 (2.98-8.44) versus 3.01 (2.36-4.36)\u2009ng/mL, P = 0.017). According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150-1.641) and an area of receiver operator characteristic curve (AUROC) of 0.715 (P = 0.017). Moreover, endocan can predict the multiple-organ dysfunction of ARDS.'] |
['To study whether autophagy participates in the neuroprotective effect of nerve growth factor (NGF) on neurons treated with alcohol.', 'The autophagy-related markers were used to explore the role of autophagy in PC12 cells exposed to alcohol or pre-incubated with NGF before initiating the treatment with alcohol (100 mM; 6 h). PC12 cells were pre-incubated with 3-methyladenine (3-MA) (10 mM; 1 h) or rapamycin (100 nM; 1 h) before co-incubated with alcohol (100 mM; 6 h) in order to investigate the relationship between apoptosis and autophagy. PC12 cells were pre-incubated with LY294002 (50 μM; 30 min) before co-incubated with NGF and alcohol in order to analyze the protein expression of PI3K/Akt/mTOR pathway via western blotting.', 'By methylthiazoltetrazolium, western blotting and flow cytometry assays, we found that cell viability decreased in a dose- and time-dependent manner after treatment with alcohol in PC12 cells. As cells were exposed to alcohol, the levels of LC3-II proteins became elevated, likewise, pre-treatment with 3-methyladenine (3-MA, an autophagic inhibitor) or rapamycin (an autophagic inducer) resulted in an increased or decreased percentage of apoptosis in contrast to other alcohol-treated groups, respectively. NGF markedly increased LC3-II production after treatment with alcohol in a dose-dependent manner. Moreover, NGF remarkably attenuated the phosphorylation effect of alcohol exposure on PI3K/Akt/mTOR pathway, which was suppressed by LY294002 (Akt inhibitor).'] |
['Controversy exists about the effect of recent aspirin use on infarct size and the likelihood of Q-wave infarction in patients who sustain myocardial infarction.', 'We performed face-to-face interviews and chart reviews on 3665 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. For the 2206 patients who did not receive thrombolytic therapy, we assessed aspirin use, peak creatine kinase levels (in 1043 patients), and electrocardiographic interpretations (in 1447 patients).', 'Of the initial 1043 patients, 317 (30. 3%) subjects reported aspirin use in the 4 days before their infarction. The mean +/- SD peak creatine kinase level for aspirin users was 701 +/- 570 IU/mL versus 851 +/- 727 IU/mL for nonusers, an 18% difference (95% confidence interval [CI], 8% to 26%; P <.001). After adjustment for confounding factors, the difference was 12% (95% CI, 2% to 21%; P =.03). Similarly, 38.9% of the aspirin users and 48.7% of the nonusers sustained a Q-wave infarction, an odds ratio of 0.67 (95% CI, 0.54 to 0.83, P <.001). The adjusted odds ratio was 0.77 (95% CI, 0.61 to 0.97, P =.03).'] |
['Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.', 'Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation.', 'Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25\u2009kg\u2009m(-2). Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25\u2009kg\u2009m(-2) experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3-13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009).'] |
['To report estimated radiation doses to the eye lens of the interventionalist from procedures performed with and without use of radiation protection measures.', 'Scattered radiation doses for seven interventional radiology fluoroscopic systems were measured by using phantoms simulating patients 16-28 cm in thickness undergoing low-, medium-, and high-mode fluoroscopy, cine cardiac imaging, and digital subtraction angiography (DSA). The radiation doses to the eye lens in low- and high-dose scenarios were estimated. Beam angulation, biplanar equipment, working distance, procedure complexity, imaging collimation, and use of eyeglasses and/or protective suspended screens were taken into account. The doses to the lens in several procedures were assessed.', 'Mean scattered radiation doses to the lens during fluoroscopy were 6.0 and 34.5 microSv/min in the low- and high-dose scenarios, respectively. For DSA, typical doses to the lens ranged from 0.77 to 3.33 microSv per image. Operation modes involving increasing or decreasing radiation doses were quantified. For hepatic chemoembolization, iliac angioplasty, pelvic embolization, and transjugular intrahepatic portosystemic shunt creation, lens doses ranged from 0.25 to 3.72 mSv per procedure when protection was not used. Lens doses in the neuroembolization procedures could exceed 10 mSv per procedure.'] |
['The midline thalamus is an important component of the circuitry in limbic seizures, but it is unclear how synaptic modulation of the thalamus affects that circuitry. In this study, we wished to understand how synaptic modulation of the thalamus can affect interregional signaling and seizure spread in the limbic network.', 'We examined the effect of γ-aminobutyric acid (GABA) modulation of the mediodorsal (MD) region of the thalamus on responses in the prefrontal cortex (PFC) by stimulation of the subiculum (SB). Muscimol, a GABA(A) agonist, was injected into the MD, and the effect on local responses to subiculum stimulation was examined. Evoked potentials were induced in the MD and the PFC by low-frequency stimulation of the SB, and seizures were generated in the subiculum by repeated 20-Hz stimulations. The effect of muscimol in the MD on the evoked potentials and seizures was measured.', 'Thalamic responses to stimulation of the subiculum were reduced in the presence of muscimol. Reduction of the amplitudes of evoked potentials in the MD resulted in an attenuation of the late, thalamic components of the responses in the PFC, as well as of seizure durations.'] |
['In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts.', 'Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially diminished by insulin.'] |
['Neutrophilic asthma is thought to be less responsive than eosinophilic asthma to anti-inflammatory therapies including corticosteroids. Chlamydia pneumoniae has been implicated in asthma, possibly by induction of interleukin (IL-8). We hypothesized that IL-8 is increased in the bronchoalveolar lavage (BAL) fluid from children with asthma and C. pneumoniae.', 'BAL fluid was analyzed for C. pneumoniae and IL-8 using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay from 2 asthma patient populations in the Bronx, NY and Massachusetts with an average age of 8 and 8.7 years old, respectively. For comparison, samples were also analyzed for C. trachomatis and Mycoplasma 16s DNA.', 'Of 18 Bronx samples analyzed, 6 (33%) were PCR-positive for C. pneumoniae, 10 (56%) for C. trachomatis, and 8 (44%) for Mycoplasma 16s DNA. IL-8 from C. pneumoniae-positive samples was 3.3-fold higher compared with negative samples (P = 0.003). There was no difference between patients tested for C. trachomatis or Mycoplasma. Of 84 Massachusetts samples analyzed, 42 (50%) were PCR-positive for C. pneumoniae, 42 (50%) for C. trachomatis, and 13 (16%) for Mycoplasma. IL-8 concentration from C. pneumoniae-positive samples was 10.49-fold higher compared with negative samples (P = 0.0001). As in the Bronx cohort, there were no differences between patients tested for C. trachomatis or Mycoplasma. Lastly, BAL neutrophilia predicted the presence of C. pneumoniae but not Mycoplasma or C. trachomatis.'] |
['Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappaB. Transcription factors of the NF-kappaB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory.', 'In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappaB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappaB p65 and reduces NF-kappaB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappaB p65 is essential for this binding.'] |
['The objective of this study was to characterize the relationship between objectively-measured physical activity (PA) and cardiovascular risk factors in 7-year-old children and test the hypothesis that it differs by race.', 'Cross-sectional study of 308 7-year-old children drawn from a major US metropolitan community. PA (moderate-to-vigorous, MVPA; light, LPA; and inactivity, IA) was measured by accelerometry (RT3). Cardiovascular risk factors included BMI, blood pressure, and serum lipids, glucose and insulin concentrations. General linear modeling was used to evaluate the independent associations between PA measures and cardiovascular risk factors and interactions by race.', 'In black children, greater time spent in PA was independently associated with lower levels of triglycerides (MVPA and LPA, both p < .01), glucose (MVPA, p < .05), and insulin (MVPA, p < .01); these associations were not evident in white children. Across races, greater inactivity was independently associated with greater low-density lipoprotein cholesterol in overweight participants (p < .01) but not in normal weight participants. No PA measure was associated with BMI, systolic blood pressure, or high-density lipoprotein cholesterol.'] |
['IQ is thought to explain social gradients in mortality. IQ scores are based roughly equally on Verbal IQ (VIQ) and Performance IQ tests. VIQ tests, however, are suspected to confound true verbal ability with socioeconomic status (SES), raising the possibility that associations between SES and IQ scores might be overestimated. We examined, first, whether two of the most common types of VIQ tests exhibited differential item functioning (DIF) favouring persons of higher SES and/or majority race/ethnicity. Second, we assessed what impact, if any, this had on estimates of the extent to which VIQ explains social gradients in mortality.', 'Data from the General Social Survey-National Death Index cohort, a US population representative dataset, was used. Item response theory models queried social-factor DIF on the Thorndike Verbal Intelligence Scale and Wechsler Adult Intelligence Scales, Revised Similarities test. Cox models examined mortality associations among SES and VIQ scores corrected and uncorrected for DIF.', 'When uncorrected for DIF, VIQ was correlated with income, education, occupational prestige and race, with correlation coefficients ranging between |0.12| and |0.43|. After correcting for DIF, correlations ranged from |0.06| to |0.16|. Uncorrected VIQ scores explained 11-40% of the Relative Index of Inequalities in mortality for social factors, while DIF-corrected scores explained 2-29%.'] |
["Vulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman's social and sexual life. The purpose of this study was to describe the species distribution and in vitroCandidaCandida spp.) isolated from patients with VVC over 8 years.", 'Species which isolated from patients with VVC in Peking University First Hospital were identified using chromogenic culture media. Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document. SPSS software (version 14.0, Inc., Chicago, IL, USA) was used for statistical analysis, involving statistical description and Chi-square test.', 'The most common strains were Candida (C.) albicans, 80.5% (n = 1775) followed by C. glabrata, 18.1% (n = 400). Nystatin exhibited excellent activity against all species (<4% resistant [R]). Resistance to azole drugs varied among different species. C. albicans: clotrimazole (3.1% R) < fluconazole (16.6% R) < itraconazole (51.5% R) < miconazole (54.0% R); C. glabrata: miconazole (25.6% R) < clotrimazole (50.5% R) < itraconazole (61.9% R) < fluconazole (73.3% R); Candida krusei: clotrimazole (0 R) < fluconazole (57.7% R) < miconazole (73.1% R) < itraconazole (83.3% R). The susceptibility of fluconazole was noticeably decreasing among all species in the study period.'] |
['To investigate the effect of antisense RNA to vascular endothelial growth factor165 (VEGF165) on human esophageal squamous cell carcinoma cell line EC109 and the feasibility of gene therapy for esophageal carcinoma.', 'By using subclone technique, the full length of VEGF165 amino acid cDNA, which was cut from pGEM-3Zf+,was cloned inversely into the eukaryotic expression vector pCEP4. The recombinant plasmid pCEP-AVEGF165 was transfected into EC109 cell with lipofectamine. After a stable transfection, dot blot, enzyme-linked immunosorbent assay (ELISA),laser confocal imaging system analysis, transmission electron microscopy and flow cytometry were performed to determine the biological characteristics of EC109 cell line before and after transfection in vitro and whether there was a reversion in the tumorigenic properties of the EC109 cell in vitro.', 'The eukaryotic expression vector pCEP-AVEGF165 was successfully constructed and transfected into EC109 cells. The expression of VEGF165 was significantly decreased in the transfected cells while the biological characteristics of the cells were not influenced by the expression of antisense gene. The tumorigenic and angiogenic capabilities were greatly reduced in nude mice, as demonstrated by reduced tumor end volume (820+/-112.5)mm(3) vs (7930+/-1035)mm(3) and (7850+/-950)mm(3), P<0.01) and microvessel density (average number: (8.5+/-1.2)mm(-2) vs (44.3+/-9.4)mm(-2) and (46.4+/-12.6)mm(-2), P<0.01) in comparison between experimental groups empty vector transfected group and control group.'] |
['The study objective was to validate the National Surgical Quality Improvement Program (NSQIP) Risk Calculator in stratifying risk estimates for patients who received surgery or stereotactic body radiation therapy for clinical stage I non-small cell lung cancer.', 'A retrospective analysis of patients with clinical stage I non-small cell lung cancer undergoing surgery (N = 279) or stereotactic body radiation therapy (N = 206) from 2009 to 2012 was performed. NSQIP complication risk estimates were calculated for both surgical and stereotactic body radiation therapy cases using the NSQIP Surgical Risk Calculator. NSQIP complication risk estimates were compared as continuous variables and by quartile ranges.', "Compared with patients undergoing video-assisted thoracoscopic surgery wedge resection, patients receiving stereotactic body radiation therapy were older, had larger tumors, had lower forced expiratory volume (FEV1) in 1 second and diffusing capacity of the lungs (DLCO) for carbon monoxide values, had higher American Society of Anesthesiologists scores, had higher rates of dyspnea, and had higher NSQIP serious complication risk estimates (all P < .05). Compared with patients undergoing video-assisted thoracoscopic surgery lobectomy, patients receiving stereotactic body radiation therapy had similar disparities, along with higher Adult Comorbidity Evaluation-27 (ACE) scores comorbidity scores, higher rates of cardiac comorbidities, and worse functional status (all P < .05). Variables associated with receiving stereotactic body radiation therapy treatment, rather than wedge resection, included increasing age, higher Adult Comorbidity Evaluation (ACE)-27 comorbidity score, dyspnea status, and decreasing FEV1 in 1 second and DLCO for carbon monoxide, but NSQIP serious complication risk score. In addition, surgical patients' actual serious complication rate (16.6% vs 8.8%) and pneumonia rate (6.0% vs 3.2%) were significantly higher than the NSQIP risk calculator predicted (all P < .05)."] |
['Elevated serum osteoprotegerin (OPG) levels represent an independent risk factor for atherosclerotic disease, although the underlying mechanism is not clear. The aim of this study was to investigate the association of serum OPG levels and circulating endothelial progenitor cell (EPC) numbers, and to explore the effect of OPG on EPC apoptosis and its underlying mechanisms.', 'Flow cytometry was used to enumerate EPCs in the peripheral blood of 91 patients with systemic lupus erythematosus (SLE). Cultured EPCs, isolated from peripheral blood, were challenged with OPG, and apoptosis was evaluated by TUNEL staining. Expression of apoptosis-related proteins was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blotting. Reactive oxygen species (ROS) were detected by flow cytometry, and the expression of NADPH oxidase (NOX) and MAP kinases (MAPK) was measured by qPCR and Western blotting.', 'The serum OPG level was independently associated with reduced numbers of EPCs in patients with SLE. In vitro treatment with OPG significantly induced apoptosis of EPCs; this effect was mediated by syndecan 4. OPG-induced apoptosis was abolished by the ROS scavenger N-acetylcysteine and the NOX inhibitor diphenyleniodonium. OPG increased ROS production through activation of NOX-2 and NOX-4 and triggered phosphorylation of ERK-1/2 and p38 MAPK. Quenching of ROS by knockdown of NOX-2 or NOX-4 transcripts inhibited phosphorylation of ERK-1/2 and p38 MAPK. Moreover, inhibitors of ERK-1/2 and p38 MAPK decreased ROS production and subsequent EPC apoptosis, indicating a feed-forward loop between NOX and MAPK to amplify ROS production related to apoptosis.'] |
['The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma.', 'In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods.', 'Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors.'] |
['Treatment of chronic hepatitis C (CHC) with pegylated interferon α (pegIFNα) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFNα signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFNα on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFNα/ribavirin.', 'In this open-label pilot study, 29 patients with CHC who failed previous therapy with (peg)IFNα/ribavirin were treated with SAMe, betaine, pegIFNα2b and ribavirin. Treatment duration was 6 or 12 months, depending on genotype, and the protocol comprised a stopping rule at week 12 if early virological response (EVR) was not achieved. Virological and biochemical response and safety were assessed throughout the treatment.', '29 patients were enrolled and treated according to the study protocol. 79% of the patients were infected with genotype 1, 72% had advanced fibrosis, 76% had previously received pegIFNα/ribavirin, and only 14% achieved EVR to the previous treatment. When treated with the study medications, 17 patients (59%) showed an EVR, only 3 (10%) however achieved a sustained virological response (SVR). SAMe and betaine were found to be safe when used with pegIFNα/ribavirin.'] |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.