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['The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings.', 'Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings.', "A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8±15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively."]
['Hypothermia is known to protect against ischemia/reperfusion (I/R) injury. The mechanisms of protection are incompletely understood and a temperature threshold for protection has not been established.', 'In anesthetized Wistar rats, partial (70%) hepatic ischemia was applied for 45 min. Three study groups were used. Group T31 (n = 6) spontaneously cooled to 31.3 +/- 0.8 degrees C, while group T34 (n = 6) spontaneously cooled to 34 degrees C and was then maintained at 34.0 +/- 0.1 degrees C using a heat lamp. The normothermic group (T37, n = 6) was maintained at 37.1 +/- 0.3 degrees C. Hepatic injury, inflammation, lipid peroxidation and metabolic function (using quantitative 1H-NMR) were assessed 24 h after reperfusion.', 'At 24 h following reperfusion, alanine aminotransferase and aspartate aminotransferase increased to 5101 +/- 2378 and 6409 +/- 4202 U/l in the normothermic T37 group (P < 0.05 vs. T34 and T31), whereas transaminases in hypothermic groups (T31 and T34) were significantly lower. Severe liver necrosis was only noted with T37. Myeloperoxidase activity was increased in the T37 group when compared with hypothermic groups (223 +/- 161 (T37) vs. 16 +/- 10 (T31) and 8 +/- 5 (T34) mU/min/mg of tissue, P<0.05 vs. T31 and T34). 1H-NMR analysis of the blood of normothermic animals revealed metabolic changes consistent with increased ischemic injury, which was almost completely ameliorated in T34 and T31 groups.']
['Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units.', 'We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications.', 'Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores.']
['Patients with single station mediastinal lymph node (N2) non-small cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2. The molecular factors which are involved in disease progression remain largely unknown. The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.', 'Gene expression analysis was performed using Agilent 4×44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.', 'We identified a 14 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between single station and multilevel N2 NSCLC. Four genes (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients. Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.']
["The discovery of Nanobodies (Nbs) with a direct toxic activity against African trypanosomes is a recent advancement towards a new strategy against these extracellular parasites. The anti-trypanosomal activity relies on perturbing the highly active recycling of the Variant-specific Surface Glycoprotein (VSG) that occurs in the parasite's flagellar pocket.", 'Here we expand the existing panel of Nbs with anti-Trypanosoma brucei potential and identify four categories based on their epitope specificity. We modified the binding properties of previously identified Nanobodies Nb_An05 and Nb_An33 by site-directed mutagenesis in the paratope and found this to strongly affect trypanotoxicity despite retention of antigen-targeting properties. Affinity measurements for all identified anti-trypanosomal Nbs reveal a strong correlation between trypanotoxicity and affinity (K(D)), suggesting that it is a crucial determinant for this activity. Half maximal effective (50%) affinity of 57 nM was calculated from the non-linear dose-response curves. In line with these observations, Nb humanizing mutations only preserved the trypanotoxic activity if the K(D) remained unaffected.']
['We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.', 'Between April 2005 and March 2012, patients (n = 158) diagnosed with metastatic colorectal cancer after at least four courses of first-line bevacizumab-based (n = 95) or cetuximab-based triplet (n = 63) were retrospectively analyzed. The KRAS genotypes were sequenced for all patients. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards models were used for univariate and multivariate analyses.', 'Cetuximab-based triplet was associated with a higher objective response rate (66.0 vs. 47.2 %, p = 0.037) and a higher conversion rate to resectability (39.7 vs. 20.0 %, p = 0.007) compared to bevacizumab-based triplet. Compared with bevacizumab-based triplet, cetuximab-based triplet significantly increased progression-free survival in patients with measurable metastatic colorectal cancer who achieved objective tumor response (responders) (median 13.1 vs. 10.5 months, p = 0.023), but no significant increase was observed for overall survival. After adjustment for group differences in baseline characteristics and combined chemotherapy agents, cetuximab-based triplet remained an independent determinant of progression-free survival in responders as compared with bevacizumab-based triplet. KRAS mutation was not a prognostic factor in patients with metastatic colorectal cancer.']
['Current data suggest great variability in serum response following lutein ingestion from various sources.', 'To compare the relative serum response during supplementation with free lutein (fL) and lutein esters (Le).', "72 volunteers (23-52 years; body mass index [BMI] >20 and <30 kg/m2; baseline serum lutein <20 µg/dL [<352 nmol/L]) were identified. Subjects, matched for gender, age, and BMI, were randomly assigned to the fL or Le group. fL and Le capsules contained 12.2 mg of free lutein or 27 mg of lutein ester (equivalent to 13.5 mg free lutein), respectively. Fasting blood was obtained at baseline and after 7, 14, 21, and 28 days of supplementation. Supplements were consumed with standard portions of dry, ready-to-eat cereal and 2% cow's milk.", 'Absolute changes in serum lutein, per mg daily dose, were significantly greater in fL vs. Le after 21 days (p \u200a=\u200a 0.0012) and remained so after 28 days (p \u200a=\u200a 0.0011) of supplementation. Serum lutein Area Under the Curve [AUC((day 0-28))] response was 17% greater for fL vs. Le (p \u200a=\u200a 0.0187). Regression models were used and determined that (1) baseline serum lutein levels and (2) the form of lutein ingested (fL > Le) influence the serum lutein response during supplementation, while subject age, gender, BMI, and serum lipids do not affect serum response.']
['Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).', 'We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).', 'Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.', 'Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67) mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P<0.001). Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 10(5)copies/mL (p<0.001). By multivariate analysis, high level (>10(5)copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while it was directly associated with the presence of promoter double T(1762)A(1764) mutations together with G(1757) (OR: 16.87, p=0.004).']
['The androgen receptor (AR) is a ligand-dependent transcription factor that mediates androgenic hormone action in cells. We recently demonstrated the involvement of phosphoinositide 3-OH kinase (PI3K) p110beta in AR transactivation and gene expression. In this study, we determined the upstream signals that lead to PI3K/p110beta activation and AR transactivation after androgen stimulation.', 'Human prostate cancer LAPC-4 and 22Rv1 cell lines were used for the experiments. AR transactivation was assessed using an androgen responsive element-driven luciferase (ARE-LUC) assay. Cell proliferation was examined using BrdU incorporation and MTT assays. Target genes were silenced using small interfering RNA (siRNA) approach. Gene expression was evaluated at the mRNA level (real-time RT-PCR) and protein level (Western blot). PI3K kinase activities were measured using immunoprecipitation-based in vitro kinase assay. The AR-DNA-binding activity was determined using chromatin-immunoprecipitation (ChIP) assay.', 'First, at the cellular plasma membrane, disrupting the integrity of caveolae microdomain with methyl-β-cyclodextrin (M-β-CD) abolished androgen-induced AR transactivation and gene expression. Then, knocking down caveolae structural proteins caveolin-1 or -2 with the gene-specific siRNAs significantly reduced androgen-induced AR transactivation. Next, silencing Gα(s) and Gα(12) genes but not other G-proteins blocked androgen-induced AR transactivation and cell proliferation. Consistently, overexpression of Gα(s) or Gα(12) active mutants enhanced androgen-induced AR transactivation, of which Gα(s) active mutant sensitized the AR to castration-level of androgen (R1881). Most interestingly, knocking down Gα(s) but not Gα(12) subunit significantly suppressed androgen-stimulated PI3K p110beta activation. However, ChIP analysis revealed that both Gα(s) or Gα(12) subunits are involved in androgen-induced AR interaction with the AR target gene PSA promoter region.']
['To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA.', 'The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed.', 'The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan-Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease-free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease-free and overall survival (both P < 0.05).']
['• To compare the influence of a 4-week course of empirical antimicrobial therapy or observation on the prostate-specific antigen (PSA) levels of asymptomatic patients with a raised baseline PSA. • To identify whether a decrease in PSA can predict the risk of prostate cancer (PCa) detection on prostate biopsy.', '• Patients were referred to our ambulatory centre because of a raised PSA level (>2.5 ng/mL) with a normal digital rectal examination. A 12-core prostate biopsy was indicated in these patients and they were offered antibiotic treatment with levofloxacin 500 mg daily for 30 days. • Patients who did not agree to use antibiotics but who still showed interest in participating underwent simple observation, serving as controls. • Total and free PSA levels at baseline and after 45 days were measured. Variation in PSA level was calculated. • All patients underwent a 12-core prostate biopsy 6 weeks after the initial visit.', '• In all, 245 men were enrolled, but 43 were lost due to follow-up. A total of 145 patients who used antibiotics and 57 controls were included in the analysis. • The median baseline PSA levels were 7.6 and 7.7 ng/mL in the antibiotic and control groups, respectively, with median follow-up levels of 6.8 and 7.0 ng/mL. The follow-up PSA level was significantly lower than the initial PSA level (P = 0.009). • Mean absolute and percentage variation in PSA level were similar in both groups (P = 0.828 and 0.128, respectively). • The overall PCa detection rate was 15.8%, and did not differ among the groups (P = 0.203). Regarding the percentage variation in PSA level, patients diagnosed with PCa tended to have their PSA level increased (22.4 vs -5.3%; P = 0.001). Indeed, a decrease of 20% in PSA was not predictive of a negative prostate biopsy (P = 0.41). • The area under the receiver operating characteristic curve for percentage PSA variation as a predictor of PCa was 0.660.']
['We investigated in postmenopausal women with primary breast cancer prior to surgical intervention whether, serum levels of different steroid hormones and hormonal precursors associated with tumor tissue estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status.', 'We enrolled 1,042 patients suffering invasive ductal carcinoma undergoing surgical resection in the National Institute of Oncology, Hungary between 2003 and 2011. Serum parameters were measured by RIA/IRMA assays; tumor tissue ER, PR and HER2 status was assessed histologically. Patients were classified according to tumor receptor status. Case-case analysis subjects were categorized into four subgroups based on serum hormone concentrations in ER, PR and HER2 receptor-negative cases, respectively.', 'Serum estrone sulfate and dehydroepiandrosterone sulfate levels correlated with each other and also with serum estrone and estradiol levels. According to case-case study the odds ratios in the highest quartile were 1.517 (p\xa0=\xa00.0305, Ptrend\xa0=\xa00.0394) for androstenedione, 1.495 (p\xa0=\xa00.0317, Ptrend\xa0<\xa00.0105) for estrone and 0.654 (p\xa0=\xa00.0273, Ptrend\xa0<\xa00.0151) for estrone sulfate/estrone ratio in PR+ vs. PR- tumors. Regarding HER2 status (HER2+ vs. HER2-), the odds ratios for estrone, estrone sulfate and estrone sulfate/estrone ratio were 0.530 (p\xa0=\xa00.0234, Ptrend\xa0=\xa00.0595), 2.438 (p\xa0=\xa00.0042, Ptrend\xa0<\xa00.0066) and 3.118 (p\xa0=\xa00.0001, Ptrend\xa0<\xa00.0001) in the highest quartile, respectively. Of note significantly increased BMI associates with PR+ and ER\xa0+/PR+ status while significantly decreased BMI was observed in HER2+ cases.']
['Cryptotanshinone, the major tanshinone isolated from Salvia miltiorrhiza Bunge, exhibits anti-inflammatory activity. However, there is no report on the effect of cryptotanshinone on recruitment of leukocytes to inflammatory sites. We therefore assessed the effects of cryptotanshinone on macrophage chemotaxis.', 'Macrophage migration induced by complement 5a (C5a) or macrophage inflammatory protein-1alpha (MIP-1alpha) was measured in vitro. Intracellular kinase translocation and phosphorylation was assessed by Western blotting.', 'RAW264.7 cell migration towards C5a (1 microg ml(-1)) was significantly inhibited by cryptotanshinone (1, 3, 10 and 30 microM) in a concentration-dependent manner. Primary human macrophages stimulated by C5a were similarly inhibited. C5a-evoked migration in RAW264.7 cells was significantly suppressed by wortmannin (phosphatidylinositol 3-kinase (PI3K) inhibitor), PD98059 (MEK1/2 inhibitor) and SB203580 (p38 mitogen-activated protein kinase (MAPK) inhibitor), but not by SP600125 (c-Jun N-terminal kinase (JNK) inhibitor), suggesting that activation of PI3K, ERK1/2 and p38 MAPK signal pathways was involved in responses to C5a. Western blotting revealed that cryptotanshinone significantly inhibited PI3K-p110gamma membrane translocation and phosphorylation of Akt (PI3K downstream effector protein) and ERK1/2 induced by C5a. However, neither p38 MAPK nor JNK phosphorylation was affected by cryptotanshinone. Wortmannin significantly attenuated C5a-induced PI3K-p110gamma translocation, Akt and ERK1/2 phosphorylation. PD98059 suppressed ERK1/2 phosphorylation but failed to modify PI3K-p110gamma translocation by C5a stimulation. Furthermore, MIP-1alpha-induced cell migration and PI3K-p110gamma translocation were also inhibited by cryptotanshinone in a concentration-dependent manner.']
['Older women are more likely to be diagnosed with primary metastasised breast cancer than their younger counterparts. Evolving treatment strategies of metastasised breast cancer have resulted in improved survival in younger patients, but it remains unclear if this improvement has occurred in older patients as well. The aim of this study was to assess changes in treatment strategies over time in relation to overall and relative survival of older patients compared to younger patients with primary metastasised breast cancer.', 'All patients with a breast cancer diagnosis and distant metastases at first presentation (stage IV), between 1990 and 2012, were selected from the Netherlands Cancer Registry. Changes in treatment over time per age-group (<65 years, 65-75 years and >75 years) were assessed using logistic regression. Overall survival over time was calculated using Cox Regression Models and relative survival was assessed using the Ederer II method.', 'Overall, 14,310 patients were included. Treatment strategies have strongly changed in the past twenty years; especially the use of chemotherapy has increased (P<0.001 in all age-groups). Overall survival of patients <65 has significantly improved (Hazard Ratio (HR) per year 0.98, 95% Confidence Interval (CI) 0.98-0.99, P<0.001), but the survival of older patients has not improved (HR 1.00, 95% CI 0.99-1.01, P=0.86 for patients aged 65-75 and HR 1.00, 95% CI 1.00-1.01, P=0.46 for patients aged >75). Similarly, relative survival has improved in patients <65 but not in women aged 65-75 and >75.']
['Postpartum patients have decreased plasma cholinesterase activity, which may slow the metabolism of mivacurium. We compared the duration of a mivacurium neuromuscular block in 11 women undergoing postpartum tubal ligation 36-99 h after delivery with that in 11 control women undergoing gynecological surgery. Anesthesia was induced with propofol and fentanyl and maintained with propofol and nitrous oxide. Neuromuscular block was monitored by electromyography, and the ulnar nerve was stimulated transcutaneously using a train-of-four pattern. Patients received a bolus dose of mivacurium 0.15 mg/kg. The median (range) duration of neuromuscular block until 25% recovery of the first twitch response was longer in the postpartum group, 19.4 (15.6-25.2) min, compared with the control group, 16.3 (11.0-23.4) min (P = 0.04). The median (range) plasma cholinesterase activity was decreased in the postpartum group, 4.0 (0.1-5.5) kU/L, compared with the control group, 7.1 (6.2-10.0) kU/L (P < 0.001). The duration of neuromuscular block was inversely correlated with cholinesterase activity (Kendall rank correlation tau = -0.43, P = 0.005). The slight prolongation of neuromuscular block should not be significant clinically.']
['Treatment with statins is considered a first line therapy in atherosclerotic disease. Intraplaque angiogenesis is involved in plaque progression and instability. It remains unclear whether the beneficial effect of statin treatment in humans is achieved through reduced intraplaque angiogenesis. The aim of this study was to evaluate the capillaries density in carotid plaques removed from patients treated with statin versus untreated patients.', 'We studied 102 patients who underwent carotid endarterectomy: 98 of them met the inclusion criteria and entered the study; 75 men and 23 women; mean age 66+/-8 years (range 42-83 years). Forty-three patients (44%) were on statin treatment at least 3 months before endarterectomy and 55 (56%) had never received statin treatment. The intensity of intraplaque angiogenesis was evaluated with immunohistochemistry using the antibody CD34. The number of capillaries per mm(2) was measured with a custom designed image tool analysis. With the exception of serum total cholesterol levels and serum low-density cholesterol levels, the two groups of patients did not vary significantly in cardiovascular risk factors and in parameters pertaining to the procedure profile. Patients on statin treatment had less capillaries per mm(2) than patients not receiving this kind of drugs (0.97+/-0.61 per mm(2) versus 1.39+/-0.98 per mm(2), p=0.031). Univariate associations between possible explanatory variables and number of capillaries per mm(2) were tested using Spearman rank R. Variables associated with a p-value <0.20 (age, serum creatinine, serum total cholesterol, serum low-density lipoprotein, serum homocysteine, presence of diabetes mellitus and statin treatment) were entered in a multivariable model. Multivariate analysis showed that statin treatment was the only independent predictor (t=-5.39, p<0.001) of intraplaque angiogenesis.']
['Esophageal squamous cell carcinoma (ESCC) is the sixth most lethal cancer worldwide and the fourth most lethal cancer in China. Genomic characterization of tumors, particularly those of different stages, is likely to reveal additional oncogenic mechanisms. Although copy number alterations and somatic point mutations associated with the development of ESCC have been identified by array-based technologies and genome-wide studies, the genomic characterization of ESCCs from different stages of the disease has not been explored. Here, we have performed either whole-genome sequencing or whole-exome sequencing on 51 stage I and 53 stage III ESCC patients to characterize the genomic alterations that occur during the various clinical stages of ESCC, and further validated these changes in 36 atypical hyperplasia samples.', 'Recurrent somatic amplifications at 8q were found to be enriched in stage I tumors and the deletions of 4p-q and 5q were particularly identified in stage III tumors. In particular, the FAM84B gene was amplified and overexpressed in preclinical and ESCC tumors. Knockdown of FAM84B in ESCC cell lines significantly reduced in vitro cell growth, migration and invasion. Although the cancer-associated genes TP53, PIK3CA, CDKN2A and their pathways showed no significant difference between stage I and stage III tumors, we identified and validated a prevalence of mutations in NOTCH1 and in the NOTCH pathway that indicate that they are involved in the preclinical and early stages of ESCC.']
['Delirium is a leading cause of hospitalization and morbidity in elderly persons. Nonconvulsive status epilepticus (NCSE) and delirium share many risk factors. We tested the hypothesis that NCSE plays an important role in delirium by performing continuous EEG (cEEG) monitoring in elderly patients with delirium of any cause.', 'Patients over 65 years old presenting with delirium in the emergency room were prospectively included and underwent either routine 20-minute EEG or cEEG within 24h after admission. Clinical, biological, and imaging characteristics, length of hospitalization, and outcome were compared between patients with possible NCSE and patients without epileptic discharges.', 'There were 32 patients in each group. Continuous EEG detected patterns compatible with NCSE in 28% and focal interictal epileptiform discharges (IEDs) in 16% of the patients. Routine EEG detected patterns compatible with NCSE in 6% and focal IEDs in 16% of the patients. History of cognitive impairment and use of antibiotics and hypernatremia were significantly associated with the presence of possible NCSE. Delirium in patients with possible NCSE was initially attributed to another cause in over 80% of the cases. Patterns compatible with NCSE were associated with a longer hospitalization stay and a higher mortality rate.']
['Depression of the Notch/Hes1 pathway has been reported to play a role in abnormal differentiation of intestinal epithelial cells (IECs) in diabetes mellitus (DM). However, the mechanism by which this pathway influences IEC differentiation has remained unclear. In this study, we have investigated the role of microRNAs (miRNAs) in regulating the Notch/Hes1 pathway in IECs of DM mice.', "Integrated comparative miRNA microarray technology was used to determine the expression profile of miRNAs in IECs of DM mice. After bioinformatic analysis, an miRNA with altered expression levels, miRNA-30e, was identified as a candidate for regulating the Notch pathway in DM. A luciferase reporter assay confirmed that miRNA-30e targeted 3'-UTR of the Notch gene. The role of miRNA-30e in regulating Notch signalling was then explored by up- and downregulating its expression in vitro and in vivo.", "Abnormal differentiation of IECs in DM mice was associated with reduced activity of the Dll4/NICD/Hes1 signal pathway. Based on bioinformatic analyses, increased expression of miRNA-30e was identified as a potential candidate for regulating Notch signalling. miRNA-30e targeted the 3'-UTR of Dll4 and downregulated Dll4 expression in primary IECs and IEC-6 cells. Exogenous miRNA-30e reduced activity of the Dll4/NICD/Hes1 pathway, and induced abnormal differentiation of IECs in normal mice. Conversely, treatment with miRNA-30e antagonist upregu-lated activity of the Dll4/NICD/Hes1 pathway in vivo, and normalized IEC differentiation in DM mice."]
['The bronchodilator test (BDT) is an important tool used in pulmonary function. Changes in forced expiratory volume in one second (FEV1) can be expressed as absolute change, or per cent of initial or predicted value. When the initial value is used, there may be a bias, as the smaller this value is, the greater the response will be. The main objective of this study is to establish whether there is any difference in using per cent of the initial spirometry value or per cent of the predicted value in order to consider a bronchodilator test positive, and if the initial obstruction of the patient influences such differences.', 'A retrospective analysis of the BDT made between October 1997 and February 2008. The results using an increase of 9% from the predicted FEV1 were compared with using 12% from the initial FEV1. The patients were divided into three groups depending on initial obstruction: no obstruction (FEV1>80% of predicted), mild (FEV1=60-80% of predicted) and moderate-severe (FEV1<60% of predicted). The kappa index of agreement between both methods was calculated.', 'A total of 4352 BDT were analysed. The agreement between both methods was high (k=0.832). In the group without initial obstruction (N=3007) the kappa index was 0.781, in the mild obstruction group (N=1067) the kappa index was 0.966 and in the moderate-severe group (N=278) it was 0.788.']
['Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma (HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies.', 'The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined.', 'LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin E2 (PGE2), Akt and phosphorylated Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT.']
['Biclustering is a popular method for identifying under which experimental conditions biological signatures are co-expressed. However, the general biclustering problem is NP-hard, offering room to focus algorithms on specific biological tasks. We hypothesize that conditional co-regulation of genes is a key factor in determining cell phenotype and that accurately segregating conditions in biclusters will improve such predictions. Thus, we developed a bicluster sampled coherence metric (BSCM) for determining which conditions and signals should be included in a bicluster.', 'Our BSCM calculates condition and cluster size specific p-values, and we incorporated these into the popular integrated biclustering algorithm cMonkey. We demonstrate that incorporation of our new algorithm significantly improves bicluster co-regulation scores (p-value = 0.009) and GO annotation scores (p-value = 0.004). Additionally, we used a bicluster based signal to predict whether a given experimental condition will result in yeast peroxisome induction. Using the new algorithm, the classifier accuracy improves from 41.9% to 76.1% correct.']
['Reactive oxygen species, such as superoxide, are being increasingly recognized as key components of a vast array of signaling pathways. Angiotensin II is a well-recognized stimulus for superoxide production through NADPH oxidase activation and opening of the mitochondrial ATP-sensitive potassium channels (mKATP). A role for this mechanism has been proposed to explain several physiological effects of the peptide. The aim of this study was to evaluate the involvement of this mechanism in the inotropic response to 100nmol/L angiotensin II.', 'Sarcomere shortening and intracellular pH (BCECF-epifluorescence technique) were evaluated in isolated cat ventricular myocytes placed in a perfusion chamber on the stage of an inverted microscope. Myocardial superoxide production was evaluated by the lucigenin quimioluminiscence method.', 'Angiotensin II (100nmol/L) increased~70% sarcomere shortening, effect that was only partially prevented by NADPH oxidase inhibition, mKATP channel blockade or inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1). Moreover, angiotensin II stimulates NHE-1 activity by a NADPH oxidase-dependent mechanism. Myocardial superoxide production was also increased by angiotensin II, and this action was completely prevented either by NADPH oxidase inhibition or mKATP channel blockade.']
['To examine using the folds of the retinal pigment epithelium (RPE) to diagnose Vogt-Koyanagi-Harada (VKH) disease.', "Retrospective clinical review of 57 Japanese patients between July 2005 and April 2009. Optical coherence tomography (OCT), fundus photographs and fluorescein angiography (FA) were studied to investigate Kendall's coefficients of concordance in seven findings by four ophthalmologists. The sensitivity and specificity of each finding were examined to confirm its efficacy. Each result was defined as positive when more than three of the ophthalmologists judged that the finding existed.", "The folds of the RPE on OCT were observed in 30/42 (71.4 %) eyes having VKH disease, but none in the other 72 eyes. Kendall's coefficient of concordance in the detection of the folds of the RPE was 0.90 and was the highest among all other findings. Sensitivity was higher in the detection of the RPE folds on OCT and in optic nerve staining on FA than other findings and the specificity was 100 % for the RPE folds and 26.7 % for the optic nerve staining."]
['Elevated uric acid (UA) level is reported to be related to the development of left ventricular hypertrophy (LVH) which is associated with high incidence of ventricular tachycardia (VT) and sudden cardiac death. However, little is known about the association between serum UA levels and the occurrence of VT. Thus, we examined the relationship between serum UA levels and the appearance of VT in patients with LVH.', 'The study subjects consisted of 167 patients (110 males, mean age 67.4 ± 12.7 years) with LVH detected by echocardiography. These patients were divided into two groups based on whether VT was presented (defined by more than 5 beats, n = 27) or not (n = 140) by 24-hour Holter ECG monitoring. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), the E/A ratio and deceleration time of transmitral flow velocity were assessed by echocardiography in each group. In addition, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), sodium, potassium, hemoglobin, total bilirubin and UA were compared in each group.', 'Echocardiographic findings did not show the difference between the two groups. However, BUN and UA levels in the VT group were significantly higher than those in the Non-VT group (p < 0.01). eGFR was significantly lower in the VT group than that in the Non-VT group (p < 0.01). A multivariate logistic regression analysis identified the UA level as an independent predictive factor for the occurrence of VT (odds ratio 1.61, 95% confidence interval 1.1-2.2, p < 0.01).']
['The rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is involved in obesity. Few studies have been conducted on patients who underwent bariatric surgery. The aim of this study was to evaluate the influence of FTO SNPs on body weight, body composition, and weight regain during a 60-mo follow-up period after bariatric surgery.', 'The rs9939609 was genotyped in 146 individuals using a real-time polymerase chain reaction TaqMan assay. Data for lifestyle, comorbidities, body weight, body mass index (BMI), excess weight loss (EWL), and body composition were obtained before and 6, 12, 18, 24, 36, 48, and 60\xa0mo after surgery. Data were analyzed by comparing two groups of patients according to rs9939609 FTO gene polymorphism. Mixed-regression models were constructed to evaluate the dynamics of body weight, BMI, and EWL over time in female patients.', 'No differences were observed between the groups during the first 24\xa0mo after surgery. After 36, 48, and 60\xa0mo, body weight, fat mass, and BMI were higher, whereas fat-free mass and EWL were lower in the FTO-SNP patient group. Weight regain was more frequent and occurred sooner in the FTO-SNP group.']
['Human airway smooth muscle cells (HASMs) are involved in the pathogenesis of asthma. By producing chemokines, HASMs play a role in the inflammatory processes observed in this disease. Eotaxin, eotaxin-2, and eotaxin-3 are important chemoattractants for eosinophils, and these chemokines are expressed during different phases of the allergic reaction. TH2 cytokines and TGF-beta can be found in increased levels in patients with asthma, and these cytokines may be involved in the regulation of chemokine expression.', 'The aim of this study was to determine the effect of TH2 cytokines and TGF-beta on the regulation of expression of eotaxin, eotaxin-2, and eotaxin-3 by HASMs.', 'HASMs were incubated for 24 hours with IL-4, IL-13, TGF-beta1, or combinations of these cytokines. Protein and mRNA levels of eotaxin and eotaxin-3 were evaluated by sandwich ELISA and reverse transcriptase-PCR.', 'IL-4 and IL-13 induced mRNA and protein for both eotaxin and eotaxin-3. Eotaxin-2 mRNA and protein were not detected in HASMs. TGF-beta alone did not induce expression of the eotaxins. However, in combination with IL-4 or IL-13, TGF-beta enhanced eotaxin production and inhibited TH2 cytokine-induced eotaxin-3 production.']
['The HLA 8.1 ancestral haplotype (HLA-B*08/DRB1*03/DQA1*05/DQB1*02) is associated with adult/juvenile idiopathic inflammatory myopathy (IIM), but confers a greater strength of association in patients possessing anti-Jo-1 or anti-PM-Scl antibodies. The HLA-DPB1 gene is centromeric to other HLA class II loci and separated by a recombination hotspot. We investigated whether HLA-DPB1 associations differ between anti-Jo-1 and anti-PM-Scl antibody-positive IIM cases.', 'Two hundred and thirty-three adult IIM patients (73% females, 49.4 +/- 13.6 years) with PM (n = 89), DM (n = 88) and myositis associated with another CTD (n = 55) and 85 juvenile DM patients (75% females, 6.2 +/- 3.6 years) were compared with 678 UK Caucasian controls. Patients/controls were genotyped for HLA-DPB1 and DRB1 alleles. Myositis-specific and associated antibodies were identified in cases using immunoprecipitation.', 'HLA-DPB1*0101 was associated with IIM overall [22 vs 13% controls, corrected probability (P(corr)) = 2 x 10(-03); odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (P(corr) = 7 x 10(-03); OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (P(corr) = 3 x 10(-5); OR 4.1; 95% CI 2.1, 7.8). No significant DPB1*0101 difference was present between anti-PM-Scl cases and controls. The HLA-DPB1*0101 association in IIM overall cases was dependent on the presence of DRB1*03. A number of HLA-DRB1*03/DPB1 haplotypes were identified, but only DRB1*03/DPB1*0101 was associated with anti-Jo-1 antibody-positive cases.']
['The CpG island methylator phenotype (CIMP) is observed in approximately 30% of colorectal cancer (CRC) cases and is characterized by the concurrent methylation of multiple CpG islands in tumor DNA. This phenotype (CIMP+) is more frequently observed in tumors with proximal location, microsatellite instability, and normal p53. Because it has previously been observed that each of these features is associated with a good survival benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy, we investigated in the present study whether CIMP+ has independent predictive value.', 'CIMP+ status was evaluated in 103 stage III CRCs from patients treated with surgery alone and for an additional 103 cases from patients treated with surgery and adjuvant 5-FU-based chemotherapy. The two cohorts were randomly pair-matched for age, sex, and tumor site, and the median length of follow-up time was 39 months.', 'CIMP+ status predicted survival benefit from 5-FU treatment independently of microsatellite instability and p53 mutation status (relative risk = 0.22; 95% confidence interval, 0.06-0.84; P = 0.027). Unmeasured, high-risk confounding factors could only account for this association if they were unequally distributed between the two patient cohorts by a factor of at least 2-fold.']
['To observe the efficacy of auto-trilevel positive airway pressure (Auto-trilevel PAP) ventilation in overlap syndrome (OS) patients with hypercapnia.', "From October 2012 to May 2014, 21 OS patients with a PaCO2> 45 mmHg (1 mmHg = 0.133 kPa) and coexisting stable chronic obstructive pulmonary diseases (COPD) and moderate-to-severe OSAS were recruited. Three different positive airway pressure (PAP) modes of ventilators (SOMNOvent auto-S, Weinmann Inc, Germany) were employed for 8 hours per night with each mode at each night and two nights' interval without any treatment among different modes. Under mode one, the expiratory positive airway pressure (EPAP) issued by bilevel positive airway pressure (BiPAP) was titrated as the minimal positive pressure for a disappearance of snoring. The same inspiratory positive airway pressure (IPAP) titrated by end tidal CO2 levels under mode 1 was used under modes 2 and 3 as well. However, the EPAP issued by BiPAP under mode 2 was 3 cmH2O (1 cmH2O = 0.098 kPa) higher than that under mode 1. Under mode 3 with autotrilevel PAP, the beginning of EPAP was set the same as that under mode 1 while the end of EPAP (EEPAP) was automatically adjusted based on upper airway patency condition. Comparisons were made for parameters before and after treatment as well as among different ventilation modes. The following parameters were compared such as nocturnal apnea hypopnea index (AHI), minimal SpO2 (miniSpO2), arousal index, sleep efficiency, morning PaCO2 and Epworth sleepiness score (ESS).", 'Compared with the parameters pre-therapy, modes 1-3 showed a significant decrease in nocturnal AHI (6.3 ± 1.3), (3.1 ± 1.0), (3.6 ± 0.6) vs (38.6 ± 11.3) events/h), arousal index ((7.0 ± 1.1), (5.1 ± 0.9), (4.2 ± 1.7) vs (27.5 ± 5.4) events/h), morning PaCO2 (42.4 ± 3.8), (47.9 ± 2.6) and (43.2 ± 3.3) vs (57.3 ± 4.3) mmHg and daytime ESS (7.2 ± 1.3, 7.4 ± 1.3 and 5.3 ± 1.5 vs 11.4 ± 2.7), but a significant increase in nocturnal miniSpO2 (82.3 ± 5.4), (89.6 ± 3.9) and (90.3 ± 3.2) vs (62.4 ± 11.3) mmHg and sleep efficiency caused (71.3 ± 5.2)%, (79.4 ± 4.3)% and (83.2 ± 4.4)% vs (59.8 ± 6.3)% (all P < 0.01). Comparison of 3 modes demonstrated that, with the same IPAP, mode 3 resulted in the lowest arousal index, daytime ESS and the highest sleep efficiency. Comparison of modes 1 and 2 revealed a statistically lower AHI but higher miniSpO2 and morning PaCO2 under mode 2 (all P < 0.01). Compared with mode 1, mode 3 showed a lower AHI, higher miniSpO2 (all P < 0.01), but there was no significant difference in PaCO2 at the end of therapy. Compared with mode 2, mode 3 showed a significant lower PaCO2 (P < 0.01), but there was no significant difference in AHI and miniSpO2.']
['Aortic valve (AV) calcification occurs via a pathophysiological process that includes lipoprotein deposition, inflammation, and osteoblastic differentiation of valvular interstitial cells. Here, we investigated the association between endoplasmic reticulum (ER) stress and AV calcification.', 'We identified ER stress activation in AV of patients with calcified AV stenosis. We generated an AV calcification model in hypercholesterolemic rabbits and mice, respectively, and found marked AV ER stress induction. Classical ER stress inhibitor, tauroursodeoxycholic acid, administration markedly prevented AV calcification, and attenuated AV osteoblastic differentiation and inflammation in both rabbit and mouse models of AV calcification via inhibition of ER stress. In cultured valvular interstitial cells (VICs), we found that oxidized low density lipoprotein (oxLDL) caused ER stress in a cytosolic [Ca](2+)i-dependent manner. OxLDL promoted osteoblastic differentiation via ER stress-mediated protein kinase-like ER kinase/activating transcription factor 4/osteocalcin and inositol-requiring transmembrane kinase and endonuclease-1α (IRE1α)/spliced X-box-binding protein 1/Runx2 pathway, and induced inflammatory responses through IRE1α/c-Jun N-terminal kinase and IRE1α/nuclear factor kappa-light-chain-enhancer of activated B cells signaling in VICs. Inhibition of ER stress by either tauroursodeoxycholic acid or 4-phenyl butyric acid could both suppress oxLDL-induced osteoblastic differentiation and inflammatory responses in VICs.']
['A nationwide survey was conducted to identify the clinical presentation of pediatric chronic intestinal pseudo-obstruction (CIPO) in Japan.', 'Data were collected via a questionnaire, ensuring patient anonymity, from facilities that treat pediatric gastrointestinal diseases in Japan.', 'Ninety-two responses were collected from forty-seven facilities. Sixty-two patients (28 males, 34 females) met formal diagnostic criteria for CIPO. The estimated pediatric prevalence was 3.7 in 1 million individuals. More than half the children (56.5%) developed CIPO in the neonatal period. Full-thickness intestinal specimens were available for histopathology assessment in forty-five patients (72.6%). Forty-one (91.1%) had no pathological abnormalities and were considered to be idiopathic. Patients were treated according to the local protocol of each facility. Forty-one patients (66.1%) had restricted oral intake of ordinary diets, and twenty-nine (46.8%) depended on parenteral nutrition. No therapeutic intervention, including medication and surgery, successfully improved oral food intake or obstructive symptoms. Only three patients (4.8%) died from enteritis or sepsis.']
['Malnutrition and low body weight are common in patients with emphysema. Previous work has demonstrated correlation between severity of airflow obstruction and body weight. Lung volume reduction surgery (LVRS) is a recent advance in the treatment of patients with severe emphysema that results in improved pulmonary function. We formed the hypothesis that improved lung mechanics after LVRS would result in body weight gain.', 'Retrospective chart review.', 'All patients who underwent bilateral LVRS for severe emphysema at the University of Michigan between January 1995 and April 1996 were eligible for the study.', 'Pulmonary function and body weight were measured preoperatively and at 3, 6, and 12 months postoperatively for patients who underwent bilateral LVRS between January 1995 and April 1996. The average weight gain in 38 patients returning for 12 months of follow-up was 3.8 +/- 0.9 kg, or 6.2% of the preoperative weight. Women gained significantly more weight than men (9.2 vs 2.2%, respectively) at 1 year. Interestingly, there was no correlation between change in weight and postoperative change in FEV(1), FVC, residual volume (RV), total lung capacity (TLC), or RV/TLC at 12 months. However, there was a statistically significant correlation between weight gained and improvement in diffusion of carbon monoxide measured 12 months postoperatively.']
['Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers.', 'The association between allelic loss and survival was analysed by univariate and multivariate tests to identify independent variables of survival.', "Loss of chromosome 2p21-16.3 reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic significance was evident in patients with Dukes' A + B as well as Dukes' C tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis, tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1 or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21-16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were independent variables of survival. Loss of 2p21-16.3 was, moreover, associated with increased loss of the other tumour suppressor loci (P = 0.012)."]
['The callosal disconnectivity theory was previously proposed to explain the pathophysiology of schizophrenia. The goal of this study was to investigate the metabolic integrity of the corpus callosum in patients with schizophrenia by proton MR spectroscopy.', 'Twelve first-episode and 16 chronic patients meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for schizophrenia and 28 age- and sex-matched control subjects were enrolled in the study. We measured the absolute concentrations of neurometabolites and T2 relaxation times of tissue water (T2B) in the genu of the corpus callosum by using the internal water-reference method. The severity of symptoms in patients was rated by means of psychopathology scales. Differences in neurometabolite concentrations and T2B values between the patients and control subjects were assessed. We also investigated the correlation of metabolite concentrations with the severity of symptoms.', 'N-acetylaspartate (NAA) concentrations were significantly lower in the first-episode as well as in chronic patients, compared with respective control subjects (P < .001). NAA concentrations in the first-episode and chronic patient groups were negatively correlated with both the Brief Psychiatry Rating Scale and the Scale for Assessment of Negative Symptoms scores (P < .001). There was a significant negative correlation between the NAA concentrations and the Scale for Assessment of Positive Symptoms scores in all patients (P = .028). T2B values were significantly higher in the patients, compared with the control subjects (P < .001).']
['The objective of this secondary analysis was to examine the effects of modafinil on the Functional Outcomes of Sleep Questionnaire (FOSQ) in patients with obstructive sleep apnea and residual excessive sleepiness with continuous positive airway pressure (CPAP) use. We also explored the association of improvement of functional status with the presenting level of subjective sleepiness.', 'Data were pooled from 2 randomized placebo-controlled studies (4-week and 12-week interventions) of modafinil in patients with residual sleepiness (Epworth Sleepiness Scale score > or =10 on CPAP).', "The analysis included 480 patients (FOSQ efficacy data n=442 patients), 292 in the modafinil group and 188 in the placebo group. The mean age (SD) of the analyzed sample was 49.7 (9.2) years; 76% were men. Following administration with modafinil, there were greater improvements from baseline in the Total score (p < 0.0001) as well as 4 of the 5 domains (p < 0.05), compared with placebo. A greater proportion of patients who received modafinil were considered responders, compared with patients who received placebo (45% vs. 25%; p < 0.001). Responder analysis based on the individual FOSQ domain items demonstrated that 18 of the 30 FOSQ items increased by at least 1 point for significantly more patients who received modafinil (p < 0.05). Improvements in functional status were not found to depend on patients' degree of subjective sleepiness at baseline."]
['The mutations responsible for cystinosis in South African patients are currently unknown. A pertinent question is whether they are similar to those described elsewhere in the world.', 'Children who were being managed for cystinosis in the Western Cape Province of South Africa between 2002 and 2013 were studied. All underwent molecular analysis to detect sequence variations in the cystinosis gene.', 'This cohort study included 20 patients, 13 of whom were Xhosa-speaking black South Africans and seven were Cape Coloureds (mixed race); none were Caucasian. All had nephropathic infantile-type cystinosis with evidence of proximal tubulopathy, with glycosuria and renal phosphate wasting. Diagnosis was confirmed in 19 cases by demonstrating an elevated cystine concentration in leukocytes. Molecular analysis of the cystinosin gene revealed that 19 patients had a G\u2009>\u2009A mutation in intron 11 (CTNS-c.971-12G\u2009>\u2009A p.D324AfsX44) which caused an out-of-frame 10-bp insertion. Of these 19 patients, 16 were homozygous for this mutation, which was the most frequent mutation identified in the alleles of the black South African and Cape Coloured patients (96 and 71 %, respectively).']
['An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction in the presence of the viral large T-antigen using a semiconservative mechanism and has been shown to contain all the proteins and enzymes required to support DNA synthesis. We are currently using the DNA synthesome as a unique model for analyzing the mechanism of action of anticancer drugs affecting DNA replication. The purpose of this study was to further investigate the mechanism of action of ara-C using the DNA synthesome isolated from the human breast cancer cell line MDA MB-468.', 'Synthesome-mediated SV40 DNA replication was performed in the presence of various concentrations of ara-CTP (the active metabolite of ara-C) and the types of daughter DNA molecules produced were analyzed lusing neutral and alkaline gel electrophoresis. We also examined the effect of ara-C on intact MDA MB-468 cell DNA synthesis and on cell proliferation. In addition, we studied the effect of ara-CTP on the activity of some of the synthesome target proteins (the DNA polymerases alpha and delta).', 'Full-length daughter DNA molecules were obtained in the presence of low concentrations of ara-CTP while at higher concentrations, there was an inhibition of full-length daughter DNA synthesis. The findings suggest that specifically the initiation phase of DNA synthesis was inhibited by ara-CTP since the production of the short Okazaki fragments was suppressed at all concentrations of the drug above 10 microM. In addition, it was found that the IC50 of ara-CTP for inhibition of synthesome-mediated in vitro DNA replication was comparable to that required to inhibit intact cell DNA synthesis. Further experimentation has shown that ara-CTP preferentially inhibits the activity of the synthesome-associated DNA polymerase alpha enzyme while the DNA polymerase delta seems to be resistant to the inhibitory effect of that drug.']
['To examine the effects of dantrolene on nitric oxide (NO) production and on the activity and protein expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) in rat alveolar macrophages.', 'Pulmonary alveolar macrophages isolated from Sprague-Dawley rats were used. After incubation of macrophages with dantrolene (1 to 100 microM) and LPS (1 microgram.ml-1) and IFN-gamma (100 u.ml-1) for 24 hr, the cell-free medium was removed for measuring the nitrite and tumour necrosis factor-alpha (TNF-alpha) levels by Griess reaction and ELISA kit, respectively. The harvested macrophages were also used to determine the activity of iNOS by using the conversion of [3H]-L-arginine to [3H]-L-citrulline method. Protein expression of iNOS was detected by Western blot analysis.', 'In rats alveolar macrophages, (i) dantrolene (1 to 100 microM) caused a dose-dependent suppression of the production of nitrite and TNF-alpha induced by LPS (1 microgram.ml-1) plus IFN-gamma (100 u.ml-1) and (ii) dantrolene (100 microM) inhibited the activity (by 37 +/- 5%, P < 0.01) and protein expression (by 39 +/- 12%, P < 0.01) of iNOS in response to LPS plus IFN-gamma.']
['The current increase of obesity and metabolic syndrome (MS) focuses attention on bisphenol-A (BPA), "obesogen" endocrine disruptor, main plastic component. Aim was to verify the role of BPA in metabolic alterations, insulin resistance, low grade inflammation and visceral obesity.', 'A cross-sectional study was performed in 76 out of 139 environmentally exposed adult males, unselected Caucasian subjects, enrolled by routine health survey at the "Federico II" University of Naples outpatient facilities. BPA plasma levels (ELISA), metabolic risk factors, homeostasis model assessment of insulin resistance index, plasma monocyte chemoattractant protein 1, interleukin-6 (IL-6) and tumor necrosis factor-alpha were performed. Clinical and biochemical parameters have been compared with BPA and pro-inflammatory cytokines levels.', 'In total 24 subjects out of 76 (32%) presented with waist circumference (WC) >102 cm, 36 (47%) had impaired fasting glucose and 24 (32%) subjects had insulin resistance [11 out 52 (21%) with WC ≤102 cm and 13 out of 24 with WC >102 cm (54%), χ(2) 6.825, p = 0.009]. BPA and pro-inflammatory cytokine levels were significantly higher in subjects with visceral adiposity (WC > 102 cm). BPA correlated with WC, triglycerides, glucose homeostasis and inflammatory markers. At the multivariate analysis WC and IL-6 remained the main predictors of BPA.']
['Patients with cutaneous melanoma (CM) on the trunk have a worse prognosis than those with extremity CM. One reason could be multiple or uncommon (outside axilla or groin) sentinel node locations (SNLs).', 'We identified 859 patients who underwent sentinel node biopsy for trunk (n\xa0=\xa0465) or extremity (n\xa0=\xa0394) CM in three Swedish healthcare regions from 2000 to 2008. We collected patient, tumor, and sentinel node characteristics through clinical registers and medical records. We investigated the distribution of SNLs in a logistic regression model, and risk of overall and melanoma-specific death through 2011 in a multivariable Cox regression model.', 'Trunk CM was associated with multiple SNLs (31 vs. 7\xa0%; odds ratio [OR] 7.1; 95\xa0% confidence interval [CI] 4.6-11.5; p\xa0<\xa00.001) but not uncommon SNLs (8 vs. 7\xa0%; OR 1.1; 95\xa0% CI 0.6-1.9; p\xa0=\xa00.75) compared with extremity CM. The increased risk of melanoma-specific death was confirmed for trunk CM (hazard ratio [HR] 1.9; 95\xa0% CI 1.3-2.9; p\xa0=\xa00.003), especially on the upper back (HR 2.3; 95\xa0% CI 1.4-3.6; p\xa0<\xa00.001) compared with extremity CM. Uncommon SNLs (HR 0.5; 95\xa0% CI 0.2-1.4; p\xa0=\xa00.21) or multiple SNLs (HR 1.1; 95\xa0% CI 0.4-2.9; p\xa0=\xa00.81) were not associated with melanoma-specific death compared with those with common/single SNL.']
['Severe pulmonary hypertension is still a cause of morbidity and mortality in children after cardiac operations. The objective of this study was to compare the vasodilator properties of inhaled nitric oxide, a novel pulmonary vasodilator, and intravenous prostacyclin in the treatment of severe postoperative pulmonary hypertension.', 'Thirteen children (aged 3 days to 12 months) with severe pulmonary hypertension after cardiac operations were given inhaled nitric oxide (20 ppm x 10 minutes) and intravenous prostacyclin (20 ng.kg-1.min-1 x 10 minutes) in a prospective, randomized cross-over study.', 'Both nitric oxide and prostacyclin resulted in a reduction in pulmonary arterial pressure, although the mean pulmonary arterial pressure was significantly lower during nitric oxide therapy (28.5 +/- 2.9 mm Hg) than during prostacyclin therapy (35.4 +/- 2.1 mm Hg; p < 0.05). The mean pulmonary to systemic arterial pressure ratio was also significantly lower during nitric oxide than prostacylin administration (0.46 +/- 0.04 versus 0.68 +/- 0.05; p < 0.01), due mainly to only prostacyclin lowering systemic blood pressure.']
['Prevalence and factors associated with sexual dysfunction in HIV-positive women are poorly known.', 'This was a cross-sectional study in a cohort of HIV-infected women. Clinically stable women were invited to participate in a female sexual dysfunction (FSD) evaluation with Female Sexual Function Index (FSFI) exploring desire, arousal, lubrication, orgasm, pain and satisfaction. An FSFI score <23 was used for defining FSD. Variables evaluated included body appearance satisfaction, interference of body changes with habits, social life and attitudinal aspects of body image, health-related quality of life, hormonal assessment, menopause, cumulative exposure to antiretroviral drug classes and immune-virological parameters. Lipodystrophy was defined according to the HIV Outpatient Study definition.', 'A total of 185 women completed the FSFI. The mean (+/-SD) age was 42 years (+/-5), 27% had CDC stage C, the mean (+/-SD) CD4+ T-cell count was 508 cells/microl (+/-251) and median HIV RNA was 1.7 log10 copies/ml (interquartile range 1.7-2.6). Among 161 evaluable patients, 59 (32%) reported FSD. In a multiple linear regression analysis, desire, arousal and satisfaction domains were associated with interference of body changes with habits, social life and attitudinal aspects of body image (beta = 0.22, 95% confidence interval [CI] 0.06-0.37; beta = 0.29, 95% CI 0.10-0.48; and beta = 0.20, 95% CI 0.02-0.38, respectively). Lubrication and orgasm domains were associated with body image satisfaction (beta = -0.49, 95% CI -0.88 - -0.10 and beta = -0.58, 95% CI -1.00 - -0.16, respectively). No significant associations with sex hormones, CDC stage, CD4+ T-cell count, HIV RNA viral load and cumulative exposure to antiretroviral drug classes were found. In women with FSD, severity of self-perceived abdominal fat accumulation showed a trend towards lower FSFI scores (ANOVA P = 0.02).']
['The gammadelta T cells serve as early immune defense against certain encountered microbes. Only a few gammadelta T cell-recognized ligands from microbial antigens have been identified so far and the mechanisms by which gammadelta T cells recognize these ligands remain unknown. Here we explored the mechanism of interaction of human gammadelta T cells in peripheral blood with Lipid A (LA).', 'First, resting gammadelta T cells (mainly Vdelta2 T cells) displayed a strong proliferative response to LA-pulsed monocyte-derived dendritic cells (moDC) and LA-pulsed paraformaldehyde-fixed moDC, but not to free LA in a TCR gammadelta-dependent manner. Second, anti-CD1b or anti-CD1c antibodies could block proliferative response of resting gammadelta T cells to LA-loaded moDC. Besides, only LA-loaded CD1b/CD1c-transfected C1R lymphoblastoma cells (CD1b-/CD1c-C1R) were able to stimulate the proliferation of human gammadelta T cells. Third, the expressions of both Toll-like receptor (TLR)2 and TLR4 on surface of LA-activated gammadelta T cells were upregulated, whereas only anti-TLR4 antibody could partially block their response to LA; Finally LA-loaded moDCs induce gammadelta T cells to produce Th1 cytokines, such as IFN-gamma.']
['Adjuvant treatment for early stage, estrogen receptor (ER) positive invasive breast cancer has been based on prognosticators such as menopausal status. The recurrence score (RS) from the 21-gene assay Oncotype DX (ODX) is predictive of a 10-y distant recurrence in this population but is rarely applied to premenopausal patients. The relationship between menopausal status and RS was evaluated.', 'An institutional review board-approved retrospective review was conducted of invasive breast cancer patients with known RS. ODX eligibility was based on National Comprehensive Cancer Network guidelines or physician discretion. Perimenopausal women were classified as premenopausal for statistical analyses. Comparisons of menopausal status and RS were made using general linear regression model and the exact Wilcoxon rank-sum test.', 'Menopausal status was available for 575 patients (142 premenopausal, 433 postmenopausal). Median age was 46 y for premenopausal and 62 y for postmenopausal. Median invasive tumor size was 1.5 cm for both cohorts. Mastectomy rate was higher in the premenopausal group (54.8%) than postmenopausal (42%; P = 0.0001). Premenopausal women had a higher local-regional recurrence rate (2.8% versus 0%; P = 0.0384) but distant recurrence and overall survival were not statistically different (P = 0.6808). Median ER H-score was lower in premenopausal (H-score = 270) than postmenopausal women (H-score = 280; P < 0.0001). Median RS was 16 for both premenopausal (range, 0-54) and postmenopausal (range, 0-63) women. Menopausal status as a categorical variable was not predictive of RS (P-value = 0.6780).']
['Allergic rhinitis (AR) is a complex chronic inflammatory disease of the nasal mucosa, caused by an interaction between genetic and environmental factors. As evidence suggests that some genetic variants may increase susceptibility to both AR and asthma, the objective of this study was to identify asthma susceptibility variants associated with AR in the Chinese population.', 'A cohort of 402 individuals with physician-diagnosed AR and 416 healthy controls were recruited from the Han Chinese population in Beijing. DNA was extracted from the peripheral blood and a total of 12 single-nucleotide polymorphisms (SNPs) shown to be associated with asthma in Japanese subjects were selected for genotyping using the SequenomMassARRAY technology platform.', 'Analysis of frequency differences of allele between the AR patients and control subjects showed that the C allele of rs204993 in the pre-B-cell leukemia homeobox 2 (PBX2) gene from the 6p21.3 locus was significantly associated with AR (p = 0.0006, pcorrected = 0.0340). Genotype analysis further confirmed the difference in distribution of this variant between AR patients and controls in the both the dominant (pT/C+C/C vs T/T = 7.37×10(-5) ) and co-dominant (pT/C vs T/T = 1.98 × 10(-4) , pC/C vs T/T = 0.004) models.']
['To examine the functional interaction between HIV-1 Tat protein and the cyclin T1 and T2 proteins which, in association with cyclin dependent kinase (CDK)9, are the regulatory subunits of the TAK/P-TEFb cellular complex strictly required for Tat transactivation.', 'HIV-1 long terminal repeat (LTR) reporter plasmid was co-transfected into human and rodent cells with expression vectors encoding Tat and vectors encoding the cyclins T1, T2a and T2b, respectively.', 'Tat-mediated transactivation of HIV-1 LTR-driven transcription was compared in the presence or absence of different cyclins T (T1, T2a and T2b), upon co-transfections into human and rodent cell lines. Protein interactions were analysed by in vitro binding assays.', 'It was found that Tat function in rodent cells is enhanced by co-expression of cyclin T1 but not cyclin T2. The N-terminal region (amino acids 1-290) of cyclin T1 is sufficient for this function and for binding to Tat and CDK9. Cyclin T2 binds to CDK9 but not to Tat. Moreover, enforced expression of cyclin T2 inhibits cyclin T1-mediated enhancement of Tat in rodent cells and it represses Tat activity in human cells.']
['The association between infant formula feeding at birth and subsequent feeding patterns in a low- or middle-income context is not clear.', 'We examined the association of infant formula feeding during the first 3 d after birth with subsequent infant formula feeding and early breastfeeding cessation in Vietnam.', 'In a cross-sectional survey, we interviewed 10,681 mothers with children aged 0-23 mo (mean age: 8.2 mo; 52% boys) about their feeding practices during the first 3 d after birth and on the previous day. We used stratified analysis, multiple logistic regression, propensity score-matching analysis, and structural equation modeling to minimize the limitation of the cross-sectional design and to ensure the consistency of the findings.', 'Infant formula feeding during the first 3 d after birth (50%) was associated with a higher prevalence of subsequent infant formula feeding [stratified analysis: 7-28% higher (nonoverlapping 95% CIs for most comparisons); propensity score-matching analysis: 13% higher (P < 0.001); multiple logistic regression: OR: 1.47 (95% CI: 1.30, 1.67)]. This practice was also associated with a higher prevalence of early breastfeeding cessation (e.g., <24 mo) [propensity score-matching analysis: 2% (P = 0.08); OR: 1.33 (95% CI: 1.12, 1.59)]. Structural equation modeling showed that infant formula feeding during the first 3 d after birth was associated with a higher prevalence of subsequent infant formula feeding (β: 0.244; P < 0.001), which in turn was linked to early breastfeeding cessation (β: 0.285; P < 0.001).']
['To investigate the effects of short-term, reduced-volume sprint interval training (SIT) compared to traditional exercise recommendations (TER) in sedentary obese men.', 'Sixteen subjects [37.8\u2009±\u20095.8\u2009years; body mass index (BMI) 32.8\u2009±\u20094.7\u2009kg/m(2)] were randomly allocated to 2\u2009weeks of either SIT (6 sessions of 8-12\u2009×\u200910\u2009s sprints) or TER [10 sessions of 30\u2009min at 65% peak oxygen consumption (VO(2peak))] cycle exercise. Fasting plasma glucose, insulin, non-esterified fatty acids (NEFA), homeostasis model assessment of insulin sensitivity (HOMA-IR), body composition and VO(2peak) were assessed at baseline and approximately 72\u2009h after the final training bout. Skeletal muscle biopsy samples were also obtained before and 72\u2009h after training and analysed for AS160 phosphorylation and COX II, COX IV, GLUT-4, Nur77 and SIRT1 protein expression.', 'No changes in BMI, body composition, VO(2peak), glucose, insulin, NEFA and HOMA-IR were observed after training, either within or between groups. Skeletal muscle markers of glucose metabolism and mitochondrial function also remained unaltered after 2\u2009weeks of exercise training.']
['Previous studies demonstrated that pharmacological blockade of CB1 cannabinoid receptors decreases the extinction of conditioned fear and spatial memory in rodents. However, the effects of CB1 cannabinoid receptor activation in this response remain unclear.', 'To evaluate the effects of the cannabinoid agonist WIN 55,212-2 (WIN) and the cannabinoid antagonist SR 147778 (SR) on the extinction of contextual fear memory in rats 24 h or 30 days after fear conditioning.', 'For fear conditioning, rats were placed in the conditioning chamber for 3 min and received a 1-s electric foot shock (1.5 mA). Retrieval testing consisted of a 3-min exposure to the conditioning chamber and extinction training consisted of successive 9-min exposures at 24-h intervals. Rats were also evaluated in the open field and water maze reversal task.', 'The administration of SR (1.0 mg/kg, i.p.) and WIN (0.25 mg/kg, i.p.) before extinction training disrupted and facilitated, respectively, the extinction of 24 h contextual fear memory. These effects were not related to any disturbance in memory retrieval, unconditioned freezing expression, or locomotor activity. WIN (0.25 mg/kg, i.p.) also facilitated the extinction of 30-day-old contextual fear memory, while the prior administration of SR (0.2 mg/kg, i.p.) antagonized this response. The facilitative effect of WIN on memory extinction does not seem to be specific for contextual fear memory because it was also observed in the water maze reversal task.']
['Acute renal failure (ARF) is a frequent complication of coronary artery bypass grafting (CABG) surgery and is strongly associated with perioperative morbidity and mortality. We hypothesized that renal artery stenosis (RAS), causing occult renal ischemia, may be an important factor contributing to development of ARF after CABG surgery.', 'Preoperative and intraoperative data on 798 consecutive adult patients undergoing CABG surgery with cardiopulmonary bypass from February 1, 1995 to February 1, 1997 (who had also undergone an abdominal aortogram for the evaluation of RAS) were recorded and entered into a computerized database. The development of ARF was defined as a rise in serum creatinine of 1 mg/dL (88.4 micromol/L) above baseline postoperatively. The association between the presence of renal artery stenosis together with preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression.', 'A total of 798 patients underwent isolated coronary bypass grafting, of which 18.7% demonstrated 50% or more RAS. ARF developed in 82 patients (10.2%), of which three (0.3%) required dialysis support. The mortality for patients who developed ARF was 14% (OR 15, P=0.0001) compared to 0.2% among those who did not develop ARF. The presence of renal artery stenosis of any severity ranging from unilateral 50% RAS to bilateral 95% RAS was not associated with the subsequent development of ARF.']
['Purine P2X and P2Y receptors (P2-R) are involved in control of renal circulation, especially in the medulla, wherein they appear to interact with angiotensin II (Ang II). Our experimental approach enabled examination of interaction with Ang II per se, in the absence of blood pressure elevation. In this whole-kidney functional study we focused on the influence of P2X1-R on perfusion of the renal medulla.', "Acute experiments were conducted with normal rats, untreated or subjected to two weeks' infusion of Ang II (osmotic minipumps). Urethane was used for anesthesia because in Ang II-treated rats it normalized elevated blood pressure. MRS2159, a P2X1-R inhibitor, was infused intravenously or directly into the medulla. Renal blood flow (RBF, Transonic renal artery probe), perfusion of the outer and inner medulla (OM-BF, IM-BF; laser-Doppler fluxes), and sodium and water excretion and urine osmolality (U", 'In untreated rats intravenous MRS2159 unexpectedly decreased RBF by 12±4% (p<0.02) and IM-BF by 7±2% (p<0.05). In Ang II-pretreated rats the inhibitor tended to increase RBF while OM-BF and IM-BF increased 14±5% and 12±2%, respectively (p<0.05 for both). Renal excretion was not affected, with or without Ang II treatment, while U']
['To clarify the incidence of spinal cord injury (SCI) after thoracic endovascular aneurysm repair (TEVAR), we investigate the intercostal/lumbar arteries that supply the Adamkiewicz artery (ICA-AKA).', 'Among 81 patients subjected to TEVAR, we retrospectively reviewed the clinical records of 50 patients (range: 57-86 (median age: 77) years, 41 males) who underwent TEVAR for part of or the whole distal descending aorta (T7 to L2) after identification of ICA-AKA by magnetic resonance angiography (MRA) or computed tomography angiography (CTA).', 'The 50 patients were classified into group A: 17 patients whose patent ICA-AKA was not covered, group B: 24 patients whose ICA-AKA was covered and group C: nine patients in whom no patent ICA-AKA was identified. Only three patients in group B suffered paraplegia and of them two recovered full ambulation. The estimated incidence of permanent and transient paraplegia was 3.7% in all TEVAR patients, 6.0% when part of or the entire distal aorta was covered and 12.5% when the patent ICA-AKA was covered. The length of aortic coverage in patients with paraplegia was >300 mm.']
['To investigate infancy predictors of impairing functional somatic symptoms (FSS) at child ages 5-7 years with a focus on problems with feeding, sleep, and tactile reactivity.', 'This study is part of a longitudinal birth cohort study, Copenhagen Child Cohort CCC2000. Child health, development, and functioning were assessed by community health nurses at 4 home visits from birth to age 10 months. FSS at ages 5-7 years were measured by the Soma Assessment Interview in 1327 children. Sociodemographic data and information on maternal psychiatric illness were obtained from the Danish National Registers.', "Multiple logistic regression analysis controlled for maternal psychiatric illness and annual household income revealed that combined infancy regulatory problems (ie, at least 2 of 3 problems of feeding, sleeping, or tactile reactivity during the first 10 months of living) predicted impairing FSS at 5-7 years (aOR = 2.9, 95% CI: 1.3-6.6). Maternal psychiatric illness during the child's first year of living was also associated with later child FSS (aOR = 7.1, 95% CI: 1.8-27.8)."]
['During the past 15 years, mounting evidence for the association between periodontal and cardiovascular disease has been presented in epidemiological studies. The aim of this study was to investigate how the severity of periodontal disease and number of remaining teeth relates to myocardial infarction (MI) and hypertension (HT).', 'Self-reported history of HT and MI was collected in 3,352 patients referred to the Department of Periodontology, Gävle County Hospital, and in 902 subjects randomly selected from the general population. Severity of periodontitis was estimated by a combination of the amount of bone loss around each tooth investigated from a full-mouth x-ray, the presence or absence of bleeding on probing (BOP), and involvement of furcations.', 'The severity of periodontitis was significantly associated with HT (prevalence 16%; P<0.0005), even after adjustment for age, gender, number of teeth, and smoking in the total sample, and with MI (prevalence 1.7%, P<0.03) after above-mentioned adjustments, but in middle-aged (40 to 60 years) subjects only. The number of diseased periodontal pockets was related to HT only (P<0.0001), and this relationship remained after the above-mentioned adjustments. The number of teeth was associated with MI (P<0.03) even after correction for age, gender, and smoking but was not related to hypertension.']
['Anedoctal reports suggest a detrimental effect of pneumatic dilation and botulinum toxin injection in patients who are potential candidates for Heller myotomy.', 'To assess symptomatic and objective outcome in patients undergoing Heller myotomy as a primary procedure or after failed endoscopic treatment.', 'Between November 1992 and December 1998, 92 patients with oesophageal achalasia were treated. Sixty patients had primary surgery; 32 patients had surgery after unsuccessful pneumatic dilation (n = 22), or botulinum toxin injection (n = 10).', 'Laparoscopic Heller myotomy plus Dor fundoplication with routine intraoperative endoscopy. Operative records, symptoms, and results of radiological, manometric and scintigraphic assessment in the two groups of patients were compared.', 'The mean operative time, the rate of intraoperative mucosal tears and the incidence of postoperative dysphagia were similar in the two groups. Mucosal tears occurred more frequently during the first 30 operations (p < 0.05). Median follow-up was 28 months (range 4-76). An abnormal oesophageal acid exposure was documented in 2 patients in the primary surgery group (7.7%), and in 2 patients in the pneumatic dilation/botulinum toxin group (13.3%) (p = ns). Lower oesophageal sphincter pressure significantly decreased in both groups (p < 0.01). The mean percentage of radionuclide residual activity in the oesophagus at 1 and 10 minutes significantly decreased in both groups (p < 0.01).']
['To test whether intensive care unit (ICU) nasal screening for methicillin-resistant Staphylococcus aureus (MRSA) predicts the presence or absence of MRSA infections requiring antimicrobial treatment.', 'A prospective cohort study.', 'Medical ICU at Barnes-Jewish Hospital, a 1252-bed urban teaching hospital.', 'Seven hundred forty-nine consecutive patients admitted to the medical ICU over a 7-mo period (November 2007 through June 2008).', 'Nasal swabs were obtained at ICU admission and weekly thereafter for MRSA detection by using polymerase chain reaction. All subjects were followed for the development of MRSA infection during their ICU stay.', 'One hundred sixty-four (21.9%) patients had positive nasal colonization with MRSA at the time of ICU admission. The predictive accuracy of MRSA nasal colonization for ICU-acquired MRSA infections, either lower respiratory tract infection or bloodstream infection, was poor (lower respiratory tract infection: sensitivity, 24.2%; specificity, 78.5%; positive predictive value, 17.7%; and negative predictive value, 84.4%; and bloodstream infection: sensitivity, 23.1%; specificity, 78.2%; positive predictive value, 11.0%; and negative predictive value, 89.7%). Addition of nasal-colonization results obtained during the ICU stay did not appreciably change the predictive accuracy of this test for identification of subsequent lower respiratory tract infections and bloodstream infections attributed to MRSA requiring antimicrobial treatment.']
['Pathophysiological mechanisms leading to chordee in patients with hypospadias and to the hidden state of buried penis in the prepubic fat remain unclear. Resection of dartos tissue usually makes the penis straight in patients with hypospadias and corrects it in those with buried penis, suggesting a common pathophysiology related to dartos tissue.', 'Tissue samples from 113 children undergoing primary penile surgery for hypospadias (94 patients), epispadias (1) or buried penis (18) were collected between November 2011 and September 2013. Tissue samples from 79 children undergoing circumcision for nonmedical reasons served as controls. All samples were stained with smooth muscle actin and analyzed by the same pathologist, who was blinded to indication for surgery. Chi-square and Fisher exact tests were applied.', 'Three different dartos tissue patterns were observed. Pattern I (normal) consisted of smooth muscle fibers of dartos tissue organized in a parallel configuration in the subcutaneous tissue. Pattern II was characterized by poorly developed and hypotrophic smooth muscle fibers. Pattern III was determined by randomly distributed smooth muscle fibers in the subcutaneous tissue, without parallel configuration. Pattern I was observed in 45 circumcision specimens (64%). Of buried penis cases 78% were considered abnormal (pattern II in 4 cases and III in 10, p = 0.001). Of hypospadias cases 70% were considered abnormal (pattern II in 31 cases, III in 32, and mixed II and III in 3, p < 0.001). The only epispadias case was designated pattern II.']
['The purpose of this study was to determine if a 9-month regimen of sub-antimicrobial doxycycline (20 mg, bid) had an effect on either the intestinal or the vaginal microflora.', 'A total of 69 periodontally diseased subjects were randomized to receive drug or placebo control for a 9-month period. Stool specimens and vaginal swabs were collected at baseline and after 3 and 9 months of therapy. Samples were examined for total anaerobic counts, opportunistic pathogens, and doxycycline-resistant (>or=4 microg/ml) bacteria. All isolates that survived sub-culture were identified and their susceptibilities determined to six antibiotics. Analyses were performed to determine if treatment differences were present.', 'The only statistically significant differences (p<0.05) between the two treatment groups occurred in the doxycycline-resistant counts at the baseline sample period for the faecal samples. This imbalance was before treatment initiation and the administration of the study drug. No between-treatment differences were detected at either the 3- or 9-month sample period either in the predominant bacterial taxa present or in their antibiotic susceptibilities.']
['We investigated whether the greater late lumen loss after coronary balloon angioplasty in the proximal left anterior descending artery (P-LAD) compared with that in other segments might be related to differences in vascular dimensions or morphology as determined by angiography and intravascular ultrasound imaging.', 'The greater late lumen loss after angioplasty in the P-LAD that has been observed in several studies has not been explained.', 'We studied 178 patients and 194 coronary artery lesions by quantitative angiography and 30 MHz intravascular ultrasound imaging after successful balloon angioplasty. Vessel wall morphology was compared among three proximal and three nonproximal segments. Follow-up quantitative angiography for late lumen loss calculation was performed in 168 lesions. Multivariate analysis was used to determine predictors of late lumen loss.', 'Absolute and relative late loss were significantly greater at the P-LAD compared with the pooled group of other segments (0.42 +/- 0.60 mm vs. 0.10 +/- 0.48 mm, p = 0.0008 and 0.14 +/- 0.24 vs. 0.03 +/- 0.17, p < 0.001). Also, a greater percentage of calcific lesions (65% vs. 44%, p = 0.034), a lower incidence of rupture (51% vs. 74%, p = 0.009) and a larger reference segment plaque area (5.4 +/- 2.2 mm2 vs. 4.7 +/- 1.9 mm2, p = 0.05) were found in the P-LAD. In multivariate analysis however, these variables were not predictive of late loss.']
['Amacrine cell neurite patterning has been extensively studied in vivo, and more than 30 subpopulations with varied morphologies have been identified in the mammalian retina. It is not known, however, whether the complex amacrine cell morphology is determined intrinsically, is signaled by extrinsic cues, or both.', 'Here we purified rat amacrine cell subpopulations away from their retinal neighbors and glial-derived factors to ask questions about their intrinsic neurite growth ability. In defined medium strongly trophic for amacrine cells in vitro, we characterized survival and neurite growth of amacrine cell subpopulations defined by expression of specific markers.', 'We found that a series of amacrine cell subtype markers are developmentally regulated, turning on through early postnatal development. Subtype marker expression was observed in similar fractions of cultured amacrine cells as was observed in vivo, and was maintained with time in culture. Overall, amacrine cell neurite growth followed principles very similar to those in postnatal retinal ganglion cells, but embryonic retinal ganglion cells demonstrated different features, relating to their rapid axon growth. Surprisingly, the three subpopulations of amacrine cells studied in vitro recapitulated quantitatively and qualitatively the varied morphologies they have in vivo.']
['Little consensus exists over the management of high-grade renal injuries, with continued debate over observation versus invasive surgery. Blunt renal artery injury (BRAI) is a high-grade injury that may result in renal dysfunction, hypertension, or failure.', 'Management of BRAI at a level I trauma centre during a decade was retrospectively reviewed to determine incidence, assess management strategy, and evaluate hospital outcomes. Data collected included demographics, injury details, standardised scoring, renal injury grade, haemodynamic stability, diagnostic modalities, medical interventions, mortality, and hospitalisation length.', 'Thirty-eight BRAI patients (21 Grade IV and 17 Grade V injuries) were admitted, representing 0.16% of trauma admissions, and consisting primarily of young males. Ultrasonography and CT was performed in 92.1% and 76.3% of patients, respectively. Primary management included exploratory laparotomy in 42.9%, angiography and embolisation in 34.3%, and observation in 22.9%. Six nephrectomies and one revascularisation were performed. The incidence of BRAI and use of angiography are higher than those reported in previous studies.']
['The aim of this study was to verify whether retinal photoreceptors, like other tissues, are subject to oxidative stress during diabetes.', 'Oxidative stress was monitored by the oxidation of preloaded dehydrorhodamine 123 into fluorescent rhodamine 123, during a period of intense illumination of isolated rod retinal receptor cells. These were obtained from 22 Syrian hamsters injected with streptozotocin (50 mg/kg body weight., intraperitoneal route) 90 days before the study began. Eleven hamsters were treated daily with melatonin (0.4 mg/kg body wt., per os), an antioxidant synthesized within photoreceptors. Isolated photoreceptors were bathed on the stage of a Leitz Orthoplan microscope, where the fluorescent lamp also served as the light stimulus (485 nm). Fluorescence irradiance was measured by photometry and stored in a personal computer for further analysis.', "The light-induced oxidant production greatly decreased and was also delayed in the streptozotocin-injected hamsters compared with the control hamsters matched for age. Similar effects were obtained in control photoreceptors after 40 min incubation with 2-2'-azobis (2-amidinopropane) dihydrochloride, a potent lipoperoxidation inducer. The effect of melatonin was to partially restore the light-induced fluorescence response."]
['Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue.', 'Experimental mouse scald burn injury.', 'University Research Laboratory.', 'C57/Bl6 Male mice, 8-12 weeks old.', 'To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn.', 'Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients.']
['In a previously reported double blind placebo-controlled trial it was shown that vaccination with pertussis toxoid during infancy reduced the incidence of pertussis in the vaccinees. Parents and siblings of participants in the trial were followed for pertussis to determine whether vaccination provided indirect protection of close contacts in a nonvaccinating country with a high incidence of pertussis.', 'A group of 3450 infants were randomized to vaccination with diphtheria, tetanus and pertussis toxoids (DTPtxd) or to diphtheria and tetanus toxoids (DT). Pertussis cases were actively sought and diagnosed by cultures and serology in vaccinees (previously reported) and in family members during 2 years after the third vaccination.', 'Pertussis as defined by the World Health Organization (paroxysmal cough of > or = 21 days and certain laboratory criteria) was diagnosed in 11 parents of DTPtxd recipients and in 26 parents of DT recipients; indirect protection was 60% (95% confidence intervals, 16 to 82%). In nonvaccinated younger siblings of DTPtxd and DT recipients there were 10 and 18 cases of pertussis, respectively; indirect protection was 43% (95% confidence intervals, -31 to 76%). When all cases of pertussis with cough > or = 7 days were included, the indirect protection was 44% (95% confidence intervals, 7 to 67%) in parents and 56% (95% confidence intervals, 9 to 81%) in younger siblings.']
['To investigate the effects of tetrandrine (Tet) on cognitive impairment induced by chronic cerebral hypoperfusion and its potential anti-inflammatory mechanism by modulating the expression of S100B, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS).', 'Chronic cerebral hypoperfusion was induced by ligation of the bilateral common carotid arteries for 8 weeks. Rats were treated with Tet (10 mg/kg or 30 mg/kg) intraperitoneally every 3 days for 4 weeks. Cognitive function of rats was evaluated by the Morris water maze. Hematoxylin eosin (H & E) and Nissl staining were used to observe neuronal damage in the hippocampal CA1 region. Immunofluorescence, quantitative real-time polymerase chain reaction (QT-PCR), and western blot were performed to measure S100B, IL-1 beta, TNF-alpha, and iNOS levels in the CA1 region of chronic cerebral hypoperfusion rats.', 'The Tet-treated group significantly decreased the escape latency of chronic cerebral hypoperfusion rats in finding the hidden platform (P <0.05). Compared with the 2-VO (two-vessel occlusion) group, more neurons with regular morphology and/or Nissl bodies in the hippocampus were observed in the Tet-treated group, suggesting attenuated neuronal damage and degeneration. Additionally, S100B, IL-1 beta, TNF-alpha, and iNOS levels were significantly (P <0.05) decreased in the CA1 region of the chronic cerebral hypoperfusion affected rats treated with Tet.']
['Besides the well-known adverse effects of valproate (VPA), disorders related to male reproductive functions have been reported. Furthermore, only a limited number of previous studies have reported the relationship between VPA dose and impairment of the hormonal axis and semen quality. A patient with reversible changes that occurred in the sperm parameters after a dose increment of VPA.', 'A 34-year-old male patient who was diagnosed with juvenile myoclonic epilepsy almost 15 years ago was admitted to our clinic. His seizures responded well to high doses of VPA treatment.', "As the VPA dose was increased, consecutive semen analyses were performed and averaged for each dose; the results showed a remarkable decline in the sperm count and a manifest loss of sperm motility. VPA treatment was gradually diminished and stopped; meanwhile, treatment with another antiepileptic (lamotrigin) was initiated to control the patient's seizures. Nine months later, the patient's semen analysis was within normal ranges. After modification of the patient's treatment regimen, he and his wife had a healthy baby."]
['Cardiovascular disease is a leading cause of morbidity and mortality after renal transplantation. We analysed whether pre-transplant transthoracic echocardiograms (TTE) predicted major adverse cardiovascular events (MACE) after transplant.', 'We retrospectively analysed clinical and TTE data from patients having renal transplantation at a single centre between 1 January 2000 and 31 December 2010. The TTE were classified as: group A - normal; group B - mild abnormalities expected in renal failure; group C - moderate to severe abnormalities likely to change management. They were also scored based on four independent risk factors [age ≥50, left ventricular (LV) end systolic diameter ≥3.5 cm, LV wall thickness ≥1.4 cm and mitral annulus calcification]. Post-transplantation clinical notes were examined for MACE (death, stroke, myocardial infarction, and surgical or percutaneous revascularisation).', 'There were 343 patients, mean age 47 (range 21-83) years, 210 of whom were male. MACE occurred in 29 (8.5%) at a mean of 3.6 (SD 3.3) years after transplantation. They were older (p ≤ 0.001), had larger LV mass (p = 0.02), LV wall thickness (p = 0.008) and left atrial size (p = 0.001) than those without MACE. The MACE rate for groups A, B and C were 1.8, 13.6 and 16.4% (p ≤ 0.001), respectively. Using the score, the risk of MACE was 4.7, 10.7, 9.2 and 40% for scores 0, 1, 2 and 3 (p = 0.023), respectively.']
['Rheum rhabarbarum (rhubarb) has long been used for the treatment of inflammation in China and other Asian countries. However, the mechanism underlying the anti-inflammatory activity of this medicinal plant is not fully understood. The present study was designed to investigate the anti-inflammatory effects of anthraquinones, the major constituents in rhubarb, and the molecular mechanism involved in their anti-inflammatory effects.', 'RAW264.7 cells were stimulated by lipopolysaccharide (LPS) in the presence or absence of the compounds examined. The proliferation of RAW264.7 cells was assayed by the Alamar-Blue method. The quantity of nitric oxide (NO) was determined by Griess assay. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. Inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor κBα (IκBα), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), and Akt/phosphoinositide 3-kinase (PI3K) protein expression levels were determined by Western blotting.', 'Aloe-emodin markedly suppressed the production of NO, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated RAW264.7 cells with no apparent cytotoxicity. The mRNA expression levels of iNOS, IL-6, and IL-1β genes were also significantly inhibited by aloe-emodin. Western blot analysis showed that aloe-emodin suppressed LPS-induced iNOS protein expression, IκBα degradation, and the phosphorylation of ERK, p38, JNK, and Akt.']
['To construct a pre-biopsy predictive model incorporating several clinical variables, including African-American (AA) or Caucasian race, to predict the risk of prostate cancer detection on prostate biopsy, as traditionally AA men have had a higher incidence of prostate cancer than Caucasian men, but previous predictive tools for prostate cancer have not incorporated the effect of race.', 'We evaluated 9473 patients undergoing initial prostate biopsy at three equal-access healthcare institutes from 1993 to 2003. At each biopsy session, patient age, race, serum prostate-specific antigen level (PSA), digital rectal examination (DRE) findings, number of biopsy cores taken, year of biopsy, and pathological findings were recorded. A logistic regression model was constructed to evaluate predictors of cancer detection based on pre-biopsy variables. The model was internally validated using the bootstrap statistical method, and a nomogram was constructed.', 'Prostate cancer was diagnosed in 1895 (33%) AA men and 991 (26%) Caucasians. AA men had a significantly higher mean serum PSA level than Caucasians, at 13.0 and 8.5 ng/mL, respectively (P < 0.001). The mean ages were similar between AA and Caucasian men (P = 0.23), but Caucasian men had a higher incidence of an abnormal DRE (P < 0.001). On multivariate analysis, age, race, year of biopsy, PSA level, DRE, and number of cores taken were all statistically significant (P < 0.001). Hazard ratios were (controlling for year of biopsy); age (1.30), Caucasian race (0.74), PSA level (1.47), DRE (1.75), and number of cores taken (1.19). The predicted model had a boot-strapped concordance index of 0.75.']
['Erectile dysfunction (ED) is frequent in patients with obstructive sleep apnea (OSA) and may act as a surrogate of endothelial dysfunction. Furthermore, impairments of vigilance and sustained attention are also commonly associated with OSA.', 'The purpose of this study was to evaluate whether there is an association between ED and sustained attention deficits.', 'A prospective cross-sectional cohort of 401 male in-patients undergoing diagnostic polysomnography for suspected OSA and a 25-minute sustained attention test was analyzed. ED was assessed using the 15-item International Index of Erectile Function (IIEF-15) questionnaire. The Epworth Sleepiness Scale (ESS) served as a measure of daytime sleepiness.', 'Severity of impaired erectile function (EF) assessed by the IIEF-15, core task parameters of the sustained attention test (i.e., CR: correct reactions; V-CR: variation of correct reactions, CE: commission errors, RT: reaction time; V-RT: variation of reaction times).', 'Three hundred eighty-one consecutive patients presenting for in-lab polysomnography were included in the analysis. Impaired EF was diagnosed in 246 patients (65%). With increasing impairment of EF, patients scored significantly worse in all vigilance test parameters and demonstrated more severely diminished vigilance (normal EF: 11.9%, moderately impaired EF: 24.1%, and severely impaired EF: 34.9%). Multivariate regression analyses including established risk factors for ED, OSA, or sleepiness revealed a significant independent association between lower scores for EF and impairments on the following vigilance test variables: odds ratio (95% confidence interval) for V-CR: 0.52 (0.34-0.81), CE: 0.87 (0.80-0.95), and V-RT: 0.91 (0.87-0.96). The ESS was independently associated with both measures of performance instability: odds ratio for V-CR: 6.94 (2.97-16.23) and V-RT: 1.28 (1.14-1.44).']
['We examined in insulin-resistant muscle if, in contrast to long-standing dogma, mitochondrial fatty acid oxidation is increased and whether this is attributed to an increased nuclear content of peroxisome proliferator-activated receptor (PPAR) gamma coactivator (PGC) 1alpha and the adaptations of specific mitochondrial subpopulations.', 'Skeletal muscles from male control and Zucker diabetic fatty (ZDF) rats were used to determine 1) intramuscular lipid distribution, 2) subsarcolemmal and intermyofibrillar mitochondrial morphology, 3) rates of palmitate oxidation in subsarcolemmal and intermyofibrillar mitochondria, and 4) the subcellular localization of PGC1alpha. Electotransfection of PGC1alpha cDNA into lean animals tested the notion that increased nuclear PGC1alpha preferentially targeted subsarcolemmal mitochondria.', 'Transmission electron microscope analysis revealed that in ZDF animals the number (+50%), width (+69%), and density (+57%) of subsarcolemmal mitochondria were increased (P < 0.05). In contrast, intermyofibrillar mitochondria remained largely unchanged. Rates of palmitate oxidation were approximately 40% higher (P < 0.05) in ZDF subsarcolemmal and intermyofibrillar mitochondria, potentially as a result of the increased PPAR-targeted proteins, carnitine palmitoyltransferase-I, and fatty acid translocase (FAT)/CD36. PGC1alpha mRNA and total protein were not altered in ZDF animals; however, a greater (approximately 70%; P < 0.05) amount of PGC1alpha was located in nuclei. Overexpression of PGC1alpha only increased subsarcolemmal mitochondrial oxidation rates.']
['To analyze the association between the genetic variations of functional region in bone morphogenetic protein (BMP7) gene and dyslipidemia in Chinese Uygur individuals.', 'The case-control study was conducted in 1514 Uygur Chinese based on epidemiological investigation. The all exons, segmental introns and the promoter regions of BMP7 gene were sequenced in 48 out of 1514 Uygur Chinese. Representative variations were then selected according to the minor allele frequency (MAF) and linkage disequilibrium, and genotyped using the TaqMan polymerase chain reaction method in 1514 Uygur Chinese, a relatively isolated general population in a relatively homogeneous environment, to observe the association between genetic variations of BMP7 gene and dyslipidemia.', 'Five novel and eight known variations in the BMP7 gene were identified. All genotype distributions were tested for deviations from Hardy-Weinberg equilibrium. There were significant differences of genotype distribution of rs6025422 between hypertriglyceridemia group and control group (P = 0.001). The levels of triglyceride (TG) showed a decreasing tendency in individuals with AA, AG and GG genotypes of rs6025422. Odd ratio (OR) value adjusted for age, gender, body mass index, smoking and alcohol drinking habits was 0.562 by logistic regression analysis (95%CI: 0.393 - 0.802, P = 0.002).']
['alpha-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC) and is a target for immunotherapy. However, there is little information on the pattern of CD4 (Th1) and CD8 (Tc1) T-cell response to AFP in patients with HCC and their association with the clinical characteristics of patients.', 'We therefore analysed CD4 and CD8 T-cell responses to a panel of AFP-derived peptides in a total of 31 HCC patients and 14 controls, using an intracellular cytokine assay for IFN-gamma.', 'Anti-AFP Tc1 responses were detected in 28.5% of controls, as well as in 25% of HCC patients with Okuda I (early tumour stage) and in 31.6% of HCC patients with stage II or III (late tumour stages). An anti-AFP Th1 response was detected only in HCC patients (58.3% with Okuda stage I tumours and 15.8% with Okuda stage II or III tumours). Anti-AFP Th1 response was mainly detected in HCC patients who had normal or mildly elevated serum AFP concentrations (P=0.00188), whereas there was no significant difference between serum AFP concentrations in these patients and the presence of an anti-AFP Tc1 response. A Th1 response was detected in 44% of HCC patients with a Child-Pugh A score (early stage of cirrhosis), whereas this was detected in only 15% with a B or C score (late-stage cirrhosis). In contrast, a Tc1 response was detected in 17% of HCC patients with a Child-Pugh A score and in 46% with a B or C score.']
['We studied the impact of the reactive oxygen species hydrogen peroxide (H2O2) and antioxidative enzymes on the pathogenesis of diabetes induced by multiple low doses of streptozotocin (MLD-STZ).', 'We isolated the islets of C57BL/6 mice. For ex vivo analyses, mice had been injected with MLD-STZ. For in vitro analyses, islets were incubated with different concentrations of STZ, with either of the two moieties of STZ, methylnitrosourea and D-glucose, with H2O2 or with alloxan. Levels of H2O2 generation were measured by the scopoletin method. We assessed mRNA expression of Cu/Zn and Mn superoxide dismutase, catalase, and glutathione peroxidase (GPX) by semiquantitative polymerase chain reaction. GPX activity was measured spectrophotometrically. In vitro, beta cell function was assayed by measuring basal and D-glucose-stimulated release of immunoreactive insulin using an ELISA kit.', 'Ex vivo, MLD-STZ significantly increased H2O2 generation in male but not in female mice. It also increased GPX activity and mRNA expression of catalase, Cu/Zn and Mn superoxide dismutase, and GPX in female but not in male mice. In vitro, STZ significantly stimulated H2O2 generation in islets of male mice only. In male islets, alloxan increased H202 generation at a highly toxic concentration, but D-glucose and methylnitrosourea did not. Both STZ and H2O2 dose-dependently inhibited the release of immunoreactive insulin after a D-glucose challenge.']
['Full visualization of the abdominal aorta using the standard midline view is often inadequate for the detection of abdominal aortic aneurysm. We evaluated whether the addition of a lateral midaxillary right upper quadrant view could improve visualization of the abdominal aorta.', 'This was a prospective observational proof-of-concept study of patients older than 50 years undergoing abdominal computed tomographic scan for any indication in the emergency department. Ultrasounds were performed by American College of Emergency Physicians-credentialed study sonographers, and images were reviewed by an ultrasound fellowship-trained reviewer. The standard midline aortic images were obtained as well as additional lateral images from a midaxillary right upper quadrant approach. Visualization of the aorta was determined to be adequate if more than two-thirds of the abdominal aorta was visualized.', 'We enrolled 60 patients. Six patients were excluded due to missing data. A total of 54 patients were analyzed. The median age was 67.5, and 37% were male. The mean body mass index was 25.9 (SD, 5.8), and mean abdominal circumference was 105.3 cm (SD, 18.1). Visualization of the aorta using the midline approach was adequate in 26 (48.2%) of 54 of the patients and 32 (59.2%) of 54 of the lateral approach. Addition of a lateral view in examinations with an inadequate midline view increased adequate aortic visualization to 41 (75.9%) of 54.']
['Overt and subtle iron overload cause diabetes by lowering insulin production and promoting insulin resistance. Via divalent metal transporters pancreatic beta cells take up non-transferrin-bound iron which by catalyzing Fenton reaction can cause oxidative stress. Due to their strict dependence on mitochondrial glucose metabolism and limited antioxidant capacity, beta cells are exquisitely vulnerable to oxidative stress and hence catalytically active iron. Intravenous (IV) iron preparations are routinely used in the management of anemia in patients with end stage renal disease. This has led to an epidemic of iron overload in this population. This study explored the effect of pharmacologically-relevant concentrations of a commonly used IV iron preparation on the beta cells in isolated pancreatic islets.', 'Isolated rat pancreatic islets were incubated for 24 hours in culture media containing vehicle or pharmacologically-relevant concentration of ferric sucrose and examined for the extent of cell death and oxidative stress.', 'Exposure to iron sucrose resulted in a concentration-dependent oxidative stress and pancreatic islet cell death predominantly affecting beta cells.']
['Intradialytic hypotension is the most common complication of modern day haemodialysis (HD). Convective modalities, including haemodiafiltration (HDF) are reported to result in greater cardiovascular stability compared to standard HD, which has been suggested to be due to improved solute transport between compartments. We therefore investigated the effect of treatment on body water by bioimpedance.', 'We measured the change in extracellular water (ECW) and intracellular water (ICW) in 263 outpatients attending for HD using cooled dialysate and 134 patients for HDF.', 'Patient cohorts were matched for demographics, dialysate composition, ultrafiltration rate, and session duration. The fall in systolic blood pressure following HD was -11.8 mm Hg (-25.3 to 2.3) and not different from that following HDF -12 mm Hg (-27 to 6). Similarly there were no differences in pretreatment serum sodium and dialysate sodium gradient [HD 1 mmol/l (-1 to 3) vs. HDF 2 mmol/l (1 to 4)], or change in serum sodium posttreatment [HD 0 mmol/l (-2 to 2) vs. HDF 1 mmol/l (-1 to 3)]. There were no differences in ICW or ECW pretreatment, and following treatment the reduction in ICW and ECW did not differ [ICW HD -3.5% (-5.7 to -1.8) vs. -4.1% (-6.0 to -1.7), ECW HD -7.1% (-9.4 to -4.7) vs. HDF -7.1% (-9.7 to -4.9)].']
['In children with Friedreich ataxia (FRDA), ataxia is assessed using the surrogate marker the International Cooperative Ataxia Rating Scale (ICARS). We aimed to determine whether ICARS scores in children with FRDA are confounded by muscle weakness.', 'In 12 children with FRDA (10 males, two females; mean age 13 y 6 mo, SD 2 y 6 mo) and 12 age-matched children without FRDA (nine males; three females), we determined the association between muscle and ataxia parameters (i.e. muscle ultrasound density (MUD), muscle force, sensory evoked potentials, and ICARS scores). Children with FRDA were included on the basis of FXN gene analysis. Children in the comparison group were included on basis of uneventful pregnancy and normal cognitive and neurological development.', 'In children with FRDA, muscle ultrasound density was homogeneously increased in the biceps, quadriceps, and tibialis anterior muscles (median 4SD). FRDA muscle weakness was significantly more pronounced in proximal than in distal muscles (-2SD vs -0.5SD respectively; p=0.004), with a stronger impairment of leg muscles than of arm muscles (-2SD vs -0. SD respectively; p=0.001). Comparing MUD between children with FRDA and an age-matched comparison group revealed a relatively strong increase in MUD in the proximal leg muscles in the FRDA group. Under the condition of persistently absent sensory evoked potentials, leg ICARS subscores in the FRDA group appeared to be positively associated with leg muscle force until a maximal plateau level of ICARS subscores was reached.']
['Although mucosal responses are important for preventing infections with HIV, the optimal strategies for inducing them remain unclear. To evaluate vaccine strategies targeting the oral mucosal lymphoid tissue inductive sites as an approach to provide immunity at distal sites, we vaccinated healthy macaques via the palatine/lingual tonsils with aldrithiol 2 (AT-2) inactivated Simian immunodeficiency virus (SIV)mac239, combined with CpG-C immunostimulatory oligonucleotide (CpG-C ISS-ODN, C274) as the adjuvant.', 'Macaques received 5 doses of C274 or control ODN C661 and AT-2 SIV on the tonsillar tissues every 6 weeks before being challenged rectally with SIVmac239, 8 weeks after the last immunization.', 'Although no T-cell or B-cell responses were detected in the blood before challenge, antibody (Ab) responses were detected in the rectum. Immunization with AT-2 SIV significantly reduced the frequency of infection compared with nonimmunized controls, irrespective of adjuvant. In the vaccinated animals that became infected, peak viremias were somewhat reduced. SIV-specific responses were detected in the blood once animals became infected with no detectable differences between the differently immunized groups and the controls.']
['This study analyzes the results of a follow-up policy in colorectal cancer at our institution and evaluates the possible benefit provided by each test performed.', 'Six hundred nineteen patients who had radical surgery and adjuvant treatment for colorectal cancer were followed up with a protocol that included carcinoembryonic antigen testing and clinical examination every three months for the first two years, every four months in the third year, and every six months in the fourth and fifth years. Chest X-ray and colonoscopy were performed yearly for five years and abdominal ultrasound was done every six months for the first three years and yearly afterward. Abdominopelvic computerized tomography was performed yearly for the first two years in cases with rectal cancer. If relapse was detected, all operable cases underwent surgery if possible.', 'Between 1993 and 1999, 619 patients were followed-up. Mean follow-up was 66.9 months. Two hundred eight relapses were detected, 83.6 percent in the first three years and 73 (35.1 percent) underwent surgical resection. Carcinoembryonic antigen testing detected 44.2 percent of recurrences and 31.9 percent of them were operated on. Imaging techniques detected a lower percentage of recurrences (18.7 percent) but were more often resectable: 52 percent and 60 percent of the recurrences detected by computerized tomography and chest X-ray, respectively, underwent surgery. Median overall survival of patients with resected relapse was 62 months, significantly higher than those who were not operable (12.4 months).']
['A change of serum lactate concentrations appeared to be useful for predicting outcomes in various acute ill settings. However, there is little information on intraoperative change of lactate level in pediatric cardiac surgery patients.', 'We conducted a retrospective observational study of 459 children who received pediatric cardiac surgery to determine the association between change of lactate level after cardiopulmonary bypass (CPB) and patient prognosis (length of ICU stay and incidence of postoperative serious adverse events (SAEs)). We defined change of lactate level after CPB (LAC⊿) as (final lactate level measurement in the operating room) - (lactate level measured at the end of CPB). To study the independent association of LAC⊿ with length of ICU stay, we used linear regression model.', 'There were 1145 lactate measurements after CPB in this study cohort. After weaning from CPB, the serum lactate levels significantly increased from 2.1 mmol/L to 2.5 mmol/L (p\u2009<\u20090.001). Patients with higher LAC⊿ had significantly longer stay in ICU (p\u2009=\u20090.017) and higher incidence of SAEs (p\u2009=\u20090.002). In multivariate linear regression analysis, higher LAC⊿ showed a significant independent association with longer length of ICU stay.']
['Intratumoral heterogeneity is a major obstacle for the treatment of cancer, as the presence of even minor populations that are insensitive to therapy can lead to disease relapse. Increased clonal diversity has been correlated with a poor prognosis for cancer patients, and we therefore examined genetic, transcriptional, and functional diversity in metastatic melanoma.', 'Amplicon sequencing and SNP microarrays were used to profile somatic mutations and DNA copy number changes in multiple regions from metastatic lesions. Clonal genetic and transcriptional heterogeneity was also assessed in single cell clones from early passage cell lines, which were then subjected to clonogenicity and drug sensitivity assays.', 'MAPK pathway and tumor suppressor mutations were identified in all regions of the melanoma metastases analyzed. In contrast, we identified copy number abnormalities present in only some regions in addition to homogeneously present changes, suggesting ongoing genetic evolution following metastatic spread. Copy number heterogeneity from a tumor was represented in matched cell line clones, which also varied in their clonogenicity and drug sensitivity. Minor clones were identified based on dissimilarity to the parental cell line, and these clones were the most clonogenic and least sensitive to drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for drug-resistant cells resulted in the adoption of a gene expression profile with features of one of the minor clones, supporting the idea that these populations can mediate disease relapse.']
['High resistance training enhances muscular strength, and recent work has suggested an important role for metabolite accumulation in this process.', 'To investigate the role of fatigue and metabolite accumulation in strength gains by comparing highly fatiguing and non-fatiguing isotonic training protocols.', 'Twenty three healthy adults (18-29 years of age; eight women) were assigned to either a high fatigue protocol (HF: four sets of 10 repetitions with 30 seconds rest between sets) to maximise metabolic stress or a low fatigue protocol (LF: 40 repetitions with 30 seconds between each repetition) to minimise changes. Subjects lifted on average 73% of their 1 repetition maximum through the full range of knee extension with both legs, three times a week. Quadriceps isometric strength of each leg was measured at a knee joint angle of 1.57 rad (90 degrees ), and a Cybex 340 isokinetic dynamometer was used to measure the angle-torque and torque-velocity relations of the non-dominant leg.', 'At the mid-point of the training, the HF group had 50% greater gains in isometric strength, although this was not significant (4.5 weeks: HF, 13.3 (4.4)%; LF, 8.9 (3.6)%). This rate of increase was not sustained by the HF group, and after nine weeks of training all the strength measurements showed similar improvements for both groups (isometric strength: HF, 18.2 (3.9)%; LF, 14.5 (4.0)%). The strength gains were limited to the longer muscle lengths despite training over the full range of movement.']
['Cardiovascular diseases are reported to be associated with both chronic rhinosinusitis (CRS) and dementia. Nevertheless, whether dementia is associated with CRS is still unknown. In the present study, we explored the association between dementia with prior CRS using a population-based data set.', 'This study used the Taiwan Longitudinal Health Insurance Database 2000 as the source of data for a case-control study. We included 8768 subjects with dementia as cases and 8768 age- and sex-matched subjects as controls. We identified cases who had received a diagnosis of CRS before having received a diagnosis of dementia. Conditional logistic regression analyses were performed to examine the association of dementia with previously diagnosed CRS.', 'Results showed that of all sampled subjects, 875 (5.0%) had been previously diagnosed with CRS. A chi-squared test showed that there was a significant difference in the prevalences of prior CRS between cases and controls (6.0% versus 4.0%; p < 0.001). The adjusted odds ratio (OR) of prior CRS for subjects with dementia was 1.44 (95% CI, 1.25∼1.66) compared with controls. Furthermore, compared with controls, the OR of prior CRS was similar for subjects with dementia for both sexes (the OR for male subjects was 1.48 and OR for female subjects was 1.41).']
['Dopaminergic (DAergic) neurons of the ventral tegmental area (VTA) are important for the rewarding and reinforcing properties of alcohol and other drugs of abuse. Regulation of the firing of DAergic VTA neurons is controlled by a number of factors, including autoregulation of firing by D2 dopamine (DA) receptors. The inhibitory effects of DA on these neurons exhibit concentration- and time-dependent desensitization, which we have termed dopamine inhibition reversal (DIR), as it requires concurrent stimulation of D1/D5 and D2 receptors.', 'Extracellular recording of DAergic VTA neurons in brain slices was used to test the effects of ethanol (EtOH) (10 to 80\xa0mM) on DIR.', 'DIR was reduced by concentrations of EtOH as low as 10\xa0mM and was blocked by higher EtOH concentrations. In addition, as we have shown that reversal of inhibition by the selective D2 agonist quinpirole can be observed in the presence of an activator of protein kinase C (PKC), we tested whether EtOH could antagonize the reversal of quinpirole inhibition in the presence of phorbol 12-myristate 13-acetate (PMA). EtOH (80\xa0mM) blocked the reversal of quinpirole seen in the presence of PMA, suggesting that the antagonism of DIR by EtOH is owing to an action at a stage in the mechanism at or distal to PKC. Once achieved, DIR is not antagonized by EtOH.']
['In a prospective randomized trial the effect of prone positioning on the duration of mechanical ventilation was evaluated in multiple trauma patients and was compared with patients ventilated in supine position.', 'Multiple trauma patients of the intensive care units of two university hospitals were considered eligible if they met the criteria for acute lung injury or the acute respiratory distress syndrome. Patients in the prone group (N = 21) were kept prone for at least eight hours and a maximum of 23 hours per day. Prone positioning was continued until a PaO2:FiO2 ratio of more than 300 was present in prone as well as supine position over a period of 48 hours. Patients in the supine group (N = 19) were positioned according to standard care guidelines.', 'The duration of ventilatory support did not differ significantly (30 +/- 17 days in the prone group and 33 +/- 23 days in the supine group). Worst case analysis (death and deterioration of gas exchange) displayed ventilatory support for 41 +/- 29 days in the prone group and 61 +/- 35 days in the supine group (p = 0.06). The PaO2:FiO2 ratio increased significantly more in the prone group in the first four days (p = 0.03). The prevalence of Acute Respiratory Distress Syndrome (ARDS) following acute lung injury (p = 0.03) and the prevalence of pneumonia (p = 0.048) were reduced also. One patient in the prone and three patients in the supine group died due to multi organ failure (p = 0.27).']
['To demonstrate that under well-defined conditions, pressure-controlled ventilators (PCV) allow settings that are as good as high-frequency oscillatory ventilators (HFOV) at preserving the function of exogenous surfactant in lung-lavaged rats.', 'Experimental, comparative study.', 'Research laboratory of a large university.', 'Sixteen adult male Sprague-Dawley rats (280-310 g).', 'Lung injury was induced by repeated lavage. After last lavage, all animals received exogenous surfactant and were then randomly assigned to two groups (n = 8 per group). The first group received PCV with small pressure amplitudes and high positive end-expiratory pressure. The second group received HFOV. In both groups, an opening maneuver was performed by increasing airway pressure to improve PaO2/F(IO2) to > or =500 torr.', 'Blood gases were measured every 30 mins for 3 hrs. Airway pressures were measured with a tip catheter pressure transducer. At the end of the study period, a pressure-volume curve was recorded and a broncho-alveolar lavage was performed to determine protein content and surfactant composition. The results showed that arterial oxygenation in both groups could be kept >500 torr during the 3-hr study period by using a mean airway pressure of 13+/-3 cm H2O in PCV and 13+/-2 cm H2O in HFOV. Further, there were no differences in the Gruenwald index, protein influx, or ratio of small to large aggregates between the study groups.']
['Disability and frailty are associated with osteoporosis, obesity, and sarcopenia. HIV-infected persons have early functional impairment, but the association between body composition and functional impairment is unknown.', 'HIV-1-infected participants on combination antiretroviral therapy with virologic suppression, aged 45-65 years, had standardized physical function measures. In a nested analysis, 30 low- and 48 high-functioning cases and controls were matched by age, gender, and time since HIV diagnosis. Bone mineral density, fat mass, and lean body mass were assessed by dual-energy x-ray absorptiometry. Odds ratios (ORs) with 95% confidence intervals were obtained from conditional logistic regression.', 'Mean age was 53 years, mean CD4(+) lymphocytes 598 cells per microliter, and 96% had plasma HIV-1 RNA <50 copies per milliliter. Low- and high-function subjects had similar CD4(+) lymphocyte count and duration and type of antiretroviral therapy. Lower T scores at the hip [OR: 3.8 (1.1 to 12.5)] and lumbar spine [OR: 2.3 (1.1 to 4.5)] and lower lean body mass [OR: 1.1 (1.0 to 1.2)] were associated with significantly greater odds of low function (P ≤ 0.03). Lower insulin-like growth hormone [IGF-1; OR: 5.0 (1.4 to 20.0)] and IGF-1 binding protein-3 [OR: 3.3 (1.7 to 9.9)] increased the odds of low functional status (P ≤ 0.02). Fat mass and lower 25-OH vitamin D did not increase the odds of low functional status (P > 0.05).']
['To compare HIV seroprevalence and sexual risk behavior among very young gay and bisexual men (aged 15-17 years) and their older counterparts (aged 18-22 years). To examine drug-use patterns and correlates of sexual risk behavior in both of these age groups.', 'An interviewer-administered cross-sectional survey of 719 gay and bisexual males between 15 and 22 years old was conducted through a venue-based sampling design. Blood specimens were collected and tested for HIV antibodies, hepatitis B, and syphilis. Interviews assessed sexual and drug-use behavior as well as psychosocial variables believed to be related to sexual risk-taking, including self-acceptance of gay or bisexual identity, perceptions of peer norms concerning safer sex, and perceptions of the ability to practice safer sex (safer sex self-efficacy).', 'Of the 719 participants, 100 (16.2%) were aged between 15 and 17 years. HIV seroprevalence was somewhat lower among those aged 15 to 17 years (2.0%) compared with those aged 18 to 22 years (6.8%). Overall, the prevalence of hepatitis-B core antibody was significantly lower in the younger age group (5.0%) than in the older group (14.1%). The men aged 15 to 17 years used alcohol, ecstasy, and heroin less frequently than those aged 18 to 22 years. The age groups did not differ in the proportion of men who reported any unprotected anal intercourse in the previous 6 months (31.2%). In both age groups, use of amphetamines, ecstasy, and amyl nitrate was associated with unprotected anal intercourse. Self-acceptance of gay or bisexual identity was related to less sexual risk for those aged 15 to 17 years. In both age groups, greater safer sex self-efficacy was linked to less HIV sexual risk-taking. In the younger group, perceptions of peer norms that support safer sex were related to less risk behavior.']
['The genes FTO and GNB3 are implicated in essential hypertension but their interaction remains to be explored. This study investigates the role of interaction between the two genes in the pathophysiology of essential hypertension.', 'In a case-control study comprising 750 controls and 550 patients, interaction between the polymorphisms of FTO and GNB3 was examined using multifactor dimensionality reduction (MDR). The influence of interaction on clinical phenotypes like systolic and diastolic blood pressure, mean arterial pressure and body mass index was also investigated. The 3-locus MDR model comprising FTO rs8050136C/A and GNB3 rs1129649T/C and rs5443C/T emerged as the best disease conferring model. Moreover, the interacted-genotypes having either 1, 2, 3, 4 or 5 risk alleles correlated with linearly increasing odds ratios of 1.91 (P\u200a=\u200a0.027); 3.93 (P\u200a=\u200a2.08E-06); 4.51 (P\u200a=\u200a7.63E-07); 7.44 (P\u200a=\u200a3.66E-08) and 11.57 (P\u200a=\u200a1.18E-05), respectively, when compared with interacted-genotypes devoid of risk alleles. Furthermore, interactions among haplotypes of FTO (H1-9) and GNB3 (Ha-d) differed by >1.5-fold for protective-haplotypes, CTGGC+TC [H2+Ha] and CTGAC+TC [H4+Ha] (OR\u200a=\u200a0.39, P\u200a=\u200a0.003; OR\u200a=\u200a0.22, P\u200a=\u200a6.86E-05, respectively) and risk-haplotypes, AAAGC+CT [H3+Hc] and AAAGC+TT [H3+Hd] (OR\u200a=\u200a2.91, P\u200a=\u200a9.98E-06; OR\u200a=\u200a2.50, P\u200a=\u200a0.004, respectively) compared to individual haplotypes. Moreover, the effectiveness of gene-gene interaction was further corroborated with a 1.29-, 1.25- and 1.38-fold higher SBP, MAP and BMI, respectively, in patients having risk interacted-haplotype H3+Hc and 2.48-fold higher SBP having risk interacted-haplotype H3+Hd compared to individual haplotypes.']
['The human G-protein beta 3 subunit gene (GNB3) and some of its variants are known to be important genetic influences involved in essential hypertension (EH). Left ventricular hypertrophy (LVH) has long been thought to be an end point of EH, rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors.', 'We carried out a retrospective, case-control study of a GNB3 825 C>T dimorphism among nationals from the United Arab Emirates (Emirati), an ethnic group characterized by no alcohol intake and no cigarette smoking, for putative correlations with EH and LVH. We investigated a sample population of 454 Emirati (231 men, 223 women) comprising groups of controls and patients with clinical diagnoses of LVH, based on echocardiographic and ECG criteria, and EH, based on blood pressure values. The GNB3 825 C>T genotypes were determined by PCR and restriction digestion.', 'The distribution of genotypes was in Hardy-Weinberg equilibrium in all three subject groups. GNB3 T825 alleles demonstrated a strong association with LVH (OR = 2.22; 95% CI: 1.29-3.83 and P = 0.0002), but not with EH.']
['Despite the well known association between interleukin-6 (IL-6) and cardiovascular mortality, no study has so far verified whether IL-6 adds prognostic information to that provided by C-reactive protein (CRP).', 'A cohort of 218 haemodialysis patients from four different dialytic centres was followed-up retrospectively. Plasma IL-6 and CRP concentrations were determined. Full information on co-morbidities was available in 162 patients.', 'With respect to the lowest quartile (< 3.6 pg/ml for IL-6, and < 2.2 mg/l for CRP), the crude relative risk (RR) of death from all causes of the upper quartile (> 13.9 pg/ml for IL-6, and > 12.8 mg/l for CRP) was 5.20 (95% confidence interval 2.06-13.011) for IL-6 and 3.16 (1.41-7.12) for CRP. When both variables were included, the estimates were 4.10 (1.30-12.96) for IL-6 and 1.29 (0.47-3.57) for CRP. As to continuous variables, the relationship between both variables and mortality tended to level off for the highest values, but became fairly linear after log transformation of the variables. For one unit SD of the log (variable), the RR was 2.09 (1.52-2.88) for IL-6 and 1.66 (1.23-2.24) for CRP. When they were included in the same model, the estimates were 1.90 (1.18-2.82) for IL-6 and 1.16 (0.81-1.66) for CRP.']
['Tempe, a Rhizopus ssp.-fermented soya bean food product, was investigated for bacteriostatic and/or bactericidal effects against cells and spores of the food-borne pathogen Bacillus cereus.', 'Tempe extract showed a high antibacterial activity against B. cereus ATCC 14579 based on optical density and viable count measurements. This growth inhibition was manifested by a 4 log CFU ml(-1) reduction, within the first 15 min of exposure. Tempe extracts also rapidly inactivated B. cereus spores upon germination. Viability and membrane permeability assessments using fluorescence probes showed rapid inactivation and permeabilization of the cytoplasmic membrane confirming the bactericidal mode of action. Cooked beans and Rhizopus grown on different media did not show antibacterial activity, indicating the unique association of the antibacterial activity with tempe. Subsequent characterization of the antibacterial activity revealed that heat treatment and protease addition nullified the bactericidal effect, indicating the proteinaceous nature of the bioactive compound.']
['Fibrin glue in combination with polyglycolic acid (PGA) mesh is effective in preventing air leakage after segmentectomy, but we frequently experienced air leakage with single-layer application. To investigate improved usage, we compared the sealing effect among single-, double- and triple-layer PGA mesh and fibrin glue in both experimental and clinical segmentectomy.', 'Ex vivo pig lungs were used for experiments. As a model of segmentectomy, the lateral segment of the left lung was removed using electrocautery. As a model of peripheral lung defect, peripheral lung tissue was resected with scissors. The inter-segmental plane and the peripheral lung defect were sealed using one of the following four methods: (i) fibrin glue alone (Group 1, n = 8), (ii) single-layer with PGA mesh and fibrin glue (Group 2, n = 8), (iii) double-layer (Group 3, n = 8) and (iv) triple-layer (Group 4, n = 8). The seal-breaking pressures among them were compared. In clinical segmentectomy, the periods of chest-tube drainage were compared retrospectively between 17 patients treated by the single-layer and 17 treated by the triple-layer method.', 'In experimental segmentectomy, the seal-breaking pressure in the triple-layer (100 ± 25 cmH2O) was significantly higher than those in the other methods (26 ± 17, 48 ± 12 and 69 ± 19 cmH2O in the Groups 1, 2 and 3, respectively, P < 0.001-0.05), while there were no significant differences among other methods. For peripheral lung defect, the seal-breaking pressures did not differ among the methods. In clinical segmentectomy, the mean chest-drainage period with the triple-layer was 2 ± 0.9 days, which was significantly shorter than 3.6 ± 2.8 days with the single-layer (P = 0.009).']
['The recovery profile of train-of-four ratio to more than 0.70 in patients with diabetes mellitus has not been well investigated.', 'Our primary objective was to evaluate the spontaneous recovery profile of neuromuscular block by vecuronium until train-of-four ratio more than 0.90 in patients with type 2 diabetes mellitus compared with controls, using first dorsal interosseous electromyography.', 'Single-centre prospective case-control study.', 'The operating theatres of Fukuoka University Hospital.', 'Fourteen adults with type 2 diabetes mellitus (diabetes mellitus group) and 14 control patients (control group) were included in this study.', 'Evoked responses to train-of-four stimuli were measured by electromyography at the first dorsal interosseous muscle. General anaesthesia was induced with propofol, fentanyl and remifentanil. Vecuronium (0.1 \u200amg\u200akg) was administered to all patients. Anaesthesia was maintained with propofol, fentanyl and remifentanil. The neuromuscular block was assessed until spontaneous recovery to train-of-four ratio more than 0.90.', 'Recovery times to train-of-four ratio 0.70 and 0.90.', 'Recovery times to train-of-four ratio 0.70 and 0.90 were significantly longer in the diabetes mellitus group than the control group (P\u200a=\u200a0.041 and P\u200a=\u200a0.027, respectively). The time from train-of-four ratio 0.25 to 0.90 was also significantly longer in the diabetes mellitus group than the control group (P\u200a=\u200a0.029). In five of 14 patients in the diabetes mellitus group, the time from train-of-four ratio 0.25 to 0.90 was longer than 60\u200a min, which is longer than the duration of action of neostigmine. The time from train-of-four ratio 0.25 to 0.90 was longer than 60\u200a min in only one of 14 in the control group.']
['We intended to examine the underlying mechanism of microRNA-25 (miR-25) in regulating small cell lung cancer (SCLC).', 'The miR-25 expression was measured by quantitative RT-PCR (qRT-PCR) in 5 SCLC cell lines and 9 human SCLC tissues. In SCLC cell line H510A cells, endogenous miR-25 was downregulated by stable transfection of antisense oligonucleotide of miR-25 (miR-25-as). Then the effects of miR-25 downregulation on SCLC growth, invasion and chemoresistance were assessed by MTT, migration and cisplatin assays, respectively. Furthermore, the effects of miR-25 downregulation on cancer cell cycle arrest, production of cell cycle proteins cyclin E2 and CDK2 were examined by cell cycle assay, western blot and luciferase assays, respectively. Finally, cyclin E2 was over-expressed in H510A cells to investigate its effect on miR-25 mediated SCLC regulation.', 'In both SCLC cells and human SCLC tumor tissues, miR-25 was overexpressed. Down-regulation of miR-25 in H510A cells significantly reduced cancer cell growth, invasive capability and resistance to cisplatin. Also, it induced G1 cell cycle arrest and downregulated cell cycle related proteins cyclin E2 and CDK2. Luciferase assay demonstrated cyclin E2 was directly targeted by miR-25. Overexpression of cyclin E2 in H510A cells reversed the cell cycle arrest and restored invasive capability impaired by miR-25 downregulation.']
['In experimental studies, nonexcitatory electrical stimulation delivered at the time of absolute myocardial refractoriness resulted in cardiac contractility modulation (CCM) with improved systolic function. This study reports the initial experience with CCM in patients with chronic heart failure.', 'Twenty-five patients, 23 males, with a mean age of 62+/-9 years and drug-refractory NYHA class III heart failure were assigned to CCM-generator implantation. The underlying heart disease was idiopathic dilated cardiomyopathy in 12 patients and coronary heart disease in 13 patients. Acute efficacy of CCM with 7.73-V stimuli delivered via two right ventricular leads was evaluated by measuring the time derivative of left ventricular pressure (dP/dt). After implantation, the CCM generator was activated for 3 h daily over 8 weeks. In 23/25 patients the CCM system was implanted successfully. Heart failure significantly improved from NYHA class III to class II in 15 patients and to class I in 4 patients (p < 0.000001), left ventricular ejection fraction improved from 22+/-7% to 28+/-8% (p = 0.0002), and the Minnesota Living with Heart Failure Score improved from 43+/-22 to 25+/-18 (p = 0.001). The 6-min walk test increased from 411+/-86 to 465+/-81 m (p= 0.02). Nine patients (39%) had intermittent sensations associated with CCM delivery. There were two (8%) non-device-related deaths during follow-up.']
['To show that resuscitation from hypothermic, hemorrhagic shock using 65 degrees C intravenous fluid results in a more rapid return to euthermia compared with 40 degrees C intravenous fluid, without significant endothelial or hemolytic injury.', 'Fourteen anesthetized beagles (10-12 kg) were cooled to a core temperature of 30 degrees C and hemorrhaged to a mean arterial pressure of 40 to 45 mm Hg for 30 minutes. The animals were randomized to receive either 65 degrees C or 40 degrees C intravenous fluid through a specially designed catheter at a rate of 80% of their blood volume per hour until euthermic (37 degrees C) or for 2 hours.', "Blood pressure, pulmonary artery pressure, heart rate, and core temperature were continuously monitored. Blood samples were collected at baseline, after hemorrhage, 2 hours of resuscitation, and at postmortem examination after 7 days of survival. Laboratory measurements included complete blood count, plasma-free hemoglobin, and osmotic fragility. Values were compared using the Student's paired or unpaired t test with p approximately 0.05 indicating significance. Postmortem examination included light microscopy of the proximal superior vena cava or right atrium.", 'Animals receiving 65 degrees C intravenous fluid warmed 3.6 degrees C/hour, significantly faster than the 40 degrees C animals (1.9 degrees C/hour). There were no significant differences in plasma-free hemoglobin or osmotic fragility. Endothelial injuries were found in two animals in each group. These defects occurred along the path of catheter insertion and not at the infusion site.']
['Bone tissue adapts to its functional environment by optimizing its morphology for mechanical demand. Among the mechanosensitive cells that recognize and respond to forces in the skeleton are osteocytes, osteoblasts, and mesenchymal progenitor cells (MPCs). Therefore, the ability to use mechanical signals to improve bone health through exercise and devices that deliver mechanical signals is an attractive approach to age-related bone loss; however, the extracellular or circulating mediators of such signals are largely unknown. Using SDS-PAGE separation of proteins secreted by MPCs in response to low-magnitude mechanical signals and in-gel trypsin digestion followed by HPLC and mass spectroscopy, we identified secreted proteins up-regulated by vibratory stimulation. We exploited a cell senescence-associated secretory phenotype screen and reasoned that a subset of vibration-induced proteins with diminished secretion by senescent MPCs will have the capacity to promote bone formation in vivo. We identified one such vibration-induced bone-enhancing (vibe) gene as R-spondin 1, a Wnt pathway modulator, and demonstrated that it has the capacity to promote bone formation in three mouse models of age-related bone loss. By virtue of their secretory status, some vibe proteins may be candidates for pre-clinical development as anabolic agents for the treatment of osteoporosis.']