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['We have previously demonstrated that insulin sensitivity and secretion at age 1 year was in part related to variation in weight and height gain during infancy. In order to determine whether genetic variation at the insulin gene could also influence these associations, we have studied the relationship between insulin gene variable number of tandem repeat (INS VNTR) genotypes, insulin secretion and early postnatal growth.', 'We assessed fasting and dynamic insulin secretion in 99 healthy infants at age 1 year, using a short intravenous glucose tolerance test (sIVGTT). Infants were genotyped at the -23 HphI locus, as a surrogate marker for INS VNTR allele classes I and III. Anthropometric data were recorded at birth and at 1 year. Data are shown as median (interquartile range).', 'Fasting insulin levels were higher in III/III infants (n = 9) than in I/I infants [n = 55; 27.4 (17.6-75.6) pmol/l vs. 18.1 (10.3-25.2) pmol/l; P < 0.05]. Insulin secretion during the sIVGTT, as estimated by the serum insulin area under the curve, was also higher in III/III infants [2417 (891-4041) pmol min/l vs. 1208 (592-2284) pmol min/l; P < 0.05]. Fasting and postload plasma glucose levels were similar in both groups. Analysis of covariance showed that genotype differences in fasting insulin sensitivity and insulin secretion were independent of size at birth, postnatal growth velocity and current body mass index.'] |
['Perceived partner concurrency, reporting that a current sexual partner has other sexual partners, may pose sexual health risks to adolescents. We examined the contextual characteristics of African American female adolescents who reported their current boyfriend was having concurrent sexual relationships.', 'Participants were African American adolescent females (N = 511; mean age = 17.6) recruited from sexual health clinics. Before participating in an STD/HIV prevention trial, the participants completed audio computer-assisted self-interviews with measures of perceived partner concurrency and individual- (e.g., depression, substance use), interpersonal- (e.g., social support, interpersonal stress), and community-level factors (i.e., neighborhood quality).', 'Twenty-seven percent of participants reported their belief that their current boyfriend had concurrent sexual partners during their relationship. In a logistic regression analysis, participants endorsing perceived partner concurrency reported less relational power (adjusted odds ratio [AOR] = .94, 95% confidence interval [CI] = .89-.98, p < .01), decreased relationship commitment (AOR = .88, 95% CI = .80-.96, p < .01), elevated perceived interpersonal stress (AOR = 1.02, 95% CI = 1.003-1.04, p < .05), and previous STD diagnoses (AOR = 2.07, 95% CI = 1.31-3.28, p < .01; overall model: χ(2) = 67.25; p < .001).'] |
['To examine in a nonclinical sample of preadolescents the possibility that somatic and cognitive-affective depressive symptoms are differentially related with the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Depression is a well-known risk factor for cardiovascular disease and mortality. Dysregulation of the ANS and the HPA axis have been proposed as underlying mechanisms. Several studies suggest that only a subset of the depression symptoms account for associations with cardiovascular prognosis.', "Self-reported somatic and cognitive-affective depressive symptoms were examined in relationship to heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and the cortisol awakening response (CAR) in 2049 preadolescents (mean age = 11.1 years; 50.7% = girls) from the Tracking Adolescents' Individual Lives Survey (TRAILS).", 'Physiological measurements were not associated with the overall measure of depressive symptoms. Somatic depressive symptoms were negatively related to HRV and BRS, and positively to the CAR; cognitive-affective depressive symptoms were positively related to HRV and BRS, and negatively to the CAR. Associations with the CAR pertained to boys only.'] |
['To investigate whether intermittent pneumatic compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD).', 'Nineteen healthy limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF--sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe.', 'Baseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .0002 for combined foot and calf compression).'] |
['The aim of this study was to determine the effects of the isopropanolic extract of black cohosh (Remifemin) on mammographic breast density and breast epithelial proliferation in healthy, naturally postmenopausal women with climacteric symptoms.', 'This was a prospective, open, uncontrolled drug safety study in which baseline status was compared with status after 6 months of treatment by blinded observers. A total of 74 women were treated with 40 mg black cohosh daily, and 65 women completed the study. Mammograms were performed, and breast cells were collected by percutaneous fine needle aspiration biopsies at baseline and after 6 months. Mammographic density was quantified according to the Wolfe classification or a percentage scale. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. Safety was monitored by adverse event reporting, laboratory assessments, and measurement of the endometrium by vaginal ultrasound.', 'None of the women showed any increase in mammographic breast density. Furthermore, there was no increase in breast cell proliferation. The mean change +/- SD in proportion of Ki-67-positive cells was -0.5% +/- 2.4% (median, 0.0; 95% CI = -1.32 to 0.34) for paired samples. The mean change in endometrial thickness +/- SD was 0.0 +/- 0.9 mm (median, 0.0). A modest number of adverse events were possibly related to treatment, but none of these were serious. Laboratory findings and vital signs were normal.'] |
['Luminex-based single-antigen human leukocyte antigen (HLA) antibody detection beads (SAB) are a major advance for the characterization of HLA-specific antibodies but their clinical utility is limited unless the analysis is performed and interpreted optimally. Here, we identify problems encountered in routine monitoring of antibody levels that may give rise to misleading results, and describe how these can be overcome to provide more meaningful clinical information.', 'HLA class I specific antibody-binding levels were determined using SAB in the sera of 42 highly sensitized patients awaiting renal transplantation. Normalization of the results against the HLA class I specific monoclonal antibody W6/32 overcame the problems caused by variation in antigen density on SAB and also suggested the presence of alloantibodies directed against multiple HLA class I epitopes of a given specificity. Routine analysis using undiluted sera gave an incomplete assessment of antibody levels. On serum dilution, three patterns of antibody binding became apparent: most sera showed a sequential reduction in immunoglobulin G (IgG) binding levels but several sera displayed antibody binding which remained unchanged (suggesting antigen saturation) or increased IgG binding on serum dilution (suggesting inhibition of IgG binding using neat serum). The presence of immunoglobulin M (IgM) HLA-specific antibodies in sera correlated with inhibition of IgG antibody binding for the corresponding specificity and treatment of sera with dithiothreitol to eliminate IgM HLA-specific blocking antibodies restored maximum IgG antibody binding levels.'] |
['A recessively transmitted fatal hypertonic infantile muscular dystrophy has been described in Canadian aboriginals. The affected infants present with progressive limb and axial muscle stiffness and develop severe respiratory insufficiency, and most die in the first year of life. We sought to determine the genetic basis of this disease.', 'We performed histochemical, immunocytochemical, electron microscopy, and molecular genetic studies in a cohort of 12 patients affected by this disease.', 'Conventional histochemical and electron microscopy studies suggested myofibrillar myopathy (MFM). Therefore, we searched for ectopic expression of multiple proteins typical of MFM. Alpha B-crystallin (αBC) expression was absent from all fibers using a monoclonal antibody raised against the entire protein. However, a monoclonal antibody directed against the first 10 residues of αBC immunostained portions of abnormal fibers. Pursuing this clue, we searched for mutations in the gene for αBC (CRYAB) in available DNA samples of 8 patients. All harbored a homozygous deletion, c.60C, predicting a Ser to Ala change at codon 21 and a stop codon after 23 missense residues (p.Ser21AlafsX24). Clinically unaffected parents were heterozygous for this mutation.'] |
['The angiotensin II type 1 receptor-associated protein (Atrap) is highly expressed in the heart, but its function in the heart is unknown. We hypothesized that cardiac Atrap may interact with proteins other than the AT1 receptor.', 'To identify potential novel interacting partners of Atrap, pull-down assays were performed. Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon resonance (SPR) spectroscopy. Atrap enhanced the SERCA-dependent Ca(2+) uptake in isolated SR membrane vesicles. Furthermore, sarcomere shortenings and [Ca(2+)]i transients (CaTs) were determined in ventricular myocytes isolated from Atrap-/- and wild-type (WT) mice. The amplitudes of CaTs and sarcomere shortenings were similar in Atrap-/- and WT myocytes. However, the CaT decay and sarcomere re-lengthening were prolonged in Atrap-/- myocytes. To further evaluate the functional relevance of the Atrap-SERCA2a interaction in vivo, left-ventricular function was assessed in WT and Atrap-/- mice. The heart rates (564 ± 10 b.p.m. vs. 560 ± 11 b.p.m.; P = 0.80) and ejection fractions (71.3 ± 1.3 vs. 72 ± 1.8%; P = 0.79) were similar in WT and Atrap-/- mice, respectively (n = 15 for each genotype). However, the maximum filling rate (dV/dtmax) was markedly decreased in Atrap-/- (725 ± 48 µL/s) compared with WT mice (1065 ± 122 µL/s; P = 0.01; n = 15).'] |
['The purpose of this study was to investigate the effects of two vasoactive agents, dopamine and dopexamine, on the depression of mesenteric blood flow caused by positive end-expiratory pressure (PEEP) during mechanical ventilation.', "Sprague-Dawley rats were mechanically ventilated with either no PEEP (control group) or increasing levels of PEEP (PEEP group) up to 20 cm H2O pressure. We evaluated PEEP's effect on blood pressure, cardiac output (CO), and the mesenteric microcirculation with a continuous infusion of 2.5 or 12.5 micrograms/kg/min dopamine or 1, 3, or 5 micrograms/kg/min dopexamine.", 'PEEP caused a 20% to 25% decrease in mean arterial pressure and a 30% decrease in CO at both 15 and 20 cm H2O of PEEP (all p < 0.05 versus baseline). Low dose dopamine partially corrected the decrease in CO to 16% and 21% below baseline at 15 and 20 cm H2O of PEEP, respectively (both p < 0.05 versus PEEP group) and partially ameliorated the depression of mesenteric blood flow associated with the application of PEEP. High dose dopamine did not positively affect either CO or mesenteric blood flow. Dopexamine had little effect on CO compared with dopamine. All three doses of dopexamine blocked the effect of PEEP on mesenteric blood flow (p < 0.05 compared with the PEEP group at all levels of PEEP, p < 0.05 compared with the low dose dopamine group at 15 and 20 cm H2O of PEEP).'] |
['Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.', 'We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.', 'Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.'] |
['Aim of this experimental animal study was to investigate the influence of vasopressin and amiodarone on cardiopulmonary resuscitation (CPR) outcome in a pig model of hypothermic cardiac arrest.', 'After surface cooling to a core temperature of 26 degrees C, ventricular fibrillation was induced in 14 12-16-week-old domestic pigs. After 15 min of untreated cardiac arrest, a manual closed chest CPR was started and pigs were randomly assigned to two treatment groups: Group 1 pigs (n = 7) received vasopressin 0.4 U kg-1 as initial drug therapy, followed by a combination vasopressin (0.4 U kg-1) and amiodarone (4 mg kg-1) as subsequent drug therapy. Subsequent drug therapy was administered in animals without permanent restoration of spontaneous circulation after a first series of electrical countershocks 10 min after drug administration. Group 2 pigs (n = 7) received saline placebo as initial drug therapy and saline placebo and amiodarone (4 mg kg-1) as subsequent drug therapy.', 'Vasopressin significantly increased coronary perfusion pressure and defibrillation success (successful defibrillation in five of seven Group 1 vs. none of seven Group 2 pigs, P = 0.02). Due to refibrillation within 30-150 s, the 60-min survival rate was not improved by vasopressin. Subsequent drug therapy with amiodarone had no further effect on defibrillation success or the refibrillation rate.'] |
['To examine the cross-sectional association of whole-knee synovitis assessed by contrast-enhanced magnetic resonance imaging (CEMRI) with radiographic tibiofemoral osteoarthritis (OA), non-CEMRI-assessed cartilage damage, and meniscal status.', 'Multicenter Osteoarthritis Study (MOST) is a cohort study of people with or at high risk of knee OA. Subjects are a subset of MOST who volunteered for both CEMRI and non-CEMRI. Using CEMRI, synovitis was assessed at 11 sites and graded 0-2 at each site. Presence of "whole-knee synovitis" was defined as the synovitis score of ≥ 1 at any site from each knee. Cartilage and meniscal damage was evaluated using non-CEMRI based on the Whole Organ MRI Score. Logistic regression was used to assess associations of synovitis with radiographic OA (Kellgren-Lawrence grade ≥ 2), widespread cartilage damage, and meniscal damage, adjusting for age, sex, and body mass index (BMI). Additional analyses were performed excluding subjects who had chondrocalcinosis on radiography and those taking antiinflammatory medications.', 'Four hundred four subjects were included (mean age 58.8 ± 7.0 yrs, BMI 29.6 ± 4.9 kg/m(2), 45.5% women). On CEMRI, the maximum synovitis score across 11 sites in each knee was 0 in 106 knees (26.2%), 1 in 135 (33.4%), and 2 in 163 (40.4%). Synovitis was associated with radiographic OA [adjusted OR (aOR) 3.25, 95% CI 1.98-5.35] and widespread cartilage damage (aOR 1.91, 95% CI 1.24-2.92). Severe meniscal damage showed a borderline significant association with synovitis (aOR 1.74, 95% CI 0.99-3.04). Additional analyses as described did not notably change the results.'] |
["The clinical uses of 2-chloro-2'-deoxyadenosine (2-CDA) or cladribine which was initially prescribed to patients with hematological and lymphoid cancers is now extended to treat patients with multiple sclerosis (MS). Previous data has shown that 2-CDA has high affinity to the brain and readily passes through the blood brain barrier reaching CSF concentrations 25% of that found in plasma. However, whether long-term administration of 2-CDA can lead to any adverse effects in patients or animal models is not yet clearly known.", "Here we show that exposure of 2-CDA to CHO cells stably expressing wild-type APP751 increased generation and secretion of amyloid β peptide (Aβ) in to the conditioned medium. Interestingly, increased Aβ levels were noticed even at non-toxic concentrations of 2-CDA. Remarkably, chronic treatment of APdE9 mice, a model of Alzheimer's disease with 2-CDA for 60 days increased amyloid plaque burden by more than 1-fold. Increased Aβ generation appears to result from increased turnover of APP as revealed by cycloheximide-chase experiments. Additionally, surface labeling of APP with biotin and immunoprecipitation of surface labeled proteins with anti-biotin antibody also indicated increased APP at the cell surface in 2-CDA treated cells compared to controls. Increased turnover of APP by 2-CDA in turn might be a consequence of decreased protein levels of PIN 1, which is known to regulate cis-trans isomerization and phosphorylation of APP. Most importantly, like many other oncology drugs, 2-CDA administration led to significant delay in acquiring a reward-based learning task in a T maze paradigm."] |
['Low levels of endogenous estrogens may play a role in the protection of bone mineral density (BMD) in healthy postmenopausal women. The aim of this study was to evaluate the effect of endogenous estradiol and testosterone on bone mass in young and older healthy postmenopausal women.', 'The study involved 99 postmenopausal women aged 55-75 years. The BMDs of the lumbar spine, proximal femur and total skeleton were determined. Measurements were taken of serum calcium, bone alkaline phosphatase, Crosslaps, estradiol, estrone, sex hormone binding globulin, testosterone, bioavailable testosterone and urine calcium. Estradiol was measured using a sensitive assay with a lower detection limit at 5 pg/ml.', 'A multivariate analysis showed that the BMD of the lumbar spine was significantly predicted by estradiol (p < 0.05), and testosterone (p < 0.0001). Likewise, testosterone was found to be an independent predictor of the BMD of the total femur (p < 0.001) and the total skeleton (p < 0.001). The population was divided into two groups: < or = 65 (Group 1) and > 65 years (Group 2) of age and also stratified according to estradiol levels: > 10 and < or = 10 pg/ml. Significant differences in BMD were found in women in Group 1 in whom estradiol levels higher than 10 pg/ml were associated with a higher BMD of the lumbar spine (+ 14%, p < 0.01), proximal femur (+ 6%, p < 0.05) and total skeleton (+ 7%, p < 0.05) compared with women with estradiol levels below 10 pg/ml. Bone alkaline phosphatase levels (p < 0.05) and serum Crosslaps (not significant) were lower in women in Group 1 with a level of estradiol more than 10 pg/ ml.'] |
['Worldwide, most infants born to mothers infected with human immunodeficiency virus (HIV) receive bacille Calmette-Guérin (BCG) vaccine. Tuberculosis is a major cause of death among infants infected with HIV in sub-Saharan Africa, and it should be prevented. However, BCG may itself cause disease (known as "BCGosis") in these infants. Information regarding the immunogenicity of BCG is imperative for the risk/benefit assessment of BCG vaccination in HIV-infected infants; however, no such data exist.', 'We compared BCG-induced CD4 and CD8 T cell responses, as assessed by flow cytometry, in HIV-infected (n=20), HIV-exposed but uninfected (n=25), and HIV-unexposed (n=23) infants, during their first year of life.', 'BCG vaccination of the 2 HIV-uninfected groups induced a robust response, which was characterized by CD4 T cells expressing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and/or interleukin (IL)-2. In contrast, HIV-infected infants demonstrated a markedly lower response throughout the first year of life. These infants also had significantly reduced numbers of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2, a finding that is thought to indicate T cell quality.'] |
['Previous reports show an association between high serum ferritin levels and metabolic syndrome (MS) in adults. In adolescents, little information is available with obesity and serum ferritin levels.', 'This is a cross-sectional study. Data were obtained from the 5th Korean National Health and Nutrition Examination Survey (K-NHANES) conducted during 2010 by the Korean Ministry of Health and Welfare. A total of 849 subjects aged 10-18 years participated in the 2010 survey. A body mass index (BMI) ≥95th percentile for age and sex or a BMI ≥25 was used to diagnose as obesity.', 'The weighted prevalence of obesity was 13.4% (62/462) in male and 8.5% (33/387) in female. We observed significantly higher serum ferritin in male than in female (mean±standard error [SE], 50.5±2.3 µU/L vs. 30.6±1.3 µU/L; P<0.0001). In male, serum ferritin is positively correlated with age (P<0.0001). White blood cell (WBC) count, serum fasting blood sugar, triglyceride (TG), total cholesterol, low-density lipoprotein, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), systolic and diastolic blood pressure, and ferritin levels were higher and high-density lipoprotein (HDL) were lower in the obesity than in the normal group. In female adolescents, WBC count, TG, insulin, and HOMA-IR were higher and HDL were lower in the obesity than in the normal group. In male, serum ferritin levels showed positive association with obesity (β=21.196, P=0.016).'] |
['Obese patients are usually thought to have an increased risk for complications in coronary artery bypass surgery.', 'Therefore, the data of 500 consecutive patients undergoing coronary artery bypass grafting at our department in 1998 by use of cardiopulmonary bypass were analyzed. Severe obesity was defined as body mass index (BMI) > or = 30.0 kg/m(2). Obese patients (n=100; group O) were compared to the remaining 400 patients (group C). Both groups were comparable with respect to sex, history of prior myocardial infarction, chronic obstructive pulmonary disease, previous stroke, duration of cardiopulmonary bypass, aortic cross-clamp time and number of distal anastomoses performed. Obese patients were slightly younger and diabetes and hypertension were more common in these patients.', 'Survival and potential complications including perioperative myocardial infarction, sternal wound infection, wound infection at the leg, renal failure, stroke, prolonged mechanical ventilation, pneumonia, reexploration for bleeding, and atrial arrhythmias were analyzed. No significant differences between obese and non-obese patients were detected.'] |
['A recently introduced, multidimensional index called BODE (body mass index [BMI], degree of airflow obstruction assessed by spirometry, grade of dyspnea, and exercise capacity), quantified by 6-min walking distance (6MWD), has excellent predictive power with respect to outcome in COPD. We investigated whether the BODE index is able to predict survival after lung volume reduction surgery (LVRS).', 'Retrospective study.', 'Tertiary university hospital.', 'One hundred eight-six COPD patients (76 women) with severe emphysema (mean +/- SD age, 64 +/- 8 years; mean FEV(1), 28 +/- 8% of predicted).', 'Bilateral thoracoscopic LVRS.', 'BMI, pulmonary function, 6MWD, and the modified Medical Research Council dyspnea score were assessed before and 3 months after LVRS, and the BODE index was calculated. The patients were followed up with respect to survival for a median time of 40 months (range, 3 to 116 months) after surgery. The mean BODE index decreased from 7.2 +/- 1.6 preoperatively to 4.0 +/- 2.0 at 3 months after LVRS (p < 0.001). The postoperative but not the preoperative BODE correlated with survival, although preoperative patient characteristics were comparable between short-term (< 5 years) and long-term (> 5 years) survivors. A decrease to a lower BODE score class was associated with a reduced mortality (hazard ratio, 0.497, 95% confidence interval, 0.375 to 0.659; p < 0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger (0.74) than that for the FEV(1) (0.63), the degree of dyspnea (0.64), or the 6MWD (0.62).'] |
['Cell cycle regulators are regarded as essential for cardiomyocyte hypertrophic growth. Given that the β-adrenoceptor antagonist propranolol blunts cardiomyocyte hypertrophic growth, we determined whether propranolol alters the expression of cell cycle-related genes in mouse hearts subjected to pressure overload.', 'Pressure overload was induced by transverse aortic constriction (TAC), whereas the expression levels of 84 cell cycle-related genes were assayed by real-time PCR. Propranolol (80\u2003mg·kg(-1) ·day(-1) ) was administered in drinking water for 14 days.', 'Two weeks after surgery, TAC caused a 46% increase in the left ventricular weight-to-body weight (LVW/BW) ratio but no significant changes in cell cycle gene expression. Propranolol, at plasma concentrations ranging from 10 to 140\u2003ng·mL(-1) , blunted the LVW/BW ratio increase in TAC mice, while significantly increasing expression of 10 cell cycle genes including mitotic cyclins and proliferative markers such as Ki67. This increase in cell cycle gene expression was paralleled by a significant increase in the number of Ki67-positive non-cardiomyocyte cells as revealed by immunohistochemistry and confocal microscopy. β-Adrenoceptor signalling was critical for cell cycle gene expression changes, as genetic deletion of β-adrenoceptors also caused a significant increase in cyclins and Ki67 in pressure overloaded hearts. Finally, we found that metoprolol, a β(1) -adrenoceptor antagonist, failed to enhance cell cycle gene expression in TAC mice.'] |
["We studied the meiofauna community at deep-sea hydrothermal vents along a gradient of vent fluid emissions in the axial summit trought (AST) of the East Pacific Rise 9°50'N region. The gradient ranged from extreme high temperatures, high sulfide concentrations, and low pH at sulfide chimneys to ambient deep-sea water conditions on bare basalt. We explore meiofauna diversity and abundance, and discuss its possible underlying ecological and evolutionary processes.", "After sampling in five physico-chemically different habitats, the meiofauna was sorted, counted and classified. Abundances were low at all sites. A total of 52 species were identified at vent habitats. The vent community was dominated by hard substrate generalists that also lived on bare basalt at ambient deep-sea temperature in the axial summit trough (AST generalists). Some vent species were restricted to a specific vent habitat (vent specialists), but others occurred over a wide range of physico-chemical conditions (vent generalists). Additionally, 35 species were only found on cold bare basalt (basalt specialists). At vent sites, species richness and diversity clearly increased with decreasing influence of vent fluid emissions from extreme flow sulfide chimney (no fauna), high flow pompei worm (S: 4-7, H'(loge): 0.11-0.45), vigorous flow tubeworm (S: 8-23; H'(loge): 0.44-2.00) to low flow mussel habitats (S: 28-31; H'(loge): 2.34-2.60)."] |
['The number of patients with oral implants has increased significantly. However, the literature addressing the effect of impact force on titanium and/or ceramic implants is inconclusive. This study sought to determine the fracture resistance to impact load of titanium and ceramic endosseous oral implants.', 'Endosseous oral implants were vertically positioned in two different mounting media: brass and a bone-simulation material. The implant configurations tested included an experimental one-piece Y-TZP implant and a commercially available titanium implant (external hex) with both titanium and zirconia abutments. The specimens were subjected to an impact load using a pendulum impact tester with tup weights varying from 0.9 to 4.5 kg delivered at a radius of 40.64 mm. Loads were delivered to the abutment at a point 4.27 mm above the implant fixture and block junction. Statistical differences (p < .05) were established using the F-test for variances and, when different, t-test assuming unequal variances.', 'For implants clamped in brass, the titanium implant with titanium abutment required the greatest energy to fracture the implant-abutment system (only the abutment screw failed). The ceramic implant and ceramic abutment on titanium implant presented the lowest fracture energy (p < .01). No significant differences were observed when different systems were inserted into the foam blocks of the bone substitute (p > .25).'] |
['To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMNCs) in the treatment of critical limb ischemia (CLI) of diabetic patients and to evaluate the safety, efficacy, and feasibility of this novel therapeutic approach.', 'Twenty-eight diabetic patients with CLI were enrolled and randomized to either the transplant group or the control group. In the transplant group, the patients received subcutaneous injections of recombinant human G-CSF (600 microg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs. All of the patients were followed up after at least 3 months.', 'At the end of the 3-month follow-up, the main manifestations, including lower limb pain and ulcers, were significantly improved in the patients of the transplant group. Their laser Doppler blood perfusion of lower limbs increased from 0.44 +/- 0.11 to 0.57 +/- 0.14 perfusion units (P < 0.001). Mean ankle-brachial pressure index increased from 0.50 +/- 0.21 to 0.63 +/- 0.25 (P < 0.001). A total of 14 of 18 limb ulcers (77.8%) of transplanted patients were completely healed after cell transplantation, whereas only 38.9% of limb ulcers (7 of 18) were healed in the control patients (P = 0.016 vs. the transplant group). No adverse effects specifically due to cell transplantation were observed, and no lower limb amputation occurred in the transplanted patients. In contrast, five control patients had to receive a lower limb amputation (P = 0.007, transplant vs. control group). Angiographic scores were significantly improved in the transplant group when compared with the control group (P = 0.003).'] |
['There is a growing interest in exercise parameters capable of objectively evaluating the functional capacity of patients with chronic obstructive pulmonary disease (COPD).', 'The purpose of the present study was to analyze breath-by-breath cardiopulmonary and gas exchange recovery responses of patients with COPD after a 6-minute walk test (6MWT).', 'Oxygen uptake (VO2) kinetics of patients were obtained using mobile telemetric cardiopulmonary monitoring during and after a 6MWT. Recovery kinetics were modelled using a 4-parameter nonlinear logistic model. Multiple linear regression was performed to assess the association between the half-time of recovery of oxygen consumption (T1/2 VO2) and exercise capacity (6-minute walking distance, 6MWD).', 'Sixty-nine patients with COPD (28 females) with a mean age of 65 ± 10 years took part in the study. After adjustment for covariates (body mass index, forced expiratory volume in 1 s, forced vital capacity, and age), T1/2 VO2 was significantly associated with 6MWD (p = 0.002).'] |
['was to investigate the effect of short-term period, moderate intensity and high volume endurance training on physiological variables in elite wheelchair basketball players.', 'Eight wheelchair basketball players were examined. The subjects participated in a two-week intervention program of mainly two training types: wheelchair basketball and wheelchair driving endurance training. The subjects performed the continuously increasing cycling exercise (CCE) at the constant 60 rpm arm cranking speed at the beginning of the program and after two weeks of the program. The initial workload was 20 W, then the workload was increased by 2 W every 5 seconds until fatigue.', 'The post training of the wheelchair basketball group in the study showed a significant improvement in the peak oxygen uptake (VO2peak) and the peak power output (POpeak). VO2peak increased by 9% from 2,32±0,16 l/min to 2,53±0,2 l/min (p<0.05). POpeak increased by 28 % from 141,75±14,23 W, to 181,63±26,3 W (p<0.05). The pre-training and post training test power output (PO [w]), relative power output (PO [w/kg]) increased significantly in all zones of energy production.'] |
['Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma.', 'Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent.', 'BALB/c mice were sensitized by intranasal administration of endotoxin(low) ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age.', 'Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxin(low) OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxin(low) OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings.'] |
['Tibial tuberosity realignment surgery is performed to improve patellofemoral alignment, but it could also alter tibiofemoral kinematics.', 'After tuberosity realignment in the malaligned knee, the reoriented patellar tendon will pull the tuberosity back toward the preoperative position, thereby altering tibiofemoral kinematics.', 'Controlled laboratory study.', 'Ten knees were tested at 40°, 60°, and 80° of flexion in vitro. The knees were loaded with a quadriceps force of 586 N, with 200 N divided between the medial and lateral hamstrings. The position of the tuberosity was varied to represent lateral malalignment, with the tuberosity 5 mm lateral to the normal position; tuberosity medialization, with the tuberosity 5 mm medial to the normal position; and tuberosity anteromedialization, with the tuberosity 10 mm anterior to the medial position. Tibiofemoral kinematics were measured using magnetic sensors secured to the femur and tibia. A repeated measures analysis of variance with a post hoc Student-Newman-Keuls test was used to identify significant (P < .05) differences in the kinematic data between the tuberosity positions at each flexion angle.', 'Medializing the tibial tuberosity primarily rotated the tibia externally compared with the lateral malalignment condition. The largest average increase in external rotation was 13° at 40° of flexion, with the increase significant at each flexion angle. The varus orientation also increased significantly by an average of 1.5° at 40° and 80°. The tibia shifted significantly posteriorly at 40° and 60° by an average of 4 mm and 2 mm, respectively. Shifting the tuberosity from the medial to the anteromedial position translated the tibia significantly posteriorly by an average of 2 mm at 40°.'] |
['Rates of chlamydia and gonorrhoea have been rising in urban centres in Canada, particularly among HIV-positive men who have sex with men (MSM). Our objective was to identify behavioural risk factors for diagnosis with chlamydia and gonorrhoea in this population, with a focus on the HIV status of sexual partners.', 'The OHTN Cohort Study follows people in HIV care across Ontario. We restricted the analysis to 1997 MSM who completed questionnaires in 2010-2013 at one of seven clinics that submit all chlamydia and gonorrhoea tests to the provincial public health laboratory; we obtained test results via record linkage. We estimated cumulative incidences using Kaplan-Meier methods and identified risk factors for diagnosis of a composite outcome (chlamydia or gonorrhoea infection) using Cox regression.', 'At follow-up, there were 74 new chlamydia/gonorrhoea diagnoses with a 12-month cumulative incidence of 1.7% (95% CI 1.1% to 2.2%). Risk factors for chlamydia/gonorrhoea diagnosis were: 5+ HIV-positive partners (HR=3.3, 95% CI 1.4 to 7.8; reference=none) and recreational drug use (HR=2.2, 95% CI 1.2 to 3.9).'] |
['Temporal lobe epilepsy (TLE) is associated with pathologic changes in hippocampal physiology and morphology. Our aim was to quantify volume reduction of the right and left hippocampus in patients with TLE and to investigate whether the degree of hippocampal atrophy is related to the side of seizure onset.', 'The volume of the right and left hippocampus was estimated for 50 controls and 101 patients with TLE, by applying the unbiased Cavalieri method on MR images.', 'Pairwise comparisons, within a multivariate analysis of variance and adjusted by using the Bonferroni correction, revealed that both right and left hippocampal volumes were, on average, significantly smaller in patients with right-sided seizure onset (R-patients) relative to those of controls (P < .001 and P = .04, respectively). Furthermore, left hippocampal volume was significantly smaller in patients with left-sided seizure onset (L-patients) compared with controls (P < .001), but the right-sided hippocampal volume was not significantly smaller (P = .71). Moreover, a correlation analysis revealed that the strong linear association between the right and left hippocampal volumes existing in the control population (r = 0.73) is partially lost in patients with TLE (r < or = 0.48), and this loss in correlation appears to be more pronounced in L-patients than in R-patients.'] |
['Patients with hypertension may be more prone to develop hypotension as a consequence of opioid administration under general anesthesia. The hemodynamic and bispectral index responses to a remifentanil bolus in neurosurgical hypertensive patients under target-controlled infusion with propofol and remifentanil are addressed.', 'Ten healthy patients and 10 patients with diagnosed hypertension under pharmacological treatment were studied. A 2 microg/kg remifentanil bolus was administered to all patients before skin incision under target-controlled infusion with propofol and remifentanil. Mean arterial pressure, heart rate, and the area under the curve for the bispectral index of the electroencephalogram were analyzed within the groups and compared between them every 30 seconds for two minutes following the bolus.', 'Two minutes after the remifentanil bolus, remifentanil predicted effect-site concentrations reached maximum values of 8.46+/-0.91 ng/ml and 9.74+/-1.29 ng/ml in the healthy and hypertensive patients, respectively. Both groups showed a significant decrease in mean arterial pressure, heart rate, and in the area under the curve for the bispectral index. Mean arterial pressure decreased by 17.3+/-10% and 24+/-9%, heart rate by 11.1+/-8% and 12+/-8%, and the bispectral index by 13+/-9.2% and 8.6+/-8.4% in the healthy and hypertensive patients, respectively, 120 seconds after the remifentanil bolus.'] |
['Although disulfiram has been used in the treatment of alcoholism due to the unpleasant sensations its concomitant ingestion with ethanol provokes, some patients reported stimulant effects after its ingestion. This issue has not been addressed in studies with animals. In mice, the stimulant effect of ethanol has been associated with increased locomotor activity and behavioural sensitization. This study sought to analyze the influence of disulfiram on the development of behavioural sensitization to the stimulant effect of ethanol.', 'Male Swiss mice pre-treated with vehicle or disulfiram (15 mg/kg) received saline or ethanol (2.0 g/kg) every other day, for 5 days. Forty-eight hours afterwards mice were challenged with Saline, and 48 h later they received Disulfiram, or Disulfiram+Ethanol or Ethanol.', 'The co-administration of disulfiram (15 mg/kg) blocked the development of behavioural sensitization induced by ethanol (2.0 g/kg). Although the acute administration of disulfiram did not alter the locomotor activity, its acute administration-induced higher levels of locomotor activity in mice previously sensitized to ethanol than in controls which received saline.'] |
['A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest.', 'PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated.', 'In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death.'] |
['Apoptosis has been implicated as the mechanism for retinal ganglion cell death in primary open-angle glaucoma (POAG), a complex neurodegenerative disease. There have been inconsistent reports regarding increased risk of POAG and a polymorphism (Arg72Pro) within the tumor suppressor gene, p53. The goal of this study was to examine the role of this polymorphism in susceptibility to POAG in a Caucasian population from the United States.', 'We generated genotypes in 191 unrelated Caucasian POAG patients and 167 unrelated Caucasian controls for the following polymorphisms within p53: rs1042522 (Arg72Pro), rs17878362 (16 bp Ins/Del), and rs1800371 (Pro47Ser) by PCR amplification followed by restriction digestion and sequence analysis.', 'There was a significant difference in genotypic frequencies for rs1042522 (Arg72Pro) between POAG patients and controls (chi(2)= 9.56, p=0.008). Individuals who were homozygous for the arginine allele have a 1.9 fold significantly increased risk of developing glaucoma (95%CI: 1.16-2.82, p=0.01). Interestingly, we found that the frequency of the arginine allele was even higher in the normal-tension glaucoma (NTG) subtype compared to high-tension POAG (0.81 versus 0.76).'] |
['von Willebrand factor (VWF) levels in healthy individuals are influenced by variations in genetic loci other than the VWF gene, whose contribution to VWF levels in patients with von Willebrand disease (VWD) is largely unknown.', 'To investigate the association between single-nucleotide polymorphisms (SNPs), VWF levels, and bleeding phenotype.', "In 364 type 1 VWD and 240 type 2 VWD patients from the nationwide cross-sectional 'Willebrand in The Netherlands' (WiN) study, we studied the association between eight SNPs in STXBP5, SCARA5, ABO, VWF, STAB2, STX2, TC2N, and CLEC4M, and VWF antigen (VWF:Ag), VWF activity (VWF:Act), and bleeding phenotype as assessed with the Tosetto bleeding score.", 'In type 1 patients, STXBP5 was associated with a lower VWF:Ag level (adjusted difference of -3.0 IU dL(-1) per allele; 95% confidence interval [CI] -6.0 to 0.1) and CLEC4M with both a lower VWF:Ag level (-4.3 IU dL(-1) per allele; 95% CI -7.9 to -0.6) and lower VWF:Act (-5.7 IU dL(-1) per allele; 95% CI -10.9 to -0.5). In type 2 patients, none of the SNPs was associated with VWF levels. None of the genetic variants was associated with bleeding score.'] |
['Hydrogen sulphide (H2 S) has been found to be involved in cardiovascular diseases, but the exact mechanism has not been clarified. The purpose of this study was to investigate whether sodium hydrogen sulphide (NaHS), the donor of H2 S, can improve diabetic cardiomyopathy by reversing disordered calcium-handling system in sarcoplasmic reticulum (SR).', 'Sprague Dawley rats were injected with streptozotocin (STZ, 60 mg/kg, i.p.) to build diabetic model. Treatment groups included: aminoguanidine group (AG, 100 mg/kg, p.o.) and NaHS group (5 mg/kg per day, s.c.).', 'Cardiac dysfunction and myocardial hypertrophy were found in diabetic model (DM) group, along with increased ROS levels and upregulated mRNA and protein expressions of NADPH p22(phox) , endothelin A receptor (ETA ) and protein kinase Cε (PKCε). Expressions of calcium-handling proteins in SR including FK506-binding proteins (FKBP12.6), sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) and calsequestrin 2 (CASQ2) were downregulated in DM group, accompanied by elevated concentration of diastolic free calcium in high glucose-incubated cardiomyocytes, indicating of calcium leak. After treated by NaHS, these abnormalities were attenuated significantly.'] |
['Right ventricular (RV) dysfunction in pulmonary hypertension (PH) is linked to adverse outcomes, but this response is considered heterogeneous because it can be associated with multiple factors.', 'RV function of 51 PH patients was calculated by averaging peak speckle-tracking longitudinal strain from RV free-wall (RV-free), and the cutoff for RV dysfunction was predefined as RV-free ≤ 19%. Right-sided heart remodelling was assessed in terms of RV end-systolic area (RVESA) and right atrial (RA) area (RA-area). Midterm reverse remodelling was defined as a relative decrease in RVESA (ΔRVESA) and RA-area (ΔRA-area) of at least 15% at 5.7 ± 4.0 months after introduction of pulmonary artery hypertension-specific drugs. Long-term outcome was tracked for 3.0 ± 2.0 years.', 'Patients with midterm RV and RA reverse remodelling showed more favourable long-term outcomes than those without (P\xa0=\xa00.01, P\xa0= 0.047, respectively). Sequential Cox models showed that a model based on hemodynamic parameters (χ(2)\xa0= 0.3) was improved by the addition of RV-free (χ(2)\xa0= 6.4; P\xa0= 0.01), and further improved by addition of ΔRVESA and ΔRA-area (χ(2)\xa0= 28.2; P < 0.001). Furthermore, preservation of baseline RV function and midterm reverse remodelling in right-sided heart was associated with an optimal outcome: a survival rate of 100%. In contrast, absence of midterm reverse remodelling in the right-sided heart of patients with impaired baseline RV function was associated with significantly worse outcome with a survival rate of 33% (P\xa0= 0.01).'] |
['The Sit-to-Stand test (SST) is accepted and utilized during functional assessments of COPD patients, along with the 6-Minute Walk test (6MWT). Since there is a lack of evidence in literature regarding the neurophysiological effectiveness of SST compared to 6MWT, the present study is justified with the purpose of assessing the neurophysiological effectiveness of SST in comparison to the 6MWT during the functional assessment of such patients, once it is known that both tests are good predictors of functional state.', 'Fourteen patients with moderate to severe COPD randomly performed the 6MWT and the SST with a 30-minute interval in between tests. Blood lactate was collected along with the median frequency (MDF), obtained with the electromyography of the muscles rectusfemoris (RF), vastus lateralis (VL), tibialis anterior (TA), and soleus (SO) for the comparison of the neurophysiological effectiveness.', 'The results of the blood lactate concentration during rest and at the end of the functional tasks along with the results from the angular coefficient (AC) obtained from the median frequency were analyzed with the Student t test. The initial and final values obtained from SST and 6MWT were compared within each activity, along with the comparison between the initial and final values for each functional test. A significant difference (p = 0.0005) was only verified between the initial and final values of SST.'] |
['Some patients with functional abdominal pain report worsening of symptoms in the upright position. Many of these have a postural tachycardia syndrome (POTS). We investigated whether the electrical activity of the stomach changes during the upright portion of a tilt table test in patients with and without POTS.', 'All of the children undergoing autonomic testing were offered enrollment in this institutional review board-approved prospective study between October 2007 and January 2009. Electrogastrography was recorded 10 minutes in the supine position and during the entire upright portion of tilt. Children were divided into 2 groups: POTS and No-POTS. Findings were correlated with this grouping using Fisher exact test and either Student t test or Wilcoxon rank sum test as appropriate.', 'Forty-nine patients participated (35 girls), with a mean age of 14.7 + 3.5 years, 25 with POTS and 24 without. The POTS and No-POTS groups did not differ in baseline normal gastric activity. The change from supine to standing showed a significant difference in the electrogastrographic tracing between the POTS and No-POTS groups (P < 0.04-0.09), best seen in channels 1 and 4. In particular, gastric activity became more abnormal in the upright position in the POTS group, whereas the opposite occurred in the No-POTS group.'] |
['The periodontal ligament (PDL) receives mechanical stress (MS) from dental occlusion or orthodontic tooth movement. Mechanical stress is thought to be a trigger for remodeling of the PDL and alveolar bone, although its signaling mechanism is still unclear. So we investigated the effect of MS on adenosine triphosphate (ATP) release and extracellular signal-regulated kinases (ERK) phosphorylation in PDL cells.', 'Mechanical stress was applied to human PDL cells as centrifugation-mediated gravity loading. Apyrase, Ca(2+)-free medium and purinergic receptor agonists and antagonists were utilized to analyze the contribution of purinergic receptors to ERK phosphorylation.', 'Gravity loading and ATP increased ERK phosphorylation by 5 and 2.5 times, respectively. Gravity loading induced ATP release from PDL cells by tenfold. Apyrase and suramin diminished ERK phosphorylation induced by both gravity loading and ATP. Under Ca(2+)-free conditions the phosphorylation by gravity loading was partially decreased, whereas ATP-induced phosphorylation was unaffected. Receptors P2Y4 and P2Y6 were prominently expressed in the PDL cells.'] |
['To investigate growth and development in a cohort of children born with very low birth weight (VLBW) treated at a single tertiary neonatal unit.', 'We studied 97 children born between January 1995 and July 1997 with BW <1,500 g. At follow-up (mean age 3.7 years) anthropometric data and data on neurological status, motor, speech and language development were collected. Small for gestational age (SGA) was defined as weight and/or length at birth <10th percentile; shortness at follow-up was defined as height <10th percentile.', "Comparison was made between the appropriate for gestational age (AGA) (n = 46) and SGA (n = 51) groups. At follow-up, 23 AGA and 35 SGA children were short, had a smaller head circumference (-1.9 vs -0.8 SDS), were lighter at birth (BW -1.3 vs -0.7 SDS), and had a higher rate of broncho-pulmonary dysplasia (BPD) (28 vs 12); no differences in neonatal characteristics or neurological status were evident. A higher frequency of motor delay occurred in the 'short' group. Short children also had a smaller head circumference (HC) (-1.6 vs -0.7). Short SGA children had a higher frequency of BPD, smaller HC (-2.1 vs -1.0), and a slightly higher proportion of suspicious neurological findings, motor delay, and speech and language delay (n.s.)."] |
['The absolute white blood cell (WBC) count and neutrophil to lymphocyte (N/L) ratio are predictors of death/myocardial infarction in patients who have undergone coronary angiography. We hypothesized that a pre-procedural elevated WBC count and an elevated N/L ratio would be a predictor of development of significant ventricular arrhythmias in subjects undergoing percutaneous coronary intervention (PCI).', 'We retrieved the data for all patients developing ventricular arrhythmia during PCI between 1999 to 2009 from our cath lab database (from 30,798 records), a total of 70 patients (Group I), and tabulated their WBC counts and absolute neutrophil and lymphocyte counts as well as N/L ratios. We compared the data with a random group of age, gender, medications and pre-existing condition matched controls (n=70) (Group II). We also adjusted for amount of myocardium under jeopardy. Group I had a significantly higher total WBC count (means 14,344 Vs 6852; 95% CI; p=0.0004); neutrophil count (means 75.79% Vs 58.06%; 95% CI; p < 0.0001) and N/L ratio (means 3.79 Vs 1.56; 95% CI; p < 0.0001) [means compared with t test].'] |
['Myofibroblasts migrating from adventitia have been suggested to constitute a majority of neointimal cells after angioplasty. We sought to examine this hypothesis by use of smoothelin, which is a marker for the quiescent smooth muscle cell (SMC) phenotype while not expressed by myofibroblasts.', 'Balloon angioplasty was performed in left iliac arteries of 25 rabbits that were killed after 3-56 days. Arterial cross-sections were immunostained for alpha-actin (general marker), smoothelin (quiescent SMC phenotype), and Ki-67 (proliferative phenotype).', 'Adventitial cells became transiently actin-positive (myofibroblasts) but did not express smoothelin at any time point. In media, angioplasty induced transient proliferation and coinciding transient decrease in smoothelin expression. Neointimal cells, present 7 days after angioplasty, were initially proliferating and smoothelin-negative but changed to non-proliferating, smoothelin-positive cells after 56 days where 82 +/- 10% of cells stained positive for smoothelin. This phenotypic modulation of medial and intimal cells began in media and moved gradually towards the lumen.'] |
['Although community-based adaptive sports have become a popular means of rehabilitation for individuals with disabilities, little is known regarding the factors that lead to sustained participation.', 'To determine the demographic, environmental, disability-related, and functional factors associated with sustained participation in a community-based adaptive sports program.', 'Retrospective cohort study.', 'Community-based adaptive sports program.', 'Adults with mobility-related disabilities.', 'Data were collected from registration forms and participation logs. Participants were described as "sustainers" if they attended ≥2 sessions, or as "nonsustainers" if they attended 0 or 1 session. We examined the associations between sustained participation and demographic, environmental, disability-related, and functional factors in bivariate and multivariable analyses.', 'Sustained participation in the adaptive sports program.', 'Of the 134 participants, 78 (58%) were sustainers and 56 (42%) were nonsustainers. In multivariable analyses, participants who ambulated independently had lower odds of being sustainers (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.11, 0.96), and those who used an ambulatory assistive device had twice the odds of being sustainers (OR = 2.0, 95% CI = 0.65, 6.2) compared to those who used a manual wheelchair. Moreover, participants who lived within 5.3 miles of the program site (OR\xa0=\xa03.8, 95% CI = 1.1, 13.0) and those who lived between 5.3 and 24.4 miles from the program site (OR = 2.8, 95% CI = 1.0, 7.7) had significantly higher odds of sustained participation than those who lived more than 24.4 miles from the program site.'] |
['To investigate the effect of the islet promoter region variant (G-->A) at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM.', 'The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests (IVGTTs) were performed in subjects with NGT. The islet promoter region of the GCK gene was amplified with polymerase chain reaction and screened for the variant (-30) using single-strand conformation polymorphism analysis.', 'The islet promoter variant (-30) of the GCK gene was found in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not differ between subjects with and without this variant in any of the three groups. Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant (-30) of the GCK gene.'] |
['This study was designed to examine associations between the number of posterior occlusal pairs of teeth and the nutritional status of older adults participating in the third National Health and Nutrition Examination Survey (NHANES III) survey.', 'Impaired dentition was assessed by number of posterior occluding pairs of teeth (grinding teeth, n=8 pairs) and complete denture status. Nutritional status was measured by nutrient intake, Healthy Eating Index (HEI) score, serum values, and body mass index (BMI). Subjects/setting Data from 5,958 participants in NHANES III ages 50 years and over with dental examination were included in the analysis. Statistical analyses performed Analysis of covariance and multivariate linear regression analyses were performed to examine associations between number of tooth pairs and nutritional status indicators controlled for potential confounders.', 'Compared with individuals with five to eight posterior occluding pairs (HEI=68.2), those with impaired dentition (no posterior pairs, one to four pairs remaining, or full dentures) had consistently lower HEI scores (HEI=64.3, 66.5, and 66.5, respectively), consumed fewer servings of fruits, and had lower serum values of beta carotene and ascorbic acid. Participants with one to four posterior pairs also had a higher mean BMI (28.0) than those with five or more pairs (27.2). Participants in one or more groups with impaired dentition had lower dietary intake levels of vitamin A, carotene, folic acid, and vitamin C, and scored less well on diet variety, cholesterol, and sodium components of the HEI.'] |
['The W allele of the G460W polymorphism in the adducin-1 gene has been occasionally associated with increased blood pressure (BP). The aim of this study was to test whether the G460W variant is associated with BP levels and BP progression rate and whether G460W associations with BP are affected by sex, body mass index (BMI), or age.', 'The G460W polymorphism was genotyped in the population-based Malmö Diet and Cancer-cardiovascular arm (MDC-CVA; n = 6103), of whom 53% had also been examined 11 +/- 4.4 years earlier in the Malmö Preventive Project (MPP).', 'Among subjects without antihypertensive treatment (AHT) in the MDC-CVA (n = 5009), there was no difference between carriers (38%) and noncarriers (62%) of the W allele in systolic BP (139.2 +/- 18.2 v 139.2 +/- 18.5 mm Hg; P = .99) or diastolic BP (85.9 +/- 9.1 v 86.1 +/- 9.2 mm Hg; P = .49). In subjects free from AHT in the MPP and MDC (n = 2637) there was no difference between carriers (38%) and noncarriers (62%) in progression of systolic BP (2.0 +/- 2.5 v 2.0 +/- 2.7 mm Hg/year; P = .45) or diastolic BP (0.59 +/- 1.6 v 0.56 +/- 1.5 mm Hg/year; P = .66) from MPP to MDC. At MDC-CVA BP was influenced by interaction between the G460W and BMI (P = .02 for systolic BP and P = .002 for diastolic BP) and by interaction between G460W and sex (P = .03 for systolic BP and P = .02 for diastolic BP), a result further confirmed by stratified analysis showing that female carriers of the W allele belonging to the upper tertile of BMI had increased systolic BP (146.1 +/- 18.6 v 141.2 +/- 18.6 mm Hg; P < .001), diastolic BP (88.7 +/- 8.7 v 86.1 +/- 8.7 mm Hg; P < .001), and prevalence of hypertension (72.5% v 61.8 %; P = .001).'] |
['The Japan-Multinational Trial Organization (JMTO) lung cancer (LC) 0003 was a prospective randomized phase III trial investigating advanced non-small cell lung cancer comparing paclitaxel (P) plus carboplatin (C) versus vinorelbine (V), gemcitabine (G) followed by docetaxel (D). This trial was conducted with Southwest Oncology Group (SWOG) 0003 using a common arm of PC. An analysis of SWOG 0003 samples showed that low osteopontin (OPN) plasma levels were highly prognostic for a better outcome. We performed an independent investigation to validate these results using samples from Japanese patients enrolled in the JMTO LC 0004, a correlative study associated with JMTO LC 0003.', 'A total of 20 ml of blood was collected before treatment from patients enrolled in JMTO LC 0003. Serum concentrations of OPN and basic fibroblast growth factor (bFGF) were measured by enzyme-linked immunosorbent assay. Effects of OPN and bFGF levels on tumor response, progression-free survival (PFS), and overall survival (OS) were examined.', 'Seventy-one samples were obtained, including 32 specimens from the PC arm and 39 from the VGD arm. There were no significant relationships between either OPN or bFGF levels with patient characteristics. In an analysis of clinical outcome, low OPN levels correlated with better OS and progression-free survival (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.97; p = 0.037, HR = 0.42; 95% CI, 0.25-0.70; p = 0.001, respectively) and high bFGF levels correlated with better OS (HR = 0.53; 95% CI, 0.31-0.90; p = 0.018).'] |
['The efficacy of cyclosporin in the management of ulcerative colitis is recognized. Not all patients respond to this treatment. Existing clinical and laboratory parameters are of little use in identifying those most likely to respond.', 'To determine whether in-vitro sensitivity to cyclosporin as measured by a lymphocyte proliferation assay is predictive of in-vivo response to therapy.', 'The study comprised seven responders with ulcerative colitis, seven non-responders, and 14 healthy matched controls. A lymphocyte proliferation assay was carried out in the presence of a range of concentrations of cyclosporin and a dose-response curve constructed for each subject. The IC(50) value, the concentration of cyclosporin that resulted in 50% inhibition of proliferation, was calculated for each subject. IC(50) values for responders, non-responders and controls were compared using a Mann-Whitney test.', 'There was a wide range of values obtained for the study group as a whole. IC(50) values for non-responders were significantly higher than those of responders (P < 0.05).'] |
['The Baby-Friendly Hospital Initiative (BFHI) has been implemented by WHO and Unicef with a view to protect, promote and support breast feeding. This paper aims to assess the influence of the BFHI on breastfeeding indicators in Brazil, using data from the 2nd Survey of Breastfeeding Prevalence, conducted in 2008.', 'Data on 64 municipalities were analysed: a total of 65,936 infants under the age of 1 year who were covered by the 2008 immunisation campaign. The outcomes of interest were breast feeding in the first hour of life in infants under 1 year of age; exclusive breast feeding on the first day after hospital discharge in infants under 4 months of age; exclusive breast feeding in infants under 2, 3 and 6 months of age; and pacifier use in infants under 6 months of age. The influence of birth in baby-friendly hospitals (BFHs) on these end points was analysed by means of Poisson regression with robust variance for complex samples.', 'Infants born in BFHs were 9% more likely to be breast fed in the first hour of life and 6% more likely to be breast fed on the first day at home. Exclusive breast feeding was 13%, 8% and 6% more likely in infants under the ages of 2, 3 and 6 months, respectively, born in BFHs. Birth in a BFH also correlated with significant less pacifier use.'] |
['Eosinophils play an important role in the pathogenesis of allergic diseases. Chemoattractants, including platelet-activating factor (PAF) and complement component 5a (C5a), induce eosinophil infiltration and promote eosinophil effector functions.', 'To compare eosinophil degranulation and superoxide anion (O2-) generation induced by various chemoattractants, and to elucidate the role of cellular adhesion on these effector functions.', 'Human eosinophils were stimulated with PAF, C5a, eotaxin, or leukotriene B4 (LTB4). O2- generation was assayed by a chemiluminescence method using a Cypridina luciferin analog as the amplifier. Degranulation and adhesion were measured by quantitating eosinophil protein X by radioimmunoassay. Expression of CD11b on eosinophils was measured by flow cytometry.', 'PAF and C5a induced significant degranulation and O2- generation from eosinophils. In contrast, the potency of eotaxin or LTB4 for these functions was much less. PAF and C5a also significantly enhanced eosinophil adhesion, whereas eotaxin and LTB4 did not. CD11b expression on eosinophils was enhanced by all four stimulants, and the order of potency to induce CD11b expression was C5a > PAF > eotaxin > LTB4.'] |
['Bacteria use transcriptional regulation to respond to environmental stresses. Specifically, exposure to antibacterial drugs is deemed to be an atypical stress, and altering transcriptional regulation in response to such stress can increase bacterial drug resistance. However, only a few transcription factors that regulate drug resistance have been reported.', 'In the present study, a GntR family transcription factor, encoded by the MSMEG_0535 (Ms0535) gene, was shown to be an isoniazid (INH) resistance regulator in Mycobacterium smegmatis. When the Ms0535 gene was overexpressed, cells showed a significant increase in INH resistance. First, the interaction between Ms0535 and its own promoter was determined, and a conserved 26-bp palindromic DNA binding motif was identified using electrophoretic mobility shift and DNaseI footprinting assays. Second, quantitative reverse transcription-PCR assays showed that Ms0535 acted as a transcriptional activator, and positively regulated its own expression, as well as that of a permease encoded by the MSMEG_0534 (Ms0534) gene. Similar to the case for the Ms0535 gene, a recombinant Ms0534-overexpressing strain also exhibited increased INH resistance compared with the wild-type strain. Furthermore, we showed that Ms0535 and Ms0534 deletion strains were more sensitive to INH than the wild-type strain. Interestingly, overexpressing Ms0534 in the Ms0535 deletion strain enhanced its INH resistance. In contrast, the Ms0534 deletion strain was still sensitive to INH even when Ms0535 was overexpressed. These findings suggest that Ms0534 is an effector protein that affects INH resistance in M. smegmatis.'] |
['Hypnotic depth but not haemodynamic responsiveness is measured with EEG-based monitors. In this study we compared heart rate variability (HRV) in unstimulated patients and stimulation-induced HRV at different levels of anaesthesia.', 'A total of 95 ASA I or II patients were randomly assigned to five groups (Group 1: BIS 45(5), remifentanil 1 ng ml(-1); Group 2: BIS 45(5), remifentanil 2 ng ml(-1); Group 3: BIS 45(5), remifentanil 4 ng ml(-1); Group 4: BIS 30(5), remifentanil 2 ng ml(-1); Group 5: BIS 60(5), remifentanil 2 ng ml(-1)). A time- and frequency-domain analysis of the RR interval (RRI) from the electrocardiogram was performed. HRV before induction, before and after a 5 s tetanic stimulus of the ulnar nerve, and before and after tracheal intubation was compared between groups, between stimuli, and between responders to intubation [systolic arterial pressure (SAP) increase >20 mm Hg, a maximal heart rate (HR) after intubation >90 min(-1) or both] and non-responders (anova).', 'Induction of anaesthesia significantly lowered HR and HRV. Mean RRI before stimulation was higher in G3 than in G1, G2, and G4 (P < 0.001), whereas the other HRV parameters were similar. Intubation induced a greater HRV response than tetanic stimulation. The mean RRI after intubation was lower in G3 compared with the other groups and the sd of the RRI after tetanic stimulation was lower in G3 compared with G5. Otherwise, unstimulated HRV and stimulation-induced HRV were similar in responders and non-responders.'] |
['The intestinal metabolic and histologic changes that occur in the gastrointestinal tract with ischemia and that form the basis of intramucosal pH and PCO2 alterations have not been well established. Recent evidence suggests that apart from technical problems with gastric tonometry, some methodologic misconceptions in the interpretation of intramucosal pH and PCO2 exist. The present study was designed to demonstrate the effects of impaired mesenteric perfusion with specific consideration to the induced intramucosal PCO2 changes using a new technique, the continuous fiberoptic CO2 sensor, and a new concept of interpretation.', 'Randomized, controlled intervention trial.', 'University animal laboratory.', 'Twelve anesthetized female pigs, weighing 67+/-6 kg.', 'The pigs were assigned to control and stenosis groups. In the stenosis group, blood flow in the superior mesenteric artery was reduced by 70% from baseline for 180 mins, followed by 120 mins of reperfusion. Serum lactate concentration, pH, PCO2, PO2, and bicarbonate concentration (cHCO3-) were determined in arterial, superior mesenteric venous, portal venous, hepatic venous, and pulmonary arterial blood. In the lumen of the ileum, intramucosal PCO2 was continuously determined by a fiberoptic CO2 sensor. At the end of the experiment, the gut was examined for histologic changes.', 'During mesenterial hypoperfusion, a sudden and significant increase in intramucosal PCO2 was observed. This increase was paralleled by increases in superior mesenteric venous PCO2 and portal venous PCO2 (p < .05) and a concomitant decrease in intramucosal pH, superior mesenteric venous pH, and portal venous pH. Arterial and mixed venous PCO2 and pH did not change. cHCO3- did not change in local or systemic blood samples.'] |
["Development of fibrosis and subsequent stricture formation in Crohn's disease (CD) increases morbidity and rates of surgery and reduces patients' quality of life. There are currently no biomarkers of intestinal fibrosis that might allow earlier identification and better management of patients at increased risk of stricture formation.", 'MicroRNA profiling of serum from CD patients was used to identify microRNAs associated with stricture formation. Differential expression of miR-19a-3p and miR-19b-3p was validated by quantitative PCR in independent CD cohort of stricturing and nonstricturing patients (n = 46 and n = 62, respectively). Levels of miR-19a-3p and miR-19b-3p were also quantified in baseline serum samples, and expression compared between CD patients who subsequently developed stricture and those who did not (n = 11 and n = 44, respectively).', 'Serum levels of miR-19a-3p and miR-19b-3p in the array were lower in CD patients with a stricturing phenotype than in control CD patients (P = 0.007 and 0.008, respectively). The reduction in miR-19a-3p and 19b-3p was verified in a second cohort (P = 0.002). The association of miR-19-3p with stricturing CD was independent of potential confounding clinical variables, including disease duration, disease activity, site, gender, and age. Serum analyses in patients with 4 years of follow-up support the hypothesis that reduced miR-19a-3p and miR-19b-3p predate stricture development with a trend toward significance (P = 0.077 and P = 0.060, respectively).'] |
['Forces acting on mitral annular devices in the setting of ischemic mitral regurgitation are currently unknown. The aim of this study was to quantify the cyclic forces that result from mitral annular contraction in a chronic ischemic mitral regurgitation ovine model and compare them with forces measured previously in healthy animals.', 'A novel force transducer was implanted in the mitral annulus of 6 ovine subjects 8 weeks after an inferior left ventricle infarction that produced progressive, severe chronic ischemic mitral regurgitation. Septal-lateral and transverse forces were measured continuously for cardiac cycles reaching a peak left ventricular pressure of 90, 125, 150, 175, and 200 mm Hg. Cyclic forces and their rate of change during isovolumetric contraction were quantified and compared with those measured in healthy animals.', 'Animals with chronic ischemic mitral regurgitation exhibited a mean mitral regurgitation grade of 2.3 ± 0.5. Ischemic mitral regurgitation was observed to decrease significantly septal-lateral forces at each level of left ventricular pressure (P < .01). Transverse forces were consistently lower in the ischemic mitral regurgitation group despite not reaching statistical significance. The rate of change of these forces during isovolumetric contraction was found to increase significantly with peak left ventricular pressure (P < .005), but did not differ significantly between animal groups.'] |
['Regulation of gene expression in trypanosomatids is mainly posttranscriptional. Tight regulation of mRNA stability and access to polysomes allows Trypanosoma cruzi to adapt to different environmental conditions during its life cycle. Posttranscriptional regulation requires association between mRNAs and specific proteins to form mRNP complexes. Proteins that lack a canonical RNA-binding domain, such as eukaryotic elongation factor-1α (EF-1α), may also associate with mRNPs. EF-1α is conserved in many organisms, and it plays roles in many cellular processes other than translation, including RNA transport, the cell cycle, and apoptosis.', 'In a previous study, EF-1α was found associated with mRNP-forming mRNAs in polysome-free fractions both in epimastigotes growing under normal conditions and in nutritionally stressed parasites. This finding suggested the possibility that EF-1α has a non-canonical function. Thus, we investigated the dynamics of EF-1α in association with T. cruzi epimastigote mRNAs under normal and stressed nutritional conditions. EF-1α is expressed throughout the parasite life cycle, but it shows a slight decrease in protein levels in the metacyclic trypomastigote form. The protein is cytoplasmically localized with a granular pattern in all forms analyzed. Following puromycin treatment, EF-1α migrated with the heaviest gradient fractions in a sucrose polysome profile, indicating that its association with large protein complexes was independent of the translation machinery. We next characterized the EF-1α-associated mRNAs in unstressed and stressed epimastigotes. We observed that specific subsets of mRNAs were associated with EF-1α-mRNPs in unstressed or stressed epimastigotes. Some mRNAs were identified in both physiological conditions, whereas others were condition-specific. Gene ontology analysis identified enrichment of gene sets involved in single-organism metabolic processes, amino acid metabolic processes, ATP and metal ion binding, glycolysis, glutamine metabolic processes, and cobalt and iron ion binding.'] |
['The cytoskeleton and associated motors play an important role in the establishment of intracellular polarity. Microtubule-based transport is required in many cell types for the asymmetric localization of mRNAs and organelles. A striking example is the Drosophila oocyte, where microtubule-dependent processes govern the asymmetric positioning of the nucleus and the localization to distinct cortical domains of mRNAs that function as cytoplasmic determinants. A conserved machinery for mRNA localization and nuclear positioning involving cytoplasmic Dynein has been postulated; however, the precise role of plus- and minus end-directed microtubule-based transport in axis formation is not yet understood.', 'Here, we show that mRNA localization and nuclear positioning at mid-oogenesis depend on two motor proteins, cytoplasmic Dynein and Kinesin I. Both of these microtubule motors cooperate in the polar transport of bicoid and gurken mRNAs to their respective cortical domains. In contrast, Kinesin I-mediated transport of oskar to the posterior pole appears to be independent of Dynein. Beside their roles in RNA transport, both motors are involved in nuclear positioning and in exocytosis of Gurken protein. Dynein-Dynactin complexes accumulate at two sites within the oocyte: around the nucleus in a microtubule-independent manner and at the posterior pole through Kinesin-mediated transport.'] |
['To investigate the effects of nicotine in combination with okadaic acid (OA) or taxol on bovine oocyte maturation and subsequent embryonic development.', 'Prospective randomized study.', 'University research laboratory.', 'Bovine ovaries, oocytes, and embryos.', 'Oocyte maturation and subsequent embryo development in the presence of nicotine in combination with okadaic acid and taxol.', 'Haploid composition, cleavage rate, IVF and parthenogenetic embryo development, blastocyst cell number.', 'The results showed that nicotine and OA or nicotine and taxol significantly decreased oocyte maturation rates. Combinations of nicotine (10 or 50 micromol/L) and OA (0.01 or 0.05 micromol/L) did not affect oocyte haploid composition; however, taxol alone or combined with nicotine caused a decrease in haploid composition compared with control. Parthenogenetic activation of oocytes that were matured in nicotine, OA, or taxol resulted in blastocyst development rates of 12%-17%, which were not different from the control. Various combinations of nicotine and OA or nicotine and taxol significantly lowered (3%-8%) blastocyst development compared with control. The average cell number of blastocysts derived from nicotine + OA- and nicotine + taxol-treated oocytes was lower than all other treatment groups and control. For oocytes fertilized in vitro, oocytes matured in OA, taxol, or combinations of nicotine and OA or taxol-containing media resulted in significantly lower cleavage rates and blastocyst development compared with the control group and the 10 micromol/L nicotine treatment group. The IVF embryos cultured in nicotine + OA-containing medium had a significantly lower blastocyst development rate.'] |
['Induction of stem cell differentiation toward functional hepatocytes is hampered by lack of knowledge of the hepatocyte differentiation processes. The overall objective of this project is to characterize key stages in the hepatocyte differentiation process.', 'We established a mouse embryonic stem (mES) cell culture system which exhibited changes in gene expression profiles similar to those observed in the development of endodermal and hepatocyte-lineage cells previously described in the normal mouse embryo. Transgenic mES cells were established that permitted isolation of enriched hepatocyte-lineage populations. This approach has isolated mES-derived hepatocyte-lineage cells that express several markers of mature hepatocytes including albumin, glucose-6-phosphatase, tyrosine aminotransferase, cytochrome P450-3a, phosphoenolpyruvate carboxykinase and tryptophan 2,3-dioxygenase. In addition, our results show that the up-regulation of the expression levels of hepatocyte nuclear factor-3alpha, -4alpha, -6, and CCAAT-enhancer binding protein-beta might be critical for passage into late-stage differentiation towards functional hepatocytes. These data present important steps for definition of regulatory phenomena that direct specific cell fate determination.'] |
['In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth.', 'Forty-two normal and thirty eight overweight women (mean±SD; age: 26.9±2.5years; pre-pregnancy BMI 26±2.2kg/m(2)) were seen during each of the three trimesters, had blood sampling and a 75g oral glucose tolerance test. At birth, neonates underwent anthropometry and cord blood sampling for c-peptide, glucose, insulin.', 'During all three trimesters maternal weight correlated positively with percent total neonatal body fat while during the second and third trimesters it correlated positively with birth weight. The second trimester maternal active ghrelin levels correlated positively with neonatal waist and were its best positive predictor. The third trimester maternal active ghrelin levels correlated positively with neonatal waist and negatively with percent total neonatal body fat, fetal cord blood insulin levels and were the best negative predictor of the latter. The third trimester maternal leptin levels correlated negatively with neonatal waist.'] |
['Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation.', 'Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery.', 'Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6).'] |
['It is common for alcoholic patients to have excess iron accumulation in the liver, which may contribute to the development of alcoholic liver disease (ALD). However, the mechanism of hepatic iron uptake in ALD is still obscure. Recently, a novel iron-regulatory hormone hepcidin was found that suppresses the absorption of iron from the small intestine and the release of iron from macrophages. To elucidate the contribution of hepcidin toward the hepatic excess iron accumulation in ALD, we examined whether alcohol loading affects hepcidin expression both in ALD patients and in an ethanol-fed mouse model.', 'Serum prohepcidin concentration was quantified by enzyme-linked immunosorbent assay. Hepatic hepcidin-1 and hepcidin-2 mRNA expressions in mouse liver were evaluated by quantitative real-time reverse-transcriptase polymerase chain reaction method. The protein expression of prohepcidin in mouse liver was examined immunohistochemically by rabbit antimouse prohepcidin antibody.', 'Serum prohepcidin concentration in ALD was significantly lower than that in healthy subjects (p<0.001). Especially, serum prohepcidin concentrations were decreased in the patients whose serum ferritin value was high. In the ethanol-fed mouse model, hepatic hepcidin-1 mRNA expression was significantly lower than that in control (p=0.04). Prohepcidin was expressed in the cytoplasm of hepatocytes of mice liver tissue sections, and its expression was decreased after ethanol loading.'] |
['Gastric carcinogenesis involves CpG island hypermethylation (CIHM) of tumor-suppressor genes. Although the CIHM of these genes occurs in non-neoplastic gastric cells, it is unclear whether this epigenetic alteration is linked with aging and/or gastric cancer risk. We investigated this linkage in noncancerous gastric mucosa infected with H. pylori.', 'Noncancerous corpus mucosa was endoscopically obtained from H. pylori-positive gastric cancer patients (n = 34), and age-matched H. pylori-positive noncancerous controls (n = 68). Genomic DNA retrieved from the mucosa was subjected to methylation-specific polymerase chain reaction for p16, Ecad, and DAPK genes. Linkage between CIHM and clinicopathologic factors was evaluated.', 'CIHM rates of DAPK, Ecad, and p16 promoters were significantly higher in noncancerous gastric mucosa of gastric cancer patients (91, 88, and 68%, respectively) than in noncancerous controls (71, 53, and 25%, respectively). Multivariate regression analysis showed a significant linkage between CIHM in noncancerous mucosa and coexistence of gastric cancer. Significant linkage between polymorphoneutrophil infiltration and CIHM was observed except for CIHM of p16. No linkage was observed between CIHM and other parameters, including age. High CIHM status (all three tested genes methylated) was associated with an increased risk of gastric cancer, with an odds ratio of 9.8 (95% confidence interval, 3.8-25.3).'] |
['While aberrant activation of the chromatin-remodeling SWI/SNF complexes has been associated with cancer development and progression, the role of each subunit in tumor cells is poorly defined. This study is aimed to characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer cells.', 'Genetic approaches and chemical inhibitors were used to manipulate the activities of SMARCE1 and its downstream targets in multiple breast cancer cell lines. Xenograft mouse models were used to analyze the role of SMARCE1 in lung metastasis in vivo. Nonadherent culture conditions were used to elucidate the role of SMARCE1 in regulating anoikis. Chromatin immunoprecipitation (ChIP), immunoprecipitation, and immunoblotting assays were designed to dissect the mechanism of action of SMARCE1. Public databases were used to investigate the relationship between SMARCE1 deregulation and breast cancer prognosis.', 'SMARCE1 knockdown reduced lung metastasis of breast cancer cells and sensitized tumor cells to anoikis. In response to loss of attachment, SMARCE1 interacted with and potentiated transcriptional activity of HIF1A, resulting in rapid PTK2 activation. Both HIF1A and PTK2 were indispensable for SMARCE1-mediated protection against anoikis by promoting activation of ERK and AKT pathways while suppressing the expression of pro-apoptotic BIM protein. Expression data analysis of a large cohort of human breast tumors revealed that high expression of SMARCE1 or PTK2 is associated with poor prognosis and tumor relapse, and PTK2 expression is positively correlated with SMARCE1 expression in basal-like and luminal B subtypes of breast tumors.'] |
['Nuclear receptor Nur77, also known as NR4A1, TR3, or NGFI-B, is expressed in human atherosclerotic lesions in macrophages, endothelial cells, T cells and smooth muscle cells. Macrophages play a critical role in atherosclerosis and the function of Nur77 in lesion macrophages has not yet been investigated.', 'This study aims to delineate the function of Nur77 in macrophages and to assess the effect of bone marrow-specific deficiency of Nur77 on atherosclerosis.', 'We investigated Nur77 in macrophage polarization using bone marrow-derived macrophages (BMM) from wild-type and Nur77-knockout (Nur77(-/-)) mice. Nur77(-/-) BMM exhibit changed expression of M2-specific markers and an inflammatory M1-phenotype with enhanced expression of interleukin-12, IFNγ, and SDF-1α and increased NO synthesis in (non)-stimulated Nur77(-/-) BMM cells. SDF-1α expression in nonstimulated Nur77(-/-) BMM is repressed by Nur77 and the chemoattractive activity of Nur77(-/-) BMM is abolished by SDF-1α inhibiting antibodies. Furthermore, Nur77(-/-) mice show enhanced thioglycollate-elicited migration of macrophages and B cells. The effect of bone marrow-specific deficiency of Nur77 on atherosclerosis was studied in low density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Ldlr(-/-) mice with a Nur77(-/-)-deficient bone marrow transplant developed 2.1-fold larger atherosclerotic lesions than wild-type bone marrow-transplanted mice. These lesions contain more macrophages, T cells, smooth muscle cells and larger necrotic cores. SDF-1α expression is higher in lesions of Nur77(-/-)-transplanted mice, which may explain the observed aggravation of lesion formation.'] |
['Roundabout (Robo) receptors and their ligand Slit are important regulators of axon guidance and cell migration. The development of Drosophila embryonic sense organs provides a neuronal migration paradigm where the in vivo roles of Slit and Robo can be assayed using genetics.', 'Here we show that Slit-Robo signaling controls migration of Drosophila larval sensory neurons that are part of the Chordotonal (Cho) stretch receptor organs. We used live imaging to show that abdominal Cho organs normally migrate ventrally during development, whereas thoracic Cho organs do not. Robo2 overexpression in cis (in the sensory neurons) or in trans (on neighboring visceral mesoderm) transforms abdominal organs to a thoracic morphology and position by blocking migration, while loss of Slit-Robo signaling produces a reverse transformation in which thoracic organs migrate ectopically. Rescue and tissue-specific knockout experiments indicate that trans signaling by Robo2 contributes to the normal positioning of the thoracic Cho organs. The differential positioning of Cho organs between the thorax and abdomen is known to be regulated by Hox genes, and we show that the essential Hox cofactor Homothorax, represses Robo2 expression in the abdominal visceral mesoderm.'] |
['To examine the prognostic impact of geminin expression, a negative regulator of DNA replication, in salivary gland carcinomas.', 'Tissues from 170 patients with salivary gland carcinoma were assembled in a tissue microarray format, and immunohistochemistry staining for geminin and Ki67 was performed. Patients were categorized into three groups using the tertile values of the labelling index (LI) for each marker as the cut-off points for constructing Kaplan-Meier survival curves. The LI for geminin was relatively low in acinic cell carcinoma (mean 1.55%) and mucoepidermoid carcinoma (mean 2.43%), intermediate in adenoid cystic carcinoma (mean 4.09%), and relatively high in salivary duct carcinoma (mean 15.22%). The geminin LI was significantly correlated with the Ki67 LI and histopathological factors, including pathological T factor, lymphatic and blood vessel infiltration, and lymph node metastasis. The increased expression of geminin was more strongly associated with reduced overall and relapse-free survival rates than with Ki67 expression and was a significant and independent prognostic factor in patient survival and tumour relapse.'] |
['Pollen allergy still represents an important cause of allergic morbidity worldwide. Accurate diagnostic methods are important to determine the disease-causing allergen.', 'To describe the sensitization patterns of patients with spring pollinosis and to make a real-life evaluation of the usefulness of a predetermined IgE molecular profile compared with other sensitization methods for choosing the composition of immunotherapy.', 'One hundred seventy-five patients with a diagnosis of spring pollinosis completed a skin prick test study with Olea europaea, Phleum pratense, palm profilin, and peach peel and an in vitro study of the application of a specific recombinant IgE protocol (nOle e1, rPhl p1-5b, rPhl p12, rPhl p7, and rPru p3). Immunotherapy using the 2 methods was compared.', 'A high sensitization to nOle e1 and rPhl p1-5b was found. Profilin, polcalcin, and lipid transfer proteins seemed irrelevant for the differential diagnosis of olea and grass pollen sensitization in the most southern area of the Iberian Peninsula. Application of the component resolved the diagnosis, and the choice of immunotherapy was changed in more than 50% of patients.'] |
['To distinguish malignant from benign branch duct (BD)-intraductal papillary mucinous neoplasm (IPMN) still remains difficult. Recently, we revealed that MSX2 was frequently expressed in pancreatic cancer and its expression was correlated with aggressive behavior of the cancer. The aim of this study was to assess the involvement of MSX2 in IPMN development and whether its expression would differentiate malignant from benign IPMN.', 'Seventeen microdissected lesions and 45 IPMN tissues were used for quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. The role of MSX2 in the pancreatic duct cell was assessed by the induced expression of MSX2 in a normal human pancreatic duct epithelial cell line (HPDE).', 'Malignant IPMN expressed significantly higher levels of MSX2 mRNA than benign IPMN lesions. MSX2 protein expression was frequently found in borderline and malignant lesions (20/29, 68.9%), while its expression was seen in only one of 16 benign IPMN tissues. Univariate analysis showed that nodules of 6 mm or more and MSX2 expression were significantly correlated with the malignancy of BD-IPMN (P = 0.022 and 0.0026, respectively), and multivariate analysis revealed that only MSX2 expression was identified as an independent factor to predict malignant BD-IPMN. HPDE cells expressing MSX2 showed increased cellular proliferation compared to control cells.'] |
['It has been reported that rs940494 and rs805296 SNPs of apolipoprotein M (apoM) gene may confer the risk in the development of type 2 diabetes (T2D) and coronary artery disease (CAD) in the Han Chinese. However, a recent study demonstrated that rs805297 polymorphism is significantly associated with reduced total high density lipoprotein (HDL) levels in rheumatoid arthritis patients. But the relationship between rs805297 SNP and CAD has not been explored. The aim of the present study was to elucidate whether the rs805297 mutant allele is implicated in CAD and links to changes in blood lipid levels in these patients.', 'Three hundred CAD patients and three hundred and twelve non-CAD patients were subjected in the present study. All subjects were confirmed by the angiography. Plasma concentrations of apoM were semi-quantitatively determined by dot-blotting analysis, and total serum lipid levels were quantified using an automated RA-1000 (Technician, USA). The genotyping of rs805297 of apoM was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).', 'Genotype and allele frequencies were not significant (P\u2009=\u20090.5798 and 0.3834, respectively) between cases and controls. Compared with the wild-type C/C genotype, carriers of the C/A and A/A genotypes did not have an increased risk of CAD, as determined by multiple logistic regression analysis, after adjustment for age, sex, BMI, history of smoking, hypertension and hypercholesterolemia. (CA, odds ratio\u2009=\u20090.49, 95% confidence interval 0.15-1.87, P\u2009=\u20090.462; AA, odds ratio\u2009=\u20090.51, 95% confidence interval 0.13-1.68, P\u2009=\u20090.534). The plasma concentration levels of apoM did not differ significantly among carriers of the three genotypes between two groups. Lastly, control subjects with A/A genotypes had lower total levels of HDL cholesterol than did those with C/C genotypes.'] |
['A study of the histologic changes of the intervertebral discs (IVDs) in biglycan (Bgn)-deficient mice.', 'In this study, we investigate whether the absence of Bgn accelerates the degenerative process in mouse intervertebral disc (IVD).', 'Proteoglycans and collagen fibrils are major components in the extracellular matrix (ECM) composition of IVD. The ECM of IVD contains several members of the small leucine repeat proteoglycans (SLRPs) family. Bgn is one member of SLRPs family, and showed a unique expression with age and degeneration in the human IVD. To date, there have been no in vivo studies to see whether SLRPs have a role in maintaining the structural integrity of IVD. To explore the functions of Bgn in the IVD, we examined discs in Bgn-deficient mice.', 'A total of 30 spine specimens were harvested from wild-type (WT) and Bgn-deficient mice. Five specimens for each genotype at 4-, 6-, and 9-month old were examined in the experiments. Histologic analysis of the IVD was performed. Histologic gradings were performed separately on nucleus pulposus, anulus fibrosus, and endplate according to the classification system proposed by Boos et al.', 'We found that Bgn-deficient mice developed an early onset of disc degeneration compared with WT mice. The degenerative scores of Bgn-deficient mice were significantly higher than those of WT mice at 4- and 9-month-old. High scores for nucleus pulposus and anulus fibrosus in Bgn-deficient mice significantly affected the difference in total degenerative scores at 9 months of age.'] |
['To investigate the role of leukotriene B4 (LTB4) and its receptor BLT1 in the pathogenesis of mouse uveitis.', 'Experimental autoimmune uveitis (EAU) was induced in B10RIII mice by immunization of interphotoreceptor retinoid binding protein (IRBP; peptide sequence 161-180) or in C57BL/6 (B6) mice by transfer of activated T cells specific for IRBP1-20. The animals were then treated with and without the BLT1 receptor antagonist, CP105696, at the disease onset after immunization or at day 0 or day 6 after T-cell transfer. EAU was also induced in wild-type B6 (WT) and BLT1-deficient (BLT1-/-) mice by reciprocal transfer of the T cells from B6 to BLT1-deficient mice and vise versa. Clinical signs of inflammation and ocular histology were compared. The chemotactic activity of LTB4 on naïve and IRBP-specific autoreactive T cells as well as effector leukocytes was examined.', 'The treatment of CP105696, greatly reduced the intensity of ongoing disease. IRBP1-20-specific T cells derived from wild-type B6 mice induced only mild uveitis in syngeneic BLT1-deficient mice and that IRBP1-20-specific T cells derived from BLT1-/- mice induced milder disease in wild-type B6 mice than those derived from wild-type B6 mice, suggesting that expression of the LTB4 receptor on both activated autoreactive T cells and effector leukocytes was necessary for ocular inflammation to occur. Consistent with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase-deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also failed to induce uveitis in the recipient mice.'] |
['Clinical trials show that larger immediate postdeployment stent diameters provide greater ultimate luminal size, whereas animal data show that arterial injury and stent design determine late neointimal thickening. At deployment, a stent stretches a vessel, imposing a cross-sectional polygonal luminal shape that depends on the stent design, with each strut serving as a vertex. We asked whether this design-dependent postdeployment luminal geometry affects late neointimal thickening independently of the extent of strut-induced injury.', 'Stainless steel stents of 3 different configurations were implanted in rabbit iliac arteries for 3 or 28 days. Stents designed with 12 struts per cross section had 50% to 60% less mural thrombus and 2-fold less neointimal area than identical stents with only 8 struts per cross section. Sequential histological sectioning of individual stents showed that immediate postdeployment luminal geometry and subsequent neointimal area varied along the course of each stent subunit. Mathematical modeling of the shape imposed by the stent on the artery predicted late neointimal area, based on the re-creation of a circular vessel lumen within the confines of the initial stent-imposed polygonal luminal shape.'] |
['The objective of this study was to explore the relation between the application of a mixture of lidocaine/prilocaine cream (eutectic mixture of local anesthetics [EMLA]) before intravenous cannula insertion and perceived pain in the pediatric patient.', 'Double-blind placebo-controlled trial.', 'A general inpatient pediatric ward.', 'We examined 26 male and 31 female patients between the ages of 4 and 12 years who required intravenous cannula insertion. Intravenous insertion was performed on 57 patients, with 29 patients in the placebo group (mean age, 8.1 years) and 28 in the EMLA group (mean age, 8.0 years).', 'Application of either EMLA cream or placebo 45 minutes before intravenous cannulation.', 'Pain was scored by the patients using a 0- to 10-cm visual analogue scale combined with a Faces pain scale as well as visual observation by a nurse. Adverse side effects were recorded in a separate table.', 'Data collected and the differences between the placebo and treated groups were tested using a Mann-Whitney U test. Those children in the EMLA group (mean pain score, 1.25) experienced less pain than those in the placebo group (mean, 8.39). There was no statistical significance between age, sex, and race.'] |
['Moderate hyperhomocysteinemia and B vitamins deficiency are thought to be risk factors for venous thromboembolism (VTE). The causality and independence of those associations are still questioned.', 'We measured fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients hospitalized with a first well-documented deep vein thrombosis and/or pulmonary embolism not related to a major acquired risk factor and 467 controls matched for gender and age.', 'Mild hyperhomocysteinemia, low serum folates, and vitamin B12 were associated with VTE independently of each other. In multivariate analysis, odds ratios (OR) (95% CI) for VTE associated with mild hyperhomocysteinemia (>15 micromol L(-1)), low serum folates (< or = 4.9 nmol L(-1)), and vitamin B12 (< or = 253 pmol L(-1)) were 1.48 (1.05-2.08), 3.14 (1.35-7.32) and 1.42 (1.03-1.98), respectively. An MTHFRC677T genotype was not significantly associated with VTE; OR (95% CI): 1.13 (0.70-1.81)'] |
['To characterize the expression profile of p73 in human normal tissues by immunohistochemistry (IHC) and to analyze the correlation between p73 expression and bladder cancer progression.', 'CJDp73 was characterized for p73alpha detection in Western blot and IHC through its application to isoform-transfected 293 cells. Normal tissues were analyzed by IHC with the CJDp73 antiserum. Transitional cell carcinoma (TCC)-derived cell lines were subjected to reverse transcription-PCR and Western blot. TCC tissue microarrays were analyzed for p73alpha expression by IHC, and the results were statistically analyzed.', 'p73 immunostaining was nuclear and restricted to epithelial cells of certain organs such as squamous epithelium of the epidermis and transitional epithelium of the bladder. The expression was also observed in certain specialized glandular epithelia such as acinar cells of breast and parotid gland. Four of seven TCC-derived cell lines had low to undetectable p73alpha protein levels. We found undetectable or low p73alpha expression in 104 of 154 (68%) TCC cases, this phenotype being more frequently observed in invasive tumors when compared with superficial lesions. This association was statistically significant (P < 0.0001). We also observed a significant association between p53, p63, and p73alpha alterations with bladder cancer progression (P < 0.0001).'] |
['To determine if neuromuscular electrical stimulation (NMES) applied to the ankle dorsiflexors during gait improves muscle volume and strength in children with unilateral spastic cerebral palsy (CP).', 'Thirty-two children (15 females, 17 males; mean age 10y 8mo, age range 5y 5mo-18y 1mo) with unilateral spastic CP and a Gross Motor Function Classification System of level I or level II were randomly assigned to either the 8-week daily NMES treatment group or control group (usual or conventional treatments). Outcomes at week 8 (post-NMES) and week 14 (carryover) included magnetic resonance imaging for muscle volumes (tibialis anterior, anterior compartment, and gastrocnemius), strength (hand-held dynamometry for isometric dorsiflexion strength and heel raises for functional strength), and clinical measures for lower limb selective motor control.', 'At week 8, the treatment group demonstrated significantly (p<0.05) increased muscle volumes for tibialis anterior, anterior compartment, medial and lateral gastrocnemius, and dorsiflexion strength not only when compared to their baseline values but also when compared to the control group at week 8. At week 14, both tibialis anterior and lateral gastrocnemius volumes in the treatment group remained significantly increased when compared to their baseline values. However, only lateral gastrocnemius volumes had significantly greater values when compared to the control group at week 14. There were no between group differences in the clinical measures for lower limb selective motor control at week 8 and 14.'] |
['A somatic mutation in GNAQ (c.548G>A; p.R183Q), encoding Gαq, has been found in syndromic and sporadic capillary malformation tissue. However, the specific cell type containing the mutation is unknown. The purpose of this study was to determine which cells in capillary malformations have the GNAQ mutation.', 'Human capillary malformation tissue was obtained from 13 patients during a clinically indicated procedure. Droplet digital polymerase chain reaction, capable of detecting mutant allelic frequencies as low as 0.1 percent, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence-activated cell sorting into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by droplet digital polymerase chain reaction.', 'Eight capillary malformations contained GNAQ p.R183Q mutant cells, two lesions had novel GNAQ mutations (p.R183L and p.R183G), and three capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2 to 11 percent. Following fluorescence-activated cell sorting, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-β-positive cell population; mutant allelic frequencies were 3 to 43 percent.'] |
['In the emergency department (ED) of a teaching hospital, rapid sequence intubation (RSI) is performed by physicians with a wide range of experience. A variety of medications have been used for RSI, with potential for inadequate or excessive dosing as well as complications including hypotension and the need for redosing. We hypothesized that the use of a standardized RSI medication protocol has facilitated endotracheal intubation requiring less medication redosing and less medication-related hypotension.', 'An RSI medication protocol (ketamine 2 mg/kg intravenously administered and rocuronium 1 mg/kg intravenously administered, or succinylcholine 1.5 mg/kg intravenously administered) was implemented for all trauma patients undergoing ED intubation at a Level I trauma center. We retrospectively reviewed patients for the 1-year period before (PRE) and after (KET) the protocol was instituted. Data collected included age, sex, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) score of the head/face, AIS score of the chest, RSI drugs, need for redosing, time to intubation, indication for RSI, and number of RSI attempts.', 'During the study period, 439 patients met inclusion criteria; 266 without protocol (PRE) and 173 with protocol (KET). Patients were severely injured with a mean ISS of 24 and median AIS score of the head/face of 3. Dosing in the KET group was appropriate with a mean dose of 1.9-mg/kg ketamine administered. Compliance after KET introduction approached 90%. Fifteen patients in the PRE group required redosing of medication versus three in the KET group (p < 0.05, χ). For patients younger than 14 years, (26 in PRE and 10 in KET), 2 patients in the PRE group required redosing and none in the KET group (not significant). In all patients, mean time from drug administration to intubation decreased from 4 minutes to 3 minutes.'] |
['Loricrin keratoderma (LK) is a group of congenital skin abnormalities characterized by the common features of honeycomb palmoplantar keratoderma and diffused ichthyosiform dermatosis. Earlier studies have shown that LK is associated with genetic defects of the loricrin gene.', 'To determine the correlation between a loricrin mutation and a heterogeneous phenotype of loricrin keratoderma.', 'We obtained DNA samples from a large family in which affected members showed more severe hyperkeratosis on the dorsal parts of their hands, mild palmoplantar keratoderma with no honeycomb-like manifestations and generalized ichthyosis. Screening of the loricrin gene was performed by direct sequencing of the entire coding region. Plasmids encoding the green fluorescent protein-tagged human loricrin were constructed and transferred to 293A cells for subcellular localization analyses.', 'Molecular analyses of the loricrin gene identified a novel insertion mutation c.545-546insG that resulted in a frameshift after codon 182. This mutation was predicted to produce a mutant protein with a frameshift of its C-terminal sequence of amino acids that embeds a newly generated nuclear localization signal (NLS), and to be 22 amino acids longer than the wild-type protein due to a delayed termination codon. The NLSs appear to result in an accumulation of mutant loricrin within nuclei.'] |
['Mesenchymal stem cells (MSCs) are multipotent cells in the bone marrow that have been found to migrate to tumors, suggesting a potential use for cancer gene therapy. MSCs migrate to sites of tissue damage, including normal tissues damaged by radiation. In this study, we investigated the effect of tumor radiotherapy on the localization of lentivirus-transduced MSCs to tumors.', 'MSCs were labeled with a lipophilic dye to investigate their migration to colon cancer xenografts. Subsequently, the MSCs were transduced with a lentiviral vector to model gene therapy and mark the infused MSCs. LoVo tumor xenografts were treated with increasing radiation doses to assess the effect on MSC localization, which was measured by quantitative polymerase chain reaction. MSC invasion efficiency was determined in an invasion assay.', 'MSCs migrated to tumor xenografts of various origins, with few cells found in normal tissues. A lentiviral vector efficiently transduced MSCs in the presence, but not the absence, of hexadimethrine bromide (Polybrene). When LoVo tumors were treated with increasing radiation doses, more MSCs were found to migrate to them than to untreated tumors. Irradiation increased MSC localization in HT-29 and MDA-MB-231, but not UMSCC1, xenografts. Monocyte chemotactic protein-1 expression in tumors did not correlate with the basal levels of MSC infiltration; however, monocyte chemotactic protein-1 was modestly elevated in irradiated tumors. Media from irradiated LoVo cells stimulated MSC invasion into basement membranes.'] |
['TLR4 is a cell-surface signaling receptor involved in the recognition and host response to Helicobacter pylori. The TLR4+896A>G polymorphism linked with impaired reactivity to bacterial lipopolysaccharide may play a role in gastric carcinogenesis.', 'We assessed associations with premalignant gastric changes in 149 relatives of gastric cancer patients, including 45 with hypochlorhydria and gastric atrophy. We also genotyped 2 independent Caucasian population-based case-control studies of upper gastrointestinal tract cancer, initially in 312 noncardia gastric carcinoma cases and 419 controls and then in 184 noncardia gastric carcinomas, 123 cardia carcinomas, 159 esophageal cancers, and 211 frequency-matched controls. Odds ratios were computed from logistic models and adjusted for potential confounding factors.', 'TLR4+896G carriers had an 11-fold (95% confidence interval [CI], 2.5-48) increased odds ratio (OR) for hypochlorhydria; the polymorphism was unassociated with gastric acid output in the absence of H pylori infection. Carriers also had significantly more severe gastric atrophy and inflammation. Seventeen percent of gastric carcinoma patients in the initial study and 15% of the noncardia gastric carcinoma patients in the replication study had 1 or 2 TLR4 variant alleles vs 8% of both control populations (combined OR = 2.3; 95% CI = 1.6-3.4). In contrast, prevalence of TLR4+896G was not significantly increased in esophageal squamous cell (2%, OR = 0.2) or adenocarcinoma (9%, OR = 1.4) or gastric cardia carcinoma (11%, OR = 1.4).'] |
['Physical activity and nutritional supplementation interventions may be used to ameliorate age-related loss of skeletal muscle mass and function. Previous reviews have demonstrated the beneficial effects of resistance exercise training (RET) combined with protein or essential amino acids (EAA) in younger populations. Whether or not older adults also benefit is unclear. The aim of this review was to determine whether regular dietary supplementation with protein/EAA during a RET regimen augments the effects of RET on skeletal muscle in older adults.', 'A literature search was conducted in August 2015 using MEDLINE, EMBASE, SPORTDiscus, and CINAHL Plus to identify all controlled trials using a RET regimen with and without protein/EAA supplementation. Outcome variables included muscle strength, muscle size, functional ability, and body composition.', 'Fifteen studies fulfilled the eligibility criteria, including 917 participants with a mean age of 77.4\xa0years. Studies involving both healthy participants and those described as frail or sarcopenic were included. Overall, results indicated that protein supplementation did not significantly augment the effects of RET on any of the specified outcomes. Exceptions included some measures of muscle strength (3\xa0studies) and body composition (2 studies). Meta-analyses were conducted but were limited because of methodologic differences between studies, and results were inconclusive.'] |
['Systemic inflammation may inhibit neutrophil (PMN) apoptosis and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma causes dysregulation of PMN apoptosis.', 'Neutrophils were isolated from trauma patients (24-72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated +/- the nuclear factor kappa beta (NFkappabeta) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFkappabeta activation was determined by Western blot for phosphorylated I kappabeta.', 'Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosis correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis and induced phosphorylation of I kappabeta in control cells. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate.'] |
['The presence of specific and common genetic etiologies for autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) was investigated for 132 candidate genes in a two-stage design-association study.', '1,536 single nucleotide polymorphisms (SNPs) covering these candidate genes were tested in ASD (n = 144) and ADHD (n = 110) patients and control subjects (n = 404) from The Netherlands. A second stage was performed with those SNPs from Stage I reaching a significance threshold for association of p < .01 in an independent sample of ASD patients (n = 128) and controls (n = 124) from the United Kingdom and a Dutch ADHD (n = 150) and control (n = 149) sample.', 'No shared association was found between ASD and ADHD. However, in the first and second ASD samples and in a joint statistical analysis, a significant association between SNP rs167771 located in the DRD3 gene was found (joint analysis uncorrected: p = 3.11 x 10(-6); corrected for multiple testing and potential stratification: p = .00162).'] |
['Cardiac sympathetic afferent reflex (CSAR) participates in sympathetic over-excitation. Superoxide anions and angiotensin II (Ang II) mechanisms are associated with sympathetic outflow and CSAR in the paraventricular nucleus (PVN). This study was designed to investigate whether PVN superoxide anions mediate CSAR and Ang II-induced CSAR enhancement response in fructose-induced insulin resistance (IR) rats.', 'CSAR was evaluated with the changes of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to the epicardial application of capsaicin (CAP) in anaesthetized rats.', 'Compared with Control rats, IR rats showed that CSAR, PVN NAD(P)H oxidase activity, superoxide anions, malondialdehyde (MDA), Ang II and AT1 receptor levels were significantly increased, whereas PVN superoxide dismutase (SOD) and catalase (CAT) activities were decreased. In Control and IR rats, PVN microinjection of superoxide anions scavengers tempol, tiron and PEG-SOD (an analogue of endogenous superoxide dismutase) or inhibition of PVN NAD(P)H oxidase with apocynin caused significant reduction of CSAR, respectively, but DETC (a superoxide dismutase inhibitor) strengthened the CSAR. PVN pre-treatment with tempol abolished, whereas DETC potentiated, Ang II-induced CSAR enhancement response. Moreover, PVN pre-treatment with tempol or losartan prevented superoxide anions increase caused by Ang II in IR rats.'] |
['Volatile anesthetics attenuate agonist-induced endothelium-dependent vasodilation of coronary arteries. This study considered the hypothesis that the anesthetics may also attenuate flow-induced endothelium-dependent vasodilation.', 'Rat subepicardial arteries of approximately 100 microm were monitored for diameter changes in vitro by a video detection system, with the midpoint luminal pressure held constant at 40 mmHg but the pressure gradient (and therefore flow) across each vessel increased from 0 to 80 mmHg, in the presence or absence of 1 or 2 minimum alveolar concentration (MAC) isoflurane or 1 or 2 MAC halothane, with or without 10 microM of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) or 10 microM of the cyclooxygenase inhibitor indomethacin.', 'Flow-induced dilation was attenuated by L-NNA or indomethacin (p < 0.001 each). It was attenuated by isoflurane in a concentration-dependent manner (P < 0.001). Attenuation by 2 MAC isoflurane persisted even in the presence of L-NNA (P < 0.01) or indomethacin (P < 0.05). On the other hand, flow-induced dilation was enhanced by 2 MAC halothane (P < 0.05). Halothane at 1 MAC had no significant effect. Enhancement by 2 MAC halothane was evident in the presence of indomethacin (P < 0.05) but not L-NNA (P = 0.40).'] |
['Patterns of concerted fluctuation in populations-synchrony-can reveal impacts of climatic variability on disease dynamics. We examined whether malaria transmission has been synchronous in an area with a common rainfall regime and sensitive to the Indian Ocean Dipole (IOD), a global climatic phenomenon affecting weather patterns in East Africa.', 'We studied malaria synchrony in 5 15-year long (1984-1999) monthly time series that encompass an altitudinal gradient, approximately 1000 m to 2000 m, along Lake Victoria basin. We quantified the association patterns between rainfall and malaria time series at different altitudes and across the altitudinal gradient encompassed by the study locations.', 'We found a positive seasonal association of rainfall with malaria, which decreased with altitude. By contrast, IOD and interannual rainfall impacts on interannual disease cycles increased with altitude. Our analysis revealed a nondecaying synchrony of similar magnitude in both malaria and rainfall, as expected under a Moran effect, supporting a role for climatic variability on malaria epidemic frequency, which might reflect rainfall-mediated changes in mosquito abundance.'] |
['Cellular senescence, a form of cell-cycle arrest, is a tumor-suppressor mechanism triggered by multiple tumor-promoting insults, including oncogenic stress and DNA damage. The role of cyclin-dependent kinase 2 (CDK2) regulation has been evaluated in models of replicative senescence, but little is known regarding its role in other senescence settings. Using in vitro and in vivo models of DNA damage-and oncogene-induced cellular senescence, it was determined that activation of the tumor-suppressor protein p53 (TP53) resulted in repression of the CDK2 transcript that was dependent on intact RB. Ectopic CDK2 expression was sufficient to bypass p53-dependent senescence, and CDK2-specific inhibition, either pharmacologically (CVT313) or by use of a dominant-negative CDK2, was sufficient to induce early senescence. Pharmacologic inhibition of CDK2 in an in vivo model of pineal tumor decreased proliferation and promoted early senescence, and it also decreased tumor penetrance and prolonged time to tumor formation in animals lacking p53. In conclusion, for both oncogene- and DNA damage-induced cellular senescence, CDK2 transcript and protein are decreased in a p53- and RB-dependent manner, and this repression is necessary for cell-cycle exit during senescence.'] |
["The parents of the children who undergo surgery experience stress during the pre-anesthetic period. Such stress influences the mental status of their children, thereby inducing their pre-anesthetic anxiety and problematic behavior at emergence. Recently, measurement of salivary biomarkers was evaluated as stress biomarkers. Especially, alpha-amylase is utilized as an excellent index for psychological stress. In the present study, we tested whether salivary amylase activity of mothers before the surgery of their children correlates with the peri-operative children's behaviors.", 'A total of 22 pairs of mothers and children were analyzed. Maternal salivary amylase activity was evaluated at the entrance of the operation room. The children underwent minor plastic surgery under general anesthesia, and induction and emergence behaviors were assessed.', "The higher the maternal salivary amylase activity, the severer the children's induction anxiety (r(s)=-0.667, n=22, P<0.0001), and the higher the maternal amylase activity, the severer the children's emergence agitation (r(s)=0.705, n=22, P<0.0001)."] |
['We investigated the association between fasting plasma glucose variability (FPG-CV) and the risk of hip fracture in elderly diabetic patients. Our finding showed a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4\xa0% showed an increased risk in hip fractures.', 'Hip fracture is a major health burden in the population and is associated with high rates of mortality and morbidity especially in elderly. It is evident that diabetes mellitus is a risk factor of osteoporosis which is a significant risk factor of hip fracture. However, epidemiological studies exploring the risks of hip fracture among type 2 diabetic patients are limited.', 'A retrospective study of 26,501 ethnic Chinese older persons enrolled in the National Diabetes Care Management program in Taiwan was conducted; related factors were analyzed with extended Cox proportional hazards regression models to competing risk data on hip fracture incidence.', 'The results show a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4\xa0% showed an increased risk in hip fractures, confirming a linear relationship between the two. After multivariate adjustment, the risk of hip fracture increased among patients with FPG-CV of 25.4-42.3\xa0% and >42.3\xa0% compared with patients with FPG-CV of ≦ 14.3\xa0% (hazard ratio, 1.35; 95\xa0% confidence interval 1.14-1.60 and 1.27; 1.07-1.52, respectively). Significant linear trends among various FPG-CV were observed.'] |
['To examine factors associated with self-reported sleep quality and duration among very old adults in China.', 'Cross-sectional analysis of the 2005 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS).', 'In-home interview with older adults in 22 provinces in mainland China.', 'A total of 15,638 individuals aged 65 and older (5,047 aged 65-79, 3870 aged 80-89, 3927 aged 90-99, and 2794 aged 100 and older, including 6688 men and 8950 women).', 'N/A.', 'Two self-reported sleep questions together with numerous sociodemographic and health status measures were used in this study. Sixty-five per cent of Chinese elders reported good quality of sleep. The average number of self-reported hours of sleep was 7.5 (SD 1.9), with 13.1%, 16.2%, 18.0%, 28.0%, 9.2%, and 15.5% reporting < or = 5, 6, 7, 8, 9, and > or =10 hours, respectively (weighted). Multivariate analyses showed that male gender, rural residence, Han ethnicity, higher socioeconomic status, and good health conditions were positively associated with good quality of sleep. All other factors being equal, octogenarians, nonagenarians, and centenarians were more likely to have good sleep quality than the young elders aged 65-79. Elders with poorer health status or older age were more likely to have either relatively shorter (< or = 6 h) or longer (> or = 10 h) sleep duration. Married elders were more likely to have an average duration between these two values. Except for some geographic variations, associations between all other factors and sleep duration were weak compared to the effects of health.'] |
['Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk.', "The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses.", 'Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort.'] |
["adverse outcomes and near misses are believed to share many characteristics in terms of clinical situations and care management problems. Little is documented concerning what prevents adverse outcomes from happening once the 'accident trajectory' begins. This two-stage pilot study set out to investigate midwives' understandings and recollections of clinical near misses.", 'anonymous self-completion questionnaire and follow-up group interviews.', 'clinically based midwives working in four maternity units in Scotland (questionnaire [n = 34]; interviews [n = 26]).', 'despite a low response rate to the questionnaire, the cited examples seem to confirm that near misses and adverse outcomes follow essentially similar routes until the former are halted by a saving intervention. Dangerous situations are created by heavy workloads, and are aggravated by sub-optimal skill-mix, poor communication and individuals making mistakes or not following accepted procedures. Overwhelmingly, what prevents this situation from resulting in an adverse outcome is an intervention by another practitioner--often reported to be by chance and not design. In the interviews, these situations were discussed with reference to unit culture, the causes of errors and near misses, helping to prevent mistakes, the consequences of near misses and staff confiding in one another.'] |
['To evaluate the prognostic impact of the number of positive nodes and the lymph node ratio (LNR) of positive to excised nodes on survival in women diagnosed with nodal micrometastatic breast cancer before the era of widespread sentinel lymph node biopsy.', 'Subjects were 62,551 women identified by the Surveillance Epidemiology and End Results database, diagnosed with pT1-2pN0-1 breast cancer between 1988 and 1997. Kaplan-Meier breast cancer-specific survival (BCSS) and overall survival (OS) were compared between three cohorts: node-negative (pN0, n=57,980) nodal micrometastasis all <or=2mm (pNmic, N=1818), and macroscopic nodal metastasis >2mm but <2 cm (pNmac, n=2753). Nodal subgroups were examined by the number of positive nodes (1-3 versus >or= 4) and the LNR (<or=0.25 versus >0.25).', 'Median follow-up was 7.3 yr. Ten-year BCSS and OS in pNmic breast cancer were significantly lower compared to pN0 disease (BCSS 82.3% versus 91.9%, p<0.001 and OS 68.1% versus 75.7%, p<0.001). BCSS and OS with pNmic disease progressively declined with increasing number of positive nodes and increasing LNR. OS with pNmic was similar to pNmac disease when matched by the number of positive nodes and by the LNR. Both pN-based and LNR-based classifications were significantly prognostic of BCSS and OS on Cox regression multivariate analysis.'] |
['Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate mucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated.', 'LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored.', 'In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression.'] |
['The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication.', 'Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively.', 'There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038).'] |
['Little is known about how bacteria establish chronic infections of mucosal surfaces. Helicobacter pylori (H. pylori), a chronic pathogen that lives in the gastric mucosa of humans, interacts with the trefoil factor family (TFF) protein TFF1, which is found in gastric mucus. We aimed to characterize the interaction of H. pylori with TFF1 and to assess the role of this interaction in mediating colonization.', 'Subcellular fractions of H. pylori were immobilized and then probed with TFF1, TFF2, or TFF3. The effect of glycosidases and preincubation with monosaccharides on the interaction and binding of TFF1 to a H. pylori adhesin was assessed. The interaction between H. pylori adhesin and TFF1 was characterized using surface plasmon resonance, flow cytometry, nondenaturing polyacrylamide gel electrophoresis, coimmunofluoresence, and incubation with tissue sections.', 'The H. pylori core oligosaccharide portion (rough form) of lipopolysaccharide (RF-LPS) bound to TFF1 and to a lesser extent TFF3; this interaction was inhibited by incubation of RF-LPS with mannosidase, glucosidase, or mixed monosaccharides. TFF1 also bound to human serum albumin-conjugated mannose and glucose. The optimum pH for binding was 5.0-6.0 for TFF1 and 7.0 for TFF3. H. pylori bound TFF1 in gastric mucus ex vivo; binding of LPS-coated latex beads to human antral gastric tissue was inhibited by TFF1.'] |
['Little is known about the effect of nonadherence among patients with coronary artery disease (CAD) on a broad spectrum of outcomes including cardiovascular mortality, cardiovascular hospitalizations, and revascularization procedures.', 'This was a retrospective cohort study of 15,767 patients with CAD. Medication adherence was calculated as proportion of days covered for filled prescriptions of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statin medications. Multivariable Cox regression assessed the association between medication nonadherence as a time-varying covariate and a broad range of outcomes, adjusting for demographics and clinical characteristics. Median follow-up was 4.1 years.', 'Rates of medication nonadherence were 28.8% for beta-blockers, 21.6% for ACE inhibitors, and 26.0% for statins. In unadjusted analysis, nonadherence to each class of medication was associated with higher all-cause and cardiovascular mortality. In multivariable analysis, nonadherence remained significantly associated with increased all-cause mortality risk for beta-blockers (hazard ratio [HR] 1.50, 95% CI 1.33-1.71), ACE inhibitors (HR 1.74, 95% CI 1.52-1.98), and statins (HR 1.85, 95% CI 1.63-2.09). In addition, nonadherence remained significantly associated with higher risk of cardiovascular mortality for beta-blockers (HR 1.53, 95% CI 1.16-2.01), ACE inhibitors (HR 1.66, 95% CI 1.26-2.20), and statins (HR 1.62, 95% CI 1.124-2.13). The findings of increased risk associated with nonadherence were consistent for cardiovascular hospitalization and revascularization procedures.'] |
['In reaching the airways inhaled allergens pass through and contact with the oral mucosa. Although they are often responsible for initiating asthmatic attacks, it is unknown whether airborne allergens can also trigger chronic inflammation of gingival epithelial cells leading to chronic periodontitis. In this study, we investigated the inflammatory responses of human gingival epithelial cells (HGECs) to airborne allergens, particularly German cockroach extract (GCE) with a focus on calcium signaling.', 'HGECs isolated from healthy donors were stimulated with GCE. Intracellular Ca(2+) concentration ([Ca(2+)]i) was measured with Fura-2-acetoxymethyl ester (Fura-2/AM) staining. Expression of inflammatory cytokines interleukin (IL)-8, IL-1β, IL-6, and NOD-like receptor family, pyridine domain-containing (NLRP) 3 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR).', 'GCE promoted increase in the [Ca(2+)]i in a dose-dependent manner. Depletion of endoplasmic reticulum (ER) Ca(2+) by the ER Ca(2+) ATPase inhibitor thapsigargin (Tg) but not the depletion of extracellular Ca(2+) abolished the GCE-induced increase in [Ca(2+)]i. Treatment of phospholipase C (PLC) inhibitor (U73122) or 1,4,5-trisinositolphosphate (IP3) receptor inhibitor (2-APB) also prevented GCE-induced increase in [Ca(2+)]i. Protease activated receptor (PAR)-2 activation mainly mediated the GCE-induced increase in [Ca(2+)]i and enhanced the expression of IL-8, NLRP3, IL-1β, and IL-6 in HGECs.'] |
['We examined the effect of oral vitamin B(12) treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC).', 'Patients (n = 88; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral treatment with (a) vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (b) vitamin B(12) and folic acid; (c) vitamin B(6); or (d) placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.', 'The intraindividual variation for patients not treated with B(12) was approximately 10% for plasma total cobalamin, total TC, apo-TC, and apo-HC, and <20% for holo-TC and TC saturation. In B(12)-treated patients, the maximum change in concentrations was observed already after 3 days for total TC (-16%), holo-TC (+54%), and TC saturation (+82%). At this time holo-HC (+20%) and plasma total cobalamin (+28%) showed an initial burst, but had increased further at 84 days. All changes were highly significant compared with the control group (P <0.0001).'] |
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