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['Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo.', 'Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area.', 'IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks.']
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['The aim of this study was to assess if there is a relationship between the outcome of laparoscopic splenectomy (LS) procedures and the size of the spleen, the learning curve, or the method of specimen retrieval.', 'Between January 1, 2002 and December 31, 2013, 70 LS procedures were performed at our department. Based on the weight of the removed spleen, patients were divided into three groups: Group 1, <350 g (n=32); Group 2, 350-1000 g (n=15); and Group 3, >1000 g (n=7). The role of the learning curve was also analyzed with the first 20 surgeries considered as the learning period. The specimen was retrieved with morcellation through the lateral port site in 54 cases, whereas in 11 cases, the large spleen was retrieved through a Pfannenstiel incision.', 'The mean duration of surgery was 122 minutes. When considered by spleen weight, durations for Groups 1-3 were 117, 128, and 134 minutes, respectively. When considered by the learning curve, durations for learning and later periods were 149 and 111 minutes, respectively (P=.002). After the learning period, larger spleens were removed (208 versus 519 g; P=.02), and there were fewer conversions. The mean postoperative hospital stay was 5.1 days. In the 11 cases where the specimen was retrieved through a Pfannenstiel incision, the mean duration of surgery was 108 minutes, and the mean spleen weight was 1032 g.']
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['Pediatric trauma uses a substantial amount of resources. Quick and cost-effective measures that can be used to identify children with clinically relevant injuries are essential to resource allocation and optimization of patient care. Admission hematocrit is rapid and inexpensive, causes minimal harm, and can potentially aid in critical decision making. We hypothesize that admission hematocrit predicts the need for transfusion in pediatric blunt trauma patients.', 'Records of trauma patients age 0 year to 17 years (2005-2013) who presented to a pediatric Level 1 trauma center were retrospectively reviewed. Data collected include demographics, computed tomographic scan findings, need for an intervention secondary to bleeding (blood transfusion, angioembolization, or operation), and admission hematocrit.', 'We found a significant decrease in admission hematocrit between patients requiring a transfusion and patients who did not (27% vs. 36%, p < 0.01). We evaluated a subset of patients who had an abdominal computed tomographic scan and found a significant decrease in admission hemocrit between those who required a transfusion for an intra-abdominal injury and those who did not (29% vs 37%, p < 0.01). In this subset, serial hematocrit values remained significantly lower in the patients requiring a transfusion up to 67 hours after admission (p = 0.04). A cutoff admission hematocrit of 35% or less has a sensitivity of 94% and a negative predictive value of 99.9% in identifying children who need a transfusion after blunt trauma.']
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['Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans.', 'Seven healthy male volunteers (18-27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of L-NMMA (4 mg kg-1 h-1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test.', 'The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (L-NMMA versus saline 1.6+/-0.2 h versus 1.9+/-0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of L-NMMA compared with saline (L-NMMA versus saline 92.1+/-3.9 min versus 66.4+/-6.4 min; p<0.005). Infusion of L-NMMA significantly increased the frequency (L-NMMA versus saline 50.4+/-6.6 versus 34.8+/-5.5 waves per 30 min; p<0.05) and amplitude (L-NMMA versus saline 20.4+/-1.5 versus 15.5+/-1.1 mmHg; p<0.01) of duodenal pressure waves.']
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['Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.', 'The objective of the study was a search for sex differences in adipose tissue function.', 'This was an exploratory study performed at a university hospital.', 'Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).', 'The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10(-7)), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).']
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['To evaluate the effects of oral anticholinergic (OAC) drugs on tear secretion in women with overactive bladder over a 3-month follow-up period.', 'In this prospective study, 108 women with a diagnosis of overactive bladder were evaluated. All patients were examined ophthalmologically at baseline (day 0), and after 1\xa0month (day 30) and 3\xa0months (day 90) of OAC treatment. Tear film break-up time (BUT) and Schirmer 1 test results were recorded. The subjective complaints of the patients including dry mouth, and burning, dryness and foreign body sensation in the eyes, were also recorded. The chi-squared test or the paired sample t test as appropriate, was used for statistical analysis.', 'The mean age of the patients was 51.8\u2009±\u20099.2\xa0years (30\xa0-\xa069\xa0years). The most frequent subjective complaints were dry mouth and dry eyes and both complaints were significant on both day 30 and day 90. Both tear film BUT and Schirmer 1 test results were significantly lower on day 30 and day 90. Dry eye measurement values worsened with prolongation of OAC treatment (p\u2009=\u20090.037 and p\u2009=\u20090.012 for BUT, and p\u2009=\u20090.046 and p\u2009=\u20090.035 for Schirmer 1 test, on day 30 and day 90, respectively).']
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['Patients with end-stage renal disease are required to limit fluid and salt intake. We examined illness representations [common-sense model (CSM)] among a sample of hemodialysis (HD) patients, investigating whether fluid-adherent patients held illness representations different from those of nonadherent patients. We also explored the utility of illness perceptions in predicting fluid nonadherence after controlling for clinical parameters, including residual renal function (KRU).', 'Illness perceptions were assessed [Revised Illness Perception Questionnaire (IPQ-R)] in 99 HD patients. Clinical parameters were collected and averaged over a 3-month period prior to and including the month of IPQ-R assessment. Depression scores, functional status, and comorbidity were also collected. Fluid nonadherence was defined using interdialytic weight gain (IDWG) and dry weight (ideal weight). Patients in the upper quartile of percent weight gain were defined as nonadherent (IDWG> or =3.21% dry weight).', 'Nonadherent patients had timeline perceptions significantly lower than those of adherent patients. Logistic regression models were computed in order to identify predictors of fluid nonadherence. After several demographic and clinical variables, including age, gender, and KRU, had been controlled for, lower consequence perceptions predicted nonadherence.']
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['To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF).', "From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10 years, 69% male, 59% had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9%). Thirty-four (21%) patients had known diabetes mellitus (DM). Oral glucose tolerance testing (OGTT) classified patients without a prior DM diagnosis as normal glucose tolerance (NGT), impaired glucose tolerance or new DM. All patients completed low-dose dobutamine echocardiography (LDDE) and 154 patients a 6-min walking distance test (6MWD). Compared with patients with NGT, patients with known DM had lower resting LVEF (33.4 vs. 39.1%, P < 0.05) and higher E/e' (13.9 vs. 11.4, P < 0.05). During LDDE, an increase in LVEF could be observed in all glycemic groups (mean 8.2% absolute increase), but the contractile reserve was lower in patients with known DM (-5.4%, P = 0.001) and new DM (-3.5%, P = 0.035) compared to patients with NGT. 6MWD was lower in known DM (349 m) and new DM (379 m) compared with NGT (467 m) (P < 0.001). Differences in clinical variables, resting echocardiographic parameters or contractile reserve, did not explain the exercise intolerance related to diabetes."]
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['Promoter hypermethylation and reduced expression of many genes have been found in gastric cancer. DNA methyltransferases are enzymes potentially affecting promoter hypermethylation.', "We analyzed proteins expression of DNA methyltransferase 1 and 3b by immunohistochemistry in 47 surgically resected gastric cancer samples for which clinicopathological characteristics, patient's outcome and methylation status of 11 selected tumor-related genes have been determined. Promoter methylation status of genes was assessed by methylation specific PCR.", 'We found that DNMT1 and 3b were up-regulated in gastric cancer and were detected in 51.1% and 57.4% of cases, respectively. Co-expression of DNMT1 and 3b was detected in 44.7%. Correlations analysis have showed that DNMT1 overexpression was significantly correlated with gastric cancer of intestinal histological type (P=0.01) and with gender of patient (P=0.01). However, there was no correlation between DNMT1 and DNMT3b overexpression in cancer and patients outcome. Moreover, there were no clear relations between the proteins expression of DNMT1 and 3b and DNA methylation status of genes. But co-expression of DNMT1 and DNMT3b was significantly associated with promoter hypermethylation of RAR-β2 (P=0.04).']
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['The HeartMate II (Thoratec Corp, Pleasanton, Calif) continuous-flow left ventricular assist device has emerged as the standard of care for patients with advanced heart failure. The objective of this study was to assess the safety and early effectiveness of concomitant tricuspid valve procedures in patients undergoing implantation of a HeartMate II device.', 'From February 2007 to April 2010, 83 patients underwent HeartMate II left ventricular assist device implantation. Of these, 37 patients had concomitant tricuspid valve procedures (32 repairs, 5 replacements) for severe tricuspid regurgitation. The effects of a tricuspid valve procedure on tricuspid regurgitation and right ventricular remodeling were assessed comparing echocardiographic findings at baseline and 30 days after left ventricular assist device implantation. Overall survival was also compared.', 'Patients undergoing a concomitant tricuspid valve procedure had more tricuspid regurgitation (vena contracta, 5.6 ± 2.1 mm vs 2.9 ± 2.0 mm; P < .001), worse right ventricular dysfunction (right ventricular end-diastolic area, 33.6 ± 6.2 mm vs 31.6 ± 8.5 mm; P = .05), higher mean right atrial pressure (17.4 ± 7.1 mm Hg vs 14.9 ± 5.1 mm Hg; P = .03), and a higher Kormos score (2.6 ± 2.1 vs 1.2 ± 1.4; P = .0008) preoperatively. One month after surgery, tricuspid regurgitation was worse in patients who underwent left ventricular assist device implantation alone (+18.6%), whereas it improved significantly in patients undergoing a concomitant tricuspid valve procedure (-50.2%) (P = .005). A corresponding significant reduction in right ventricular end-diastolic area (33.6% ± 6.2% vs 30.1% ± 9.7%; P = .03) and a trend toward better right ventricular function (55.5% ± 79.7% vs 35.7% ± 60.5%; P = .28) were noted in patients undergoing a concomitant tricuspid valve procedure. Survival was comparable between the 2 groups.']
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['Methylxanthines, like caffeine, have been thought to reverse the antiinflammatory effects of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated whether patients with RA taking MTX with a higher dietary caffeine intake have a worse clinical response to MTX than those with a lower intake.', 'Patients with RA enrolled in a prospective cohort study and currently taking MTX were divided equally into low, moderate, and high caffeine consumers. MTX clinical response was defined by the Disease Activity Score (DAS)28, Multidimensional Health Assessment Questionnaire (MDHAQ) score, and duration of morning stiffness. Regression models were used to study the relationship between caffeine intake and MTX response adjusting for age, sex, and other relevant variables at study enrollment.', "Two hundred and sixty-four patients with RA taking MTX had an average caffeine intake of 211.7 mg and average MTX dose of 16.0 mg/wk. The low caffeine group comprised 87 patients, the moderate 86, and the high 91. In 3 multivariate models, there was no statistical difference in MTX efficacy between groups, as measured by DAS28 score, MDHAQ score, and duration of morning stiffness at study enrollment. Moderate and high caffeine group had higher DAS28 scores, physician's global assessment, and swollen joint counts, but differences were not significant."]
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['The effects of oral contraceptive use on chlamydial infections and ensuing PID are not well understood. In this study, the effects of oral contraceptives on the clinical course of acute chlamydial salpingitis were investigated.', 'Monkeys (n = 4) in which salpingeal auto-transplants had been established were given oral contraceptive pills consisting of a combination of estrogen and progesterone (Norlestrin 1/50, Parke-Davis, Ann Arbor, MI). After one complete cycle of hormone treatment, monkeys were inoculated with C. trachomatis serovar E in the subcutaneous salpingeal pockets while under continuous hormone treatment. Inoculated pockets were biopsied serially for isolation of organisms and histopathological evaluation. Two monkeys not given oral contraceptives were studied in parallel.', 'The duration of infection as evidenced by recovery of organisms was not appreciably different between the treated and untreated monkeys. Chlamydia could be recovered from pocket tissues through day 10 post-infection in control and treated animals, and on day 14 post-infection in one of two control animals. Thereafter all isolation became negative. The inflammatory infiltrate consisted primarily of mononuclear cells (50-100 cells per 40 x field).']
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['Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease.', 'Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed.', "Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC."]
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['The glycoprotein erythropoietin (EPO) has been shown to be protective in models of neuronal disease and reduced apoptosis of retinal ganglion cells (RGC) after transection of the optic nerve and in glaucoma. In this study we assessed in vivo the properties of EPO on survival of RGC after ischemia and optic nerve compression, as well as on postischemic visual function. Furthermore, the safety of intravitreal injection was assessed.', 'In all experiments, EPO was administered intravitreally in male Brown Norway rats. Ocular ischemia was induced by elevating the intraocular pressure for 55 min. The calibrated optic nerve compression was performed for 10 s. RGC were marked stereotactically and quantified by fluorescence microscopy. The retinal function was quantified by electroretinography (ERG) and the whole visual pathway by visual evoked potential (VEP).', 'EPO (2 and 20 units per eye, n=9-21) increased the survival of RGC after ischemia by 21+/-21% and 127+/-31% (mean +/- SEM) and after optic nerve compression by 28+/-12% and 58+/-13%. With EPO (20 units), postischemic function was increased, in ERG by 71+/-13% (a-wave) and 75+/-19% (b-wave) and in VEP by 264+/-65% (p=0.053). Neither the ERG parameters, nor the VEP, nor the number of RGC differed significantly after intravitreal injection of EPO (5, 50, and 200 units, n=6-7) in healthy eyes.']
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['Indoleamine 2,3-dioxygenase (IDO) inhibits T-cell proliferation by catalyzing the conversion of l-tryptophan to l-kynurenine. IDO-induced immune tolerance weakens the clinical outcomes of immunotherapies. Sodium butyrate (NaB), one of the histone deacetylase inhibitors (HDACIs), has potential anti-tumor effects. Our previous studies revealed that NaB could inhibit IFN-γ induced IDO expression in nasopharyngeal carcinoma cells, CNE2. In the present study, we aim to investigate to the mechanism of NaB interfering with the interferon-gamma (IFN-γ)-mediated IDO expression signaling transduction.', 'IDO expression and STAT1 phosphorylation in CNE2 cells were analyzed by western blotting and STAT1 acetylation was evaluated by immunoprecipitation. STAT1 nuclear translocation and NF-κB activity were detected by transient transfection and reporter gene assay.', 'We found that NaB inhibited IFN-γ-induced IDO expression in CNE2 cells via decreasing phosphorylation and nuclear translocation of STAT1, but not via down-regulation of IFN-γ-receptor (IFNGR). Immunoprecipitation assays revealed that NaB increased STAT1 acetylation. Furthermore, NaB elevated the activity of NF-κB in CNE2 cells, and blocking the NF-κB activity had no effect on the IFN-γ-induced IDO expression.']
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['Dual antiplatelet therapy with aspirin and clopidogrel is currently recommended in off-pump coronary artery bypass (OPCAB). However, no data exist concerning platelet reactivity on clopidogrel after OPCAB. The aim of this study was to assess the relationship between platelet reactivity and late major adverse cardiovascular events (MACEs) after OPCAB.', 'In this prospective, single-center, observational study, on-clopidogrel platelet reactivity was measured using a point-of-care assay (VerifyNow system; Accumetrics Inc, San Diego, CA) in 859 patients who underwent OPCAB with 1 or more vein grafts. The primary end point was late MACEs (30 days-1 year) including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. Receiver operating characteristic curve analysis was used to estimate the cutoff value of P2Y12 reaction units (PRUs) for MACEs.', 'The optimal cutoff value for posttreatment reactivity for the incidence of late MACEs was ≥188 PRU (area under the curve 0.72, 95% CI 0.68-0.75, P = .002). The incidence of late MACEs was significantly higher in the high platelet reactivity (HPR; ≥188 PRU) group than in the low platelet reactivity (<188 PRU) group (3.6% vs. 1.4%, P = .040). Kaplan-Meier analysis revealed 1-year MACE-free survival rates of 98.4% ± 0.5% and 95.9% ± 1.3% in the low platelet reactivity and HPR groups, respectively (P = .034). According to a Cox regression hazard model, HPR was an independent risk factor for late MACE-free survival (hazard ratio 3.51, 95% CI 1.27-9.69, P = .015).']
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["Chronic allograft dysfunction (CAD) is the main cause of late transplant failure. Although several etiologies have been postulated, toxicity for calcineurin inhibitors (CNIs) is one of the most important causes of CAD, characterized by arteriolar hyalinosis, luminal narrowing, increased glomerulosclerosis, and tubulointerstitial damage. It's known that in transplant patients with CAD, fibrogenic mediators such as transforming growth factor beta (TGF-beta) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI.", 'This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus.', 'We studied twelve renal transplant patients with CAD on CNI treatment. TGF-beta in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment.', 'TGF-beta urine levels decreased from 24.7 +/- 11.2 to 12.8 +/- 5.1 ng/24 h (P = .049). In plasma, a similar decrease trend was observed (22.2 +/- 32 to 10.3 +/- 3 ng/mL), although it was not significant (P = .079). Endothelin-1 showed a decrease (8.1 +/- 3 to 5.2 +/- 1.1 pmol/L; P = .1) and VEGF in plasma increased from 34.3 +/- 37 to 92.2 +/- 86 pg/mL (P = .051).']
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['Children born large for gestational age (LGA) are prone to develop insulin resistance later in life. One factor that affects insulin sensitivity is the hormone adiponectin. The aim of this study was to determine whether being LGA has an impact on serum adiponectin and leptin levels and insulin resistance parameters during childhood, taking into account the severity of overweight.', 'Serum levels of adiponectin, leptin, fasting glucose and insulin, homeostasis model assessment insulin resistance index (HOMA-IR), and anthropometric indices were evaluated in groups of non-obese children aged 6.5-8 years, born appropriate for gestational age (AGA, n = 40) or LGA (n = 41), matched for age, gender, height, weight and body mass index. The LGA group was divided in two subgroups according to the degree of overweight: (a) LGA with birthweight 90th-97th percentile (n = 25); and (b) LGA with birthweight > 97th percentile (n = 16).', 'LGA children had a higher mean serum adiponectin level than AGA children: 17.0 +/- 9 vs. 11.1 +/- 5 (microg/ml) (P < 0.01). LGA children had also higher insulin 6.2 +/- 2.8 vs. 4.8 +/- 2.4 (microU/ml) (P < 0.05) and HOMA-IR 1.32 +/- 0.66 vs. 1.02 +/- 0.55 (P < 0.01) than AGA children. Children born LGA > 97th percentile had a significantly higher mean serum leptin level than both AGA and LGA 90th-97th percentile children (17 +/- 13, 9.6 +/- 9.5, 7.8 +/- 7.9 ng/ml, respectively, P < 0.05), and more severely affected insulin resistance indices than LGA 90th-97th percentile children. In the regression analysis, birthweight was found to be an independent predictor of adiponectin serum levels.']
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['Prognostic risk models have had limited success in predicting coronary events in subjects with multiple risk factors. We and others have proposed an alternative approach using radiographically detectable coronary calcium. We evaluated and compared the predictive value of these 2 approaches for determining coronary event risk in asymptomatic adults with multiple coronary risk factors. In addition, we assessed the predictive value of a risk model that included calcium score and cardiac risk-factor data.', 'We recruited 1196 asymptomatic high-coronary-risk subjects who then underwent risk-factor assessment and cardiac electron-beam CT (EBCT) scanning and were followed up for 41 months with a 99% success rate. We applied the Framingham model and our data-derived risk model to determine the 3-year likelihood of a coronary event. The mean age of our cohort was 66 years, and mean 3-year Framingham risk was 3.3+/-3.6%. Sixty-eight percent (818 subjects) had detectable coronary calcium. There were 17 coronary deaths (1.4%) and 29 nonfatal infarctions (2. 4%). The receiver operating characteristic (ROC) curve areas calculated from the Framingham model, our data-derived risk model, and the calcium score were 0.69+/-0.05, 0.68+/-0.05, and 0.64+/-0.05, respectively (P=NS). When calcium score was included as a variable in the data-derived model, the ROC area did not change significantly (0.68+/-0.05 to 0.71+/-0.04; P=NS).']
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[': Ischemia/reperfusion (IR)-induced acute kidney injury (AKI) is a common clinical syndrome. Stem/progenitor cell therapy is a promising option to foster the intrinsic capacity for kidney regeneration. However, there are still several challenges to be resolved, including the potential risks during cell culture, low retention rate after transplantation, and unclear effect on the progression of chronic kidney disease (CKD). Recently, nonexpanded adipose stromal vascular fraction (SVF) has been regarded as an attractive cell source for cell-based therapy. Preconditioning with ischemia has been suggested as a useful method to promote the retention and survival of transplanted cells in vivo. In this study, freshly isolated autologous SVF was transplanted to the kidney of rats before ischemia, and then an IR-induced AKI model was established. Postischemic administration of SVF to the kidney was performed after renal IR injury was induced. A higher cell retention rate was detected in the preischemic group. Preischemic administration of SVF showed stronger functional and morphologic protection from renal IR injury than postischemic administration, through enhancing tubular cell proliferation and reducing apoptosis. Progression of kidney fibrosis was also significantly delayed by preischemic administration of SVF, which exhibited stronger inhibition of transforming growth factor-β1-induced epithelia-mesenchymal transition and microvascular rarefaction. In addition, in vitro study showed that prehypoxic administration of SVF could significantly promote the proliferation, migration, and survival of hypoxic renal tubular epithelial cells. In conclusion, our study demonstrated that preischemic administration of nonexpanded adipose SVF protected the kidney from both acute IR injury and long-term risk of developing CKD.']
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['Energy expenditure measurements, performed while patients are in standardized resting conditions, are often used as an indicator of care by which to evaluate the adequacy of nutrition support regimens. Little attention has been directed toward examining potential errors incurred by deriving daily energy needs based on a single 15- to 20-minute measurement. This study was designed to differentiate energy expenditure during periods of sleep (defined as time spent in any of the standard sleep stages) and wakefulness in pediatric burn patients.', 'Twenty-four-hour indirect calorimetry, polysomnography, and physiologic assessments (mean arterial pressure, heart rate, body temperature, oxygen saturation, and respiratory rate) were conducted simultaneously in 14 patients, who were thermally injured and tracheally intubated, for a total of 45 24-hour intervals.', 'Mean age of the patients was 10.8+/-1.2 years. Mean total body surface area of the injury was 55.7+/-4.7%, and mean full-thickness burn was 48.8+/-6.0%.', 'A nested general linear analysis of variance model was used to evaluate the association between sleep, wakefulness, and energy needs; adjustments were made for postburn day and multiple test runs per patient.', 'On average, subjects slept 699+/-46 minutes/day. They experienced a large number of awakenings from sleep (mean=53+/-6.3 awakenings per 24 hours). Patients had mean energy expenditure of 2,529+/-396 kcal/day while awake and 2,360+/-291 kcal/day while asleep, and these mean values did not differ significantly. No differences in physiologic measurements during the awake and sleep states were found.']
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['Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown.', 'In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle-brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System.', 'The prevalence of PAD (defined as ABI < or =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P < 0.001).']
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['Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway.', 'Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder.', 'Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway.']
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['The primary goal of periodontal treatment is regeneration of the periodontium. Current theories suggest that the periodontal ligament (PDL) cells have the capacity to participate in restoring connective and mineralized tissues, when appropriately triggered. We evaluated whether human PDL cell sheets could reconstruct periodontal tissue.', 'To obtain the cell sheet, human PDL cells were cultured on temperature-responsive culture dishes with or without osteogenic differentiation medium. The cell sheets were transplanted on periodontal fenestration defects of immunodeficient rats. Forty rats were divided in two groups: in one group, cell sheets cultured with control medium were transplanted and in the other, cell sheets cultured with osteogenic differentiation medium were transplanted. The defects were analysed histologically and histomorphologically after healing.', 'Most of the experimental group exhibited a new cementum-like layer and new attachment of collagen fibres to the layer. Histomorphological analyses indicated significant periodontal regeneration. The control group revealed dense extracellular matrix and fibre formation, but an obvious cementum layer was not observed.']
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['In order to search for novel antibacterial compounds we used a previously developed screening strain designed specifically to discover inhibitors of the bacterial initiator protein, DnaA. This strain (SF53) is not viable at 30 degrees C due to overinitiation. Therefore, compounds that are able to restore growth to SF53 cells are likely to cause either partial or complete inhibition of DnaA function. In this study we used SF53 cells to screen the Library of Pharmacologically Active Compounds (LOPAC).', 'An SF53 screen of LOPAC in 384-well plates was performed. The effects of compounds identified as positive were studied further by growth assays specific for replication proteins as well as an in vitro assay of the activity of purified DNA gyrase.', 'One of the compounds that tested positive in this screening was the benzazepine derivate (+/-)-6-chloro-PB hydrobromide (S143). We found that the substance did not target DnaA directly, but that it most probably reduces overinitiation by inhibiting DNA gyrase. Benzazepines have not previously been reported as gyrase inhibitors.']
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['The purpose of this study was to examine differences in novel markers of cardiovascular disease (CVD) in women with type 2 diabetes stratified according to cardiorespiratory fitness.', 'A total of 28 women (mean age 57 +/- 6 years) with type 2 diabetes who were free from overt CVD were placed into low cardiorespiratory fitness (LCF) or average cardiorespiratory fitness (ACF) groups based on a graded exercise test to exhaustion. A group of eight women without type 2 diabetes were also examined and served as healthy control subjects. The median VO(2peak) value was used as a cutoff for group determination. We assessed both conventional CVD risk factors, including blood pressure, BMI, and lipid profile, as well as novel CVD risk factors, such as left ventricular filling dynamics, arterial stiffness, fasting insulin, and C-reactive protein (CRP).', 'VO(2peak) values were 69 +/- 14 and 91 +/- 24% of predicted values for sedentary age-matched healthy individuals in the LCF and ACF groups, respectively. BMI was significantly greater in the LCF group (P < 0.05); however, no differences were observed in age, lipid profile, or resting hemodynamics. CRP was 3.3-fold higher in the LCF group (6.3 +/- 41. vs. 1.9 +/- 1.7 mg/l, P < 0.05), whereas other novel markers of CVD were not significantly different between the groups. Significant negative relationships were observed between VO(2peak) and both CRP (r = -0.49) and the homeostasis model assessment index (r = -0.48) (P < 0.05).']
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['Apoptosis of natural killer (NK) cells is increased in patients with coronary artery disease (CAD) and may explain why NK cell levels are altered in these patients. Soluble forms of Fas and Fas ligand (L) are considered as markers of apoptosis. Here, we investigated whether plasma levels of Fas and FasL were associated with NK cell apoptosis and NK cell levels in CAD patients.', 'Fas and FasL in plasma were determined by ELISA in 2 cohorts of CAD patients; one longitudinal study measuring circulating NK cells and apoptotic NK cells by flow cytometry 1 day, 3 months and 12 months after a coronary event and one cross-sectional study measuring NK cell apoptosis ex vivo. Both studies included matched healthy controls. Fas and FasL were also determined in supernatants from NK cells undergoing cytokine-induced apoptosis in cell culture.', 'In the 12-month longitudinal study, plasma FasL increased by 15% (p<0.001) and NK cell levels by 31% (p<0.05) while plasma Fas did not change. Plasma FasL and NK cell levels were significantly related at 3 months and 12 months, r=0.40, p<0.01. Furthermore, plasma FasL, but not plasma Fas, correlated with NK cell apoptosis ex vivo in CAD patients, r=0.54, p<0.05. In vitro, cytokine-induced apoptosis of NK cells resulted in abundant release of FasL.']
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['Transfusion of aged blood has been associated with increased morbidity and mortality in critically ill patients. During storage, erythrocytes release increasing numbers of microvesicles (red blood cell-derived microvesicles [RBC-MV]). We hypothesized that RBC-MV mediate some of the deleterious effects of aged blood transfusions.', 'We established a murine transfusion model using RBC-MV purified from aged mouse erythrocytes. Injection of RBC-MV into healthy mice had no effect. However, they aggravated pulmonary leukocyte sequestration and peripheral blood leukopenia induced by lipopolysaccharides. Lipopolysaccharide-induced proinflammatory cytokines were significantly increased in plasma after RBC-MV injection. These effects were not seen in C5aR-deficient mice. In vitro, RBC-MV bound C3 fragments after incubation with plasma but failed to bind immunoglobulins, C1q, or mannose-binding lectin. Preventing thrombin generation inhibited complement activation in vitro and in vivo and reversed the proinflammatory effects of RBC-MV in lipopolysaccharide-primed mice. Finally, the RBC-MV-induced phenotype was recapitulated using phosphatidylserine-expressing liposomes, suggesting that surface expression of phosphatidylserine by RBC-MV was mechanistically involved.']
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["Atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice, is often managed with a rhythm control strategy. Despite the emphasis on symptom relief as the motivation for a rhythm controlling strategy in AF, it remains unclear what factors affect the patient's experienced severity of AF symptoms. We hypothesize that demographic variables may affect AF symptom severity as many AF symptoms (palpitations, dyspnea, fatigue) are nonspecific and may require particular patient insight.", 'We assessed demographic variables, cardiac and noncardiac comorbidities, AF burden, and AF-specific self-reported symptom severity in a cohort of 300 outpatients with AF presenting to outpatient electrophysiology clinics.', 'In unadjusted analyses, decreased educational attainment, unemployed working status, and non-Caucasian race were associated with worsened AF symptom severity. After adjusting for potential confounders, the association of decreased educational attainment with worsened AF symptom severity persisted.']
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['To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse.', 'The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR.', 'The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007-0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51-101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97-12.84; P = 0.001) were independent predictive factors for CNS relapse.']
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['Transgenic mice have become an important tool to elucidate the genetic foundation of the human language faculty. While learning is an essential prerequisite for the acquisition of human speech, it is still a matter of debate whether auditory learning plays any role in the development of species-specific vocalizations in mice. To study the influence of auditory input on call development, we compared the occurrence and structure of ultrasonic vocalizations from deaf otoferlin-knockout mice, a model for human deafness DFNB9, to those of hearing wild-type and heterozygous littermates.', "We found that the occurrence and structure of ultrasonic vocalizations recorded from deaf otoferlin-knockout mice and hearing wild-type and heterozygous littermates do not differ. Isolation calls from 16 deaf and 15 hearing pups show the same ontogenetic development in terms of the usage and structure of their vocalizations as their hearing conspecifics. Similarly, adult courtship 'songs' produced by 12 deaf and 16 hearing males did not differ in the latency to call, rhythm of calling or acoustic structure."]
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['Emerging evidence suggests that pulse pressure is an independent predictor of risk for cardiovascular mortality. New studies in diverse populations are needed to further establish the applicability of this finding. Thus, the purpose of this study is to examine the relationship between pulse pressure and cardiovascular mortality in a cohort of Puerto Rican men after 12 years of follow-up.', 'The Puerto Rico Heart Health Program is a study of coronary disease risk factors in men aged 35-79 years at baseline who had an initial examination during the years 1962-1965. It was attended by 9824 subjects representing 80% of the total age-specific male residents in 4 rural and 3 urban areas of Puerto Rico. Cardiovascular risk factors including systolic and diastolic blood pressures were monitored prospectively. This study includes 9106 men free of overt CHD at baseline who were stratified by quartiles of pulse pressure in mmHg: quartile 1, <or=38, quartile 2, 39-46; quartile 3, 47-56; and quartile 4, >or=57. The odds ratio of cardiovascular mortality was calculated using logistic regression analysis. After adjusting for age, education, smoking status, hypercholesterolemic status, physical activity, diabetic status and mean arterial pressure, we found that those in the highest quartile of pulse pressure (pulse pressure>=57) had significantly higher cardiovascular mortality than those in the lowest quartile (reference group) (OR=1.38 95% CI=1.01-1.88).']
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['Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity.', 'Salt-depleted rats were randomized to treatment with VH (vehicles 1\xa0mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1\xa0mg/kg body weight/day intraperitoneally), CsA (20\xa0mg/kg body weight/day subcutaneously) and CsA\xa0+\xa0ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups.', 'CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration.']
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['The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension.', 'Prospective, longitudinal study.', 'Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility.', 'The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months.', 'The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year).', 'Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression (P<0.02).']
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['To determine whether there is a significant correlation between the pulse-wave analysis in the optic nerve head circulation determined by laser speckle flowgraphy (LSFG), and brachial-ankle pulse wave velocity (baPVW), carotid intima-media thickness (IMT), and age.', "Thirty-three patients who visited the Vascular Function Section in our hospital were included. Age was 57.3 ± 12.6 years, with a range from 29 to 80 years. baPVW, carotid IMT, and pulse wave analysis in optic nerve head circulation using LSFG were conducted on subjects, and this parameter is named blowout time (BOT). The following items were analyzed as other systemic parameters: age, blood pressure, pulse pressure, heart rate, body mass index, and mean arterial blood pressure; other ocular parameters were intraocular pressure and ocular perfusion pressure. Pearson's correlation coefficients were used to determine the relationship between the BOT, baPWV, IMT, age, and other parameters. In addition, multiple regression analysis was used to determine independent factors for age.", 'BOT was significantly correlated with age (r = -0.85, P <0.0001), pulse pressure (r = -0.36, P = 0.04), baPWV (r\u2009=\u2009-0.72, P <0.0001), and IMT (r = -0.64, P < 0.0001). The result of multiple regression analysis showed that baPWV (odds ratio = 0.93, 95% confidence interval = 0.03-1.82 P = 0.04) and BOT (-2.26, -3.27 to -1.26, <0.0001) were independent contribution factors to age.']
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['Infections produce severe respiratory muscle weakness, which contributes to the development of respiratory failure. An effective, safe therapy to prevent respiratory muscle dysfunction in infected patients has not been defined. This study examined the effect of eicosapentaenoic acid (EPA), an immunomodulator that can be safely administered to patients, on diaphragm force generation following endotoxin administration.', 'Rats were administered the following (n = 5/group): (a) saline, (b) endotoxin, 12 mg/kg IP, (c) endotoxin + EPA (1.0 g/kg/d), and (d) EPA alone. Diaphragms were removed and measurements made of the diaphragm force-frequency curve, calpain activation, caspase activation, and protein carbonyl levels.', 'Endotoxin elicited large reductions in diaphragm specific force generation (P < 0.001), and increased diaphragm caspase activation (P < 0.01), calpain activation (P < 0.001) and protein carbonyl levels (P < 0.01). EPA administration attenuated endotoxin-induced reductions in diaphragm specific force, with maximum specific force levels of 27 +/- 1, 14 +/- 1, 23 +/- 1, and 24 +/- 1 N/cm2, respectively, for control, endotoxin, endotoxin + EPA, and EPA treated groups (P < 0.001). EPA did not prevent endotoxin induced caspase activation or protein carbonyl formation but significantly reduced calpain activation (P < 0.02).']
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['To determine if the chemokine monocyte chemo-attractant protein-1 (MCP-1) is produced locally in patients with bladder cancer and to analyse a possible correlation between tumour stage, grade and metastatic spread, and the urinary and systemic levels of MCP-1. PATIENTS SUBJECTS AND METHODS: Urine and serum samples were obtained from 60 patients with bladder cancer and 20 control subjects. Tumour stage, grade, metastasis and nodal status were assessed. MCP-1 levels in serum and urine were determined using a sandwich enzyme-linked immunosorbent assay. Two transitional cell cancer cell lines (grade I and grade III) were analysed for MCP-1 production under normal and nutritive-stress cell culture.', 'The correlation of urinary MCP-1 levels with tumour stage, grade and distant metastasis was highly significant. Patients with stage T2-T4 bladder cancer had three to fourfold higher mean MCP-1 concentrations (pg/mL) in their urine than those with T1 stage tumours or than the controls (controls 260; T1 359; T2 967; T3 917; T4 1829; P < 0.005). A tumour grade of > GI and the existence of distant metastasis (M1) also correlated significantly with higher urinary MCP-1 levels (GI 373; GII 661; GIII 1111; M0 644; M1 1379; P < 0.05). No differences in circulating serum MCP-1 level were detected between controls and patients. The low-grade (GI) RT4 bladder cancer cell line produced only traces of MCP-1, which did not change under nutritional stress; in contrast, the highly malignant T24 bladder cancer cell line (GIII) spontaneously secreted large amounts of MCP-1 (approximately 7000 pg/mL) which increased under nutritive stress to 13,000 pg/mL.']
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['Little is known about the prevalence of falls and the related risk factors in the general population of community-living older people in Germany.', 'To assess the prevalence and related predictors of different types of falls in a sample of community-dwelling 65 years and older people in Germany living in a metropolitan area. Study design and setting prospective cohort study in 622 community dwelling people aged > or =65 years.', 'A total of 107 persons (17.2%) reported falling at least once (occasional fallers), while 36 (5.7%) experienced two or more falls (recurrent fallers) in the last 6 months. Main predictors for all fallers were age (OR 1.8; 95% CI 1.1-3.0), being female (OR 1.7; 95% CI 1.1-2.2), living alone (OR 1.9; 95% CI 1.2-2.9), poor health status (OR 3.3; 95% CI 2.1-5.3), varifocals (OR 1.7; 95% CI 1.0-3.1), disturbance of memory (OR 1.7; 95% CI 1.0-3.0), depression (OR 4.8; 95% CI 2.5-9.2), sleep disturbances (OR 2.7; 95% CI 1.7-4.3), incontinence (OR 2.1; 95% CI 1.3-4.9), dizziness (OR 3.0; 95% CI 1.9-5.0), 3 medical conditions or more (OR 3.3; 95% CI 2.1-5.1), lower physical functioning and mobility. Two of the strongest predictors were reported falls (OR 4.9; 95% CI 3.1-7.7) and recurrent falls (OR 10.0; 95% CI 5.0-20.0) in the last 6 months.']
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['Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome.', 'Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome.', "150 PTC patients; 40 Hashimoto's thyroiditis (HT) patients; 21 healthy controls; 27.239 healthy Caucasians (for HLA typing).", 'HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course.', 'The frequency of TPO- and Tg-specific CD8+ T cells in PTC patients was largely increased compared to healthy controls (TPO and Tg: p < 0.005 and p < 0.005) and was similar to those in HT patients. HLA-DQB1*03 positive PTC patients had a significantly lower risk (RR: 0.170, 95% CI: 0.037 to 0.755, p < 0.05) and HLA-DRB1*03 positive and HLA-DQB1*02 positive PTC patients a significantly higher risk (HLA-DRB1*03: RR: 4.400, 95% CI: 1.378 to 14.05, p < 0.05; HLA-DQB1*02: RR: 3.692, 95% CI: 1.102 to 12.38, p < 0.05) for distant metastases, compared to patients with other haplotypes. HLA-DQB1*03 positive PTC patients revealed an increased responsiveness of tumor epitopes in vitro. These tumor epitope-specific CD8+ T cells were also found in lymph node metastases of HLA-DQB1*03 positive PTC patients.']
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['Cysteinyl leukotrienes (CysLTs) play important roles in the pathogenesis of eosinophilic airway inflammation characterized by bronchoconstriction, mucus secretion and airway hyper-responsiveness via cysteinyl leukotriene receptor 1 (CysLTR1)-mediated mechanism. CysLTR1-selective antagonists have anti-bronchoconstrictive and anti-inflammatory effects in asthma, particularly aspirin-intolerant asthma (AIA).', "To investigate the association of CysLTR1 with AIA development, we identified three single nucleotide polymorphisms (SNPs), -634C>T, -475A>C, -336A>G, in the 5' upstream region of CysLTR1 gene using a direct sequencing method in 105 AIA patients, 110 ASA-tolerant asthma (ATA) patients and 125 normal healthy controls (NC).", 'Significant differences were observed in allele frequencies of the three SNPs within male subjects; Male AIA patients had higher frequencies of the minor alleles of these three SNPs than male control groups (P=0.03 for AIA vs. NC; P=0.02 for AIA vs. ATA). Moreover, three-SNP haplotype, ht2 [T-C-G], was associated with increased disease risk (odds ratio (OR)=2.71, P=0.03 for AIA vs. NC; OR=2.89, P=0.02 for AIA vs. ATA) in males. CysLTR1 haplotypes were also associated with altered gene expression; luciferase activity was significantly enhanced with the ht2 [T-C-G] construct in comparison with the ht1 [C-A-A] construct in human Jurkat cells (P=0.04).']
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['Ezetimibe, as a cholesterol absorption inhibitor, has been shown protecting against atherosclerosis when combined with statin. However, side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin. Herein, the study aimed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size.', 'ApoE-/- male mice that were fed a saturated-fat supplemented diet were randomly assigned to different therapeutic regimens: vehicle, ezetimibe alone (10 mg/kg/day), atorvastatin (20 mg/kg/day) or combination of ezetimibe and atorvastatin through the drinking water. On 28 days, mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels. As a result, ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin, which was mediated by lowering serum cholesterol concentrations, inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines, such as monocyte chemoattractant protein (MCP-1) and tumor necrosis factor (TNF-α). In contrast to ezetimibe administration, atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects. There were no significance differences in lesion areas and serum concentrations of cholesterol, oxidized LDL and inflammatory cytokines between combination therapy and monotherapy (either ezetimibe or atorvastatin). There were significant correlations between the lesion areas and serum concentrations of cholesterol, MCP-1 and TNF-α, respectively. However, there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL.']
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['Acanthamoebae polyphaga Mimivirus (APM) is the largest known dsDNA virus. The viral particle has a nearly icosahedral structure with an internal capsid shell surrounded with a dense layer of fibrils. A Capsid protein sequence, D13L, was deduced from the APM L425 coding gene and was shown to be the most abundant protein found within the viral particle. However this protein remained poorly characterised until now. A revised protein sequence deposited in a database suggested an additional N-terminal stretch of 142 amino acids missing from the original deduced sequence. This result led us to investigate the L425 gene structure and the biochemical properties of the complete APM major Capsid protein.', 'This study describes the full length 3430 bp Capsid coding gene and characterises the 593 amino acids long corresponding Capsid protein 1. The recombinant full length protein allowed the production of a specific monoclonal antibody able to detect the Capsid protein 1 within the viral particle. This protein appeared to be post-translationnally modified by glycosylation and phosphorylation. We proposed a secondary structure prediction of APM Capsid protein 1 compared to the Capsid protein structure of Paramecium Bursaria Chlorella Virus 1, another member of the Nucleo-Cytoplasmic Large DNA virus family.']
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['Heterotopic ossification (HO) develops frequently after modern high-energy penetrating war injuries. The purpose of this prospective study was to identify and characterize the unique cytokine and chemokine profile associated with the development of HO as it pertained to the systemic inflammatory response after penetrating combat-related trauma.', 'Patients with high-energy penetrating extremity wounds were prospectively enrolled. Surgical debridement along with the use of a pulse lavage and vacuum-assisted-closure device was performed every 48-72 hours until definitive wound closure. Wound bed tissue biopsy, wound effluent, and serum were collected before each debridement. Effluent and serum were analyzed for 22 relevant cytokines and chemokines. Tissue was analyzed quantitatively for bacterial colonization. Correlations between specific wound and patient characteristics were also analyzed. The primary clinical outcome measure was the formation of HO as confirmed by radiographs at a minimum of 2 months of follow-up.', 'Thirty-six penetrating extremity war wounds in 24 patients were investigated. The observed rate of HO in the study population was 38%. Of the 36 wounds, 13 (36%) demonstrated HO at a minimum follow-up of 2 months. An elevated injury severity score was associated with the development of HO (P = 0.006). Wound characteristics that correlated with the development of HO included impaired healing (P = 0.005) and bacterial colonization (P < 0.001). Both serum (interleukin-6, interleukin-10, and MCP-1) and wound effluent (IP-10 and MIP-1α) cytokine and chemokine bioprofiles were individually associated and suggestive of the development of HO (P < 0.05).']
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['Aberrant gene promoter methylation is a critical event in tumorigenesis. The aim of this study was to explore the promoter hypermethylation of p16 and DAPK1 during the progression of cervical precancerous lesions.', 'A series of 98 cervical neoplasms (72 cervical intraepithelial neoplasia and 26 cervical carcinomas) were evaluated. The promoter methylation status of p16 and DAPK1 was assessed from cervical scrapings by methylation-specific polymerase chain reaction.', 'For p16, the frequency of promoter hypermethylation showed an increasing trend from normal to dysplastic to invasive squamous cancer specimens, and this increase reached statistical significance (P < 0.0001). However, there was no significant difference in the promoter methylation state of DAPK1 with regard to the various grades of cervical lesions (P = 0.077). Specifically, methylation of p16 was a frequent event in the cervical carcinoma samples, and these figures were statistically significant compared with the normal and cervical intraepithelial neoplasia I cases (P = 0.015 and P = 0.021, respectively).']
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['Campylobacter spp. are important causative agents of gastrointestinal infections in humans. The most frequently isolated strains of this bacterial genus are Campylobacter jejuni and Campylobacter coli. To date, genetic methods for bacterial identification have not been used in Bulgaria. We optimized the multiplex PSR assay to identify Campylobacter spp. and differentiate C. jejuni from C. coli in clinical isolates. We also compared this method with the routinely used biochemical methods.', 'To identify Campylobacter spp. and discriminate C. coli from C. jejuni in clinical isolates using multiplex PCR assay.', 'Between February 2014 and January 2015 we studied 93 stool samples taken from patients with diarrheal syndrome and identified 40 species of Campylobacter spp. in them. The clinical material was cultured in microaerophilic atmosphere, the isolated strains being biochemically diff erentiated (hydrolysis of sodium hippurate for C. jejuni, and hydrolysis of indoxyl acetate for C. coli). DNA was isolated from the strains using QiaAmp MiniKit (QIAGEN, Germany). Twenty strains were tested with multiplex PCR for the presence of these genes: cadF, characteristic for Campylobacter spp., hipO for C. jejuni and asp for C. coli.']
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Our experiments identified two basic processes determining immobilization. First, the rate of drop drying that depends on the drop volume and the ambient relative humidity. Oligonucleotides in a dried spot react unspecifically with the surface and long reaction times are needed. 3D hydrogel surfaces allow for immobilization in a liquid environment under diffusive conditions. Here, oligonucleotide immobilization is much faster and a specific reaction with the reactive linker group is observed. Second, the effect of increasing probe concentration as a result of drop drying. On a 3D hydrogel, the increasing concentration of probe molecules in nL spotting volumes accelerates immobilization dramatically. In case of μL volumes, immobilization depends on whether the drop is allowed to dry completely. At non-drying conditions, very limited immobilization is observed due to the low oligonucleotide concentration used in microarray spotting solutions. The results of our study provide a general guideline for microarray assay development. They allow for the initial definition and further optimization of reaction conditions for the immobilization of oligonucleotides and other probe molecule classes to different surfaces in dependence of the applied spotting and reaction volume.
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['Dietary fish oil potentiates the susceptibility of cellular membranes to lipid peroxidation, although it is also known to have beneficial effects on the development of cardiovascular diseases.', 'The effects of dietary fish oil against doxorubicin-induced cardiomyopathy, in which free radicals and lipid peroxidation are involved, were investigated in rats.', 'Sprague-Dawley rats (100 g) were fed a standard diet or a high fish oil diet (containing 10% fish oil) throughout the experimental period. Four weeks after starting each diet, experimental rats were treated with doxorubicin (cumulative dose 15 mg/kg) or vehicle (0.28 M dextrose solution). After three weeks of doxorubicin treatment, the cardiac performance, myocardial lipid peroxidation and myocardial vitamin E level were assessed.', 'Compared with control rats, doxorubicin-treated rats showed a significantly increased mortality rate (P<0.05), and significantly decreased systolic blood pressure and left ventricular fractional shortening (P<0.01). The myocardial thiobarbituric acid-reactive substance level was significantly higher in doxorubicin-treated rats than in control rats (P<0.01), while the myocardial vitamin E level was significantly lower (P<0.05). Dietary fish oil enhanced the myocardial lipid peroxidation caused by doxorubicin, which was associated with a further decrease in myocardial vitamin E level. As a result, the rats treated with both doxorubicin and the high fish oil diet showed the highest mortality rate and the lowest cardiac performance of all the experimental groups.']
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['Ultrasound is a potential therapeutic tool for dental tissue repair, but its biological effects on odontoblasts have not been well characterized. In this study, the effects of low-intensity low-frequency ultrasound on the viability, proliferation, and differentiation of odontoblast-like cells were investigated.', 'Cell viability and proliferation were assessed after the treatment of adherent clonal MDPC-23 odontoblast-like cells with a 25-mW/cm(2) 45-kHz ultrasound. An in vitro scratch wound healing assay was used to investigate the ultrasound effects on cell migration. Long-term cultures were used to study odontogenic differentiation and extracellular mineralization.', 'Ultrasound exposure for up to 30 minutes did not significantly affect odontoblast-like cell viability but significantly increased cell numbers after 2 days in culture. Ultrasound did not influence the scratch wound closure rate in the absence or presence of the mitogen inhibitor mitomycin C, indicating that ultrasound did not influence cellular migration. Single and consecutive exposures to ultrasound resulted in the enhancement of in vitro mineralization after 14 days in culture with an osteogenic differentiation medium. This coincided with the up-regulation of gene expression of collagen type I, osteoadherin, dentine matrix protein 1, and osteocalcin as well as the expression of cell markers alkaline phosphatase and nestin.']
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['Chemerin is a novel adipokine that is correlated with adipocyte differentiation, glucose metabolism, and inflammation. We aimed to investigate the relation between serum chemerin level and subclinical atherosclerosis markers as exemplified by brachial artery pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), epicardial fat thickness (EFT), and carotid plaque presence in diabetes and prediabetes.', 'Age-, body mass index (BMI)-, and gender-matched patients with type 2 DM (n=30), prediabetes (n=25), and normal glucose tolerance (n=25) were included in this cross-sectional study. Serum chemerin level, lipid parameters, glucose metabolism marker, baPWV, CIMT, EFT, and anthropometric were recorded. The independent risk factors for atherosclerosis markers were determined by linear and/or multiple logistic regression analysis.', 'baPWV and carotid plaque presence were higher in the diabetes group than in prediabetes and control groups (p=0.039 and p=0.035 respectively), whereas serum chemerin levels were similar among groups (p=0.338). Chemerin levels were not correlated with PWV, CIMT, and epicardial fat thickness overall or in the subgroups. Overall and in the diabetes group, chemerin levels were positively correlated with the key components of metabolic syndrome as BMI, total body fat percentage, waist circumference, triglyceride, and systolic and diastolic blood pressure (BP). After adjusting for age, gender, and BMI, only the association between chemerin and systolic BP remained significant. Chemerin was not found as an independent risk factor for predicting atherosclerosis in diabetes and prediabetes.']
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['Pigment epithelium-derived factor (PEDF), a serine protease inhibitor, is secreted from the adipose tissue and circulates at high concentrations. A recent study found that PEDF played a causal role in obesity-induced insulin resistance and metabolic dysfunctions in mice. Here we investigated whether circulating PEDF levels predicted the development of the metabolic syndrome (MetS) in a 10-yr prospective study.', 'Baseline plasma PEDF levels were measured with an ELISA in 520 nondiabetic subjects, recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. Multiple logistic regression was used to analyze whether PEDF was an independent factor related to the MetS at baseline. The role of PEDF in predicting the development of the MetS over 10 yr was analyzed using Cox regression analysis.', 'Plasma levels of PEDF were significantly higher in men than women. At baseline, sex-adjusted PEDF levels were significantly higher in subjects with MetS (P < 0.001), and the association remained significant (odds ratio: 1.17, P = 0.015), even after adjustment for covariates. Among the components of the MetS, PEDF was independently associated with hypertriglyceridemia (P = 0.026) and hypertension (P = 0.005). Of the 396 subjects without the MetS at baseline, a total of 80 had developed the MetS over 10 yr. High baseline sex-adjusted PEDF was an independent predictor of the development of the MetS in men (hazard ratio: 1.25, P = 0.034) but not in women.']
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['Intraocular pressure is increased during laparoscopic surgeries performed in a steep Trendelenburg position. This study compared the effects of propofol with those of sevoflurane on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy in a 30° Trendelenburg position.', 'Sixty-six patients were randomly allocated to a maintenance anesthetic consisting of remifentanil and sevoflurane (Sevoflurane Group) or remifentanil and propofol (Propofol Group). Intraocular pressure (IOP) was measured at nine predefined time points, including baseline (T0), five minutes after establishing pneumoperitoneum (T2), 30\xa0min after establishing the Trendelenburg position with pneumoperitoneum (T3), five minutes after returning to the horizontal position (T4), and immediately after tracheal extubation (T6). The primary outcome was the change in intraocular pressure from T0 to T3.', 'The results of linear mixed model analysis showed that intraocular pressure differed between the two groups (P\xa0=\xa00.0039). At T3, the mean (SD) IOP was greater in the Sevoflurane Group [23.5 (4.3) mmHg] than in the Propofol Group [19.9 (3.8) mmHg] (P\xa0=\xa00.0019). At T2 and T6, IOP was also greater in the Sevoflurane Group than in the Propofol Group (P\xa0=\xa00.038 and P\xa0=\xa00.009, respectively). There was a statistically significant increase in intraocular pressure from baseline to T3 (pneumoperitoneum and steep Trendelenberg) in the Sevoflurane Group [6.0 (5.0) mmHg; P\xa0<\xa00.001] but not in the Propofol Group [2.1 (5.1) mmHg; P\xa0=\xa00.136]. None of the patients experienced ocular complications.']
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['Glucocorticoid-induced leucine zipper (GILZ) represents an anti-inflammatory mediator, whose downregulation has been described in various inflammatory processes. Aim of our study was to decipher the regulation of GILZ in vascular inflammation.', 'Degenerated aortocoronary saphenous vein bypass grafts (n = 15), which exhibited inflammatory cell activation as determined by enhanced monocyte chemoattractrant protein 1 (MCP-1, CCL2) and Toll-like receptor 2 (TLR2) expression, showed significantly diminished GILZ protein and mRNA levels compared to healthy veins (n = 23). GILZ was also downregulated in human umbilical vein endothelial cells (HUVEC) and macrophages upon treatment with the inflammatory cytokine TNF-α in a tristetraprolin (ZFP36, TTP)- and p38 MAPK-dependent manner. To assess the functional implications of decreased GILZ expression, we determined NF-κB activation after GILZ knockdown by siRNA and found that NF-κB activity and inflammatory gene expression were significantly enhanced. Importantly, ZFP36 is induced in TNF-α-activated HUVEC as well as in degenerated vein bypasses. When atheroprotective laminar shear stress was employed, GILZ levels in HUVEC increased on mRNA and protein level. Laminar flow also counteracted TNF-α-induced ZFP36 expression and GILZ downregulation. MAP kinase phosphatase 1 (MKP-1, DUSP1), a negative regulator of ZFP36 expression, was distinctly upregulated under laminar shear stress conditions and downregulated in degenerated vein bypasses.']
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['Constraint-based reconstruction and analysis (COBRA) is used for modeling genome-scale metabolic networks (MNs). In a COBRA model, extreme pathways (ExPas) are the edges of its conical solution space, which is formed by all viable steady-state flux distributions. ExPa analysis has been successfully applied to MNs to reveal their phenotypic capabilities and properties. Recently, the COBRA framework has been extended to transcriptional regulatory networks (TRNs) and transcriptional and translational networks (TTNs), so efforts are needed to determine whether ExPa analysis is also effective on these two types of networks.', "In this paper, the ExPas resulting from the COBRA models of E.coli's MN, TRN and TTN were horizontally compared from 5 aspects: (1) Total number and the ratio of their amount to reaction amount; (2) Length distribution; (3) Reaction participation; (4) Correlated reaction sets (CoSets); (5) interconnectivity degree. Significant discrepancies in above properties were observed during the comparison, which reveals the biological natures of different biological processes. Besides, by demonstrating the application of ExPa analysis on E.coli, we provide a practical guidance of an improved approach to compute ExPas on COBRA models of TRNs."]
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['To explore the protective effects of N-acetylcysteine (NAC) on cochlear damage occurring in irradiated guinea pigs.', 'Seventy-two guinea pigs were randomly divided into 4 groups (n = 18 each). Control group received neither NAC nor irradiation, irradiation group received total cranium irradiation of 70 Gy, irradiation & saline group cranium irradiation of 70 Gy and saline solution through a round window and NAC group cranium irradiation of 70 Gy and NAC through a round window. The right ear received radiation. The animals were sacrificed at Day 14 post-irradiation. The specimens were dehydrated, embeded in paraffin and serially cut into 5-µm slices. Sections were stained with immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The cochlear basal membranes were observed for malondialdehyde (MDA) and superoxide dismutase (SOD) with scanning electron microscope.', 'The cilium of hair cells had no clear loss and apoptotic number of spiral ganglion cells decreased in NAC group. The average optical density value of Caspase 3 in spiral ganglion in NAC group significantly decreased versus the irradiation group (0.08 ± 0.02 vs 0.10 ± 0.01, P < 0.01). The level of MDA of NAC group also decreased versus the irradiation group (0.33 ± 0.05 vs 0.84 ± 0.13, P < 0.05). The level of SOD in the NAC group increased versus the irradiation group (10.7 ± 3.0 vs 8.7 ± 1.3, P < 0.05). The ratio of apoptotic cell in SGC in the NAC group at Day 14 (7.8% ± 1.8%) decreased versus the irradiation group (32.0% ± 8.7%) at Day 14.']
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["Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and ¹²³I-FP-CIT as the dopamine transporter ligand.", 'Thirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right- and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with ¹²³I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms.', 'Comparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate.']
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['Vascular stiffening, a risk factor for cardiovascular disease, is accelerated, particularly in women with obesity and type 2 diabetes. Preclinical evidence suggests that dipeptidylpeptidase-4 (DPP-4) inhibitors may have cardiovascular benefits independent of glycemic lowering effects. Recent studies show that consumption of a western diet (WD) high in fat and simple sugars induces aortic stiffening in female C57BL/6J mice in advance of increasing blood pressure. The aims of this study were to determine whether administration of the DPP-4 inhibitor, linagliptin (LGT), prevents the development of aortic and endothelial stiffness induced by a WD in female mice.', 'C56Bl6/J female mice were fed a WD for 4 months. Aortic stiffness and ex vivo endothelial stiffness were evaluated by Doppler pulse wave velocity (PWV) and atomic force microscopy (AFM), respectively. In addition, we examined aortic vasomotor responses and remodeling markers via immunohistochemistry. Results were analyzed via 2-way ANOVA, p < 0.05 was considered as statistically significant.', 'Compared to mice fed a control diet (CD), WD-fed mice exhibited a 24 % increase in aortic PWV, a five-fold increase in aortic endothelial stiffness, and impaired endothelium-dependent vasodilation. In aorta, these findings were accompanied by medial wall thickening, adventitial fibrosis, increased fibroblast growth factor 23 (FGF-23), decreased Klotho, enhanced oxidative stress, and endothelial cell ultrastructural changes, all of which were prevented with administration of LGT.']
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['Tumor volume is an important prognosticator for predicting prostate cancer recurrence following radical prostatectomy (RP). We assessed the ability of the visual estimate of the percent of carcinoma (VEPC) to predict recurrence.', 'As performed by 1 surgeon (MSS), 1,114 men underwent radical prostatectomy between 1992 and February 2002. Patients who had less than 12 months of followup, who underwent salvage RP or in whom VEPC was not assessed in the pathology specimen were excluded. VEPC and other clinical variables were analyzed. We performed univariate analysis using the Kaplan-Meier log rank test. Multivariate analysis using Cox proportional hazards regression was performed.', 'A total of 692 patients with a mean age of 61 +/- 7 years met the criteria for this analysis. Mean followup was 52 +/- 30 months. Of the patients 17% had biochemical recurrence. Mean VEPC was 25% and 13% in those with and without recurrence, respectively. On univariate analysis all variables were significant predictors of recurrence. However, multivariate analysis showed that the only significant predictors of recurrence were patient age, initial prostate specific antigen 10 ng/ml or greater, RP Gleason 8 to 10, extraprostatic extension, seminal vesicle involvement and VEPC. Based on disease-free survival curves patients were stratified into 3 broad groups, namely low, intermediate and high volume. The HR for biochemical recurrence was 2.1 for the intermediate VEPC group (9.1% to 20%) and 2.7 for the high VEPC group (greater than 20%). In the reference group it was less than 9% (low volume).']
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['The purpose of our study is to evaluate imaging features suggestive of a conjoined nerve root on routine axial MRI.', 'Two radiologists and two surgeons retrospectively reviewed the MRI of three cases in which a conjoined nerve root was discovered during operation and found three suggestive signs on routine axial MR images: "corner" (asymmetric morphology of the anterolateral corner of the dural sac), "fat crescent" (intervening extradural fat between the asymmetric dura and the nerve root), and "parallel" signs (visualization of the entire parallel course of the nerve root at the disc level). Two radiologists prospectively found these signs during routine MRI interpretation sessions over a period of 6 months. If one or a combination of signs were noted on axial MR images, contiguous axial scans were additionally obtained. Three cases that were previously found during operations were also included. Prevalence and confidence scores for each sign were assessed on axial T1- and T2-weighted images.', 'Twelve patients showed one or a combination of the three signs, 9 had contiguous axial MR scans. Five cases were confirmed by operation. The prevalence of the corner, fat crescent, and parallel signs were 12 out of 12 (100%), 6 out of 12 (50%), and 8 out of 12 (67.7%) on axial T1-weighted images. The overall diagnostic confidence was higher on T1- than on T2-weighted images (P<0.05).']
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['We studied three different injection techniques of sciatic nerve block in terms of block onset time and efficacy with 0.75% ropivacaine. A total of 75 patients undergoing foot surgery were randomly allocated to receive sciatic nerve blockade by means of the classic posterior approach (group classic; n = 25), a modified subgluteus posterior approach (group subgluteus; n = 25), or a lateral popliteal approach (group popliteal; n = 25). All blocks were performed with the use of a nerve stimulator (stimulation frequency, 2 Hz; intensity, 2-0.5 mA) and 30 mL of 0.75% ropivacaine. Onset of nerve block was defined as complete loss of pinprick sensation in the sciatic nerve distribution with concomitant inability to perform plantar or dorsal flexion of the foot. In the three groups, an appropriate sciatic stimulation was elicited at <0.5 mA. The failure rate was similar in the three groups (group popliteal: 4% versus group classic: 4% versus group subgluteus: 8%). The onset of nerve block was slower in group popliteal (25 +/- 5 min) compared with group classic (16 +/- 4 min) and group subgluteus (17 +/- 4 min; P < 0.001). There was no significant difference in the onset of nerve block between group classic and group subgluteus. No differences in the degree of pain measured at the first postoperative administration of pain medication were observed among the three groups. We conclude that the three approaches resulted in clinically acceptable anesthesia in the distribution of the sciatic nerve. The subgluteus and classic posterior approaches generated a significantly faster onset of anesthesia than the lateral popliteal approach.']
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['While ischemic preconditioning confers significant protection against subsequent prolonged periods of ischemia, the mechanisms triggering protection remain speculative. We hypothesize that a sub-lethal oxidative stress during ischemic preconditioning induces defense mechanisms preventing subsequent lethal injury.', 'We used mouse models of partial and total hepatic ischemia for 75 min. Ischemic preconditioning consisted of 10-min ischemia and 15-min reperfusion prior to the prolonged ischemic insult.', 'Tissue levels of peroxides increased about three times after 10 min of ischemia and normalized within 15 min of reperfusion. This limited oxidative stress during ischemic preconditioning prevented the negative effects of subsequent prolonged ischemia as assessed by AST-levels, TUNEL-staining of hepatocytes and animal survival. N-Acetylcysteine inhibited the mild oxidative burst of ischemic preconditioning, and fully reversed the protective effects of preconditioning. The protective role of a sub-lethal oxidative stress was supported by the benefit of delivery of an H2O2-analog through the portal vein prior to a long ischemic insult. This challenge conferred similar protection as ischemic preconditioning.']
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['Coma is associated with poor outcome in patients with basilar artery occlusion.', 'We sought to assess whether the posterior circulation Acute Stroke Prognosis Early CT Score and the Pons-Midbrain Index applied to CT angiography source images predict the outcome of comatose patients in the Basilar Artery International Cooperation Study.', 'Basilar Artery International Cooperation Study was a prospective, observational registry of patients with acute basilar artery occlusion with 48 recruiting centers worldwide. We applied posterior circulation Acute Stroke Prognosis Early CT Score and Pons-Midbrain Index to CT angiography source images of Basilar Artery International Cooperation Study patients who presented with coma. We calculated adjusted risk ratios to assess the association of dichotomized posterior circulation Acute Stroke Prognosis Early CT Score (≥8 vs. <8) and Pons-Midbrain Index (<3 vs. ≥3) with mortality and favourable outcome (modified Rankin Scale score 0-3) at one month.', 'Of 619 patients in the Basilar Artery International Cooperation Study registry, CT angiography source images were available for review in 158 patients. Among these, 78 patients (49%) presented with coma. Compared to non-comatose patients, comatose patients were more likely to die (risk ratios 2.34; CI 95% 1.56-3.52) and less likely to have a favourable outcome (risk ratios 0.44; CI 95% 0.24-0.80). Among comatose patients, a Pons-Midbrain Index\u2009<\u20093 was related to reduced mortality (adjusted RR 0.66; 95% CI 0.46-0.96), but not to favourable outcome (adjusted RR 1.19; 95% CI 0.39-3.62). Posterior circulation Acute Stroke Prognosis Early CT Score dichotomized at\u2009≥\u20098 vs. <8 was not significantly associated with death (adjusted RR 0.70; 95% CI 0.46-1.05).']
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['To investigate the role of miR-181c in glycolysis of cancer-associated fibroblasts (CAFs) and explore the mechanism.', 'Human lung CAFs and normal fibroblasts (NFs), isolated from fresh human lung adenocarcinoma tissue specimens by primary culture of tissue explants, were transfected with a miR -181c mimics, a miR-181c inhibitor, a siRNA siRNA-HK2 or the vector HK2-vector via Lipofectamine(TM) 2000. Quantitative real-time PCR was used to analyze the changes in miR-125b expression in the transfected cells; hexokinase-2 (HK2) protein expression in the cells was detected using Western blotting, and the cellular glucose uptake was assessed with 2-NBDG. Lactate production in the cells was examined and expression of HK2 mRNA was detected with dual luciferase reporter gene assay.', 'No obvious difference was found in the cell morphology between CAFs and NFs. Compared with the NFs, the CAFs showed obviously increased glucose uptake, lactate production and HK2 protein expression with decreased expressions of the miR-181 family (P<0.05). Transfection with the miR-181 inhibito- rsignificantly increased glucose uptake, lactate production and HK2 protein expression in the NFs. In CAFs, transfection with the miR-181 mimics caused significantly lowered glucose uptake, lactate production and HK2 protein expression of. Knockdown of endogenous HK2 by siRNA abolished miR-181 mimics-mediated decrease of glucose uptake and lactate production in CAFs, while transfection with miR-181 mimics suppressed HK2 overexpression-induced enhancement of glucose uptake and lactate production in NFs.']
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['To evaluate whether infliction of peritoneal trauma would promote tumor cell adherence to damaged peritoneal surfaces; to investigate whether peritoneal damage could promote tumor growth of extraperitoneal tumors; and to evaluate whether the amount of trauma correlated with the degree of tumor cell adherence and local and distant tumor growth.', 'After potentially curative resection of colorectal carcinoma, the most common site for recurrence is locoregional. We previously demonstrated that surgical trauma induces a cascade of events leading to adhesion formation. The same mechanisms may be responsible for improved tumor cell adherence and growth facilitation in early local recurrence.', 'A reproducible rat model was used in which peritoneal damage was inflicted by standardized rubbing of the peritoneum with surgical gauzes of different texture. In the first experiment, tumor cell adherence and growth at traumatized and nontraumatized peritoneal sites were assessed semiquantitatively 3 weeks after perioperative intra-abdominal injection of CC-531 tumor cells. In the second experiment, the effect of peritoneal trauma on ectopic tumor growth was investigated (CC-531 implanted under the renal capsule). In the final experiment, we evaluated how soon after peritoneal traumatization tumor cell adhesion and growth-promoting factors were active and whether they could be passively transferred to naïve nontraumatized abdominal cavities.', 'A significant correlation between the amount of peritoneal trauma and the degree of tumor take at damaged peritoneal surfaces was found (p < or = 0.018). Tumor take at remote peritoneal sites not directly traumatized was also significantly higher after severe trauma than after moderate trauma of the peritoneum (p < or = 0.005). In addition, a significant correlation between the degree of peritoneal trauma and the growth of ectopic tumors under the renal capsule was observed (p < or = 0.009). The final experiment demonstrated that within a few hours after infliction of peritoneal trauma, tumor growth-promoting effects could be passively transferred to naïve recipients.']
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['Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression.', 'A standard model of controlled LVH induction by supracoronary banding (A=baseline) was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to release the pressure gradient was performed 8.3+/-1 months later (B). The animals were killed after another 10.1+/-2 months (C). At all time points, hemodynamic evaluations and quantitative analysis of mRNA and protein expression for matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18 g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01, and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After surgical correction (C), there was a complete regression of gene expression to baseline measures.']
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['The aim of this study was to investigate the expression of receptor for advanced glycation end products (RAGE) on the surface of circulating endothelial cells (CECs) in patients with Kawasaki disease (KD).', 'The positive rate of RAGE on the surface of CECs (CECs-RAGE/CECs) and the fluorescence intensity of RAGE on the surface of CECs (FI-RAGE-CECs) were evaluated in 89 patients with KD in the acute stage (A-KD), subacute stage (SA-KD), or convalescent stage (C-KD).', 'CECs-RAGE/CECs and the FI-RAGE-CECs increased significantly in patients with KD. The CECs-RAGE/CECs was significantly higher in C-KD patients with coronary artery lesions (CALs) than in those without CALs. The FI-RAGE-CECs level was significantly higher in SA-KD and C-KD patients with CALs than in A-KD patients. In SA-KD and C-KD patients, the CECs-RAGE/CECs and FI-RAGE-CECs levels decreased in intravenous immunoglobulin (IVIG)-respondent patients but increased progressively in IVIG-resistant patients and were significantly higher in IVIG-resistant patients than in IVIG-respondent patients.']
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['Vascular smooth muscle (SM) cell phenotypic modulation plays an important role in arterial stiffening associated with aging. Serum response factor (SRF) is a major transcription factor regulating SM genes involved in maintenance of the contractile state of vascular SM cells.', 'We investigated whether SRF and its target genes regulate intrinsic SM tone and thereby arterial stiffness.', 'The SRF gene was inactivated SM-specific knockout of SRF (SRF(SMKO)) specifically in vascular SM cells by injection of tamoxifen into adult transgenic mice. Fifteen days later, arterial pressure and carotid thickness were lower in SRF(SMKO) than in control mice. The carotid distensibility/pressure and elastic modulus/wall stress curves showed a greater arterial elasticity in SRF(SMKO) without modification in collagen/elastin ratio. In SRF(SMKO), vasodilation was decreased in aorta and carotid arteries, whereas a decrease in contractile response was found in mesenteric arteries. By contrast, in mice with inducible SRF overexpression, the in vitro contractile response was significantly increased in all arteries. Without endothelium, the contraction was reduced in SRF(SMKO) compared with control aortic rings owing to impairment of the NO pathway. Contractile components (SM-actin and myosin light chain), regulators of the contractile response (myosin light chain kinase, myosin phosphatase target subunit 1, and protein kinase C-potentiated myosin phosphatase inhibitor) and integrins were reduced in SRF(SMKO).']
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['The inability to make profitable long-term decisions has been implicated in several psychiatric disorders. There is emerging evidence to support a role for dopamine (DA) in decision making, but our understanding of the role of noradrenaline (NA) and serotonin (5-HT) in decision making, and of possible interactions between the three monoamines, is limited. Moreover, impulsivity has been associated with aberrant decision making, but the underlying mechanisms are incompletely understood.', 'The purpose of this study is to improve our understanding of the neuropharmacological mechanisms of decision making and impulse control.', 'We investigated the effects of amphetamine (0.25-1.0\xa0mg/kg) and selective reuptake inhibitors of DA (GBR12909; 2.5-10\xa0mg/kg), NA (atomoxetine; 0.3-3.0\xa0mg/kg), and 5-HT (citalopram; 0.3-3.0\xa0mg/kg) in a rat gambling task (rGT). Since the rGT allows for detection of impulsive action, i.e., premature responding, we also assessed the relationship between decision making and impulsivity.', 'In the rGT, rats developed an optimal choice strategy from the first session onwards. Elevation of endogenous DA or NA levels increased and decreased impulsivity, respectively, but did not alter decision making. However, simultaneous blockade of DA and NA disrupted decision making, reflected by a relative decrease in choice for the advantageous choice options. Increasing 5-HT neurotransmission did not affect decision making or impulsivity.']
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['Several reports have indicated that the measurement of parathyroid gland size assists the management of patients with secondary hyperparathyroidism. This study examined whether parathyroid gland enlargement influenced the response of secondary hyperparathyroidism to cinacalcet.', 'Clinically stable hemodialysis patients with secondary hyperparathyroidism that was resistant to conventional treatment received cinacalcet for 6 months. Based on the parathyroid gland size measured by ultrasonography, the patients were divided into group S (gland <500 mm(3)) and group L (gland >or=500 mm(3)). Serum levels of intact parathyroid hormone (intact PTH), bone-specific alkaline phosphatase, osteocalcin, and cross-linked N-terminal telopeptide of type 1 collagen were measured over time.', 'Twenty-four patients completed the study. In group S, all markers of bone metabolism and intact PTH were significantly decreased after 3 months of cinacalcet treatment. In contrast, there were no significant changes of these parameters, except for intact PTH, after 3 months in group L. After 6 months of cinacalcet treatment, however, all of the markers of bone metabolism were significantly decreased in both groups.']
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['We evaluated the use of continuous infusion of ketamine to reduce intraoperative remifentanil side effects, such as bradycardia and hypotension, and to improve postoperative analgesia from balanced anesthesia with remifentanil.', 'Forty patients undergoing spine surgery under remifentanil-based anesthesia were randomly assigned to intraoperative ketamine group and saline (control) group. Balanced anesthesia was maintained with infusion of propofol (2-4 mg x kg(-1) x hr(-1)), remifentanil (6-8 microg x kg(-1) hr(-1)) and vecuronium (60-80 microg x kg(-1) x hr(-1)) with nitrous oxide (60%) and with or without ketamine (300-400 microg x kg(-1) x hr(-)). All patients were given scheduled NSAIDs by their own doctor at the end of surgery. Intraoperative bradycardia (HR <50) and hypotension (SBP <80), and postoperative additional NSAIDs request were recorded.', 'Adverse events, such as bradycardia and hypotension, were less frequent in the ketamine group (P < 0.05). Less additional NSAIDs was required in the ketamine than in the control group (P < 0.05). Emergence time from anesthesia was within 5 min in both groups.']
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["Alcoholism is characterized by impaired decision-making (i.e., choosing intoxication in the face of mounting negative consequences). This impairment may involve a reduced brain response to the negative consequences of behavior, which supports an inclination to engage in risky behaviors. The feedback error-related negativity (F-ERN) is hypothesized to reflect the valence attached to the negative consequences of behavior. Performance on the Balloon Analogue Risk Task (BART) measures risk-taking propensity. We recorded F-ERNs during the BART and during a BART simulation, where individuals observed the rewards and consequences of (someone else's) BART performance.", 'EEGs were recorded on 22 actively drinking, treatment-naïve alcoholics during the BART and BART simulation. F-ERNs were measured and their association with psychological and alcohol use measures was examined.', 'F-ERNs over fronto-central electrode sites were observed to balloon pops in the BART and BART simulation. F-ERNs during the BART were more than twice the amplitude of F-ERNs during the BART simulation. Smaller F-ERN amplitudes from the BART (but not the BART simulation) were associated with a greater family history density of alcohol problems.']
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['Periodontal ligament (PL) width is precisely maintained throughout the lifetime of adult mammals, but the biological mechanisms that regulate the spatial locations of the cell populations for bone, cementum, and PL are unknown.', 'As bisphosphonates induce ankylosis in mouse molar teeth, we used ethane-1-hydroxy-1, 1-bisphosphonate-(HEBP, Etidronate; Didronel) in combination with a periodontal window wound model to identify those cell populations involved in the regulation of PL width during the reformation of cellular domains after wounding. Four groups of Wistar rats were wounded by drilling through the alveolar bone and extirpation of the PL. Rats were administered HEBP for 1 week and then sacrificed or allowed to recover for an additional week prior to sacrifice. Control rats were sacrificed after 1 or 2 weeks. One hour prior to sacrifice, rats were injected with 3H-thymidine to label proliferating cells. Tissue sections were immunohistochemically stained for osteopontin (OPN) or bone sialoprotein (BSP) or were prepared for in situ hybridization (BSP) to identify extra- and intracellular expression of these non-collagenous bone proteins associated with periodontal healing.', 'HEBP treatment for 1 week induced a twofold increase in the thickness of the alveolar bone matrix in which weak immuno-staining for OPN and BSP mRNA signal was seen. During the recovery phase the increased bone width was reduced but was still considerably thicker than in control (P < 0.001). OPN staining as well as the BSP mRNA signal were much more intense than at 1 week. HEBP induced a > 40% reduction of PL width which returned to normal dimensions following the recovery phase. HEBP also modulated PL cell proliferation and differentiation: PL cell counts and labelling indices were reduced fivefold after 1 week of HEBP but returned to control values after the recovery phase. In controls, PL cells did not express OPN and BSP, but after HEBP treatment, and particularly after the recovery phase, PL cells expressed both of these markers intensely. In contrast, gingival and pulp connective tissues that were contiguous with the PL were not stained for OPN and did not express BSP mRNA after HEBP treatment.']
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['To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy.', 'Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry.', 'Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3.']
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['B cells positively contribute to immunity by antigen presentation to CD4(+) T cells, cytokine production, and differentiation into antibody secreting plasma cells. Accumulating evidence implies that B cells also possess immunoregulatory functions closely linked to their capability of IL-10 secretion.', 'Colitis development was followed in CD4(+) CD25(-) T cell transplanted SCID mice co-transferred with B cells exposed to an enterobacterial extract (ebx-B cells). B and T cell cytokine expression was measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA).', 'We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-γ)-producing T(H) 1 cells and increased frequencies of Foxp3-expressing T cells.']
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['Design of effective vaccines against the human immunodeficiency virus (HIV-1) continues to present formidable challenges. However, individuals who are exposed HIV-1 but do not get infected may reveal correlates of protection that may inform on effective vaccine design. A preliminary gene expression analysis of HIV resistant female sex workers (HIV-R) suggested a high expression CD26/DPPIV gene. Previous studies have indicated an anti-HIV effect of high CD26/DPPIV expressing cells in vitro. Similarly, high CD26/DPPIV protein levels in vivo have been shown to be a risk factor for type 2 diabetes. We carried out a study to confirm if the high CD26/DPPIV gene expression among the HIV-R were concordant with high blood protein levels and its correlation with clinical type 2 diabetes and other perturbations in the insulin signaling pathway.', 'A quantitative CD26/DPPIV plasma analysis from 100 HIV-R, 100 HIV infected (HIV +) and 100 HIV negative controls (HIV Neg) showed a significantly elevated CD26/DPPIV concentration among the HIV-R group (mean 1315 ng/ml) than the HIV Neg (910 ng/ml) and HIV + (870 ng/ml, p < 0.001). Similarly a FACs analysis of cell associated DPPIV (CD26) revealed a higher CD26/DPPIV expression on CD4+ T-cells derived from HIV-R than from the HIV+ (90.30% vs 80.90 p = 0.002) and HIV Neg controls (90.30% vs 82.30 p < 0.001) respectively. A further comparison of the mean fluorescent intensity (MFI) of CD26/DPPIV expression showed a higher DPP4 MFI on HIV-R CD4+ T cells (median 118 vs 91 for HIV-Neg, p = 0.0003). An evaluation for hyperglycemia, did not confirm Type 2 diabetes but an impaired fasting glucose condition (5.775 mmol/L). A follow-up quantitative PCR analysis of the insulin signaling pathway genes showed a down expression of NFκB, a central mediator of the immune response and activator of HIV-1 transcription.']
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['Toll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including septic cardiomyopathy, ischemia/reperfusion, heart failure, and cardiac hypertrophy. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 is also involved in the development of cardiac hypertrophy.', 'Tlr2 deficient and wild type mice were subjected to transverse aortic constriction (TAC) or sham operation procedure. Left ventricular, heart and lung weights as well as hemodynamic parameters were determined after 3, 14 or 28 days. Real-time RT PCR was used to evaluate left ventricular gene expression. Protein content was determined via ELISA.', 'TAC increased systolic left ventricular pressure, contraction and relaxations velocities as well as the heart weight in both genotypes. Tlr2 deficiency significantly enhanced cardiac hypertrophy after 14 and 28 days of TAC. Left ventricular end-diastolic pressure and heart rate increased in Tlr2(-/-) TAC mice only. Fourteen days of TAC led to a significant elevation of ANP, BNP, TGFβ and TLR4 mRNA levels in Tlr2(-/-) left ventricular tissue.']
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['Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings.', 'To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi.', 'Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples.', 'A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples.']
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['Epidemiologic studies implicate air pollutant exposure during pregnancy as a risk factor for wheezing in offspring. Ozone exposure is linked to exacerbations of wheezing in children.', 'To determine if maternal pulmonary exposure to traffic-related particles during pregnancy augments ozone-induced airway hyperresponsiveness in offspring.', 'C57BL6 time-mated mice were given NIST SRM#1648 (particulate matter [PM]) 0.48 mg, saline vehicle, or no treatment by tracheal insufflation twice weekly for 3 weeks. PM exposure augmented maternal lung inflammation and placental TNF-alpha, Keratinocyte-derived cytokine (KC), and IL-6 (measured at gestation Day 18). After parturition, dams and litters were exposed to air or ozone 1 ppm 3 h/d, every other day, thrice weekly for 4 weeks. Respiratory system resistance in pups was measured at baseline and after administration of nebulized methacholine.', 'Ozone increased airway hyperresponsiveness, but the increase was greatest in pups born to PM-treated dams. Whole-lung TNF-alpha, IL-1beta, KC, IL-6, and MCP-1 were increased in ozone-treated pups, with the greatest increase in pups born to dams given PM. Airway epithelial mucous metaplasia estimated by periodic acid-Schiff Alcian blue staining was increased in ozone-exposed pups born to PM-treated dams. Alveolar development, determined by morphometry, and airway smooth muscle bulk, estimated using alpha-actin histochemistry, were unaffected by prenatal or postnatal treatment.']
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['Soy isoflavones have numerous biological properties that suggest that they may protect against colorectal cancer. Colorectal epithelial cell proliferation has been used extensively as an intermediate endpoint biomarker for colorectal neoplasia.', 'We tested the hypothesis that supplementation with soy protein containing isoflavones decreases colorectal epithelial cell proliferation.', 'A 12-mo randomized intervention was conducted in men and women aged 50-80 y with recently diagnosed adenomatous polyps. One hundred fifty participants were enrolled and randomly assigned to an active treatment group (58 g protein powder/d containing 83 mg isoflavones/d; +ISO) or a control group (ethanol-extracted soy-protein powder containing 3 mg isoflavones; -ISO). Biopsy specimens from the cecum, sigmoid colon, and rectum were collected at baseline and at the 12-mo follow-up. Ki-67 antibody immunohistostaining was used to detect cell proliferation. One hundred twenty-five participants completed the study, and proliferation was measured in the first 91 who completed the study.', 'In the sigmoid colon, cell proliferation increased by 0.9 (95% CI: 0.09, 1.9) labeled nuclei per crypt more (11%) in the +ISO group than in the -ISO group over the 12-mo intervention, which was opposite the direction predicted. The number of labeled nuclei per 100 mum crypt height also increased more in the +ISO than in the -ISO group. In the cecum and sigmoid colon, but not in the rectum, the proliferation count increased as the serum genistein concentration increased. Proliferation distribution and crypt height were not changed by treatment at any site.']
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['Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1aΔ itr3cΔ double mutant of C. neoformans was attenuated for virulence in a murine model of intra-cerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain.', 'To understand the immune pathology associated with infection by the itr1aΔ itr3cΔ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1aΔ itr3cΔ mutant cells, indicating that inositol utilization pathways play a role in capsule production.']
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['The purpose of this study was to assess whether the addition of intravenous magnesium sulphate (Mg) at the induction of anaesthesia to a balanced anaesthetic protocol including wound infiltration, paracetamol and tramadol resulted in improved analgesic efficiency after radical prostatectomy.', 'We conducted a randomized, double-blind, controlled study. Thirty ASA I or II males scheduled to undergo radical retropubic prostatectomy with general anaesthesia were prospectively assigned to one of the two groups (n = 15 each). The Mg group (Gr Mg) received 50 mg kg-1 of MgSO4 in 100 mL of isotonic saline over 20 min immediately after induction of anaesthesia and before skin incision. The patients in the control group (Gr C) received the same volume of saline over the same period. At the time of abdominal closure, wound infiltration with 190 mg (40 mL) of ropivacaine was performed in both groups. Pain was assessed by a 10-point visual analogue scale in the recovery room starting from the time of tracheal extubation. Standardized postoperative analgesia included paracetamol and tramadol administered via a patient-controlled analgesia device.', 'In the postoperative period, both groups experienced an identical pain course evolution. Cumulative mean tramadol dose after 24 h was 226 mg in the magnesium group and 446 mg in the control group (P < 0.001). Postoperative nausea occurred in two patients in each group. Two vs. eight patients required analgesic rescue in magnesium and control groups, respectively (P = 0.053).']
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['Histologic grade, completeness of resection, and presence of metastases are traditionally regarded as the primary factors in predicting survival for retroperitoneal soft tissue sarcoma (RPSTS). We sought to examine the importance of histologic type as a prognostic factor among patients with RPSTS.', 'We identified 2337 cases of RPSTS in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2004. After excluding 273 cases of age <18, identification by autopsy only, or absence of histologic confirmation, we arrived at a final study cohort of 2064 patients. Overall survival (OS) and disease-specific survival (DSS) were estimated using the Kaplan-Meier method. Multivariate analysis was performed using a Cox proportional hazards model, adjusting for age, gender, race, histologic type, histologic grade, tumor size, extent of resection, and SEER summary stage.', 'Among 33 histologic types, leiomyosarcoma (28.7%), well-differentiated/dedifferentiated liposarcoma (20.3%), liposarcoma not otherwise specified (NOS) (11.9%), malignant fibrous histiocytoma (MFH-11.0%), and sarcoma NOS (10.7%) were the most prevalent. Grade distribution was low, 24.2%; intermediate, 16%; high 34.3%, and unknown, 25.5%. Surgery was performed in 85.8%, and radiotherapy was administered to 22.8%. With a median follow-up of 38 mo, median OS\xa0was 78, 35, 25, 18, and 10 mo for liposarcoma, leiomyosarcoma, other\xa0histologies, MFH, and sarcoma NOS, respectively (P\xa0<\xa00.0001). Median DSS was 120, 53, not reached, 30, and 13 mo for liposarcoma, leiomyosarcoma, other histologies, MFH, and sarcoma NOS, respectively\xa0(P < 0.0001). On multivariate analysis, histologic type was associated with statistically significant differences in both OS and DSS.']
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['In adults, binding of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) to lymphocyte alpha4beta7 integrin directs cell trafficking to gut, whereas interaction of peripheral node addressins (PNAd) with lymphocyte L-selectin targets immune cells to peripheral lymph nodes (PLNs). Because nothing is known about these addressins during human development, we studied the expression and function of MAdCAM-1 (and PNAd for comparison) in fetuses and children.', 'Series of human tissue samples obtained from fetuses (7-40 weeks), children (2 months-7 years), and adults were immunostained with monoclonal antibodies. The function of the addressins and their lymphocyte counter-receptors was tested in in vitro binding assays on fetal and adult tissues.', 'Unlike in adults, MAdCAM-1 is widely expressed from embryonic week 7 onwards, and it only gradually becomes polarized to mucosal vessels after birth. In utero MAdCAM-1 functionally governs lymphocyte adhesion to vessels both in the gut and PLNs by binding to alpha4beta7 integrin. The later induction of PNAd gradually starts to dominate the binding of lymphocytes to PLNs during childhood.']
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['Pulmonary metastases are common in patients with primary colorectal cancer (CRC). Heat-shock protein 27 (Hsp27) is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs) are also thought to play a role as prognostic and predictive markers in various malignancies including CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. Therefore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases.', 'FFPE tissue samples from 51 pulmonary metastases (PMs) and 33 paired primary tumors were evaluated for alpha-SMA, CD31, Hsp27 and vimentin expression by immunohistochemistry and correlated with clinicopathological variables. 25 liver metastases served as control group. Moreover, serum samples (n=10) before and after pulmonary metastasectomy were assessed for circulating phospho-Hsp27 and total Hsp27 by ELISA.', 'Stromal expression of Hsp27 was observed in all PM and showed strong correlation with alpha-SMA (P<0.001) and vimentin (P<0.001). Strong stromal Hsp27 was associated with higher microvessel density in primary CRC and PM. Moreover, high stromal Hsp27 and αSMA expression were associated with decreased recurrence-free survival after pulmonary metastasectomy (P=0.018 and P=0.008, respectively) and overall survival (P=0.031 and P=0.017, respectively). Serum levels of phospho- and total Hsp27 dropped after metastasectomy to levels comparable to healthy controls.']
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['This study evaluated the involvement of tumour necrosis factor α (TNF-α) in orofacial thermal and mechanical hyperalgesia induced by an inflammatory stimulus or by chronic constriction of the infraorbital nerve (CION) using etanercept (Eta), a TNF-receptor fusion protein that inhibits TNF-α action.', 'Animals were treated with Eta (0.5 and 5.0\u2009mg/kg, s.c.) or dexamethasone (Dex, 0.5, 1.0 and 2.0\u2009mg/kg, s.c.) and orofacial thermal (cold and heat) and mechanical hyperalgesia induced by an inflammatory stimulus (carrageenan, Cg 50 and 100\u2009μg/lip) or by chronic CION, a model of neuropathic pain in the orofacial region was evaluated. Treatments with Dex or Eta were carried out before Cg or before or after CION.', 'Eta or Dex abolished inflammatory thermal and mechanical hyperalgesia. Also, each drug, when given at the day of the surgery and the subsequent day, was effective to abolish thermal and mechanical hyperalgesia induced by CION, assessed on day 4 and on day 13 after the surgery, respectively. However, Eta, but not Dex, given after the CION, abolished thermal and mechanical hyperalgesia and reduced TNF-α level in the trigeminal ganglion.']
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['P. gingivalis is a gram-negative anaerobic bacterium and a major periodontal pathogen. LPS produced by P. gingivalis promotes osteoclast formation. TECK is a CC chemokine whose expression is increased in gingival epithelial cells exposed to P. gingivalis LPS. In this study, we investigated the effect of TECK in osteoclastogenesis induced by P. gingivalis LPS.', 'Real time reverse transcriptase polymerase chain reaction (RTPCR) analysis and western blotting were performed to confirm TECK in MG63, human osteoblast cell line and primary murine osteoblasts and CCR9 in RAW 264.7 cells and murine bone marrow macrophages (BMMs) as osteoclast precursors. P. gingivalis LPS-treated BMMs and Raw 264.7 cells were cultured with or without TECK or TECK antibody to examine the effect of TECK on osteoclast formation. Cocultures with murine osteoblasts and bone marrow cells were also treated with or without TECK or TECK antibody. Luciferase assay and western blotting were used to determine whether TECK-CCR9 induced osteoclastogenesis was mediated through NFATc1 or NF-kB signaling.', 'TECK was shown to be expressed by osteoblasts, and its receptor, CCR9, by osteoclast precursors. TECK increased P. gingivalis LPS-induced osteoclast numbers in an in vitro osteoclast formation assay using osteoclast precursors. The enhanced osteoclast formation by TECK was mediated by NFATc1, but not by NF-kB signaling.']
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['Darbepoetin, a long-acting erythropoietin derivative, attenuates cardiomyocyte apoptosis and improves short-term (3 days) cardiac function, but the mechanisms responsible are unknown. We investigated potential mechanisms by which darbepoetin exerts cardioprotection following myocardial infarction in mice and the significance of the erythropoietin receptor (EPOR)-common beta-chain (c-beta-chain) heteroreceptor.', 'Mice underwent 60 min coronary occlusion followed by treatment with vehicle or a single dose of darbepoetin. Effects on gene expression, apoptosis and neutrophil accumulation in infarcted left ventricle were assessed 24 h later. Cardiac function, effects on vascularization and fibrosis were assessed 28 days later. The significance of EPOR-c-beta-chain heteroreceptor was examined 28 days after infarction using mice deficient in c-beta-chain.', 'Twenty-four hours after darbepoetin, mRNAs encoding haeme oxygenase-1 (HO-1), iNOS and brain natriuretic peptide (BNP) were markedly elevated only in infarcted regions, and the frequency of apoptotic cells attenuated. Inflammation was also attenuated with reductions in neutrophil numbers. Darbepoetin also elevated mRNAs encoding angiogenic factors: placental growth factor, monocyte chemoattractant protein-1 and interleukin-1beta. Twenty-eight days after treatment, CD31+ vessels in the infarct zone doubled and fibrosis reduced. Cardiac haemodynamics were improved. Darbepoetin also improved cardiac haemodynamics in c-beta-chain-deficient mice, increased HO-1 and iNOS expression and vessel numbers and attenuated fibrosis.']
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['Linker histone H1 has been studied in vivo and using reconstituted chromatin, but there have been few systematic studies of the effects of the cellular environment on its function. Due to the presence of many other chromatin factors and specific chaperones such as RanBP7/importin beta that regulate histone H1, linker histones likely function differently in vivo than in purified systems.', 'We have directly compared H1 binding to sperm nuclei in buffer versus Xenopus egg extract cytoplasm, and monitored the effects of adding nuclear import chaperones. In buffer, RanBP7 decondenses sperm nuclei, while H1 binds tightly to the chromatin and rescues RanBP7-mediated decondensation. H1 binding is reduced in cytoplasm, and H1 exhibits rapid FRAP dynamics in cytoplasm but not in buffer. RanBP7 decreases H1 binding to chromatin in both buffer and extract but does not significantly affect H1 dynamics in either condition. Importin beta has a lesser effect than RanBP7 on sperm chromatin decondensation and H1 binding, while a combination of RanBP7/importin beta is no more effective than RanBP7 alone. In extracts supplemented with RanBP7, H1 localizes to chromosomal foci, which increase after DNA damage. Unlike somatic H1, the embryonic linker histone H1M binds equally well to chromatin in cytoplasm compared to buffer. Amino-globular and carboxyl terminal domains of H1M bind chromatin comparably to the full-length protein in buffer, but are inhibited ∼10-fold in cytoplasm. High levels of H1 or its truncations distort mitotic chromosomes and block their segregation during anaphase.']
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['We analyzed 9 cases by immunohistochemical studies in order to elucidate the mechanisms of cartilage destruction in relapsing polychondritis (RP), which often involves the external auricle and respiratory tract through immunological disorder.', 'Cartilage tissues were obtained during surgical operations. Cell species in the granulation tissues, especially near the cartilage, were identified by cell-surface markers [CD3, CD4, CD8, CD20, CD45 (LCA), and CD68]. The proteolytic enzymes expressed in the cells in the perichondral granulation and in chondrocytes themselves were analyzed by immunohistochemical studies using anti-matrix metalloproteinase (MMP) -1, -3, -8, -9, and -13, and cathepsin D, K, L, and elastase antibodies. Apoptosis and nitric oxide (NO), an apoptosis-related factor, were also examined using ApopTag and antinitrotyrosine antibody, respectively.', 'Among cell species that infiltrated in perichondral granulation, LCA, CD68 (monocytes/macrophages), and CD4 cells were dominant in number; MMP-8, MMP-9, and elastase were expressed only in the perichondral granulation; whereas MMP-3 and cathepsin K and L were detected in both chondrocytes and granulations. Out of 9 cases examined, 6 revealed apoptotic cells in excess of 50% of chondrocytes. There was a strong correlation between the number of apoptotic cells and the number of MMP-3-positive (r = 0.83) and cathepsin K-positive cells (r = 0.92). Abundant NO-expressing cells were observed in the chondrocytes in degenerated cartilage, similar to apoptosis.']
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['Tumor cells can metastasize by entering existing vessels or new vessels actively recruited into the primary tumor. Invasion of the lymphatics and blood vessels in the periphery of the tumor seems to be a prerequisite step in the metastatic process. The aim of this study was to correlate peripheral lymphatic vessel infiltration (PLI) and peripheral blood vessel infiltration (PVI) in a cohort of patients with invasive ductal carcinoma of the breast with various other prognostic parameters and outcome.', 'The study population consisted of 236 female patients with invasive ductal breast carcinomas, who had been operated between 2011 and 2013. The registered data included age at diagnosis, histological subtype, tumor size, TNM stage, histological grade, estrogen (ER) and progesterone receptors (PR), HER-2, p53, and PLI and PVI.', 'Pathological examination revealed that 22.5% of the patients had PVI and 37.3% had PLI at the tumor front. PVI correlated with younger age (p<0.05), higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05), higher N stage (p<0.05) and positive Ki67 expression (p<0.05). Similarly, PLI correlated with higher histologic grade (p<0.05), advanced TNM stage (p<0.05), higher T stage (p<0.05) and higher N stage (p<0.05). Statistical analysis did not reveal significant correlation between the presence of tumor blood and lymphatic vessels with infiltration in overall (OS) and disease-free survival (DFS).']
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['To determine the antiplatelet effect of cilostazol (Pletal) and its interaction with dipyridamole in in vitro and in vivo rabbit models, and to see if it can be dissociated from bleeding time prolongation.', 'In vitro collagen-induced platelet aggregation was measured by an impedance-based aggregometer. The in vivo antithrombotic effect was evaluated in a rabbit carotid artery cyclic flow reduction (CFR) model, in which repetitive thrombosis was induced by mechanical injuries of the artery and stenosis. Template bleeding time was determined in rabbit ear arterioles and hindlimb nail cuticles.', 'In vitro platelet aggregation was slightly inhibited by 4 microM cilostazol (22 +/- 6%), and modestly by 13 microM (57 +/- 3% of aggregation). While dipyridamole itself up to 13 microM had no significant inhibition, it potentiated the effect from cilostazol: in the presence of 4 microM dipyridamole, 4 microM cilostazol inhibited aggregation by 47 +/- 6%. Dipyridamole also potentiated the CFR reducing effect of cilostazol: combination of dipyridamole (no effect by itself) and cilostazol at 1 microM decreased CFRs to levels achieved by 3-4 microM cilostazol alone. Bleeding times were similar in controls and animals treated with cilostazol, or with cilostazol and dipyridamole. In contrast, aspirin (4 mg/kg), while reducing CFRs, significantly increased bleeding time.']
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['Ventilator-associated pneumonia (VAP) is one of the leading causes of morbidity in critically ill surgical patients. Certain pathogens (e.g., methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa) have been associated with an excess mortality rate from sepsis in several studies, but not in the surgical setting specifically or when protocol-driven antibiotic therapy is administered.', 'We sought to determine which factors and, in particular, whether the individual pathogen affected the mortality rate in our surgical intensive care unit (ICU), where a rotational antibiotic system has been employed continuously since 1997. We hypothesized that the type of pathogen and illness severity were the primary influences on the mortality rate of patients with VAP.', 'A total of 198 consecutive patients from a university surgical ICU, with clinical signs of VAP confirmed by quantified isolation of significant numbers of a pathogen (> or =10(4) colony-forming units [cfu]/mL) from bronchoalveolar (BAL) fluid obtained by fiberoptic bronchoscopy, were identified prospectively from January 2001 to November 2004. The data collected were age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) III score, multiple organ dysfunction score, unit day of diagnosis, time (h) to antibiotic administration (TTA), appropriateness of initial therapy (AIT), unit and hospital length of stay, and mortality rate. Pathogens were classified as non-lactose-fermenting gram-negative bacilli (NGNB), lactose-fermenting gram-negative bacilli (LGNB), methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, yeast, community-acquired pneumonia (e.g., Streptococcus pneumoniae), or other pathogens. Patients with a polymicrobial isolate were placed in the "other" category.', 'The overall mortality rate was 32.3% vs. 55% as predicted by APACHE III normative data. The overall AIT was 92%. The mortality rate for NGNB infections was 35.6% vs. 29.4% for LGNB infections (p = NS). By logistic regression, neither TTA, AIT, nor pathogen influenced the mortality rate.']
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['To test the hypothesis that children enrolled in Medicaid managed care health plans that provide asthma-specific communication to providers would be more likely to have adequate asthma medication filling.', 'We conducted a historical cohort study of 4498 children (2-17 years old) with moderate-severe asthma in Washington State and Tennessee Medicaid managed care programs from 2000 to 2002. Interviews with health plans were conducted to identify communication strategies health plans used to improve asthma care by providers in the plan. The main outcome measure was guideline-recommended filling of asthma preventer medications.', 'Children in plans that provided specific feedback to providers about asthma quality and notified providers when children had an asthma-related event had the highest mean days plus or minus SE of filling in the 365-day follow-up period (164.6 +/- 13 days) compared with children in plans with neither (135.3 +/- 10.8 days; P < .05). In children with the greatest asthma severity, enrollment in a plan with both features was associated with 27.1 additional days of filling (95% CI, 0.7-53.4 days) during the follow-up period.']
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['To evaluate the accuracy and precision of "deep-forehead" temperature with rectal, esophageal, and tympanic membrane temperatures, compared with blood temperature.', 'We studied 41 ASA physical status 1 or 2 patients undergoing abdominal and thoracic surgery scheduled to require at least three hours. "Deep-forehead" temperature was measured using a Coretemp thermometer (Terumo, Tokyo, Japan). Blood temperature was measured with a thermistor of a pulmonary artery. Rectal, tympanic membrane, and distal esophageal temperatures were measured with thermocouples. All temperatures were recorded at 20 min intervals after the induction of anesthesia. We considered blood temperature as the reference value. Temperatures at the other four sites were compared with blood temperature using correlation, regression, and Bland and Altman analyses. We determined accuracy (mean difference between reference and test temperatures) and precision (standard deviation of the difference) of 0.5 degrees C to be clinically acceptable.', '"Deep-forehead" temperature correlated well with blood temperature as well as other temperatures, the determination coefficients (r2) being 0.85 in each case. The bias for the "deep-forehead" temperature was 0.0 degrees C, which was the same as tympanic membrane temperature and was smaller than rectal and esophageal temperatures. The standard deviation of the differences for the "deep-forehead" temperature was 0.3 degrees C, which was the same as rectal temperature.']
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['To analyze the difficulty of discriminating Japanese nonsense monosyllables in each of several grades of high-frequency hearing loss and to evaluate the limitations of amplification.', 'We collected retrospective data on the discrimination of Japanese nonsense monosyllables by patients with three grades of high-frequency hearing loss who fulfilled or nearly fulfilled the Japanese criteria for EAS. Discrimination of the twenty monosyllables included in the 67-S speech audiometric test, which is approved by the Japan Audiological Society, was evaluated under quiet conditions.', 'One hundred and five ears of ninety-one adults with high-frequency hearing loss were tested. We classified the ears according to hearing threshold at 1000 Hz; Group 1: <45 dB; Group 2: ≥45 dB and <70 dB; Group 3: ≥70 dB. Under the best conditions, the best speech discrimination scores were 72.3 ± 18.6% (mean ± SD, N=11), 56.9 ± 19.9% (N=57) and 38.1 ± 22.6% (N=37) in Group 1, Group 2 and Group 3, respectively. For most of the monosyllables, discrimination score declined gradually as high-frequency hearing loss became more severe. The high incidence in the Japanese language of [k], an easy consonant to distinguish, may be an advantage for patients with high-frequency hearing loss who use hearing aids. By employing a new confusion matrix that displays consonants and the following vowels separately, we were able to reveal the interactions of those two components. We observed that discrimination of preceding nasal consonants and that of the following vowels were not independent in patients with high-frequency hearing loss.']
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['Remission is the ultimate goal in systemic lupus erythematosus (SLE). In this study, we applied four definitions of remission agreed on by an international collaboration (Definitions of Remission in SLE, DORIS) to a large clinical cohort to estimate rates and predictors of remission.', 'We applied the DORIS definitions of Clinical Remission, Complete Remission (requiring negative serologies), Clinical Remission on treatment (ROT) and Complete ROT. 2307 patients entered the cohort from 1987 to 2014 and were seen at least quarterly. Patients not in remission at cohort entry were followed prospectively. We used the Kaplan-Meier approach to estimate the time to remission and the time from remission to relapse. Cox regression was used to identify baseline factors associated with time to remission, adjusting for baseline disease activity and baseline treatment.', 'The median time to remission was 8.7, 11.0, 1.8 and 3.1\u2005years for Clinical Remission, Complete Remission, Clinical ROT and Complete ROT, respectively. High baseline treatment was the major predictor of a longer time to remission, followed by high baseline activity. The median duration of remission for all definitions was 3\u2005months. African-American ethnicity, baseline low C3 and baseline haematological activity were associated with longer time to remission for all definitions. Baseline anti-dsDNA and baseline low C4 were associated with longer time to Complete Remission and Complete ROT. Baseline low C4 was also negatively associated with Clinical Remission.']
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['Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2.', 'Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages.']
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['The aim of the present study was to examine the effects of onion as functional ingredient on the oxidative status, lipoprotein levels (total cholesterol-TC, HDL-C, LDL-C), triacylglycerides (TAG) and vascular reactivity of mesenteric arteries in hypercholesterolemic Wistar rats.', "Twenty-four animals were fed with three different diets [control, high-cholesterol diet (HC) and high-cholesterol enriched with onion diet (HCO)]. After seven weeks of experimental feeding the rats were euthanized for blood and tissues collection. TC, HDL-C, LDL-C and TAG were measured, and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging capacity and ferric reducing antioxidant power (FRAP) were determined in plasma. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assayed in erythrocyte lysates. Endothelium-dependent vasodilation to acetylcholine was evaluated in mesenteric arterial segments. NADPH oxidase (NOX) was also measured by lucigenin-derived chemiluminiscence.", 'The dietary cholesterol content significantly affected plasma lipoprotein levels, increased superoxide generation from NOX, and caused impaired endothelium-dependent vasodilation in the rat mesenteric arteries. Onion ingredient improved antioxidant status in HCO group, as it was evidenced by ABTS(•+) and FRAP values and SOD and GPx enzyme activities compared to the HC-fed group, reduced the increment in NOX activity and reversed endothelial dysfunction promoted by the HC diet. Scavenging of superoxide with TEMPOL or inhibition of NOX with apocynin improved endothelium-dependent vasodilation only in HC-fed rats.']
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['Anatomic sublobar resection is being assessed as a substitute to lobectomy for primary lung cancers. However, persistent air leak after anatomic sublobar resection is prevalent and increasing surgical morbidity and costs. The use of electrocautery is being popularized recently in anatomic sublobar resection. We have retrospectively evaluated the safety and efficacy of intersegmental plane dissection using electrocautery.', 'Between April 2009 to September 2010, 47 patients were treated with segmentectomy for clinical T1N0M0 non-small cell lung cancers. The intersegmental plane was dissected using electrocautery alone or in combination with staplers. We evaluated the methods of dividing intersegmental plane (electrocautery alone or combination with electrocautery and staplers), intraoperative blood loss, duration of chest tube placement, duration of surgery, preoperative FEV1.0%, incidence of prolonged air leak, length of postoperative hospital stay, postoperative pulmonary function at 6 months after surgery and the cost for sealing intersegmental plane.', 'Among the 47 patients, 22 patients underwent intersegmental plane dissection with electrocautery alone and 25 patients did in combination with electrocautery and staplers. The mean number of stapler cartridges used was only 1.3 in electrocautery and staplers group. Mean age, gender, number of patients whose FEV1%\u2009< 70% were similar between two groups. There was no statistical difference between electrocautery alone and combination with electrocautery and staplers group in duration of surgery (282 vs. 290 minutes), intraoperative blood loss (203 vs.151 ml), duration of chest tube placement (3.2 vs. 3.1 days), postoperative hospital stay (11.0 vs.10.0 days), postoperative loss of FEV1.0 (13 vs.8 %), loss of FVC (11 vs. 6 %) or incidence of minor postoperative complications [9 % (2/22) vs. 16 % (4/25), p = 0.30)]. However, incidence of prolonged air leak was higher in electrocautery alone group than in combination with electrocautery and staplers group [14 % (3/22) vs. 4 % (1/25), p = 0.025)]. The cost of materials for sealing air leaks amounted to €964 per patient in the electrocautery alone group and €1594 per patient in combination with electrocautery and staplers group.']
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['Allergy is commoner in developed than in developing countries. Chronic worm infections show inverse associations with allergy, and prenatal exposures may be critical to allergy risk.', 'To determine whether anthelminthic treatment during pregnancy increases the risk of allergy in infancy.', "A randomised, double-blind, placebo-controlled trial on treatment in pregnancy with albendazole versus placebo and praziquantel versus placebo was conducted in Uganda, with a 2 × 2 factorial design; 2507 women were enrolled; infants' allergy events were recorded prospectively. The main outcome was doctor-diagnosed infantile eczema.", 'Worms were detected in 68% of women before treatment. Doctor-diagnosed infantile eczema incidence was 10.4/100 infant years. Maternal albendazole treatment was associated with a significantly increased risk of eczema [Cox HR (95% CI), p: 1.82 (1.26-2.64), 0.002]; this effect was slightly stronger among infants whose mothers had no albendazole-susceptible worms than among infants whose mothers had such worms, although this difference was not statistically significant. Praziquantel showed no effect overall but was associated with increased risk among infants of mothers with Schistosoma mansoni [2.65 (1.16-6.08), interaction p = 0.02]. In a sample of infants, skin prick test reactivity and allergen-specific IgE were both associated with doctor-diagnosed eczema, indicating atopic aetiology. Albendazole was also strongly associated with reported recurrent wheeze [1.58 (1.13-2.22), 0.008]; praziquantel showed no effect.']
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['The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has become a potential target for the prevention and treatment of breast cancer. However, recent in vitro and in vivo studies have raised the question of whether activation of PPARgamma leads to the promotion or reduction of tumor formation. Studies using several cancer cell lines, animal models, and a variety of PPARgamma agonists have shown discordant results, including changes in cellular proliferation, differentiation, and apoptosis of cancer cells and tumors.', 'We studied the effects of low-, moderate-, and high-dose treatment of the PPARgamma ligands 15-deoxy-delta1214 prostaglandin J2 (15dPGJ2) and troglitazone (TGZ) on parameters of cell growth, differentiation, and apoptosis in the epithelial breast cancer cell line MDA-MB-231.', 'The biologic effects of these compounds depend largely on ligand concentration and the degree of PPARgamma activation. For example, low concentrations of 15dPGJ2 (<2.5 microM) and TGZ (<5 microM) increased cellular proliferation, but concentrations of 15dPGJ2 > or = 10 microM and of TGZ at 100 microM blocked cell growth. TGZ (100 microM) slowed cell cycle progression, and 15dPGJ2 (10 microM) caused an S-phase arrest in the cell cycle and induced morphological characteristics consistent with apoptosis. Expression of CD36, a marker of differentiation in these cells, was induced by 2.5 microM 15dPGJ2 or 5 to 100 microM TGZ. However, higher concentrations of 15dPGJ2 did not alter CD36 expression. Transcriptional activation studies demonstrated that 15dPGJ2 is a more potent PPARgamma ligand than TGZ. Regardless of the ligand used, though, low transcriptional activation correlated with an increased cellular proliferation, whereas higher levels of activation correlated with cell cycle arrest and apoptosis.']
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