text
stringlengths 1.03k
99.1k
|
|---|
['Systemic inflammatory response syndrome (SIRS) is common after abdominal aortic aneurysm (AAA) repair. The aim of this study was to analyze the impact of a multimodal fast track (FT) regimen on incidence rates of SIRS after elective infrarenal AAA repair.', 'Post hoc analysis of a randomized controlled trial including 99 patients after either traditional (TC) or FT care. Basic FT elements were no bowel preparation, reduced preoperative fasting, patient controlled epidural analgesia, enhanced postoperative feeding and mobilization. The presence of SIRS, organ failure and mortality, length of stay (LOS) on intensive care unit (ICU) were analyzed during the postoperative course.', 'The incidence of SIRS in the FT treatment arm was significantly lower as compared to TC: 28% vs. 50%, P = 0.04. The rate of any organ failure (AOF) and multiple organ failure (MOF) was lower in the FT group: AOF: 16% vs. 36%, P = 0.039; MOF: 2% vs. 12%; P = 0.112. LOS on ICU showed a slight advantage for FT care: 20 hours vs. 32 hours (P = 0.183).'] |
["Tsetse flies are obligatory blood feeders, accessing capillaries by piercing the skin of their hosts with the haustellum to suck blood. However, this behaviour presents a considerable risk as landing flies are exposed to predators as well as the host's own defense reactions such as tail flicking. Achieving a successful blood meal within the shortest time span is therefore at a premium in tsetse, so feeding until replete normally lasts less than a minute. Biting in blood sucking insects is a multi-sensory response involving a range of physical and chemical stimuli. Here we investigated the role of heat and humidity emitted from host skin on the biting responses of Glossina pallidipes, which to our knowledge has not been fully studied in tsetse before.", 'The onset and duration of the biting response of G. pallidipes was recorded by filming movements of its haustellum in response to rapid increases in temperature and/or relative humidity (RH) following exposure of the fly to two airflows. The electrophysiological responses of hygroreceptor cells in wall-pore sensilla on the palps of G. pallidipes to drops in RH were recorded using tungsten electrodes and the ultra-structure of these sensory cells was studied by scanning and transmission electron microscopy.', 'Both latency and proportion of tsetse biting are closely correlated to RH when accompanied by an increase of 13.1°C above ambient temperature but not for an increase of just 0.2°C. Biting persistence, as measured by the number of bites and the time spent biting, also increases with increasing RH accompanied by a 13.1°C increase in air temperature. Neurones in wall-pore sensilla on the palps respond to shifts in RH.'] |
['To investigate the association between elevated body mass index (BMI) and ovarian reserve.', 'Cross-sectional study.', 'Academic institutions.', 'Two hundred ninety women with infertility. Diminished ovarian reserve (DOR) was defined as day 3 FSH>10 IU/L.', 'None.', 'Random serum antimullerian hormone (AMH) levels and number of oocytes retrieved during assisted reproductive technology cycle.', 'Increasing BMI was associated with lower random serum AMH levels in infertile women with DOR but not in women with normal ovarian reserve (NOR). Among women with DOR, mean random serum AMH levels were 33% lower in overweight and obese women compared with women with normal weight. The same association was not true for women with NOR. Out of 290 women evaluated for infertility, 109 women underwent a controlled ovarian hyperstimulation (COH)-IVF cycle. Women with elevated BMI and DOR had lower number of oocytes retrieved compared with women with normal BMI and DOR (6.4±4.3 vs. 9.4±6), an association that was not observed among women with NOR.'] |
['Acute coronary syndromes account for half of all deaths secondary to cardiovascular disease and represent a significant economic burden in the United States. Therefore, assessing hospitalization costs relative to Medicare reimbursement for these patients is important in understanding the impact of these patients on hospitals. We hypothesized that hospitalization costs for acute myocardial infarction patients treated with percutaneous coronary intervention (PCI) were higher than their associated Medicare payments.', "Using the Nationwide Inpatient Sample, we evaluated hospitalization costs for patients treated with PCI from 2001 through 2009 by multiplying hospital charges by the group average cost-to-charge ratio for each patient's hospitalization. Primary end points examined were total hospital costs and trends over time, which were correlated with clinical outcomes and insurance payments. Costs were inflation adjusted with 2009 as the reference year.", 'Median hospitalization costs of PCI increased from $15 889 (interquartile range [IQR] = $12 057-$21 204) in 2001 to $19 349 (IQR = $14 660-$26 282) in 2009. From 2004 to 2009, inflation-adjusted costs for PCI decreased at a rate of 0.3% per year. In 2009, a total of 265,531 patients received PCI for acute myocardial infarction. Of these, 143 654 were <65 years old, and 121 876 were ≥65 years old. Average 2009 Medicare payments ranged from $9303 to $17 500 depending on the Medicare Severity-Diagnosis Related Groups (MS-DRG) billed, leaving hospitals at a loss of anywhere from $4493 to $7940 per patient when comparing costs and reimbursements across all included MS-DRG codes.'] |
['Although it has been reported that the increase in blood pressure improves arterial oxygen saturation (SaO(2)) in children with tetralogy of Fallot, no prospective study has demonstrated that an increase in blood pressure induces an increase in pulmonary blood flow in these patients. The purpose of this study was to see whether a phenylephrine-induced increase in systemic blood pressure increased pulmonary blood flow, resulting in improved arterial oxygenation in tetralogy of Fallot.', 'In 14 consecutive children with tetralogy of Fallot (2-32 months old), transesophageal pulsed Doppler signals of left upper pulmonary venous flow (PVF) velocity were recorded before and four minutes after 10 micro g x kg(-1) of phenylephrine i.v. Simultaneously, arterial blood gas analysis and hemodynamic measurements were performed. The minute distance (MD) was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF.', 'Phenylephrine iv increased mean arterial blood pressure from 54 +/- 8 mmHg to 73 +/- 10 mmHg. This phenylephrine-induced hypertension significantly increased SaO(2) and MD (92.0 +/- 7.5 vs 95.0 +/- 5.0% and 1318 +/- 344 vs 1533 +/- 425 cm x min(-1), respectively). There was a significant correlation (r = 0.72) between the change in MD and the change in SaO(2).'] |
['Human vascular smooth muscle cells (VSMC) prepared by enzyme dispersal have been reported to proliferate more slowly and remain more differentiated than VSMC derived by explant culture. The aim of this study was to investigate whether these differences are attributable to the production of transforming growth factor beta (TGF beta), a major modulator of VSMC properties in culture, by enzyme dispersal, but not explant, cultures.', 'Human aortic VSMC cultures were prepared by enzymatic dissociation of aortic media or by outgrowth of cells from explants derived from the vessel media. Properties, including rate of proliferation and differentiation, of the two different types of culture obtained from 10 donors (age 3-54 years, of either sex) were compared. The role of TGF beta as mediator of these differences was investigated.', 'VSMC from enzyme dispersal cultures proliferated with a long doubling time in 20% fetal calf serum of 68(SEM 2) h, reaching a low saturation density with no "hills and valleys", and the cells were predominantly of stellate morphology. VSMC from explant cultures proliferated with a shorter doubling time of 35(2) h, reached a higher saturation density with "hills and valleys", and showed a spindle shaped morphology. The enzyme dispersed cells, but not the explant cells, released TGF beta into the medium. Addition of exogenous TGF beta to the explant cells extended the doubling time, while addition of a neutralising antibody to the enzyme dispersed cells decreased the doubling time. Tamoxifen, an anti-oestrogenic drug, decreased the rate of proliferation of the explant cells (ED50 = 50 nM; n = 3) but not enzyme dispersed cells by stimulating production of TGF beta. The explant and enzyme dispersal cultures also differed in response to growth factors. The explant cultures stimulated DNA synthesis in response to platelet derived growth factor (PDGF) AA and BB. Enzyme dispersal cultures stimulated DNA synthesis in response to PDGF-BB but response to AA was weaker and also variable.'] |
['Oxidative stress is closely associated with cardiac fibrosis. However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction. This study was aimed to investigate the effect of PEP-1-SOD1 fusion protein on angiotensin II (ANG II)-induced collagen metabolism in rat cardiac myofibroblasts (MCFs).', 'MCFs were pretreated with SOD1 or PEP-1-SOD1 fusion protein for 2\xa0h followed by incubation with ANG II for 24\xa0h. Cell proliferation was measured by Cell Counting Kit-8. Superoxide anion productions were detected by both fluorescent microscopy and Flow Cytometry. MMP-1 and TIMP-1 were determined by ELISA. Intracellular MDA content and SOD activity were examined by commercial assay kits. Protein expression was analyzed by western blotting.', 'PEP-1-SOD1 fusion protein efficiently transduced into MCF, scavenged intracellular O2 (-), decreased intracellular MDA content, increased SOD activity, suppressed ANG II-induced proliferation, reduced expression of TGF-β1, α-SMA, collagen type I and III, restored MMP-1 secretion, and attenuated TIMP-1 secretion.'] |
['Partial Epilepsy with Pericentral Spikes (PEPS) is a novel Mendelian idiopathic epilepsy with evidence of linkage to Chromosome 4p15. Our aim was to identify the causative mutation in this epilepsy syndrome.', 'We re-annotated all 42 genes in the linked chromosomal region and sequenced all genes within the linked interval. All exons, intron-exon boundaries and untranslated regions were sequenced in the original pedigree, and novel changes segregating correctly were subjected to bioinformatic analysis. Quantitative polymerase chain reaction was performed to examine for potential copy number variation (CNV).', '29 previously undescribed variants correctly segregating with the linked haplotype were identified. Bioinformatic analysis demonstrated that six variants were non-synonymous coding sequence polymorphisms, one of which, in Q8IYL2 (Gly400Ala), was found in neither Caucasian (n=243) and ancestry-matched Brazilian (n=180) control samples, nor subjects from the 1000 Genome Project. No gene duplications or deletions were identified in the linked region.'] |
['Homocysteine (Hcy) and inflammatory cytokines have been linked to adverse outcomes in persons with cardiovascular and kidney diseases and recent reports suggest that cytokine-mediated inflammatory infiltrates may be an important contributor to the pathogenesis the aforementioned diseases. Although some reports suggest that Hcy directly influences inflammatory cytokine production, this proposition has not been supported by data from other studies. The objective of the current study was to a) utilize an in vitro cellular model to identify cytokines that may be affected by Hcy and b) examine the role of mitogen activated protein kinase (MAPK) and phosphatidyl inositol 3- (PI3) Kinase in Hcy modulated cytokine production.', 'Primary rat glomerular mesangial cells (MC, passage 8 to 15), isolated by standard sieving methodology, were exposed to Hcy (15, 50 or 100 muM) with L-cysteine (L-Cys; 100 muM) serving as a control. An antibody array was used to identify cytokines that were modulated when MCs were exposed to Hcy. Gene expression was assessed by quantitative RT-PCR, while western blotting analysis was used to assess cellular protein levels in the presence and absence of inhibitors of MAPK and PI3 Kinase. Finally, leukocyte adhesion assay was used to examine the effect of Hcy on leukocyte adhesion to glomerular MCs that were maintained in media without, and with, kinase inhibitors.', 'We identified macrophage inflammatory protein 2 (MIP-2) as a key cytokine that manifested increases in both protein and mRNA following exposure of glomerular MC to pathophysiologic Hcy levels (50 muM). Further analyses revealed that Hcy-induced MIP-2 was dependent on activation of p38 MAPK and PI3 kinase. MIP-2 enhanced leukocyte adhesion to MC and this MIP-2-enhanced leukocyte adhesion was also dependent on activation of p38 MAPK and PI3K. Finally, we demonstrate that leukocyte adhesion to MC is specifically inhibited by anit-MIP2 antibody.'] |
['Little is known about the prevalence of heart failure among very old people, although hospitalisation rates for chronic heart failure are very high. Recently, brain natriuretic peptides have emerged as important diagnostic and prognostic serum markers for congestive heart failure.', 'The main purpose of our study was to determine whether there is a cut-off for NT-proBNP for detecting the echocardiographic features of left ventricular systolic and/or diastolic dysfunction and clinical heart failure among old people living in nursing homes. Secondarily, we investigated the medium-term prognostic power of the neurohormone levels.', 'We screened 101 old people (80% females, aged 84+/-9 years) from two nursing homes. We prospectively evaluated whether we could effectively stratify patients using a combination of (1) restrictive clinical criteria, (2) NT-proBNP measurements (Elecsys System, Roche Diagnostics) and (3) echocardiography for all patients.', 'Forty-two percent of the subjects had left ventricular dysfunction: 11% systolic, 23% diastolic and 8% both systolic and diastolic. The mean NT-proBNP concentration was 2806+/-7028 pg/ml in the 42 patients with left ventricular systolic and/or diastolic dysfunction, compared with 365+/-456 pg/ml in the 59 patients with normal left ventricular function (p<0.01, Z=-4.8 Mann-Whitney U test). The neurohormone proved to be a good predictor of events within 6 months [area under the receiver-operated curve (ROC)=0.79].'] |
["High-grade serous ovarian cancer (HGSOC) that is resistant to platinum-based chemotherapy has a particularly poor prognosis. Response to platinum has both prognostic survival value and dictates secondary treatment strategies. Using transcriptome analysis, we sought to identify differentially expressed genes/pathways based on a tumor's platinum response for discovering novel predictive biomarkers.", 'Seven primary HGSOC tumor samples, representing two extremes of platinum sensitivity/timing of disease recurrence, were analyzed by RNA-Seq, Ingenuity Pathways Analysis (IPA) and Upstream Regulator Analysis (URA), and used to explore differentially expressed genes and prevalent molecular and cellular processes. Progression-free and overall survival (PFS, OS) was estimated using the Kaplan-Meier method in two different sample sets including GEO and TCGA data sets.', 'IPA and URA highlighted an IRF1-driven transcriptional program (P=0.0017; z-score of 3.091) in the platinum sensitive improved PFS group. QRT-PCR analysis of 31 HGSOC samples demonstrated a significant difference in PFS between low and high IRF1 expression groups (P=0.048) and between groups that were platinum sensitive versus not (P=0.016). In a larger validation data set, increased levels of IRF1 were associated with both increased PFS (P=0.043) and OS (P=0.019) and the effect on OS was independent of debulking status (optimal debulking, P=0.025; suboptimal, P=0.041).'] |
['p120-catenin (p120) is an armadillo family protein that binds to the cytoplasmic domain of classical cadherins and prevents cadherin endocytosis. The role of p120 in vascular development is unknown.', 'The purpose of this study is to examine the role of p120 in mammalian vascular development by generating a conditionally mutant mouse lacking endothelial p120 and determining the effects of the knockout on vasculogenesis, angiogenic remodeling, and the regulation of endothelial cadherin levels.', 'A conditional Cre/loxP gene deletion strategy was used to ablate p120 expression, using the Tie2 promoter to drive endothelial Cre recombinase expression. Mice lacking endothelial p120 died embryonically beginning at embryonic day 11.5. Major blood vessels appeared normal at embryonic day 9.5. However, both embryonic and extraembryonic vasculature of mutant animals were disorganized and displayed decreased microvascular density by embryonic day 11.5. Importantly, both vascular endothelial cadherin and N-cadherin levels were significantly reduced in vessels lacking p120. This decrease in cadherin expression was accompanied by reduced pericyte recruitment and hemorrhaging. Furthermore, p120-null cultured endothelial cells exhibited proliferation defects that could be rescued by exogenous expression of vascular endothelial cadherin.'] |
['Neurite outgrowth inhibitor-A (Nogo-A), myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein are three myelin-associated proteins that act as inhibitors to central nervous system regeneration. Neurite outgrowth inhibitor-A imposes the strongest effect on inhibiting axonal regeneration after traumatic brain injury. Alpha-tocopherol, a member of the vitamin E family, is recognized as an active antioxidative substance. Its use has not been well studied in brain injury research, especially in axonal regeneration research.', 'We obtained 99 intact adult male Sprague-Dawley rats (200-250 g) from the Experimental Animal Center of Central South University. We used the modified method of Freeney to generate moderate brain injury in the rats. We injected 600 mg/kg α-tocopherol intraperitoneally daily as traumatic brain injury (TBI) treatment. Then, we performed behavioral tests in the corresponding time point, examined brain tissues after hematoxylin-eosin staining to identify changes in cell morphology, and performed immunohistochemical staining and quantitative real-time polymerase chain reaction to detect the expression of NoGo and Nogo receptor (NgR) in brain tissue.', 'For the Neurological Severity Scores of rats, there were obvious differences among the three groups at the corresponding time points. Standard hematoxylin-eosin staining showed that the brain structure of a sham-operated group of rats was clear, uniform, and compact. A TBI group exhibited hemorrhage, edema, inflammatory cell infiltration, condensed nuclei, and necrosis. We also saw glial cells and fibrous tissue proliferation. The α-tocopherol-treated TBI group had similar but less severe changes than the TBI group. Expression of Nogo-A and NgR increased after TBI compared with the sham-operated group. However, Nogo-A and NgR expression was significantly lower in the α-tocopherol-treated TBI group compared with the TBI group. Similarly, results showed that functional neurological deficits among rats in the α-tocopherol-treated TBI group were less pronounced than in the TBI group (model group).'] |
['The mitotic spindles are among the most successful targets of anti-cancer chemotherapy, and they still hold promise as targets for novel drugs. The anti-mitotic drugs in current clinical use, including taxanes, epothilones, vinca alkaloids, and halichondrins, are all microtubule-targeting agents. Although these drugs are effective for cancer chemotherapy, they have some critical problems; e.g., neurotoxicity caused by damage to neuronal microtubules, as well as innate or acquired drug resistance. To overcome these problems, a great deal of effort has been expended on development of novel anti-mitotics.', "We identified novel microtubule-targeting agents with carbazole and benzohydrazide structures: N'-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-methylbenzohydrazide (code number HND-007) and its related compounds. We investigated their activities against cancer cells using various methods including cell growth assay, immunofluorescence analysis, cell cycle analysis, tubulin polymerization assay, and tumor inhibition assay in nude mice.", 'HND-007 inhibits tubulin polymerization in vitro and blocks microtubule formation and centrosome separation in cancer cells. Consequently, it suppresses the growth of various cancer cell lines, with IC50 values in the range 1.3-4.6μM. In addition, HND-007 can inhibit the growth of taxane-resistant cancer cells that overexpress P-glycoprotein. Finally, HND-007 can inhibit HeLa cell tumor growth in nude mice.'] |
['We and others have reported that experimentally induced short sleep does not affect resting metabolic rate and leads to increased laboratory-measured 24-h energy expenditure. Here, we aimed to determine if sleep timing and/or quality are related to physical activity (PA) levels.', 'Measures of PA via waist actigraphy, sleep diary, and sleep quality questionnaires were collected over a 7-18-day period in 22 adults (mean age\u2009±\u2009standard deviation (SD): 35.8\u2009±\u20094.6 years, and mean body mass index\u2009±\u2009SD: 23.8\u2009±\u20091.1\u2009kg/m(2)) who were on their habitual sleep-wake and activity schedules.', 'During the recording period, mean (±SD) bedtime and wake times were 00:17\u2009±\u20091:07\u2009h (range: 22:02-02:07\u2009h) and 08:20\u2009±\u20091:14\u2009h (range: 06:30-10:11\u2009h), respectively. After controlling for sleep duration, later bedtime, wake time, and midpoint of sleep were associated with less time spent in moderate-to-vigorous PA (p\u2009=\u20090.013, p\u2009=\u20090.005, and p\u2009=\u20090.007, respectively), and increased time in sedentary PA (p\u2009=\u20090.016, p\u2009=\u20090.013, and p\u2009=\u20090.013, respectively).'] |
["Wilson's disease (WD) is an inherited copper metabolism disorder that leads to dysfunction of affected tissues, mostly in the liver and brain. Anti-copper treatment should prevent clinically overt WD in pre-symptomatic patients but this has not been supported by strong evidence. Our aim was to evaluate the long-term effectiveness of treatment in clinically pre-symptomatic patients, with particular emphasis on patient compliance with treatment.", 'Data were analyzed for 87 consecutive patients with no clinical symptoms of WD who were identified between 1957 and 2009 by family screening. All of them since diagnosis were treated with either zinc sulphate (Zn) (66.7%) or D-penicillamine (DPA) (33.3%).', 'During a median follow-up of 12 years (range 3-52), 55 (63%) patients remained without clinical symptoms, 13 (15%) developed neuropsychiatric symptoms and 21 (24%) developed hepatic dysfunction, including five deaths from hepatic failure. Non-compliance for at least three consecutive months was observed in 39 patients, and in 29 cases this extended for more than 12 months. Multivariate analysis showed that the odds of developing symptomatic WD were independently increased by non-compliance (odds ratio 24.0, 95% confidence interval 6.0-99.0). According to Kaplan-Meier analysis patients who were compliant to treatment had a significantly higher likelihood of remaining symptom-free, and their overall survival was similar to the survival rate observed in the general population.'] |
['Both hospital and surgeon volume influence outcomes. With introduction of new technologies, some procedures are now performed less frequently. ERCP has replaced the need for common duct exploration (CDE) in most cases of choledocholithiasis. We explored the secular trends and outcomes of CDE and how they have changed relative to introduction of ERCP.', "The National Hospital Discharge Survey database was analyzed for the years 1979 to 2001. Procedural frequency of ERCP and CDE was determined. Charlson and Elixhauser comorbidity indices were used to characterize patients' disease burden for the years 1993 to 2001. Length of stay, mortality, and complication rates for each procedure were determined.", 'At the beginning of the study period, an estimated 47,000 CDEs were performed annually. These declined to 7,700 per year as ERCP increased to 42,500 procedures per year at the end of the study period. CDE complication rates increased from 3.4% to 17.4% over the same period. Comorbidity analysis for the years 1993 to 2001 revealed that ERCP and CDE patients had equivalent disease burdens. Technical complication rates rose in parallel to the increased overall CDE complication rate.'] |
['One particularly important individual dynamic known to influence the experience of pain is neuroticism, of which little is known about in visceral pain research. Our aim was to study the relationship between neuroticism, psychophysiologic response, and brain processing of visceral pain.', 'Thirty-one healthy volunteers (15 male; age range, 22-38 years) participated in the study. The Eysenck Personality Questionnaire was used to assess neuroticism. Skin conductance level, pain ratings, and functional magnetic resonance imaging data were acquired during anticipation of pain and painful esophageal distention. The effect of neuroticism was assessed using correlation analysis.', 'There was a wide spread of neuroticism scores (range, 0-22) but no influence of neuroticism on skin conductance level and pain tolerance or pain ratings. However, a positive correlation between brain activity and neuroticism during anticipation was found in regions associated with emotional and cognitive pain processing, including the parahippocampus, insula, thalamus, and anterior cingulate cortex. These regions showed a negative correlation with neuroticism during pain (P < .001).'] |
['Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes. Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis. To date, no studies assessing the effect of inadequate folate status on DNA methylation in older women (aged >63 y) have been reported.', 'The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women (aged 60-85 y) to evaluate whether DNA methylation could be used as a functional indicator of folate status.', 'Healthy, postmenopausal women (n = 33) consumed a moderately folate-depleted diet (118 microg folate/d) for 7 wk, followed by 7 wk of folate repletion with 200 or 415 microg/d, each provided as 2 different dietary treatments for a total of 4 treatment groups (n = 30). Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay.', 'Incorporation of [(3)H]methyl groups increased significantly (P: = 0.0025) in response to folate depletion, suggesting undermethylation of DNA. No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values.'] |
['Offspring of women with hypertensive disorders of pregnancy are at increased risk of cardiovascular complications later in life, but the mechanisms underlying these associations are unclear. Our aim was to examine whether adjusting for birth weight and familial adiposity changed the association of hypertensive disorders of pregnancy with offspring blood pressure.', 'Using data from 6343 nine-year-old participants in the Avon Longitudinal Study of Parents and Children, we examined the association between hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) and offspring blood pressure. Both preeclampsia and gestational hypertension were associated with systolic and diastolic blood pressures in the 9-year-old offspring; after adjustment for parental and own adiposity and for other potential confounders, the mean difference in systolic blood pressure was 2.05 mm Hg (95 confidence interval, 0.72 to 3.38) and 2.04 mm Hg (95 confidence interval, 1.42 to 2.67) for preeclampsia and gestational hypertension, respectively, compared with those with no hypertensive disorders of pregnancy. Equivalent results for diastolic blood pressure were 1.00 mm Hg (95 confidence interval, -0.01 to 2.10) and 1.07 mm Hg (95 confidence interval, 0.60 to 1.54). The association of preeclampsia with offspring systolic and diastolic blood pressures attenuated toward the null with further adjustment for birth weight and gestational age, whereas these adjustments did not attenuate the association of gestational hypertension with offspring blood pressure.'] |
['Plant development is exquisitely sensitive to light. Seedlings grown in the dark have a developmentally arrested etiolated phenotype, whereas in the light they develop leaves and complete their life cycle. Arabidopsis de-etiolated 1 (det1) mutants develop like light-grown seedlings even when grown in the dark. DET1 encodes a nuclear protein that appears to act downstream from multiple photoreceptors to regulate morphogenesis and gene expression in response to light. However, its function has remained unknown.', 'We used microarrays to examine defects in transcription in dark-grown det1 seedlings. We found extensive changes in gene expression, including many of the transcriptional responses observed in light-treated wild-type seedlings. We used an epitope-tagging approach to determine the basis of DET1 function. GFP-DET1 rescues the det1 phenotype, is localized to the nucleus, and forms an approximately 350 kDa complex, which is required for full DET1 activity. We affinity-purified the DET1 complex and identified an approximately 120 kDa copurifying protein that is the plant homolog of UV-Damaged DNA Binding Protein 1 (DDB1), a protein implicated in the human disease xeroderma pigmentosa. A null mutation in Arabidopsis DDB1A results in no obvious phenotype on its own, yet it enhances the phenotype of a weak det1 allele.'] |
['Pulmonary function tests predict respiratory complications and mortality after lung resection through thoracotomy. We sought to determine the impact of pulmonary function tests upon complications after thoracoscopic lobectomy.', 'A model for morbidity, including published preoperative risk factors and surgical approach, was developed by multivariable logistic regression. All patients who underwent lobectomy for primary lung cancer between December 1999 and October 2007 with preoperative forced expiratory volume in 1 second (FEV1) or diffusion capacity to carbon monoxide (Dlco) 60% or less predicted were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Pulmonary complications were defined as atelectasis requiring bronchoscopy, pneumonia, reintubation, and tracheostomy.', 'During the study period, 340 patients (median age 67) with Dlco or FEV1 60% or less (mean % predicted FEV1, 55+/-1; mean % predicted Dlco, 61+/-1) underwent lobectomy (173 thoracoscopy, 167 thoracotomy). Operative mortality was 5% (17 patients) and overall morbidity was 48% (164 patients). At least one pulmonary complication occurred in 57 patients (17%). Significant predictors of pulmonary complications by multivariable analysis for all patients included Dlco (odds ratio 1.03, p=0.003), FEV1 (odds ratio 1.04, p=0.003), and thoracotomy as surgical approach (odds ratio 3.46, p=0.0007). When patients were analyzed according to operative approach, Dlco and FEV1 remained significant predictors of pulmonary morbidity for patients undergoing thoracotomy but not thoracoscopy.'] |
['Children with moderate acute malnutrition (MAM) are often treated with fortified blended flours, most commonly a corn-soy blend (CSB). However, recovery rates remain <75%, lower than the rate achieved with peanut paste-based ready-to-use supplementary foods (RUSFs). To bridge this gap, a novel CSB recipe fortified with oil and dry skim milk, "CSB++," has been developed.', 'In this trial we compared CSB++ with 2 RUSF products for the treatment of MAM to test the hypothesis that the recovery rate achieved with CSB++ will not be >5% worse than that achieved with either RUSF.', 'We conducted a prospective, randomized, investigator-blinded, controlled noninferiority trial involving rural Malawian children aged 6-59 mo with MAM. Children received 75 kcal CSB++ · kg(-1) · d(-1), locally produced soy RUSF, or an imported soy/whey RUSF for ≤12 wk.', 'The recovery rate for CSB++ (n = 763 of 888; 85.9%) was similar to that for soy RUSF (795 of 806, 87.7%; risk difference: -1.82%; 95% CI: -4.95%, 1.30%) and soy/whey RUSF (807 of 918, 87.9%; risk difference: -1.99%; 95% CI: -5.10%, 1.13%). On average, children who received CSB++ required 2 d longer to recover, and the rate of weight gain was less than that with either RUSF, although height gain was the same among all 3 foods studied.'] |
['So far, there have been no reports assessing double tract (DT) reconstruction after distal gastrectomy for gastric cancer, which maintains the duodenal passage of food. The aim of this study was to evaluate the clinical results of DT reconstruction compared with Roux-en-Y (RY) and Billroth I (BI) reconstruction following distal gastrectomy.', 'Outcomes following DT (33 patients), RY (38 patients), or BI (47 patients) reconstructions were investigated retrospectively. These outcomes included postoperative esophagogastroscopic findings, the angle of His measured from postoperative esophagogastrography, and the quality of life, determined by the Gastrointestinal Symptom Rating Scale (GSRS) 1 year after surgery.', 'The degree and extent of gastritis was significantly lower in patients who had undergone DT or RY compared with BI reconstruction (P\u2009<\u20090.05). The angle of His was significantly greater in patients who had undergone BI rather than RY or DT reconstruction (P\u2009<\u20090.05) and was significantly greater in patients with reflux esophagitis (P\u2009<\u20090.05). Using the GSRS, patients who underwent DT or RY reconstructions had significantly lower reflux and indigestion than patients who had undergone BI reconstruction. The length of the lesser curvature of the remnant stomach did not differ significantly between the three reconstruction procedures.'] |
['Several nutrients act as phytoestrogens, being anti-adipogenic when consumed with a fat-rich diet. Their effect on a low-fat diet (LFD) background is unknown. We tested soy and genistein effects on adipose tissue in LFD-fed mice and genistein activity in the 3T3-L1 adipogenesis model.', 'C57BL/6 J male mice were fed an 8.5% soy-supplemented LFD (SS-LFD) or a soy-free LFD (SF-LFD) for 147 days. Groups of 3-week-old (pubertal) and 6-week-old (adult) mice on the SF-LFD were also treated with 17ß-estradiol (E2, 5 µg/kg/day) ip or pure genistein (5 mg/kg/day) by gavage for 15 days. Body fat deposition and gene expression profiles were evaluated. E2 and genistein effects on ERα, ERβ and PPARγ transcriptional activities were characterized in ERα- or ERβ-transfected 3T3L1 cells during differentiation, by the use of reporter plasmids.', 'The SS-LFD group increased fat mass compared with the SF-LFD group. Genistein alone increased while E2 decreased fat pads in the 15-day-treated mice. In visceral fat, genistein differentially regulated 13 metabolic pathways compared to E2. PPARγ-controlled genes were downregulated by E2, while they were upregulated by genistein. In 3T3-L1 cells, genistein activated ERβ-driven transcription, differentiation and lipid accumulation, while inhibited ERα-driven transcription, without effects on lipid accumulation. E2 activated both ERs only in preadipocytes. In differentiated untransfected cells, genistein inhibited PPARγ, while activated PPARγ in the presence of ERβ.'] |
['To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent.', 'Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking agents. Patients were divided into 3 groups based on reason for discontinuation of the first: nonresponse, loss of response, or adverse events. The primary outcome was the change from baseline of the disease activity (by DAS28) at 6 months, corrected for the baseline DAS28 score. Secondary outcomes were the change from baseline at 3 months, EULAR response rates, and the percentages of patients who reached a DAS28 score < or = 3.2 at 3 and at 6 months.', 'In total, 49 patients who failed due to nonresponse, 75 due to loss of response, and 73 due to adverse events were included. At 6 months, the change of DAS28 score from baseline did not differ significantly between the groups (-0.6 to -1.3; p > or = 0.173) and similar good and moderate response rates were found (12% to 18%, p > or = 0.523, and 34% to 55%, p > or = 0.078, respectively). The secondary outcomes were also comparable between the 3 groups.'] |
['In the past, traditional Chinese medicine (TCM) drugs (TCD) had in part severe shortcomings regarding quality and safety. The current state of knowledge in this field was evaluated.', 'Expert interviews by using standardized questionnaires, systematic literature research of studies from Germany published in 1998–2013, systematic inquiries to surveillance authorities and information centers for intoxications as well as investigation of certificates of analysis of the TCM granulate ‘Tianwang buxin dan’ from 8 available sources in Germany and analyses of its content of lead, cadmium, and mercury.', 'Current quality and safety risks comprise self-medication, TCM-unexperienced pharmacies, Internet sale and granulates. 11 studies published between 1998 and 2008 evaluated the quality and safety of TCD in Germany. Also in newer studies, the values found for heavy metals, pesticides, and microbiological contaminants of TCD in part exceeded the maximum permissible values. 28 reports of adverse events were made to the Center for Therapy Safety in Chinese Drug Therapy (CTCA) within the years 2004–2012. A definite causality was determined in 2 cases (allergic reaction, reaction of the circulatory system); 7 of the 28 reports had a likely causality. 61 of 104 (59%) certificates of ‘Tianwang buxin dan’ from 8 different sources could be obtained. 45 of 61 certificates (74%) complied with the requirements according to the pharmacy work rules. Shortcomings were, amongst others, lacking analyses (identity, aflatoxines, microbiology, pesticides). Critical values were exceeded neither in the certificates nor in the analyses arranged by us.'] |
['The aim of this study was to investigate the effect of single-nucleotide polymorphisms (SNPs) in the gene encoding the human alpha(2)-Heremans-Schmid glycoprotein (AHSG) on obesity and insulin action in adipocytes.', 'We screened 24 individuals for SNPs in AHSG. Six haplotype-tagging SNPs were genotyped in 188 lean and 176 obese otherwise healthy women for whom common blood chemistry phenotypes were also available. Adipocyte lipolysis and lipogenesis phenotypes were quantified in a subset of 117 lean and 174 obese women.', "The -469T>G SNP, which is located in the 5' region of AHSG, was associated with insulin-mediated inhibition of lipolysis and stimulation of lipogenesis, as well as basal and 8-bromocyclic AMP-stimulated lipolysis. Three AHSG SNPs were associated with circulating levels of cholesterol. None of the six genotyped SNPs or inferred haplotypes were associated with BMI, calculated percent body fat, waist circumference, circulating levels of glucose or insulin, or homeostasis model assessment of insulin resistance, which was used as an estimate of in vivo insulin sensitivity."] |
['Toxoplasma gondii is a highly prevalent protozoan that can infect all warm-blooded animals, including humans. Its definitive hosts are Felidae and its intermediate hosts include various other mammals and birds, including pigs. It is found in the meat of livestock which is a major source of human infection. Hence the control of toxoplasmosis in pigs is important for public health. We previously showed that dextran sulfate (DS), especially DS10 (dextran sulfate MW 10 kDa), is effective against T. gondii infection both in vitro and in mice. In this study, we asked whether DS affects T. gondii infection of pigs, one of the main animal sources of toxoplasmosis transmission to humans.', 'Fourteen-day-old male pigs (n\u2009=\u200910) were infected with T. gondii and then immediately treated with different doses of DS10; clinical, pathological, and immunological analyses were performed 5 days post-infection.', 'DS10 had an inhibitory effect on toxoplasmosis in pigs. Intravenous injection of DS10 prevented the symptoms of toxoplasmosis and reduced the parasite burden and inflammation induced by T. gondii infection. High-dose DS10 (500 μg per head) caused reversible hepatocellular degeneration of the liver; middle-dose DS10 (50 μg per head) was effective against toxoplasmosis in pigs without causing this side effect.'] |
['The purpose of this study was to examine the association of knee injuries with subsequent changes in body mass index and body composition during maturation in young females.', 'A prospective longitudinal study design was employed to evaluate young females active in soccer or basketball (N=862). Participants who completed at least 1-year follow-up to provide consecutive annual measures of BMIZ and %fat were included in the study analysis to determine the effect of knee injuries on the trajectory of these obesity markers in youth.', 'Of the 71 reported knee injuries, 12 (17%) occurred in athletes at the prepubertal stage, 24 (34%) in athletes at the pubertal stage, and 35 (49%) in postpubertal athletes. Controlling for the effects of maturation, female athletes who reported knee injury demonstrated a greater yearly increase in BMIZ (LS means and 95% CI for the injured group=0.039 (-0.012 to 0.089), for the non-injured group=-0.019 (-0.066 to 0.029), and group difference=0.057 (0.005 to 0.11), p=0.03) and in %body fat (LS means and 95% CI for the injured group=1.05 (0.45 to 1.65), for the non-injured group=0.22 (-0.21 to 0.064), and group difference=0.83 (0.21 to 1.45), p=0.009), compared to those without knee injuries. This indicates that the athletes with knee injuries will increase their body mass index percentile by up to 5\u2005units more than someone of the same age without an injury, and in body fat by up to 1.5%, compared to their non-injured peers.'] |
['The degree to which inflammation contributes to the development of posthemorrhagic vasospasm is controversial. In the present study, we investigated the relationship between various inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1alpha, IL-1beta, and IL-6) and the development of experimental vasospasm.', 'Posthemorrhagic vasospasm was produced in the rat femoral artery model. A latex pouch was placed around each femoral artery, and one pouch was injected with autologous blood and the other with saline as an internal control. Animals were killed at various time points (1 h to 16 d) after surgery (blood exposure), and the degree of vasospasm was assessed by image analysis of artery cross sectional area. Levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay, and the ability of a polyclonal antibody against rat IL-6 to inhibit vasospasm was tested.', 'The rat femoral artery model produced a biphasic vasospasm response, with maximal chronic delayed vasospasm occurring at 8 days after hemorrhage. Enzyme-linked immunosorbent assay revealed a significant increase in IL-6 concentrations in blood-exposed arteries relative to saline-exposed arteries at multiple time points (6, 12, 24, and 48 h) after hemorrhage (P < 0.0001). A relative increase in IL-1alpha levels was noted at 24 hours (P < 0.01). IL-1beta levels were similarly elevated in both blood- and saline-exposed arteries, and tumor necrosis factor-alpha levels were not detectable. Administration of a neutralizing polyclonal antibody against rat IL-6 directly into the blood-exposed periarterial pouch at the time of initial surgery resulted in a dose-dependent reduction in the degree of vasospasm compared with vehicle-treated controls at 8 days after hemorrhage (P < 0.05).'] |
['Fatty acid metabolism is influenced by training and diet with exercise training mediating this through activation of nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in skeletal muscle. This study investigated the effect of training and high fat or normal diet on PPARalpha expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks (31.5 h in total), while the other leg (UT) served as control. During the 4 weeks six subjects consumed high fat (FAT) diet and seven subjects maintained a normal (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs before and after training. After the biopsy, one-leg extension exercise was performed in random order with both legs 30 min at 95% of workload max. A training effect was evident as citrate synthase activity increased (P < 0.05) by 15% in the trained, but not the control leg in both groups. During exercise respiratory exchange ratio was lower in FAT (0.86 +/- 0.01, 0.83 +/- 0.01, mean +/- SEM) than CHO (0.96 +/- 0.02, 0.94 +/- 0.03) and in UT than T legs, respectively. The PPARalpha protein (144 +/- 44, 104 +/- 28, 79 +/- 15, 79 +/- 14, % of pre level) and PPARalpha mRNA (69 +/- [2, 2], 78 +/- [7, 6], 92 +/- [22, 18], 106 +/- [21, 18], % of pre level, geometric mean +/- SEM) expression remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T), respectively. After the training and diet CS, HAD, PPARalpha, UCP2, UCP3 and mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both groups and LDHA mRNA was lower (P < 0.05) only in FAT.'] |
['Group B Streptococcus (GBS) is the leading cause of bacterial meningitis in newborn infants. Because GBS is able to invade, survive, and cross the blood-brain barrier, we sought to identify surface-expressed virulence factors that contribute to blood-brain barrier penetration and the pathogenesis of meningitis.', 'Targeted deletion and insertional mutants were generated in different GBS clinical isolates. Wild-type and mutant bacteria were analyzed for their capacity to adhere to and invade human brain microvascular endothelial cells (hBMECs) and to penetrate the blood-brain barrier using our model of hematogenous meningitis.', 'Analysis of a GBS (serotype V) clinical isolate revealed the presence of a surface-anchored serine-rich protein, previously designated serine-rich repeat 1 (Srr-1). GBS Srr-1 is a glycosylated protein with high molecular weight. Deletion of srr1 in NCTC 10/84 resulted in a significant decrease in adherence to and invasion of hBMECs. Additional mutants in other GBS serotypes commonly associated with meningitis showed a similar decrease in hBMEC invasion, compared with parental strains. Finally, in mice, wild-type GBS penetrated the blood-brain barrier and established meningitis more frequently than did the Deltasrr1 mutant strain.'] |
['Several studies have identified relationships between weight loss and adipokine levels; however, none have looked at the combined effect of aerobic exercise training with the consumption of a low- or a high-glycemic diet. We examined the effects of 12 wk of aerobic exercise combined with either a low-glycemic index diet (∼40 U) plus exercise (LoGIX) or a high-glycemic index diet (∼80 U) diet plus exercise (HiGIX) on plasma leptin and adiponectin (total and high molecular weight [HMW]) in 27 older obese adults (age = 65 ± 0.5 yr, body mass index = 34.5 ± 0.7 kg·m).', 'Insulin sensitivity was calculated from an oral glucose tolerance test. Fasting HMW adiponectin and leptin were quantified from plasma samples obtained before the insulin sensitivity index obtained from the oral glucose tolerance test. Glucose and insulin measures were obtained before and every 30 min during the test. Dual-energy x-ray absorptiometry and computerized tomography were used to determine body composition and to quantify subcutaneous and visceral abdominal adiposity, respectively.', 'Fasting leptin was significantly decreased in both groups (LoGIX: preintervention = 33.8 ± 4.7, postintervention = 19.2 ± 4.5; HiGIX: preintervention = 27.9 ± 4.2, postintervention = 11.9 ± 2.2 ng·mL; P = 0.004), and HMW adiponectin was significantly increased (LoGIX: preintervention = 1606.9 ± 34.6, postintervention = 3502.3 ± 57; HiGIX: preintervention = 3704.8 ± 38.1, postintervention = 4284.3 ± 52.8 pg·mL; P = 0.003) after the 12-wk intervention. Total body fat was reduced after both interventions. Visceral fat mass was inversely correlated with HMW adiponectin, whereas subcutaneous fat correlated with leptin.'] |
['To assess the effects of different exercise intensities and antioxidant supplementation on plasma protein modification.', 'Trained men (n = 41) from a homogenous population were randomly assigned to perform cycle ergometer exercise either at 70% or 80% of individual .VO2max. Each intensity group was randomly assigned to receive either juice powder concentrate (JPC 70%, n = 11; JPC 80%, n = 10) or placebo (Plac 70%, n = 10; Plac 80%, n = 10) capsules for 28 wk. Four controlled exercise bouts and blood collections were conducted at baseline and study weeks 4, 16, and 28. Blood samples were drawn before (BE), immediately after (IE), and 30 min (30M) and 30 h (30H) postexercise. These samples were analyzed to estimate concentrations of carbonyl groups on plasma proteins (CP) and the redox state of human serum albumin (HSA).', 'In the Plac group, CP concentrations increased at 80% of .VO2max IE and 30M, returning to preexercise concentrations by 30H (P < 0.05). At both 16 and 28 wk, the Plac groups had significantly higher BE and 30H CP concentrations than the JPC groups (P < 0.05). The reduced fraction of HSA, human mercaptalbumin (HMA), decreased at all four exercise tests at both exercise intensities IE and 30M, returning to preexercise values by 30H (P < 0.05). Supplementation had no influence on HSA.'] |
['Everolimus (RAD001, Afinitor) is an mTORC1 pathway inhibitor, and vatalanib (PTK/ZK) is a pan VEGF-R tyrosine kinase inhibitor (TKI). These two drugs have been shown to have overlapping but also distinct anti-angiogenic effects. Consequently, we investigated the pharmacokinetics (PK) and pharmacodynamics (PD) of their combination in vivo.', 'Murine melanoma B16/BL6 cells were grown orthotopically in BL6/C57 mice by injection into the derma of both ears to create a primary tumour which metastasized rapidly to the cervical lymph nodes. Mice were treated daily p.o. with PTK/ZK (100 mg/kg) or everolimus (1 mg/kg) or their combination, and anti-tumour efficacy (PD) assessed. In the same model, plasma PK of everolimus was measured following single doses of the monotherapy or combination schedules.', 'Two independent experiments showed that combination of everolimus and PTK/ZK caused at least additive increases in anti-tumour activity compared to either monotherapy, without increases in toxicity. Pooling the data to improve the statistical power demonstrated the interactions to be synergistic. PK modelling showed that although PTK/ZK increased everolimus plasma concentrations by about twofold, this PK drug-drug interaction could not account for the increased anti-tumour effect of the combination. Modelling of the PTK/ZK dose-response curve in this model suggested that any effect of everolimus on the PK of PTK/ZK was unlikely to affect efficacy. Measurement of changes in tumour and plasma VEGF levels at the endpoint of therapy confirmed earlier observations of differential effects of these two agents.'] |
["Erectile dysfunction (ED) is a prevalent condition that impacts on both patients and their female partners. ED may therefore be regarded as a shared sexual concern for couples. The current analysis of the Female Experience of Men's Attitudes to Life Events and Sexuality (FEMALES) study data addresses women's perceptions, beliefs, and attitudes concerning their partner's ED, and whether these are associated with the likelihood of the male partner seeking medical advice and utilizing phosphodiesterase type 5 inhibitors.", "The current research sought to explore the association of female partners' perceptions of male partners' ED and male partners' medical consultation and treatment seeking for ED.", "Questionnaires were sent to partners of men who participated in the Men's Attitudes to Life Events and Sexuality (MALES) 2004 study, and who consented to their partner's involvement. A modified version of the questionnaire used in the MALES study was developed for the FEMALES study, reflecting the female partner's perspective.", "A 65-item questionnaire assessing women's perceptions, beliefs, and attitudes regarding various aspects of ED.", "Women's perceptions of the nature and causes of their partner's ED were significantly associated with men's treatment seeking and utilization. Significant associations were observed between women's level of satisfaction with the relationship before ED onset; perceptions of the impact of ED on quality of life; desire to deal with ED; attitudes to ED treatment; and the treatment-seeking behavior of the male partner. Multivariate regression analyses identified a mixture of female and male partner perceptions and attitudes that uniquely accounted for >30% of the variance in men's ED treatment-seeking behavior and treatment utilization."] |
['Sepsis and septic shock are commonly present in the ICU and accompanied by significant morbidity, mortality, and cost. The frequency of secondary adrenal insufficiency in sepsis remains open to debate and a challenge to identify and treat appropriately. Animal models of sepsis using genetic or surgical initiation of adrenal insufficiency resulted in increased mortality, but the mechanisms are still unclear. The present study investigates the impact of adrenal inflammation in septic mice challenged with cecal ligation and puncture.', 'Prospective experimental study.', 'University laboratory.', 'C57BL/6N wild-type mice.', 'Sepsis, induced by cecal ligation and puncture for 24 and 48 hours.', 'Both septic and control mice were carefully monitored (every 30 min) for up to 48 hours and divided into survivors and nonsurvivors. We observed a significant and massive increase of interleukin-6, interleukin-1β, and tumor necrosis factor-α in adrenal protein extracts of nonsurvivors compared with sham animals and survivors. This pattern was partly reflected in liver and lung but not in plasma samples. Notably, a significant increase in nonsurvivors compared with survivors was only found for lung interleukin-6. In line with these findings, we detected a higher degree of leukocyte infiltration and hemorrhage in the adrenal glands of deceased mice. Evaluation of the hypothalamic-pituitary-adrenal axis response in these animals revealed an increase of adrenocorticotropic hormone, which was only partly reflected in the corticosterone level. Notably, using the adrenocorticotropic hormone stimulation test, we found an impaired adrenocorticotropic hormone response, particularly in nonsurvivors, which significantly correlated with the number of infiltrated leukocytes.'] |
['Antibodies to human granulocyte colony-stimulating factor receptor (HuG-CSFR) are widely available and have been used in numerous studies to evaluate the expression of this protein on normal and malignant cells of hematopoietic and nonhematopoietic origin. Spurred by recent studies that demonstrated that two commonly used antibodies against the erythropoietin and thrombopoietin receptors can in fact bind to completely unrelated and more broadly expressed proteins, we screened 27 commercially available monoclonal and polyclonal antibodies with claimed specificity to HuG-CSFR to determine if they are specific to this receptor.', 'Antibodies were evaluated by Western blotting, flow cytometry, and immunohistochemistry using 293T cells engineered to overexpress HuG-CSFR protein, immortalized human hematopoietic cell lines expressing endogenous G-CSFR, and purified human neutrophils.', 'Only two monoclonal antibodies and one polyclonal antibody could be employed using defined Western blotting or flow cytometry protocols to detect G-CSFR protein in cell lysates or on the surface of cells that express G-CSFR messenger RNA with no binding to cells that did not express the gene. None of the antibodies were suitable for immunohistochemistry. Competitive inhibition with soluble G-CSFR extracellular domain and small inhibitory RNA-mediated knock-down of G-CSFR messenger RNA further demonstrated the limited specificity of these antibodies for HuG-CSFR expressed on the cell surface.'] |
['The number of negative lymph nodes (NLNs) can be used for predicting clinical outcomes for patients with esophageal carcinoma as it is believed to reflect the extent of lymphadenectomy. However, when patients are treated with the same surgical procedure, its prognostic value is not clear.', 'We reviewed the records of 332 patients with thoracic esophageal squamous cell carcinoma (ESCC) who underwent three-field lymphadenectomy (3FLND) and had at least 15 lymph nodes removed. We used Kaplan-Meier estimates to compute overall survival (OS), the log-rank tests to assess the equality of survival rates, and Cox regression analyses to evaluate the association between survival and NLN count after adjusting for potential confounders.', 'At a median follow-up interval of 36 months, the median OS was 47 months and the 5-year survival rate was 47.0 %. NLN count was independently associated with OS, and higher numbers of NLNs were linked to better OS (hazard ratio [HR] 0.970; 95 % confidence interval [CI] 0.955-0.986); the effect did not change after we stratified patients into node-negative (HR 0.966; 95 % CI 0.933-1.000) and node-positive (HR 0.973; 95 % CI 0.955-0.991) groups.'] |
["Spermatic cord torsion can lead to testis ischemia (I) and subsequent ischemia-reperfusion (I/R) causing germ cell-specific apoptosis. Previously, we demonstrated that the hypoxia-inducible factor-1 (HIF-1) transcription factor, a key regulator of physiological responses to hypoxia, is abundant in Leydig cells in normoxic and ischemic testes. We hypothesize that testicular HIF-1 activates the expression of antiapoptotic target genes to protect Leydig cells from apoptosis. In silico analysis of testis genes containing a consensus hypoxia response element (HRE, 5'-RCGTG-3') identified myeloid cell leukemia-1 (Mcl-1) as a potential HIF-1 target gene. The purpose of this study was to determine whether HIF-1 shows DNA-binding activity in normoxic and ischemic testes and whether Mcl-1 is a target gene of testicular HIF-1.", 'The testicular HIF-1 DNA-binding capacity was analyzed in vitro using a quantitative enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assays (EMSA). MCL-1 protein expression was evaluated by immunoblot analysis and immunohistochemistry. The binding of testicular HIF-1 to the Mcl-1 gene was examined via chromatin immunoprecipitation (ChIP) analysis.', 'The ELISA and EMSA assays demonstrated that testicular HIF-1 from normoxic and ischemic testes binds DNA equally strongly, suggesting physiological roles for HIF-1 in the normoxic testis, unlike most tissues in which HIF-1 is degraded under normoxic conditions and is only activated by hypoxia. MCL-1 protein was determined to be abundant in both normoxic and ischemic testes and expressed in Leydig cells. In a pattern identical to that of HIF-1 expression, the steady-state levels of MCL-1 were not significantly affected by I or I/R and MCL-1 co-localized with HIF-1α in Leydig cells. Chromatin immunoprecipitation (ChIP) analysis using a HIF-1 antibody revealed sequences enriched for the Mcl-1 promoter.'] |
['Does circuit class therapy result in a greater incidence or severity of shoulder pain compared with individual therapy? Is the incidence influenced by the degree of active shoulder control?', 'Controlled trial with intention-to-treat analysis.', 'Sixty-eight people (6 drop-outs) undergoing inpatient rehabilitation after stroke.', 'Participants received either individual therapy or group circuit class therapy.', 'Incidence of shoulder pain over the previous 24 hours was measured as a yes/no response while severity of shoulder pain was measured using a visual analogue scale at admission, Week 4, and discharge.', 'There was no greater chance of participants receiving circuit class therapy having shoulder pain at Week 4 (OR 0.95, 95% CI 0.32 to 2.80) or discharge (OR 0.38, 95% CI 0.11 to 1.45) than participants receiving individual therapy. Of those participants who reported pain, there was no difference between groups in the severity of pain at Week 4 (mean difference -0.2 cm, 95% CI -3.2 to 2.7) or discharge (mean difference -2.1 cm, 95% CI -4.8 to 0.6). There was a greater chance of participants who had no active shoulder control having shoulder pain at Week 4 (OR 5.8, 95% CI 1.6 to 20.4) and at discharge (OR 3.8, 95% CI 1.0 to 13.9) than participants who had active shoulder control.'] |
['Using the technique of differential hybridization of Atlas Human cDNA expression arrays, we previously reported the isolation of a G protein coupled receptor, CXCR-4, which is overexpressed in glioblastoma multiforme tumor tissue (GMTT) compared to normal brain tissue (NBT).', 'Using gene specific reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization, we studied its expression in a variety of brain and breast tumor tissue samples. To demonstrate the requirement of CXCR-4 in glioblastoma cell proliferation an antisense construct was overexpressed. Glioblastoma cells were also treated with antibodies against CXCR-4 and its ligand, SDFbeta-1.', 'Expression analysis indicated that CXCR-4 is overexpressed in 57% of the primary glioblastoma tissues and in 88% of the glioblastoma cell lines analyzed. Overexpression of CXCR-4 in glioblastoma cell lines enhanced their soft agar colony-forming capability. Expression of anti-sense CXCR-4 in glioblastoma cell lines caused neurite outgrowth and cellular differentiation. Treatment of glioblastoma cell lines with CXCR-4 and SDFbeta-1 specific antibodies caused inhibition of glioblastoma cell proliferation.'] |
['To determine whether pulmonary function decreases as a function of severity of pectus excavatum, and whether reduced function is restrictive or obstructive in nature in a large multicenter study.', 'We evaluated preoperative spirometry data in 310 patients and lung volumes in 218 patients aged 6 to 21 years at 11 North American centers. We modeled the impact of the severity of deformity (based on the Haller index) on pulmonary function.', 'The percentages of patients with abnormal forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow from 25% exhalation to 75% exhalation, and total lung capacity findings increased with increasing Haller index score. Less than 2% of patients demonstrated an obstructive pattern (FEV(1)/FVC <67%), and 14.5% demonstrated a restrictive pattern (FVC and FEV(1) <80% predicted; FEV(1)/FVC >80%). Patients with a Haller index of 7 are >4 times more likely to have an FVC of ≤80% than those with a Haller index of 4, and are also 4 times more likely to exhibit a restrictive pulmonary pattern.'] |
['Hepatoma-derived growth factor (HDGF) is a nucleus-targeted growth factor playing an important role in the development and progression of cancers. This study investigated the correlation of HDGF expression and prognosis in patients with pancreatic ductal carcinoma.', 'HDGF expression in pancreatic cancer cell lines was analyzed by Western blotting. HDGF expression was analyzed by immunohistochemistry for 50 patients with primary ductal carcinoma of the pancreas (33 male and 17 female) ranging in age from 48 to 80 years (median, 65 years) receiving surgical treatment. Cancer cells showing stronger staining than the noncancerous ducts were regarded as positive. Cases showing positive staining in < 90% and > 90% of tumor cells were regarded as HDGF labeling index (LI) levels 1 and 2, respectively. HDGF LI was determined separately for the nucleus and the cytoplasm.', 'Western blotting showed HDGF expression in pancreatic cancer cells similar to that of hepatic cell lines. Twenty-three (46%) and 27 (54%) cases and 22 (44%) and 28 (56%) cases showed HDGF LI levels 1 and 2 for the nucleus and the cytoplasm, respectively. Patients with nuclear HDGF LI level 1 showed a significantly better 5-year survival rate (37.0%) than those with level 2 (6.8%; P = 0.023). No significant difference was observed in the cytoplasmic HDGF LI classification. Multivariate analysis revealed nuclear HDGF LI to be an independent prognosticator.'] |
['There have been many studies on plasma butyrylcholinesterase in liver dysfunction. However, no data is available about acetylcholinesterase in human cirrhosis, although profound changes have been described in cirrhotic rat models.', 'Human serum and liver acetylcholinesterase and its molecular forms were determined enzymatically, after butyrylcholinesterase immunodepletion. The distinct species of acetylcholinesterase, with a distinct C-terminus, were determined by western blotting, and the level of liver transcripts by real-time PCR. Liver acetylcholinesterase was also evaluated by immunocytochemistry.', 'In patients with liver cirrhosis, the activity of plasma acetylcholinesterase (rich in light species), appeared to be apparently unaffected. However, the levels of the soluble readthrough (R) acetylcholinesterase form, an acetylcholinesterase species usually associated with stress and pathology, was increased compared to controls. Human liver acetylcholinesterase activity levels were also unchanged, but protein levels of the acetylcholinesterase-R and other acetylcholinesterase subunit species were increased in the cirrhotic liver. This increase in acetylcholinesterase protein expression in the cirrhotic liver was confirmed by PCR analysis. Immunohistological examination confirmed that acetylcholinesterase immunoreactivity is increased in parenchymal cells of the cirrhotic liver.'] |
['Platelet-activating factor (PAF) is a potent stimulator of eosinophils. Recently, treatment with a protein kinase C (PKC) inhibitor which generally inhibits PKC isoforms has been shown to modulate several eosinophil functions in distinct manners, in that PKC inhibition enhanced CD11b expression and cellular adhesion, but inhibited superoxide generation and degranulation in PAF-stimulated human eosinophils. These results suggested that distinct PKC isoforms were likely to be involved in each eosinophil function induced by PAF. We have therefore investigated whether or not the PKC isoforms involved in PAF-induced CD11b expression and superoxide generation were different.', 'Human eosinophils prepared from healthy volunteers were treated with PKC inhibitors, bis-indolylmaleimide I (BisI; a general PKC inhibitor), myristoylated PKC inhibitor peptide (myr-psiPKC; a PKCalpha, beta and delta inhibitor) and rottlerin (a PKCdelta inhibitor), followed by stimulation with PAF. CD11b expression was determined using flow cytometry and superoxide generation was evaluated using a cytochrome c reduction assay.', 'BisI treatment led to enhancement of PAF-induced CD11b expression, while myr-psiPKC and rottlerin did not. In contrast, PAF-induced superoxide generation was inhibited by treatment with BisI, myr-psiPKC and rottlerin.'] |
['We have previously shown GM3 to positively regulate TNF-alpha expression via a PI3K/Akt pathway in mouse melanoma B16 cells [Wang et al.: Biochem Biophys Res Commun 2007;356:438-443]. The GM3 signal was shown to be located upstream of Akt, but whether it is located upstream of PI3K and which molecule is the effector of PI3K remain to be clarified.', 'We used inhibitors of PI3K and mTOR, and siRNA directed to Rictor, Raptor and Rho-GDP dissociation inhibitor beta (Arhgdib).', 'PI3K inhibitors LY294002 and LY303511 were shown to suppress TNF-alpha expression that is stimulated by GM3 in B16 cells, suggesting that the GM3 signal is located upstream of the PI3K-Akt pathway. Rapamycin suppressed TNF-alpha expression, indicating mTOR to be involved in the pathway. Either siRNA Raptor or siRNA Rictor suppressed TNF-alpha expression, but the latter suppressed the effects of GM3 on TNF-alpha expression and Akt phosphorylation at Ser(473), indicating the GM3 signal to be transduced via Rictor/mTOR and Akt (Ser(473)), leading to TNF-alpha stimulation. Finally, Arhgdib, the tumor suppressor gene whose expression is associated with GM3, was shown to be upstream of TNF-alpha.'] |
['A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNFalpha gene at position G-308A has been associated with increased TNFalpha levels. The relationship between predicted TNFalpha genotype and circulating TNFalpha levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNFalpha G-308A polymorphism, TNFalpha postoperative levels, and clinical outcome after coronary revascularization surgery.', 'We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNFalpha G-308A polymorphism using sequence specific primer-polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA).', 'The prevalence of AA, AG, and GG TNFalpha-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNFalpha (p = 0.009). Higher levels of TNFalpha were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification.'] |
['In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation.', 'In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation.', 'One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5+/-6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4+/-22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence.The 5-year estimated overall survival rate was 62.2% in all patients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors.'] |
['The Wnt pathway plays an important role in embryonic development, and defects in this pathway have been implicated in the tumorigenesis. The Dickkopf 3 (DKK3) is a putative Wnt signaling inhibitor that is frequently inactivated in human cancers. However, the expression of DKK3 in ovarian cancer remains unknown.', 'We investigated the expression of DKK3 in silico using the Digital Differential Display. DKK3 mRNA expression was also analyzed by real-time RT-PCR in ovarian carcinomas and normal ovarian tissues. DKK3 protein expression was determined by immunohistochemistry in the same ovarian carcinomas and normal ovarian tissues.', 'A significantly reduced expression of DKK3 (P < 0.05) was found after comparison of normal ovary- and tumor-derived libraries in the Cancer Genome Anatomy Project (CGAP). DKK3 mRNA expression was reduced in 63% (35 of 56) of tumors compared with normal ovarian samples (P < 0.02). Analysis of 13 matched pairs of ovarian carcinomas and adjacent normal tissues showed significant transcriptional downregulation of DKK3 (>twofold) in 9 paired carcinomas (69%). Loss or weak membranous expression of DKK3 protein was observed in 66% of ovarian cancers (37 of 56) including all tumors with low transcriptional level of DKK3 gene analyzed by real-time PCR.'] |
['The transforming growth factor-β (TGF-β) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential Tgfbr2 gene still maintain normal tissue homeostasis. Here, transgenic mice expressing rtTA from the human keratin 14 (K14) promoter were used to generate an inducible dominant-negative TGF-β receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF-β signaling disruption by Doxycycline treatment in K14+ epithelial stem cells.', 'We showed that in mice lacking TGF-β signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF-β signaling.'] |
['Amyotrophic lateral sclerosis (ALS) is a fatal disease characterised by combined upper and lower motor neuron degeneration. An early and accurate diagnosis is important for patient care and might facilitate the search for a more effective therapy. MRI was used to study the whole cortical mantle, applying an unbiased surface based approach to identify a marker of upper motor neuron involvement in ALS.', 'Surface based cortical morphology analyses were performed on structural, 3T MRI data of 45 patients with ALS and 25 matched healthy controls in a case control study design. These analyses consisted of measuring cortical thickness, surface area and volume. The effects of disease progression were examined by correlating cortical measures with progression rate and by longitudinal measures in 20 patients.', 'Cortical morphology analyses revealed specific thinning in the precentral gyrus, considered the primary motor cortex, in patients with ALS compared with controls (p=6.3×10(-8)). Surface area was reduced in the right inferior parietal region (p=0.049) and volume--the product of cortical thickness and surface area--was reduced in the right precentral gyrus (p=0.031). From these findings, it appears that cortical thickness is superior in detecting the degenerative effects of ALS. Relative cortical thinning in temporal regions was related to faster clinical progression (right inferior temporal gyrus: p=3.3×10(-4)).'] |
['A synchronism exists between the respiratory and cardiac cycles. However, the influence of the inspiratory muscle weakness in chronic obstructive pulmonary disease (COPD) on cardiac autonomic control is unknown. The purpose of the present investigation was to evaluate the influence of respiratory muscle strength on autonomic control in these patients.', 'Ten chronic obstructive pulmonary disease patients (69+/-9 years; FEV(1)/FVC 59+/-12% and FEV(1) 41+/-11% predicted) and nine age-matched healthy volunteers (64+/-5 years) participated in this study. Heart-rate variability (HRV) was obtained at rest and during respiratory sinusal arrhythmia maneuver (RSA-M) by electrocardiograph.', 'Chronic obstructive pulmonary disease patients demonstrated impaired cardiac autonomic modulation at rest and during RSA-M when compared with healthy subjects (p<0.05). Moreover, significant and positive correlations between maximal inspiratory pressure (MIP) and the inspiratory-expiratory difference (DeltaIE) (r = 0.60, p<0.01) were found.'] |
['The brain region that shows reductions in regional cerebral blood flow (rCBF) earliest is the posterior cingulate cortex (PCC), which is thought to have a relationship with cognitive function. We made a hypothesis that the PCC hypoperfusion is a result of cholinergic dysfunction and can be restored by cholinergic enhancement. This present longitudinal study aimed to detect the restoration of PCC rCBF in response to donepezil, an acetylcholine esterase inhibitor.', 'We evaluated rCBF changes in the PCC, precuneus and anterior cingulate cortex using perfusion single-photon emission computed tomography (SPECT), statistical analysis and region of interest analysis, prospectively. We allocated 36 patients with mild AD to either the responder or non-responder groups based on changes in Mini-Mental State Examination scores. The patients were followed up for 18\u2009months.', 'The PCC rCBF significantly increased in responders after 6\u2009months of donepezil therapy. Statistical maps at baseline showed a typical decreased pattern of mild AD and obvious rCBF restoration in the bilateral PCC at 6\u2009months in responders. Changes in Mini-Mental State Examination scores and the AD assessment scale cognitive scores significantly correlated with rCBF changes in the PCC of responders.'] |
['Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD.', 'A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients.', 'A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary non-function (n=4).'] |
['To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea.', 'b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epithelium-derived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining.', 'No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed.'] |
['Ramie (Boehmeria nivea L.), popularly known as "China grass", is one of the oldest crops in China and the second most important fiber crop in terms of area sown. Ramie fiber, extracted from the plant bast, is important in the textile industry. However, the molecular mechanism of ramie fiber development remains unknown.', 'A whole sequencing run was performed on the 454 GS FLX + platform using four separately pooled parts of ramie bast. This generated 1,030,057 reads with an average length of 457 bp. Among the 58,369 unigenes (13,386 contigs and 44,983 isotigs) that were generated through de novo assembly, 780 were differentially expressed. As a result, 13 genes that belong to the cellulose synthase gene family (four), the expansin gene family (three) and the xyloglucan endotransglucosylase/hydrolase (XTH) gene family (six) were up-regulated in the top part of the bast, which was in contrast to the other three parts. The identification of these 13 concurrently up-regulated unigenes indicated that the early stage (represented by the top part of the bast) might be important for the molecular regulation of ramie fiber development. Further analysis indicated that four of the 13 unigenes from the expansin (two) and XTH (two) families shared a coincident expression pattern during the whole growth season, which implied they were more relevant to ramie fiber development (fiber quality, etc.) during the different seasons than the other genes.'] |
['Medical doctors need to be competent to teach patients, their families, students, and the health care team. In a previous study we determined that although the residents attach great importance to have teaching skills, they do not feel prepared to meet this role.', 'To assess self-perception of learning in a formal course of training how to teach for residents.', 'In 2004 we implemented the course "Residents as Clinical Teachers", based on the Stanford Faculty Development Center for Medical Teachers Model (SFDC), for residents of a Medical School. Residents of all the post graduate programs were invited to take the course as an elective during the period 2004-2011. At the end of the course each resident completed the pre/post Seminar Series Housestaff/student Questionnaire; assessing perceptions of learning, expressed in a Likert scale from 1-5.', 'The implementation of the course in 111 residents significantly improved self-perception of general preparation for teaching and improved self-perception of preparedness in each educational category. The personal goals most commonly established by participants were on feedback (52,2%), control of session (44%) and communication of goals (40%). Barriers for teaching most frequently identified were lack of time to do clinical teaching (51,3%) and environmental limitations (16,2%). The main impact of the course reported by residents were acquisition of teaching skills or tools for teaching (39,6%), enhancing of motivation (14%), and a richer understanding of teaching principles (14%).'] |
['It is not fully understood whether intracellular calcium and/or reactive oxygen species (ROS) are involved in nuclear factor-kappaB (NF-kappaB) activation by proinflammatory cytokines. Silymarin exhibits anti-inflammatory and antioxidant effects but the effect of silymarin in human mesangial cells is largely unknown.', 'NF-kappaB binding activity was measured by electrophoretic mobility shift assay. Intracellular calcium was monitored by confocal microscopy using Fluo-3 and intracellular ROS production was determined by flow cytometry. Monocyte chemoattractant protein-1 (MCP-1) expression was measured by Northern blot analysis and ELISA.', 'NF-kappaB was activated within 30 min by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). Intracellular ROS was not produced until 30 min and also antioxidants such as N-acetylcysteine and tiron had no effect on the TNF-alpha- or IL-1beta-induced NF-kappaB activation. Intracellular calcium was increased by TNF-alpha and IL-1beta. Furthermore, a calcium chelator, BAPTA-AM, attenuated the NF-kappaB activation. Silymarin dose-dependently inhibited the TNF-alpha- or IL-1beta-induced NF-kappaB activation and MCP-1 expression. Silymarin also inhibited TNF-alpha-induced intracellular calcium.'] |
['Carotid ultrasound appears to be useful in the assessment of cardiovascular risk. In this study, we have assessed the carotid intima-media thickness (CIMT) in a group of individuals without a history of cardiovascular events.', 'A sample of 431subjects (189 [43.9%] males and 242 [56.1%] females) was obtained from an urban population using a stratified-cluster method in Mashhad stroke and heart atherosclerosis disorder study. None of the subjects had a history of the cardiovascular event. Carotid artery duplex ultrasound was used to determine the CIMT in all subjects, and to identify those with an abnormal value (CIMT [+]; i.e., CIMT ≥ 0.8 mm). Dietary intake of participants was assessed using a questionnaire for 24-h dietary recall. The relationship between anthropometric, biochemical and dietary data and CIMT were assessed.', 'The mean age of subjects was 48.7 ± 8.0 years. Of the 431 patients, 118 (27.4%) were found to be CIMT (+). Of the cardiovascular parameters assessed, only age (odds ratio [OR] [95% confidence interval (CI)], 1.11 [0.56-4.34]; P < 0.01) and male gender (OR [95% CI], 1.14 [0.63-2.23]; P < 0.05) were significant independent predictors of ultrasound defined CIMT. Crude and total energy adjusted intake were not associated with the presence of CIMT (+).'] |
['This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expression of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. A prospective correlation of preoperative platelet TXA2/PGH2 receptor-mediated activity with lower extremity graft patency was sought.', 'Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome measures were primary graft patency rate at 3 months, platelet TXA2/PGH2 receptor activity by equilibrium binding with 125I-BOP, and aggregation to the TXA2-mimetic U46619.', 'Preoperative platelet TXA2/PGH2 receptor density was higher (Bmax, 3100 +/- 1300 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 was lower (26 +/- 6 nmol/L vs 57 +/- 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased receptor density. Early graft thrombosis was more likely in patients with a platelet TXA2/PGH2 receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180).'] |
['Mesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation.', 'A Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCs in vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function.', 'Here, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3.'] |
['Recent guidelines do not support local wound exploration (LWE) or diagnostic peritoneal lavage (DPL) in the evaluation of patients with anterior abdominal stab wounds (AASWs), favoring computed tomography scanning or serial examinations. In patients without immediate indications for laparotomy, we hypothesized that LWE/DPL would identify patients requiring surgery while limiting unnecessary hospital admissions.', 'Patients sustaining penetrating trauma at our level I trauma center over a 3-year period were reviewed.', 'During the study period, 139 patients with AASW followed our LWE/DPL algorithm. Fifty-six patients had LWE without fascial penetration: 46 were discharged immediately, 10 required admission. Fifty-eight patients had fascial penetration on LWE but negative DPL: 37 were observed for less than 24 hours, 19 were observed for more than 24 hours, and 2 patients developed peritonitis requiring exploration. Twenty-five patients had positive LWE/DPL: 13 had therapeutic laparotomy, 12 had nontherapeutic laparotomy.'] |
['Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. Whether WAS mutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.', 'We aimed to identify the degree and pattern of skewing in the variable region of the TCR β-chain (Vβ) in different T-cell subsets from patients with WAS.', 'The TCR repertoire diversity in total peripheral T\xa0cells, sorted CD4(+) and CD8(+) T cells, and CD45RA(+) (CD45RA(+)CD45RO(-) cells) and CD45RO(+) (CD45RA(-)CD45RO(+) cells) CD4(+) and CD8(+) T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementarity-determining region 3 of TCRβ transcripts in CD45RA(+)CD4(+) and CD45RA(+)CD8(+) T cells, CD45RO(+)CD4(+) T cells, CD8(+) terminally differentiated effector memory T (Temra) cells, and naive CD8(+) T cells (CD8(+)CD45RO(-)CCR7(+) cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.', 'The TCR repertoire diversity in CD45RO(+)CD4(+) T cells and CD8(+) Temra cells of patients with WAS was significantly skewed in comparison with that seen in age-matched control subjects.'] |
['Various infectious agents are associated with atherosclerosis. This analysis was performed to investigate relation between seropositivity for anti-Borrelia IgG and carotid atherosclerosis.', 'The cross-sectional Study of Health in Pomerania was conducted in a general community living in a region with endemic Lyme disease. A random sample of 2483 individuals aged 45-79 years was available for the present analysis. Carotid atherosclerosis was sonographically assessed as intima-media thickness of the common carotid artery and as prevalent atherosclerotic plaques in the extracranial carotid arteries. IgG antibodies to Borrelia were determined by ELISA.', 'IgG antibodies to Borrelia were found positive (> 10 IU/mL) in 108 subjects (4.3%). Persons with and without positive anti-Borrelia IgG antibodies differed with respect to carotid intima-media thickness values (0.863 +/- 0.017 mm versus 0.792 +/- 0.004 mm; p < 0.001) and prevalent carotid plaques (odds ratio 2.65, 95% confidence interval 1.53-4.61; p = 0.001), respectively. Seropositivity for anti-Borrelia IgG was also associated with both atherosclerotic endpoints when age, sex and further atherogenic risk factors and confounders were included in multivariable statistical models.'] |
['To investigate the changes in sound localization ability in the horizontal plane after canaloplasty in unilateral congenital aural atresia (CAA) patients.', 'Prospective interventional study.', 'Tertiary referral center.', 'Twenty-eight patients with unilateral CAA were enrolled. All patients had unilateral conductive hearing loss.', 'Canaloplasty.', 'Pure tone audiometry, sound localization test, and the Speech, Spatial, and Quality questionnaire (SSQ) were administered preoperatively, 6 and 12 months postoperatively. For the sound localization test, 8 loudspeakers were positioned in a circle at 45-degree intervals, and patients were instructed to identify the speaker from which sound was coming. Mean correct response rate and mean error degree were calculated for each patient. The correct lateralization rate to the ipsilesional/contralesional stimuli was also calculated.', 'Mean hearing threshold decreased from preoperatively 63.8 to 39.4 dB 12 months after canaloplasty. Mean correct response rate and error degree at preoperative evaluation were 26.0% and 60.7 degrees, respectively, and these were respectively improved to 58.5% and 27.8 degrees postoperatively. Respective mean correct lateralization rate to ipsilesional stimuli after canaloplasty improved from 20.6% to 84.0%, and that to contralesional stimuli slightly improved from 93.8% to 98.8%. Patients with good postoperative hearing (<40 dBHL) showed better sound localization results. In addition, self-assessment scores of spatial domain in the SSQ questionnaire were significantly improved after the operation.'] |
['Adenosine is a potent vasodilator of vascular smooth muscle. Endothelium-derived nitric oxide (NO) elicits vasodilation. We have previously reported that adenosine stimulates the production of NO from porcine carotid arterial endothelial cells (PCAEC) via a receptor-mediated mechanism. This study was to determine whether adenosine also enhances NO production from human arterial endothelium and to define the involvement of adenosine A1 and A2 receptors.', 'Human iliac arterial endothelial cells (HIAEC) and PCAEC were harvested and cultured in dishes. NO production was evaluated with a NO electrode sensor which measured continuously real-time NO production.', 'NO content of the medium bathing HIAEC and PCAEC was significantly increased with adenosine (100 micromol/L). Ethylcarboxamidoadenosine (NECA), a nonselective adenosine receptor agonist, and carboxyethyl-phenethylamino-ethylcarboxamidoadenosine (CGS-21680), a selective adenosine A2a receptor agonist, increased NO production by HIAEC and PCAEC with respective EC50 values of 3.32 and 6.96 nmol/L for NECA and 30.97 and 29.47 nmol/L for CGS-21680. Chlorofuryl-triazolo-quinazolinamine (CGS-15943; 1 micromol/L), an adenosine A1 and A2 receptor antagonist, and aminofuryltriazolotriazinyl-aminoethylphenol (ZM-241385; 1 micromol/L), a selective adenosine A2a receptor antagonist, inhibited the effect of CGS-21680. Chlorocyclopentyl-adenosine (CCPA; 1 micromol/L), an adenosine A1 receptor agonist, significantly depressed NO production by both HIAEC and PCAEC: This effect was inhibited by cyclopentyl-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist.'] |
['The aim was to identify predictors of outcome in patients with localized prostate cancer treated with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT).', 'A total of 448 patients with prostate cancer received EBRT alone (n = 361, group 1) or ADT followed by EBRT (n = 87, group 2). In group 2, ADT was initiated 3 months before EBRT. After baseline prostate-specific antigen (PSA) determination (PSA(preRT)), PSA was assessed during the 6th week of the EBRT course (PSA(6wRT)) in group 1. In group 2, PSA was measured again 3 months after the start of ADT, before EBRT (PSA(ADT-preRT)).', 'In group 1, median PSA(6wRT)/PSA(preRT) was 0.72 and median prostate-specific antigen velocity (PSAV) was -1.5 ng/ml/month. In the multivariate analysis, prognostic groups and PSA(6wRT)/PSA(preRT) (or PSAV) independently predicted biochemical failure (BF), clinical failure (CF), and prostate cancer-specific survival. In group 2, the median PSA(ADT-preRT) was 1.3 ng/ml. In the high-risk group, an undetectable PSA(ADT-preRT) (< or =0.2 ng/ml) predicted BF (P < 0.01) and CF (P = 0.007).'] |
['Propionibacterium acnes, a ubiquitous skin bacterium, stimulates keratinocytes to produce a number of proinflammatory cytokines and may contribute to inflammatory acne. The aim of the study was to investigate whether P. acnes-induced proinflammatory cytokine release is mediated by P. acnes-induced activation of p38 mitogen-activated protein kinase (p38 MAPK or p38) in human keratinocytes.', 'Immunohistochemistry was used to evaluate p38 phosphorylation in human skin samples with or without acne. Primary human keratinocytes and epidermal skin equivalents were exposed to viable P. acnes. Phosphorylation of MAPKs without or with p38 inhibitors was examined by Western blot and cytokine secretion was detected by Enzyme-Linked Immunosorbent Assay (ELISA).', 'Increased levels of phospho-p38 were observed in human acne lesions, predominantly in follicular and perifollicular keratinocytes. Exposure of cultured human keratinocytes to viable P. acnes resulted in phosphorylation of multiple members of the MAPK family, including rapid and transient activation of p38 and extracellular signal-related kinase (ERK1/2) and relatively slow but sustained activation of c-Jun N-terminal kinases (JNK1/2). Viable P. acnes induced the secretion of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and IL-8 from human keratinocytes. The phosphorylation of p38 (phospho-p38) and the secretion of cytokines induced by P. acnes in cultured keratinocytes were inhibited by SB203580, a p38α/β inhibitor. Furthermore, SCIO-469, a selective inhibitor of p38α, showed similar effects in cultured keratinocytes. Topical treatment of SCIO-469 inhibited the P. acnes-induced phospho-p38 and cytokine secretion in human epidermal equivalents.'] |
['The functional consequences of vascular remodeling in rat aorta allografts were studied at different times after transplantation (Tx).', 'At days 1, 3, 7, 14, 28, and 56 after Tx, rat aorta allografts (Dark Agouti [DA]-to-Lewis) were mounted as isolated organs, and their contractile properties tested with phenylephrine, KCl, or endothelin-1. Controls were native DA-aortae and DA-syngeneic grafts. Changes in alpha smooth muscle actin and morphology were assessed by immunoblotting and histology.', 'PostTx syngeneic grafts presented similar functional and morphological properties to native aortae. In allografts, no morphological changes was detected at day 7 after Tx, but phenylephrine-induced vasoconstriction was reduced by 60%. Signs of medial smooth muscle cell (SMC) loss and adventitial inflammation were observed at day 14 after Tx, without neointima formation. A complete loss of contractile property was observed at day 28 after Tx in association with a 75% decrease in alpha-SMC actin, severe adventitial inflammation, and reduced medial cellularity. At this time, neointima was restricted to both edges of allografts. At day 56 after Tx, allografts were also not functional and exhibited neointima on their entire length. All these changes were prevented by treating recipients with cyclosporine (7.5 mg/kg/day).'] |
['Hepatotoxicity is an important side effect of thiopurine analog treatment for inflammatory bowel disease. A variety of histopathologic findings have been observed in patients with inflammatory bowel disease with thiopurine-induced hepatotoxicity, including nodular regenerative hyperplasia, vascular injury, and cholestasis.', 'To describe the histologic features shared by 3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease.', "We identified 3 patients with inflammatory bowel disease who developed hepatotoxicity due to 6-mercaptopurine from the educational files of the Department of Pathology at Massachusetts General Hospital (Boston). Histology slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with diastase digestion, and iron stains) and patients' medical records were reviewed retrospectively.", 'All 3 patients were receiving 6-mercaptopurine monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and presented with elevated aminotransferase levels. Biopsies from all 3 cases exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid-laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment, as well as centrilobular steatosis. Aminotransferase levels trended downward and either normalized or remained at borderline elevated levels after 6-mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients).'] |
['Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned.', 'We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study.'] |
['Information needs in cancer patients are high but often not fulfilled. This study aimed to examine the level of perceived information, information satisfaction, and unmet needs in a large sample of cancer patients. Further, we explored associations with emotional distress and quality of life accounting for gender.', 'In a multicenter, cross-sectional study in Germany, 4020 cancer patients (mean age 58 years, 51 % women) were evaluated. We obtained self-reports of information level, information satisfaction, and unmet needs, measured depressive symptoms with the Patient Health Questionnaire (PHQ-9), symptoms of anxiety with the Generalized Anxiety Disorder Scale (GAD-7), and health-related quality of life with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).', 'Seventy-two to 88 % of participants reported to be well informed regarding various aspects of their disease, except of psychological support (38 %). However, unmet information needs were also prevalent in 36 to 48 %. Gender differences found were generally small. Although men felt less informed about psychological support, they expressed fewer needs for further information regarding this topic. Irrespective of gender, patients who were less satisfied with information received and had more unmet needs reported more anxiety, depression, and lower quality of life. Up to three quarters of those classified as most severely distressed reported unmet needs for information about psychological support.'] |
['Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.', 'We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.'] |
['Liver regeneration after massive hepatectomy or living donor liver transplantation is critical. The apelin-APJ system is involved in the regulation of cardiovascular function, inflammation, fluid homeostasis, the adipo-insular axis, and angiogenesis, but its function in liver regeneration remains unclear.', 'We investigated the impact of pharmacologic blockade of the apelin-APJ system, using the specific APJ antagonist F13A on liver regeneration after hepatectomy in mice.', 'F13A-treated mice had significantly higher serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 than control mice, due to F13A-promoted activation of Kupffer cells. Compared with untreated mice, F13A enhanced the signal transducer and activator of transcription 3 and mitogen-activated protein kinase pathways, stimulated cell-cycle progression, and promoted hepatocyte proliferation and liver regeneration without inducing apoptosis or inflammation in regenerating livers. In vitro, Kupffer cells expressed APJ and were activated directly by F13A treatment, releasing TNF-α and IL-6. Moreover, F13A-treated mice had a higher survival rate than untreated mice in the extended hepatectomy model.'] |
['The understanding of RNA structure is a key feature toward the comprehension of RNA functions and mechanisms of action. In particular, non-coding RNAs are thought to exert their functions by specific secondary structures, but an efficient annotation on a large scale of these structures is still missing.', "By using a novel high-throughput method, named chemical inference of RNA structures, CIRS-seq, that uses dimethyl sulfate, and N-cyclohexyl- N'-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate to modify RNA residues in single-stranded conformation within native deproteinized RNA secondary structures, we investigate the structural features of mouse embryonic stem cell transcripts. Our analysis reveals an unexpected higher structuring of the 5′ and 3′ untranslated regions compared to the coding regions, a reduced structuring at the Kozak sequence and stop codon, and a three-nucleotide periodicity across the coding region of messenger RNAs. We also observe that ncRNAs exhibit a higher degree of structuring with respect to protein coding transcripts. Moreover, we find that the Lin28a binding protein binds selectively to RNA motifs with a strong preference toward a single stranded conformation."] |
['Hematopoietic stem cells (HSC) have traditionally been frozen using the cryoprotectant DMSO in dextran-40, saline or albumin. However, the process of freezing and thawing results in loss of HSC numbers and/or function.', 'This study investigated the use of CryoStor for the freezing of HSC from cord blood (CB). CB donations (n = 30) were collected under an Institutional Ethics Committee-approved protocol, volume reduced and frozen using three different methods of cryoprotection. Aliquots were frozen with either 10% DMSO in dextran-40, 10% DMSO in CryoStor or 5% DMSO in CryoStor. Prior to freezing samples were separated for nucleated cell (NC) and CD34+ counts and assessment of CD34+ viability. Aliquots were frozen and kept in vapor phase nitrogen for a minimum of 72 h. Vials were rapidly thawed at 37 degrees C and tested for NC and CD34+ counts and CD34+ viability and colony-forming unit (CFU) assay.', 'Cells frozen with CryoStor in 10% DMSO had significantly improved NC (P < 0.001), CD34+ recovery, viable CD34+ (P < 0.001) and CFU numbers (P < 0.001) compared with dextran in 10% DMSO. CryoStor in 5% DMSO resulted in significantly improved NC (P < 0.001) and CFU (P < 0.001).'] |
['Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.(1) The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.(2) The objective of this study was to determine the incidence of and predictors for PGD.', 'A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine > or = 0.07 microg/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group. (2) The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (> or = 4.5 hours) were independent predictors of PGD.'] |
['The inflammatory insult associated with cardiopulmonary bypass (CPB) continues to result in morbidity for neonates undergoing complex repair of congenital cardiac defects. Complement and contact activation are important mediating processes involved in this injury. Complement factor 1 esterase inhibitor (C1-inh), a natural inhibitor of complement, kallikrein, and coagulation pathways, may be decreased in children undergoing cardiac operations requiring CPB. We tested the hypothesis that C1-inh supplementation will ameliorate the cardiac and pulmonary dysfunction in a model of neonatal CPB.', 'Fifty-two neonatal pigs were randomly assigned to receive 0 IU (n = 22), 500 IU (n = 15), 1,000 IU (n = 8), or 1,500 IU (n = 7) of C1-inh. Doses were delivered 5 minutes before starting 90 minutes of normothermic CPB. Pulmonary and cardiovascular measures were taken before and 5, 30, and 60 minutes after CPB.', 'Five animals did not survive CPB. The C1-inh concentration post-CPB increased monotonically with increasing dose (p < 0.001). Weight gain was significantly less in the 1,500 IU group (0.24 +/- 0.10 kg versus 0.38 +/- 0.09 kg, p = 0.001). Dynamic compliance increased with C1-inh dose from 0 to 500 IU by 23% +/- 4% (p < 0.001), but the increase leveled off at the higher doses. Alveolar-arterial O2 gradient decreased with C1-inh dose (p = 0.009). Time derivative of left ventricular pressure (dP/dt(max)) increased significantly with increasing dose (p = 0.016). At the highest dose of C1-inh, the time constant of isovolumic relaxation was increased (p = 0.018).'] |
['To investigate the effect of matrix metalloproteinase (MMP) inhibition on fibroblast-mediated matrix contraction and production.', "Free-floating fibroblast-populated type I collagen lattices were prepared with human Tenon's capsule fibroblasts. Lattice areas were photographed and digitally analyzed to indicate the degree of lattice contraction. Quantitative competitive reverse transcription-polymerase chain reaction (QCRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to quantify mRNA and protein respectively for MMP-1, -2, and -3 by fibroblasts during lattice contraction. Gelatin zymography demonstrated activity of MMPs released into the conditioned medium of contracting lattices. Concentrations of the broad-spectrum MMP inhibitors ilomastat, CellTech (Slough, UK), and BB-94 were added to the contracting fibroblast-populated collagen lattices. Secreted C-terminal propeptide of type I collagen was measured in conditioned medium of contracting lattices by ELISA. Fibroblast proliferation in the presence of concentrations of ilomastat was measured by using the reagent water-soluble tetrazolium-1 (WST-1).", "During contraction of type I collagen lattices, Tenon's capsule fibroblasts expressed MMP-1, -2, and -3 mRNA and protein. Zymography demonstrated the release of four gelatinolytic species into the conditioned medium of contracting lattices (57, 72, 91, and 100 kDa). Inclusion of MMP inhibitors in the zymogram-developing buffer reduced the proteolytic activity of the detected bands. MMP inhibition (1-100 microM) significantly reduced fibroblast-mediated collagen lattice contraction (P < 0.05), and this effect was found to be reversible. Ilomastat also significantly inhibited production of collagen in a dose-dependent manner (P < 0.05). No effect on fibroblast proliferation was found in the presence of ilomastat."] |
['Activation of the small GTPase, Rac, requires post-translational modification by isoprenylation. Statins interfere with this process by blocking the synthesis of isoprenoid intermediates. The protein kinase Akt is a multifunctional regulator of cell behavior that has been linked to Rac activation. We have shown that lipopolysaccharide (LPS) stimulation leads to Rac activation in THP-1 cells. Therefore, we hypothesized that LPS stimulation would also activate Akt, a downstream effector of Rac, and that this may be blocked by statin pretreatment.', 'THP-1 cells were maintained in 1% fetal calf serum with or without 20 microM simvastatin for 24 h, followed by LPS stimulation for increasing time. Cytoskeletal changes were observed using Alexa-Phalloidin. Akt was immunoprecipitated from total cell lysate. Activated Akt was detected by immunoblotting with a phospho-Akt antibody and was quantified by image densitometry.', 'LPS stimulation of THP-1 cells results in membrane ruffling and cell polarization. Furthermore, LPS increased Akt activation in THP-1 cells when compared with the nonstimulated controls. Akt phosphorylation peaked after 15 min of LPS stimulation and was suppressed by pretreatment with simvastatin.'] |
['Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs), which participate in tumor invasion, therapeutic resistance, and tumor relapse leading to poor outcome and limited therapeutic options. Histone deacetylatase sirtuin 1 (SIRT1) has been shown to be up-regulated in human cancers; however, its role in liver CSCs is unknown. In this study, we explored the biological functions of SIRT1 in liver CSCs. Our data show that SIRT1 is highly expressed in liver CSCs and decreases during differentiation. In addition, high levels of SIRT1 predict a decreased probability of survival in patients with HCC. SIRT1 is responsible for the maintenance of self-renewal and tumorigenicity of liver CSCs, and overexpression of exogenous SIRT1 can restore self-renewal of non-CSCs. We demonstrated that SOX2 is a main downstream regulator of SIRT1-mediated self-renewal and tumorigenicity potential of liver CSCs. Mechanistically, SIRT1 regulates transcription of the SOX2 gene by way of chromatin-based epigenetic changes, which are dependent on DNA methylation. This effect is achieved by alternation of histone modification and interaction with DNA methyltransferase 3A, resulting in hypermethylation of SOX2 promoter. Furthermore, we demonstrated that insulin growth factor signaling plays an important role in maintaining SIRT1 expression through increased SIRT1 protein stability.'] |
['The simultaneous rise in the prevalence of asthma and obesity in the world, have demonstrated the importance of the development of treatment strategies. The purpose of this study was to evaluate the short- and long-term results of interdisciplinary therapy on inflammatory biomarkers and lung function in asthmatics obese adolescents.', 'Seventy-six post-pubertal obese adolescents were recruited, including 50 non-asthmatics [body mass index (BMI), 36 ± 5 kg/m(2) ) and 26 asthmatics (BMI, 39 ± 4 kg/m(2) ). Body composition was measured by plethysmography, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin, leptin, and C-reactive protein (CRP) were analyzed. Asthma and lung function were evaluated according to the American Thoracic Society criteria. Patients were submitted to 1-year weight loss interdisciplinary intervention consisting of medical, nutritional, exercise, and psychological therapy.', 'After interdisciplinary intervention, the lung function and pro/anti-inflammatory adipokines improved significantly in both groups. Most importantly, there was an increase in adiponectin [4 (1.86-12.9) to 5.1 (2.48-16)], a reduction in CRP [2,073 (385-9,174) to 1,538 (205-7,083)] and leptin concentrations [59 (29-69) to 33 (9-49)] in the asthmatics patients. Furthermore, it was observed a reduction in asthma severity after treatment. In addition, Δ adiponectin was an independent factor to improve lung function after therapy in both groups.'] |
['A total cavopulmonary connection (TCPC) is a widely performed surgical procedure for Fontan candidates. High-risk candidates who have undergone the bidirectional Glenn procedure (BDG) before TCPC have shown good results. The exact mechanism of this procedure, however, is still poorly understood. We hypothesized that a volume reduction with BDG improved ventricular contractility, thereby optimizing mechanical efficiency after TCPC.', 'We measured percent normal systemic ventricular end-diastolic volume (%N-EDV), contractility (end-systolic elastance; E(es)), afterload (effective arterial elastance; E(a)), and mechanical efficiency (ventriculoarterial coupling; E(a)/E(es)) on the basis of the cardiac catheterization data before and after TCPC. Eighteen patients who underwent staged TCPC after BDG (staged group) were compared with 29 patients who underwent primary TCPC (primary group). E(es) and E(a) were approximated as follows: E(es)=mean arterial pressure/minimal ventricular volume, and E(a)=maximal ventricular pressure/(maximal ventricular volume-minimal ventricular volume), and E(a)/E(es) was then calculated. The ventricular volume was normalized with the body surface area. A canine experimental model with conductance catheter was used to validate the accuracy of this approximation of E(es) and E(a). %N-EDV decreased after TCPC in both groups. In the staged group, a smaller ventricular volume resulted in better contractility (E(es)). Although afterload (E(a)) increased in both groups, the increment of E(a) was smaller in the staged group. These changes resulted in an improvement of E(a)/E(es) in the staged group, whereas E(a)/E(es) increased in the primary group.'] |
['The epidermal growth factor (EGF) stimulates rapid tyrosine phosphorylation of the EGF receptor (EGFR). This event precedes signaling from both the plasma membrane and from endosomes, and it is essential for recruitment of a ubiquitin ligase, CBL, that sorts activated receptors to endosomes and degradation. Because hyperphosphorylation of EGFR is involved in oncogenic pathways, we performed an unbiased screen of small interfering RNA (siRNA) oligonucleotides targeting all human tyrosine phosphatases.', 'We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex. DEP-1 silencing enhanced tyrosine phosphorylation of endosomal EGFRs and, accordingly, increased cell proliferation. In line with functional interactions, EGFR and DEP-1 form physical associations, and EGFR phosphorylates a substrate-trapping mutant of DEP-1. Interestingly, the interactions of DEP-1 and EGFR are followed by physical segregation: whereas EGFR undergoes endocytosis, DEP-1 remains confined to the cell surface.'] |
['The objective of this study was to evaluate the exercise capacity of subjects given an autologous transfusion or a polymerized bovine hemoglobin solution to define the pharmacodynamics and pharmacokinetics of a new hemoglobin-based oxygen carrier (HBOC-201).', "Six normal healthy male subjects (ages 25 to 45 years) participated in this randomized, single-blind, two-way crossover study, which took place at Upjohn Research Clinics in Kalamazoo, Mich. A radial artery catheter was inserted in each subject before serial cardiac output and pulmonary function tests and phlebotomy of 15% blood volume (750 ml plus another 250 ml for study laboratories yields 1000 ml, or about 150 gm human hemoglobin). This was followed by isovolemic hemodilution with Ringer's lactate plus an autologous blood transfusion (or HBOC-201) and 1 week later 45 gm bovine hemoglobin of HBOC-201 (or autologous transfusion). Bicycle exercise stress tests to anaerobic threshold (approximately 65% of predicted maximum aerobic capacity) were done before phlebotomy and at approximately 45 minutes after the autologous transfusion or HBOC-201 infusion.", 'Subjects had similar exercise and diffusion capacity but lower lactate levels (for up to 24 hours) during HBOC-201 (which paralleled plasma HBOC-201 levels) than during autologous transfusion periods. Oxygen use (uptake) and carbon dioxide production at rest were greater during the HBOC-201 infusion than during the autologous transfusion period. The half-life of HBOC-201 was about 23 hours.'] |
['The relationship between somatic and psychiatric comorbidity in patients with somatic diseases and diverse outcome variables like mortality, costs, and duration of treatment is often examined and confirmed. In the last years, quality of life (QoL) as another important outcome variable received more attention.', 'The present review comprises a summary of associations between comorbidity and QoL in patients with somatic diseases. For this reason a search for somatic diseases was performed, including metabolic, respiratory tract, musculoskeletal, cardiovascular, cancer, digestive system, and general somatic diseases. Four hundred eighty-one studies were found, of which 45 fulfilled the inclusion criteria.', 'Overall, there are mostly significant negative correlations between comorbidity and QoL. Predominantly, this applies to somatic-psychiatric comorbidity, which accounts for 70.3% (psychosocial aspects of QoL) to 100% (QoL in general) significantly lowered QoL results. Somatic-somatic comorbidities are primarily associated with somatic aspects of QoL (56.5-80.7% significant results), while psychosocial aspects as well as QoL in general are significantly associated in 8.3% to 71.7% of all calculations.'] |
['Sublesional osteoporosis predisposes individuals with spinal cord injury (SCI) to an increased risk of low-trauma fracture. The aim of the present work was to investigate the effect of treatment with resveratrol (RES) on sublesional bone loss in spinal cord-injured rats.', 'Complete SCI was generated by surgical transaction of the cord at the T10-12 level. Treatment with RES (400\u2009mg·kg(-1) body mass per day(-1) , intragastrically) was initiated 12\u2009h after the surgery for 10 days. Then, blood was collected and femurs and tibiae were removed for evaluation of the effects of RES on bone tissue after SCI.', 'Treatment of SCI rats with RES prevented the reduction of bone mass including bone mineral content and bone mineral density in tibiae, preserved bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in tibiae, and preserved mechanical strength including ultimate load, stiffness, and energy in femurs. Treatment of SCI rats with RES enhanced femoral total sulfhydryl content, reduced femoral malondialdehyde and IL-6 mRNA levels. Treatment of SCI rats with RES suppressed the up-regulation of mRNA levels of PPARγ, adipose-specific fatty-acid-binding protein and lipoprotein lipase, and restored mRNA levels of Wnt1, low-density lipoprotein-related protein 5, Axin2, ctnnb1, insulin-like growth factor 1 (IGF-1) and receptor for IGF-1 in femurs and tibiae.'] |
['The class III histone deacetylase SIRT1 is a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, and has been reported to serve diverse roles in various biological processes, such as caloric restriction, apoptosis, neuronal protection, cell growth, differentiation and tumourigenesis. With respect to tumourigenesis, there have been conflicting data supporting whether SIRT1 act as a tumour promoter or as a tumour suppressor.', 'SIRT1 protein expression, determined by immunohistochemistry, was investigated in human normal colonic mucosa, adenoma, adenocarcinoma and metastatic tissue samples.', 'All normal colonic mucosa showed SIRT1 expression with no exception, and 42 (80.8%) of 52 adenomatous polyps were positive for SIRT1. However, only 208 (41.9%) of 497 colorectal adenocarcinomas were positive. Moreover, 45 (35.7%) of 126 metastatic tissues were positive. Collectively, the SIRT1 expression was gradually decreased during carcinogenesis and tumour progression. The associations between SIRT1 expression and clinicopathological parameters revealed that loss of SIRT1 expression was associated with proximal tumour location, mucinous histology and defective mismatch repair protein expression. This suggests that loss of SIRT1 expression is associated with the microsatellite instability phenotype of colorectal adenocarcinoma. In survival analyses, the loss of SIRT1 expression was significantly associated with overall survival (p=0.027, log-rank test) in univariable analysis, but multivariable analysis failed to achieve significance.'] |
['Evidence suggests that electroacupuncture (EA) protects against arrhythmia and myocardial injury induced by myocardial ischaemia-reperfusion. However, to our knowledge, it remains unknown whether EA could alleviate bupivacaine-induced cardiotoxicity. Therefore, we aimed to explore the effect of EA pretreatment on bupivacaine-induced cardiac arrest and outcomes of cardiopulmonary resuscitation (CPR) in rats.', '24 adult male Sprague-Dawley rats were randomly divided into two groups: EA (n=12), and minimal acupuncture (MA) (n=12). Rats in both groups were needled at bilateral PC6, ST36, and ST40. Needles in the EA group were electrically stimulated for 60\u2005min. ECG and invasive arterial blood pressure measurements were recorded. Two hours after EA or MA, 10\u2005mg/kg bupivacaine was infused intravenously at a rate of 5\u2005mg/kg/min in all rats. Rats suffering cardiac arrest were immediately subjected to CPR. At the end of the experiment, arterial blood samples were taken from surviving rats for blood gas analysis.', 'The time from bupivacaine infusion until 20% prolongation of the QRS and QT interval, and the time to cardiac arrest, were notably increased among the rats pretreated with EA. Moreover, EA pretreatment significantly improved mean arterial pressure and heart rate at all monitored points after bupivacaine infusion. The proportion of animals surviving was higher in the EA group (9/12) than the MA group (3/12) at the end of experiment (p=0.039).'] |
['To examine how often a significant publication bias (PB) existed when the assessment of PB was not reported in systematic reviews.', 'All systematic reviews with meta-analyses of interventions and risk/prognostic factors published in the general medical journals with the top 10 impact factors in 2011 and 2012 were included. The results regarding PB were extracted. When the assessment of PB was not reported, we examined the presence of PB using the Egger test and contour-enhanced funnel plot and the impact of unreported PB by regression-based method.', 'Among all the identified 116 reviews, the assessment of PB was not reported in 36 reviews (31.0%), particularly in reviews without a comprehensive literature search. Of these 36 reviews, seven (19.4%) were found to have a significant PB. The original pooled results may have been overestimated by a median of 50.9% if corrected for PB. Among the 28 reviews with PB including both reviews that did or did not report the assessment of PB, seven reviews (25.0%) did not report the presence of PB.'] |
['Recently described slow-cooling cryopreservation protocols involving elevated sucrose concentration have improved survival frequencies of human oocytes, potentially overcoming a major hurdle that has limited the adoption of oocyte storage. Because implantation rates of embryos from frozen oocytes remain generally low, it is still debated whether, irrespective of survival rates, this form of cryopreservation leads inevitably to the disruption or complete loss of the metaphase II (MII) spindle.', 'Human oocytes with an extruded polar body I (PBI) were cryopreserved using a slow-cooling method including 1.5 mol/l propane-1,2-diol (PrOH) and alternative sucrose concentrations (either 0.1 or 0.3 mol/l) in the freezing solution. Fresh control and frozen-thawed survived oocytes were analysed by confocal microscopy to evaluate MII spindle and chromosome organizations.', 'Of the 104 oocytes included in the unfrozen group, 76 (73.1%) displayed normal bipolar spindles with equatorially aligned chromosomes. Spindle and chromatin organizations were significantly affected (50.8%) after cryopreservation involving lower sucrose concentration (61 oocytes), whereas these parameters were unchanged (69.7%) using the 0.3 mol/l sucrose protocol (152 oocytes).'] |
['This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in\xa0Switzerland.', 'Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three).', 'From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors.'] |
['The widespread use of coronary stents has exposed a growing population to the risk of stent thrombosis, but the importance in terms of risk of ST-segment elevation myocardial infarctions (STEMIs) remains unclear.', 'We studied five years follow-up data for 2,098 all-comer patients treated with coronary stents in the randomized SORT OUT II trial (mean age 63.6 yrs. 74.8% men). Patients who following stent implantation were readmitted with STEMI were included and each patient was categorized ranging from definite- to ruled-out stent thrombosis according to the Academic Research Consortium definitions. Multivariate logistic regression was performed on selected covariates to assess odds ratios (ORs) for definite stent thrombosis.', '85 patients (4.1%), mean age 62.7 years, 77.1% men, were admitted with a total of 96 STEMIs, of whom 60 (62.5%) had definite stent thrombosis. Notably, definite stent thrombosis was more frequent in female than male STEMI patients (81.8% vs. 56.8%, p =\u200a .09), and in very late STEMIs (p = 0.06). Female sex (OR 3.53 [1.01-12.59]) and clopidogrel (OR 4.43 [1.03-19.01]) was associated with increased for definite stent thrombosis, whereas age, time since stent implantation, use of statins, initial PCI urgency (STEMI [primary PCI], NSTEMI/unstable angina [subacute PCI] or stable angina [elective PCI]), and glucose-lowering agents did not seem to influence risk of stent thrombosis.'] |
['Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described.', 'The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.', 'Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.'] |
["Extracellular Tat released from HIV-1-infected cells is a mitogenic and motogenic factor for endothelial and Kaposi's sarcoma (KS)-derived cells and is angiogenic in vivo. Here we show for the first time that Tat induces migration of human dendritic cells in a concentration-dependent manner and that the Arg-Gly-Asp (RGD) and basic Tat peptides contribute to dendritic and monocyte cell migration. In vivo, Tat stimulates invasion of macrophages into a matrigel sponge.", 'Monocyte and dendritic cell chemotaxis was assessed using the Boyden chamber assay.', 'Tat induced migration of monocyte-derived dendritic cells at the same levels as the N-formyl-Met-Leu-Phe peptide, and of monocytes at levels comparable to RANTES. Peptide mapping of the chemotactic activity of Tat showed that the RGD domain, which has been shown to support integrin-mediated cell migration, and the basic domain which binds and activates the tyrosine kinase receptor KDR on endothelial cells, both had activity. Antibody-blocking experiments indicate that responses to the RGD domain was inhibited by beta1 and alpha vbeta3 integrin blocking antibodies. Combination of the Tat RGD and basic peptides did not show additive effects; however, Tat co-operated with macrophage-chemotactic protein or RANTES in inducing monocyte migration.'] |
['Dark chocolate is reported to decrease platelet activation but the underlying mechanism is still undefined. Dark chocolate is rich in polyphenols that could exert an antiplatelet action via inhibition of oxidative stress. The aim of the present study was to assess if dark chocolate inhibits platelet reactive oxidant species (ROS) formation and platelet activation.', 'Twenty healthy subjects (HS) and 20 smokers were randomly allocated to receive 40 g of dark (cocoa > 85%) or milk chocolate (cocoa < 35%) in a cross-over, single-blind study. There was an interval of 7 days between the two phases of the study. At baseline and 2 h after chocolate ingestion, platelet recruitment (PR), platelet ROS, platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), Thromboxane (TxA2) and platelet activation of NOX2, the catalytic sub-unit of NADPH oxidase, and serum epicatechin were measured.', 'Compared with HS, smokers showed enhanced PR, platelet formation of ROS and eicosanoids and NOX2 activation. After dark chocolate, platelet ROS (-48%, P < 0.001), 8-iso-PGF2α (-10%, P < 0.001) and NOX2 activation (-22%, P < 0.001) significantly decreased; dark chocolate did not affect platelet variables in HS. No effect of milk chocolate was detected in both groups. Serum epicatechin increased after dark chocolate in HS (from 0.454 ± 0.3 nm to 118.3 ± 53.7 nm) and smokers (from 0.5 ± 0.28 nm to 120.9 ± 54.2 nm). Platelet incubation with 0.1-10 μm catechin significantly reduced PR, platelet 8-iso-PGF2α and ROS formation and NOX2 activation only in platelets from smokers.'] |
['Increasing evidence on associations between mental health and chronic diseases like cardio-vascular disease and diabetes together with the fact that little is known about the prevalence of anxiety/depression and associated risk factors among Iraqi immigrants to Sweden, warrants a study in this group. The aim was to study the prevalence of anxiety and depression in immigrants from Iraq compared to native Swedes and compare socioeconomic and lifestyle-related factors associated with these conditions.', 'A population-based, cross-sectional study of residents of Malmö, Sweden, aged 30-75 years, born in Iraq or Sweden. The overall response rate was 49% for Iraqis and 32% for Swedes. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Associations were studied using multivariate logistic regression models. The outcome was odds of depression and/or anxiety.', 'Compared to Swedes (n\u2009=\u2009634), anxiety was three times as prevalent (52.6 vs. 16.3%, p\u2009<\u20090.001) and depression five times as prevalent (16.3 vs. 3.1%, p\u2009<\u20090.001) in Iraqi immigrants (n\u2009=\u20091255). Iraqis were three times more likely to be anxious and/or depressed compared to Swedes (odds ratio (OR) 3.02, 95% confidence interval (CI) 2.06-4.41). Among Iraqis, physical inactivity (<150 min/week) (OR 2.00, 95% CI 1.49-2.69), economic insecurity (OR 2.16, 95% CI 1.56-3.01), inability to trust people (OR 1.75, 95% CI 1.28-2.39) and smoking (OR 1.43, 95% CI 1.02-2.01), were strongly associated with anxiety/depression. Among Swedes, living alone (OR 2.10, 95% CI 1.36-3.25) and economic insecurity (OR 2.38, 95% CI 1.38-4.12) showed the strongest associations with anxiety/depression. Country of birth modified the effect of physical inactivity (P(interaction) =0.058) as well as of marital status (P(interaction) =0.001).'] |
['17beta-estradiol (E2) negatively modulates neointima formation, leukocyte infiltration, and proinflammatory mediator expression after vascular injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E2 in elderly postmenopausal women have not confirmed a vasoprotective effect. This study tested the hypothesis that responsiveness to E2 is lost in injured arteries of aged (12-mo-old) OVX rats.', 'E2- or vehicle-treated OVX rats underwent balloon injury of the carotid artery and were killed after 2 weeks for morphometric examination of arteries, after 24 hours for assessment of leukocyte infiltration, and after 2 hours for quantification of proinflammatory mediator mRNA expression.', 'Neointima formation was significantly reduced in aged compared with young vehicle-treated rats. E2 treatment had directionally opposite effects on intima/media ratios in aged (+75%) and young (-40%) rats. Injury induced increases in infiltrating total leukocytes, neutrophils, monocytes/macrophages, and expression of proinflammatory mediators in arteries of aged rats; E2 had no effect on these inflammatory responses to injury. Estrogen receptor alpha and beta protein expression were similar in carotid arteries of young and aged rats on immunofluorescence testing.'] |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.