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['US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM).', 'HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count <200 cells per cubic millimeter or <350 cells per cubic millimeter at diagnosis.', 'HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no previous HIV diagnosis; 272 (21.2%) reported no HIV test in previous 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the previous 6 months (relative risk [RR]: 1.08, 95% confidence interval [CI]: 1.03 to 1.13), being unemployed (RR: 1.04, CI: 1.01 to 1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0 to 1.05). New HIV diagnoses were more likely among infrequent testers compared with men tested in the previous year (18.4% vs. 4.4%; odds ratio: 4.8, 95% CI: 3.2 to 7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells per cubic millimeter including 17 (20.2%) with CD4 <200 cells per cubic millimeter.']
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['To validate the AUDIT test for identifying women with excess alcohol consumption and/or dependency syndrome (DS).', 'Descriptive study to validate a test.', 'Two primary care centres and a county drug-dependency centre.', '414 women from 18 to 75 recruited at the clinic. Interventions. Social and personal details were obtained through personal interview, their alcohol consumption was quantified and the AUDIT and MALT questionnaires were filled in. Then the semi-structured SCAN interview was conducted (gold standard; DSM-IV and CIE-10 criteria), and analyses were requested (GGT, GOT, GPT, VCM). 186 patients were given a follow-up appointment three-four weeks later (retest).', 'Intra-observer reliability was evaluated with the Kappa index, internal consistency with Cronbach s alpha, and the validity of criteria with indexes of sensitivity and specificity, predictive values and probability quotients. To evaluate the diagnostic performance of the test and the most effective cut-off point, a ROC analysis was run.', '11.4% (95% CI, 8.98-13.81) were diagnosed with alcohol abuse (0.5%) or DS (10.9%). The Kappa coefficients of the AUDIT items ranged between 0.685 and 0.795 (P<.001). Internal reliability, with Cronbach s alpha, was 0.932 (95% CI, 0.921-0.941). Test sensitivity was 89.6% (95% CI,76.11-96.02) and specificity was 95.07% (95% CI, 92.18-96.97). The most effective cut-off point was at 6 points.']
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['Several prior studies have linked serum prealbumin (PA) as a predictor for perioperative infection. However, whether peripheral blood PA levels can be used as an indicator of stroke-associated infection (SAI) is still unclear. In this study, we attempt to find whether serum PA is a meaningful predictor in SAI after an ischemic stroke, so as to provide theoretical basis for clinical treatment.', 'Consecutive patients with acute ischemic stroke who were admitted to our hospital were enrolled and serum PA was collected. A prospective study was conducted to observe the predictive value of PA in the SAI incident in ischemic stroke patients.', 'Of 104 patients, 29 (27.9%) developed an SAI after 7 d of follow-up. The stroke with SAI group had significantly lower PA levels than the stroke without SAI group (\u2009\u2009p < 0.05). The optimal cutoff value for predicting SAI was PA ≤ 191 mg/L, with sensitivity and specificity of 58.62% and 81.33%, respectively. Kaplan-Meier survival analysis showed that stroke patients with low serum PA level (PA ≤ 191 mg/L) had a higher SAI rates (log-rank test, χ']
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['The objective of this study was to examine the role of protein kinase C zeta (PKCzeta) in interleukin (IL)-8-mediated activation of Mac-1 (CD11b/CD18) in human neutrophils.', 'Neutrophils were stimulated with IL-8 in the presence or absence of pharmacologic inhibitors of PKC or a myristoylated PKCzeta pseudosubstrate. The resulting changes in Mac-1 surface expression, affinity, and avidity, as measured by clustering, were determined by using a combination of flow cytometry and immunofluorescence (IF). Colocalization of Mac-1 with PKCzeta was also probed using IE Finally, neutrophil adhesion to matrix proteins was examined under static conditions and adhesion to tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells was examined under flow conditions, using a parallel-plate flow chamber', 'PKCzeta and Mac-1 colocalized following stimulation with IL-8. Blocking PKCzeta prevented IL-8-induced Mac-1 clustering while simultaneously increasing Mac-1 affinity. To determine the relative contribution of affinity versus avidity in neutrophil adhesion, we examined adhesion under both static and flow conditions, and found that blocking PKCzeta prevented neutrophil adhesion, despite increased affinity of Mac-1.']
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["Metabolic syndrome (MetS) clusters risk factors for age-related conditions including cardiovascular disease and diabetes. Shorter telomere length (TL), a cellular marker for biological age, may predict an individual's deteriorating metabolic condition.", 'We examined whether shorter baseline TL is associated with a worse metabolic profile and with less favorable trajectories of MetS components over a 6-year follow-up.', 'PARTICIPANTS were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study with 6-year follow-up.', 'This study included 2848 participants age 18-65 years.', 'Baseline TL from leukocytes was determined using qPCR and MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, systolic blood pressure, and fasting glucose) were determined at baseline, and after 2 and 6 years. Cross-sectional and longitudinal analyses were adjusted for relevant sociodemographic, lifestyle, and health factors.', 'Shorter baseline TL was cross-sectionally associated with HDL (β = -0.016, SE = 0.008, P = .05), waist circumference (β = 0.647, SE = 0.238, P = .007), triglycerides (β = 0.038, SE = 0.009, P < .001), and fasting glucose (β = 0.011, SE = 0.003, P < .001), as well as with the total number of MetS components (β = 0.075, SE = 0.023, P = .001) and the presence of MetS (OR = 1.19; 95% CI, 1.07-1.33; P = .002). Although baseline differences progressively reduced over time, shorter baseline TL was still significantly associated with unfavorable scores of most MetS components at the 2- or 6-year follow-up.']
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['Transketolase-like (TKTL) 1 is one of the key enzymes for anaerobic sugar degradation even in the presence of oxygen (aerobic glycolysis). Transketolase-dependent reactions supply malignant tumors with ribose and NADPH. Therefore, TKTL1 activity could be crucial for tumor proliferation and survival. The aim of the study was to evaluate the expression of TKTL1 in colorectal cancer (CRC) and its regulation under hypoxic conditions.', 'We studied TKTL1 mRNA and protein expression in CRC cell lines and human CRC biopsies by quantitative real-time PCR, Western blotting and immunohistochemistry. Regulation of TKTL1 under oxygen depletion was analyzed by cultivating cells either in a three-dimensional spheroid model or in a hypoxia incubator chamber.', 'TKTL1 mRNA was heterogeneously expressed in monolayers of cells with high levels in HT-29 and SW480. TKTL1 protein was also clearly detectable in HT-29 and SW480. Hypoxia-inducible factor (HIF)-1α protein expression correlated with TKTL1 protein expression in SW480 spheroids over time. On the one hand, induction of hypoxia in T84 spheroids did not induce TKTL1; on the other hand, hypoxia by incubation at 1% O₂ in a hypoxia incubator chamber clearly showed an upregulation of TKTL1. In 50% of CRC patients, TKTL1 protein expression was upregulated in tumor compared to non-tumor tissue. The immunohistochemical staining of TKTL1 in CRC patient samples resulted in 14 positive and 30 negative samples.']
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['To determine whether conjunctivochalasis (CCh) interferes with tear flow from the fornix to the tear meniscus and depletes the fornix tear reservoir.', 'Comparative case series.', 'The study group of 24 CCh patients (8 asymptomatic and 16 symptomatic), 9 of whom underwent operative correction, was compared with a control group of 13 normal subjects.', 'After instilling a 5-μl fluorescein drop into the inferior fornix, the inferior tear meniscus was depleted using a capillary tube. The tear meniscus height, with and without blinking, was recorded and calculated by video meniscometer from sequential captured images.', 'The recovery rate of the original meniscus height was compared among groups at each time point after maximal depletion.', "The recovery rate of the tear meniscus was significantly slower in symptomatic than asymptomatic CCh patients when compared with normal subjects. Blinking 5 times facilitated such recovery in normal subjects and in asymptomatic CCh patients to the same extent as the normal, but not in symptomatic CCh patients. Deepening of the inferior fornix by removing degenerated Tenon's and reconstruction by cryopreserved amniotic membrane improved the recovery rate in symptomatic CCh patients to the same extent as normal subjects."]
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['Wide geographic variations in cardiac rehabilitation (CR) participation in the United States have been demonstrated but are not well understood. Socioeconomic factors such as educational attainment are robust predictors of many health-related behaviors, including smoking, obesity, physical activity, substance abuse, and cardiovascular disease. We investigated potential associations between state-level differences in educational attainment, other socioeconomic factors, CR program availability, and variations in CR participation.', 'A retrospective database analysis was conducted using data from the US Census Bureau, the Centers for Disease Control and Prevention, and the 1997 Medicare database. The outcome of interest was CR participation rates by state, and predictors included state-level high school (HS) graduation rates (in 2001 and 1970), median household income, smoking rates, density of CR program (programs per square mile and per state population), sex and race ratios, and median age.', 'The relationship between HS graduation rates and CR participation by state was significant for both 2001 and 1970 (r = 0.64 and 0.44, respectively, P < .01). Adding the density of CR programs (per population) and income contributed significantly with a cumulative r value of 0.74 and 0.71 for the models using 2001 and 1970, respectively (Ps < .01). The amount of variance accounted for by each of the 3 variables differed between the 2000 and 1970 graduation rates, but both models were unaltered by including additional variables.']
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['Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others.', 'Total CSF tau level was assayed in a population of ALS patients (n = 57) and controls (n = 110) using a specific ELISA method.', 'No significant differences in the median CSF tau levels between ALS cases and controls were found [ALS: 126 pg/ml (78-222); controls: 112 pg/ml (71-188), P = ns]. In the ALS group, the bulbar-onset patients showed increased CSF tau levels as compared with the spinal-onset cases. These differences might be related to the higher age of the bulbar-onset patients. Further, no correlations were found between CSF tau concentrations and the rate of progression of the disease.']
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['In pig-to-primate organ transplantation, hyperacute rejection can be prevented, but the organ is rejected within days by acute vascular rejection, in which induced high-affinity anti-Gal alpha1-3Gal (alphaGal) IgG and possibly antibodies directed against new porcine (non-alphaGal) antigenic determinants are considered to play a major role. We have explored the role of an anti-CD40L monoclonal antibody in modifying the humoral response to porcine hematopoietic cells in baboons pretreated with a nonmyeloablative regimen.', 'Porcine peripheral blood mobilized progenitor cells obtained by leukapheresis from both major histocompatibility complex-inbred miniature swine (n=7) and human decay-accelerating factor pigs (n=3) were transplanted into baboons. Group 1 baboons (n=3) underwent whole body (300 cGy) and thymic (700 cGy) irradiation, T cell depletion with ATG, complement depletion with cobra venom factor, short courses of cyclosporine, mycophenolate mofetil, porcine hematopoietic growth factors, and anti-alphaGal antibody depletion by immunoadsorption before transplantation of high doses (2-4 x 10(10)/cells/kg) of peripheral blood mobilized progenitor cells. In group 2 (n=5), cyclosporine was replaced by eight doses of anti-CD40L monoclonal antibodies over 14 days. The group 3 baboons (n=2) received the group 1 regimen plus 2 doses of anti-CD40L monoclonal antibodies (on days 0 and 2).', 'In group 1, sensitization to alphaGal (with increases in IgM and IgG of 3- to 6-fold and 100-fold, respectively) and the development of antibodies to new non-alphaGal porcine antigens occurred within 20 days. In group 2, no sensitization to alphaGal or non-alphaGal determinants was seen, but alphaGal-reactive antibodies did return to their pre- peripheral blood mobilized progenitor cells transplant levels. In group 3, attenuated sensitization to alphaGal antigens was seen after cessation of cyclosporine and mycophenolate mofetil therapy at 30 days (IgM 4-fold, IgG 8-30-fold), but no antibodies developed against new porcine determinants. In no baboon did anti-CD40L monoclonal antibodies prevent sensitization to its own murine antigens.']
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['Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly.', 'Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (-6 degrees ) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles.', 'HDBR transiently reduced muscle sympathetic nerve activity, RR, heart rate variability and baroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained.']
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['To determine the association between CCR5 and CCR2b genotype and the clinical manifestation of first and subsequent AIDS-defining illnesses (ADIs).', 'The distribution of ADIs was examined by CCR5 and CCR2b genotype in a subset of homosexual men enrolled in the Sydney AIDS Prospective Study. The expected number of ADIs was calculated from rates observed in the same tertiary hospital over the same period.', 'Information on initial ADI was collected for 117 homosexual men diagnosed with AIDS before January 1998. Of these individuals, 17 were heterozygous for the CCR5-Delta32 mutation and 11 were heterozygous for CCR2b-64I. The number of observed cases of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) and cryptosporidiosis reported as a first ADI was substantially fewer in people heterozygous for the CCR5-Delta32 mutation than for those without the mutation, despite similar age, CD4 T-cell count at AIDS diagnosis, year of AIDS diagnosis and receipt of antiretroviral treatment. In addition, among individuals heterozygous for CCR5-Delta32 there were fewer cases of PCP, toxoplasmosis, MAC, and cryptosporidiosis observed as subsequent ADIs compared to the number expected, based on rates measured in the same hospital during the same period (seven observed vs. 24 expected, RR = 0.3, 95% CI = 0.01-0.6). The distribution of first and subsequent ADIs did not differ from the number expected in individuals heterozygous for the CCR2b-64I mutation.']
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['To examine consistency (interrater reliability) of applying guidance for grading strength of evidence in systematic reviews for the Agency for Healthcare Research and Quality Evidence-based Practice Center program.', 'Using data from two systematic reviews, authors tested the main components of the approach: (1) scoring evidence on the four required domains (risk of bias, consistency, directness, and precision) separately for randomized controlled trials (RCTs) and observational studies and (2) developing an overall strength of evidence grade, given the scores for each of these domains.', 'Conclusions about overall strength of evidence reached by experienced systematic reviewers based on the same evidence can differ greatly, especially for complex bodies of evidence. Current instructions may be sufficient for straightforward quantitative evaluations that use meta-analysis for summarizing RCT findings. In contrast, agreement suffered when evaluations did not lend themselves to meta-analysis and reviewers needed to rely on their own qualitative judgment. Three areas raised particular concern: (1) evidence from a combination of RCTs and observational studies, (2) outcomes with differing measurement, and (3) evidence that appeared to show no differences in outcomes.']
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['H. pylori infection significantly attenuated the expression of HSP70 in gastric mucosal cells. However, the role of HSP70 cancellation in H. pylori-associated cell damages is largely unclear.', 'Small interfering RNA (siRNA) was used to down-regulate HSP70 in gastric epithelial cell lines AGS. The transfected cells were then incubated with H. pylori and the functions of HSP70 suppression were observed by viability assay, cell cycle analyses and TUNEL assay. HSP70 target apoptotic proteins were further identified by Western blot.', 'The inhibition of HSP70 has further increased the effect of growth arrest and apoptosis activation triggered by H. pylori in gastric epithelial cells. The anti-proliferation function of HSP70 depletion was at least by up-regulating p21 and cell cycle modulation with S-phase accumulation. An increase of apoptosis-inducing factor (AIF) and cytosolic cytochrome C contributes to the activation of apoptosis following down-regulation of intracellular HSP70. Extracellular HSP70 increased cellular resistance to apoptosis by suppression the release of AIF and cytochrome c from mitochondria, as well as inhibition of p21 expression.']
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['Core2 1-6-N-glucosaminyltransferase-I (C2GlcNAcT-I) modification of adhesion molecules is required for optimal binding to target ligands. The objective of this study was to determine the role of C2GlcNAcT-I in the recruitment of Ly-6C(hi) monocytes to atherosclerotic lesions and in lesion formation in mice.', 'In a whole-blood binding assay, Ly-6C(hi) monocytes and certain lymphocytes and natural killer cells from wild-type mice bound to P- and E-selectin. C2GlcNAcT-I deficiency abrogated leukocyte binding to P- and E-selectin in this assay as well as in an in vitro flow chamber assay. Moreover, C2GlcNAcT-I deficiency decreased Ly-6C(hi) monocyte interactions with atherosclerotic arteries under physiological flow conditions and also inhibited monocyte recruitment to the peritoneal cavity in mice challenged with thioglycollate. In apolipoprotein E-deficient (apoE(-/-)) mice, lack of C2GlcNAcT-I resulted in fewer and smaller atherosclerotic lesions in mouse aortas. Atherosclerosis was also suppressed in C2GlcNAcT-I(-/-)/apoE(-/-) chimeric mice transplanted with C2GlcNAcT-I(+/+) bone marrow cells.']
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['The Cqm1 α-glucosidase of Culex quinquefasciatus larvae acts as the midgut receptor for the binary toxin of the biolarvicide Lysinibacillus sphaericus. Mutations within the cqm1 gene can code for aberrant polypeptides that can no longer be properly expressed or bind to the toxin, leading to insect resistance. The cqm1 REC and cqm1 REC-2 alleles were identified in a laboratory selected colony and both displayed mutations that lead to equivalent phenotypes of refractoriness to L. sphaericus. cqm1 REC was first identified as the major resistance allele in this colony but it was subsequently replaced by cqm1 REC-2 , suggesting the better adaptive features of the second allele. The major aim of this study was to evaluate the occurrence of cqm1 REC-2 and track its origin in field populations where cqm1 REC was previously identified.', 'The screening of the cqm1 REC-2 allele was based on more than 2000 C. quinquefasciatus larvae from five localities in the city of Recife, Brazil and used a multiplex PCR assay that is also able to identify cqm1 REC . Full-length sequencing of the cqm1 REC-2 and selected cqm1 samples was performed to identify further polymorphisms between these alleles.', 'The cqm1 REC-2 allele was found in field samples, specifically in two heterozygous individuals from a single locality with an overall frequency and distribution much lower than that observed for cqm1 REC . The full-length sequences from these two cqm1 REC-2 copies were almost identical to the cqm1 REC-2 derived from the resistant colony but displayed more than 30 SNPs when compared with cqm1 and cqm1 REC . The cqm1 REC and cqm1 REC-2 resistant alleles were found to be associated with two distinct sets of wild-type cqm1 variants found in field populations.']
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['To assess the effectiveness of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive therapy (IST).', 'Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000\u2009U, subcutaneously, three times a week). rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared.', 'Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.). Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011, resp.). The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups.']
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['Pathological angiogenesis is an intrinsic component of chronic intestinal inflammation, which results in remodeling and expansion of the gut microvascular bed. Endoglin is essential for endothelial cell function and physiological angiogenesis. In this study we investigated its potential role in the regulation of inflammation by testing the response of Endoglin heterozygous (Eng(+/-)) mice to experimental colitis.', 'C57BL/6 Eng(+/-) and littermate control mice drank water supplemented with 3% dextran sulfate sodium (DSS) for 5 days and were monitored for up to 26 days for clinical signs of colitis. Inflammation, crypt damage, and angiogenic index were scored on histological sections of distal colon. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins were measured by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and/or Western blots. Vascular permeability was assessed using Evans Blue.', 'Eng(+/-) and control mice developed acute colitis, which peaked at day 9. While control mice recovered by days 19-26, Eng(+/-) mice progressed to chronic colitis and showed numerous vascular protrusions penetrating into the serosa of the inflamed distal colon. Prior to DSS induction, VEGF levels and vascular permeability were higher in the distal colon of Eng(+/-) mice, while angiopoietin 1 and 2 levels were unchanged. In the chronic phase of colitis, VEGF levels were increased in both groups of mice and remained significantly higher in the Eng(+/-) mice.']
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['To evaluate if placental histopathological changes of vascular insufficiency correlate with circulating angiogenic factors in patients with preeclampsia.', 'Subjects were selected from a previous prospective cohort study of preeclampsia based on the availability of plasma anti-angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and placental histology specimens. Preeclamptic patients were divided into two groups based on plasma levels of these factors described as a ratio: anti-angiogenic preeclampsia with sFlt1/PlGF ratio ≥85 and normal angiogenic preeclampsia with sFlt1/PlGF\u2009<\u200985. The placental lesions of vascular insufficiency that were studied specifically included atherosis, infarcts, syncytial knots, acute and chronic abruption, hematoma, and fetal thrombosis. The data are shown as median (quartile 1 and quartile 3) or n (%) when appropriate.', 'The anti-angiogenic preeclampsia group (N\u2009=\u200948) presented at an earlier gestational age (weeks) than the normal angiogenic group (N\u2009=\u200928); {32 (28, 34) versus 35 (32, 36), p\u2009=\u20090.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus 147 (132, 158), p\u2009=\u20090.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34, 37), p\u2009<\u20090.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus 2655 (2285, 3343), p\u2009<\u20090.001}. Several pathologic lesions were found significantly more often in the anti-angiogenic preeclampsia group; atherosis {27.7% versus 3.6%, p\u2009<\u20090.05}, infarcts {58.3% versus 3.6%, p\u2009=\u20090.002}, and syncytial knots {81.3% versus 39.3%, p\u2009<\u20090.001}.']
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['The compound, diazoxide (DZ), is known to induce preconditioning through its effect as a mitochondrial K(ATP) channel opener and succinate dehydrogenase inhibitor. Our team tested the hypothesis that pharmacological induction of ischemic preconditioning with DZ can offer cytoprotection and preserve vital tissues after hemorrhagic shock and stroke.', 'Sprague-Dawley male rats received an intraperitoneal injection of sterile saline or 5 mg/kg DZ in saline 24 h prior to 1 h of hemorrhagic shock, by approximately 40% total blood loss volume (Shock Study), or a permanent unilateral common carotid ligation just before shock (Stroke + Shock Study). While remaining under isoflurane anesthesia, animals then received 81 mL/kg intravenous sterile saline over the next 45 min for recovery and survived for another 24 h.', 'When DZ was administered 24 h prior to shock, it significantly reduced hyperglycemia, which in vehicle-treated animals persisted after resuscitation. DZ also attenuated hyperlactatemia during the 1-h shock period. With more severe trauma from combined stroke and shock, DZ also decreased hyperlactatemia and hyperglycemia levels but the reduction was only significant for hyperglycemia. The expression levels of heat shock proteins 25 (HSP25) and 70 (HSP70) were used as biomarkers for response of the kidney and liver to DZ and combined stroke and shock. Compared to vehicle-treated animals, DZ-treated rats subjected to shock and stroke exhibited increased HSP25 and HSP70 in kidney and liver tissue.']
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['To study the basal and ACTH stimulated production of corticosterone by adrenal cortex on one hand and the binding and degradation of corticosterone in the liver of adult rats which were treated with monosodium glutamate (MSG) during the neonatal period.', 'Male offsprings of Sprague-Dawley rats were injected i.p. with MSG (4 mg/g of b.w. in saline) on alternated days for the first 10 days of life, their littermates being used as controls. On the 21st postnatal day they were weaned and used for the observation at the age of 65-75 days. After sacrifice the level of corticosterone in serum and the release of corticosterone from incubated adrenals under basal and ACTH stimulated conditions (ACTH in 6 concentrations from 1.25 to 80 mU/ml medium) were estimated. In addition, glucocorticoid binding to cytosol receptors in the liver and muscle tissues was determined. Corticosterone degradation rate was measured by decrease of corticosterone concentration added to the medium after the incubation with liver slices.', 'Adult rats neonatally treated with MSG had reduced weight of adrenal glands, while plasma corticosterone levels and its basal production by adrenals in vitro were significantly higher than in controls. In MSG treated rats the stimulation of corticosterone production by ACTH was diminished. Glucocorticoid binding to liver cytosolic receptors was significantly decreased, while that in muscle tissue was only slightly elevated. Moreover, a decreased corticosterone degradation rate in liver slices was observed in rats treated neonatally with MSG.']
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['Since the hepatic extracellular matrix is remodeled in liver regeneration, we investigated whether increased collagenase activity in the liver can induce hepatocyte proliferation in vivo.', 'To increase hepatic collagenase activity, human matrix metalloproteinase-1 was delivered to the rat liver by the recombinant adenoviral vector Ad5MMP-1.', 'Hepatic delivery of Ad5MMP-1 increased the 5-bromo-2-deoxyuridine labeling index and mitotic index in hepatocytes, causing an increase in the dry liver weight; control adenovirus, Ad5LacZ, had minimal effect. Hepatocyte proliferation started approximately 48 h after infection with Ad5MMP-1 and ended after about 2 weeks. The increase in the dry liver weight also returned to baseline after 2 weeks. Transient liver injury by Ad5MMP-1, reflected by increased aspartate and alanine aminotransferase levels, peaked around 1 week, and was associated with hepatocyte apoptosis. Collagenase-induced hepatocyte proliferation was accompanied by cytoplasmic accumulation of beta-catenin and a transient decrease in E-cadherin expression.']
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['In utero hematopoietic stem-cell transplantation has been shown to induce donor-specific tolerance in small-animal models. However, tolerance has been difficult to achieve in large-animal studies.', "Outbred swine underwent in utero transplantation of fully major histocompatibility complex (MHC)-mismatched CD3-depleted bone marrow mixed with fresh bone marrow to achieve a final CD3 content of 1.5%. Transplantation was performed at 50 to 55 days' gestation and two animals survived long term and demonstrated multilineage peripheral blood hematopoietic chimerism. These two long-term survivors were analyzed for in vitro evidence of donor-specific tolerance by mixed leukocyte reaction (MLR), cell-mediated lysis (CML), and antibody testing and in vivo by kidney transplantation.", 'Both animals demonstrated in vitro donor-specific unresponsiveness by MLR and CML and did not demonstrate anti-donor antibody production. Donor matched kidney transplants were performed without immunosuppression and functioned for more than 100 days, with no evidence for rejection.']
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['To investigate whether common variants across the LBP gene contribute to the development of severe sepsis. Sepsis is the leading cause of multiple system organ dysfunction and death in critically ill patients. The lipopolysaccharide-binding protein is an acute-phase protein that plays a dominant role in the genesis of sepsis by initiating signal transduction pathways leading to the activation of the inflammatory host response.', 'Prospectively enrolled case-control study of adults with severe sepsis.', 'A network of intensive care units.', 'We enrolled 175 patients meeting international definition criteria for severe sepsis and 357 population-based controls for comparison.', 'Genotyping of the LBP gene was performed and disease association was tested. Serum lipopolysaccharide-binding protein levels were measured in patients and related to genetic variants.', "A haplotype window analysis revealed that a common 4-SNP risk haplotype from the 5'-flanking region of the LBP gene, comprising positions -1978 to -763 from the transcription start site, was strongly associated with susceptibility to severe sepsis. Risk haplotype homozygous carriers had an increased risk for severe sepsis (odds ratio = 2.21; 95% confidence interval = 1.39-3.51; unadjusted p < .001; adjusted p < .025). Mean serum lipopolysaccharide-binding protein levels from inclusion to 7th day were significantly higher in homozygous carriers patients (130.1 [102.9-164.5] and 98.9 [79.7-122.8] microg/mL, respectively) than in noncarriers (101.6 [87.9-117.5] and 58.7 [51.4-67.2] microg/mL, respectively) (p = .046)."]
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['The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model.', '113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO\xa0+\xa0EPO-treated group. EPO (50 U/10\xa0g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult.', 'Body weights of BCAO\xa0+\xa0EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO\xa0+\xa0EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO\xa0+\xa0EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO\xa0+\xa0EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO\xa0+\xa0EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO\xa0+\xa0EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals.']
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['Even though anaemia has been shown to be a risk factor for adverse cardiovascular disease, there is scarce evidence of its relationship with angiographically proven coronary artery disease (CAD). The aim of this study was to evaluate the relationship between haemoglobin (Hb) levels and the extent of CAD.', 'We measured Hb, mean corpuscular volume and red blood cell count in 2363 consecutive patients undergoing coronary angiography. Patients were divided into four groups according to quartile values of Hb (≤12.2 g/dl, group 1; 12.3-13.5 g/dl, group 2; 13.6-14.6 g/dl, group 3; >14.6 g/dl, group 4).', 'Patients with lower Hb were older (P<0.001), there was a predominance of women (P<0.0001), and patients had diabetes (P<0.0001), hypertension (P=0.024), renal failure (P<0.0001), previous coronary artery bypass graft (P<0.0001), previous cerebrovascular accident (P=0.039) and platelet count (P<0.0001). In terms of angiographic features, low Hb levels were associated with a larger prevalence of calcified lesions (P<0.001), but a lower prevalence of thrombus-containing lesions (P<0.001). Hb was not associated with the prevalence of CAD [odds ratio (OR) (95% confidence interval (CI))=0.96 (0.89-1.04), P=0.35], whereas an association was observed with the severity of CAD [OR (95% CI)=0.92 (0.85-0.99), P=0.032] that was not confirmed after correction for baseline confounding factors [OR (95% CI)=0.98 (0.89-1.09), P=0.76]. Similar findings were observed for mean corpuscular volume and red blood cell count.']
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['The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature.', 'Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen.', 'All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes.']
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['The Wave complex activates the Arp2/3 complex, inducing actin polymerization in lamellipodia and membrane ruffles. The Wave complex is composed of five subunits, the smallest of which, Brick1/Hspc300 (Brk1), is the least characterized. We previously reported that, unlike the other subunits, Brk1 also exists as a free form.', 'Here we report that this free form of Brk1 is composed of homotrimers. Using a novel assay in which purified free Brk1 is electroporated into HeLa cells, we were able to follow its biochemical fate in cells and to show that free Brk1 becomes incorporated into the Wave complex. Importantly, incorporation of free Brk1 into the Wave complex was blocked upon inhibition of protein synthesis and incorporated Brk1 was found to associate preferentially with neosynthesized subunits. Brk1 depleted HeLa cells were found to bleb, as were Nap1, Wave2 or ARPC2 depleted cells, suggesting that this blebbing phenotype of Brk1 depleted cells is due to an impairment of the Wave complex function rather than a specific function of free Brk1. Blebs of Brk1 depleted cells were emitted at sites where lamellipodia and membrane ruffles were normally emitted. In Brk1 depleted cells, the electroporation of free Brk1 was sufficient to restore Wave complex assembly and to rescue the blebbing phenotype.']
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['It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women.', '20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions.', 'Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri.']
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['Informational masking (IM) refers to the problem of understanding target speech in the simultaneous presence of a masking speech signal. The adverse effects are attributable to the additional information provided by the competing talker. Cochlear implant (CI) recipients are not able to understand speech satisfactorily in situations such as these. The aim of the present study is to examine the extent to which CI recipients are able to use differences between the speakers with respect to level (target-to-masker ratio, TMR) and fundamental frequency (f0) in order to improve speech intelligibility.', 'Target (TS) and masker sentences (MS) were selected from the Oldenburg Sentence Test (OlSa) and were modified and superimposed. The TS were explicitly labelled using a keyword. The MS were changed with respect to TMR and f0. The TS intelligibility of different modifications was measured in six post-lingually deafened CI recipients and six normal listeners (NL).', 'The NL revealed speech understanding close to 100% even for small differences in f0 of 40 Hz or level differences of 5 dB. In CI recipients, a significant change in intelligibility could only be demonstrated with increased TMR, but not with differences in f0.']
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['to investigate intraocular pressure (IOP) and ocular blood flow (OBF) changes as well as the individual normal range of IOP in patients with age-related macular degeneration (AMD) with or without concomitant glaucoma after intravitreal anti-vascular endothelial growth factor (VEGF) therapy.', 'Group 1 included 34 patients (34 eyes) with AMD and no glaucoma, group 2-34 patients (34 eyes) with both AMD and glaucoma. In all patients the IOP and OBF were measured (with Ocular Blood Flow Analyzer) and the individual normal range of lOP calculated before the treatment, on the third day after the injection and at the 1-month follow-up visit. Statistical analysis was performed by STATISTICA 10.', 'In group 1 there were no significant changes in ocular blood flow at different times after ranibizumab injection. In group 2 a considerable decrease in OBF was detected 1 month after the injection (p<0.001). In group 1 the intraocular pressure was at the same level before and after the treatment. In group 2 the IOP significantly decreased on the third day after the anti-VEGF injection (p=0.03) but was back to the initial level in 1 month. The individual normal range of lOP, when calculated on the third day after the injection, appeared to be much lower than before due to a moderate decrease in both IOP and OBF. At the 1-month follow-up the individual normal range of IOP was back to initial values in non-glaucoma patients but remained low in the glaucoma group due to reduced OBF.']
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['Dome liver lesions (those in segments VII or VIII) pose a challenge to standard laparoscopic resection. The use of additional intercostal and transthoracic trocars (ITTs) potentially facilitates resection over standard subcostal laparoscopic (SSL) techniques.', 'A retrospective review of a prospectively collected liver resection database was performed, selecting all minor resections of segments VII and VIII using the ITT and SSL approaches. The techniques of intercostal transdiaphragmatic access are described and the surgical outcomes of the two groups compared.', 'A total of 19 patients were analysed. The ITT group included 8 patients and the SSL group included 11. The groups were comparable in median lesion size (20\u2009mm in the ITT group and 26\u2009mm in the SSL group). Blood loss, operative times, morbidity and conversion rates were similar. There was no lung injury or postoperative clinical pneumothorax in any patient undergoing transdiaphragmatic access. Median hospital stay was significantly shorter in the ITT group (2 days) than in the SSL group (6 days) (P = 0.032).']
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['Little is known about the clinical efficacy of co-therapy of enprostil, a prostaglandin E2 analogue, with a histamine H2-receptor antagonist. We aimed to assess the additive benefit of enprostil in combination with cimetidine for treating gastric ulcer in a prospective multicenter randomized controlled trial.', 'In 43 hospitals 171 intention-to-treat (ITT) patients, diagnosed as having gastric ulcer by endoscopy, were randomly allocated to receive either enprostil 25microg b.i.d. and cimetidine 400mg b.i.d. (Group E=85), or cimetidine 400mg b.i.d. alone (Group C=86) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks.', 'Per protocol (PP) analysis comprised 166 patients (E=82, C=84). Despite no significant advantage at 4 weeks (E=55.3%, C=42.2%), the combination yielded higher healing rates at 8 weeks by ITT (E=89.4%, C=68.6%; p<0.001) and PP analysis (E=92.7%, C=70.2%; p<0.001). Symptom relief rates [E, C] at 2, 4, and 8 weeks were [80.2%, 68.3%] (not significant), [97.4%, 88.3%] (p<0.05), and [95.6%, 87.0%] (p<0.05), respectively. Significant advantage was observed in the patients aged 40 or older, with solitary ulcer (>5mm in diameter), and without smoking or drinking habits. No adverse effects were critical.']
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['Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined.', 'Previously genome-wide association study-identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos.', 'The C-allele (frequency\u2009=\u200926%) of rs2943650 was significantly associated with higher BF% overall (β = 0.34\u2009±\u20090.11% per allele; P\u2009=\u20090.002) and in women (β = 0.41\u2009±\u20090.14% per C-allele; P\u2009=\u20090.003), but not in men (β = 0.28\u2009±\u20090.18% per C-allele; P\u2009=\u20090.11), though there was no significant sex difference. Using the inverse normal-transformed data to compare effect sizes, it was found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β = 0.054\u2009±\u20090.018SD vs. β = 0.008\u2009±\u20090.011SD per C-allele; P\u2009=\u20090.03). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P\u2009<\u20090.05).']
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['Injury-mediated corneal epithelial wound healing in vivo is mediated through different cell signaling pathways depending on whether or not the basement membrane is removed. Given this dependence, we ascertained if c-jun N-terminal kinase (JNK/SAPK) mitogen-activated protein kinase (MAPK) cell signaling mediates this response in vivo and in vitro, irrespective of the presence or absence of the basement membrane. Furthermore, in vitro the relative contribution was determined by the JNK/SAPK pathway to that of its p38 and ERK MAPK counterparts in mediating injury-induced increases in cell migration.', 'Corneal epithelial debridement was performed in C57BL/6 mice and their organ-cultured eyes without removal of the basement membrane. In rabbits, following basement membrane removal by keratectomy, fluorescein-staining monitored reepithelialization was performed as in the mice. Immunohistochemistry evaluated changes in JNK phosphorylation status and localization. JNK inhibitor I and its inactive analogue determined if JNK signaling activation contributes to wound healing. BrdU staining assessed cell proliferation. A scratch wound assay of healing rates in SV40-immortalized human corneal epithelial cell line (HCEC) evaluated the relative contributions by p38 and ERK and JNK MAPK signaling activation to wound healing. A TUNEL assay probed for apoptosis after wound closure of HCEC. MTT assay evaluated corneal epithelial viability.', 'Two hours following mice corneal epithelial debridement, phospho-JNK was transiently upregulated in the nucleus, whereas total JNK was constitutively expressed. JNK inhibitor I suppressed epithelial spreading in organ-cultured mouse eyes and rabbit corneal blocks, irrespective of the presence or absence of basement membrane. No proliferation was detected at the wound edges. In HCEC, a p38 (SB203580) and a JNK pathway inhibitor (JNK inhibitor I) inhibited migration rates more than U0126-induced ERK, whereas the JNK inhibitor I inactive analogue had no effect. JNK pathway inhibition wound closure in this region was not associated with either any TUNEL or BrdU-positive cells. Cell viability was unaffected by any of these MAPK inhibitors.']
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['The neurofunctional correlates of movement ideation, which should be distinguished from motor imagery, have not been fully investigated. This functional Magnetic Resonance Imaging (fMRI) experiment revealed the brain activation patterns associated with different motor processes, including ideation.', 'Fifteen healthy participants underwent fMRI and performed three tasks using the right index finger: 1. execution of a simple prespecified movement; 2. execution of a simple voluntary movement; 3. ideation of a simple voluntary movement without execution. A number of t-test comparisons across conditions were carried out.', 'The execution ofa simple prespecified finger movement activated the right inferior parietal cortex and substantia nigra, the left middle frontal gyrus, and thalamus, and bilaterally the post-central gyri, the superior parietal lobule and the cerebellum. Execution of a simple voluntary movement activated the left anterior cingulate cortex. The ideation of a voluntary simple movement activated the left inferior, middle and superior temporal gyri and the inferior frontal gyri bilaterally.']
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['We tested the hypothesis that 20-HETE production contributes to platelet derived growth factor (PDGF)-BB stimulated migration of VSMC in a cell culture model.', 'Studies were performed with A10 cells which are a rat vascular smooth muscle derived cell line. Migration was determined using a Boyden chamber chemotactic assay.', 'Pre-treatment of cells with two doses of 20-HETE (100 and 500 nM) significantly increased PDGF-BB stimulated VSMC migration by 34-58% of control; whereas, prior incubation of cells with inhibitors of 20-HETE production, 17-ODYA (1-25 M) or HET0016 (100 nM), significantly decreased PDGF-BB stimulated migration by 40-90%. 20-HETE mediated increase in PDGF-BB migration was completely prevented by the 20-HETE antagonist, WIT-002. In order to determine what second messenger pathways are involved in the 20-HETE mediated stimulation of VSM migration, experiments were performed with specific inhibitors of tyrosine kinase (tyrphostin 25, 10 microM), mitogen-activated extracellular signal-regulated kinase (MEK, PD98059, 20 microM and U0126, 10 microM), protein kinase C (Myr-PKC, 50 microM), and phosphoinositide 3-kinases (PI3Ks) (wortmannin, 50 nM). Blockade of MEK and PI3K all abolished the increase in 20-HETE mediated migration.']
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['Mycophenolate mofetil (MMF) has been shown to be effective for systemic treatment of psoriasis. MMF is the prodrug of mycophenolic acid (MPA), the pharmacologically active compound. The measurement of plasma MPA levels could be useful for optimizing therapeutic management using MMF.', 'To investigate whether plasma trough levels of MPA correlate with the efficacy and safety of oral MMF in the treatment of patients with psoriasis.', 'Six patients (four women and two men, mean age 58 years) with severe chronic plaque-type psoriasis were treated with oral MMF 1 g twice daily. The Psoriasis Area and Severity Index (PASI), routine laboratory examinations and plasma MPA trough levels, measured by an enzyme-multiplied immunoassay (EMIT), were determined at 2 weeks and 1, 3, 5 and 7 months.', 'All the patients experienced a marked improvement within the first 15 days and continued to do so for 5-7 months. Two patients achieved complete remission. MMF was well tolerated. MPA levels showed a wide intra- and interindividual variability. There was no significant correlation between MPA trough levels and the reduction of the PASI or the presence of adverse effects, but a good correlation with therapeutic compliance.']
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['Systemic chemotherapy is being used increasingly in patients with colorectal cancer. The effects of prior systemic adjuvant or palliative chemotherapy on morbidity following hepatic resection for metastases are not well defined.', 'To assess the peri-operative impact of systemic chemotherapy on liver resection for colorectal cancer hepatic metastases.', 'Ninety-six resections for colorectal cancer hepatic metastases performed from July 2001 to July 2003 (93% > or =2 segments) were reviewed. Pre-operative demographics, peri-operative features, and post-operative outcomes were collected prospectively. Type of chemotherapy and the temporal relationship of chemotherapy to the liver resection were analyzed.', 'Fifty-three of 96 patients (55%) received a mean of 5.7 cycles (6.1 months) of systemic chemotherapy prior to hepatic resection, with a median interval of 12 months from end of chemotherapy to liver resection (range 1-75 months). Thirty-five received 5-fluorouracil/leucovorin (5-FU/LV) alone, nine had irinotecan (CPT-11) in addition to 5-FU/LV, and nine were not specified. Pre-operative age, sex, co-morbidities, ASA score, biochemical and liver enzyme profiles, tumor number, and extent and technique of hepatic resection were the same in the chemotherapy and non-chemotherapy cohorts. Mean tumor size was smaller (4.5 cm vs. 5.8 cm) and synchronous metastases were half as common (25% vs. 49%) in the chemotherapy group. Liver resection operative time was equivalent (270 min) in the two groups. Higher estimated blood loss (EBL) (1,000 ml vs. 850 ml), but fewer transfusions (23% vs. 15%) were associated with the chemotherapy group. Although not statistically significant, post-operative liver enzyme peaks were higher in the chemotherapy group (AST = 402 U/L vs. 302 U/L, P = 0.09 and ALT = 433 U/L vs. 312 U/L, P = 0.1). Peak changes in INR and serum bilirubin did not differ. Complications and length of stay (LOS) did not differ between the groups. The only post-operative death was in the non-chemotherapy group. Interestingly, hepatic steatosis was present in 28% of the non-chemotherapy cases and 57% of the chemotherapy resection specimens (P = 0.005) and was marked (>30%) in 7% and 10%, respectively. Further analysis of the chemotherapy group based on the interval between completion of chemotherapy and the hepatic resection (<6 months, 7-12 months, 1-2 years, and >2 years) revealed a trend towards worse outcomes in most categories for those in the >2 years cohort. When comparing the 5-FU/LV alone, to the CPT-11 group there were no significant differences except higher intra-operative blood loss in the group receiving 5-FU/LV alone (1,295 ml vs. 756 ml, P = 0.01).']
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["Noninvasive in vivo imaging of biologic processes using PET is an important tool in preclinical studies. We observed significant differences in 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake in arthritic ankles and carcinomas between dynamic and static PET measurements when mice breathed oxygen. Thus, we suspected that air or oxygen breathing and the anesthesia protocol might influence (18)F-FLT tracer uptake.", 'We injected arthritic, healthy, and CT26 colon carcinoma-bearing mice with (18)F-FLT before static or dynamic small-animal PET measurements. The spontaneously oxygen- or air-breathing mice were kept conscious or anesthetized with ketamine and xylazine during (18)F-FLT uptake before the 10-min static PET measurements. For dynamic PET scans, mice were anesthetized during the entire measurement. (18)F-FLT uptake was reported in percentage injected dose per cubed centimeter by drawing regions of interest around ankles, carcinomas, and muscle tissue. Additionally, venous blood samples were collected before (18)F-FLT injection and after PET measurement to analyze pH, carbon dioxide partial pressure (pCO(2)), and lactate values.', 'A significantly reduced (18)F-FLT uptake was measured in arthritic ankles and in CT26 colon carcinomas when the mice breathed oxygen and were conscious during tracer uptake, compared with mice that were anesthetized during (18)F-FLT uptake. Breathing air completely abolished this phenomenon. Analysis of blood samples that were obtained from the mice before (18)F-FLT injection and after the PET scan implicated respiratory acidosis that was induced by oxygen breathing and consciousness during tracer uptake. Acidosis was found to be the primary factor responsible for the reduced (18)F-FLT uptake, as reflected by increased pCO(2) and reduced pH and lactate values.']
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['High circulating levels of group IIA secretory phospholipase A2 (sPLA2-IIA) activity and mass are independent cardiovascular risk factors. Therefore, inhibition of sPLA2-IIA may be a target for the treatment of atherosclerotic cardiovascular disease. The present study evaluated the effects of sPLA2-IIA inhibition with varespladib acid in a novel mouse model, human apolipoprotein B (apoB)/human cholesteryl ester transfer protein (CETP)/human sPLA2-IIA triple transgenic mice (TTT) fed a Western-type diet.', 'sPLA2-IIA expression increased atherosclerotic lesion formation in TTT compared with human apoB/human CETP double transgenic mice (P<0.01). Varespladib acid effectively inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of varespladib acid to TTT had no impact on atherosclerosis, which could be attributed to a proatherogenic plasma lipoprotein profile that appears in response to sPLA2-IIA inhibition because of increased plasma CETP activity. In the TTT model, sPLA2-IIA decreased CETP activity by reducing the acceptor properties of sPLA2-IIA-modified very low-density lipoproteins specifically because of a significantly lower apoE content. Increasing very low-density lipoprotein-apoE content by means of adenovirus-mediated gene transfer in sPLA2-IIA transgenic mice restored the acceptor properties for CETP.']
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['Although necrosis is an important phenomenon with implications for grading and prognostication in meningiomas, the alternate form of cell death, apoptosis, has not been extensively studied. In this series, we aimed to determine whether apoptosis in meningiomas correlated with histological types and grading. We also looked for a relationship between expression of apoptosis-related genes bcl-2, p53, c-myc and apoptosis meningiomas.', 'Fifty-one meningiomas of diverse histological subtypes and grades were investigated with in situ end-labelling of DNA fragments as well as immunohistochemical analysis of three apoptosis-related genes: p53, bcl-2 and c-myc. Our results showed that the apoptosis index was significantly higher in high-grade meningiomas (0.12%, n = 12) in than the benign meningiomas (0.023%, n = 39) P = 0.001) but there was no difference among the different histological subtypes of the benign meningiomas (P = 0.125). There is no obvious relationship between p53, bcl-2 and c-myc staining and apoptosis index in this group of meningiomas.']
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['Discovery of cancer drivers is a major goal of cancer research. Driver genes and pathways are often predicted using mutation frequency, assuming that statistically significant recurrence of specific somatic mutations across independent samples indicates their importance in cancer. However, many mutations, including known cancer drivers, are not observed at high frequency. Fortunately, abundant information is available about functional "active sites" in proteins that can be integrated with mutations to predict cancer driver genes, even based on low frequency mutations. Further, considering active site information predicts detailed biochemical mechanisms impacted by the mutations. Post-translational modifications (PTMs) are active sites that are regulatory switches in proteins and pathways. We analyzed acetylation and ubiquitination, two important PTM types often involved in chromatin organization and protein degradation, to find proteins that are significantly affected by tumor somatic mutations.', 'We performed computational analyses of acetylation and ubiquitination sites in a pan-cancer dataset of 3200 tumor samples from The Cancer Genome Atlas (TCGA). These analyses were targeted at different levels of biological organization including individual genes, pathway annotated gene sets, and protein-protein interaction networks.', 'Acetylation and ubiquitination site mutations are enriched in cancer with significantly stronger evolutionary conservation and accumulation in protein domains. Gene-focused analysis with the ActiveDriver method reveals significant co-occurrences of acetylation and ubiquitination PTMs and mutation hotspots in known oncoproteins (TP53, AKT1, IDH1) and highlights candidate cancer driver genes with PTM-related mechanisms (e.g. several histone proteins and the splicing factor SF3B1). Pathway analysis shows that PTM mutations in acetylation and ubiquitination sites accumulate in cancer-related processes such as cell cycle, apoptosis, chromatin regulation, and metabolism. Integrated mutation analysis of clinical information and protein interaction networks suggests that many PTM-specific mutations associate with decreased patient survival.']
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['Histological evidence of primary tumor regression (RG) is observed in 35% or fewer patients with cutaneous melanoma. Some advocate a lower threshold for sentinel lymph node (SLN) biopsy when RG is present.', 'We identified 1,349 patients presenting to our center with clinically localized cutaneous melanoma between 1995 and 2004. Of these, 344 demonstrated histological RG in their primary melanoma. A retrospective analysis of their medical records was performed to obtain clinical and pathological information.', 'The median Breslow depth for the 344 patients with RG was 1.1 mm versus 1.5 mm for 1,005 patients with no regression (NRG) (P < 0.005). SLN biopsy was performed in 64% of patients with RG and 72% without. Positive SLN was more common in those with NRG than in those with RG (18% vs 10%, P = 0.005). Only one RG patient with thin melanoma (</=1 mm, Clark IV) had a positive SLN. When stratified by Breslow depth, patients with RG had lower rates of SLN positivity in all groups (</=1.0mm, >1.0 and </=2.0mm, >2 and </=4 mm, and >4.0 mm). Recurrence was more common in patients with NRG (21% vs 12%; P < 0.005). Both local and systemic recurrence occurred more commonly in patients with NRG (4% vs 1%, P = 0.002 and 8% vs 3%, P < 0.005, respectively)']
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['Omeprazole is less effective in healthy subjects than in patients with duodenal ulcers. The aim of this study was to determine whether Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcers.', 'In 16 patients with duodenal ulcers, baseline intragastric acidity was measured before and 4-6 weeks after the cure of H. pylori infection. In 17 patients with duodenal ulcers, 24-hour pH metry was performed during treatment with 20 mg omeprazole once daily before as well as after eradication of H. pylori. Intragastric acidity was measured using a glass electrode placed 5 cm below the cardia. H. pylori infection was assessed by [13C] urea breath test, culture, histology, and rapid urease test.', 'H. pylori eradication resulted in marked decrease of the pH-increasing effect of omeprazole (24-hour median gastric pH, 5.5 vs. 3.0; P<0.002) that was most pronounced during nighttime (median gastric pH, 6.4 vs. 2.1; P=0.001). On the other hand, baseline intragastric pH remained unchanged after eradication (median gastric pH, 1.0 vs. 1.1; P=0.5).']
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['Advances in endoscopic submucosal dissection (ESD) techniques have led to the development of expanded criteria for endoscopic resection of early gas-tric cancer (EGC). The aim of this study was to evaluate the short- and long-term outcomes for ESD using indication cri-teria.', 'A total of 1,105 patients underwent ESD for EGC at six medical centers. The patients were classified into the following two groups based on the lesion size, presence of ulceration and pathological review an absolute criteria group (n=517) and an expanded criteria group (n=588).', 'The curative resection rates (91.1% vs 91.3%, p=0.896) were similar in the absolute criteria group and the expanded criteria group. The en bloc resection rates (93.4% and 92.3%, respectively; p=0.488) and complete resection rates (98.3% and 97.4%, respectively; p=0.357) did not differ between the groups. The cumulative disease-free survival rates and the overall survival rates were similar between the groups (p=0.778 and p=0.654, respectively). Independent factors for the curative resection of EGC included tumor lo-cation (upper vs middle and lower, 2.632 [1.128-6.144] vs 3.497 [1.560-7.842], respectively) and en bloc resection rate 12.576 [7.442-21.250].']
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['Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway.', 'We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets.']
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['The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival.', 'There are many known prognostic indicators following surgery for colorectal cancer (CRC). However, the impact of anastomotic leakage has not been adequately assessed.', 'Consecutive patients undergoing resection between 1971 and 1999 were recorded prospectively in the Concord Hospital CRC database. Total anastomotic leakage was defined as any leak, whether local, general, or radiologically diagnosed. Patients were followed until death or to December 31, 2002. The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival. Confidence intervals (CI) were set at the 95% level.', 'From an initial 2980 patients, 1722 remained after exclusions. The total leak rate was 5.1% (CI 4.1-6.2%). In patients with a leak, the 5-year overall survival rate was 44.3% (CI 33.5-54.6%) compared to 64.0% (CI 61.5-66.3%) in those without leak. In proportional hazards regression-after adjustment for age, gender, urgent resection, site, size, stage, grade, venous invasion, apical node metastasis and serosal surface involvement-anastomotic leakage had an independent negative association with overall survival (hazard ratio [HR] 1.6, CI 1.2-2.0) and cancer-specific survival (HR 1.8, CI 1.2-2.6).']
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['To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis.', "Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.", 'UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization.']
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['The purpose of the study was to compare the rate of secondary resurfacing in a consecutive series of five different total knee arthroplasty (TKA) systems. It was our hypothesis that different TKA design features such as sulcus angle or trochlear height influence the rate of secondary resurfacing.', 'A retrospective study was performed on data from patients who underwent TKA without primary patellar resurfacing from 2004 to 2012 in an university-affiliated hospital. The study cohort included 784 TKA patients (m:f\xa0=\xa0302:482, mean age at surgery\xa0±\xa0SD 71\xa0±\xa010). Five different cruciate-retaining TKA systems were used consecutively (Group A, Triathlon, Stryker, Switzerland (n\xa0=\xa0296), Group B, PFC Sigma, DepuySynthes, Switzerland (n\xa0=\xa0215), Group C, LCS, DepuySynthes, Switzerland (n\xa0=\xa081), Group D, Balansys, Mathys, Switzerland (n\xa0=\xa0128), Group E, Duracon, Stryker, Switzerland (n\xa0=\xa064)). Data were retrospectively obtained from hospital archives. Patients demographics, age at surgery, type of TKA were noted. In addition, TKA component position was assessed on radiographs with respect to "The knee society total knee arthroplasty roentgenographic evaluation and scoring system" (TKA-RESS). Pearson Chi-square test was used to compare differences between groups (p\xa0<\xa00.05). There were no significant differences between the groups in terms of age, gender, and radiological outcomes.', 'Twenty-six of 784 patients (3.3\xa0%) underwent secondary resurfacing due to patellofemoral pain. In group A 4/296 patients (1.4\xa0%), in group B 15/215 patients (7\xa0%), in group C 5/81 patients (6.2\xa0%), in group D 1/128 patients (0.8\xa0%), in group E 1/64 patients (1.6\xa0%) underwent secondary patellar resurfacing during follow-up. Significantly higher rates of secondary patellar resurfacing were seen in groups B and C when compared to the others (p\xa0<\xa00.001). It was found that the trochlear height in these TKA was higher than in the others.']
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['The aim of the study was to conduct a meta-analysis of epidemiological and case control studies to determine whether arterial hypertension is specifically associated with an increased risk of vascular dementia (VaD).', 'Longitudinal and cross-sectional prospective studies using operationalised criteria to define VaD and hypertension, with a normal control comparison group were systematically reviewed. Cochrane Library, Embase, Medline, and PsycInfo data sources were searched along with reference lists of included articles and reviews. Original, prevalence or incidence studies were included if operationalised criteria for hypertension and VaD as well as number of cases with and without hypertension in VaD and non-demented groups were provided. Intervention studies and post-stroke and CADASIL studies were excluded.', 'Eleven studies recruiting either volunteers or clinical patients, or which were population-based, examined a total of 768 people with VaD and 9857 control cases. A meta-analysis of the six longitudinal studies showed that hypertension was significantly associated with increased risk of incident VaD (odds ratio, OR: 1.59, CI: 1.29-1.95, p\u2009<\u20090.0001). A similar association between hypertension and the risk of prevalent VaD was found in the five cross-sectional studies (OR: 4.84, CI: 3.52-6.67, p\u2009<\u20090.00001).']
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['The effects of intrapulmonary artery (i.p.a.) administration of dihydroergotamine mesylate (DHE) were evaluated.', 'Conscious beagle dogs (n=4) were given DHE via the i.p.a. or i.v. route as two 0.014 mg kg(-1) doses and a 0.14 mg kg(-1) dose given 60 min apart. A recovery period of > or =45 h occurred before crossover to the alternative route. Physiological parameters were monitored by telemetry or direct measurement, and venous blood samples were collected for pharmacokinetic assessments.', 'No meaningful differences between i.v. and i.p.a. treatments were observed for heart rate, systemic pressures and vascular pressures. Aortic resistance increased 8, 27 and 70%, respectively, following three doses of i.v. DHE compared with 11, 37 and 57%, respectively, with i.p.a. DHE. Carotid artery resistance increased 22, 40 and 87%, respectively, following three doses of i.v. DHE, compared with 17, 45 and 67%, respectively, following i.p.a. DHE. Increases in coronary artery resistance were of similar magnitude following i.v. and i.p.a. DHE administration. Increases in left ventricular systolic and diastolic pressures were seen following all doses of i.v. and i.p.a. DHE. Changes following DHE 0.014 mg kg(-1) were minimal and not clinically significant. With DHE 0.14 mg kg(-1) by either route, emesis was the most common adverse event.']
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['It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge.', 'Elite adventure racers (n\u200a=\u200a10) and healthy volunteers (n\u200a=\u200a11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspiratory breathing load.']
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['To investigate whether RGD peptide-exposing long circulating polyethylene glycol (PEG) liposomes (RGD-PEG-L) targeted to alphavbeta3 integrins expressed on angiogenic vascular endothelial cells (VECs) are able to bind VECs at sites of inflammation and whether such liposomes containing dexamethasone phosphate (DEXP) can be used as carriers to interfere with the development of experimental arthritis.', 'Binding and internalization of RGD-PEG-L were studied by fluorescence-activated cell sorting and confocal microscopy using fluorescently labeled liposomes. Radiolabeled liposomes were used to test in vivo pharmacokinetics and inflammation site targeting in lipopolysaccharide (LPS)-induced inflammation and adjuvant-induced arthritis (AIA) in rats. In vivo inflammation targeting was visualized by intravital microscopy using fluorescently labeled RGD-PEG-L. Therapeutic efficacy of DEXP-encapsulating RGD-PEG-L compared with nontargeted liposomes was evaluated in rats with AIA.', 'RGD-PEG-L bound to and were taken up by proliferating human VECs in vitro. In vivo, increased targeting of radiolabeled RGD-PEG-L to areas of LPS-induced inflammation in rats was observed. Specific association with the blood vessel wall at the site of inflammation was confirmed by intravital microscopy. One single intravenous injection of DEXP encapsulated in RGD-PEG-L resulted in a strong and long-lasting antiarthritic effect in rat AIA.']
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['To investigate the role of p38MAPK signaling pathway in interleukin (IL)-1beta induced transdifferentiation and its functional influences in human renal proximal tubular cell line HK-2 cells.', 'Human renal proximal tubular cells, cell line HK-2, were cultured and then co-incubated with IL-1beta (10 ng/ml) for 24 hours. The expression and distribution of cytokeratin and alpha-smooth muscle actin (SMA), markers of transdifferentiation of renal proximal tubular cells, were detected by immunofluorescence staining and confocal microscopy. Western blot technique was used to detect the expression of alpha-SMA 2, 4, 6, 12, 24, and 48 hours after IL-1beta stimulation. The morphology of cells was monitored from the 1st to the 5th day. Expression of alpha-SMA, phosphorylation of p38MAPK was assayed by western blot. Specific p38MAPK inhibitor SB203580 was added into the culture of HK-2 cells, 24 hours later IL-1beta was added for 24 hours Cell-cell adhesion and migration assay were performed. Inverted microscopy was used to examine the morphology of cells after stimulation of IL-1beta for 24 hours. Western blot technique was used to detected total and phosphorylated p38MAPK after stimulation of IL-1beta for 2, 5, 15, 30, 60 and 120 min.', 'The phosphorylation of p38MAPK was increased after treatment of IL-1beta, and reached the level of 1.7 times the basic level 5 - 30 minutes after stimulation (P < 0.05). Almost no expression of alpha-SMA was shown in the control group. Two hours after IL-1beta stimulation, the expression of alpha-SMA was increased a little followed by an up-regulated expression of alpha-SMA 6 to 48 hours after the stimulation. The expression of alpha-SMA was down-regulated by 40% in the SB203580 group in comparison with that in the control (P < 0.01) and by 50% in comparison with that in the IL-1beta group (P < 0.001). The cell number was not significantly different between the IL-1beta group and control group (P > 0.05). A decreased expression of cytokeratin and disordered distribution of alpha-SMA were shown in the cells 24 hours after stimulation of IL-1beta. The morphology of cells remained unchanged 1 to 5 days after IL-1beta stimulation. The cell-cell adhesion was almost identical in the groups with IL-1beta and/or SB203580 no in comparison with that in the control group (P > 0.05). The migration ability of HK-2 cells was 2.2 times that in the control group in the IL-1beta group (P < 0.05) and decreased by 35% in the SB203580 group (P < 0.01). SB203580 uppercased the IL-1beta-induced expression of alpha-SMA and the enhancement of cell migration ability were suppressed by 51% (P < 0.05).']
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["Couroupita guianensis Aublet, 'macacarecuia', 'abricó-de-macaco', 'castanha-de-macaco' and 'amêndoa-dos-andes', is found in tropical regions and is widely used in the treatment of tumors, pain, and inflammatory processes.", 'Ethanol extract and hexane and ethyl acetate fractions were evaluated in models of inflammatory pain (formalin-induced licking) and acute inflammation (carrageenan-induced peritonitis).', 'Ethanol extract, hexane and ethyl acetate fractions (10, 30 or 100 mg/kg, p.o.) and the reference drugs dexamethasone (5 mg/kg), morphine (5 mg/kg, s.c.), and acetylsalicylic acid (100 mg/kg, p.o.) were tested in formalin-induced licking response and carrageenan-induced peritonitis.', 'All three doses from Couroupita guianensis fractions significantly reduced the time that the animal spent licking the formalin-injected paw in first and second phases. However, only higher doses (30 and 100 mg/kg) were able to inhibit the leukocyte migration into the peritoneal cavity after carrageenan injection. In this model, the 100 mg/kg dose almost abolished the cell migration. It was also observed that protein concentration resulted from extravasation to the peritoneum and nitric oxide (NO) productions were significantly reduced. Cytokines production was differently affected by the treatment. TNF-α production was reduced after ethanol extract and ethyl acetate fraction pre-treatment whereas hexane fraction had effect only with 100 mg/kg dose. IL-1β production was inhibited only after hexane fraction pre-treatment. The inhibitory effect observed was not due to a direct cytotoxic effect on cells nor to a NO-scavenger activity. The effect was due to a direct inhibition on NO production by the cells.']
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['The periodontal ligament (PDL) is continually exposed to mechanical loading caused by mastication or occlusion. Physiological loading is thus considered a key regulator of PDL tissue homeostasis; however, it remains unclear how this occurs. We recently reported that an appropriate magnitude of mechanical stretch can maintain PDL tissue homeostasis via the renin-angiotensin system. In the present study, we investigated the expression of interleukin-11 (IL-11) in human primary PDL cells (HPDLCs) exposed to stretch loading, the contribution of angiotensin II (Ang II) to this event and the effects of IL-11 on osteoblastic/cementoblastic differentiation of human PDL progenitor cells (cell line 1-17).', 'Human primary PDL cells, derived from human tissues, with or without antagonists against the Ang II receptors AT1 or AT2, were subjected to cyclical stretch loading with 8% elongation for 1\xa0h. Expression of IL-11 was measured by ELISA in these cultures and by immunohistochemistry in the sectioned maxillae of rats. The osteoblastic/cementoblastic potential of cell line 1-17 was determined using cell proliferation, gene expression and Alizarin Red staining.', 'Positive staining for IL-11 was observed in the PDL of rat maxillae and in cultures of HPDLCs. In HPDLCs exposed to stretch, expression of the IL11 gene and the IL-11 protein were up-regulated, concomitant with an increase in Ang II and via AT2. Recombinant human IL-11 (rhIL-11) stimulated an increase in expression of mRNA for the cementoblast-specific marker, CP-23, and for the osteoblastic markers, osteopontin and bone sialoprotein, and promoted proliferation in cell line 1-17. In addition, rhIL-11 also increased the degree of mineralized nodule formation in cell line 1-17 cultures treated with CaCl2 .']
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['Accumulation of the excitatory neurotransmitter glutamate in ischemic brain tissue contributes to neuronal cell death. Volatile anesthetics at clinically relevant concentrations are neuroprotective in in vivo models of brain ischemia and reduce glutamate release in vivo and in vitro, but they appear to have weaker neuroprotective effects than hypothermia. The purpose of this study was to determine whether isoflurane reduces glutamate release in hypoxic brain slices, how large this effect is compared to that of hypothermia, and if it is diminished by hyperthermia.', 'Glutamate released from rat cortical brain slices during chemical anoxia (100 microM NaCN) was measured continuously with a fluorescence assay. The release rate was compared at three temperatures (28 degrees C, 37 degrees C, and 39 degrees C) with and without isoflurane at concentrations equipotent to 1 minimum alveolar concentration. At the same three temperatures, glutamate release rates before and after exposure to isoflurane were compared.', 'Isoflurane reduced glutamate release from brain slices during chemical anoxia at 37 degrees C (19.6%, P < 0.01) and at 39 degrees C (25.4%, P < 0.01), but not at 28 degrees C. The reduction in glutamate release with hypothermia was similar to that with isoflurane. Hyperthermia (39 degrees C) caused greater glutamate release under basal and anoxic conditions than normo- and hypothermia. Isoflurane caused a slight increase in basal glutamate release rates, although this effect was smaller than the increase caused by hyperthermia.']
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['Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 (COX-2) overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.', 'The effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag/Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE(2) and celecoxib levels were determined.', 'CC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 microg/ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 microg/ml were needed to affect tumor cell viability.']
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['To determine the morningness-eveningness (ME) distribution of emergency medicine (EM) residents.', "A voluntary, modified ME questionnaire was administered to all EM residents in the United States at the time of the 1995 American Board of Emergency Medicine's annual In-Training Examination.", 'Seventy-eight percent (2,047/2,614) of the surveys were returned. ME scores ranged from 24 to 76, with a median score of 49 (interquartile range 44, 56). The scores were distributed differently from those of the normal population (p < 0.001), being skewed toward eveningness. There was a correlation (r = 0.13, p < 0.0001) between resident age and ME score, with older residents being more morning-oriented. Males were more morning-oriented than females (p = 0.005), and respondents with children living at home also were significantly more morning-oriented (p < 0.001). Stepwise logistic regression showed that the influence of age, gender, and children was cumulative (r = 0.19) but accounted for only 4% of the observed variability.']
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['Tumor necrosis factor alpha (TNFalpha) is associated with trauma-induced hearing loss. Local treatment of cochleae of trauma-exposed animals with a glucocorticoid is effective in reducing the level of hearing loss that occurs post-trauma (e.g., electrode insertion trauma-induced hearing loss/dexamethasone treatment).', 'Dexamethasone (Dex) protects auditory hair cells (AHCs) from trauma-induced loss by activating cellular signal pathways that promote cell survival.', 'Organ of Corti explants challenged with an ototoxic level of TNFalpha was the trauma model with Dex the otoprotective drug. A series of inhibitors were used in combination with the Dex treatment of TNFalpha-exposed explants to investigate the signal molecules that participate in Dex-mediated otoprotection. The otoprotective capacity of Dex against TNFalpha ototoxicity was determined by hair cell counts obtained from fixed explants stained with FITC-phalloidin labeling with investigators blinded to specimen identity.', 'The general caspase inhibitor Boc-d-fmk prevented TNFalpha-induced AHC death. There was a significant reduction (p<0.05) in the efficacy of Dex otoprotection against TNFalpha ototoxicity when the following cellular events were blocked: (1) glucocorticoid receptors (Mif); (2) PI3K (LY294002); (3) Akt/PKB (SH-6); and (4) NFkappaB (NFkappaB-I).']
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['Neurofilaments (Nfs) are protein biomarkers of neurodegeneration in human disease. There is in vivo evidence of changes of the Nf stoichiometry in the cerebrospinal fluid (CSF) of patients. The protein-structural implications of these findings are not known but may be assessed indirectly using simulations studies.', 'Monte Carlo simulations were performed using a coarse-grained model of a Nf brush. Based on the published in vivo CSF data the tested Nf stoichiometries (NfL:NfM:NfH) were 16:11:4 for multiple system atrophy (MSA), 24:5:2 for relapsing remitting multiple sclerosis (RRMS), and 30:0:1 for clinically isolated syndromes (CIS). Simulations were performed in a wide range of ionic strength (1 mM-100 mM) for dephosphorylated and phosphorylated NF isoforms.', 'At lower ionic strengths (1 mM, 10 mM), NfM is the main determinant for the radius of gyration (R(g)) ranging from ≈15 nm in the dephosphorylated state at 10 mM ionic strength to ≈27 nm at 1mM ionic strength if fully phosphorylated. At high ionic strength (100mM) NfH becomes the main determinant with R(g) of 14.8±0.2 nm if dephosphorylated and 15±0.2 nm if phosphorylated. There was no significant difference in the structures of the three Nf sidearms for MSA, RRMS or CIS.']
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['Aldosterone levels are high early after admission for ST elevation myocardial infarction (STEMI) concomitantly with high risk of sudden death and life-threatening ventricular arrhythmia.', 'We assessed the hypothesis that early aldosterone blockade on admission for primary percutaneous coronary intervention (PCI) may be associated with a reduction of life-threatening ventricular arrhythmia in a prospective cohort-nested case (n=159) versus historical control (n=623) study. All cases were treated on admission by 200mg IV bolus of potassium canrenoate, followed by 25mg PO spironolactone daily during the coronary care unit stay. The primary endpoint--in-hospital composite of death, resuscitated cardiac arrest and ventricular tachycardia--was assessed by logistic regression models adjusted on major pre-specified variables and validated by a bootstrap procedure and propensity-score based analyses.', 'Aldosterone blockade was associated with lower risks of the primary endpoint (adjusted ORs 0.26, 95% CI [0.13-0.57]), resuscitated cardiac arrest (adjusted OR 0.39, 95% CI [0.16-0.94]), ventricular tachycardia or fibrillation (adjusted ORs 0.23, 95% CI [0.12-0.45]), as well as ventricular arrhythmia requiring resuscitation or anti-arrhythmic therapy (adjusted OR 0.41, 95% CI [0.19-0.88]). All findings were confirmed by the bootstrap procedure. The benefit on death or resuscitated cardiac arrest seemed sustained at 6month follow-up.']
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['As an acute-phase protein synthesized in response to systemic inflammation, the C-reactive protein (CRP) has been shown to be an independent prognostic factor for patients with castration-resistant prostate cancer (CRPC). The aim of this study was to investigate the association between CRP and progression-free survival (PFS), overall survival (OS) and radiological response in CRPC patients treated with docetaxel.', '115 histologically confirmed CRPC patients who were treated with docetaxel chemotherapy from 2008 to 2013 were selected. Univariable and multivariable Cox regression models were used to predict the association of CRP as a dichotomous variable with PFS and OS after chemotherapy initiation.', 'None of the clinicopathological features were associated with the CRP. In Kaplan-Meier analysis, the median PFS (9.8 vs. 7.5 months, p < 0.001) and OS (26.5 vs. 13.5 months, p = 0.002) were higher in patients who did not have an elevated CRP than in those with an elevated CRP. In univariable analysis, the pretreatment CRP was significantly associated with PFS (p < 0.001) and OS (p = 0.003).In multivariable analysis, patients with a CRP > 8 mg/l were at significantly higher risk of tumor progress (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.401-3.403; p = 0.001) and death (HR 2.003; 95% CI 1.285-3.121; p = 0.002) than patients with a CRP ≤ 8 mg/l.']
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['Use of fluoroscopy and bone landmarks to guide percutaneous common femoral artery (CFA) access has decreased access site complications compared with palpation alone. However, only limited case series have examined the benefits of ultrasound to guide CFA access during peripheral vascular intervention (PVI). We evaluated the effect of routine vs selective use of ultrasound guidance (UG) on groin hematoma rates after PVI.', 'The Vascular Study Group of New England database (2010-2014) was queried to identify the complication of postprocedural groin hematoma after 7359 PVIs performed through CFA access. Hematoma (including pseudoaneurysms) was defined as minor (requiring compression or observation), moderate (requiring transfusion or thrombin injection), and major (requiring operation). Both procedure-level and interventionalist-level analyses were performed. Multivariable Poisson regression models were used to compare hematoma rates of interventionalists based on routine (≥80% of PVIs) and selective (<80%) utilization of UG in the adjusted overall sample and in multiple subgroups.', 'The overall postprocedural groin hematoma rate after PVI was 4.5%, and the rate of combined moderate and major hematoma was 0.8%. Among 114 interventionalists with ≥10 PVI procedures, routine and selective UG was used by 31 (27%) and 83 (73%) interventionalists, respectively. Routine UG was protective against hematoma (rate ratio [RR], 0.62; 95% confidence interval [CI], 0.46-0.84; P < .01). Subgroup analysis revealed that routine UG was also protective against hematoma under the following circumstances: age >80 years (RR, 0.47; 95% CI, 0.27-0.85; P = .01), body mass index ≥30 (RR, 0.51; 95% CI, 0.29-0.90; P = .02), and sheath size >6F (RR, 0.43; 95% CI, 0.23-0.79; P < .01).']
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['Cytochrome P450 monooxygenases (P450s) catalyze oxidation of various substrates using oxygen and NAD(P)H. Plant P450s are involved in the biosynthesis of primary and secondary metabolites performing diverse biological functions. The recent availability of the soybean genome sequence allows us to identify and analyze soybean putative P450s at a genome scale. Co-expression analysis using an available soybean microarray and Illumina sequencing data provides clues for functional annotation of these enzymes. This approach is based on the assumption that genes that have similar expression patterns across a set of conditions may have a functional relationship.', 'We have identified a total number of 332 full-length P450 genes and 378 pseudogenes from the soybean genome. From the full-length sequences, 195 genes belong to A-type, which could be further divided into 20 families. The remaining 137 genes belong to non-A type P450s and are classified into 28 families. A total of 178 probe sets were found to correspond to P450 genes on the Affymetrix soybean array. Out of these probe sets, 108 represented single genes. Using the 28 publicly available microarray libraries that contain organ-specific information, some tissue-specific P450s were identified. Similarly, stress responsive soybean P450s were retrieved from 99 microarray soybean libraries. We also utilized Illumina transcriptome sequencing technology to analyze the expressions of all 332 soybean P450 genes. This dataset contains total RNAs isolated from nodules, roots, root tips, leaves, flowers, green pods, apical meristem, mock-inoculated and Bradyrhizobium japonicum-infected root hair cells. The tissue-specific expression patterns of these P450 genes were analyzed and the expression of a representative set of genes were confirmed by qRT-PCR. We performed the co-expression analysis on many of the 108 P450 genes on the Affymetrix arrays. First we confirmed that CYP93C5 (an isoflavone synthase gene) is co-expressed with several genes encoding isoflavonoid-related metabolic enzymes. We then focused on nodulation-induced P450s and found that CYP728H1 was co-expressed with the genes involved in phenylpropanoid metabolism. Similarly, CYP736A34 was highly co-expressed with lipoxygenase, lectin and CYP83D1, all of which are involved in root and nodule development.']
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['Diabetes has adverse effects on the retinal microvasculature. The purpose of this study was to compare the effects of inhalation of hypoxic, hyperoxic and normoxic-hypercapnic gas mixtures on retinal vessel diameter in people with and without diabetes.', 'Sixty-one participants (aged 24-50 years) 29 with (male : female ratio 2.6 : 1) and 32 without (male : female ratio 0.7 : 1) diabetes, inhaled hypoxic, hyperoxic and normoxic-hypercapnic gas mixtures for 3-5 mins. The diameters of arterioles and venules were measured using digital retinal images taken before and after gas inhalation.', 'There was no significant difference in the diameters of arterioles and venules prior to gas inhalation in people with and without diabetes. Inhalation of the hyperoxic gas mixture caused a statistically significant decrease in arteriolar and venular diameters without altering mean arterial pressure significantly. Arteriolar vasoconstriction in response to the hyperoxic gas mixture was significantly reduced in people with diabetes (3.95% versus 7.75%; p = 0.04), but venular vasoconstriction did not differ significantly. A hypoxic gas mixture caused increased arteriolar and venular diameter and a normoxic-hypercapnic gas mixture had no significant effect on vessel diameter. Responses to hypoxic and normoxic-hypercapnic gas did not differ significantly between diabetes and non-diabetes subjects.']
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['Sleep quality declines with age, with less time in deep or slow wave sleep (SWS) and reduced amplitude of the delta waves that characterize it. Age-related declines also occur in lean body mass, growth hormone (GH), and insulin-like growth factor 1 (IGF-1). These changes in sleep quality and anabolic status may be related, as administration of GH or growth hormone releasing hormone (GHRH) can enhance SWS and decrease awakenings in young men. Here we examine the relationship between plasma IGF levels and delta sleep quality in older men.', 'The sleep EEG of 30 healthy elderly men (64 +/- 6 yrs; range 50-75) was recorded on the second of 2 consecutive nights. Plasma samples were drawn within 3 weeks of EEG recording, and IGF levels were assayed by RIA after acid extraction.', 'IGF explained 28% (semi-partial correlation coefficient r = .53; p = .003) of the variance in average delta energy per epoch of SWS, after age-related variance was removed. Higher IGF was associated with higher average delta energy. Similar results were obtained for total delta energy during SWS (r = .37, p = .04) 4nd time spent in SWS (r = .42, p = .02). Other measures of sleep quality (e.g., wakefulness, REM sleep) were not correlated with IGF. The IGF delta relationship was minimally influenced by moderator variables such as thyroxine (T3, T4), and/or body mass index (BMI).']
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['Naïve and memory T cells can utilize unique regulatory pathways to promote protection but prevent self-reactivity. A bacterial superantigen SEB exploits unique TCR proximal signaling processes in memory CD4 T cells to induce clonal anergy. The aim of this study was to determine if SEB could antagonize memory CD4 T cells ', 'BALB/c mice were primed with TNP-RGG to elicit memory B cells and also immunized with an ovalbumin peptide to elicit memory helper T cells. Another group of TNP-RGG immunized mice were used as adoptive transfer recipients of exogenous DO11.10 memory T cells. Mice were challenged with TNP-OVA with or without prior administration of SEB. B cells secreting IgM or IgG TNP-specific Ab were enumerated by ELISPOT as indicators of primary versus secondary humoral immunity.', 'Comparing the SEB and non-SEB-treated groups, the SEB-treated group failed to produce TNP-specific IgG in response to challenge with TNP-OVA, even if they were previously immunized with OVA. All groups produced IgM, indicating that the primary Ab responses and naïve helper T cells were not impacted by SEB. SEB had no negative impact when DO11.10 × Fyn']
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['We investigated whether parental history of hypertension (FH+) enhances the impact of depressed mood, indexed by Beck Depression Inventory (BDI), on ambulatory blood pressure (ABP).', 'Twenty-four-hour ABP, urinary norepinephrine (NE), and cortisol were obtained in 314 unmedicated normotensive and hypertensive men and women (age 18-64 years) who also completed the BDI.', 'Subjects with a positive family history of hypertension (N = 177) exhibited significantly greater mean body mass index (BMI) and ABP compared with subjects without (N = 137). Importantly, when covarying for age, BMI, gender, and race, linear regressions revealed significant FH by BDI interactions. Higher BDI scores were significantly associated with higher 24-hour ABP in FH+ subjects, but not in FH- participants. Relationships were significantly stronger in those with two hypertensive parents vs. those with one vs. those with no hypertensive parents. Increases in BDI scores were significantly related to greater heart rate (HR) and 24-hour urinary NE in both FH+ and FH- groups, although no evidence of a mediational role for NE in the effect of BDI score on blood pressure (BP) or HR was seen.']
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['To compare the effect of totally thoracoscopic with conventional, open repair of atrial septal defect.', 'Forty atrial septal defect cases were divided into two groups by surgical approach: totally thoracoscopic approach (group A, n\u2009=\u200920) and conventional open approach (group B, n\u2009=\u200920). In group A, surgical procedures were performed through three portal incisions in the right lateral chest wall under thoracoscopic vision without the aid of a computerized robotic surgical system. Notably, all operations were completed by one surgeon who had just begun using this technique. In group B, the atrial septal defects were repaired in conventional open fashion. Clinical outcomes and serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), intercellular adhesion molecule 1 (ICAM-1), and creatine kinase isoenzyme-myocardial band (CK-MB) for the two groups were evaluated and compared.', 'All operations were performed successfully without serious complications. Durations of cardiopulmonary bypass (CPB), CPB setup, aortic cross-clamping, and operative procedure were significantly longer in group A than in group B (P\u2009<\u20090.05). The recovery times for body temperature and laboratory values of leukocytes were significantly shorter for group A than for group B (P\u2009<\u20090.05). There were no differences in durations of postoperative assisted ventilation or intensive care unit and hospital stays, volumes of blood transfused intraoperatively or thoracic drainage, or medical costs between the two groups. Serum levels of inflammatory factors (TNF-α, IL-6, IL-10, and ICAM-1) and CK-MB increased significantly in both groups after surgery. However, 6\xa0h and 12\xa0h after surgery, levels of these inflammatory factors and CK-MB were significantly lower in group A than in group B (P\u2009<\u20090.05).']
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['Decreased spinal excitability contributes to the immobilizing effects of halogenated ethers during general anaesthesia. Recurrent spinal responses such as F-waves reflect spinal excitability and are suppressed by volatile anaesthetics. To evaluate whether F-waves are suitable for monitoring immobility, the concentration-dependent effects of sevoflurane on F-waves were compared with effects on the Bispectral Index (BIS). The predictive power of all parameters for movement responses to noxious stimuli was tested. In addition, the effect of the noxious stimulus itself on F-waves was investigated.', 'In 28 patients, F-waves were recorded during sevoflurane anaesthesia at a frequency of 0.2 Hz at the lower limb. To insert a laryngeal mask, the sevoflurane concentration was initially increased to approximately 4%, which caused a complete extinction of F-waves. The sevoflurane concentration was then reduced until the F-waves recovered. BIS and spectral edge frequency (SEF(95)) were recorded continuously. The t(1/2ke0) and EC(50) values of the F-wave persistence and amplitude were calculated using a standard pharmacokinetic-pharmacodynamic model. During decreasing sevoflurane concentration motor responses to tetanic electrical stimulation (50 Hz, 60 mA, 5 s, volar forearm) were tested in seven patients and MAC(tetanus) was calculated using logistic regression.', 'Sevoflurane reduces the F-wave amplitude with an EC(50) of 0.79 vol% at a far lower concentration than the calculated MAC(tetanus) (1.5 vol%), whereas the F-wave persistence yields an EC(50) of 1.4 vol%. Spinal and EEG parameters predicted the motor responses to movement better than chance alone, but did not differ significantly from each other.']
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['Prostacyclin (PGI2) that is released from the vascular endothelium plays an important role in vasodilatation and thrombo-resistance, and it has long been suspected to protect cell survival. How it does so has never been clear. Recently, it has been shown that the NADPH oxidase 4 (Nox4) improves endothelial cell functions and promotes angiogenesis in vivo, but it was not known how to boost Nox4 therapeutically to exploit its protective functions in the vasculature. Here, we identified such a stimulus.', 'The selective and stable prostacyclin receptor (IP-R) agonist cicaprost increases the expression of Nox4 in human endothelial cells of several types, including endothelial progenitor cells. The elevation of cellular cyclic-AMP increased Nox4 expression and H2O2 production and prevented endothelial cell apoptosis. We delineate the intracellular signaling that promotes cytoprotection: Cicaprost acts via the IP-R/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein pathway. Importantly, the up-regulation of Nox4 by cicaprost also enhanced endothelial cell proliferation, migration, and angiogenesis, with all effects being substantially decreased by Nox4 gene silencing. Finally, cicaprost enhanced the growth of blood vessels into subcutaneous sponges implanted in mice, an effect that was also blocked by Nox4 gene silencing.', 'The prostacyclin analogue cicaprost induces Nox4 via IP receptor-cAMP/PKA/CREB pathway. The activation of this pathway protects endothelial cells and enhances pro-angiogenic activity both in vitro and in vivo.']
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["Resveratrol is a polyphenol present in red wine for which the capability of directly interfering with the hallmark of Alzheimer's disease (AD), i.e. toxic β-amyloid protein (Aβ) aggregation, has been shown recently. Since the stimulation of proteostasis could explain reduced Aβ-aggregation, we searched for proteostasis targets of resveratrol.", 'The transgenic Caenorhabditis elegans strain CL2006, expressing Aβ1-42 under control of a muscle-specific promoter and responding to Aβ-toxicity with paralysis, was used as a model. Target identification was accomplished through specific knockdowns of proteostasis genes by RNA interference. Effects of resveratrol on protein aggregation were identified using ProteoStat(®) Detection Reagent, and activation of proteasomal degradation by resveratrol was finally proven using a specific fluorogenic peptide substrate.', 'Resveratrol at a concentration of 100 µM caused a 40 % decrease in paralysis. UBL-5 involved in unfolded protein response (UPR) in mitochondria proved to be necessary for the prevention of Aβ-toxicity by resveratrol. Also XBP-1, which represents an endoplasmic reticulum-resident factor involved in UPR, was identified to be necessary for the effects of resveratrol. Regarding protein degradation pathways, the inhibition of macroautophagy and chaperone-mediated autophagy prevented resveratrol from reducing paralysis as did the inhibition of proteasomal degradation. Finally, resveratrol reduced the amount of lysosomes, suggesting increased flux of proteins through the autophagy pathways and activated proteasomal degradation.']
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['To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis.', 'Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization.', 'In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined.']
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['We studied obstetric delivery practices for fetal gastroschisis and correlated this with neonatal outcomes. Our objectives were to identify changes in delivery practices over time and to determine if these changes resulted in improved neonatal outcomes.', 'After IRB approval, maternal and neonatal records from 219 gastroschisis births between 1990 and 2008 were reviewed. Obstetrical data and neonatal data were collected. Univariate comparisons were made between maternal delivery variables and neonatal outcomes. Significant and clinically relevant obstetrical variables were combined for multivariate linear regression modeling.', 'The practice of elective cesarean delivery (ELCS) shifted to spontaneous vaginal delivery (sVD) over time (p <0.001). Babies born by sVD had longer hospitalization than those born by ELCS (median 36.0 vs 21.6days, p <0.05). Gestational age (GA) and birth weight were similar between groups. Babies born by induced VD (iVD) had short hospitalization (median 22.5days). A linear regression model demonstrated that spontaneous onset of labor (SOL) and GA were independently related to LOS.']
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['Intestinal barrier failure may lead to systemic inflammation and distant organ injury in patients following severe injury. Enteric glia cells (EGCs) have been shown to play an important role in maintaining gut barrier integrity through secretion of S-Nitrosoglutathione (GSNO). We have recently shown than Vagal Nerve Stimulation (VNS) increases EGC activation, which was associated with improved gut barrier integrity. Thus, we sought to further study the mechanism by which EGCs prevent intestinal barrier breakdown utilizing an in vitro model. We postulated that EGCs, through the secretion of GSNO, would improve intestinal barrier function through improved expression and localization of intestinal tight junction proteins.', 'Epithelial cells were co-cultured with EGCs or incubated with GSNO and exposed to Cytomix (TNF-α, INF-γ, IL-1β) for 24 hours. Barrier function was assessed by permeability to 4kDa FITC-Dextran. Changes in tight junction proteins ZO-1, occludin, and phospho-MLC (P-MLC) were assessed by immunohistochemistry and immunoblot.', 'Co-culture of Cytomix-stimulated epithelial monolayers with EGCs prevented increases in permeability and improved expression and localization of occludin, ZO-1, and P-MLC. Further, treatment of epithelial monolayers with GSNO also prevented Cytomix-induced increases in permeability and exhibited a similar improvement in expression and localization of occludin, ZO-1, and P-MLC.']
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['This study assessed how positive expiratory pressure (PEP) affected pulmonary function, functional capacity, and subjective cough difficulty in individuals with chronic obstructive pulmonary diseases (COPD).', 'This was a prospective, randomized, controlled study. Subjects were recruited from an outpatient department at a university hospital. Thirty-two patients with COPD were allocated to either PEP + FET (forced expiratory technique) group (n = 16) or FET only group (n = 16). Subjects in PEP + FET and FET groups were in a clinically stable condition before and during the study. Subjects in the PEP + FET group received PEP breathing using a mouth adjunct to FET, and the FET group was administered FET for 4 weeks only. Patients received weekly follow-up during the study period. Pulmonary function, 6-minute walk tests, and subjective cough difficulty scores were measured before and after the 4-week interventions.', 'Subjects in the PEP + FET group had a significantly increased diffusing capacity (DLCO) compared to preintervention (p < 0.05) and after intervention in the FET group (p < 0.05). DLCO significantly increased in the PEP + FET group from 18.0 +/- 7.3 to 20.1 +/- 7.2 mL/min/mmHg. The 6-minute walking distance (6MWD) also increased significantly from 516.8 +/- 94.1 to 570.6 +/- 60.4 m in the PEP + FET group (p < 0.001) after intervention, compared to that for the FET group (p < 0.05). Additionally, the PEP + FET group had significantly lower cough difficulty scores compared to those at baseline and in the FET group.']
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['The loss of skeletal muscle mass and strength during aging, sarcopenia, increases the risk for falls and dependency. Resistance exercise (RE) training is effective at improving muscle mass and strength in older adults; however, aging is associated with reduced training-induced hypertrophy. Recent research has illustrated an impaired muscle protein synthetic response following an acute bout of RE in older adults but much less is known regarding the effect of acute RE on muscle protein breakdown (MPB). We hypothesize that the ubiquitin proteasome system and the autophagosomal-lysosomal system may regulate the overall rate of MPB during postexercise recovery.', 'Muscle biopsies of the vastus lateralis were sampled from 16 older (age = 70±2 years) and 16 younger (age = 27±2 years) participants at baseline and at 3, 6, and 24 hours following an acute bout of RE. In conjunction with stable isotopic techniques to measure MPB, we utilized immunoblotting and RT-PCR to examine protein and mRNA expression for key signaling molecules in both the ubiquitin proteasome system and the autophagosomal-lysosomal system.', 'MuRF1 mRNA expression increased, whereas GABARAP mRNA decreased after RE in both younger and older adults (p < .05). The LC3B-II/LC3B-I protein ratio decreased in both groups after RE (p < .05), but MPB was not different 24 hour post-RE in either group (p > .05).']
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['Cardiac hypertrophy occurs in response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway has previously been strongly associated with hypertrophic signaling in the heart, and with the control of cell size in multiple contexts. This pathway is tightly regulated by many factors, including a host of kinases and phosphatases that function at multiple steps in the signaling cascade. For example, the PTEN (phosphatase and tensin homolog) tumor suppressor protein is a phosphoinositide 3-phosphatase that, by metabolizing phosphatidylinositol 3,4,5-trisphosphate (PtdIns[3,4,5]P(3), PIP3), acts in direct antagonism to growth factor-stimulated PI3K. Inhibition of PTEN leads to cardiomyocyte hypertrophy. Another polyphoinositide phosphatase, inositol polyphosphate-5-phosphatase F (Inpp5f) has recently been implicated in regulation of cardiac hypertrophy. Like PTEN, this phosphatase can degrade PtdIns(3,4,5)P(3) and thus modulates the PI3K/Akt pathway.', 'To characterize the role of Inpp5f in regulating cardiac hypertrophy.', 'We generated homozygous Inpp5f knockout mice and cardiac specific Inpp5f overexpression transgenic mice. We evaluated their hearts for biochemical, structural and functional changes. Inpp5f knockout mice have augmented hypertrophy and reactivation of the fetal gene program in response to stress when compared to wild-type littermates. Furthermore, cardiac overexpression of Inpp5f in transgenic mice reduces hypertrophic responsiveness.']
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['A phenomenon of cross-talk has been noted that electrical stimulation of one part of the gut affects another part of the gut. This study was designed to investigate whether the effect of electrical stimulation of one part of the gut on another part of the gut was related to the organ or the distance between the stimulation site and the affected organ, and the mechanism of ileum electrical stimulation on rectal tone.', 'This study was performed in 13 healthy dogs (16-28 kg) in the fasting state. Experiments were performed to study 1) effects of gastric electrical stimulation, duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation on rectal tone, and 2) the sympathetic and nitrergic pathways involved in the effects of ileum electrical stimulation on rectal tone. A computerized barostat was used to assess rectal tone.', 'All methods of stimulations significantly inhibited rectal tone. Duodenal electrical stimulation was least effective in reducing rectal tone. The percentage of increase in rectal volume was distance-related with duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation but organ-specific with gastric electrical stimulation. The inhibitory effect of ileum electrical stimulation on rectal tone was abolished by N omega-nitro-L-arginine but not guanethidine.']
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['To determine the role of microvenous valves in the superficial venous system in the prevention of reflux and skin changes in the progression of venous insufficency.', 'The venous anatomy of 15 amputated lower limbs, eight free from clinical venous disease and seven with varicose veins and ulcers, was examined using retrograde venography corrosion casting. Prior to amputation, all limbs were scanned by duplex ultrasound to confirm the presence or absence of reflux in the great (GSV) and small saphenous veins or their tributaries. The resulting resin casts were photographed and mapped to show the position, orientation, and competency of valves in the superficial venous network. Casts were also examined by scanning electron microscopy.', 'Retrograde venous filling was demonstrated in the "normal" limbs despite a competent GSV. Microvalves were identified down to the sixth generation of tributaries from the GSV. Only in regions where incompetence existed in microvalves out to the third (ie, the "boundary") generation was the resin able to penetrate deeper into microvenous networks of the dermis. This was despite the presence of subsequent competent valves, which were able to be bypassed in the network. In limbs with varicose veins and venous ulcers, reflux into the small venous networks and capillary loops was more extensive with more dense networks and greater tortuousity.']
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['Combinatorial therapies that target multiple signaling pathways may provide improved therapeutic responses over monotherapies. In the present study, we evaluated the effect of celecoxib and AEE788 alone and in combination on cell proliferation, invasion, migration, angiogenesis, morphological changes, actin filament organization and apoptosis induction in the human colon cancer cell lines.', 'Effect of celecoxib and AEE788 alone and in combination on colon cancer cell lines was evaluated by cell proliferation assay, morphological analysis, cell cycle analysis, scratch-wound healing and chorioallantoic membrane assays, zymography, nuclear fragmentation and western blot analyses.', 'Either drug alone or in combination inhibited human colonic adenocarcinoma cell lines HCT 15 and HT 29 in a dose-dependent manner. Microscopic analysis revealed inhibition of cell membrane extensions, cell shrinkage, and disorganization of actin filaments. Additionally, either drug alone or in combination inhibited HCT 15 migration, invasion and angiogenesis by suppressing matrix metalloproteinase-2 and -9 activities. Increased reactive oxygen generation, loss of mitochondrial membrane potential, cleavage of PARP, caspase-3 activation and DNA ladder formation characterized the induction of apoptosis by celecoxib and/or AEE788 treatment. Either drug individually induced apoptosis via down-regulation of the anti-apoptotic proteins Bcl(2) and Bcl-x(L), and up-regulation of pro-apoptotic protein Bax, cleavage of PARP, activation of caspase-3 and inhibition of vascular endothelial growth factor receptor signaling pathways.']
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['Many behavior change programs are delivered in group settings to manage implementation costs and to foster support and interactions among group members in order to facilitate behavior change. Understanding the group dynamics that evolve in group settings (e.g., weight management, Alcoholics Anonymous) is important, yet rarely measured. This article examined the relationship between social network ties and group cohesion in a group-based intervention to prevent obesity in children.', 'The data reported are process measures from an ongoing community-based randomized controlled trial. A total of 305 parents with a child (3-6 years) at risk of developing obesity were assigned to an intervention that taught parents healthy lifestyles. Parents met weekly for 12 weeks in small consistent groups. Two measures were collected at Weeks 3 and 6: a social network survey (people in the group with whom one discusses healthy lifestyles) and the validated Perceived Cohesion Scale. We used lagged random and fixed effects regression models to analyze the data.', 'Cohesion increased from 6.51 to 6.71 (t= 4.4,p< .01). Network nominations tended to increase over the 3-week period in each network. In the combined discussion and advice network, the number of nominations increased from 1.76 to 1.95 (z= 2.59,p< .01). Cohesion at Week 3 was the strongest predictor of cohesion at Week 6 (b= 0.55,p< .01). Number of new network nominations at Week 6 was positively related to cohesion at Week 6 (b= 0.06,p< .01). In sum, being able to name new network contacts was associated with feelings of cohesion.']
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['Nicotine plays an important role in cigarette-smoke-associated airway disease. The present study was designed to examine if nicotine could induce airway hyperresponsiveness through kinin receptors, and if so, explore the underlying mechanisms involved.', 'Murine tracheal segments were cultured for 1, 2 or 4 days in serum-free DMEM medium in presence of nicotine (1 and 10 microM) or vehicle (DMSO). Contractile responses induced by kinin B1 receptor agonist, des-Arg9-bradykinin, and B2 receptor agonist, bradykinin, were monitored with myographs. The B1 and B2 receptor mRNA expressions were semi-quantified using real-time PCR and their corresponding protein expressions assessed with confocal-microscopy-based immunohistochemistry. Various pharmacological inhibitors were used for studying intracellular signaling pathways.', 'Four days of organ culture with nicotine concentration-dependently increased kinin B1 and B2 receptor-mediated airway contractions, without altering the kinin receptor-mediated relaxations. No such increase was seen at day 1 or day 2. The airway contractile responses to 5-HT, acetylcholine and endothelin receptor agonists remained unaffected by nicotine. Two different neuronal nicotinic receptor antagonists MG624 and hexamethonium blocked the nicotine-induced effects. The enhanced contractile responses were accompanied by increased mRNA and protein expression for both kinin receptors, suggesting the involvement of transcriptional mechanisms. Confocal-microscopy-based immunohistochemistry showed that 4 days of nicotine treatment induced activation (phosphorylation) of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38. Inhibition of JNK with its specific inhibitor SP600125 abolished the nicotine-induced effects on kinin receptor-mediated contractions and reverted the enhanced receptor mRNA expression. Administration of phosphodiesterase inhibitors (YM976 and theophylline), glucocorticoid (dexamethasone) or adenylcyclase activator (forskolin) suppressed the nicotine-enhanced airway contractile response to des-Arg9-bradykinin and bradykinin.']
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['The absorption of carbon dioxide (CO2) used for positive pressure pneumoperitoneum may lead to an increased CO2 load. CO2 elimination during laparoscopy has not been investigated previously in paediatrics. The aim of this study was to characterise the pattern of CO2 elimination during laparoscopic surgery in infants and children.', 'Twenty children undergoing laparoscopy and 19 children undergoing laparotomy for elective abdominal operations were studied. Pneumoperitoneum was achieved using insufflation of unheated CO2. CO2 elimination (metabolically produced + absorbed; milliliters per kilogram per minute) was measured minute by minute during the operation by indirect calorimetry. End-tidal CO2 (kPa) was recorded every 10 minutes. The above variables were assessed before CO2 insufflation, during pneumoperitoneum, and after desufflation.', 'Before insufflation, CO2 elimination was 4.6 +/- 0.3 ml/kg/min and increased after 15 minutes of pneumoperitoneum to 5.2 +/- 0.3 (P <.001). Post desufflation, CO2 elimination decreased toward preinsufflation values, but did not return to baseline by the end of operation (5.8 +/- 0.3; P <.001). End-tidal CO2 was 4.7 +/- 0.2 preinsufflation, peaked at 1 hour (5.3 +/- 0.2; P <.001) and subsequently decreased in response to ventilatory adjustments. The total amount of CO2 insufflated was positively correlated with patient age (r2 = 0.27; P <.01). CO2 elimination was age related, as indicated by multilevel model analysis and by negative correlations between maximum increase in CO2 elimination and both age (r2 = 0.27; P <.01) and weight (r2 = 0.29; P <.01). These data suggest that the younger or smaller the child, the larger the increase in CO2 elimination. Seven patients (35%) responded to desufflation with a sharp transient increase in CO2 elimination, which did not appear to be related to patient age, length of pneumoperitoneum, abdominal pressure, or type of operation.']
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['To evaluate the direct in vitro cytotoxicity of vasoactive agents (papaverine, phentolamine, and prostaglandin E(1) [PGE(1)]) to human penile cavernosal smooth muscle cells. Intracavernous pharmacotherapy with vasoactive agents for male erectile dysfunction has been associated with long-term complications such as a reduction in penile smooth muscle content and fibrosis.', "Human penile cavernosal tissue explants (1 to 2 mm(3) size) were obtained with proper institutional review board approval from patients undergoing penile prosthesis implantation. Primary culture was initiated in Dulbecco's modified Eagles medium containing 10% fetal bovine serum, and monolayer cavernosal cells were grown in 48-well tissue culture dishes. At 60% to 80% confluence, cells were labeled overnight with (51)Na(2)CrO(4) (1.5 microCi) and then incubated with therapeutic concentrations of papaverine (1.5 to 30 mg/mL), phentolamine (0.5 mg/mL), and PGE(1) (5 microg/mL) alone, as well as in combination, for 30 minutes at 37 degrees C. At the end of incubation, an aliquot of supernatant was collected in scintillation vials. The release of cell-free chromium in supernatants was determined in a liquid scintillation counter, and results were expressed as the percentage of cytotoxicity.", 'Papaverine induced a significant dose-dependent increase in chromium release from the cavernosal cells. At therapeutic concentrations, papaverine (30 mg/mL) produced up to 60% cytotoxicity; PGE(1) (5 microg/mL) resulted in 40% toxicity. The combination of papaverine with either PGE(1) or phentolamine had a cumulative toxic effect, and maximal toxicity (70%) was observed with the triple combination.']
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['Changes in the deduced amino acid sequence of the envelope 2 (E2) region of the GB virus C/hepatitis G virus (GBV-C/HGV) were analyzed to investigate whether or not the region contributes to persistent infection with the virus.', 'Eight patients with acute hepatitis C and 1 patient with acute hepatitis of unknown etiology were included in the study. GBV-C/HGV RNA was detected in 6 patients, including the patient with hepatitis of unknown origin. The nucleotide sequence of the E2 region of hepatitis C virus (HCV) and GBV-C/HGV was determined by direct sequencing of polymerase chain reaction products in 5 patients with HCV infection and in 6 patients with GBV-C/HGV infection twice during the period of early infection and several months or years later in each patient.', 'The mean substitution rate of the deduced amino acid sequence in the E2 region was over 100 times lower (p < 0.001) in GBV-C/HGV (0.01 +/- 0.04/month/100 sites) than in HCV (2.4 +/- 1.7/month/100 sites). The amino acid sequence of the loop domain of GBV-C/HGV-E2 did not change in any of the 6 patients. On the other hand, the sequence of the hypervariable region of HCV-E2 changed remarkably (5.9 +/- 4.3/month/100 sites). No amino acid substitution in the loop domain was observed in 7 additional patients who showed persistent GBV-C/HGV viremia for more than 2 years.']
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['Corticotropin-releasing hormone (CRH) is a major regulator of adrenocorticotropic hormone and the production of glucocorticoids by the adrenal gland. Abnormal regulation of CRH and endogenous glucocorticoids has been implicated in the pathogenesis of asthma.', 'We postulated that CRH deficiency could increase asthma severity by disrupting hypothalamus-pituitary-adrenal axis function and the induction of glucocorticoids through inflammatory and physiologic stress. However, CRH is expressed by several types of immune cells and might be induced at sites of inflammation, where it has local immunostimulatory actions. Thus CRH deficiency could decrease asthma severity.', 'To test these possibilities, we subjected CRH-knockout mice to an ovalbumin-induced airway inflammation protocol that mimics many features of asthma.', 'CRH-knockout mice had an increase in airway inflammation of approximately 80% to 300% and an increase in goblet cell hyperplasia of approximately 70% compared with wild-type mice. In contrast, IgE induction was unaffected by CRH deficiency. The increased inflammation in knockout mice was associated with increased tissue resistance, elastance, and hysteresivity. Levels of IL-4, IL-5, IL-13, RANTES, IFN-gamma, and eotaxin were all increased in knockout mice. Serum corticosterone levels were decreased in knockout mice and might account for some of the differences between knockout and wild-type mice.']
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["Exposure of the American bullfrog Lithobates catesbeianus tadpoles to low temperature affects many biological processes including lipid metabolism and the thyroid hormone (TH) signaling pathway, resulting in arrest of TH-induced metamorphosis. To clarify what molecular events occur in this phenomenon, we investigated the glycerophospholipid and fatty acid (FA) compositions, the activities of mitochondrial enzymes and the transcript levels of related genes in the liver of control (26\xa0°C) and cold-treated (4\xa0°C) tadpoles with or without 5\xa0nM 3,3',5-triiodothyronine (T3).", 'Exposure to T3 decreased the tail height and polyunsaturation of FAs in the glycerophospholipids, and increased plasma glucose levels and transcript levels of primary TH-response genes including TH receptor, and some energy metabolic (cox4, srebp1 and fas) and FA chain elongase genes (elovl3 and elovl5). However, these T3-induced responses were abolished at 4\xa0°C. Exposure to cold temperature enhanced plasma glucose, triglyceride and free FA levels, monounsaturation of FAs, mitochondrial enzymes activities (cytochrome c oxidase and carnitine palmitoyltransferase; U/g liver), with the upregulation of the genes involved in glycogenolysis (pygl), gluconeogenesis (pck1 and g6pc2), FA β-oxidation (acadl), and cholesterol uptake and synthesis (hmgcr, srebp2 and ldlr1), glycerophospholipids synthesis (pcyt1, pcyt2, pemt, and pparg), and FA monounsaturation (scd1) and chain elongation (elovl1 and elovl2). T3 had little effect on the cold-induced changes.']
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['Balance impairments have been identified in people with osteoporosis. Although an association between thoracic kyphosis and impaired balance has been reported, the specific role of vertebral fractures has not been considered. This study aimed to investigate the independent effects of osteoporotic vertebral fracture and thoracic kyphosis on balance characteristics in an osteoporotic population.', 'Twenty-two individuals with osteoporosis were divided into groups with (n=10) and without (n=12) radiologically diagnosed fracture, and into groups with low (n=11) and high (n=11) thoracic kyphosis. Force-plate-derived balance parameters were recorded during three static standing tasks of 70-s duration. Balance measures were compared between fracture and kyphosis groups, and significant differences were further explored through subgroup analyses, to tease out the relationships between confounded independent variables (fracture and kyphosis) and balance measures.', 'In the anterior-posterior direction, the range and root mean square of shear forces (p=0.048 and p=0.032, respectively), and range of displacement of the centre of pressure (p=0.049) were greater in the fracture group. There were no differences between groups when comparison was based on the magnitude of thoracic kyphosis (all p>or=0.264). Analyses of subgroups supported these findings.']
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['Our group and others have shown that serial intra-lesional injections of common warts with skin testing reagents such as Candida, mumps and Trichophyton are effective in regressing injected and non-injected warts. Anti-HPV T-cell responses appear to be induced. The goal of this study was to understand the mechanisms of how Candida skin testing reagent enhances immune responses.', 'The following immunological features were studied to understand how Candida induces immune responses in healthy subjects: (1) proliferative capacity of T-cells upon exposure to Candida through monocyte-derived human Langerhans cells (LCs) measured using alamarBlue, (2) cytokine (IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN-γ, and TNF- expression upon Candida stimulation of LCs by quantitative reverse transcription (qRT)-PCR and cytokine secretion by ELISA, (3) expression of pattern recognition receptors (PRRs) known to associate with Candida albicans (DC-SIGN, dectin-1, dectin-2, galectin-3, mincle, mannose receptor, Toll-like receptors 1, 2, 4, 6, and 9) on LCs by qRT-PCR, (4) role of dectin-1 in IL-12 production by antibody blocking, and (5) induction of Th1, Th2, and/or Th17 responses by intracellular cytokine staining of CD4 cells exposed to Candida pulsed LCs for IFN-γ, IL-4, and IL-17A.', 'T-cell proliferation upon stimulation with Candida-pulsed LCs was significantly higher compared to proliferation in the absence of Candida (p=0.004). The most frequently expressed cytokine in stimulated LCs was IL-12p40 mRNA, and IL-12p40 and IL-12p70 were also detected at protein levels. All other cytokine mRNAs examined were detected in the following order of decreasing frequency: IL23Ap19, IFN-γ, IL-1β, IL-6, IL-8, and IL-10. LCs expressed all PRRs examined. Anti-dectin-1 inhibited IL-12p40 mRNA production upon Candida stimulation of LCs from some healthy subjects. IFN-γ secretion was increased and IL-4 secretion was decreased in CD4 cells of a few healthy subjects, but IL-17A was essentially unchanged upon Candida treatment.']
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["Melatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.", 'An overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD\u2009+\u2009RBD+), ten PD patients without RBD (PD\u2009+\u2009RBD-), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.', 'From the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.']
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['High-level emergency medical care requires transfer of evidence-based knowledge into practice. Our study is the first to investigate the feasibility of checklists in improving prehospital emergency care.', 'Three checklists based on standard operating procedures were introduced: General principles of prehospital care, acute coronary syndrome and acute asthma/acutely exacerbated chronic obstructive pulmonary disease. Subsequent to prehospital care and immediately before transport, information on medical history, diagnostic and therapeutic procedures was obtained. Data of 740 emergency missions were recorded prospectively before (control group) and after implementation of checklists and compared using the χ-test (significance level P<0.05).', "Documentation on patients' history (pre-existing diseases: 69.1 vs. 74.3%; medication: 55.8 vs. 68.0%; allergies: 6.2 vs. 27.7%) and diagnostic measures (oxygen saturation: 93.2 vs. 98.1%; auscultation: 11.1 vs. 19.9%) as well as basic treatment procedures (application of oxygen: 73.2 vs. 85.3%; intravenous access: 84.6 vs. 92.2%) increased significantly. Subanalysis of acute coronary syndrome cases showed a significant increase of 12-lead ECG use (74.3 vs. 92.4%), administration of oxygen (84.2 vs. 98.6%), ASA (71.7 vs. 81.9%), heparin (71.1 vs. 84.0%), β blockers (39.5 vs. 57.1%) and morphine (26.8 vs. 44.6%). In the chronic obstructive pulmonary disease subgroup, oxygen supply (78.8 vs. 98.5%) and application of inhalative and intravenous β2-mimetics (42.4 vs. 66.7% and 12.1 vs. 37.9%) increased significantly."]
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['The X-linked inhibitor of apoptosis (XIAP) belongs to a family of proteins that suppresses apoptosis by inhibition of caspases in some cancers. It confers resistance to apoptosis induction by chemotherapeutic agents. The aim of this study was to evaluate the influence of XIAP in pancreatic cancer.', 'Tissue samples from 43 patients with pancreatic adenocarcinoma (median age of 67 years, range from 39-81 years) were analyzed. Pancreatic samples from healthy organ donors (10) and chronic pancreatitis patients (10) served as controls. XIAP expression and localization analysis was carried out by quantitative RT-PCR and immunohistochemistry (IHC). XIAP silencing was achieved by transfection of specifically designed siRNA oligonucleotides. Proliferation and chemotherapy experiments were performed by MTT cell growth assays.', 'There was a 2.1-fold increase of median XIAP mRNA levels in pancreatic cancers compared to controls. Kaplan-Meier analysis indicated a tendency for reduced patient survival with increasing levels of XIAP mRNA (higher levels: 13.4 months; lower levels: 16.1 months). IHC revealed strong XIAP staining in tubular complexes and pancreatic cancer cells. XIAP silencing resulted in a slight reduction of the proliferation of Capan-1 and T3M4 pancreatic cancer cells. In addition, XIAP silencing resulted in increased sensitivity of both cell lines to gemcitabine.']
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['Several studies have shown, that circulating tumor cells (CTC) have a negative prognostic value in colorectal cancer patients. Aim of this study was to evaluate the role of CTC in specifically rectal cancer patients regarding the influence on overall survival and to elucidate the impact of CTC in predicting response after chemoradiation (RCTX).', 'In this prospective monocentric study 267 patients with rectal cancer were included. Patients with locally advanced tumors were treated with RCTX followed by surgery. The primary endpoints were: Evaluation of CTC at the time of surgery and correlation with main tumor characteristics, response to neoadjuvant RCTX and overall survival (OS). CTC were detected in the blood using CK20 RT-PCR.', 'Sixty-three patients were treated with neoadjuvant RCTX. In 46.8% of the patients receiving neoadjuvant RCTX CTC were detected, which was significantly higher than in the group without RCTX (p=0.002). Histopathologic regression after RCTX was evident in 27.8% of the patients. In the subgroup of responders after RCTX we found CTC at a significantly lower rate than in non-responders (p=0.03). No significant association was found between CTC detection and tumor characteristics and OS. The OS was significantly improved for responders compared to non-responders (p=0.007).']
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['Risk of cardiovascular events is higher in patients with chronic kidney disease. The objective is to evaluate whether glomerular filtration rate (GFR) on admission is an independent predictor of short-term mortality in acute myocardial infarction (AMI), after adjusting with physiologic derangements in an acute setting.', '220 consecutive patients with an admitting diagnosis of AMI were enrolled in a 1-year prospective observational study at a tertiary care teaching institute. Data were gathered for history, physical examination and laboratory findings. GFR was calculated based on the Modification of Diet in Renal Disease formula. Abnormal categories of physiological derangement indicators were weighted based on APACHE II guidelines. The endpoint was defined as in-hospital all-cause mortality.', 'There were 31 deaths (14.1%). The GFR (mean +/- SD) in survivors as compared to deceased patients was 68.2 +/- 33.8 and 41.7 +/- 25.1 ml/min/1.73 m2, respectively (p < 0.001). The mean age, white blood cell count, blood urea nitrogen, potassium and blood sugar were higher on admission in patients who died in hospital (p < 0.05), while the mean albumin, mean arterial pressure, pulse and respiratory rate were lower in this group compared to survivors (p < 0.05). After adjusting with other covariates, each 10 ml/min/1.73 m2 decrease in GFR was associated with a 1.29 times increased risk of mortality (95% CI 1.08-1.53, p = 0.004).']
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['To date no semiochemicals affecting the pre-oviposition behaviour of the malaria vector Anopheles gambiae sensu lato have been described. Water vapour must be the major chemical signal emanating from a potential larval habitat, and although one might expect that gravid An. gambiae s.l. detect and respond to water vapour in their search for an aquatic habitat, this has never been experimentally confirmed for this species. This study aimed to investigate the role of relative humidity or water vapour as a general cue for inducing gravid An. gambiae sensu stricto to make orientated movements towards the source.', 'Three experiments were carried out with insectary-reared An. gambiae s.s. One with unfed females and two with gravid females during their peak oviposition time in the early evening. First, unfed females and gravid females were tested separately in still air where a humidity difference was established between opposite ends of a WHO bioassay tube and mosquitoes released individually in the centre of the tube. Movement of mosquitoes to either low or high humidity was recorded. Additionally, gravid mosquitoes were released into a larger air-flow olfactometer and responses measured towards collection chambers that contained cups filled with water or empty cups.', 'Unfed females equally dispersed in the small bioassay tubes to areas of high and low humidity (mean 50% (95% confidence interval (CI) 38-62%). In contrast, gravid females were 2.4 times (95% CI 1.3-4.7) more likely to move towards high humidity than unfed females. The results were even more pronounced in the airflow olfactometer. Gravid females were 10.6 times (95% CI 5.4-20.8) more likely to enter the chamber with water than a dry chamber.']
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['To evaluate whether a uterus with a small septum (arcuate uterus or class VI according to the American Fertility Society (AFS) classification) behaves similarly to a uterus with a larger septum (septate or subseptate uterus or AFS class V).', 'Observational study included 826 singleton deliveries to 730 women with a history of hysteroscopic resection of the uterine septum. Data on deliveries were obtained from the National Perinatal Registry of Slovenia (NPIS). Multiple gestations were excluded. We analysed and compared perinatal outcomes before and after hysteroscopic resection in two groups of women: in women with a small uterine septum (Group A) and in those with a larger uterine septum (Group B). Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4-cm long yellow tip of the electric knife to the length of the resected septum. A small uterine septum was defined as having a length of 1.3-1.5 cm.', 'The preterm birth rate in Group A (n=420) was 33.9% before and 7.2% after hysteroscopic resection (P<0.001); the preterm birth rate in Group B (n=406) was 36.5% before and 8.0% after hysteroscopic resection (P<0.001). The very preterm birth rate in Group A was 12.5% before and 3.1% after hysteroscopic resection (P<0.001); the very preterm birth rate in Group B was 15.0% before and 2.9% after hysteroscopic resection (P<0.001). After surgery, we registered a decreased need for neonatal intensive care, as well as a significant decrease in stillbirth and neonatal death rates in both groups of patients.']
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['Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels.', 'Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay.', 'There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls.']
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