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['To determine the effect of body mass index (BMI) on clinical and pathological characteristics at time of diagnosis and on risk of biochemical recurrence after radical prostatectomy among Dutch men diagnosed with prostate cancer.', 'In total, 1,116 prostate cancer patients with known BMI, diagnosed between 2003 and 2006, were identified from the population-based cancer registry held by the Comprehensive Cancer Centre East, The Netherlands. Of these, 504 patients underwent a radical prostatectomy. Patients were categorized as normal weight (BMI < 25 kg/m(2)), overweight (BMI 25-30 kg/m(2)), or obese (BMI ≥ 30 kg/m(2)). Multivariable proportional hazards regression models, adjusted for age, prediagnostic PSA levels, and pathological characteristics were used to evaluate BMI as a prognostic factor for biochemical recurrence after radical prostatectomy.', 'Overall, clinical and biopsy characteristics did not significantly differ among BMI groups. Pathological characteristics after radical prostatectomy did not significantly differ among BMI groups, except for tumor stage, which was highest in obese patients (P = 0.017). For patients treated with radical prostatectomy, 5-year risk (95% Confidence Intervals) of biochemical recurrence was 30% (23-37%) for normal weight, 32% (25-39%) for overweight, and 25% (9-41%) for obese patients (log rank P = 0.810). BMI was not an independent prognostic factor for biochemical recurrence in multivariable proportional hazards regression analyses (HR 0.99 per kg/m(2), 95% CI: 0.93-1.06).']
['To explore the influence of concealed penis on the morphology of the corpus cavernosum in rats.', 'Rat models of concealed penis were established by intra-pocket-suture of the root of the penis. Fifty rats were equally assigned to Groups A (2-month) and B (4-month), each further divided into a buried (n = 15) and a normal subgroup (n = 10). Changes in the morphology of the penile cavernous tissue were observed under the light microscope and transmission electron microscope.', 'Compared with Group A, Group B showed significant ultra-structural pathological changes in the corpus cavernosum, including abnormal arrangement of endothelial and smooth muscle cells, massive hyperplasia of interstitial tissues, narrowed cavernous sinus, atrophic smooth muscle cells, degenerated mitochondria, dilated endoplasmic reticula, decreased dense bodies and contractile fibers, and cytoplasmic vacuolization. No significant differences were found in the appearance and weight of the corpus cavernosum between the buried and normal groups (P > 0.05).']
['Hepatic stellate cells (HSC) play a major role in the progression of liver fibrosis.', 'The aim of our study was to investigate whether rat HSC cultured on a nanofiber membrane (NM) retain their quiescent phenotype during both short- and long-term culture and whether activated HSC revert to a quiescent form when re-cultured on NM.', 'Rat HSC cultured for 1\xa0day on plastic plates (PP) were used as quiescent HSC, while cells cultured for 1\xa0week on PP were considered to be activated HSC. Quiescent or activated HSC were subsequently plated on PP or NM and cultured for an additional 4\xa0days at which time their gene expression, stress fiber development, and growth factor production were determined. For long-term culture, HSC were grown on NM for 20\xa0days and the cells then replated on PP and cultured for another 10\xa0days.', 'Expression of marker genes for HSC activation, stress fiber development, and growth factor production were significantly lower in both quiescent and activated HSC cultured on NM than in those cultured on PP. After long-term culture on NM, activation marker gene expression and stress fiber development were still significantly lower in HSC than in PP, and HSC still retained the ability to activate when replated onto PP.']
['Endoscopic injection of dextranomer/hyaluronic acid (Dx/HA) copolymer is an increasingly established treatment for primary vesicoureteral reflux (VUR) in children. We performed a retrospective analysis to assess this treatment for VUR associated with either double ureters or a small kidney.', 'The study included 68 children with duplex ureters and 40 with a small kidney (1 kidney contributing 10% to 35% of total renal function) who underwent endoscopic treatment with Dx/HA copolymer for VUR. Followup consisted of voiding cystourethrography 3 and 12 months after injection. Positive response was defined as reflux grade 0 or I. As many as 2 repeat injections were offered to nonresponders, and those with persistent reflux were referred for open surgery. Long-term clinical followup with renal function testing was continued for 4 to 9 years.', 'A positive response was observed in 63% of children with duplex ureters, with only 17 (25%) patients requiring open surgery. Among children with a small kidney the response rate was 70%, and open surgery was performed in 9 (23%). In both treatment groups a positive response to treatment was sustained throughout the followup period in all cases. The treatment was well tolerated, with no complications associated with the procedure.']
['The preoperative diagnosis of branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be very difficult, since low-risk and high-risk lesions can be difficult to differentiate even after cytological analysis. The purpose of this study was to evaluate the preoperative diagnostic value of endoscopic ultrasonography (EUS) in differentiating low-risk and high-risk IPMNs.', 'We retrospectively identified 36 patients who underwent preoperative EUS for branch duct IPMNs. The pathological diagnosis after surgical resection was low-grade dysplasia (n = 26), moderate dysplasia (n = 1), high-grade dysplasia or carcinoma in situ (n = 5), and invasive carcinoma (n = 4). We divided the patients into two groups: low risk (low-grade dysplasia or moderate dysplasia) and high risk (high-grade dysplasia or carcinoma). We focused on the diameter of the cystic dilated branch duct, the main pancreatic duct, and the mural nodule as measured using the EUS findings.', 'The cystic dilated branch duct diameter (31.5 mm vs. 41.9 mm, P = 0.0225) was significantly correlated with low-risk and high-risk IPMNs, but the main pancreatic duct diameter (5.37 mm vs. 5.44 mm, P = 0.9418) was not significantly correlated with the low-risk and high-risk IPMNs. The mural nodule diameter of the papillary protrusions (4.3 mm vs. 16.4 mm, P < 0.0001) and the width diameter of the mural nodule (5.7 mm vs. 23.2 mm, P < 0.0001) were significantly correlated with low-risk and high-risk IPMNs.']
['To assess subclinical haemostatic activation and clinical variables to predict bleeding during radical retropubic prostatectomy (RP), as haemostatic activation is common in cancer and might be useful for predicting outcomes, but routine coagulation screening does not correlate with bleeding.', 'Clinical data and blood samples were collected from 153 patients (median age 63 years; prostate-specific antigen, PSA, level 5.92 ng/mL) before RP and lymph node dissection. Plasma was assayed for d-dimer and thrombin-antithrombin complex (TAT). Univariable then multivariable analyses were used to identify associations between plasma markers and clinical variables for bleeding and thrombosis.', 'Most patients (77%) were stage T1c and most (76.5%) had organ-confined cancer (< or =pT2). Pathological Gleason scores were < or =6 in 68 (44.4%) and > or =8 in 14 (9%) of the patients. The median (range) estimated blood loss (EBL) was 400 (50-3000) mL, the median decrease in haemoglobin level 3.5 (-0.1, 6.6) g/dL, and eight men (5.2%) required a transfusion. In the univariable analysis, a lower TAT before RP (P < 0.001) and d-dimer level (P = 0.023) correlated with a greater decline in haemoglobin level. The platelet count, international normalised ratio, and activated partial thromboplastin time (aPTT) did not predict the EBL nor change in haemoglobin level; the eight transfused patients had lower platelet counts before RP (P = 0.004). Higher surgical volume predicted a lower EBL (P < 0.001) and lower decrease in haemoglobin (P < 0.05). Multivariable linear regression showed that TAT remained significant for the decrease in haemoglobin, and surgical volume for EBL and decrease in haemoglobin.']
['Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.', 'The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.', 'Serum vitamin D concentrations were measured in 2160 women aged 18-79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.', 'Age was negatively correlated with LTL (r = -0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.']
['Transforming growth factor-β-activated kinase-1 (TAK1) is thought to play a key role in the initiation of Smad-independent TGF-β signaling. This study investigated the role of TAK1 in the epithelial-mesenchymal transition (EMT) lens epithelial cells.', "TAK1 was overexpressed in the HLE B-3 cell line by transfecting TAK1-pcDNA3 and TAK1-binding protein 1 (TAB1)-pcDNA3 plasmids. The expression levels of TAK1, phospho-TAK1, E-cadherin, and fibronectin were detected by Western blot analysis and immunocytofluorescence to analyze the effects of overexpression. The levels of α-SMA and type I collagen were analyzed by real-time PCR. Quantitative data were analyzed by Student's t test or one-way analysis of variance (ANOVA) (multiple comparisons using LSD test).", 'Western blot analysis showed in the TAK1-pcDNA3 plasmids group, expression of TAK1 proteins (1.00±0.03) with a maximum upregulation of approximately 80% at 24 h than it was in the control group (0.19±0.09)(t=8.02, P< 0.01); Western blot analysis showed in the TAB1-pcDNA3 plasmids group, expression of TAB1 proteins (1.00±0.02) with a maximum upregulation of approximately 78% at 24 h than it was in the control group (0.22±0.08)(t=7.63, P<0.01). The levels of E-cadherin/Beta-actin had significant differences among control, overexpression of TAK1 together with TAB1, overexpression of TAK1, and overexpression of TAB1 (1.00±0.02, 0.12±0.03, 0.98±0.09, 0.92±0.08;F=31.03, P<0.01). The levels of fibronectin/Beta-actin had significant differences among control, overexpression of TAK1 together with TAB1, overexpression of TAK1, and overexpression of TAB1 (0.11±0.03, 1.00±0.05, 0.16±0.04, 0.21±0.05;F=35.12, P<0.01). Overexpression of TAK1 with TAB1 resulted in upregulated expression of fibronectin, and downregulated expression of E-cadherin. The expression of E-cadherin was increased and the expression of fibronectin was decreased by TAK1 siRNA and TAK1 chemical inhibitors in the presence of TGF-β2.']
["We are not aware of any previous studies of the relationship between patients' expectations regarding rotator cuff repair and the actual outcome. We hypothesized that preoperative expectations are predictive of the outcome of rotator cuff repair.", 'One hundred and twenty-five patients who underwent unilateral primary repair of a chronic rotator cuff tear were included in the study. All operations were performed by a single surgeon. Each patient prospectively completed the Simple Shoulder Test (SST); the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; three visual analogue scales for shoulder pain, shoulder function, and quality of life; and the Short Form-36 (SF-36) preoperatively and at one year (mean and standard deviation, 54.1 +/- 7.6 weeks) postoperatively. Preoperative expectations were quantified with use of six questions from the Musculoskeletal Outcomes Data Evaluation and Management System (MODEMS) questionnaire.', "Greater preoperative expectations correlated with better postoperative performance on the SST, DASH, each visual analogue scale, and the SF-36 (p values ranging from <0.0001 to 0.03) as well as with greater improvement from the baseline scores on the DASH and SF-36 (p values ranging from <0.0001 to 0.018). A rigorous multivariate analysis controlling for age, gender, smoking, Workers' Compensation status, symptom duration, number of previous operations, number of comorbidities, tear size, and repair technique confirmed that greater expectations were a significant independent predictor of both better performance at one year and greater improvement on the SST, the DASH, each visual analogue scale, and the SF-36 (p values ranging from <0.001 to 0.042)."]
['Nitrogen dioxide (NO2 ), a by-product of combustion produced by indoor gas appliances such as cooking stoves, is associated with respiratory symptoms in those with obstructive airways disease. We conducted a three-armed randomized trial to evaluate the efficacy of interventions aimed at reducing indoor NO2 concentrations in homes with unvented gas stoves: (i) replacement of existing gas stove with electric stove; (ii) installation of ventilation hood over existing gas stove; and (iii) placement of air purifiers with high-efficiency particulate air (HEPA) and carbon filters. Home inspection and NO2 monitoring were conducted at 1 week pre-intervention and at 1 week and 3 months post-intervention. Stove replacement resulted in a 51% and 42% decrease in median NO2 concentration at 3 months of follow-up in the kitchen and bedroom, respectively (P = 0.01, P = 0.01); air purifier placement resulted in an immediate decrease in median NO2 concentration in the kitchen (27%, P < 0.01) and bedroom (22%, P = 0.02), but at 3 months, a significant reduction was seen only in the kitchen (20%, P = 0.05). NO2 concentrations in the kitchen and bedroom did not significantly change following ventilation hood installation. Replacing unvented gas stoves with electric stoves or placement of air purifiers with HEPA and carbon filters can decrease indoor NO2 concentrations in urban homes.']
['Advances in the care of burn injuries have resulted from the efforts of regional patient-based specialist teams at burn care centers.', 'We conducted this study to assess the four-year epidemiology of burn injuries in Rasht, Iran.', 'In this cross-sectional study, medical records of 2274 burn patients, treated at Velayat hospital from January 2007 to December 2010 in Rasht, Iran, were assessed. Age, sex, level of education, occupation, severity and degree of burn, burn surface area, burn cause and outcome of patients were evaluated.', 'In our study the overall mortality rate was 8.7%; 65.7% of patients were men and 34.3% were women. Mean age of patients was 31.47 ± 22.67 years. Mean Total Burn Surface Area (TBSA) was 15.24 ± 18.4. Lowest TBSA was 0.5% and highest TBSA was 100%. Significant associations were observed between age (P = 0.0001), place of residence (P = 0.004), level of education (P = 0.0001), unemployment (P = 0.0001), marital status (P = 0.021), causes of burn (P = 0.0001), TBSA (P = 0.0001) and mortality rate. In our study, no significant difference was observed between age and sex (P = 0.071).']
['Pre-eclampsia is associated with ocular changes. The aim of this study was to examine the macular changes of patients with early-onset severe pre-eclampsia using optical coherence tomography (OCT).', 'This prospective study was performed at Tygerberg Academic Hospital, a secondary and tertiary referral centre in Cape Town, South Africa. Twenty women with early onset pre-eclampsia and 20 women without hypertensive or vascular complications, matched for gestational age, were examined before and after delivery.', 'There was a trend showing a positive correlation between increased central retinal thickness and increasing proteinuria in patients with pre-eclampsia antepartum (left eye r=0.52, p=0.04) and postpartum (left eye r=0.60, p=0.01). A positive correlation between average central 1mm and proteinuria was noted antepartum (left eye r=0.63, p=0.01) and postpartum (right eye r=0.52, p=0.03). There were no significant correlations between blood pressure and any of the retinal parameters. Two of the 23 patients with pre-eclampsia developed serous retinal detachments, both of which resolved completely postpartum.']
['Fascin is an actin-bundling protein critical for tumor invasion. TGF-β could induce fascin expression in gastric cancer cells. In this study, we attempted to explore the role of p-smad3L in the expression of fascin induced by TGF-β in gastric cancer cells.', 'Pseudopodia were evaluated by immunofluorescence. Fascin expression was detected by RT-PCR and western blot. Smad3 siRNA was used to repress the endogenous smad3. The phosphorylations of smad3 linker region at sites s204, s208 and s213 were detected by western blot. The fascin promoter reporter activity was measured by dual luciferase assay.', 'TGF-β could increase the formation of pseudopodia and the expression of fascin in gastric cancer cells. Smad3 depletion abrogated the expression of fascin induced by TGF-β. The phosphorylation of smad3 linker region at serine 204, 208 and 213 was enhanced in gastric cancer cells after TGF-β treatment. The fascin promoter reporter activity was significantly enhanced with TGF-β treatment in both wild-type Smad3 group and Smad3EPSM group (P<0.05). Furthermore, the fascin promoter reporter activity in the wild-type Smad3 transfectant cells was significantly higher than that in Smad3EPSM cells (P<0.05).']
['Sensory conflicts in the vestibular system lead to motion sickness of which space motion sickness (SMS) is a special case. SMS affects up to 70% of the astronauts during the first 3 days in space. The search for effective countermeasures has led to several nonpharmacological and pharmacological approaches. The current study focuses on the effects of lorazepam (1 mg), meclizine (25 mg), promethazine (25 mg), and scopolamine (0.4 mg) on the vestibular system, with special focus on the canal and otolith functions separately.', 'The study had a placebo-controlled, single blind, repeated measures design. Sixteen healthy volunteers were subjected to a total of 7 test sessions, the first and last being without intake of medication. Semicircular canal function was evaluated by means of electronystagmography and otolith function with unilateral centrifugation. The horizontal semicircular canal function was characterized by the vestibulo-ocular reflex (VOR) gain measured during earth vertical axis rotation as well as the total caloric response. The function of the utricles was represented by the utricular sensitivity, reflecting the ocular counter roll relative to the virtual induced head tilt.', 'Promethazine significantly decreased the semicircular canal and utricular parameters. Both scopolamine and lorazepam caused only a decrease in the utricular sensitivity, whereas meclizine only decreased the semicircular canal-induced VOR gain.']
["Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, and physical endurance and reduces fat accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5' AMP-activated protein kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPKalpha1 or -alpha2 to determine whether the metabolic effects of resveratrol are mediated by AMPK.", 'Mice deficient in the catalytic subunit of AMPK (alpha1 or alpha2) and wild-type mice were fed a high-fat diet or high-fat diet supplemented with resveratrol for 13 weeks. Body weight was recorded biweekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro.', 'Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKalpha1(-/-) mice. In the absence of either AMPKalpha1 or -alpha2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis, and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD-to-NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly.']
['Emotional abnormalities are prominent features of schizophrenia. While the capacity for emotions is essential to social adaptation, little is known about the role of emotional experience in the social dysfunction observed in schizophrenia.', 'This study examined the contribution of emotional experience, neurocognition, and social cognition to functional outcome in schizophrenia.', 'Self-reported emotional experience (anhedonia, affect intensity, and emotion frequency) was assessed in 33 stable schizophrenic/schizoaffective patients and 33 healthy controls. Symptoms, neurocognition, social cognition, and functional outcome were also assessed.', 'Patients and controls exhibited good internal reliability on all self-report scales, except for negative affect intensity. Patients reported equally intense but less frequent positive emotions, more intense and frequent negative emotions, and more anhedonia. Results of hierarchical regression analyses showed that emotional experience accounted for significant amounts of variance of social adjustment independent of neurocognition and social cognition.']
['Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model.', 'Tartrate resistant acid phosphatase (TRAP) staining was employed to evaluate osteoclast formation. mRNA level of transcription factor and protein levels of signaling molecules were determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. Effect of HRT or fHRT on OVX-induced bone loss was evaluated using OVX rats orally administered HRT, or fHRT with 300 mg/kg for 12 weeks. Micro-CT analysis of femora was performed to analyze bone parameter.', 'HRT or fHRT treatment significantly decreased TRAP activity and the number of TRAP positive multinuclear cells on osteoclastogenesis. Interestingly, these inhibitory effects of HRT were enhanced by fermentation. Furthermore, fHRT significantly inhibited mRNA and protein expression of nuclear factor of activated T cells cytoplasmic 1, which leads to down-regulation of NFATc1-regulated mRNA expressions such as TRAP, the d2 isoform of vacuolar ATPase V(0) domain, and cathepsin K. Administration of fHRT significantly inhibited the decrease of bone mineral density, and improved bone parameter of femora more than that of HRT and vehicle in OVX rats.']
['The present study was undertaken to determine if tyrosine phosphorylation signal transduction pathways, which are known to be activated in polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS), play a role in priming of PMN oxidative burst and protection of PMN from apoptosis by LPS, and to determine if an interface between these two signaling pathways exists.', 'PMN were combined with or without 10-fold serial dilutions (0.1 ng-1 microgram/ml) of LPS and incubated at 37 degrees C/5% CO2. After 24 h PMN apoptosis was assessed using fluorescence microscopy and DNA agarose gel electrophoresis. Additional PMN were pretreated with the tyrosine kinase inhibitors genistein and herbamycin A before addition of LPS. Tyrosine phosphorylation was detected by immunoblotting. Oxidant production was quantitated by following the oxidation of a chromophore to its fluorescent product.', 'LPS delayed the onset of apoptosis and prolonged the survival of PMN in a dose-dependent fashion. Both tyrosine kinase inhibitors blocked the protective effect of LPS on PMN apoptosis; however, only genistein blocked the priming effect of LPS on PMN oxidative burst.']
['(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism.', 'The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients.', 'Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n\u2009=\u20098) or KET-NRs (n\u2009=\u200913) based upon the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a ≥50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry.', 'Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02\u2009±\u20090.21 μM) than in KET-NRs (4.68\u2009±\u20090.81 μM), p\u2009<\u20090.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r\u2009=\u20090.77, p\u2009<\u20090.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2\u2009±\u20099.6 μM vs 242.9\u2009±\u20095.6 μM, respectively; p\u2009<\u20090.0001).']
['The current standard of care for Glioblastoma Multiforme (GBM) consists of fractionated focal irradiation with concomitant temozolomide (TMZ) chemotherapy. A promising strategy to increase the efficacy of TMZ is through interference with the DNA damage repair machinery, by poly(ADP-ribose) polymerase protein inhibition(PARPi). The objective of the present study was to investigate the therapeutic benefit of combination therapy in patient-derived glioma stem-like cells (GSC).', 'Combination therapy feasibility was tested on established GBM cell lines U373 and T98. We developed an in vitro drug-screening assay based on GSC cultures derived from a panel of primary patient tissue samples (n\u2009=\u200920) to evaluate the effect of PARPi (ABT-888) monotherapy and combination therapy with TMZ. Therapeutic effect was assessed by viability, double stranded breaks, apoptosis and autophagy assays and longitudinal microscopic cell monitoring was performed. O-6-methylguanine-DNA methyltransferase (MGMT) status was determined by methylation assay and protein expression by western blots.', 'PARPi monotherapy was found to decrease viability by more than 25% in 4 of the 20 GSCs (20%) at 10 μM. TMZ monotherapy at 50 μM and 100 μM was effective in 12 and 14 of the 20 GSCs, respectively. TMZ resistance to 100 μM was found in 7 of 8 MGMT protein positive cultures. Potentiation of TMZ therapy through PARPi was found in 90% (n\u2009=\u200920) of GSCs, of which 6 were initially resistant and 7 were sensitive to TMZ monotherapy. Increased induction of double stranded breaks and apoptosis were noted in responsive GSCs. There was a trend noted, albeit statistically insignificant, of increased autophagy both in western blots and accumulation of autophagosomes.']
['Cystic fibrosis results from mutations in the ABC transporter CFTR (cystic fibrosis transmembrane conductance regulator), which functions as a cAMP-regulated anion channel. The most prevalent mutation in CFTR, the Phe(508) deletion, results in the generation of a trafficking and functionally deficient channel. The cellular machineries involved in modulating CFTR trafficking and function have not been fully characterized. In the present study, we identified a role for the COPI (coatomer protein I) cellular trafficking machinery in the development of the CFTR polypeptide into a functional chloride channel. To examine the role of COPI in CFTR biosynthesis, we employed the cell line ldlF, which harbours a temperature-sensitive mutation in epsilon-COP, a COPI subunit, to inhibit COPI function and then determined whether the CFTR polypeptide produced from the transfected gene developed into a cAMP-regulated chloride channel.', 'When COPI was inactivated in the ldlF cells by an elevated temperature pulse (39 degrees C), the CFTR polypeptide was detected on the cell surface by immunofluorescence microscopy and cell-surface biotinylation. Therefore, CFTR proceeded upstream in the secretory pathway in the absence of COPI function, a result demonstrated previously by others. In contrast, electrophysiological measurements indicated an absence of cAMP-stimulated chloride efflux, suggesting that channel function was impaired. In comparison, expression of CFTR at the same elevated temperature (39 degrees C) in an epsilon-COP-rescued cell line [ldlF(ldlF)], which has an introduced wild-type epsilon-COP gene in addition to the mutant epsilon-COP gene, showed restoration of cAMP-stimulated channel activity, confirming the requirement of COPI for channel function.']
['Acute pancreatitis (AP) is an inflammatory response to pancreatic injury that is clinically classified as mild AP or severe AP, depending on specific criteria. Rahman and colleagues [Gastroenterology 2004;126:1312-1322] reported that genetic variation in the glutathione S-transferase theta-1 gene (GSTT-1) is associated with susceptibility and severity of AP in England. Our aim was to determine whether the same GSTT-1 polymorphism affects the severity of AP in a population from Pittsburgh, Pa., USA.', 'Ninety-one consecutive patients with AP (19 severe) were prospectively evaluated. The GSTT-1 haplotypes were determined by PCR amplification in all patients and 268 controls. The resulting genotypes were classified as functional (GSTT-1*A/*A or *A/null) and nonfunctional (GSTT-1 null/null) phenotypes.', 'The relative frequencies of functional GSTT-1 phenotypes were similar in subjects with severe AP (15 of 19, 78.9%) and mild AP (61 of 72, 84.7%; p = 0.54) and in the controls (228 of 268, 85.1%; p = 0.66). Furthermore, the GSTT-1 functional and nonfunctional phenotypes were not associated with serum C-reactive protein levels (11.9 vs. 7.3 mg/dl; p = 0.19), interleukin-6 levels (74 vs. 60 pg/ml; p = 0.9), APACHE II scores (7 vs. 9; p = 0.26), or 48-hour Ranson scores (1 vs. 1; p = 0.63).']
['Transcription-induced chimerism, a mechanism involving the transcription and intergenic splicing of two consecutive genes, has recently been estimated to account for approximately 5% of the human transcriptome. Despite this prevalence, the regulation and function of these fused transcripts remains largely uncharacterised.', 'We identified three novel transcription-induced chimeras resulting from the intergenic splicing of a single RNA transcript incorporating the two neighbouring 3p21.3 tumour suppressor locus genes, RBM6 and RBM5, which encode the RNA Binding Motif protein 6 and RNA Binding Motif protein 5, respectively. Each of the three novel chimeric transcripts lacked exons 3, 6, 20 and 21 of RBM6 and exon 1 of RBM5. Differences between the transcripts were associated with the presence or absence of exon 4, exon 5 and a 17 nucleotide (nt) sequence from intron 10 of RBM6. All three chimeric transcripts incorporated the canonical splice sites from both genes (excluding the 17 nt intron 10 insertion). Differential expression was observed in tumour tissue compared to non-tumour tissue, and amongst tumour types. In breast tumour tissue, chimeric expression was associated with elevated levels of RBM6 and RBM5 mRNA, and increased tumour size. No protein expression was detected by in vitro transcription/translation.']
['H11 kinase is a serine/threonine kinase preferentially expressed in the heart, which participates in cardiac cell growth and also in cytoprotection during ischemia. A cardiac-specific transgenic mouse overexpressing H11 kinase (2- to 7-fold protein increase) has been generated, and is characterized by cardiac hypertrophy with preserved function and protection against irreversible damage during ischemia/reperfusion. In this study, we tested whether H11 kinase also participates in the metabolic adaptation to cardiac hypertrophy and ischemia.', 'A yeast two-hybrid screen using H11 kinase as a bait in a human heart library revealed a potential interaction with phosphoglucomutase (PGM), the enzyme converting glucose 6-phosphate into glucose 1-phosphate. Interaction between H11 kinase and PGM was confirmed by co-immunoprecipitation. To test the biochemical relevance of this interaction, PGM activity was measured in the heart from wild type and transgenic mice, showing a 20% increase of Vmax in the transgenic group, without change in KM. Glycogen content was increased proportionately to the expression of the transgene, reaching a 40% increase in high-expression transgenic mice (7-fold increase in H11 kinase protein) versus wild type (p < 0.01). Increased incorporation of glucose into glycogen was coupled to a 3-fold increase in the protein expression of the glucose transporter GLUT1 in plasma membrane of transgenic mice (p < 0.01).']
['Larynx cancer is the most common form of head and neck squamous cell carcinoma (HNSCC). Radiotherapy is a major treatment modality and is implicated in the possible formation of second primary tumours (SPT). The aims of this retrospective study were to establish the incidence of SPTs and their correlation with previous radiotherapy and to establish overall survival and the SPT diagnostic time lag from the index tumour according to subtype as well as radiotherapy status.', 'In a retrospective study of 987 patients with larynx SCCs (1967-2004) associations between radiotherapy, diagnosis of SPTs, median SPT diagnostic time lag, disease-free survival and overall survival were analysed.', 'In total, 184 (18.6%) patients developed metachronous SPTs with an overall survival of 93.0 (standard error 6.8 months). One hundred and seventy (92.4%) underwent radiotherapy, whereas 14 (7.6%) patients were not exposed to radiotherapy. No significant increased incidence of SPT was shown in the radiotherapy group. A statistically non-significant increase in SPT diagnostic time lag trend was noted for both HNSCC SPTs (radiotherapy vs non-radiotherapy; 76.0 [standard error 6.7] vs 50.0 [standard error 23.0]) and lung SPTs (45.0 [standard error 12.1] vs 24.0 [standard error 4.9]) months.']
['To assess whether radiographic findings predict outcomes among children hospitalized with pneumonia.', "This retrospective study included children <18 years of age from 4 children's hospitals admitted in 2010 with clinical and radiographic evidence of pneumonia. Admission radiographs were categorized as single lobar, unilateral or bilateral multilobar, or interstitial. Pleural effusions were classified as absent, small, or moderate/large. Propensity scoring was used to adjust for potential confounders, including need for supplemental oxygen, intensive care, and mechanical ventilation, as well as hospital length of stay and duration of supplemental oxygen.", 'There were 406 children (median age, 3 years). Infiltrate patterns included: single lobar, 61%; multilobar unilateral, 13%; multilobar bilateral, 16%; and interstitial, 10%. Pleural effusion was present in 21%. Overall, 63% required supplemental oxygen (median duration, 31.5 hours), 8% required intensive care, and 3% required mechanical ventilation. Median length of stay was 51.5 hours. Compared with single lobar infiltrate, all other infiltrate patterns were associated with need for intensive care; only bilateral multilobar infiltrate was associated with need for mechanical ventilation (adjusted odds ratio [aOR]: 3.0, 95% confidence interval [CI]: 1.2-7.9). Presence of effusion was associated with increased length of stay and duration of supplemental oxygen; only moderate/large effusion was associated with need for intensive care (aOR: 3.2, 95% CI: 1.1-8.9) and mechanical ventilation (aOR: 14.8, 95% CI: 9.8-22.4).']
['Superparamagnetic iron oxide nanoparticles (IONPs) have been used as magnetic resonance imaging contrast agents for various research and diagnostic purposes, such as the detection of neuroinflammation and blood-brain-barrier integrity. As the central resident macrophage-like cells, microglia are responsible for managing foreign agents invading the CNS. The present study investigated the direct effect of IONPs on the production of pro-inflammatory cytokines by murine microglia stimulated with lipopolysaccharide (LPS).', 'Primary murine microglial cells were pretreated with IONPs (1-50 μg Fe/mL) for 30 min and then stimulated with LPS (100 ng/mL) for 24 h. Confocal microscopy is used to visualize the intracellular IONP distribution and secretory lysosomes after staining with LysoTracker and Rab27a, respectively. The production of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was quantified by ELISA. The activity of IL-1β converting enzyme (ICE) and TNF-α converting enzyme (TACE) was measured by fluorescent microplate assay using specific substrates. The lysosomal number, alkalinity, permeability and cathepsin B activity were determined by flow cytometry with ectodermal dysplasia-1, lysosensor and acridine orange staining, and using cathepsin B specific substrate, respectively.', 'Confocal imaging revealed that IONPs were markedly engulfed by microglia. Exposure to IONPs attenuated the production of IL-1β, but not TNF-α. Concordantly, the activity of ICE, but not the TACE, was suppressed in IONP-treated cells. Mechanistic studies showed that IONPs accumulated in lysosomes and the number of lysosomes was increased in IONP-treated cells. In addition, exposure to IONPs increased lysosomal permeability and alkalinity, but decreased the activity of cathepsin B, a secretory lysosomal enzyme involved in the activation of ICE.']
['Increased platelet counts has been reported to be a sequela of pancreas transplantation and even incriminated in the increased rate of thrombosis of pancreas grafts. The aim of the study was to measure the platelet counts after simultaneous kidney-pancreas transplantations compared to kidney transplants alone in diabetic patients.', 'This retrospective case-control study included 57 patients who received simultaneous pancreas and kidney transplants (SPK), from 1985 to 2000 and had functioning grafts for more than 1 month. The control patients were 38 type I diabetic recipients of kidney transplants alone (KTA), matched for sex, era, and immunosuppression. The platelet counts, white cell counts, and hemoglobin were analyzed on the preoperative day, weeks 1 to 6, 3 months, 6 months and 1 year.', 'The mean age of the SPK group was significantly lower than that of the KTA group (39.8+/-8.3 versus 48.2+/-11.7, P<.01). Significantly higher platelet counts were demonstrated during weeks 2 to 6, which persisted at 3 months and at 1 year among the SPK compared to the KTA group. Although significantly higher white cell counts and lower hemoglobin levels were seen among the SPK versus KTA group during weeks 3 to 6, it did not persist after 3 months.']
['Sorafenib is a potent inhibitor against Raf kinase and several receptor tyrosine kinases that has been approved for the clinical treatment of advanced renal and liver cancer. Combining sorafenib with other agents has been shown to improve its antitumour efficacy by not only reducing the toxic side effects but also preventing primary and acquired resistance to sorafenib. We have previously observed that tetrandrine exhibits potent antitumour effects in human hepatocellular carcinoma. In this study, we investigated the synergistic antitumour activity of sorafenib in combination with tetrandrine.', 'This was a two-part investigation that included the in vitro effects of sorafenib in combination with tetrandrine on cancer cells and the in vivo antitumour efficacy of this drug combination on tumour xenografts in nude mice.', 'Combined treatment showed a good synergistic antitumour effect yet spared non-tumourigenic cells. The potential molecular mechanism may be mainly that it activated mitochondrial death pathway and induced caspase-dependent apoptosis in the cancer cells. Accumulation of intracellular reactive oxygen species (ROS) and subsequent activation of Akt may also be involved in apoptosis induction.']
['Severe alopecia areata (AA) may have a chronic relapsing course and is often resistant to current treatments.', 'The aim of our study was to evaluate whether topical immunotherapy with squaric acid dibutylester (SADBE) is able to improve the course of severe AA and to reduce the severity of relapses.', "Fifty-four patients affected by severe AA treated with SADBE who were followed for a period of at least 2 years were selected as the study group. Data collected were compared with those of a matched control group of 54 patients who did not receive any treatment. Student's t-test, analysis of variance (ANOVA) and Pearson's chi-squared test were utilized for data analysis.", 'At the end of therapy, in comparison with the control group, the treatment group showed a statistically significant (p < 0.001) improvement. At follow-up, there was no significant change in relapse rate (treated 44% vs control 52%). However, relapses in the treated group were significantly less severe compared with the control group (p < 0.001).']
['Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats.', 'Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32.', 'Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT.']
['The possibility to prevent nucleus pulposus-induced structural changes of the dorsal root ganglion (DRG) by selective tumor necrosis factor-alpha (TNF-alpha) inhibition was assessed in an experimental model in the rat spine.', 'To evaluate the role of TNF-alpha in the mediation of nucleus pulposus-induced structural changes by using selective inhibition and to confirm the effect of TNF-alpha inhibitor at the point of histologic findings.', 'TNF-alpha is known to be released from the nucleus pulposus, and has been suggested to play a key role in chemical damage of the adjacent nerve tissue. The TNF-alpha inhibitor prevents the reduction of nerve conduction velocity and may limit the nerve fiber injury, intracapillary thrombus formation, and intraneural edema formation caused by nucleus pulposus. However, there is no report on the effect of the inhibitor regarding histologic findings and the appearance of the TNF-alpha in the DRG exposed to nucleus pulposus.', '1) Rats were treated with an intraperitoneal injection of infliximab. Nucleus pulposus from the disc was obtained 1, 3, 7, 14, and 21 days after the injection. The TNF-alpha-positive cells were observed using immunohistochemistry. 2) Disc herniation of the nucleus pulposus was made on the L4-L5 disc in rats. Two groups were treated with selective TNF-alpha inhibitor 1 day before or 3 hours after surgery. The other group received no TNF-alpha inhibitor. The L4 DRG was resected 1, 3, 7, 14, and 21 days after surgery. The specimens were processed for hematoxylin and eosin staining and immunohistochemistry using rabbit antisera to TNF-alpha. The histologic findings and TNF-alpha-positive cells were observed by light microscopy.', '1) While positively stained immunoreactive TNF-alpha appeared between 7 and 21 days, no immunoreactive TNF-alpha was observed 1 and 3 days after injection in the nucleus pulposus. 2) The histologic changes of the DRG caused by nucleus pulposus were smaller in the infliximab treatment group than those in the nontreatment group. The number of immunoreactive TNF-alpha cells was high 1 and 3 days after surgery in the DRGs of disc herniation rats that were treated without an injection of the inhibitor, low on day 7 and 14, and very low on day 21 after surgery. No immunoreactive TNF-alpha was observed in the DRGs of the TNF-alpha inhibitor treatment groups on day 1, 3, and 21 after surgery. Weakly stained cells were sometimes observed in rats at day 7 and 14 after surgery.']
['Test computer-assisted modeling techniques using prehospital vital signs of injured patients to predict emergency transfusion requirements, number of intensive care days, and mortality, compared to vital signs alone.', 'This single-center retrospective analysis of 17,988 trauma patients used vital signs data collected between 2006 and 2012 to predict which patients would receive transfusion, require 3 or more days of intensive care, or die. Standard transmitted prehospital vital signs (heart rate, blood pressure, shock index, and respiratory rate) were used to create a regression model (PH-VS) that was internally validated and evaluated using area under the receiver operating curve (AUROC). Transfusion records were matched with blood bank records. Documentation of death and duration of intensive care were obtained from the trauma registry.', 'During the course of their hospital stay, 720 of the 17,988 patients in the study population died (4%), 2,266 (12.6%) required at least a 3-day stay in the intensive care unit (ICU), 1,171 (6.5%) required transfusions, and 210 (1.2%) received massive transfusions. The PH-VS model significantly outperformed any individual vital sign across all outcomes (average AUROC = 0.82), The PH-VS model correctly predicted that 512 of 777 (65.9%) and 580 of 931 (62.3%) patients in the study population would receive transfusions within the first 2 and 6\xa0hours of admission, respectively.']
['The complement system, a key component that links the innate and adaptive immune responses, has three pathways: the classical, lectin, and alternative pathways. In the present study, we have analyzed the levels of various complement components in blood samples from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients and found that the level of complement activation is associated with disease severity.', 'Patients with DHF had lower levels of complement factor 3 (C3; p = 0.002) and increased levels of C3a, C4a and C5a (p<0.0001) when compared to those with the less severe form, DF. There were no significant differences between DF and DHF patients in the levels of C1q, immunocomplexes (CIC-CIq) and CRP. However, small but statistically significant differences were detected in the levels of MBL. In contrast, the levels of two regulatory proteins of the alternative pathway varied widely between DF and DHF patients: DHF patients had higher levels of factor D (p = 0.01), which cleaves factor B to yield the active (C3bBb) C3 convertase, and lower levels of factor H (p = 0.03), which inactivates the (C3bBb) C3 convertase, than did DF patients. When we considered the levels of factors D and H together as an indicator of (C3bBb) C3 convertase regulation, we found that the plasma levels of these regulatory proteins in DHF patients favored the formation of the (C3bBb) C3 convertase, whereas its formation was inhibited in DF patients (p<0.0001).']
['Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer.', 'Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology.', 'The median overall survival of the study population was 2.2\xa0years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5\xa0ng/mL, the median overall survival was 3.0\xa0years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level <11.5\xa0ng/mL and 1.3\xa0years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5\xa0ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4).']
['Fig trees (Moraceae) have remarkable enclosed inflorescences called figs or syconia. The flowers are pollinated by host-specific fig wasps that enter the fig to lay their eggs. This nursery pollination system is one of the most studied of tropical mutualism interactions, but the source of the volatiles that attract fig wasps to their specific host figs has not been confirmed. The fragrance is the basis of host selection and, therefore, of reproductive isolation among sympatric Ficus species. This study locates and characterizes the glands likely to be responsible for pollinator attraction and also protection from herbivory in the figs of nine Ficus species representing all the major lineages within the genus.', 'Figs with receptive pistillate flowers were examined using light and scanning electron microscopy. Tests for histolocalization of substances were employed to detect glandular activity throughout the figs.', 'A great diversity of glands is found throughout the fig, and for the first time, the sites producing fragrances are identified. Scent glands are present on the ostiolar bracts and the outer layers of the fig receptacle. Laticifers and phenolic-producing idioblasts, epidermis, and trichomes associated with fig protection occur on the ostiolar bracts, the fig receptacle, and floral tissues.']
['Recently, the focus on neuroinflammation is intensified as its complex pathophysiological role has emerged in multiple central nervous system(CNS) disorders. Chotosan (CTS), known as a traditional herbal formula, is often utilized to treat relevant nervous system diseases in China. It was demonstrated effectively to alleviate cognitive deficit associated with aging, diabetes, hypoperfusion and cerebral ischemia. However, the effects of CTS on Aβ1-42-induced cognitive dysfunction remain unclear. Here, we further investigated the effects of chotosan on memory performance, neuroinflammation and apoptotic responses.', 'The learning and memory ability is evaluated by Morris water maze (MWM) task and Y-maze test following intrahippocampal infusion of aggregated Aβ1-42. The expression level of toll-like receptor 4 (TLR-4), NF-κB p65, Bcl-2 and Bax was examined by Western blot. TLR-4 level is also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the generation of inflammatory mediators. The caspase-3 activity is analyzed by commercial kits.', 'The repeated treatment with CTS (750mg/kg or 375mg/kg per day) for 3 weeks significantly restored Aβ1-42-induced memory impairment in mice. Meanwhile, this treatment also remarkably reduced TLR-4 and NF-κB p65 expression accompanying with the diminished release of proinflammatory cytokines including TNF-α and IL-1β in hippocampus. The neuronal apoptosis is also inhibited as evidenced by increase in Bcl-2/Bax ratio and decrease in pro-apoptotic protein caspase-3 activity compared to that of the model mice.']
['Interferon alpha (IFNα) is widely used for the treatment of viral hepatitis but substantial toxicity hampers its clinical use. In this work, we aimed at improving the efficacy of IFNα therapy by increasing the IFNα half-life and providing liver tropism. We selected apolipoprotein A-I (ApoA-I) as the stabilizing and targeting moiety. We generated plasmids encoding IFNα, albumin bound to IFNα (ALF), or IFNα linked to ApoA-I (IA) and mice were treated either by hydrodynamic administration of the plasmids or by injection of the corresponding recombinant proteins or high-density lipoproteins containing IA. The plasma half-life of IA was intermediate between IFNα and ALF. IA was targeted to the liver and induced higher hepatic expression of interferon-stimulated genes than IFNα or even ALF. IA exhibits stronger in vivo antiviral activity than IFNα and the hematologic cytopenic effects of IA are milder than those observed when using IFNα or ALF. In contrast to IFNα, IA does not cause activation-dependent cell death of lymphocytes in vitro. Accordingly, in vivo studies showed that IA boosts T-cell immune responses more efficiently than IFNα or ALF. The difference in immunostimulatory activity between IFNα and IA disappears in scavenger receptor class B type I (SR-BI) knockout mice, suggesting that crosstalk between SR-BI and IFNα receptor is essential for enhanced induction of cytotoxic T cells by IA.']
['Tissue exudates contain low levels of serum complement proteins, and their regulatory effects on prostate cancer progression are largely unknown. We examined specific serum complement components in coordinating the activation of tumor suppressors p53 and WWOX (also named FOR or WOX1) and kinases ERK, JNK1 and STAT3 in human prostate DU145 cells.', 'DU145 cells were cultured overnight in 1% normal human serum, or in human serum depleted of an indicated complement protein. Under complement C1q- or C6-free conditions, WOX1 and ERK were mainly present in the cytoplasm without phosphorylation, whereas phosphorylated JNK1 was greatly accumulated in the nuclei. Exogenous C1q rapidly restored the WOX1 activation (with Tyr33 phosphorylation) in less than 2 hr. Without serum complement C9, p53 became activated, and hyaluronan (HA) reversed the effect. Under C6-free conditions, HA induced activation of STAT3, an enhancer of metastasis. Notably, exogenous C1q significantly induced apoptosis of WOX1-overexpressing DU145 cells, but not vehicle-expressing cells. A dominant negative and Y33R mutant of WOX1 blocked the apoptotic effect. C1q did not enhance p53-mediated apoptosis. By total internal reflection fluorescence (TIRF) microscopy, it was determined that C1q destabilized adherence of WOX1-expressing DU145 cells by partial detaching and inducing formation of clustered microvilli for focal adhesion particularly in between cells. These cells then underwent shrinkage, membrane blebbing and death. Remarkably, as determined by immunostaining, benign prostatic hyperplasia and prostate cancer were shown to have a significantly reduced expression of tissue C1q, compared to age-matched normal prostate tissues.']
['Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we showed that delayed chemotherapy-induced nausea and vomiting control could be potentially improved by skipping the administration of a 5-hydroxytryptamine 3 (5-HT3) antagonist on day 2. We report here a trial confirming our previous findings.', 'A phase III randomized placebo-controlled trial was conducted in which patients received intravenously ondansetron 16 mg, dexamethasone 20 mg, and ranitidine 50 mg before highly/moderately emetogenic chemotherapy (day 1). Starting on day 2, all patients received metoclopramide 10 mg per oral every 8 hours (days 2, 3, and 4), dexamethasone 8 mg daily (days 2 and 3), and ranitidine 150 mg every 12 hours (days 2 and 3). Patients were randomized to receive either granisetron 0.5 mg per oral (days 2 and 3) (group A) or placebo instead of granisetron on day 2 and granisetron 0.5 mg on days 3 and 4 (group B).', 'Seventy-three patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of chemotherapy-induced nausea and vomiting in group A (P = 0.04). Complete delayed protection from nausea and vomiting (DCPNV) from day 2 to 5 was similar in both groups (30% vs. 32%; P = 0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea and vomiting (P = 0.001) and study group (P = 0.06) were independently associated with DCPNV. Selecting patients who achieved acute complete protection from nausea and vomiting, we observed that group B had a superior DCPNV (85% vs. 50%, P = 0.02).']
['The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. The discovery of drugs for the treatment of immediate-type allergic disease is a very important subject in human health. Isodon japonicus Hara (Labiatae) (IJAE) has been used for centuries as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of IJAE on the immediate-type allergic reaction and studied its possible mechanisms of action, focusing on the mast cell-mediated allergic reaction.', 'IJAE extracts were anally administered to mice for high and fast absorption. Compound 48/80-induced mortality and compound 48/80- or immunoglobulin E (IgE)-induced histamine release were measured to evaluate the antiallergic effects of IJAE. The effect of IJAE on the model of local allergic reaction in vivo, passive cutaneous anaphylaxis (PCA), was investigated. The production of tumor necrosis factor-alpha (TNF-alpha) was measured by Western blotting.', 'IJAE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. IJAE decreased the PCA reaction activated by anti-dinitrophenyl (DNP) IgE antibody. IJAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, IJAE decreased the production of TNF-alpha in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells.']
['Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.', 'We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.', 'We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.']
['Stem cell factor (SCF), and its receptor (c-kit) play key roles in the expansion and differentiation of hematopoietic progenitor cells, in melanoblasts and primordial germ cells, making it possible that SCF and c-kit are involved in neoplastic processes deriving from these cells. C-kit has been described to be expressed at different levels in neuroblastoma and in soft tissue sarcoma of neuroectodermal origin, and seems to be required for survival processes. In this study we investigate how c-kit expression is regulated and whether a SCF autocrine loop is essential for survival of sarcoma cell lines.', 'C-kit modulation and internalization was evaluated incubating cells with rhSCF. Cell differentiation and proliferation experiments were performed to test whether c-kit expression is related to cell cycle progression or to differentiation processes. Cell cultures were treated with neutralizing antibody and antisense oligonucleotides in order to assess the possible significance of the SCF autocrine loop.', 'In vitro SCF stimulation induces c-kit down-regulation; this phenomenon could be connected with receptor internalization, and new protein synthesis is necessary for its re-expression. The cell proliferation arrest in G0/G1 does not modify c-kit expression while down-regulation of c-kit was demonstrated after cells had been treated with differentiating agents. SCF neutralization does not influence either the S phase or apoptosis in sarcoma cell lines.']
['COG0523 proteins are, like the nickel chaperones of the UreG family, part of the G3E family of GTPases linking them to metallocenter biosynthesis. Even though the first COG0523-encoding gene, cobW, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family.', 'Based on a combination of comparative genomics, literature and phylogenetic analyses and experimental validations, the COG0523 family can be separated into at least fifteen subgroups. The CobW subgroup involved in cobalamin synthesis represents only one small sub-fraction of the family. Another, larger subgroup, is suggested to play a predominant role in the response to zinc limitation based on the presence of the corresponding COG0523-encoding genes downstream from putative Zur binding sites in many bacterial genomes. Zur binding sites in these genomes are also associated with candidate zinc-independent paralogs of zinc-dependent enzymes. Finally, the potential role of COG0523 in zinc homeostasis is not limited to Bacteria. We have predicted a link between COG0523 and regulation by zinc in Archaea and show that two COG0523 genes are induced upon zinc depletion in a eukaryotic reference organism, Chlamydomonas reinhardtii.']
['To correlate the concentration of nitrite (the stable metabolite of nitric oxide) in seminal plasma with sperm number and motility, leukocytospermia, and sperm culture.', 'Prospective study.', 'Academic research institution.', 'Seventy normozoospermic or dyspermic men enrolled in an artificial insemination/in vitro fertilization program.', 'Semen samples (n = 70) were checked for sperm concentration, total sperm count, sperm motility, seminal leukocyte concentration, and sperm culture; similarly, the concentration of nitrite in seminal plasma was measured by Griess reaction.', 'Measurement of nitrite concentration in seminal plasma and its correlation with sperm concentration, total sperm count, sperm motility, leukocytospermia, and sperm culture.', 'The concentration of nitrite in seminal plasma does not correlate with sperm concentration, total sperm count, or with the proportion of immotile or rapid-forward motile spermatozoa. Moreover, the concentration of nitrite in seminal plasma is not significantly increased when sperm culture is positive, nor does it correlate with leukocyte concentration in semen.']
['Fast inward Na current (I(Na)) carried by the voltage-gated Na channel (Na(V)1.5) is critical for action potential (AP) propagation and the rapid upstroke of the cardiac AP. In addition, a small fraction of Na(V)1.5 channels remains open throughout the plateau of the AP, and this current is termed as late I(Na). In patients with mutant Na(V)1.5-based congenital long Q-T (LQT) syndrome, mutant channels pass more late I(Na) compared to wild-type channels in unaffected patients. Although LQT mutant Na(V)1.5 channels are well studied, there is no careful evaluation of the effects of cardiac APs on early and late current. This is important with the recent documentation of nonequilibrium I(Na).', 'We measured AP-stimulated I(Na) through Na(V)1.5 wild-type and two LQT mutant channels (DeltaKPQ and N1325S). Three distinct AP morphologies were used: human embryonic stem cell-derived cardiac myocyte (hES-CM) APs with a relatively slow upstroke and canine endocardial and epicardial ventricular myocytes with rapid upstrokes.', 'All three APs elicited both early and late I(Na). For wild-type Na(V)1.5, the hES-CM AP elicits more early and late I(Na) than either the endocardial or epicardial AP. The mechanism for this difference is that the hES-CM has a relative slow dV/dt(max) that causes a maximal open channel probability. Slower upstroke stimulation also allows greater Na flux through wild-type and N1325S channels, but not the DeltaKPQ mutant.']
['To determine if there were any differences in fall risk and actual falls between those who were prescribed and those who were not prescribed psychotropic and psychoactive medications in a skilled nursing facility.', 'An observational, retrospective cohort study of prospective patient data in a skilled nursing facility.', 'A public skilled nursing facility of more than 100 beds.', "Patient charts and consultant pharmacists' drug regimen review monthly report records for 177 patients who were residents for 30 or more days over a 19-month period during 1996-1997 were tabulated.", 'A fall risk using an assessment method that incorporated patient fall history, conditions, diseases, and medications associated with falls was performed on each resident.', 'Patient demographics, medication usage, fall risk, and fall occurrences.', 'Falls occurred in 107 of 177 (60.5%) residents over the study period. There were 428 documented falls. Fall rates appeared to be directly related to the number of psychotropic drugs, but not other psychoactive medications, until two or more were used concurrently.']
['In muscle-invasive bladder cancer there is an urgent need to identify relatively non-toxic radiosensitising agents for use in elderly patients. Histone deacetylase inhibitors radiosensitise tumour cells but not normal cells in vitro and variously downregulate DNA damage signalling, homologous recombination (HR) and non-homologous end-joining (NHEJ) repair proteins. We investigated panobinostat (PAN) as a potential radiosensitiser in bladder cancer cells.', 'Clonogenic assays were performed in RT112 bladder cancer cells, and RT112 cells stably knocked down for RAD51 or Ku80 by shRNAi. Resolution of γH2AX foci was determined by immunofluorescence confocal microscopy, cell cycle progression by FACS analysis and protein expression by western blotting.', 'PAN had a greater radiosensitising effect in Ku80KD than RT112 or RAD51KD cells; enhancement ratios 1.35 for Ku80KD at 10nM (IC(20) for Ku80KD) and 1.31 for RT112 and RAD51KD at 25 nM (IC(40) for both). PAN downregulated MRE11, NBS1 and RAD51, but not Ku70 and Ku80, increased γH2AX foci formation in a dose-dependent manner and delayed γH2AX foci repair after ionising radiation.']
['Mycobacterium indicus pranii (MIP), popularly known as Mw, is a cultivable, non-pathogenic organism, which, based on its growth and metabolic properties, is classified in Runyon Group IV along with M. fortuitum, M. smegmatis and M. vaccae. The novelty of this bacterium was accredited to its immunological ability to undergo antigen driven blast transformation of leukocytes and delayed hypersensitivity skin test in leprosy patients, a disease endemic in the Indian sub-continent. Consequently, MIP has been extensively evaluated for its biochemical and immunological properties leading to its usage as an immunomodulator in leprosy and tuberculosis patients. However, owing to advances in sequencing and culture techniques, the citing of new strains with almost 100% similarity in the sequences of marker genes like 16S rRNA, has compromised the identity of MIP as a novel species. Hence, to define its precise taxonomic position, we have carried out polyphasic taxonomic studies on MIP that integrate its phenotypic, chemotaxonomic and molecular phylogenetic attributes.', 'The comparative analysis of 16S rRNA sequence of MIP by using BLAST algorithm at NCBI (nr database) revealed a similarity of > or =99% with M. intracellulare, M. arosiense, M. chimaera, M. seoulense, M. avium subsp. hominissuis, M. avium subsp. paratuberculosis and M. bohemicum. Further analysis with other widely used markers like rpoB and hsp65 could resolve the phylogenetic relationship between MIP and other closely related mycobacteria apart from M. intracellulare and M. chimaera, which shares > or =99% similarity with corresponding MIP orthologues. Molecular phylogenetic analysis, based on the concatenation of candidate orthologues of 16S rRNA, hsp65 and rpoB, also substantiated its distinctiveness from all the related organisms used in the analysis excluding M. intracellulare and M. chimaera with which it exhibited a close proximity. This necessitated further analysis of MIP with more sensitive and segregating parameters to ascertain its precise taxonomic position as a new species. The analysis of MIP and its comparison with other mycobacterial reference strains based on cellular and biochemical features, growth characteristics and chemotaxonomic studies like FAME profiling confirmed that MIP is uniquely endowed with diverse metabolic attributes that effectively distinguishes it from all the closely related mycobacteria including M. intracellulare and M. chimaera.']
['Ferroportin (Fpn) is a multiple transmembrane protein required for iron export into the systemic circulation, in cooperation with hephaestin (Heph). Despite the importance of Fpn in iron transport, there is controversy about its topology and functional state upon interaction with Heph.', 'The topology of Fpn was determined using monospecific antisera against its different epitopes, in sheets of cells from duodenum that were or were not permeabilized with detergent. Immunoprecipitation and blue native polyacrylamide gel electrophoresis, followed by immunoblot analysis, were used to determine the extent of interactions between Fpn and Heph. Antisera against the intracellular, C-termini of divalent metal transporter (Dmt1) and Heph served as controls.', 'Immunofluorescence analysis with antisera against amino acids 172-193 of Fpn (anti-Fpn 172) detected Fpn only in permeabilized cells, whereas anti-Fpn 232 (amino acids 232-249), anti-Fpn 370 (amino acids 370-420), and anti-Fpn C (the C-terminus) detected Fpn in nonpermeabilized and permeabilized cells. Immunoprecipitation studies showed that Fpn and Heph coprecipitated with either anti-Fpn or anti-Heph. Blue native polyacrylamide gel electrophoresis studies revealed that a fraction of Fpn comigrates with Heph; the apparent interaction decreases after iron ingestion.']
['Few data are available on the influence of a colonoscope length for trainees, which could affect both the duration of training and colonoscopy quality. We conducted this study to validate which scope needs more duration for training to reach technical competence and to shows better quality indicators during diagnostic colonoscopy.', 'We conducted a prospective randomly assigned study from April 2010 to February 2011 at Asan Medical Center. Among the 1329 patients enrolled, 1200 colonoscopies were analyzed. We compared cecal intubation rate, adenoma detection rate, cecal intubation time (<20 min), and withdrawal time between the trainees using the intermediate-length colonoscope and those using long-length colonoscope.', 'Trainees who used the long-length colonoscope showed a higher overall cecal intubation rate (88.2% vs. 81.0%, p = 0.001) and adenoma detection rate (49.7% vs. 34.2%, p < 0.001) than those using the intermediate-length colonoscope. The successful cecal intubation rate improved significantly and reached the requisite standard of competence (>90%) after 90 procedures in the long-length colonoscope group. However, the trainees using the intermediate-length colonoscope reached the requisite standard of competence after 150 procedures. Logistic regression analysis revealed that prolonged cecal intubation was associated with the use of the intermediate-length colonoscope, poor colon preparation, a small number of esophagastroduodenoscopy or sigmoidoscopy procedures conducted, and pain during procedures.']
['A significant increase in oesophageal acid exposure during early recumbent period has been demonstrated.', 'To determine if acid reflux during the early recumbent period occurs in the recumbent-asleep or recumbent-awake period using a novel integrative actigraphy and pH programme.', 'Thirty-nine subjects with heartburn at least three times a week were included. Subjects underwent pH testing concomitantly with actigraphy. Simultaneously recorded actigraphy and pH data were incorporated using a novel integrative technique to determine sleep and awake periods. Characteristics of acid reflux were compared between the recumbent-awake and recumbent-asleep periods.', 'Seventeen (44.7%) subjects had acid reflux events during recumbent-awake period as compared to seven (18.4%) in the corresponding recumbent-asleep period (P = 0.046). The mean number of acid reflux events in recumbent-awake period was significantly higher than in the corresponding recumbent-asleep period (8.1 +/- 4.4 vs. 3.2 +/- 1.5, P < 0.001). In the recumbent-awake period, 38.4% of acid reflux events were associated with GERD-related symptoms as compared with 3.7% of acid reflux events during the corresponding recumbent-asleep period (P = 0.01).']
['The results of previous studies investigating the association between atrial fibrillation (AF) and central sleep apnea (CSA) in patients with left ventricular (LV) systolic dysfunction are contradictory.', 'We prospectively enrolled 267 patients in this cross-sectional study with LV ejection fractions ≤50%, who were screened for sleep disordered breathing using cardiorespiratory polysomnography after patients with predominantly obstructive sleep apnea or insufficient sleep studies had been excluded.', 'AF at study entry was found in 70 of 267 patients (26%). CSA with an apnea/hypopnea index (AHI) ≥15/hour was present in 116 patients (43%) and 67 patients (25%) had severe CSA with an AHI > 30/hour. Univariate analysis revealed a significant association between AF and severe CSA, age, male gender, arterial hypertension, left atrial diameter, brain natriuretic peptide, chronic kidney disease, New York Heart Association class, digitalis, and the lack of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Multivariate analysis revealed a significant association between AF and severe CSA (odds ratio [OR]: 5.21; 95% confidence interval [CI]: 1.67-16.27, P = 0.01), age (OR: 1.22 per 5-year increase; 95% CI: 1.05-1.40, P = 0.01), left atrial diameter (OR 1.61 per 5-mm increase; 95% CI: 1.22-2.01, P < 0.01), and digitalis (OR: 2.7; 95% CI: 1.26-5.79, P = 0.01).']
['This study was conducted to determine if interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) mRNA expression increase in response to muscle contraction caused by repetitive electrical stimulation of the rat masseter muscle.', 'Male Wistar rats weighing 140-160 g were divided randomly into the following three groups: electrical stimulation (ES) group (n=21), carrageenan injection (CI) group (n=24), and ES under dantrolene sodium (muscle relaxant) injection (ESDI) group (n=7). ES or CI was done to the left masseter; and mock ES or mock CI to the right. Muscle tissues on both sides were sampled for total RNA isolation. Real-time RT-PCR was performed, with the cyclophilin A (CypA) mRNA level in each sample as an internal control. Mean relative IL-6 (il-6/cypA) and IL-1beta (il-1beta/cypA) mRNA levels were compared between the experimental and mock-treated sides within each group.', 'Mean IL-6/CypA levels in the ES- or CI-treated muscle significantly increased, without any significant incremental change observed in either mock-treated muscle. Interestingly, the increase in the il-6/cypA level caused by the ES was suppressed by the injection of dantrolene sodium in the ESDI group. Furthermore, the mean il-1beta/cypA level in the CI-treated masseter also significantly increased without any significant incremental change observed in the mock-treated muscle. However, there was no significant difference in the mean il-1beta/cypA levels in the masseter between the ES- and the mock-treated sides.']
['Progenitor cells isolated from cardiac explant-derived cells improve cardiac function after myocardial infarction (MI). To fully realize the therapeutic potential of these cells, it is essential to develop a safe and efficient delivery method. Therefore, the objective of this study was to determine the efficacy of our newly developed approach to retrograde coronary vein (RCV) infusion of cardiac c-Kit(+) cells in a small-animal model of congestive heart failure (CHF).', 'Sprague-Dawley rats underwent experimental MI. After 21 days, cardiac explant-derived c-Kit(+) cells were delivered to both sham and CHF animals using RCV delivery. Vehicle-treated (serum-free medium) sham and CHF animals were used as controls. Cardiac function and heart tissues were evaluated 21 days post-transplantation.', 'RCV-delivered cells were retained in infarcted hearts for at least 21 days after transplantation. At 21 days post-RCV infusion, the majority of transplanted c-Kit(+)/GFP(+) cells were localized in the left ventricle. Compared with vehicle-treated CHF animals, RCV-treated rats showed a significant improvement in cardiac function. Furthermore, RCV-treated rats exhibited an increase in capillary density, a decrease in total heart collagen, and a reduction in both infarct size and cardiomyocyte hypertrophy when compared with vehicle-treated CHF rats.']
['To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals.', 'Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders.', 'Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available.']
['Human beta-defensins 1 and 2 (hBD-1, -2) are antimicrobial peptides found in several epithelia including corneal epithelium. Breach of the epithelium leaves the cornea vulnerable to infection so we sought to determine if there is an increase in defensin expression after injury.', 'The epithelium from human cadaver corneas was collected by scraping (original samples). The corneas were then placed into organ culture to permit regeneration of the epithelium. Samples of re-grown epithelium were collected when healing was partially and 100% complete as determined by fluorescein staining. Total RNA was extracted from original and re-grown samples and used in RT-PCR reactions using primers specific for hBD-1 and hBD-2 and the constitutively expressed gene glyceraldehyde-3-phosphate dehydrogenase. Immunoblotting was performed to detect defensin peptide in original and re-grown samples.', 'hBD-1 mRNA was detected in all original epithelial tissue samples (n = 10) examined suggesting that it is constitutively expressed. hBD-2 mRNA was detectable in only two of the ten samples. Of six corneas placed in to organ culture, hBD-1 mRNA expression was unchanged in the re-grown epithelial samples compared to the original epithelium samples, however the expression of hBD-2 mRNA was markedly increased. hBD-1 and hBD-2 peptides showed the same pattern of expression as their respective transcripts.']
['To investigate the mechanisms underlying the activation of ATP-sensitive potassium channels (K(ATP)) by iptakalim in cultured rat mesenteric microvascular endothelial cells (MVECs).', 'Whole-cell KATP currents were recorded in MVECs using automated patch clamp devices. Nucleotides (ATP, ADP and UDP) were added to the internal perfusion system, whereas other drugs were added to the cell suspension on NPC-1 borosilicate glass chips.', 'Application of iptakalim (10 and 100 μmol/L) significantly increased the whole-cell K(ATP) currents, which were prevented by the specific K(ATP) blocker glibenclamide (1.0 μmol/L). The opening of K(ATP) channels by iptakalim depended upon the intracellular concentrations of ATP or NDPs: iptakalim activated K(ATP) channels when the intracellular ATP or NDPs were at 100 or 1000 μmol/L, and was ineffective when the non-hydrolysable ATP analogue ATPγS (1000 μmol/L) was infused into the cells. In contrast, the K(ATP) opener pinacidil activated K(ATP) channels when the intracellular concentrations of ATP or NDPs ranged from 10 to 5000 μmol/L, and even ATPγS (1000 μmol/L) was infused into the cells.']
['Four experiments were devised to test the possible role of estrone fatty esters as adipose tissue signals carried by the blood within lipoproteins.', 'Oleoyl-estrone was synthesized and incorporated in liposomes; it was administered i.v. (to mimic lipoprotein delivery) for 14-day periods using implantable osmotic minipumps. The study included the finding of oleoyl-estrone in blood lipoproteins, the correlations of the effects of body weight to the dose and the uptake of labelled oleoyl-estrone by tissues, its internalization and disposal.', 'Normal-weight Wistar female rates were used. Pooled human blood was used as source of HDL3.', 'Oleoyl-estrone was identified in rat white adipose tissue and in human blood HDL3 lipoprotein fraction. Changes in body weight, food intake, oxygen consumption, respiratory quotient and nitrogen balance were measured in chronically injected rats. The uptake and hydrolysis of oleoyl-estrone by tissues was also determined following its acute administration.', 'Oleoyl-estrone induced a dose-dependent loss of weight, with decreased food intake. In 14 days, and compared with controls at the end of this period, a dose of 0.78 mumol/day induced the loss of 16.4 +/- 5.5% of body weight; the difference was maximal for doses of 15 mumol/day or higher: 24.7 +/- 3.1%. Under oleoyl-estrone treatment, body protein was preserved (positive nitrogen balances) and fat stores were wasted: lowered respiratory quotient, and deficit in energy balance; a dose of 0.78 mumol/day induced the loss of 9.6 +/- 2.2 g of total body lipids in 14 days. Most of oleoyl-estrone taken up by tissues was hydrolysed; however, in part it reached intact the cell nucleus of incubated adipocytes. Oleoyl-estrone effects were different from those of free estrone.']
['Pregnant women consume caffeine daily. The aim of this study was to examine the association between maternal caffeine intake from different sources and (a) gestational length, particularly the risk for spontaneous preterm delivery (PTD), and (b) birth weight (BW) and the baby being small for gestational age (SGA).', 'This study is based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. A total of 59,123 women with uncomplicated pregnancies giving birth to a live singleton were identified. Caffeine intake from different sources was self-reported at gestational weeks 17, 22 and 30. Spontaneous PTD was defined as spontaneous onset of delivery between 22+0 and 36+6 weeks (n = 1,451). As there is no consensus, SGA was defined according to ultrasound-based (Marsal, n = 856), population-based (Skjaerven, n = 4,503) and customized (Gardosi, n = 4,733) growth curves.', 'The main caffeine source was coffee, but tea and chocolate were the main sources in women with low caffeine intake. Median pre-pregnancy caffeine intake was 126 mg/day (IQR 40 to 254), 44 mg/day (13 to 104) at gestational week 17 and 62 mg/day (21 to 130) at gestational week 30. Coffee caffeine, but not caffeine from other sources, was associated with prolonged gestation (8 h/100 mg/day, P <10-7). Neither total nor coffee caffeine was associated with spontaneous PTD risk. Caffeine intake from different sources, measured repeatedly during pregnancy, was associated with lower BW (Marsal-28 g, Skjaerven-25 g, Gardosi-21 g per 100 mg/day additional total caffeine for a baby with expected BW 3,600 g, P <10-25). Caffeine intake of 200 to 300 mg/day increased the odds for SGA (OR Marsal 1.62, Skjaerven 1.44, Gardosi 1.27, P <0.05), compared to 0 to 50 mg/day.']
['To investigate if rifampicin is both an inducer and an inhibitor of repaglinide metabolism, it was determined whether the timing of rifampicin co-administration influences the pharmacokinetics of repaglinide.', 'Male volunteers ( n=12) participated in a randomised, two-period, crossover trial evaluating the effect of multiple doses of 600 mg rifampicin once daily for 7 days on repaglinide metabolism. Subjects were, after baseline measurements of repaglinide pharmacokinetics, randomised to receive, on either day 7 or day 8 of the rifampicin administration period, a single dose of 4 mg repaglinide and vice versa in the following period.', 'When repaglinide was given, together with the last rifampicin dose, on day 7, an almost 50% reduction of the median repaglinide area under the plasma concentration-time curve (AUC) was observed. Neither the peak plasma concentration (C(max)), time to reach C(max) (t(max)) nor terminal half-life (t(1/2)) was statistically significantly affected. When repaglinide was given on day 8, 24 h after the last rifampicin dose, an almost 80% reduction of the median repaglinide AUC was observed. The median C(max) was now statistically significantly reduced from 35 ng/ml to 7.5 ng/ml. Neither t(max) nor t(1/2) was significantly affected.']
["The influence of the inner wall of Schlemm's canal on aqueous outflow facility remains poorly understood. We examined the relationship between inner wall pore characteristics and outflow facility in living primate eyes in which facility had been pharmacologically increased by ethacrynic acid (ECA) infusion and in contralateral control eyes.", "Outflow facility (two-level constant pressure perfusion) was measured in eight pairs of living monkey eyes before and after administration of a bolus dose of either 0.125 mM ECA or vehicle. After exsanguination, eyes were fixed in situ under constant-pressure conditions (mean fixation pressure approximately 19 mm Hg). The density and diameter of inner wall pores and the number and area of platelet aggregates on the inner wall of Schlemm's canal were measured by scanning electron microscopy.", 'In ECA-treated eyes, outflow facility increased 63% (P < 0.0001), intracellular pore density decreased 46% (P = 0.0094), intracellular pore size increased 27% (P = 0.049), platelet aggregate density increased 158% (P < 0.0001), and area covered by platelets increased 210% (P = 0.012) relative to contralateral controls. Although the average density and size of intercellular pores were essentially unaffected by ECA, an increased density of large (> or = 1.90 microm) intercellular pores was seen in ECA-treated eyes. The density of intracellular pores increased with the duration of fixative perfusion. Other than a weak negative correlation between outflow facility and intracellular pore density in ECA-treated eyes (P = 0.052), facility was not correlated with inner wall pore features.']
['The purpose of this study was to develop an in situ immune marker model to predict postoperative oncological outcomes in patients with colorectal cancer (CRC).', 'Immunohistochemistry for 13 immune cell markers was performed on tumor tissue microarrays from 300 CRC patients who underwent curative resection from January 2000 to January 2006. Genetic algorithm was applied for the construction of an in situ immune marker model.', 'The infiltration of CD3+ cells, CD45RO+ cells, and FOXP3+ cells, but not the infiltration of Tryptase+ cells, in the tumor was significantly associated with better clinical outcome in overall survival (OS) and disease-free survival (DFS) of CRC patients, as assessed by univariate analysis (P\xa0<\xa00.05). Based on the genetic algorithms, a total of 6 markers, including CD3, CD45RO, IL17, CD15, Tryptase, and FOXP3, were selected to construct an immune marker model. Our model was identified to have an independent predictive capability for both OS and DFS in Cox multivariable model (P\xa0<\xa00.001). This was further confirmed by the ROC analysis (area under curve: OS, 0.669; DFS, 0.684).']
['An association between coronary heart disease (CHD) and clinically diagnosed periodontitis has been found in several epidemiological studies. However, seroepidemiologic evidence based on prospective data on this association is totally lacking.', 'The aim of the study was to investigate serum antibodies to major periodontal pathogens for their prediction of myocardial infarction (MI) in men free of CHD at baseline.', 'Cases and controls were ascertained from a random population sample of 4255 men aged 30 to 59 years at baseline. The study cases included 63 men with nonfatal MI or coronary death within the follow-up time of 10 years. Age-matched control subjects (n=63) were randomly chosen from the same cohort. Serum antibody levels to two major periodontopathogenic bacteria, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined.', 'There was no significant association between the risk for MI and IgG- or IgA-class antibody levels to A. actinomycetemcomitans or IgG-class antibody levels to P. gingivalis. However, a high P. gingivalis IgA-class antibody level predicted MI independently of classical cardiovascular risk factors. The risk for MI increased by increasing quartiles of antibody levels (P for the trend 0.021). Compared with the first quartile, the multivariate odds ratios of MI in the second, third and fourth quartiles were 2.47 (95% CI 0.75-8.11), 3.30 (1.03-10.58) and 3.99 (1.22-13.10), respectively.']
['The rapid administration of bee venom in cumulative doses exceeding the quantity contained in one bee sting is well tolerated by most of the patients during 3.5 h of ultra-rush bee venom immunotherapy (VIT). The mechanism of this tolerance is unknown.', 'The aim of the study was to verify the hypothesis that either slow mediator depletion of mast cells or blockade of their surface receptor mechanisms by increasing doses of allergen might be the major mechanisms of tolerance induced by ultra-rush VIT.', 'Nine bee venom allergic patients with a history of severe systemic reactions after a bee sting, positive skin tests and bee venom specific serum IgE antibodies were treated as follows: on the first day a cumulative dose of 111 micrograms was administered over 3.5 h under intensive care conditions. Further injections were given on day 7, day 21 and thereafter at 4 week intervals. Intradermal tests with codeine phosphate (non-specific mast cell degranulation) and bee venom were performed before the initiation of VIT and 30 min after the last injection on the same day as well as before the subsequent bee venom injections.', 'No significant changes of skin reactivity to both codeine phosphate and bee venom were observed on day 1 (before initiation of VIT and after the last injection on the same day).']
['The association of short sleep duration with cortisol secretion has not been thoroughly examined in large community dwelling populations and the relative importance of short sleep duration and sleep disturbance is unclear.', 'The objective of the study was to assess the relationships between self-reported sleep duration, sleep disturbance, and salivary cortisol secretion.', 'This was a cross-sectional analysis using data from phase 7 (2002-2004) of the Whitehall II study. Sleep disturbances were assessed using a modified version of the Jenkins Scale.', 'The occupational cohort was originally recruited in 1985-1989.', 'Analyses included 2751 participants with complete cortisol measures and who collected their first sample within 15 min of waking, were not on medication affecting cortisol secretion, and had complete information for all covariates.', 'Six saliva samples were taken on waking, waking + 0.5, 2.5, 8, and 12 h and bedtime for the assessment of the cortisol awakening response and the slope in cortisol secretion across the day.', 'In mutually adjusted analyses, both sleep duration and disturbances were independently associated with a flatter diurnal slope in cortisol secretion, such that evening cortisol secretion was raised in those reporting short sleep duration and high sleep disturbance. Short sleep duration was also associated with the cortisol awakening response. These effects were independent of a number of covariates, including waking time on day of sampling and stress on the day of cortisol assessment.']
['Zinc is abundant in pancreas, being required by endocrine islet cells for hormone secretion and by exocrine acinar cells as pancreatic juice component. ZnT8 is a member of the SLC30A family of zinc transporters whose overexpression in cultured pancreatic beta cells leads to increased insulin secretion in response to glucose, suggesting a possible role in regulating glycemia. ZnT8 was therefore proposed as a therapeutic target for diabetes, and recent genome-wide association studies identified polymorphisms in the ZNT8 gene conferring increased type 2 diabetes risk.', 'As limited information was available on the biochemical properties of ZnT8 and on its endogenous expression, we have raised a specific polyclonal antibody and immunostained protein extracts, cell lines and tissue sections. We show that ZnT8 forms a very stable dimer that requires biological membranes to properly assemble. We demonstrate localization of murine ZnT8 to the secretory granules in pancreatic beta and alpha islet cells. Moreover, we show that ZnT8 is also expressed in other secretory cell types, namely the cubical epithelium that lines thyroid follicles and the cortex of the adrenal gland, suggesting a more widespread role in endocrine secretion.']
['This study assesses if there exists a high-risk period for cerebrovascular events (CeV) after transcatheter aortic valve implantation (TAVI).', 'Even though acute strokes after TAVI have been described, it is uncertain if stroke rates continue to remain high in the early months after TAVI. Furthermore, the optimal dose and duration of thromboprophylaxis is unclear.', 'Patients who underwent TAVI were evaluated at baseline, at discharge, at 1 and 6 months, and yearly. Risk factors for CeV events, procedural details, and antithrombotic therapy were recorded. Outcomes assessed were CeV events and death. The timing of such events, predictors, and impact on survival were analyzed.', 'A total of 253 patients were assessed. Median age was 85 years. The median Society of Thoracic Surgeons score was 8.1% (interquartile range [IQR]: 5.5% to 12.0%). Risk factors included smoking (47%), hypertension (70%), dyslipidemia (66%), and diabetes mellitus (25%). Twenty-three percent had known cerebrovascular disease and 39% had atrial fibrillation. Median follow-up was 455 days (IQR: 160 to 912 days) at which time 23 patients experienced a CeV event. The incidence was highest in the first 24 h but remained high for 2 months. In-hospital mortality rate after a CeV event was 21%. A prior history of CeV disease was an independent predictor of an event (hazard ratio: 4.23, 95% CI: 1.60 to 11.11, p = 0.004).']
['To examine the relationship between physiological status at the emergency department-ward interface and emergency calls (medical emergency team or cardiac arrest team activation) during the first 72\xa0hours of hospital admission.', 'Ward adverse events are related to abnormal physiology in emergency department however the relationship between physiology at the emergency department-ward interface and ward adverse events is unknown.', 'Descriptive and exploratory design.', 'The study involved 1980 patients at three hospitals in Melbourne Australia: i) 660 randomly selected adults admitted via the emergency department to medical or surgical wards during 2012 and who had an emergency call; and ii) 1320 adults without emergency calls matched for gender, triage category, usual residence, admitting unit and age.', 'The median age was 78\xa0years and 48·8% were males. The median time to the first emergency call was 18·8\xa0hours and ≥1 abnormal parameters were documented in 34·9% of patients during the last hour of ED care and 47·1% of patients during first hour of ward care. Emergency calls were significantly more common in patients with heart rate and conscious state abnormalities during the last hour of emergency care and abnormal oxygen saturation, heart rate or respiratory rate during the first hour of ward care. Medical emergency team afferent limb failure occurred in 55·3% patients with medical emergency team activation criteria during first hour of ward care.']
['Mucolytics can improve disease outcome in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The objectives of this study were to investigate the effects of erdosteine (ER), a mucolytic agent with antioxidant activity, on systemic inflammation, symptoms, recurrence of exacerbation, and time to first exacerbation postdischarge in hospitalized patients with AECOPD.', 'Patients admitted to hospital with AECOPD were randomized to receive either ER 900 mg daily (n=20) or a matching control (n=20). Treatment was continued for 10 days until discharge. Patients also received standard treatment with steroids, nebulized bronchodilators, and antibiotics as appropriate. Serum C-reactive protein levels, lung function, and breathlessness-cough-sputum scale were measured on hospital admission and thereafter at days 10 and 30 posttreatment. Recurrence of AECOPD-requiring antibiotics and/or oral steroids and time to first exacerbation in the 2 months (days 30 and 60) postdischarge were also assessed.', 'Mean serum C-reactive protein levels were lower in both groups at days 10 and 30, compared with those on admission, with significantly lower levels in the ER group at day 10. Improvements in symptom score and forced expiratory volume in 1 second were greater in the ER than the control group, which reached statistical significance on day 10. ER was associated with a 39% lower risk of exacerbations and a significant delay in time to first exacerbation (log-rank test P=0.009 and 0.075 at days 30 and 60, respectively) compared with controls.']
['To provide a mathematical introduction to the Wichita (KS, USA) clinical dataset, which is all of the nongenetic data (no microarray or single nucleotide polymorphism data) from the 2-day clinical evaluation, and show the preliminary findings and limitations, of popular, matrix algebra-based data mining techniques.', 'An initial matrix of 440 variables by 227 human subjects was reduced to 183 variables by 164 subjects. Variables were excluded that strongly correlated with chronic fatigue syndrome (CFS) case classification by design (for example, the multidimensional fatigue inventory [MFI] data), that were otherwise self reporting in nature and also tended to correlate strongly with CFS classification, or were sparse or nonvarying between case and control. Subjects were excluded if they did not clearly fall into well-defined CFS classifications, had comorbid depression with melancholic features, or other medical or psychiatric exclusions. The popular data mining techniques, principle components analysis (PCA) and linear discriminant analysis (LDA), were used to determine how well the data separated into groups. Two different feature selection methods helped identify the most discriminating parameters.', 'Although purely biological features (variables) were found to separate CFS cases from controls, including many allostatic load and sleep-related variables, most parameters were not statistically significant individually. However, biological correlates of CFS, such as heart rate and heart rate variability, require further investigation.']
['Annexin 1 (ANXA1) has analgesic effects in inflammatory pain. We aimed to investigate the anti-nociceptive role of ANXA1, at the dorsal root ganglion (DRG) level, through an interaction with formyl-peptide-receptor-like 1 (FPR2/ALX).', "Inflammatory pain was evoked by injecting complete Freund's adjuvant (CFA, 50 μl) into the hindpaw of male Sprague-Dawley rats. The distribution of ANXA1 and FPR2/ALX in L4/5 DRGs was evaluated by immunofluorescence. The expression of ANXA1 was measured by western blot. The involvement of FPR2/ALX in the anti-nociception of ANXA1 was investigated by thermal (irradiant heat) and mechanical (von Frey filament) pain tests with intrathecal (i.t.) ANXA1-derived peptide (Anxa1(2-26)), FPR2/ALX agonist 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), and antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe (Boc1).", 'ANXA1 and FPR2/ALX localized in the satellite glial cells and neurones in L4/5 DRGs. CFA treatment (n=20) increased ANXA1 expression in L4/5 DRGs within 7 days (P<0.01). I.T. Anxa1(2-26) (20 and 100 µg µl(-1)) and BML-111 (10 and 100 nmol) reduced CFA-induced thermal and mechanical nociception within 48 h (n=40) (P<0.05). However, i.t. Boc1 10 µg intensified inflammatory pain (P<0.05) and reversed the anti-nociceptive effect of Anxa1(2-26) (n=25) (P<0.05). Moreover, ANXA1 expression increased in L4/5 DRGs after i.t. Anxa1(2-26) (20 µg µl(-1)) (P<0.05) and BML-111 (10 nmol) (P<0.01) but decreased after i.t. Boc1 (10 and 100 µg) alone (P<0.01) or Boc1 (10 µg) co-injection with Anxa1(2-26) (20 µg µl(-1)) (P<0.05).']
['Plasma level of plasminogen activator inhibitor (PAI)-1 is genetically determined by a polymorphism in the promoter region, involving two alleles, 4G and 5G. Plasma PAI-1 concentrations are higher in subjects homozygous for the 4G allele than other genotypes (5G/5G and 4G/5G). Such genetic variation in fibrinolytic system may affect the long-term renal transplant outcome.', 'We determined PAI-1 4G/5G-promoter genotype polymorphism among our renal transplant recipients between 1985 and 2001. Primary event was defined as doubling of baseline serum-creatinine level.', 'Over a median period of 79 months, 130 patients with 132 kidney grafts were assessed. Baseline clinical variables were comparable among three genotype groups. There was no association between primary event and PAI-1 genotype among the entire cohort. However, among subjects with prior acute rejection episodes, those homozygous for 4G had significantly higher risk of serum creatinine doubling than the other two genotypes (relative risk 2.45, 95% confidence interval 1.19-5.04). PAI-1 genotype does not predict primary events in patients without rejection (relative risk 0.57, 95% confidence interval 0.07-4.17).']
['Observation status, in contrast to inpatient status, is a billing designation for hospital payment. Observation-status stays are presumed to be shorter and less resource-intensive, but utilization for pediatric observation-status stays has not been studied. The goal of this study was to describe resource utilization characteristics for patients in observation and inpatient status in a national cohort of hospitalized children in the Pediatric Health Information System.', 'This study was a retrospective cohort from 2010 of observation- and inpatient-status stays of ≤2 days; all children were admitted from the emergency department. Costs were analyzed and described. Comparison between costs adjusting for age, severity, and length of stay were conducted by using random-effect mixed models to account for clustering of patients within hospitals.', 'Observation status was assigned to 67\u2009230 (33.3%) discharges, but its use varied across hospitals (2%-45%). Observation-status stays had total median costs of $2559, including room costs and $678 excluding room costs. Twenty-five diagnoses accounted for 74% of stays in observation status, 4 of which were used for detailed analyses: asthma (n = 6352), viral gastroenteritis (n = 4043), bronchiolitis (n = 3537), and seizure (n = 3289). On average, after risk adjustment, observation-status stays cost $260 less than inpatient-status stays for these select 4 diagnoses. Large overlaps in costs were demonstrated for both types of stay.']
['To investigate the relationship between microalbuminuria (MAU) and atrial fibrillation (AF) and to further evaluate whether the heart rate dependency of MAU in patients without AF is maintained in patients with a history of AF.', 'The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) included 18,900 patients without and 1705 patients with a history of AF suffering from hypertension and other risk factors for cardiovascular disease in 26 countries worldwide from September 2005 to March 2006. Heart rate, blood pressure, urinary albumin excretion, and an estimated glomerular filtration rate were determined among other parameters. The prevalence of MAU was higher at higher heart rate in both patients with and without a history of AF. Prevalence of MAU was about 10% higher in patients with a history of AF (P < 0.001). Male gender, the presence of diabetes mellitus, a higher heart rate, and a higher diastolic blood pressure were independently associated with increased odds for MAU in patients without and with a history of AF.']
['Insulin receptors are ubiquitously found in the human brain, comprising the olfactory bulb, essential for odor processing, and the hippocampus, important for spatial memory processing.', 'The present study aimed at examining if intranasal insulin, which is known to transiently increase brain insulin levels in humans, would improve odor-cued reactivation of spatial memory in young men.', 'We applied a double-blind, placebo-controlled, counterbalanced within-subject design.', "The study was conducted at the research unit of a university hospital. Interventions/Participants/Main Outcome Measures: Following intranasal administration of either insulin (40 I.U.) or placebo, male subjects (n = 18) were exposed to eight odors. During each odor exposure, a green-colored field was presented on a 17-in. computer screen. During immediate recall (comprising 3 runs), the participants were re-exposed to each odor cue, and were asked to select the corresponding field (with visual feedback after each response). The delayed recall was scheduled ∼10 min later (without feedback). To test if insulin's putative effect on odor-place memory would be domain-specific, participants also performed a separate place and odor recognition task.", 'Intranasal insulin improved the delayed but not immediate odor-cued recall of spatial memory. This effect was independent of odor type and in the absence of systemic side effects (eg, fasting plasma glucose levels remained unaltered). Place and odor recognition were unaffected by the insulin treatment.']
['To evaluate the role of VEGF-dependent Claudin 5 production for the development of ascites via influencing endothelial permeability in peritoneal tissue of ovarian cancer patients.', 'This study investigates the mechanisms of formation of ascites in ovarian cancer patients, performing RT-PCR, VEGF-ELISA and immunohistochemical dual staining for CD31 and Claudin 5. In addition, in order to analyze the connectivity of VEGF, Claudin 5, and endothelial permeability, an endothelial cell/ovarian cancer cell-co-culture-system was established and evaluated performing Western blot analysis and a permeability assay.', 'Firstly, VEGF-gene expression was demonstrated for all ovarian cancer and peritoneal biopsies. In addition, quantification of VEGF in the serum and ascites of ovarian cancer patients revealed significantly increased values. We subsequently demonstrated Claudin 5 production in the peritoneal vessels, which was weaker than in the vessels of the controls. Evaluation of endothelial permeability finally showed a VEGF-dependent regulation via Claudin 5 suggesting a mechanism for the development of ascites in ovarian cancer patients.']
['To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC).', 'Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates.', 'In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade.']
['External quality assessment (EQA) with commutable samples is essential for assessing the quality of assays performed by laboratories, particularly when the emphasis is on their standardization status and interchangeability of results.', 'We used a panel of 20 fresh-frozen single-donation serum samples to assess assays for the measurement of creatinine, glucose, phosphate, uric acid, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. The commercial random access platforms included: Abbott Architect, Beckman Coulter AU, Ortho Vitros, Roche Cobas, Siemens Advia, and Thermo Scientific Konelab. The assessment was done at the peer group level and by comparison against the all-method trimmed mean or reference method values, where available. The considered quality indicators were intraassay imprecision, combined imprecision (including sample-matrix interference), bias, and total error. Fail/pass decisions were based on limits reflecting state-of-the-art performance, but also limits related to biological variation.', 'Most assays showed excellent peer performance attributes, except for HDL- and LDL cholesterol. Cases in which individual assays had biases exceeding the used limits were the Siemens Advia creatinine (-4.2%), Ortho Vitros phosphate (8.9%), Beckman Coulter AU triglycerides (5.4%), and Thermo Scientific Konelab uric acid (6.4%), which lead to considerable interassay discrepancies. Additionally, large laboratory effects were observed that caused interlaboratory differences of >30%.']
['Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA.', 'A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined.', 'The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001).']
['Ischemic preconditioning (IP) has been used to reduce ischemia-reperfusion injury in several models. It remains unknown whether IP is sufficient to prevent deep hypothermic circulatory arrest (DHCA) cardiopulmonary bypass (CPB) induced lung injury.', 'Twenty-four piglets were randomly divided into four groups: routine CPB (CPB), CPB + DHCA (DHCA), CPB + IP + DHCA (IP-1) and CPB + hypoxia-ischemia preconditioning + DHCA (IP-2). Lung static compliance (Cstat) and pulmonary vascular resistance (PVR) were measured as indicators of lung function at three points during CPB. TNF-α, IL-8 and IL-10 expressions were detected by radioimmunoassay. CD18 expression was determined by flow cytometer. Some lung tissues were excised to measure the wet/dry weight ratio (W/D) and some were fixed to observe pathological changes.', 'Cstat significantly decreased whereas PVR increased in DHCA group. IP prevented DHCA-induced lung functional impairment, especially IP-2 treatment. More cytokines were produced after CPB in all groups, but with varying level. Left atrium/pulmonary artery ratio of CD18 expression on monocytes decreased only in DHCA group, whereas which on polymorphonuclear neutrophils decreased in DHCA group, IP-1 group at 1h post-CPB and IP-2 group. Although lung W/D was increased in IP-2 group compared with pre-CPB, but significantly lower than that in DHCA group. Histological findings showed less lung injuries in IP groups than DHCA group.']
['Infection with H. pylori is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of H. pylori infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.', 'DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.', 'Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.']
['Many genes responsible for the bioactivation of endogenous estrogen to reactive quinonoid metabolites, including cytochrome P450 (CYP) 1A1, 1A2, and 1B1, are well-known target genes of the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).', 'The purpose of this research was to investigate the roles of TCDD-mediated altered gene expression in the induction of aldehydic DNA lesions (ADLs) by 17β-estradiol (E2) in human MDA-MB-231 and MCF-7 breast cancer cells.', 'We demonstrated that increases in the number of oxidant-mediated ADLs, including abasic sites and aldehydic base/sugar lesions, were detected in MDA-MB-231 cells exposed to E2. The DNA-damaging effects of E2 in MDA-MB-231 cells were prevented by pretreatment of cells with TCDD. In contrast, we did not observe statistically significant increases in the number of ADLs in MCF-7 cells exposed to E2. However, with TCDD pretreatment, an approximately twofold increase in the number of ADLs was detected in MCF-7 cells exposed to E2.']
['Pancreatic fistula (PF) is a common postoperative complication following distal pancreatectomy. The prolonged prefiring compression (PFC) technique to reduce PF has been described by Nakamura and colleagues in Japan. The present study assessed if this technique can be applied to the United Kingdom patient population in a tertiary referral center and replicate the low incidence of PF after the laparoscopic approach to distal pancreatectomy (Lap-DP).', 'This is a retrospective study of all patients who underwent Lap-DP using the modified PFC technique by the senior author between June 2011 and July 2014. The modified PFC technique involved compression of the pancreatic parenchyma with an endo-stapler for a 3-minute period prior to firing and further 1-minute compression after firing prior to removal of the stapler, which is a small variant to the original technique of maintaining a 2-minute compression post firing.', 'Twenty patients (15 females; median age, 66 [range, 25-77] years) underwent Lap-DP using the PFC technique during the study period. Six patients had splenic-preserving Lap-DP. Median operating time was 240 minutes (range, 150-420 minutes) with a median length of hospital stay of 6 days (range, 3-22 days). Six patients (30%) developed Type A (biochemically noted as high drain fluid amylase) PF, and none of the patients had Type B/C PF. In the splenic preservation group, 1 patient had complete splenic infarction requiring laparoscopic splenectomy on Day 3, and 1 patient had partial infarction requiring prolonged hospital stay for pain relief. One patient required prolonged respiratory support due to severe preexisting lung disease. Overall mortality was zero.']
['The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA).', 'A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low grade and 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed.', 'High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039).']
['Parenteral nutrition (PN) suppresses spontaneous food intake in rats by stimulating dopamine in lateral hypothalamic area (LHA), which is attenuated by vagotomy. Sensors for glucose and for some individual amino acids exist in hepatoportal areas sending signals via hepatic vagal afferents to LHA. Hypothesizing that the decrease in spontaneous food intake occurs because a PN amino acid solution is recognized by portal vein sensors, we measured afferent nerve discharges in hepatic vagus in response to PN.', 'Hepatic vagus was divided in 11 rats, and an isolated nerve filament was placed on recording electrodes. Afferent firing rate was recorded before and after injecting during 1 minute a well-balanced crystalline amino acid mixture into either the portal or peripheral vein. Isotonic glucose was used as standard solution.', 'A significant decrease in hepatic vagal afferent discharge rate was recorded after both intraportal and intravenous injection of the PN amino acid mixture. The mean discharge rate was inversely related to the concentration of the solution. Successive injections produced further decreases in discharge rate, and the effect was more sustained.']
['We have previously described the antifibrotic role of the soluble guanylate cyclase (sGC). The mode of action, however, remained elusive. In the present study, we describe a novel link between sGC signalling and transforming growth factor β (TGFβ) signalling that mediates the antifibrotic effects of the sGC.', 'Human fibroblasts and murine sGC knockout fibroblasts were treated with the sGC stimulator BAY 41-2272 or the stable cyclic guanosine monophosphate (cGMP) analogue 8-Bromo-cGMP and stimulated with TGFβ. sGC knockout fibroblasts were isolated from sGCI(fl/fl) mice, and recombination was induced by Cre-adenovirus. In vivo, we studied the antifibrotic effects of BAY 41-2272 in mice overexpressing a constitutively active TGF-β1 receptor.', 'sGC stimulation inhibited TGFβ-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFβ-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGFβ target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGFβ-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGFβ target gene expression, confirming that non-canonical TGFβ pathways mediate the antifibrotic sGC activity.']
['The need for emergent colon surgery is a common cause of severe sepsis/septic shock and mortality among surgical patients. We wanted to benchmark our outcomes against those of the National Surgical Quality Improvement Program (NSQIP). We hypothesized that having acute care surgeons to provide comprehensive perioperative care and rapid source control surgery would improve outcome.', 'We queried the 2005 to 2007 NSQIP dataset and our prospective database for patients with severe sepsis/septic shock requiring emergency colon surgery. Demographics, Acute Physiology and Chronic Health Evaluation II score, sepsis source, and hospital mortality data were obtained for all patients.', 'Both cohorts were similar with regard to age and sex. The overall mortality rate for patients in our dataset was 28.3% compared with 40.1% in the NSQIP dataset (P = .06). The average Acute Physiology and Chronic Health Evaluation II score for our patients was 31 ± 8.2 with a predicted mortality rate of 73% (P < .0001 when compared with actual mortality rate of 28.3%).']
['Carbohydrate (CHO) quantification is used to adjust pre-meal insulin in intensive insulin regimens. However, the precision in CHO quantification required to maintain postprandial glycaemic control is unknown. We determined the effect of a +/-10-g variation in CHO amount, with an individually calculated insulin dose for 60 g CHO, on postprandial glycaemic control.', 'Thirty-one children and adolescents (age range 9.5-16.8 years), 17 using continuous subcutaneous insulin infusion (CSII) and 14 using multiple daily injections (MDI), participated. Each subject consumed test lunches of equal macronutrient content, differing only in carbohydrate quantity (50, 60, 70 g CHO), in random order on three consecutive days. For each participant, the insulin dose was the same for each meal, based on their usual insulin : CHO ratio for 60 g CHO. Activity was standardized. Continuous glucose monitoring was used.', 'The CSII and MDI subjects demonstrated no difference in postprandial blood glucose levels (BGLs) for comparable carbohydrate loads (P > 0.05). The 10-g variations in CHO quantity resulted in no differences in BGLs or area under the glucose curves for 2.5 h (P > 0.05). Hypoglycaemic episodes were not significantly different (P = 0.32). The 70-g meal produced higher glucose excursions after 2.5 h, with a maximum difference of 1.9 mmol/l at 3 h (P = 0.01), but the BGLs remained within international postprandial targets.']
["Surgery to monitor and resect epileptogenic foci may be undertaken in 2 stages, providing an opportunity to use skull-fixated fiducials implanted during the first stage to improve the accuracy of cortical resection during the second stage. This study compared the intrinsic accuracy of skin-based and skull-fixated fiducial markers in registering frameless stereotaxy during pediatric epilepsy surgery. To the authors' knowledge, these modalities of registration have not previously been directly compared in this population.", 'The authors undertook a retrospective review of pediatric patients who underwent resection of epileptogenic foci in 2 stages with frameless stereotactic assistance, performed by a single surgeon at Oregon Health & Science University. For the first stage (subdural grid implantation), 9 skin fiducial markers were used to register anatomical data in a frameless stereotactic station. Intraoperatively, four 3-mm screws were placed circumferentially around the craniotomy. Postoperatively, thin-slice brain MR and CT images were obtained and fused. For the second stage, the 4 screws were used as fiducial markers to register the stereotactic anatomical data. For both stages, accuracy (difference in millimeters from zero of the manual fiducial registration compared with the computer model) was determined using navigation software. The intrinsic accuracy of these 2 methods of fiducial registration was compared using a paired Student t-test.', 'Between 2004 and 2009, 40 pediatric patients with epilepsy underwent frameless stereotactic surgical procedures. Fourteen patients who had 2-stage procedures using skin-based and skull-fixated registration with complete accuracy data were included in this retrospective review. Mean registration error was significantly lower using skull-fixated fiducials (1.35 mm, 95% CI 1.09-1.60 mm) than using skin-based fiducials (1.85 mm, 95% CI 1.56-2.13 mm; p = 0.0016).']
['Oxygen minimum zones (OMZs) are expanding in the World Ocean as a result of climate change and direct anthropogenic influence. OMZ expansion greatly affects biogeochemical processes and marine life, especially by constraining the vertical habitat of most marine organisms. Currently, monitoring the variability of the upper limit of the OMZs relies on time intensive sampling protocols, causing poor spatial resolution.', "Using routine underwater acoustic observations of the vertical distribution of marine organisms, we propose a new method that allows determination of the upper limit of the OMZ with a high precision. Applied in the eastern South-Pacific, this original sampling technique provides high-resolution information on the depth of the upper OMZ allowing documentation of mesoscale and submesoscale features (e.g., eddies and filaments) that structure the upper ocean and the marine ecosystems. We also use this information to estimate the habitable volume for the world's most exploited fish, the Peruvian anchovy (Engraulis ringens)."]
['Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.', 'We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity.', 'The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance.']
['The Belgian legislation imposes single embryo transfer (SET) on women of <36 years in their first treatment cycle to avoid multiple pregnancies. The aim of this study is to assess the impact of this legislation on the outcome of preimplantation genetic diagnosis (PGD) for inherited diseases in young women undergoing SET.', 'A retrospective analysis of PGD cycles for monogenic disorders and translocations in women <36 years on their first treatment cycle. Two groups of patients were defined according to the implementation of the Belgian legislation: (i) double embryo transfer (DET), January 2001-June 2003 (ii) SET, July 2003-June 2005. The primary and secondary outcome measures were delivery per embryo transfer and multiple pregnancy rates, respectively. A subgroup analysis for monogenic disorders and translocations was performed.', '62 cycles were included in the DET group and 73 cycles in the SET group. The mean age, number of cumulus-oocyte complexes, number of fertilized oocytes, number of biopsied and cryopreserved embryos were comparable between both groups. There was no significant difference in the delivery rates between the DET and the SET groups (33.9% versus 27.4%, respectively). Multiple pregnancies were avoided when SET was performed. When monogenic disorders and chromosomal translocations were separately evaluated, no significant difference in the delivery rate after SET was observed.']
['It is difficult to predict acute thrombotic cardiovascular events in the clinic. Few studies have reported the presence of plasma exosomes containing microRNAs (miRNAs) in cardiovascular events. Therefore, we aimed to investigate the levels of miR-223, miR-339 and miR-21 in plasma exosomes before thrombosis in mouse models of carotid tandem stenosis, as well as the mechanisms underlying the origin and function of these exosomal miRNAs.', 'Plasma samples were collected from the carotid tandem stenosis and sham control groups of our successfully developed atherothrombosis mouse models before thrombosis. Platelets from healthy volunteers and mice were purified to obtain thrombin stimulated platelet-derived exosomes. Exosomes were isolated via differential ultracentrifugation, and western blotting and transmission electron microscopy were used for their identification. The total RNA was extracted, and quantitative real-time PCR was performed to determine the expression levels of miR-223, miR-339 and miR-21. DAVID Tools were used to analyze the pathways that were enriched among the miRNA target genes. Immuno-fluorescence staining was performed to identify the protein expression levels of platelet-derived exosome target genes in vascular smooth muscle cells (SMCs) in vitro and in vivo.', 'The levels of miR-223, miR-339 and miR-21, which are associated with platelet activation, were elevated in pooled mouse plasma exosomes before thrombosis and enriched in thrombin-stimulated platelet-derived exosomes in vitro. Platelet-derived growth factor receptor-beta (PDGFRβ) was a target of these miRNAs, and PDGFRβ expression in vascular smooth muscle cells (SMCs) was inhibited following incubation with platelet-derived exosomes. Platelet-derived exosomes could also inhibit PDGF-stimulated SMC proliferation. Furthermore, a decrease in PDGFRβ expression was observed in vascular SMCs around thrombotic areas in vivo.']
['The endothelial cell-specific form of nitric oxide synthases (ecNOS) may play an important role in vascular development, maintenance of vascular tone, and tumor growth in human prostate cancer. Estrogens have been shown to upregulate ecNOS expression in different human cell culture systems. Estrone sulfate (E1S) is the most abundant circulating estrogen, and may serve as a prehormone for the terminal biologically active estrogen estradiol-17beta (E2) in men.', 'The effects of E1S and E2 on mRNA expression of ecNOS were studied in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative, LNCaP-r. The cells were grown in steroid-depleted medium and incubated for 2-4 or 48 hr with 0-100 nM of E1S and E2, respectively. ecNOS mRNA levels were determined using RT-PCR and are expressed as arbitrary units after correction for control HGPRT gene mRNA levels.', 'Treatment for 48 hr with 10 and 100 nM E1S significantly (P<0.05) increased ecNOS mRNA levels in LNCaP-FGC cells. Significantly higher (P<0.05) ecNOS mRNA levels also were found in LNCaP-FGC cells treated with E2 for 2-4 hr, irrespective of E2 concentration. The level of ecNOS mRNA was significantly lower (P<0.05) in untreated LNCaP-r than in LNCaP-FGC. LNCaP-r cells incubated with 100 nM E2 for 48 hr had a significantly higher (P<0.05) level of ecNOS mRNA than control LNCaP-r cells.']
['Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear.', 'The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women.', 'In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d.', 'Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter.']
['Impaired response to antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel (CLO) has been associated with an increased risk of stent thrombosis and ischemic events after coronary stent implantation. We sought to investigate whether patients with a low response (LR) to ASA or CLO are at increased risk for periprocedural and short-term ischemic events after coronary stent implantation.', 'A total of 219 patients pretreated with ASA and CLO underwent percutaneous coronary intervention (PCI) with stent implantation. Whole blood impedance platelet aggregometry was performed with the Multiplate analyzer (Dynabyte, Munich, Germany) to test the response to ASA (ASPI test) and CLO (ADP test) within 12 to 18 hours after PCI. Patients were classified as ASA-LR, CLO-LR, dual LR, and controls. Study end points included myocardial infarction, stent thrombosis, and death assessed during the periprocedural period and at 30 days.', 'Acetylsalicylic acid-LR was present in 34 (16%), CLO-LR in 33 (15%), and dual LR in 19 (9%) patients. Percutaneous coronary intervention-related myocardial infarction was encountered in 19 (9%) patients, with the highest incidence in dual-LR group (26.3%, P = .039). Composite ischemic events at 30 days were significantly more frequent in the dual-LR group than in other groups (36.8% vs 8.8% ASA-LR vs 6.1% CLO-LR vs 6.8% controls, P < .001). In multivariable analysis, dual LR (odds ratio 7.35, 95% CI 2.21-24.42, P < .001) and multivessel PCI (odds ratio 4.56, 95% CI 1.33-15.62, P = .016) were independently associated with ischemic events at 30 days.']
['To examine the variables relative to the response of oxybutynin treatment in children with daytime urinary incontinence.', "The records of patients seen for voiding problems between 1999 and 2003 were reviewed. Patients taking oxybutynin for 3 months or longer were included in the study. Patients with structural or neurologic bladder abnormalities and those taking oxybutynin at the initial visit were excluded. Age, sex, uroflowmetry findings, postvoid residual urine volume, duration and severity of symptoms before oxybutynin, urinary tract infection history, constipation, and the duration, dosage, and adverse effects of oxybutynin treatment were evaluated. Data were analyzed using Fisher's exact test for categorical variables, the two-sample t test or Wilcoxon rank-sum test for continuous and ordinal variables, and the linear mixed model analysis for uroflow data.", 'Eighty-one patients met the inclusion criteria. After an average follow-up of 1.2 years, 31 (38.3%) were dry, 25 (30.9%) had experienced significant improvement, 19 (23.5%) had experienced slight improvement, and 6 (7.4%) were unchanged. No significant differences were detected between those who became dry and those with little to no improvement with respect to age, sex, duration of symptoms, follow-up, uroflow pattern, postvoid residual urine volume, or bladder capacity. Those children presenting with decreased frequency of wetting episodes were significantly more likely to obtain daytime continence. The most common side effects were constipation (18.5%), dry mouth (17.3%), and flushing (13.6%).']
['Erythropoietic protoporphyria (EPP) is an inherited disease characterised by a ferrochelatase (FECH) deficiency, the latest enzyme of the heme biosynthetic pathway, leading to the accumulation of toxic protoporphyrin in the liver, bone marrow and spleen. We have previously shown that a successful gene therapy of a murine model of the disease was possible with lentiviral vectors even in the absence of preselection of corrected cells, but lethal irradiation of the recipient was necessary to obtain an efficient bone marrow engraftment. To overcome a preconditioning regimen, a selective growth advantage has to be conferred to the corrected cells.', 'We have developed a novel bicistronic lentiviral vector that contains the human alkylating drug resistance mutant O(6)-methylguanine DNA methyltransferase (MGMT G156A) and FECH cDNAs. We tested their capacity to protect hematopoietic cell lines efficiently from alkylating drug toxicity and correct enzymatic deficiency.', "EPP lymphoblastoid (LB) cell lines, K562 and cord-blood-derived CD34(+) cells were transduced at a low multiplicity of infection (MOI) with the bicistronic constructs. Resistance to O(6)-benzylguanine (BG)/N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) was clearly shown in transduced cells, leading to the survival and expansion of provirus-containing cells. Corrected EPP LB cells were selectively amplified, leading to complete restoration of enzymatic activity and the absence of protoporphyrin accumulation."]
['Dendritic cells (DCs) pulsed with HBsAg efficiently reverse the immune tolerance to hepatitis B virus (HBV) and induce HBV-specific cytotoxic T lymphocyte (CTL) responses in transgenic mice and healthy volunteers. However, it is not clear whether HBV core antigen (HBcAg)-pulsed DCs can effectively induce CD4(+) helper T cells polarization into Th1, which contribute to the induction and maintenance of HBV-specific CD8(+) T cells in chronic hepatitis B (CHB) patients. To address this issue, we conducted this study and investigated whether HBcAg-pulsed DCs could polarize Th1 cells and induce an HBcAg-specific CTL response.', 'HBcAg-pulsed DCs were generated from 21 CHB patients. The capacity of the HBcAg-pulsed DC vaccine to stimulate CD4(+) and CD8(+) T cells to produce IFN-gamma and IL-4 was estimated by intercellular cytokine staining, and the HBcAg-pulsed DCs derived from 10 humam leucocyte antigen (HLA)-A2(+) CHB patients were tested for the induction of HBV-specific CTLs from autologous T cells by pentamer staining. The cytotoxicity of these CTLs was evaluated in vitro by flow cytometry.', 'The HBcAg-pulsed DCs derived from CHB patients exhibited a stronger capacity to stimulate autologous CD4(+) and CD8(+) T cells to release IFN-gamma rather than IL-4, which could induce HBV core 18-27 specific CTLs, suggesting a specific cytotoxicity against T2 cells that had been loaded with the HBV core 18-27 peptide in vitro.']