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['To investigate the effect of experimental tumor bearing on acute inflammation models in rats.', 'Four and 7 days after Walker tumor implantation in the right armpit, carrageenan or dextran- induced edema in the contralateral paw, carrageenan induced neutrophil migration into peritoneal cavities, cutaneous vascular permeability induced by bradykinin, histamine, serotonin, substance P, capsaicin or compound 48/80, and mesenteric mast cell degranulation induced by compound 48/80 were evaluated. The control group did not receive tumor implantation. Statistical analysis was performed using one way analysis of variance (ANOVA) followed by the Bonferroni test.', 'On the 7(th) day after tumor inoculation, there were significant decreases in both carrageenan and dextran- induced paw edema. Tumor bearing did not change the neutrophil infiltration induced by carrageenan. There were decreases in cutaneous vascular permeability induced by compound 48/80, serotonin or bradykinin, but not that induced by histamine, substance P. A significant inhibition of mesenteric mast cell degranulation induced by compound 48/80 was observed, on the 4(th) and 7(th) days after tumor inoculation.'] |
['IL-1beta is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production.', 'ACZ885, a fully human monoclonal antibody that neutralizes the bioactivity of human IL-1beta, was generated to study the potent and long-lasting neutralization of IL-1beta in mechanistic animal models as well as in a proof-of-concept study in patients with rheumatoid arthritis (RA).', 'The mouse IL-1 receptor cross-reacts with human IL-1beta, and it was demonstrated that ACZ885 can completely suppress IL-1beta-mediated joint inflammation and cartilage destruction in mice. This observation prompted us to study the safety, tolerability and pharmacodynamic activity of ACZ885 in RA patients in a small proof-of-concept study--the first to be conducted in humans. Patients with active RA despite treatment with stable doses of methotrexate were enrolled in this dose escalation study. The first 32 patients were split into four cohorts of eight patients each (six were randomly assigned to active treatment and two to placebo). ACZ885 doses were 0.3, 1, 3 and 10 mg/kg, administered intravenously on days 1 and 15. To explore efficacy within 6 weeks of treatment, an additional 21 patients were randomly assigned to the 10 mg/kg cohort, resulting in a total of 20 patients dosed with 10 mg/kg and 15 patients treated with placebo. There was clinical improvement (American College of Rheumatology 20% improvement criteria) at week 6 in the 10 mg/kg treatment group; however, this did not reach statistical significance (P = 0.085). A statistically significant reduction in disease activity score was observed after 4 weeks in the 10 mg/kg group. Onset of action was rapid, because most responders exhibited improvement in their symptoms within the first 3 weeks. C-reactive protein levels decreased in patients treated with ACZ885 within 1 week. ACZ885 was well tolerated. Three patients receiving ACZ885 developed infectious episodes that required treatment. No anti-ACZ885 antibodies were detected during the study.'] |
['Historically, alpha-fetoprotein (AFP) levels in insulin-dependent diabetes (IDDM) have shown an approximately 20% decrement, and a correction factor is used to standardize multiples of the median (MOMs). With new laboratory methods and improved precision, we sought to re-evaluate the correctness of this approach.', 'Consecutive biochemical screens were conducted among 60,287 nondiabetic patients and 307 patients with IDDM. Analyses were conducted in one laboratory, and comparisons were made with use of standard formula weight adjustments including a 20% correction factor for IDDM. Patients were then stratified according to maternal weight.', 'Nondiabetic patients averaged 1.00 MOM, IDDM patients 0.91 MOM with no adjustments, 0.96 MOM adjusting for weight only, and 1.20 MOM adjusting for weight and diabetes status. To explain the "overcorrection," analysis by maternal weight showed significant overrepresentation of IDDM patients at 175 pounds or above. In fact, the mean weight in pounds for nondiabetic subjects was 151 +/- 35 and for those with IDDM 174 +/- 52 (P <.001). With use of an upper limit weight cutoff of 200 pounds, results are within 4% of normal.'] |
['To sustain cell growth, cancer cells exhibit an altered metabolism characterized by increased lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the production of monounsaturated fatty acids that are essential for membrane biogenesis, and is required for cell proliferation in many cancer cell types. Although estrogen is required for the proliferation of many estrogen-sensitive breast carcinoma cells, it is also a repressor of SCD-1 expression in liver and adipose. The current study addresses this apparent paradox by investigating the impact of estrogen on SCD-1 expression in estrogen receptor-α-positive breast carcinoma cell lines.', 'MCF-7 and T47D mammary carcinomas cells and immortalized MCF-10A mammary epithelial cells were hormone-starved then treated or not with 17β-estradiol. SCD-1 activity was assessed by measuring cellular monounsaturated/saturated fatty acid (MUFA/SFA) ratios, and SCD-1 expression was measured by qPCR, immunoblot, and immunofluorescence analyses. The role of SCD-1 in cell proliferation was measured following treatment with the SCD-1 inhibitor A959372 and following SCD-1 silencing using siRNA. The involvement of IGF-1R on SCD-1 expression was measured using the IGF-1R antagonist AG1024. The expression of SREBP-1c, a transcription factor that regulates SCD-1, was measured by qPCR, and by immunoblot analyses.', '17β-estradiol significantly induced cell proliferation and SCD-1 activity in MCF-7 and T47D cells but not MCF-10A cells. Accordingly, 17β-estradiol significantly increased SCD-1 mRNA and protein expression in MCF-7 and T47D cells compared to untreated cells. Treatment of MCF-7 cells with 4-OH tamoxifen or siRNA silencing of estrogen receptor-α largely prevented 17β-estradiol-induced SCD-1 expression. 17β-estradiol increased SREBP-1c expression and induced the mature active 60 kDa form of SREBP-1. The selective SCD-1 inhibitor or siRNA silencing of SCD-1 blocked the 17β-estradiol-induced cell proliferation and increase in cellular MUFA/SFA ratios. IGF-1 also induced SCD-1 expression, but to a lesser extent than 17β-estradiol. The IGF-1R antagonist partially blocked 17β-estradiol-induced cell proliferation and SCD-1 expression, suggesting the impact of 17β-estradiol on SCD-1 expression is partially mediated though IGF-1R signaling.'] |
['Postoperative blood loss after prostate surgery is thought to be associated with an increase in urinary fibrinolytic activity. Tranexamic acid (TXA) is both a potent inhibitor of plasminogen and urokinase activators and a low molecular weight substance that is excreted unchanged in the urinary tract and can be administered both orally and intravenously. We investigated the effect of TXA on the amount of blood loss during transurethral resection of the prostate (TURP).', 'Forty patients with registry numbers ending in even numbers were allocated to the treatment group; those ending in odd numbers were used as controls and received no treatment. The treatment group received 10 mg/kg TXA by intravenous infusion during the first half hour of the operation, while the control group of patients received no medication. Serum hemoglobin was measured before and after surgery. The volume and hemoglobin concentration of the irrigation fluid, resected prostate weight, and duration of resection were recorded.', 'The mean loss of hemoglobin per gram of resected prostate tissue was 1.25 g in the TXA group and 2.84 g in the control group. Total hemoglobin loss in the irrigating fluid and hemoglobin loss per 1 gram of prostate tissue was lower in the group of patients given TXA than in the control group (p = 0.018 and p <0.001).'] |
['The analgesic effect of oral sucrose in newborn infants undergoing painful procedures is generally accepted. For blood sampling, some studies have shown that venepuncture (VP) is less painful than heel lance (HL).', 'To determine the least painful and most effective method among blood sampling by VP or HL with or without sucrose.', 'Randomised, double blind, placebo controlled trial.', 'A total of 100 healthy, full term newborn infants being screened for inborn errors of metabolism were randomly allocated to one of four experimental groups (25 infants in each). Intervention and', 'Seven specially trained nurses took turns to carry out blood sampling two minutes after administration of oral sucrose or water. Neonatal pain was assessed by the neonatal facial coding system (NFCS), as well as by crying.', 'Without sucrose, the NFCS score was higher in the HL group than the VP group during blood sampling (median 58 v 23, p<0.001). Oral sucrose significantly reduced the score of the HL group (58 v 47, p<0.01) and also tended to reduce the score of the VP group (23 v 2, p<0.1). However, the HL with sucrose group still had a higher score than the VP without sucrose group (47 v 23, p<0.01). Crying and the total procedure time showed the same trends as the NFCS score.'] |
['To compare 4-year changes in cognitive performance among elderly subjects according to category of fasting blood glucose (FBG) using American Diabetes Association criteria.', "Subjects without any detectable cognitive dysfunction were selected from the Epidemiology of Vascular Aging (EVA) Study, a cohort of community-dlwelling people aged 59-71 years at baseline. They were classified into glucose categories (normal, impaired fasting glucose [IFG], or diabetic) based on FBG values or known diabetes. Their cognitive abilities were assessed by a global test (Mini Mental Status Examination [MMSE]) and eight domain-specific tests, and they were reassessed 4 years later. Serious cognitive worsening was defined as a score evolution into the worst 15% of the sample's distribution of score differences (4-year score minus baseline score) for each test.", 'At baseline, age-, sex-, and education-adjusted scores for all cognitive tests except one were similar across glucose categories. After 4 years, diabetic subjects had a lower performance on all tests except the MMSE, with differences reaching statistical significance on four tests. Adjusted odds ratios for serious worsening over 4 years in diabetic subjects, with reference to normal subjects, were >2 for four tests (P < 0.05) and bordering this value for two others (P < 0.09). Further adjustment for blood pressure or potential cognition-affecting substances (alcohol, tobacco, and medications) did not modify these results.'] |
['Quantifying chromosomal instability (CIN) has both prognostic and predictive clinical utility in breast cancer. In order to establish a robust and clinically applicable gene expression-based measure of CIN, we assessed the ability of four qPCR quantified genes selected from the 70-gene Chromosomal Instability (CIN70) expression signature to stratify outcome in patients with grade 2 breast cancer.', 'AURKA, FOXM1, TOP2A and TPX2 (CIN4), were selected from the CIN70 signature due to their high level of correlation with histological grade and mean CIN70 signature expression in silico. We assessed the ability of CIN4 to stratify outcome in an independent cohort of patients diagnosed between 1999 and 2002. 185 formalin-fixed, paraffin-embedded (FFPE) samples were included in the qPCR measurement of CIN4 expression. In parallel, ploidy status of tumors was assessed by flow cytometry. We investigated whether the categorical CIN4 score derived from the CIN4 signature was correlated with recurrence-free survival (RFS) and ploidy status in this cohort.', 'We observed a significant association of tumor proliferation, defined by Ki67 and mitotic index (MI), with both CIN4 expression and aneuploidy. The CIN4 score stratified grade 2 carcinomas into good and poor prognostic cohorts (mean RFS: 83.8±4.9 and 69.4±8.2 months, respectively, p\u200a=\u200a0.016) and its predictive power was confirmed by multivariate analysis outperforming MI and Ki67 expression.'] |
['The objective of the study was to study the etiology of and factors determining the emergency department disposition of infants sustaining burn injuries.', 'A retrospective chart review was performed on all patients 12 months or younger with a burn injury presenting to our emergency department over a 5-year period. We collected the chief complaint and diagnosis, patient demographics, and circumstances surrounding the burn injury from the emergency department charts. Univariable statistics, multiple imputation, and multivariable regression were performed to determine differences between races and factors leading to admission.', 'During the study period, 344 patients meeting inclusion criteria were treated in our emergency department. Scalds (53.2%) and contact burns (39.8%) were the most common causes of burns among the study group. Significant differences were observed between races for mechanism of burn, interhospital transport, and total body surface area affected (P < 0.05). White patients were more likely to have higher body surface affected and to be transferred from another facility (P < 0.05). Increased severity of burn, burns located on the hand, and concern for abuse resulted in higher likelihood of admission (P < 0.01). No significant differences in disposition or mechanism of burn were present between English-speaking and non-English-speaking patients.'] |
['Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state.', 'To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state.', 'We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA.', 'The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%.'] |
['We investigated to what degree environmental exposure (childhood trauma, urbanicity, cannabis use, and discrimination) impacts symptom connectivity using both continuous and categorical measures of psychopathology.', 'Outcomes were continuous symptom dimensions of self-reported psychopathology using the Self-report Symptom Checklist-90-R in 3021 participants from The Early Developmental Stages of the Psychopathology (EDSP) study and binary DSM-III-R categories of mental disorders and a binary measure of psychotic symptoms in 7076 participants from The Netherlands Mental Health Survey and Incidence Study (NEMESIS-1). For each symptom dimension in the EDSP and mental disorder in the NEMESIS-1 as the dependent variable, regression analyses were carried out including each of the remaining symptom dimensions/mental disorders and its interaction with cumulative environmental risk load (the sum score of environmental exposures) as independent variables.', 'All symptom dimensions in the EDSP and related diagnostic categories in the NEMESIS-1 were strongly associated with each other, and environmental exposures increased the degree of symptom connectivity in the networks in both cohorts.'] |
['Vaccination of chimpanzees against hepatitis C virus (HCV) using T-cell-based vaccines targeting nonstructural proteins has not resulted in the same levels of control and clearance as those seen in animals reexposed after HCV clearance. We hypothesized that the outcome of infection depends on the different subtypes of activated T cells. We used multicolor flow cytometry to evaluate activation (CD38+/HLA-DR+) and proliferation (Ki67+/Bcl-2-low) profiles of CD4+ and CD8+ T cells in peripheral blood before and after challenge in chimpanzees vaccinated using DNA/adenovirus, mock-vaccinated, and chimpanzees that had spontaneously cleared infection (rechallenged). The frequencies of activated or proliferating CD8+ T cells peaked at 2 weeks postchallenge in the vaccinated and rechallenged animals, coinciding with reductions in viral titers. However, the magnitude of the responses did not correlate with outcome or sustained control of viral replication. In contrast, proliferation of the CD8+ T cells coexpressing HLA-DR either with or without CD38 expression was significantly higher at challenge in animals that rapidly cleared HCV and remained so throughout the follow-up period.'] |
['Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients.', 'Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed.', 'Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study.', 'The study comprised a retrospective, questionnaire-based review.', 'One hundred seventy-eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P = .037) or had high serum folate concentration (P = .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypocobalaminemia (< 100 ng/L) was associated with shorter survival (P = .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis ( < or = 4 years or > 4 years), and clinical signs at diagnosis also made no difference.'] |
['The aim of the present study was to investigate the relationship between atherosclerotic progression rate as measured by carotid artery IMT during very long-term follow-up in clinically healthy men and a number of baseline risk factors of potential importance for atherosclerosis progression including apoA-I, apoB, apoB/apoA-I ratio, other lipid variables including LDL particle size, body composition variables, blood pressure, smoking, fasting blood glucose and insulin, and also hsCRP.', 'Low-density lipoprotein (LDL) is associated with increased carotid IMT progression rate during long-term follow-up, whereas the relationship between newer biomarkers such as apoB/apoA-I ratio and carotid artery IMT progression rate has been less investigated.', '58-year-old men identified by screening in the community (n=391) with varying degrees of obesity and insulin sensitivity were examined with high-resolution B-mode ultrasound at baseline and after 3, and 8.9 years of follow-up (n=305 investigated after 8.9 years). The carotid arteries were examined bilaterally, and the mean intima-thickness was calculated for 10mm sections of the composite of common carotid arteries and bulbs (IMT(composite)). Serum levels of apoB and apoA-I were measured using a turbidimetric method. Uni- and multi-variable analyses were performed to study the relationship between carotid IMT(composite) progression rate and risk factors.', 'In a multi-variable analysis including all baseline variables only the apoB/apoA-I ratio (p=0.003; beta=0.181, standard error=0.003) and serum insulin (p=0.026; beta=-0.133, standard error=0.000) was significantly related to IMT(composite) progression rate.'] |
['Melatonin may attenuate organ damage via direct antioxidative properties, and was recently demonstrated to reduce cardiac and hepatic injury through receptor-dependent effects. However, the relevance of an isolated activation of melatonin receptors for organ protection, excluding direct antioxidant effects, has not been established yet. This study was designed to investigate whether therapy with melatonin receptor agonist and hypnotic substance ramelteon may improve liver function, hepatic perfusion, and hepatic integrity after hemorrhagic shock in rat.', 'Prospective, randomized, controlled study.', 'University research laboratory.', 'Male Sprague-Dawley rats (n = 10 per group).', "Animals underwent hemorrhagic shock (mean arterial pressure 35 +/- 5 mm Hg for 90 mins) and were resuscitated with shed blood and Ringer's lactate (2 hrs). At the end of shock, animals were treated with ramelteon (1.0 mg/kg intravenously), melatonin receptor antagonist luzindole plus ramelteon (each 1.0 mg/kg intravenously), or vehicle.", "In vitro, ramelteon displayed no relevant antioxidant capacity in an 2,2'-Azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assay, compared with melatonin. In vivo, liver function was assessed by plasma disappearance rate of indocyanine green, and intravital microscopy was performed for evaluation of hepatic perfusion index, nicotinamide adenine dinucleotide phosphate autofluorescence, and hepatic integrity. Compared with vehicle controls, ramelteon therapy significantly improved plasma disappearance rate of indocyanine green (7.89 +/- 2.12% vs. 13.67 +/- 2.51%; p = 0.006), hepatic perfusion index (352.04 +/- 111.78 pl/sec/mm vs. 848.81 +/- 181.38 pl/sec/mm; p = 0.002), nicotinamide adenine dinucleotide phosphate autofluorescence and hepatocellular injury. Coadministration of luzindole abolished the protective effect of ramelteon with respect to liver function and nicotinamide adenine dinucleotide phosphate autofluorescence."] |
['To compare qualitative and quantitative measures of the contrast-enhanced dual-echo Dixon technique with the commonly used standard three-dimensional (3D) gradient echo (spectrally selective fat suppression) technique (SS-FS) in breast MRI exams (bMRI).', 'A total of 19 women, with prescheduled bMRI exam, were recruited to our study between 2006 and 2008. Dixon and standard SS-SF techniques were used on both breasts of each patient. Image quality was rated in five categories: fat suppression quality, fat suppression uniformity, lesion margin clarity, lesion visibility, and axillary visibility. For quantitative assessment, we calculated the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of lesion to breast, SNR efficiency, and CNR efficiency.', 'Of 19 patients evaluated, 13 had a primary breast malignancy and 6 had benign lesions or negative exams. Dixon images were rated higher in four of five qualitative categories (P < 0.0001) and required a shorter scan time. Dixon images yielded significantly higher SNR (43.8) and CNR (40.1) values than did 3DGRE images (SNR = 34.8, CNR = 25.3; P < 0.05). SNR efficiency (36.30) and CNR efficiency (33.79) values for Dixon images were also higher than were 3DGRE images (SNR efficiency =25.7, CNR efficiency = 19.1; P < 0.05).'] |
['To assess the feasibility of seeding adipose-derived stem cells (ADSCs) onto bladder acellular matrix grafts (BAMGs) for bladder reconstruction in a rabbit model.', 'Autologous ADSCs were isolated, expanded and identified by flow cytometry. In the experimental group, ADSCs were seeded onto BAMGS for reconstructing bladder defects in 12 male rabbits. Unseeded BAMGs were used for bladder reconstruction in the control group of 12 rabbits. Cystography was performed at 4, 12 and 24 weeks after grafts implantation. Following cystography, the animals were killed and grafts were harvested; H&E and immunohistochemical staining were performed with cytokeratin AE1/AE3, smooth muscle alpha-actin and S-100 markers.', 'Flow cytometry demonstrated that the ADSCs expressed CD90, CD44, CD105, CD166 and CD34, but not CD45 or CD106. The cells demonstrated good biocompatibility with BAMGs. At 24 weeks, in the experimental group, the reconstructed bladders reached a mean volume of 94.68 +/- 3.31% of the pre-cystectomy bladder capacity. Complete regeneration of smooth muscle and nerve tissue was evident. Regenerated SMCs, urothelium and nerve cells stained positively for alpha-smooth muscle actin, AE1/AE3 and S-100. In the control group, the mean bladder volume was 69.33 +/- 5.05% of the pre-cystectomy volume; histologically, the control group was characterized by multi-layered urothelium without evidence for organized muscle or nerve tissue.'] |
['To clarify the role of Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs).', "PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2, STAT1, STAT3, and ERK was determined by Western blotting using anti-phospho-specific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine.", 'PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGF-induced activation of STAT1 and STAT3 was inhibited by a Src inhibitor PP1 and a JAK2 inhibitor AG490, whereas PDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense oligonucleotide.'] |
['To investigate the bioequivalence of esomeprazole MUPS 40 mg tablets administered with and without a hard gelatine capsule.', 'Bioequivalence of the esomeprazole MUPS 40 mg tablet administered without (Reference) and with a hard gelatine capsule (Test) was evaluated using a randomized, two-period crossover study. In each study period 49 healthy male Caucasian subjects received a single oral dose of 40 mg esomeprazole. Blood samples were collected at specified time intervals, and serum was separated and analyzed for esomeprazole concentrations using a validated HPLC-MS method. The primary parameters were AUC (extent of absorption) and Cmax (rate of absorption). The time-to-peak plasma concentration, tmax, and the elimination half-life, t1/2, were determined as secondary characteristics. Point estimates and 90%-confidence intervals were obtained for the ratio of the population medians of Test and Reference, using a multiplicative model and a parametric analysis except in the case of tmax, where an additive model and a non-parametric analysis was used. Bioequivalence of Test and Reference was concluded if the 90%-confidence intervals were entirely within the predefined equivalence ranges.', 'The AUC(0-infinity) and Cmax-ratios (Test/Reference) were 1.00 and 1.01, respectively. The 90%-confidence intervals for AUC(0-infinity) (0.94-1.06) and Cmax (0.93-1.09) of these ratios were within the predefined equivalence range of 0.80-1.25 and 0.75-1.33, respectively. The ratios and 90%-confidence intervals of the secondary characteristics t1/2 and tmax were also within the respective predefined equivalence ranges. Both esomeprazole formulations were well tolerated and safe.'] |
['To explore the views of hospitalised school-aged children with complex healthcare needs related to spiritual care. This could help inform national policies and raise awareness of the impact that a stay in an acute paediatric hospital can have on the spiritual needs of some of the children who use the NHS.', 'Pictures used in previous (US) studies were used to facilitate story telling, enabling children to talk about concepts that may not have emerged through direct conversation. A convenience sample of five hospitalised children were presented with the pictures one at a time and asked open-ended questions about each picture. Data analysis involved identifying emerging themes from the transcriptions using a grounded theory approach.', "The main themes to emerge from the interview data were: the role of the child's relationships with family, friends and healthcare professionals; the impact of the hospital environment on the child; coping with invasive procedures; belief--children's views about their health and belief system."] |
['Serum response factor (SRF) is a transcription factor that binds to a CarG box motif within the serum response element of genes that are expressed in response to mitogens. SRF plays essential roles in muscle and nervous system development; however, little is known about the role of SRF during liver growth and function. To examine the function of SRF in the liver, we generated mice in which the Srf gene was specifically disrupted in hepatocytes. The survival of mice lacking hepatic SRF activity was lower than that of control mice; moreover, surviving mutant mice had lower blood glucose and triglyceride levels compared with control mice. In addition, Srf(loxP/loxP)AlfpCre mice were smaller and had severely depressed levels of serum insulin-like growth factor 1 (IGF-1). Srf-deficient livers were also smaller than control livers, and liver cell proliferation and viability were compromised. Gene array analysis of SRF depleted livers revealed a reduction in many messenger RNAs, including those encoding components of the growth hormone/IGF-1 pathway, cyclins, several metabolic regulators, and cytochrome p450 enzymes.'] |
["The sensory nerve neuropeptide substance P (SP) regulates cardiac fibrosis in rodents under pressure overload conditions. Interestingly, SP induces transient increased expression of specific genes in isolated rat cardiac fibroblasts, without resultant changes in cell function. This suggests that SP 'primes' fibroblasts, but does not directly activate them. We investigated whether these unusual findings are specific to rodent fibroblasts or are translatable to a larger animal model more closely related to humans.", 'We compared the effects of SP on genes associated with extracellular matrix (ECM) regulation, cell-cell adhesion, cell-matrix adhesion and ECM in cardiac fibroblasts isolated from a non-human primate and Sprague-Dawley rats.', 'We found that rodent and non-human primate cardiac fibroblasts showed similar responses in genes that relate to ECM regulation and cell adhesion in response to SP. There were large discrepancies in ECM component genes, however, this did not result in collagen or laminin synthesis in rat or non-human primate fibroblasts in response to SP.'] |
["Although most musculoskeletal illness is managed by primary care providers, and not by surgeons, evidence suggests that primary care physicians may receive inadequate training in musculoskeletal medicine. We evaluated the musculoskeletal knowledge and self-perceived confidence of fully trained, practicing academic primary care physicians and tested the following hypotheses: (1) a relationship exists between a provider's musculoskeletal knowledge and self-perceived confidence, (2) demographic variables are associated with differences in the knowledge-confidence relationship, and (3) specific education or training affects a provider's musculoskeletal knowledge and clinical confidence.", 'An examination of basic musculoskeletal knowledge and a 10-point Likert scale assessing self-perceived confidence were administered to family practice, internal medicine, and pediatric faculty at a large, regional, academic primary care institution serving both rural and urban populations across a five-state region. Subspecialty physicians were excluded. Individual examination scores and self-reported confidence scores were correlated and compared with demographic variables.', 'One hundred and five physicians participated. Ninety-two physicians adequately completed the musculo-skeletal knowledge examination. Fifty-nine (64%) of the ninety-two physicians scored < 70%. Higher examination scores were associated with male gender (p = 0.01) and participation in a musculoskeletal course (p = 0.009). Practitioners who took elective courses demonstrated higher scores compared with those who took required courses (p = 0.014). Greater musculoskeletal confidence was associated with the number of years in clinical practice (p = 0.045), male gender (p = 0.01), residency training in family practice (p < 0.00001), and prior participation in a musculoskeletal course (p = 0.0004). Physicians demonstrated greater confidence with medical issues than with musculoskeletal issues (mean confidence scores, 8.3 and 5.1, respectively; p < 0.00001). Higher scores for musculoskeletal knowledge correlated significantly with increasing levels of musculoskeletal confidence (r = 0.416, p < 0.0001).'] |
['Inhibition of cyclooxygenase-2 has been proposed to be a potential mechanism for the chemoprevention of gastrointestinal tumors by nonsteroidal anti-inflammatory drugs. This study investigates the mechanisms by which the cyclooxygenase-2 inhibitor SC236 induces apoptosis of gastric cancer cell lines and its downstream signaling pathway.', 'Two gastric cancer cell lines, AGS and MKN28, were treated with SC236 and assessed for cell growth and apoptosis. The involvement of mitogen-activated protein kinase and Akt kinase/protein kinase B (Akt/PKB) pathways and their downstream signalings were studied in the AGS cell line.', 'SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB. The specific p38 inhibitor SB203580 and the dominant-negative stress-activated protein kinase/jun kinase both failed, while the constitutively active form of Akt/PKB was able to block SC236-induced apoptosis. SC236-induced apoptosis was coupled with release of cytochrome c and activation of caspases.'] |
['Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are a frequent cause of X-linked retinitis pigmentosa. The RPGR transcript undergoes complex alternative splicing to express both constitutive (Rpgr(ex1-19)) and Rpgr(ORF15) variants. Because functional studies of Rpgr suggest a role in intracellular protein trafficking through the connecting cilia, the goal of this study was to identify potential binding partners for Rpgr(ORF15) and to identify the domains on whirlin necessary for Rpgr binding.', 'The C-terminus of mouse Rpgr(ORF15) was used as bait in a yeast two-hybrid system. Whirlin expression was analyzed using RT-PCR and Western blot analysis. Protein-protein interactions were confirmed using in vitro binding assays and coimmunoprecipitation. Subcellular colocalization was analyzed using immunohistochemistry on retinal cryosections.', 'Yeast two-hybrid analysis identified whirlin, a PDZ-scaffold protein, as a putative binding partner for Rpgr(ORF15). The RPGR(ORF15)-whirlin interaction was confirmed using in vitro binding assays and coimmunoprecipitation from retinal tissue, and both proteins were shown to colocalize in the photoreceptor connecting cilia in vivo. Results from RT-PCR, Western blot analysis, and immunocytochemistry demonstrated that whirlin expressed multiple isoforms in photoreceptors with variable subcellular localization.'] |
['The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC), and is correlated with poor prognosis, making it an attractive target for monoclonal antibody (mAb) therapy. A component of the therapeutic efficacy of IgG1 mAbs is their stimulation of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells bearing the CD16 receptor. As NK cells are functionally impaired in cancer patients and may be further compromised upon chemotherapy, it is crucial to assess whether immunotherapeutic strategies aimed at further enhancing ADCC are viable.', 'CRC patients before, during and after chemotherapy were immunophenotyped by flow cytometry for major white blood cell populations. ADCC-independent NK cell functionality was assessed in cytotoxicity assays against K562 cells. ADCC-dependent killing of EGFR(+) A431 cancer cells by NK cells was measured with a degranulation assay where ADCC was induced by GA201, an anti-EGFR mAb glyco-engineered to enhance ADCC.', 'Here, we confirm the observation that NK cells in cancer patients are dysfunctional. However, GA201 was able to induce robust NK cell-dependent cytotoxicity in CRC patient NK cells, effectively overcoming their impairment.'] |
['To determine whether interleukin-6 (IL-6) stimulates rat muscle satellite cell proliferation in culture, and if so, to clarify the signalling mechanisms.', 'Primary satellite cells were isolated from thirty male F344 rats, 11\xa0weeks of age. IL-6 at concentrations of 0.01, 0.1, 1, 10 or 100\xa0ng/ml was added to culture media.', 'IL-6 at 0.01-1\xa0ng/ml induced dose-dependent increase in cell proliferation. After treatment with 1\xa0ng/ml IL-6, cell proliferation increased by 31%, and p-STAT3(+) /MyoD(+) cells increased in number compared to those in control media (P\xa0<\xa00.05). Inhibitors of JAK2 (AG 490) and STAT3 (STAT3 peptide) blocked the increase in BrdUrd(+) cell numbers at 6\xa0h post stimulation with 1\xa0ng/ml IL-6 (P\xa0<\xa00.05). Furthermore, cyclin D1 mRNA expression and cyclin D1(+) /MyoD(+) cell numbers significantly increased in cultures treated with 1\xa0ng/ml IL-6 compared to those in control media (P\xa0<\xa00.05). In contrast, treatment with 10 and 100\xa0ng/ml IL-6 did not stimulate cell proliferation. Treatment with 10\xa0ng/ml IL-6 induced greater SOCS3 mRNA expression than with 1\xa0ng/ml IL-6 and control media. Moreover, co-localization of SOCS3 and myogenin was observed after treatment with 10\xa0ng/ml IL-6.'] |
["The root of Bupleurum falcatum L. (BF) has been used in traditional Korean and Chinese medicines for over 2000 years to treat infections, fever, and chronic liver diseases. Among the many active compounds in BF ethanol extract (BFE), saikosaponins exert pharmacological activities including anti-inflammatory effects. Activated microglial cells release a variety of pro-inflammatory substances, leading to neuronal cell death and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The aim of the present study was to investigate the mechanism of the anti-neuroinflammatory effects of BFE using lipopolysaccharide (LPS)-stimulated microglial cells and LPS-intraperitoneal injected C57BL/6 mice.", 'Dried roots of BF were extracted with 70% ethanol (tenfold volume) on a stirring plate for 24h at room temperature to prepare BFE. Pure saikosaponins (SB3, SB4, and SD) were prepared by solvent extraction and column chromatography fractionation. BV2 murine microglial cells were treated with BFE or saikosaponins for 4h and stimulated with LPS. Generation of nitric oxide (NO), inflammatory cytokines, and reactive oxygen species (ROS) from activated microglial cells were monitored. The effects of BFE on NF-κB activation were determined using RT-PCR, reporter assay, and immunostaining. The in vivo effects of BFE were also assessed by immunohistochemical staining of tissue sections from LPS-injected mouse brains.', 'Treatment with BFE or saikosaponins dose-dependently attenuated LPS-induced production of NO, iNOS mRNA, and ROS by 30-50%. They reduced LPS-mediated increases in the mRNA levels of IL-6, IL-1β, and TNF-α by approximately 30-70% without affecting cell viability, and decreased LPS-mediated NF-κB activity via reducing p65/RELA mRNA, transcriptional activity, and nuclear localization of NF-κB. BFE also reduced LPS-induced activation of microglia and astrocytes in the hippocampus and substantia nigra of LPS-injected mice.'] |
['This retrospective study was undertaken to provide data on occurrence, significance and therapy of ventricular tachyarrhythmia (VT) clusters (VTCs) in patients with dilated cardiomyopathy (DCM) and implantable cardioverter defibrillators (ICDs).', 'Data on the clinical significance of VTCs are lacking in patients with DCM and ICDs.', 'Baseline characteristics of 106 consecutive patients with DCM and ICDs were prospectively collected, and chart reviews and episode data retrospectively analyzed. A VTC was defined as > or =3 sustained VTs/24 h.', 'During a mean follow-up of 33+/-23 months, 73 patients (68.9%) had recurrent VT or ventricular fibrillation (VF), 43 patients (40.6%) suffered only single VTs and 30 patients (28.3%) experienced 52 clusters of VTs. Actuarial survival free of VT or VF was 44.6%, 33.0% and 26.5%, and survival free of VTC was 77.3%, 72.2% and 67.1% after one, two and three years, respectively. Independent predictors of VT clusters were heart failure before ICD implantation (p = 0.033), presenting monomorphic VT (p = 0.044), EF <0.40 (p = 0.014) and inducible mVT, especially with right bundle branch block and superior axis configuration (p<0.001). Survival free of recurrent VTCs was 50.8%, 38.1% and 19.0% after one, two and three years, respectively. Once a VTC had occurred, only 56.7%, 46.4%, 30.9% and 15.5% of patients survived and were not transplanted after one, two, three and four years, respectively. Survival was even more reduced if a VTC was associated with cardiac decompensation: 65.6% and 21.9% after one and two years, respectively.'] |
['Allergic rhinitis (AR) precedes and is often associated with bronchial asthma. Indeed, local and systemic inflammations in both conditions are very similar. Cysteinyl-leukotrienes (cys-LTs) are generated during early- and late-phase allergic reactions and induce smooth-muscle contraction, microvascular leakage, and mucous hypersecretion. Cys-LTs are detected in exhaled breath condensate (EBC) of asthmatics and regardless of bronchial symptoms, they are also found in EBC of rhinitic patients.', 'To evaluate cys-LTs in EBC of allergic patients and to assess the activity of nasal fluticasone propionate (FP) on EBC cys-LTs levels.', 'Cys-LTs coefficient of variation (CV) was evaluated from different EBC in 5 healthy volunteers. Cys-LTs levels from EBCs in 13 healthy controls and 56 allergic rhinitic (n=31) and rhinitic/asthmatic (n=25) patients were also evaluated at baseline. Subsequently patients were randomized to receive either FP 100 microg/day per nostril or placebo for 2 weeks and then re-evaluated for EBC cys-LTs.', 'The CV was 14.12%. EBC cys-LTs in allergic patients were significantly higher than in healthy subjects (70.9 vs. 20.6 pg/mL (median), P<0.05), while it did not differ between asthmatic/rhinitic and purely rhinitic patients. Treatment significantly reduced cys-LTs (from 93.6 to 19.9 pg/mL, P<0.001). This effect was evident both in asthmatic/rhinitic and in rhinitic patients.'] |
['It has been suggested that arnica can reduce postoperative edema and ecchymosis associated with cosmetic surgical procedures and improve outcome. Despite a high incidence of arnica use among upper blepharoplasty patients, evidence to support its treatment effect is lacking. The authors performed a randomized, double-blind, placebo-controlled trial to investigate the efficacy of arnica ointment after upper blepharoplasty.', 'One hundred thirty-six bilateral upper blepharoplasty patients were randomized between arnica ointment 10% and placebo ointment. In both study arms, one periorbital area was designated as the treatment side (either arnica or placebo ointment), and the contralateral side served as an untreated (no ointment) internal control. As the primary endpoint, the overall periorbital appearance as based on light photography and judged by a medical and nonmedical panel, was assessed after 3 days, 7 days, and 6 weeks. Secondary endpoints were swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome.', 'There was no significant difference between arnica and placebo in overall judgment of periorbital appearance 3 days, 7 days, and 6 weeks after surgery. Furthermore, swelling, ecchymosis, erythema, pain, and patient satisfaction with recovery and outcome did not differ between arnica and placebo. Postoperative outcome in untreated eyelids was not different from eyelids treated with either arnica or placebo on any of the studied outcome measures.'] |
['Pancreatic cancer has an extremely dismal clinical course and high fatality rate. Knowing that, adipokines could regulate insulin resistance, inflammation, immunity and carcinogenesis. Accordingly, an understanding of adipokines in relation to pancreatic cancer could be useful to improve disease outcome. We aimed to determine serum retinol binding protein-4 (RBP-4) and neutophil gelatinase-associated lipocalin (NGAL) levels in pancreatic cancer patients. Moreover, we assessed their association with tumor severity and with each other.', 'A total of 23 pancreatic cancer patients and 20 healthy controls were enrolled. Fifteen of the pancreatic cancer patients underwent Whipple resection and were examined before and after operation. Serum glucose, insulin, lipid profile, CA19-9, RBP-4 and NGAL were estimated by ELISA.', 'Significant elevation in serum concentrations of RBP-4 (64.4 ± 5.6 ng/ml) and NGAL (142(80-235) ng/ml) at p < 0.001 was found in pancreatic cancer patients. Both RBP-4 and NGAL were significantly lower after operation than before operation. Moreover, NGAL was elevated in advanced pathological T stage. Interestingly, RBP-4 and NGAL levels were positively correlated (r = 0.484, p = 0.05) and they are associated with some of the lipid profile parameters.'] |
['Postmenopausal women undergoing chronic hemodialysis are at risk of uremic bone disease and postmenopausal osteoporosis. There are few reports discussing the effects of raloxifene hydrochloride on chronic hemodialysis patients. We investigated whether differences in the effects of raloxifene on bone mineral density (BMD) are dependent on the level of intact parathyroid hormone (iPTH).', '47 postmenopausal hemodialysis patients with osteoporosis were divided into two groups, i.e. Group A, with treatment, and Group B, without treatment by raloxifene hydrochloride (60 mg/day, three times per week) for 1 year. We evaluated the changes in BMD at the distal one-third of the radial bone and aortic calcification index (ACI) by plain abdominal computerized tomography. Furthermore, we compared the BMD and ACI results for patients with similar iPTH levels within each group.', 'After 1 year of raloxifene treatment, patients with iPTH levels of < 250 pg/ml in Group A showed significantly less BMD deterioration than similar patients in Group B (A: -0.31 +/- 1.7% vs. B: -3.71 +/- 0.7%, p = 0.04). However, raloxifene showed no difference in patients with iPTH levels of > or = 250 pg/ml in the two groups (A: -3.49 +/- 0.7% vs. B: -6.10 +/- 1.9%, p = 0.09). Among the patients with iPTH levels of < 250 pg/ml, changes in the ACI values were 1.30 +/- 0.3% for Group A and 1.67 +/- 1.0% for Group B. Among the patients with iPTH levels of (3) 250 pg/ml, the ACI values were 2.58 +/- 0.7% for Group A and 3.01 +/- 1.2% for Group B.'] |
['A growing body of evidence identifies the renin-angiotensin system as a key factor in the onset and progression of renal damage in chronic partial obstruction, which often represents a complex diagnostic challenge. A prospective study was undertaken to evaluate the role of captopril mercaptoacetyltriglycine-3 (MAG-3) renography as an early diagnostic test of obstruction. We report the results in a subgroup of children who underwent surgical correction for pyeloureteral obstruction.', 'Pyeloplasty was performed in 12 patients, including 10 males, 2 to 72 months old (median age 7) with unilateral hydronephrosis, including normal renal function and blood pressure. Basal and captopril enhanced diuretic renography with 99mtechnetium MAG-3 was performed within 24 hours using the same hydration and diuretic stimulus (0.75 mg./kg. furosemide), and 0.75 mg./kg. captopril was administered orally 60 to 90 minutes before scintigraphy.', 'No adverse effects or modifications of the blood pressure were observed after captopril administration. The diuretic response was deeply worsened by angiotensin converting enzyme inhibition in each hydronephrotic kidney even when the basal study was only slightly abnormal (15-minute washout basal -27 +/- 16%, after captopril -9 +/- 13, p <0.005). After surgical correction the diuretic washout during angiotensin inhibition appeared normal in all patients (15-minute washout -56 +/- 14%). Separate renal function and parenchymal transit of MAG-3 were not modified by angiotensin converting enzyme inhibition, preoperatively or postoperatively.'] |
['Cisplatin is a widely used gastric cancer (GC) chemotherapy; however, genetic factors regulating GC responses to cisplatin remain obscure. Identifying genes regulating cisplatin resistance could aid clinicians in tailoring treatments, by distinguishing cisplatin sensitive patients from those who might benefit from alternative platinum therapies, and highlight novel targeted strategies for overcoming cisplatin resistance. Here integrated epigenomics is applied to identify genes associated with GC cisplatin resistance.', '20 GC cell lines were subjected to gene expression profiling, DNA methylation profiling and drug response assays. The molecular data were integrated to identify genes highly expressed and unmethylated specifically in cisplatin-resistant lines. Candidate genes were functionally tested by several in vitro and in vivo assays. Clinical impact of candidate genes was also assessed in a cohort of 197 GC patients.', 'Epigenomic analysis identified bone morphogenetic protein 4 (BMP4) as an epigenetically regulated gene highly expressed in cisplatin-resistant lines. Functional assays confirmed that BMP4 is necessary and sufficient for the expression of several prooncogenic traits, likely mediated through stimulation of the epithelial-mesenchymal transition. In primary tumours, BMP4 promoter methylation levels were inversely correlated with BMP4 expression, and patients with high BMP4-expressing tumours exhibited significantly worse prognosis. Therapeutically, targeted genetic inhibition of BMP4 caused significant sensitisation of GC cells to cisplatin. Notably, BMP4-expressing GCs also did not exhibit cross resistance to oxaliplatin.'] |
["Central adiposity has been implicated as a risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), possibly promoting the progression from inflammation to metaplasia and neoplasia. We performed a systematic review and meta-analysis of studies to evaluate the association between central adiposity and erosive esophagitis (EE), BE, and EAC, specifically exploring body mass index (BMI)-independent and gastroesophageal reflux (GERD)-independent effects of central adiposity on the risk of these outcomes.", 'We performed a systematic search of multiple databases through March 2013. Studies were included if they reported effect of central adiposity (visceral adipose tissue area, waist-hip ratio, and/or waist circumference) on the risk of EE, BE, and EAC. Summary adjusted odds ratio (aOR) estimates with 95% confidence intervals (CIs), comparing highest category of adiposity with the lowest category of adiposity, were calculated by using random-effects model.', 'Forty relevant articles were identified. Compared with patients with normal body habitus, patients with central adiposity had a higher risk of EE (19 studies; aOR, 1.87; 95% CI, 1.51-2.31) and BE (17 studies; aOR, 1.98; 95% CI, 1.52-2.57). The association between central adiposity and BE persisted after adjusting for BMI (5 studies; aOR, 1.88; 95% CI, 1.20-2.95). Reflux-independent association of central adiposity and BE was observed in studies that used GERD patients as controls or adjusted for GERD symptoms (11 studies; aOR, 2.04; 95% CI, 1.44-2.90). In 6 studies, central adiposity was associated with higher risk of EAC (aOR, 2.51; 95% CI, 1.54-4.06), compared with normal body habitus.'] |
['In surgical graft replacement of the descending aorta graft, one-lung ventilation (OLV) is required to provide adequate surgical view and to allow removal of blood from the left lung. It is best to use a double-lumen tube (DLT) to assure OLV but it is sometimes difficult to place the left-sided DLT due to thoracic aneurysm or the dissection lumen. We retrospectively investigated tracheobronchial anatomy by chest X-ray and chest computed tomography (CT) in 29 cases of descending aorta replacement to determine how best to manage difficult placement of the left-sided DLT.', 'From our database of 29 patients who had undergone descending aorta replacement between February 1, 2005, and December 31, 2009, we investigated the association between difficulty in placing the left-sided DLT and tracheobronchial anatomy by chest X-ray and CT.', 'We could not place a left-sided DLT in 3 of 29 cases. Two of these cases were planned surgery for aortic aneurysm and the other was an emergency operation for acute aortic dissection. We could manage the two cases safely using a right-sided DLT. We compared chest X-ray and chest CT images of these 3 cases with the other 26 cases and found that compression of the tracheobronchial tree was prevalent in the cases of difficult placement of the left-sided DLT.'] |
['Probiotic bacteria have a beneficial effect on intestinal inflammation. In this study, we have examined the effect of lactic acid and commensal Gram positive (+) bacteria conditioned media (CM) on tumour necrosis factor alpha (TNF-alpha) release and the mechanisms involved.', 'Lipopolysaccharide (LPS) induced TNF-alpha secretion by peripheral blood mononuclear cells or the THP-1 cell line was monitored in the presence or absence of bacteria CM obtained from two probiotic strains, Bifidobacterium breve (Bb) and Streptococcus thermophilus (St), and three commensal bacterial strains (Bifidobacterium bifidum, Ruminococcus gnavus, and unidentified Streptococcus). Bb and St bacteria CM were allowed to cross filter grown intestinal epithelial cell monolayers (HT29-19A) to assess intestinal transport of active bacterial products. These products were characterised and their effect on LPS binding to THP-1 cells and nuclear factor kappa B (NF kappa B) activation assessed.', 'Dose dependent inhibition of LPS induced TNF-alpha secretion was noted for both probiotic bacteria CM (64% and 71% inhibition for Bb and St, respectively) and to a lesser extent commensal bacteria CM (21-32% inhibition). Active products from Bb and St were resistant to digestive enzymes and had a molecular mass <3000 Da. Their inhibitory effect was preserved after transepithelial transport across intestinal cell monolayers, mainly in inflammatory conditions. LPS-FITC binding to THP-1 cells and NF kappa B activation were significantly inhibited by Bb and St CM.'] |
['In preclinical reports, restriction of dietary methionine intake was shown to enhance metabolic flexibility, improve lipid profiles, and reduce fat deposition. The present report is the outcome of a "proof of concept" study to evaluate the efficacy of dietary methionine restriction (MR) in humans with metabolic syndrome.', 'Twenty-six obese subjects (six male and 20 female) meeting criteria for metabolic syndrome were randomized to a diet restricted to 2 mg methionine/kg body weight per day and were provided capsules containing either placebo (n = 12) or 33 mg methionine/kg body weight per day (n = 14). Energy expenditure, body composition, insulin sensitivity, and biomarkers of metabolic syndrome were measured before and after 16 wk on the respective diets.', 'Insulin sensitivity and biomarkers of metabolic syndrome improved comparably in both dietary groups. Rates of energy expenditure were unaffected by the diets, but dietary MR produced a significant increase in fat oxidation (MR, 12.1 ± 6.0% increase; control, 8.1 ± 3.3% decrease) and reduction in intrahepatic lipid content (MR liver/spleen attenuation ratio, 8.1 ± 3.3% increase; control ratio, 2.2 ± 2.1% increase) that was independent of the comparable reduction in weight and adiposity that occurred in both groups.'] |
['Visceral obesity is shown to be a predictor of morbidity and mortality. We evaluated the association of measurements of generalized adiposity and visceral fat area (VFA), with abnormalities of metabolic syndrome (MS).', 'Seventy-six women (47.9 +/- 9.2 years) with BMI of 38.7 +/- 5.4 kg/m(2) underwent anthropometric measurements, laboratory procedures, bioeletrical impedance, and abdominal computed tomography (CT) scan. Diagnosis of MS was based on the presence of abdominal obesity and at least two of the following components: hypertension, dyslipidemia, and glucose intolerance and/or hyperinsulinemia.', 'BMI was correlated with both components of adipose tissue--subcutaneous (r = 0.66, P < 0.01) and VFA (r = 0.33, P < 0.02)--and leptin levels (r = 0.38, P < 0.01). In contrast, VFA was correlated with 2-h glucose and insulin levels (r = 0.32 and 0.35, P < 0.05, respectively), triglyceride, HDL cholesterol, and uric acid (r = 0.33, -0.34 and 0.24, P < 0.05, respectively). Subjects with high VFA, matched for BMI, showed greater plasma glucose area under the curve (621 +/- 127 vs. 558 +/- 129 mg x h(-1) x dl(-1), P < 0.05), 2-h insulin (804 +/- 599 vs. 579 +/- 347 pmol/l, P < 0.05), and uric acid levels (0.33 +/- 0.07 vs. 0.26 +/- 0.06 mmol/l, P < 0.05) than subjects with low VFA. In logistic regression analysis, waist circumference, VFA, and 2-h insulin were identified as independent predictors of MS. Receiver operating characteristic curve analysis pointed out the values of 104 cm for waist circumference (58.1% specificity, 84.1% sensitivity), 158.5 cm(2) for VFA (78.1% specificity, 52.3% sensitivity), and 559.8 pmol/l for 2-h insulin (71.9% specificity, 69.8% sensitivity); the presence of at least two of the three variables resulted in a degree of concordance of 76%.'] |
['Measurement of proteolytic activity in feces is a traditional method for the diagnosis of exocrine pancreatic insufficiency (EPI). A drawback of this method is the occurrence of falsely low results that may lead to a false-positive diagnosis of EPI. We hypothesized that intestinal loss of serum proteinase inhibitors in protein-losing enteropathy (PLE) may inhibit fecal proteolytic activity and be a potential source of false low results.', 'The objective of this study was to determine the effect of PLE on fecal proteolytic activity in dogs.', 'Fecal proteolytic activity was measured using a radial diffusion casein digestion assay in 12 samples from 4 clinically healthy control dogs and 30 samples from 16 dogs with PLE. Gastrointestinal protein loss was assessed using an ELISA to determine fecal canine alpha 1-proteinase inhibitor concentration. The relationship between the concentration of canine alpha 1-proteinase inhibitor in the feces and the diameter cleared in the casein digestion assay was determined. The mean clearing diameter was compared between control dogs and dogs with PLE.', "A significant negative correlation was observed between fecal canine alpha1-proteinase inhibitor concentration and casein clearing diameter (P <.001, Pearson r =.6317, r2 =.3999). Mean clearing diameter was significantly lower in dogs with PLE than in control dogs (12.63 vs 16.83 mm, P <.001, two-tailed Student's t-test)."] |
['An important inter-individual variability in the response of insulin sensitivity following a fish oil supplementation has been observed. The objective was to examine the associations between single nucleotide polymorphisms (SNPs) within sterol regulatory element binding transcription factor 1 (SREBF1) gene and the response of insulin sensitivity to a fish oil supplementation.', 'Participants (n\u2009=\u2009210) were recruited in the greater Quebec City area and followed a 6-week fish oil supplementation protocol (5 g/day: 1.9-2.2 g EPA; 1.1 g DHA). Insulin sensitivity was assessed by the quantitative insulin sensitivity check index (QUICKI). Three tag SNPs (tSNPs) within SREBF1 gene were genotyped according to TAQMAN methodology.', 'Three tSNPs (rs12953299, rs4925118 and rs4925115) covered 100% of the known genetic variability within SREBF1 gene. None of the three tSNPs was associated with either baseline fasting insulin concentrations (rs12953299, rs4925118 and rs4925115) (p\u2009=\u20090.29, p\u2009=\u20090.20 and p\u2009=\u20090.70, respectively) or QUICKI (p\u2009=\u20090.20, p\u2009=\u20090.18 and p\u2009=\u20090.76, respectively). The three tSNPs (rs12953299, rs4925118 and rs4925115) were associated with differences in the response of plasma insulin levels (p\u2009=\u20090.01, p\u2009=\u20090.005 and p\u2009=\u20090.004, respectively) and rs12953299 as well as rs4925115 were associated with the insulin sensitivity response (p\u2009=\u20090.009 and p\u2009=\u20090.01, respectively) to the fish oil supplementation, independently of the effects of age, sex and BMI.'] |
['To examine the prognostic significance of lumican and decorin, two abundant small leucine-rich proteoglycans in breast tissue stroma.', 'Lumican and decorin expression was examined in a cohort of 140 invasive breast carcinomas by Western blot analysis. All cases were axillary lymph node-negative and treated by adjuvant endocrine therapy.', 'Lumican and decorin expression was highly correlated (r = 0.45, P < 0.0001), but although low levels of lumican were associated with large tumor size (P = 0.0496), negative estrogen receptor (P = 0.0024) and progesterone receptor status (P = 0.0116), and increased host inflammatory response (P = 0.0077), low decorin levels were associated only with large tumor size (P = 0.0496). However, using univariate analysis, low levels of lumican and decorin were both associated with a shorter time to progression (P = 0.0013 and 0.0262) and poorer survival (P = 0.001 and 0.0076). In multivariate analysis using the Cox regression model, low decorin was also shown to be an independent predictive factor for recurrence (hazard ratio 2.25: 95% confidence interval 1-5, P = 0.047) and survival (hazard ratio 3.39: 95% confidence interval 1.2-9.6, P = 0.021).'] |
['To determine the role of P and its nuclear receptor PR in the growth of ectopic uterine tissue of mice with or without a disrupted PR gene.', 'Animal study.', 'Academic medical center.', 'Female wild-type (WT) and transgenic knockout mice for P receptor (PRKO).', 'Endometriosis was induced in the following groups of ovariectomized adult mice: [1] untreated WT, [2] estradiol (E(2))-treated WT, [3] P-treated WT, [4] E(2) + P-treated WT, [5] untreated PRKO, [6] E(2)-treated PRKO, and [7] E(2) + P-treated PRKO (n = 5 in each group).', 'The size of ectopic uterine tissue in WT and PRKO mice were compared between the groups subjected to treatments with P or E(2). Tissue proliferating cell nuclear antigen (PCNA) levels were compared among these groups.', 'Treatment with P only significantly decreased the size of WT ectopic uterine tissue. The untreated PRKO ectopic uterine tissue was significantly larger than WT tissue. Estradiol increased the size of ectopic uterine tissues, and this E(2)-dependent growth could be suppressed by P in WT tissues but not in PRKO tissues. Finally, the hormone-dependent changes in ectopic uterine tissue size were accompanied by comparable alterations in PCNA levels.'] |
['Integral to the function and morphology of the epithelium is the lattice of cell-cell junctions known as adherens junctions (AJs). AJ stability and plasticity relies on E-Cadherin exocytosis and endocytosis. A mechanism regulating E-Cadherin (E-Cad) exocytosis to the AJs has implicated proteins of the exocyst complex, but mechanisms regulating E-Cad endocytosis from the AJs remain less well understood.', 'Here we show that Cdc42, Par6, or aPKC loss of function is accompanied by the accumulation of apical E-Cad intracellular punctate structures and the disruption of AJs in Drosophila epithelial cells. These punctate structures derive from large and malformed endocytic vesicles that emanate from the AJs; a phenotype that is also observed upon blocking vesicle scission in dynamin mutant cells. We demonstrate that the Drosophila Cdc42-interacting protein 4 (Cip4) is a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp in Drosophila. Accordingly, Cip4, WASp, or Arp2/3 loss of function also results in defective E-Cadherin endocytosis.'] |
['Despite tremendous progress in understanding the mechanisms of constitutive and alternative splicing, an important and widespread step along the gene expression pathway, our ability to deliberately regulate gene expression at this step remains rudimentary. The present study was performed to investigate whether a theophylline-dependent "splice switch" that sequesters the branchpoint sequence (BPS) within RNA-theophylline complex can regulate alternative splicing.', 'We constructed a series of pre-mRNAs in which the BPS was inserted within theophylline aptamer. We show that theophylline-induced sequestering of BPS inhibits pre-mRNA splicing both in vitro and in vivo in a dose-dependent manner. Several lines of evidence suggest that theophylline-dependent inhibition of splicing is highly specific, and thermodynamic stability of RNA-theophylline complex as well as the location of BPS within this complex affects the efficiency of splicing inhibition. Finally, we have constructed an alternative splicing model pre-mRNA substrate in which theophylline caused exon skipping both in vitro and in vivo, suggesting that a small molecule-RNA interaction can modulate alternative splicing.'] |
['To investigate if caesarean section (CS) increases the risk for childhood asthma and gastroenteritis with reference made to children born with vaginal delivery (VD).', 'Retrospective study of data from linked Swedish medical service registers--Medical Birth Registry (MBR) and Hospital Discharge Registry (HDR). Data were obtained from women without any background/perinatal morbidity noted, and from children without any neonatal complications. Children that had reached at least 1 year of age and were found in the HDR were considered as cases, whereas children not found in the HDR or hospitalized for other causes than asthma or gastroenteritis were defined as controls. Odds ratios (OR) stratified for year of birth, maternal age, parity and smoking in early pregnancy were calculated. Investigations were made comparing the risk for in hospital treatment for asthma or gastroenteritis in CS children and in VD siblings of CS children. The overall inpatient morbidity in CS and VD children were also investigated.', 'The OR for asthma in CS children was 1.31 [95% confidence interval (CI) 1.23-1.40]. The same OR, 1.31, was found for gastroenteritis (95% CI 1.24-1.38). The OR for CS children having experienced both asthma and gastroenteritis was further increased (1.74, 95% CI 1.36-2.23). The risk for asthma in VD siblings of CS children was not significantly increased, whereas VD siblings experienced a slightly increased risk for gastroenteritis. CS children had an increased overall in hospital morbidity when compared to VD children.'] |
['To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results.', 'Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce.', 'Prospective follow-up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12-week gestation until term delivery (>37 weeks) and their neonates.', 'The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)-Ab] assessed at 12-, 24- and 36-week gestation.', 'Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24- and 36-week gestation. Higher maternal TSH levels (>97·5th percentile, as defined in 810 women without TPO-Ab at 12 weeks) at one or more times during pregnancy (O.R: 2·26, 95% CI: 1·20-4·29) and lower gestational age (O.R: 1·22, 95% CI: 1·05-1·41) are independently related to lower screening TT4 levels.'] |
['This study examined the association between disturbed sleep and poorer daytime function in older women.', 'Observational study.', '2,889 women, mean age 83.5 years, participating in the 2002-2004 examination of the Study of Osteoporotic Fractures.', 'N/A.', 'Participants wore actigraphs for an average +/- SD of 4.1 +/- 0.83 24-hour periods. Actigraphy measured sleep variables were total sleep time and hours awake after sleep onset during the night and daytime napping behavior. Neuromuscular performance measurements included gait speed, chair stands, and grip strength. Functional limitations were assessed as self-reported difficulty with one or more of 6 instrumental activities of daily living (IADL). In fully adjusted, multivariable models, women who slept <6 hours per night walked 3.5% slower than those who slept 6.0-6.8 hours. Those who slept > or =7.5 hours took 4.1% longer to complete 5 chair stands than those who slept 6.8-7.5 hours. With higher wake after sleep onset (> or =1.6 hours compared to <0.7 hours) gait speed was 9.1% slower; it took 7.6% longer to complete 5 chair stands, and odds of functional limitation were 1.8 (95% CI: 1.4, 2.4) higher. Women with 1.0-1.8 hours of daytime sleep had higher odds (1.4 [95% CI: 1.1, 1.8]) of a functional limitation than those with <0.5 hours. Sleep variables did not appear to be associated with grip strength.'] |
['Lactase phlorizin hydrolase (LPH) activity is high in infants but declines 80%-90% before adulthood in most mammals, including humans. However, 95% of whites show autosomal dominant inheritance of a lifelong high lactose digesting capacity (LDC). This study attempted to clarify the molecular mechanism(s) of this phenomenon (posttranslational vs. pretranslational).', 'A race- and sex-balanced cohort (n = 20) was studied, and lactose tolerance and levels of jejunal lactase protein, activity, and messenger RNA (mRNA) were measured.', 'These data confirm that black heritage predicts low LDC, and white heritage predicts high LDC. Lactase breath hydrogen and determination of lactase/sucrase ratio (L/S) from jejunal biopsy specimens divide the group by high and low LDC phenotypes concordantly. All subjects with an L/S ratio > 0.5 had immunodetectable LPH protein and measurably higher LPH mRNA levels than the remaining subjects. LPH mRNA levels are highly correlated with lactase specific activity (r = 0.80) and L/S ratio (r = 0.88).'] |
['Lipoprotein(a) [Lp(a)] is an independent risk factor for aortic valve stenosis and aortic valve calcification (AVC) in the general population. In this study, we determined the association between AVC and both plasma Lp(a) levels and apolipoprotein(a) [apo(a)] kringle IV repeat polymorphisms in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH).', 'A total of 129 asymptomatic heterozygous FH patients (age 40-69\xa0years) were included in this study. AVC was detected using computed tomography scanning. Lp(a) concentration and apo(a) kringle IV repeat number were measured using immunoturbidimetry and immunoblotting, respectively. Univariate and multivariate logistic regression were used to assess the association between Lp(a) concentration and the presence of AVC.', 'Aortic valve calcification was present in 38.2% of patients, including three with extensive AVC (>400\xa0Agatston units). Lp(a) concentration was significantly correlated with gender, number of apo(a) kringle IV repeats and the presence and severity of AVC, but not with coronary artery calcification (CAC). AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and CAC score. After adjustment for all significant covariables, plasma Lp(a) concentration remained a significant predictor of AVC, with an odds ratio per 10-mg\xa0dL(-1) increase in Lp(a) concentration of 1.11 (95% confidence interval 1.01-1.20, P\xa0=\xa00.03).'] |
["Lacritin is a tear glycoprotein with prosecretory, prosurvival, and mitogenic properties. We examined lacritin levels in the tears of Sjögren's syndrome (SS) patients and explored the therapeutic potential of topical lacritin for the treatment of keratoconjunctivitis sicca.", 'Tears from healthy controls (n = 14) and SS patients (n = 15) were assayed for lacritin using a C-terminal antibody. In a paired-eye study, autoimmune regulator (Aire) knockout (KO) mice (n = 7) were treated three times daily for 21 days with 10 μL of 4 μM lacritin (left eye) or vehicle (PBS) control (right eye). Tear secretion and ocular surface integrity were assessed at baseline and after treatment. Immunohistochemical staining of CD4+ T cells, cytokeratin-10 (K10), and cytokeratin-12 (K12) expression in the cornea and CD4+ T cell infiltration in the lacrimal glands were assessed.', 'Lacritin monomer (421.8 ± 65.3 ng [SS] vs. 655.8 ± 118.9 ng [controls]; P = 0.05) and C-terminal fragment protein (125 ± 34.1 ng [SS] vs. 399.5 ± 84.3 ng [controls]; P = 0.008) per 100 μL of tear eluate were significantly lower in SS patients. In Aire KO mice treated with lacritin, tear secretion increased by 46% (13.0 ± 3.5 mm vs. 8.9 ± 2.9 mm; P = 0.01) and lissamine green staining score significantly decreased relative to baseline (-0.417 ± 0.06 vs. 0.125 ± 0.07; P = 0.02). Expression of K10 but not K12 in the cornea was significantly decreased in lacritin-treated eyes. Focal CD4+ T cell infiltration of the lacrimal glands was significantly reduced on the lacritin-treated side versus the untreated side.'] |
['Specific aspects of care have been identified as important in order to provide high-quality care for patients with diabetes, including the need for patients to understand their condition. Little research has specifically explored the views and understanding of older people with diabetes in primary care.', "To explore views on quality of diabetes care and to gauge patients' understanding of their condition in order to identify areas for improvement in care.", 'During August and September 2012, 13 semi-structured interviews were held with people with diabetes aged over 75 years, recruited from an inner-city general practice. The interviews focused on three areas: (1) their understanding of diabetes, (2) their views on the information they had received, and (3) their views on the quality of their care. The qualitative data were analysed using N-Vivo and techniques derived from framework analysis.', 'A basic understanding of diabetes was shared among the responders, but certain gaps were identified, notably misunderstandings regarding hypoglycaemia and diabetic coma. Information was valued most if given in person; written information may not be impactful. Educational input attenuated over time and patients did not actively seek updating. Personal care was appreciated, but many patients expressed a desire to be kept better informed about their treatment.'] |
['Recent studies have focused on the diagnostic and prognostic significance of CD24 and CD44 expression in human cancers. This study aimed to explore changes in CD44 and CD24 expression levels in patients with gastric cancer and to assess their prognostic values.', 'CD44 and CD24 expression levels were investigated immunohistochemically in tumor samples from 290 patients with non-cardia gastric adenocarcinoma, of whom 77 had paired adjacent normal gastric mucosa. CD24 and CD44 mRNA levels were determined by quantitative polymerase chain reaction in 34 patients. Serum anti-Helicobacter pylori IgG was detected by enzyme-linked immunosorbent assay. Relationships between CD44 and CD24 protein expression levels and tumor parameters were analyzed and their prognostic values were evaluated by Cox proportional hazards models.', 'CD24 and CD44 expression levels were significantly higher in patients with gastric cancer compared with those in paired controls (45.5% vs. 0.0%, and 61.0% vs. 0.0%, P < 0.001). Among 290 patients, the overall survival rate was significantly higher in CD44(-) compared with CD44(+) patients (log-rank test, P = 0.035). However, there was no significant correlation between CD24 expression and overall survival time (log-rank test, P = 0.115). Multivariate regression analysis indicated that positive CD44 expression (P = 0.029), TNM staging (P < 0.001), and lymphovascular invasion (P = 0.016), but not CD24 expression (P = 0.065), were independent prognostic factors in gastric cancer.'] |
['To compare the incidence of hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) before and after universal HBV vaccination and to identify factors underlying the change.', 'This study included 471 hospitalized children with nephrotic syndrome (NS) and 488 long-term follow-up hepatitis B surface antigen (HBsAg)-carrier children. Horizontal transmission (negative maternal HBsAg status) of HBVMN and HBV was assessed, and the incidence of HBVMN was compared before and after initiation of the universal HBV vaccination program started in 1984.', 'The frequency of HBVMN in children with NS was 11.6% between 1974 and 1984, 4.5% between 1984 and 1994, 2.1% between 1994 and 2004, and 0% between 2004 and 2009. Similarly, the number of HBsAg-seropositive children with NS (mainly via horizontal infection) decreased after universal vaccination. The prevaccination frequency of HBV horizontal transmission in chronic HBsAg carriers from the general population was 36.5% compared with 5% in the postvaccination period. The incidence of HBVMN in these carriers revealed a parallel decline.'] |
['The Mediterranean diet (MedD) has long been associated with lower incidence of cardiovascular disease. Little information is available on association between MedD, vitamins intake and arrhythmias. We sought to investigate the relationship between adherence to MedD, antioxidants intake and spontaneous conversion of atrial fibrillation (AF).', 'A group of 800 subjects was included in a case-control study; 400 of them had a first detected episode of AF. Nutritional parameters were assessed by a self-administered food frequency validated questionnaire and completed by an interviewer-administered 7 days diet recall. Adherence to MedD was evaluated using the Mediterranean Score and intake of antioxidants from food was calculated. Adherence to the Med Diet was lower in patients that developed AF compared to control (mean Med Score: 22.3\xa0±\xa03.1 vs 27.9\xa0±\xa05.6; p\xa0<\xa00.001). The median value was 23.5 (Q1-Q3 range 23-30) in patients with AF and 27.4 (Q1-Q3 range 26-33). The estimated intake of total antioxidants was lower in patients with AF (13.5\xa0±\xa08.3 vs 18.2\xa0±\xa09.4\xa0mmol/d; p\xa0<\xa00.001). Patients in the highest quartile of Mediterranean Score had higher probability of spontaneous conversion of atrial fibrillation (OR1.9; 95%CI 1.58-2.81). High levels of antioxidants intake were also associated with an increasing probability of spontaneous conversion of arrhythmia (O.R. 1.8; 95%CI 1.56-2.99; P\xa0<\xa00.01).'] |
['To explore whether EEG and MRI abnormalities in the "healthy" hemisphere influence seizure and cognitive outcome after functional hemispherectomy.', 'This is a retrospective consecutive cohort study of 43 children who underwent functional hemispherectomy between 1994 and 2008. Results of preoperative EEG recordings were reviewed for the existence of (inter)ictal epileptic or background abnormalities in the contralateral hemisphere. Preoperative MRIs were reexamined for the existence of unequivocal contralateral abnormalities. Postoperative seizure status was assessed, and of 34 children, IQ or mental developmental index (MDI) scores were obtained preoperatively and postoperatively. Seizure freedom was defined as Engel 1A. Contralateral EEG and MRI abnormalities were studied in relation to seizure and cognitive outcome.', 'Thirty-three children achieved seizure freedom (77%). Of the 11 patients with contralateral MRI abnormalities, only 45% were seizure free, compared with 88% of the 32 patients without contralateral MRI lesions (p = 0.030). Children with contralateral MRI abnormalities more often were severely retarded after surgery (MDI/IQ <55; 90% vs 42%, p = 0.030). Postoperative MDI/IQ scores improved in none of the children with, but in 38% of those without contralateral MRI abnormalities (p = 0.034). Contralateral epileptic or background EEG abnormalities did not affect seizure outcome or postoperative cognitive performance. Four of 6 children with bilateral epileptic encephalopathy reached seizure freedom.'] |
['The value of C-reactive protein concentrations in the assessment of prognosis in patients with advanced lymphoma has not been clearly defined.', "Patients with a diagnosis of non-Hodgkin's lymphoma (n = 108) and Hodgkin's lymphoma, (n = 39) and who had measurements of C-reactive protein were studied retrospectively and the data was reviewed over 8 years.", 'Median survival, from the time of sampling, was 7.4 months. On univariate analysis there was a significant relationship between the duration of cancer specific survival and tumour type (p < 0.05), circulating concentrations of albumin (p < 0.001) and C-reactive protein (p < 0.001). In contrast, only C-reactive protein concentration was a predictor of death from intercurrent disease (p < 0.05). On multivariate analysis, C-reactive protein concentration remained a strong independent predictor of both death from cancer and intercurrent disease (p < 0.001). The hazard ratio associated with a unit increase in stratified C-reactive protein concentration was 8.18 (95% CI 4.80 - 13.95) for cancer specific death and 2.11 (95% CI 1.22 - 3.64) for intercurrent death.'] |
['The aim of this study was to investigate whether fatty and clear cell areas in large regenerative nodules (LRN), dysplastic nodules (DN), and hepatocellular carcinoma (HCC) show higher degree of genomic mutation compared to non-fatty/clear cell area in the same nodule or non-lesional tissue.', 'We examined 22 nodular lesions (9 HCC, 5 DN and 8 LRN) from seven cirrhotic livers removed at transplantation. Frozen sections were used for manual microdissection of areas with fatty/clear cell change. DNA from microdissected tissue was amplified using arbitrarily primed polymerase chain reaction (AP-PCR), and PCR products were run on polyacrilamide gel generating a "fingerprint" band pattern. Autoradiographs were analysed using Adobe Photoshop version 6.0. Fingerprints from lesional tissue were compared to reference tissue and the total number of bands in excess or defect was calculated and divided by the total number of bands identified, obtaining the genomic damage fraction (GDF).', 'Increasing GDF average values were seen from cirrhotic liver (0.13+/-0.04), to LRN (0.16+/-0.1), DN (0.28+/-0.08) and HCC (0.30+/-0.07). A statistically significant difference in GDF values was documented between cirrhotic liver and DN (p=0.008) and HCC (p=0.005) and between HCC and LRN (p=0.02). No significant difference was documented between DN and HCC, and between LRN and cirrhotic liver. Eleven nodules containing fat/clear cell areas were compared to the other 11 nodules without fat/clear cell areas. The GDF was not different between the two groups: 0.29+/-0.11 versus 0.25+/-0.12; p=0.5. The average value of genomic damage fraction between fat/clear cell areas (0.29+/-0.11) and no fat/clear cell areas (0.25+/-0.1) within the same nodules were not significantly different (p=0.11).'] |
['Culturing Helicobacter pylori (Hp) has a low sensitivity rate, and is affected by factors such as the number of biopsies, transport, and culture conditions. Hp detection is also influenced by omeprazole, antibiotics, bismuth salts, or benzocaine use. Disinfection procedures based on glutaraldehyde are highly effective in eliminating any Hp contamination of endoscopic equipment. However, the possibility that some residual glutaraldehyde present in biopsy forceps after decontamination could affect Hp viability has not yet been investigated.', 'Antral specimens from 25 patients with active gastric or duodenal ulcer obtained with three forceps (sterilized with ethylene oxide, glutaraldehyde, or glutaraldehyde-phenolate) were streaked on appropriate media, and results of culture evaluated.', 'Helicobacter pylori was isolated in 17 patients. Positivity of culture was independent of the way the forceps were sterilized, and the number of colonies (mean +/- SD) was similar for the three types of forceps (475 +/- 312, 533 +/- 242, and 550 +/- 225 colony-forming units [CFUs] for ethylene oxide, glutaraldehyde, and glutaraldehyde-phenolate, respectively). Moreover, the incubation time since isolation was also similar (6.0 +/- 1.3, 5.8 +/- 1.2, and 5.7 +/- 1.2 days for ethylene oxide, glutaraldehyde, and glutaraldehyde-phenolate disinfected forceps, respectively).'] |
['To evaluate potential variations in the plasma metabolomic profile of endometriosis patients as a consequence of pathophysiologic alterations associated with this disorder.', 'Prospective study. For each subject, a plasma sample was collected after overnight fasting and before surgery.', 'University medical center.', 'The clinical cohort included 50 endometriosis patients, diagnosed at early (n = 6) and advanced (n = 44) stages of the disease, and 23 healthy women. All volunteers underwent diagnostic laparoscopy to visually confirm the presence or absence of endometriotic lesions.', 'Metabolomic profiling of plasma samples based on ', 'Comparative identification of metabolites present in plasma from endometriosis patients and healthy women.', 'The plasma metabolomic profile of endometriosis patients was characterized by increased concentration of valine, fucose, choline-containing metabolites, lysine/arginine, and lipoproteins and decreased concentration of creatinine compared with healthy women. Metabolic alterations identified in the plasma metabolomic profile of endometriosis patients correlate with pathophysiologic events previously described in the progression of this disease.'] |
['Portal vein ligation (PVL) and portal vein embolization (PVE) are used to induce hypertrophy of the future remnant liver before major liver resection. The aim of our study was to compare the hypertrophy response of the liver after PVL versus PVE in a rabbit model.', 'Twenty rabbits were divided into an embolization group (n = 10) and a ligation group (n = 10). Both groups were divided in 2 subgroups of 5 rabbits that were humanely killed after days 7 and 14. The portal vein branches to the 3 cranial liver lobes (80% of the liver) were occluded. Regeneration of the caudal liver lobe was measured using volumetry based on computed tomography on days 3, 7, 10, and 14. Immunohistochemistry for Ki-67 and RAM11 was performed to quantify proliferating cells and macrophages. In addition, tissue tumor necrosis factor-α and interleukin-6 were assessed.', 'The caudal liver volume increased over time in both groups (P < .001), but this increase was greater after PVE than after PVL (P = .001) with a mean degree of hypertrophy of 15% ± 4% and 20% ± 2%, respectively. When comparing the groups on the separate time points, a difference was found on days 10 and 14 (P = .008 and P = .016, respectively). These data were confirmed by Ki-67 staining, which showed a greater number of proliferating hepatocytes on day 7 after embolization (P = .016). Cytokine analysis of liver tissue did not show significant differences between the ligation and embolization groups on days 7 and 14.'] |
['The pathophysiology of acute kidney injury (AKI) after cardiac surgery is not completely understood. Recent evidence suggests a pivotal role for the endothelium in AKI. In experimental models of AKI, the endothelial specific receptor Tie2 with its ligands Angiopoietin (Ang) 1 and Ang2 are deranged. This study investigates their status after cardiac surgery, and a possible relation between angiopoietins and AKI.', 'From a cohort of 541 patients that underwent cardiac surgery, blood and urine was collected at 5 predefined time points. From this cohort we identified 21 patients who had at least 50% post-operative serum creatinine increase (AKI). We constructed a control group (n = 21) using propensity matching. Systemic levels of Ang1, Ang2, and sTie2 were measured in plasma and the AKI markers albumin, kidney injury molecule-1 (KIM-1) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in the urine.', 'Ang2 plasma levels increased over time in AKI (from 4.2 to 11.6 ng/ml) and control patients (from 3.0 to 6.7 ng/ml). Ang2 levels increased 1.7-fold more in patients who developed AKI after cardiac surgery compared to matched control patients. Plasma levels of sTie2 decreased 1.6-fold and Ang1 decreased 3-fold over time in both groups, but were not different between AKI and controls (Ang1 P = 0.583 and sTie2 P = 0.679). Moreover, we found a positive correlation between plasma levels of Ang2 and urinary levels of NAG.'] |
['The prevalence of both low testosterone levels and depression increases with age. Currently, there is no consensus regarding the existence of an association. Our study analyses the cross-sectional association of testosterone levels with depressive symptoms and its prospective association with the development of incident depressive symptoms.', 'Longitudinal population-based study; based on the data of the Longitudinal Aging Study Amsterdam (LASA) including 608 men aged >or=65 years (median age 75.6 years).', 'Linear and logistic regression between total and free testosterone levels and depressive symptoms as measured by the Center of Epidemiologic Studies Depression (CES-D) scale, taking into account medical and lifestyle factors. Cox Proportional Hazards model was used to assess incident depressive symptoms.', 'Unadjusted linear regression between square-root transformed CES-D scores and free testosterone levels showed a significant inverse association as a continuous variable (beta = -0.10, P < 0.05), lowest quartile compared to highest (beta = 0.12, P < 0.05) and with a threshold value of 170 pmol/l (beta = 0.13, P < 0.05). The results remained significant for the group below threshold after adjustment for all confounders (beta = 0.09, P < 0.05). Cox Proportional Hazards Model showed a decreased risk for incident depressive symptoms for men with higher free testosterone levels [HR = 0.997 CI (0.995-1.000)]. Men with the threshold value below 220 pmol/l were at increased risk of incident depressive symptoms [HR = 1.989 CI (1.173-3.374)].'] |
['To investigate existing caries risk factors in preschool children and to illustrate their caries risk profiles graphically with aid of a computer-based program.', "All 2-year-old children from a small town in northern Sweden were invited and 87% (n = 125) accepted to participate. Data was collected with a questionnaire concerning the child's normal diet and sugar consumption. Special care was taken to note the intake of sweet drinks and sugary between-meal products. Questions on general health and medication, toothbrushing frequency with parental help and use of fluorides were also included. The caries prevalence was recorded with mirror and probe and the level of oral mutans streptococci was enumerated with a chair-side technique. The obtained data were computerised in a risk assessment program (Cariogram) and a graphical profile of each child was constructed.", "The caries prevalence was 6%, and 18% had detectable levels of oral mutans streptococci. The sugar consumption was strikingly high with 82% and 97% having ice cream and sweets once a week or more often. In 22% of the families, toothbrushing with parental help was not a daily routine. Of the children, 51% displayed a low chance (0-20%) of avoiding caries in the future. The frequency of sugar consumption was the most pertinent factor in the children's caries risk profiles."] |
['To assess the effect of newborn circumcision on the incidence and medical costs of urinary tract infection (UTI) during the first year of life for patients in a large health maintenance organization.', 'Kaiser Permanente Medical Care Program of Northern California (KPNC).', 'The population consisted of members of KPNC. The study group consisted of a cohort of 28 812 infants delivered during 1996 at KPNC hospitals; of the 14 893 male infants in the group, 9668 (64.9%) were circumcised. A second cohort of 20 587 infants born in 1997 and monitored for 12 months was analyzed to determine incidence rates.', 'Retrospective study of all infants consecutively delivered at 12 facilities.', 'Diagnosis of UTI was determined from the KPNC computerized database using the International Classification of Diseases, Ninth Revision code for inpatients and KPNC Outpatient Summary Clinical Record codes for outpatients. A sample of 52 patient charts was reviewed to confirm the International Classification of Diseases, Ninth Revision and KPNC Outpatient Summary Clinical Record codes and provide additional data.', 'Infants <1 year old who were born in 1996 had 446 UTIs (292 in females; 154 in males); 132 (86%) of the UTIs in males occurred in uncircumcised boys. The mean total cost of managing UTI was 2 times as high in males ($1111) as in females ($542). This higher total cost reflected the higher rate of hospital admission in uncircumcised males with UTIs (27.3%) compared with females (7.5%); mean age at hospitalization for UTI was 2.5 months old for uncircumcised boys and 6.5 months old for girls. In 1996, total cost of managing UTI in uncircumcised males ($155 628) was 10 times higher than for circumcised males ($15 466) despite the fact that uncircumcised males made up only 35.1% of the male patient base in 1996, reflecting the more frequent occurrence of UTI in uncircumcised males (132 episodes) than in circumcised males (22 episodes), and the larger number of hospital admissions in uncircumcised males (38) than in circumcised males (4). The incidence of UTI in the first year of life was 1:47 (2.15%) in uncircumcised males, 1:455 (.22%) in circumcised males, and 1:49 (2. 05%) in females. The odds ratio of UTI in uncircumcised:circumcised males was 9.1:1.'] |
['Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease.', 'The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively.', 'No inflammation was found in 49 men (17%), while 153 (53%) and 85 (30%) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44%) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95% CI 1.02-4.24), but not after adjusting for pathologic features.'] |
["The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes.", 'A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis.', 'CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas.'] |
['Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells.', 'In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting.', 'T24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected.'] |
['To evaluate family history (FH) of type 2 diabetes (T2DM) as a risk factor for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM and related metabolic traits in South East Asia and to compare the effects of a paternal versus maternal history.', 'We studied 4717 men and women (68% Chinese, 18% Malays and 14% Asian Indians) living in Singapore. FH was considered positive if at least one first degree relative had T2DM. Obesity, fasting lipids, glucose and insulin levels were measured for all subjects. Insulin resistance (IR) was estimated by homeostasis model assessment (HOMA). An oral glucose tolerance test was carried for all subjects except those on diabetes medication.', 'A positive FH was associated with increased risk of IFG/IGT (OR=1.67, 95% CI=1.42-1.97) and T2DM (OR=2.95, 95% CI=2.36-3.70) as well as higher levels of obesity, HOMA-IR, fasting triglyceride (TG), and lower levels of high density lipoprotein (HDL) cholesterol and HOMA-beta. A maternal history of T2DM appeared to have a greater impact on obesity-related traits than a paternal history of T2DM. Compared to individuals with no FH of T2DM, a maternal history was associated with (i) greater body mass index (BMI) (24.15kg/m(2) vs. 23.42kg/m(2), p=0.016) and waist-to-hip ratio (WHR) (0.874 vs. 0.865, p=0.037) in men; and (ii) greater WHR (0.788 vs. 0.779, p=0.004), fasting triglyceride (1.23mmol/L vs. 1.09mmol/L, p<0.001), HOMA-IR (2.02 vs. 1.75, p<0.001), fasting plasma glucose (5.25mmol/L vs. 5.18mmol/L, p=0.005) and 2-h plasma glucose (6.01mmol/L vs. 5.78mmol/L, p=0.001) and lower HDL-C (1.41mmol/L vs. 1.47mmol/L, p=0.031) in women.'] |
['An Arabidopsis β-glucosidase, AtBG1 is known to hydrolyze glucose-conjugated, biologically inactive abscisic acid (ABA) to produce active ABA, which increases the level of ABA in plants. Since an increase of ABA in plants confers tolerance against abiotic stress such as drought, we introduced the pCAMBIA3301 vector harboring the AtBG1 gene into creeping bentgrass through Agrobacterium-mediated transformation. After transformation, putative transgenic plants were selected using the BASTA resistance assay at a concentration of 0.8%. Genomic integration of the AtBG1 gene was confirmed by genomic PCR and Southern blot analysis, and gene expression was validated by Northern blot and Western blot analyses. Interestingly, the transgenic bentgrass plants overexpressing AtBG1 had a dwarf phenotype with reduced growth rates when compared to wild-type creeping bentgrass. In addition, the transgenic plants accumulated higher ABA levels and displayed enhanced drought tolerance. These results suggest that the expression of AtBG1 in plants induces the accumulation of higher ABA levels, which results in the formation of dwarf creeping bentgrass and enhances the survival in water-limiting environments.'] |
['To demonstrate the microcirculatory and wound healing effects of Aloe vera on induced second degree burn wounds in rats.', 'A total of 48 male Wistar rats were equally divided into 4 groups as follows: sham controls, untreated burn-wound rats, those treated with once-daily application of normal saline (NSS) and those treated with once-daily application of lyophilized Aloe vera gel. The animals in each group were equally subdivided into 2 subgroups for the study of cutaneous microcirculation and wound healing on day 7 and 14 after burn. Dorsal skinfold chamber preparation and intravital fluorescence microscopic technique were performed to examine dermal microvascular changes, including arteriolar diameter, postcapillary venular permeability and leukocyte adhesion on postcapillary venules.', 'On day 7, the vasodilation and increased postcapillary venular permeability as encountered in the untreated burn were found to be reduced significantly (p < 0.05) in both the NSS- and Aloe vera-treated groups, but to a greater extent in the latter. Leukocyte adhesion was not different among the untreated, NSS- and Aloe vera-treated groups. On day 14, vasoconstriction occurred after the wound had been left untreated. Only in the Aloe vera-treated groups, was arteriolar diameter increased up to normal condition and postcapillary venular permeability was not different from the sham controls. The amount of leukocyte adhesion was also less observed compared to the untreated and NSS- treated groups. Besides, the healing area of the Aloe vera-treated wound was better than that of the untreated and NSS- treated groups during 7 and 14 days after burn.'] |
['Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare group of tumors with a wide spectrum of clinical behavior. However, there are no known clinically relevant biomarkers to predict metastasis.', 'To investigate differential gene expression signatures of metastatic vs non-metastatic NETs, we studied cell cycle regulatory genes in 19 metastatic and 22 non-metastatic colorectal NETs by PCR arrays. Immunohistochemistry (IHC) and quantitative real-time RT-PCR were performed to verify the results and another set of 38 GEP-NETs were further studied for validation.', 'We first delineated six candidate genes for metastasis including ATM, CCND2, RBL2, CDKN3, CCNB1, and GTSE1. ATM was negatively correlated with metastatic NETs (p<0.001) with more than 2-fold change compared to non-metastatic NETs. Overexpression of ATM protein by IHC was strongly correlated with high ATM mRNA levels and low Ki-67 labeling index. Patients with ATM-negativity by IHC showed significantly decreased overall survival than patients with ATM-positivity (median OS, metastatic vs non-metastatic NETs; 2.7 years vs not reached; p = 0.003) and 85.7% of metastatic NETs were ATM-negative. In another validation set of GEP-NETs, decreased mRNA of ATM gene was associated with metastasis and remained significant (p = 0.023).'] |
['Dermatophyte infections are often accompanied by a striking inflammatory reaction, alleviation of which has often been achieved by the concomitant but controversial use of topical steroidal agents. Recent investigations have suggested the presence of inherent anti-inflammatory properties associated with certain antifungal agents, particularly those within the allylamine class. Butenafine, the first and only approved representative of the benzylamine antifungals, possesses a chemical structure and antifungal activity similar to the allylamines. Although several studies have demonstrated excellent antimycotic efficacy, none has addressed anti-inflammatory properties associated with butenafine.', 'This study was designed to determine whether butenafine, a benzylamine antifungal, expresses anti-inflammatory activity in vivo.', 'A randomized single-blinded control investigation comparing the attenuation of UVB irradiation-induced erythema by butenafine, its proprietary base cream, and no application (negative control) was performed in humans.', 'Butenafine demonstrated a significant and marked decrease in UVB-induced erythema as compared with both the base cream and the unaltered control.'] |
['We determine whether the change in numeric descriptive scale for pain after sublingual nitroglycerin use can predict cardiac etiology of chest pain.', 'A prospective study of a convenience sample of patients who had chest pain, presented to the emergency department from May 24, 2001, to April 30, 2002, and received sublingual nitroglycerin during their evaluation was performed. The 11-point numeric descriptive scale for chest pain was recorded before and after the initial dose of sublingual nitroglycerin. Cardiac-related pain was defined as chest pain in a patient with a discharge diagnosis of myocardial infarction or the diagnosis of coronary artery disease based on a positive diagnostic study (cardiac catheterization or noninvasive stress imaging). Change in the numeric descriptive scale was divided into 4 categories: (1) significant/complete reduction; (2) moderate reduction; (3) minimal reduction; and (4) no change.', 'The study cohort was composed of 664 patients: 345 women (52%) and 319 men (48%), mean age 52 years (+/-12.4 years). Cardiac-related chest pain was identified in 122 patients (18%). In the overall patient population, 125 (19%) patients had no change in pain, 206 (31%) patients had minimal reduction, 145 (22%) patients had moderate reduction, and 188 (28%) patients had significant or complete reduction in pain. There was no significant difference in any subgroup of numeric descriptive scale response to sublingual nitroglycerin administration in patients with and without a diagnosis of cardiac chest pain.'] |
['Type VIIcollagen, the major component of anchoring fibrils, has been suggested to be involved with tumor cell invasion in a laminin-5-dependent manner in skin squamous cell carcinoma. However, the significance of type VII collagen expression in esophageal squamous cell carcinoma (ESCC) has been unknown to date. Therefore, we examined the expression of type VIIcollagen in ESCC, and confirmed the association between type VIIcollagen expression and clinicopathologic characteristics.', 'We immunohistochemically examined the expression of type VII collagen and laminin-5 gamma2 chain in surgical specimens of primary tumors in 109 patients with ESCC.', 'Positive cytoplasmic expression of type VII collagen was detected in 35%. Significant correlation between the expression of type VII collagen and laminin-5 gamma2 chain expression was observed. In the type VII collagen-negative group, the 5-year survival rate was significantly better than in the positive group. Multivariate analysis indicated that the positive expression of type VII collagen was an independent prognostic factor.'] |
['Systemic low-grade inflammation has repeatedly been associated with depression in old age, but the relationship with apathy is less clear. The present study assessed whether C-reactive protein (CRP) is differentially associated with symptoms of apathy and depression.', 'A population-based cohort study was carried-out. At baseline and after two and four years of follow-up, CRP levels were assessed and symptoms of apathy and depression were measured using the 15-item Geriatric Depression Scale. Logistic regression analysis was used to investigate the cross-sectional and longitudinal associations of CRP with symptoms of apathy and depression.', 'Two thousand forty-seven community-dwelling participants (70-78 years) without a history of cardiovascular disease or stroke were studied. A cross-sectional association was found between CRP and apathy symptoms at three time points (odds ratio (OR) per natural log unit increase in CRP: baseline visit = 1.40, 95% CI = 1.12-1.75; two-year follow-up visit = 1.62, 95% CI = 1.17-2.25; four-year follow-up visit = 1.51, 95% CI = 1.03-2.21). This did not change after adjustment for demographics and depressive symptoms, and was slightly attenuated after adjustment for cardiovascular risk factors. No cross-sectional association was found with depressive symptoms. Baseline CRP did not predict incident apathy or depressive symptoms during four years of follow-up.'] |
['We investigated the effect of carbohydrate availability and euglycaemic hyperinsulinaemia on intramuscular and plasma amino acids in 14 healthy men (age 26.5 +/- 0.9 years, b.m.i. 22.9 +/- 0.5 kg/m2).', 'Insulin was infused (1.5 mU/kg/min) for 240 min both after a carbohydrate depleting exercise and after carbohydrate loading. Muscle samples were taken before and after hyperinsulinaemia. Plasma and intramuscular amino acid concentrations were measured.', 'Insulin-mediated glucose disposal was similar after carbohydrate depletion (65.2 +/- 1.9 micromol/kg/min) and loading (66.9 +/- 2.8 micromol/kg/min). Carbohydrate depletion was associated with decreased alanine and increased branched chain amino acid (BCAA) concentrations in muscle and plasma. Blood lactate was lower after carbohydrate depletion (477 +/- 25 micromol/l) than loading (850 +/- 76 micromol/l, p < 0.001). In carbohydrate depletion, hyperinsulinaemia resulted in a greater increase in intramuscular (from 927 +/- 48 nmol/g muscle to 2029 +/- 104 nmol/g muscle, p < 0.001), than plasma (from 197 +/- 6.7 micromol/l to 267 +/- 11 micromol/l, p < 0.001) alanine. After carbohydrate loading muscle alanine did not rise significantly (from 1546 +/- 112 nmol/g muscle to 1781 +/- 71 nmol/g muscle) whereas plasma alanine decreased (from 339 +/- 26 micromol/l to 272 +/- 13 micromol/l, p < 0.05).'] |
['Herbal medicines played a major role in the treatment of hepatic disorders, and a number of medicinal plants and their compounds were widely used for the treatment of these disorders, and oxidant stress injury was one of the mechanism of liver injury.', "Antioxidant activity of Nelumbo nucifera leaves (NU) extracts was assayed by the methods of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical and ferric reducing antioxidant power (FRAP) in vitro. By intraperitoneal injection carbon tetrachloride (CCl4) to establish acute liver injury model in mice, the levels of Glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT), superoxide dismutase (SOD) and the content of and maleicdialdehyde (MDA) were detected to evaluate hepatoprotective effect of NU using corresponding test kit.", 'EtOAC (NUEA) and n-BuOH extracts (NUBU) of N. nucifera leaves had good scavenging DPPH and ABTS radical activity and ferric reducing antioxidant power in vitro. DPPH radical scavenging activity and ferric reducing antioxidant power of NUEA (IC50= 6.68±0.29 µg/mL, RACT50=1749.82±67.03 µmol/g) and NUBU (IC50= 4.61±0.01 µg/mL, RACT50=1995.27±135.71 µmol/g ) were higher than that of BHT (IC50=8.76±0.20 µg/mL, RACT50=1581.68±97.41 µmol/g) and Dangfeiliganning (IC50=28.06±0.17 µg/mL, RACT50=1028.55±3.28 µmol/g). ABTS radical scavenging activity of NUEA (IC50= 5.32±0.12 µg/mL) and NUBU (IC50= 8.16±0.27 µg/mL) were higher than that of Dangfeiliganning (IC50= 9.76±0.16 µg/mL). Thus, hepatoprotective effect of NUEA and NUBU was evaluated on CCl4-induced acute liver injury mice. The results showed that the levels of GOT and GPT in each treatment group significantly decreased (p<0.001 and p<0.01, p<0.05, respectively) except for the group of NUEA (130.8 mg/kg) (p>0.05). The contents of malondialdehyde (MDA) in liver in groups of NUEA (523 mg/kg), NUBU (840.5 and 420.5 mg/kg, repectively) had significant decrease (p<0.001 and p<0.05, respectively), and the level of SOD in liver for each treatment group could significantly decrease (p<0.001, p<0.05, respectively).'] |
['Previous studies showed that insulin stimulated directly calcitonin (Ct) secretion in the pig thyroid, while dexamethasone stimulated the production of Ct and Ct mRNA in medullary thyroid carcinoma (MTC) cell lines. The objective of this study was to investigate if hyperinsulinemia during the oral glucose tolerance test (GTT) stimulates Ct secretion in normal subjects as well as to examine the relationship between serum cortisol and Ct.', 'In 26 normal subjects (9 men and 17 women) with detectable basal serum Ct, aged 22-70 yr [51.5±14.6 (mean±SD), median 55.5], we measured serum or plasma Ct, cortisol, ACTH, insulin, and blood glucose before (0 min) and at 30, 60, 90, and 120 min after ingestion of 75 g glucose.', 'During GTT mean serum cortisol increased slightly by 9.3% at 30 min, whereas mean serum insulin increased 9.4-fold, reaching a peak value at 60 min. Median serum Ct increased by 51% (p<0.001) in normal subjects (by 27% in men, p=0.004, and by 44% in women, p<0.001) at 30 min and remained significantly higher thereafter (up to 120 min) when compared to median baseline level. Regression analysis showed that basal serum cortisol, but not basal serum insulin, was correlated with basal serum Ct (p=0.01). Peak concentrations of Ct were also correlated with peak concentrations of cortisol at 30 min (p<0.001) but not at later time points. Serum insulin was correlated with serum Ct at the serum insulin peak level (60 min), and at later time points (90 and 120 min) (p=0.001). Multiple and simple regression analysis showed that calcitonin-AUC (Area Under Curve) values correlated with insulin-AUC (p=0.003), and also with cortisol-AUC (p=0.02) values, the standardized effect of insulin-AUC on Calcitonin-AUC being greater than that of cortisol-AUC.'] |
['Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important modulator of the function of the central nervous system (CNS). We have demonstrated that TNF-alpha or Leu-Ile, a TNF-alpha inducer, inhibits methamphetamine-induced rewarding effects and sensitization. In this study, we investigated the effects of TNF-alpha or Leu-Ile on morphine (MOR)-induced rewarding effects and sensitization.', 'Levels of TNF-alpha messenger RNA (mRNA) and protein were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-alpha or Leu-Ile on MOR-induced rewarding effects and sensitization were investigated by conditioned place preference and locomotor activity tests. Extracellular dopamine levels were examined using in vivo microdialysis. Effects of TNF-alpha or Leu-Ile on MOR-induced antinociceptive effect and withdrawal symptoms were examined by hot plate test and naloxone-precipitated withdrawal.', 'Morphine induced TNF-alpha mRNA expression via dopamine and opioid receptors. Posttreatment with TNF-alpha or Leu-Ile attenuated the MOR-induced place preference and sensitization even after their development, as well as pretreatment with TNF-alpha or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced place preference was not observed in TNF-alpha knockout mice. Tumor necrosis factor-alpha or Leu-Ile inhibited the increase in extracellular dopamine levels in the nucleus accumbens induced by repeated MOR treatment.'] |
['The purpose of the present study was to determine the value of virtual reality (VR) training for a multimodality training program of basic laparoscopic surgery.', 'Participants in a two-day multimodality training for laparoscopic surgery used box trainers, live animal training, and cadaveric training on the pulsating organ perfusion (POP) trainer in a structured and standardized training program. The participants were divided into two groups. The VR group (n = 13) also practiced with VR training during the program, whereas the control group (n = 14) did not use VR training. The training modalities were assessed using questionnaires with a five-point Likert scale after the program. Concerning VR training, members of the control group assessed their expectations, whereas the VR group assessed the actual experience of using it. Skills performance was evaluated with five standardized test tasks in a live porcine model before (pre-test) and after (post-test) the training program. Laparoscopic skills were measured by task completion time and a general performance score for each task. Baseline tests were compared with laparoscopic experience of all participants for construct validity of the skills test.', 'The expected benefit from VR training of the control group was higher than the experienced benefit of the VR group. Box and POP training received better ratings from the VR group than from the control group for some purposes. Both groups improved their skill parameters significantly from pre-training to post-training tests [score +17 % (P < 0.01), time -29 % (P < 0.01)]. No significant difference was found between the two groups for laparoscopic skills improvement except for the score in the instrument coordination task. Construct validity of the skills test was significant for both time and score.'] |
['In addition to their well-known role as potent effector cells in patients with allergic disease, mast cells have important immunomodulatory roles regulating tolerance in allograft rejection models. The roles of mast cells in oral tolerance development have not previously been examined.', 'We sought to evaluate the importance of mast cells, IgE-mediated mast cell activation, and histamine receptor 1 or 2 blockade on oral tolerance development in mice.', 'Oral tolerance was assessed in 2 mast cell-deficient murine strains (Kit(W-sh/W-sh) and Kit(W/W-v) mice) and control mice. Mice were fed ovalbumin (OVA) or peanut butter for 1 week and then immunized and boosted with relevant protein antigens. Antibody responses were assessed by using ELISA. The oral antihistamines pyrilamine and ranitidine were administered during tolerance induction to OVA. IgE-mediated mast cell activation was initiated during oral tolerance induction or OVA immunization. OVA-specific regulatory T\xa0cells were assessed in the Peyer patches, mesenteric lymph nodes, and spleens by using flow cytometry after adoptive transfer.', 'Oral tolerance was successfully induced to OVA and peanut butter in mast cell-deficient mice. Kit(W-sh/W-sh) mice had higher proportions of antigen-specific regulatory T cells in the mesenteric lymph nodes than mast cell-containing control mice. However, mast cell reconstitution studies suggested this effect was mast cell independent. Oral antihistamine treatments with pyrilamine or ranitidine did not impair tolerance and neither did IgE-mediated activation.'] |
['Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) has been used to treat EBV-induced posttransplant lymphoproliferative disease (PTLD) in solid-organ recipients. This study defines, in detail, the temporal relationship between adoptive transfer and the clinical response, EBV DNA load, and CTL response to EBV latent and lytic antigens in a patient with a subcutaneous PTLD presentation treated with adoptive transfer of autologous CTL.', 'A heart transplant patient developed multiple subcutaneous PTLD deposits and was treated with a total of six doses (20 x 106 CTL per dose) of cultured autologous polyclonal EBV-specific CTL by adoptive transfer.', 'Complete regression occurred after the sixth CTL dose, and the patient has remained disease-free from 47 weeks to the present (136 weeks). Real-time polymerase chain reaction analysis showed a reduction in viral load after therapy. Enzyme-linked immunospot analysis using defined EBV CTL epitopes showed that the CTL precursor frequency (pCTL) toward a lytic antigen epitope was elevated early in the course of disease but tended to decrease to lower levels after long-term regression of PTLD. The most dramatic result was seen in relation to three latent CTL epitopes studied. Long-term regression of PTLD was characterized by high pCTL toward the latent antigens.'] |
['Although non-alcoholic fatty liver disease (NAFLD) is now a common cause of chronic liver disease, discriminating between simple steatosis and non-alcoholic steatohepatitis (NASH), especially early-stage NASH, remains difficult. We investigated the clinical usefulness of measuring the spleen volume as a marker of early-stage NASH.', 'We evaluated computed tomography (CT) images obtained in 84 patients with histologically diagnosed NAFLD (22 with simple steatosis, 62 with NASH with mild fibrosis [stages 1-2]). We defined the data obtained by the following formula as a spleen-body index (SBI): SBI = maximal CT axial section area of the spleen (cm(2))/body surface area (BSA) (cm(2)) x 10(4). We compared the SBI between patients with simple steatosis and those with NASH with mild fibrosis.', 'The mean SBI of the simple steatosis group was 15.8 +/- 3.9, while that of the NASH with mild fibrosis group was 18.7 +/- 5.7. This difference between the two groups was significant (P = 0.0314). A multiple logistic regression analysis showed that the SBI was significantly correlated with the discrimination of simple steatosis and NASH with mild fibrosis. The area under the receiver-operator curve was 0.661 for distinguishing between simple steatosis and NASH with mild fibrosis (P = 0.026, 95% confidence interval = 0.532-0.789).'] |
['To evaluate whether time to pregnancy (TTP) is associated with neurological condition of 2-year-old children born to subfertile parents.', 'Data collected in a prospective, assessor-blinded follow-up study were used for cross-sectional analyses.', 'Participants were the singletons of the Groningen assisted reproductive technique cohort study: all children were born to subfertile couples (n=209). The active waiting TTP of the couples obtained from fertility charts was recorded in years and months, and was converted to decimal years.', 'The presence of minor neurological dysfunction (MND), assessed with the Hempel examination.', 'MND was present in 16 (7.7%) children. TTP of children with MND (median 4.1, range 1.6-13.2) was significantly longer than that of children without MND (median 2.8, range 0.1-13.3; Mann-Whitney U test p=0.014). Logistic regression analysis on the contribution of TTP to MND resulted in a crude OR of 1.27 (95% CI 1.06 to 1.54). After correction for gestational age, parental age and parental level of education, the association remained statistically significant: OR=1.30 (95% CI 1.05 to 1.61).'] |
['The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity.', 'Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors.', "Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P < .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P < .005) and overall (P < .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P < .03 for disease-free and P < .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age."] |
['Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity.', 'By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1.'] |
['Riata implantable cardioverter-defibrillator leads are prone to failure by conductor externalization and/or electrical dysfunction. The objectives of this study were to determine the predictors of the Riata lead failure, to assess the association of conductor externalization and electrical lead failure, and to analyse the rates of lead failure over time.', "Of 273 implanted Riata leads in our centre, 197 were investigated according to the Riata recall protocol, including electrical measurements by device interrogation and annually fluoroscopy. During a mean follow-up period of 5.6 ± 1.4 years, Riata lead failure was 18.8% (37 of 197) for externalization and 17.3% (34 of 197) for electrical lead failure. Electrical lead failure was correlated with time after implant. Externalization and electrical dysfunction co-existed in only 6 of 197 (3%) patients and were not related (Phi's coefficient -0.013, P = 0.85). During the second annual screening, 145 (73.6%) patients underwent fluoroscopy and 9 patients had novel externalizations resulting in an incidence of 6.72%/patient/year which was higher than expected based on cross-sectional analysis. Besides, there was a significant increase in the extent of externalization (17.65 ± 11.14 mm vs. 21.77 ± 11.95 mm, P = 0.001). In multivariate Cox regression analysis, non-ischaemic cardiomyopathy and impaired LVEF were independent predictors of externalization, and 7 Fr lead was a predictor of electrical lead failure."] |
["To assess the inter-informant reliability, intra-informant reliability and internal consistency of the NEO-FFI as a measure of premorbid personality in patients with Alzheimer's Disease (AD).", 'One hundred and five persons with NINCDS-ADRDA probable AD for the assessment of inter-informant reliability and internal consistency, and 30 for the assessment of intra-informant reliability.', 'Premorbid personality was rated retrospectively by close relatives remembering the patient as he/she had been when aged in his/her forties. One hundred and five AD patients were rated by two separate informants. Thirty AD patients were rated by the same informant on separate occasions one year apart.', 'Inter-informant reliability for the five domain scores of the NEO-FFI was shown to range from fair to good when measured using the single measure Intraclass Correlation Co-efficient (ICC) (0.52-0.64), and to range from good to excellent when measured using the average ICC (0.68-0.78). Intra-informant reliability for four out of the five domains was shown to be excellent when measured using the single ICC (0.81-0.92), and good for the remaining domain (0.72). Intra-informant reliability was found to be excellent for all five domains when measured using the average ICC (0.84-0.96). Internal consistency of the five domains was good.'] |
['Concern about potential harmful effects of early maternal hypothyroidism (MH) on fetal brain development has led to calls for universal screening early in, or even before, pregnancy. However, evidence in humans that adverse effects are irreversible if thyroid hormone replacement is initiated after the first trimester is limited. Severe MH due to thyrotropin (TSH) receptor blocking antibodies (Abs) is associated with profound cognitive delay in the offspring if MH is untreated or inadequately treated; here, we sought to determine the outcome if treatment is given in early pregnancy.', 'We identified three women who had TSH receptor blocking Ab-induced MH during pregnancy and were treated with L-thyroxine (L-T4), starting at 27 weeks, 5 weeks, and the first month of gestation. The corresponding pretreatment serum TSH levels in the two women in whom data were available were 68 and 65 mU/L, falling to 6 mU/L at 25 and 24 weeks of gestation, respectively. The third woman with MH required 0.5 mg of L-T4 to normalize her thyroid hormone levels by 4 months of gestation. Their infants were also treated with L-T4 after neonatal screening that identified congenital hypothyroidism (CH). Neuropsychological tests to assess intelligence, language, memory, and visual-motor performance were administered to these three infants at 5.4 years of age (range 5.1-6.1) and to three sibling controls at 6.8 years (range 9.1-3.0).', 'Children born after MH had average or above average results on all parameters. Comparative scores of the neuropsychological tests in sibling pairs for full-scale intelligence quotient (IQ) and performance IQ were variable; some scores were higher and some were lower in CH children.'] |
['Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor.', 'Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression.', 'After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16.'] |
['Transforming growth factor beta inducible early gene-1 (TIEG-1), a member of the Krüppel-like factor, was identified as a primary response gene for TGF-β. The role of TIEG-1 in skin repair has been mainly addressed in vivo on TIEG-1 null mice model and the mechanism remains unexplored.', 'We investigated the modulation of TIEG-1 expression in normal human skin fibroblasts by either down-expressing or overexpressing the gene. We evaluated reactive oxygen species production and the cell viability of treated cells. The effect of TIEG-1 overexpression was monitored by wound healing assay and immunofluorescence staining of actin fibers organization and alpha-smooth muscle actin (α-SMA). Western blots were carried out to identify the level of expression or phosphorylation of key proteins such as cofilin, Rho GTPases, and p38 mitogen-activated protein kinase (p38 MAPK).', 'TIEG-1 down-regulation had a deleterious effect on the cell viability. It was significantly reduced (65±5%) and exposure to ultraviolet further increased this effect (47±3%). By contrast, cells overexpressing TIEG-1 had a reduced reactive oxygen species production (75%) compared to control and mock-transfected cells. This overexpression also resulted in formation of actin stress fibers and increased α-SMA expression and an enhanced wound healing feature. RhoB GTPase was upregulated and phosphorylation of cofilin and p38 MAPK was observed.'] |
['The present study analyzed the relationship between TP53 codon 72 polymorphisms and the clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel chemotherapy.', 'Three hundred patients with advanced gastric cancer treated with paclitaxel and capecitabine combination chemotherapy were enrolled in the present study. Genomic DNA was extracted from peripheral blood leukocytes and determined using allele specific polymerase chain reaction (AS-PCR). Correlation between TP53 codon 72 polymorphisms and treatment response, gastric cancer survival was analyzed.', 'The Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to capecitabine plus paclitaxel chemotherapy in patients with gastric cancer when compared to the Arg/Arg genotype (30.6 vs. 63.2%, p value 0.000). Multivariate survival analysis also showed that the progression free survival (PFS) and overall survival (OS) for patients with Pro/Pro genotypes of TP53 codon 72 were worse than for those with the Arg/Arg genotype (hazard ratio [HR]\xa0=\xa02.177, p\xa0=\xa00.009; HR\xa0=\xa02.145, p\xa0=\xa00.038, respectively).'] |
['Surgery remains the treatment of choice in patients with potentially resectable lung carcinoma. Both the British Thoracic Society and American Chest Physician guidelines for the selection of patients with lung cancer surgery suggest the use of a shuttle walk test to predict outcome in patients with borderline lung function. The guidelines suggest that if the patient is unable to walk 250 m during a shuttle walk test, they are high risk for surgery. However, there is no published evidence to support this recommendation. Therefore, we undertook a prospective study to examine the relationship between shuttle walk test and surgical outcome in 139 patients undergoing assessment for possible lung cancer surgery.', "The shuttle walk test was performed in 139 potentially resectable patients, recruited over a 2 year period, prior to surgery. One hundred and eleven patients underwent surgery. Outcome of surgery, including duration of hospital stay, complication and mortality rates was recorded. Student's t-test was used to compare the shuttle walk distance in patients with good and poor outcome from surgery.", 'Mean age of patients undergoing surgery was 69 years (42-85). Mean shuttle walk distance was 395 m (145-780), with a mean oxygen desaturation of 4% (0-14) during the test. Sixty nine patients had a good surgical outcome and 34 had a poor outcome. The shuttle walk distance was not statistically different in the two outcome groups.'] |
['Recent evidence suggests trauma involving total body tissue damage increases the acute coagulopathy of trauma (ACOT) by various mechanisms, especially in massive transfusion (MT). Our hypothesis was that MT patients injured by explosion will have a higher international normalization ratio (INR) at admission than MT patients injured by gunshot wound (GSW).', 'A retrospective review was performed on US military injured in Operation Iraqi Freedom/Operation Enduring Freedom from March 2003 to September 2008, who received MT (≥ 10 red blood cells in 24 hours) and had an INR on admission. Two cohorts were created based on mechanism. Admission vital signs, labs, transfusion, and mortality data were compared.', 'Seven hundred fifty-one MT patients were identified. Four hundred fifty patients had admission INR and were injured by either GSW or explosion. Patients demonstrated similar injury severity scale and Glasgow Coma Scale. Patients injured by explosion presented with higher INR, greater base deficit, and more tachycardic than patients injured by GSW. Transfusion of blood products was similar between both groups.'] |
['To investigate the effect of luteolin on methamphetamine (MA)-induced behavioral sensitization and mitogen-activated protein kinase (MAPK) signal transduction pathway activation in mice.', 'Mice received a single dose of MA to induce hyperactivity or repeated intermittent intraperitoneal injections of MA to establish an MA-induced behavioral sensitization mouse model. The effect of luteolin on the development and expression of MA-induced hyperactivity and behavioral sensitization was examined. The expression and activity of ΔFosB and the levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), phosphorylated c-Jun N-terminal kinase (pJNK), and phosphorylated p38 mitogen-activated protein kinase (pp38) in the caudate putamen (CPu) were measured by western blot.', 'Luteolin significantly decreased hyperactivity as well as the development and expression of MA-induced behavioral sensitization in mice. ΔFosB, pERK1/2, and pJNK levels in the CPu were higher in MA-treated mice than in control mice, whereas the pp38 level did not change. Injection of luteolin inhibited the MA-induced increase in ΔFosB, pERK1/2, and pJNK levels, but did not affect the pp38 level.'] |
['Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique.', 'Sixty-nine OSCC patients diagnosed between 1998-2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model.', 'Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p\u2009=\u20090.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent predictor of DSS in OSCC [HR 0.241 (0.078-0.745), p\u2009=\u20090.013].'] |
['Biofuels offer a viable alternative to petroleum-based fuel. However, current methods are not sufficient and the technology required in order to use lignocellulosic biomass as a fermentation substrate faces several challenges. One challenge is the need for a robust fermentative microorganism that can tolerate the inhibitors present during lignocellulosic fermentation. These inhibitors include the furan aldehyde, furfural, which is released as a byproduct of pentose dehydration during the weak acid pretreatment of lignocellulose. In order to survive in the presence of furfural, yeast cells need not only to reduce furfural to the less toxic furan methanol, but also to protect themselves and repair any damage caused by the furfural. Since furfural tolerance in yeast requires a functional pentose phosphate pathway (PPP), and the PPP is associated with reactive oxygen species (ROS) tolerance, we decided to investigate whether or not furfural induces ROS and its related cellular damage in yeast.', 'We demonstrated that furfural induces the accumulation of ROS in Saccharomyces cerevisiae. In addition, furfural was shown to cause cellular damage that is consistent with ROS accumulation in cells which includes damage to mitochondria and vacuole membranes, the actin cytoskeleton and nuclear chromatin. The furfural-induced damage is less severe when yeast are grown in a furfural concentration (25 mM) that allows for eventual growth after an extended lag compared to a concentration of furfural (50 mM) that prevents growth.'] |
['To examine the levels of breast milk neurotrophins 1.5, 3.5, and 6 months of lactation and long chain polyunsaturated fatty acids (LCPUFA) at day 3, 1.5, 2.5, 3.5 and 6 months of lactation in mothers with preeclampsia and compare them with normotensive women. Their associations with growth parameters in children are also examined.', 'Women with preeclampsia (n=101) and normotensive women (n=144) with singleton pregnancies were recruited for this study. Milk samples were collected and anthropometry was recorded at the first 6 months. The LCPUFA composition of milk samples was analyzed by using gas chromatography at all time points and neurotrophins were analyzed at 1.5, 3.5 and 6 months by Emax Immuno Assay System using Promega kits.', 'Milk DHA levels were higher at day 3 (9.5%), and 1.5 (23%) and 3.5 (40%) months in mothers with preeclampsia as compared to controls. Milk nerve growth factor (NGF) levels were lower in preeclampsia group as compared to control group at 1.5 (20%) and 3.5 months (27.7%). Milk brain derived neurotrophic factor (BDNF) levels were lower at 1.5 months (10.5%) in the preeclampsia group as compared to control group.'] |
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