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['AMPactivated protein kinase α (AMPKα) is closely involved in the process of cardiac hypertrophy. Asiatic acid (AA), a pentacyclic triterpene, was found to activate AMPKα in our preliminary experiment. However, its effects on the development of cardiac hypertrophy remain unclear. The present study was to determine whether AA could protect against cardiac hypertrophy.', 'Mice subjected to aortic banding were orally given AA (10 or 30mg/kg) for 7 weeks. In the inhibitory experiment, Compound C was intraperitoneally injected for 3 weeks after surgery.', 'Our results showed that AA markedly inhibited hypertrophic responses induced by pressure overload or angiotensin II. AA also suppressed cardiac fibrosis in vivo and accumulation of collagen in vitro. The protective effects of AA were mediated by activation of AMPKα and inhibition of the mammalian target of rapamycin (mTOR) pathway and extracellular signal-regulated kinase (ERK) in vivo and in vitro. However, AA lost the protective effects after AMPKα inhibition or gene deficiency.']
['To identify long-term sensorimotor and cognitive deficits and to evaluate structural alterations in brain ischemic mice.', 'C57Bl/6J male mice were subjected to 30 min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6 months. Cortical and subcortical damage were analyzed by MRI multiparameter analysis and histopathology.', 'tMCAo mice showed significant sensorimotor deficits in the rotarod, negative geotaxis, neuroscore, and beam walk tests. They also showed impairment in exploratory behavior in the open field test and in spatial learning in the Morris water maze. T2-weighted MRI revealed a volume reduction in injured brain areas at 12 and 24 weeks postinjury. Brain atrophy was shown by MRI and conventional postmortem analysis. Diffusion tensor imaging on the external capsule showed increased values of axial and radial diffusivity. Fiber tracking revealed a reduction in the number and length of ipsilateral fibers.']
['Positron emission tomography (PET) identifies cancer deposits by detecting sites of gamma emissions that are released from radioactively labeled molecules targeting tumor to formulate a PET image. Correlating preoperative PET scans with intraoperative findings remains a challenge. We investigated whether high-energy gamma emissions detected by a novel hand-held PET probe would detect tumors and offer a real-time method to localize tumor intraoperatively. Furthermore, we investigated the novel beta probe, which detects emissions at a shorter range than gamma emissions, making them undetectable by PET scanners, but potentially valuable for close range intraoperative detection of tumor deposits.', 'Six-to-eight-week-old athymic mice were injected with one of four possible tumor cell lines: gastric, pancreas, squamous cell and breast cancer. After tumors reached at least 1 cm in size, they were euthanized and imaged with a micro-PET imager. Hand-held gamma and beta probes were then used in vivo and ex vivo to measure high-energy gamma and beta emissions.', 'The portable PET probes detected high-energy gamma and beta emissions from all tumors evaluated. These emissions were reproducible and we established that beta emissions correlate with high-energy gamma emissions and conventional PET scans. There was a strong positive correlation (R = 0.8) between gamma and beta counts. Beta emission showed a stronger correlation than gamma emission with overall tissue radioactivity.']
['Cirrhotic patients are predisposed to intestinal bacterial overgrowth with translocation of bacterial products which may deteriorate liver hemodynamics. Having shown that short-term administration of rifaximin improves liver hemodynamics in decompensated cirrhosis, we conducted this study to investigate the effect of intestinal decontamination with rifaximin on the long-term prognosis of patients with alcohol-related decompensated cirrhosis (Child-Pugh >\u20097) and ascites.', 'Patients who had received rifaximin and showed improved liver hemodynamics were enrolled in the current study and continued to receive rifaximin (1200\u2009mg/day). Each patient was matched by age, sex, and Child-Pugh grade to two controls and followed up for up to 5 years, death or liver transplantation. Survival and risk of developing portal hypertension-related complications were compared between rifaximin group and controls.', 'Twenty three patients fulfilled the inclusion criteria and matched with 46 controls. Patients who received rifaximin had a significant lower risk of developing variceal bleeding (35% vs. 59.5%, P\u2009=\u20090.011), hepatic encephalopathy (31.5% vs. 47%, P\u2009=\u20090.034), spontaneous bacterial peritonitis (4.5% vs. 46%, P\u2009=\u20090.027), and hepatorenal syndrome (4.5% vs. 51%, P\u2009=\u20090.037) than controls. Five-year cumulative probability of survival was significantly higher in patients receiving rifaximin than in controls (61% vs. 13.5%, P\u2009=\u20090.012). In the multivariate analysis, rifaximin administration was independently associated with lower risk of developing variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, and higher survival.']
['Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults.', 'Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup.', 'For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI.']
['Controlled laboratory cross-sectional study. Objectives To assess strength differences of the hip rotator and abductor muscle groups in young adults with chronic hip joint pain (CHJP) and asymptomatic controls. A secondary objective was to determine if strength in the uninvolved hip of those with unilateral CHJP differs from that in asymptomatic controls.', 'Little is known about the relationship between hip muscle strength and CHJP in young adults.', 'Thirty-five participants with CHJP and 35 matched controls (18 to 40 years of age) participated. Using handheld dynamometry, strength of the hip external rotators and internal rotators was assessed with the hip flexed to 90° and 0°. To assess external rotator and internal rotator strength, the hip was placed at the end range of external rotation and internal rotation, respectively. Strength of the hip abductors was assessed in sidelying, with the hip in 15° of abduction. Break tests were performed to determine maximum muscle force, and the average torque was calculated using the corresponding moment arm. Independent-sample t tests were used to compare strength values between (1) the involved limb in participants with CHJP and the corresponding limb in the matched controls, and (2) the uninvolved limb in participants with unilateral CHJP and the corresponding limb in the matched controls.', 'Compared to controls, participants with CHJP demonstrated weakness of 16% to 28% (P<.01) in all muscle groups tested in the involved hip. The uninvolved hip of 22 subjects with unilateral CHJP demonstrated weakness of 18% and 16% (P<.05) in the external rotators (0°) and abductors, respectively, when compared to the corresponding limb of the matched controls.']
['High concentrations of fibroblast growth factors (FGFs) are found in the heart. Even higher levels are measured during ischemia. Exogenous administration of FGF to ischemic myocardium promotes synthesis of collateral coronary circulation and induces local myocardial hypertrophy. The kinetics and the contribution of the heart and lungs to circulating basic FGF (bFGF) levels during cardiac surgery were characterized.', 'Plasma bFGF levels were measured in seven adults undergoing coronary artery bypass operations and 11 neonates undergoing congenital cardiac anomaly repair during cardiopulmonary bypass.', 'In both the adult and the neonatal groups, bFGF plasma levels increased significantly immediately after removal of the aortic cross-clamp (adult group 15.43+/-6.3 aorta cross-clamped versus 29+/-4.1 after release, P=0.011; neonatal group 17.09+/-9.43 aorta cross-clamped versus 43.55+/-14.25 after release, P=0.004) and declined thereafter. In the adult group, higher levels of bFGF were recorded in blood recovered from the coronary sinus than in the aortic root during aortic cross-clamping (63.14+/-14.42 versus 43.86+/-12.05, P=0.011), and in both, levels were significantly higher than the peripheral measurements.']
['To compare in a 3 month, multicenter, double blind, parallel study the efficacy and safety of a nonsteroidal antiinflammatory drug, aceclofenac, 100 mg bid orally, with that of tenoxicam, 20 mg orally at bedtime, in the treatment of adult patients with active ankylosing spondylitis (AS).', "A total of 273 patients (135 in the aceclofenac group and 138 in the tenoxicam group) entered the study. Eight efficacy variables were assessed: morning stiffness, visual analog pain scale, control of additional paracetamol, modified Schöber's test, C7 line-iliac crest distance, lateral flexion of the spine, thoracic expansion, and occiput-wall distance.", 'Seven of the 8 variables improved significantly in both groups, with no differences between the 2 groups in any variable at the end of the study. Six percent of patients taking aceclofenac and 5% of patients taking tenoxicam withdrew because of unsatisfactory therapeutic action. Forty-two adverse events possibly or probably related to treatment were observed in the aceclofenac group and 37 in the tenoxicam group. However, only 2.2% of patients in the aceclofenac group and 1.4% in the tenoxicam group withdrew for this reason.']
['During robot assisted hysterectomies and prostatectomies, surgical exposure demands the application of a CO2 pneumoperitoneum with a very steep Trendelenburg position (40 degrees). The extent to which oxygenation and ventilation might be compromised intra-operatively remains poorly documented.', "Dead-space ventilation and venous admixture were determined in 18 patients undergoing robot assisted hysterectomy (n = 6) or prostatectomy (n = 12). Anesthesia was maintained with desflurane in O2 or O2/air, with the inspired O2 fraction left at the discretion of the attending anesthesiologist. Controlled mechanical ventilation was used, but 15 min after assuming the Trendelenburg position and up until resuming the supine position pressure controlled ventilation was used. Dead-space ventilation and venous admixture were determined using Bohr's formula and Nunn's iso-shunt diagram, respectively, at the following 7 stages of the procedure: 15 min after induction; 5 min after applying the CO2 pneumoperitoneum (intra-abdominal pressure 12 mm Hg) but while still supine; 5, 60, and 120 min after assuming the Trendelenburg positioning; and 5 and 15 min after reassuming the supine position.", 'Venous admixture did not change. Dead-space ventilation increased after Trendelenburg positioning, and returned to baseline values after resuming the supine position. However, individual patterns varied widely.']
['Mortality and morbidity in burn cases can be reduced with early diagnosis. Many markers are used for early diagnosis of burn complications like sepsis. In this current study, the relationship between numerical/morphologic granulocyte abnormalities and complications was investigated in pediatric burns. It was aimed to introduce histopathologic marker(s) for burn-related complications.', 'Thirty-two pediatric burn cases hospitalized between December 2006 and December 2009 were included in the study. A total of 192 complete blood count and peripheral blood smear results were analyzed comparatively. Findings were used to identify any correlation among white blood cell count and peripheral blood smear changes (the appearance of immature granular cells, toxic granulation, purple granules and Döhle bodies) and complications such as bacteriemia, sepsis, wound infections, severe anemia, and graft failure.', 'White blood cell count changes and the appearance of immature granular cells were not suitable for use as a diagnostic marker for complications. Nevertheless, there was a statistically significant correlation between the appearance of toxic granulation, purple granules and Döhle bodies and subsequent complications (p: <0.0001, 0.041, 0.001, respectively).']
['In animals, prolyl 4-hydroxylases (P4Hs) are regarded as oxygen sensors under hypoxia stress, but little is known about their role in the response to waterlogging in maize.', 'A comprehensive genome-wide analysis of P4H genes of maize (zmP4H genes) was carried out, including gene structures, phylogeny, protein motifs, chromosomal locations and expression patterns under waterlogging.', 'Nine zmP4H genes were identified in maize, of which five were alternatively spliced into at least 19 transcripts. Different alternative splicing (AS) events were revealed in different inbred lines, even for the same gene, possibly because of organ and developmental specificities or different stresses. The signal strength of splice sites was strongly correlated with selection of donor and receptor sites, and ambiguous junction sites due to small direct repeats at the exon/intron junction frequently resulted in the selection of unconventional splicing sites. Eleven out of 14 transcripts resulting from AS harboured a premature termination codon, rendering them potential candidates for nonsense-mediated RNA degradation. Reverse transcription-PCR (RT-PCR) indicated that zmP4H genes displayed different expression patterns under waterlogging. The diverse transcripts generated from AS were expressed at different levels, suggesting that zmP4H genes were under specific control by post-transcriptional regulation under waterlogging stress in the line HZ32.']
['Transjugular intrahepatic portosystemic shunts (TIPS) have become a widely accepted tool in the treatment of patients with symptomatic portal hypertension. The aim of our study was to assess glycogen phosphorylase BB (GPBB) concentration in relation to echocardiographic and haemodynamic parameters in patients before and after TIPS insertion.', "The study population consisted of 55 patients (38 men and 17 women, age 55.6±8.9 years, range 37-74 years) with liver cirrhosis treated with transjugular portosystemic shunting. GPBB, echocardiographic, and haemodynamic parameters were measured before TIPS insertion and 24 h after the procedure. GPBB concentrations were assessed using the Cardiac Array for Evidence Investigator protein biochip. Correlation between parameters was assessed using the Spearman's coefficient.", 'Serum post-procedural GPBB concentrations were increased in comparison with baseline (5.58 vs. 2.67 μg/L, P<0.001). GPBB concentration after TIPS significantly correlated with baseline systemic vascular resistence (r=0.330; P=0.017) and cardiac index (r=0.313; P=0.025).']
['Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.', 'DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.', 'The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs.']
['Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a (1/2) site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an estrogen receptor (ER) (1/2) site response element (ERE1) 225 nt upstream to the RE-T.', 'Here we report the identification of a second ER (1/2) site (ERE2) located 145 bp downstream of the RE-T and establish that both EREs can impact p53-mediated transactivation of FLT1-T in a manner that is cell type and ER level dependent. Gene reporter assays and ChIP experiments conducted in the breast cancer-derived MCF7 cells revealed that the ERE2 site was sufficient for p53-mediated ERalpha recruitment and transactivation of the FLT1-T promoter/reporter construct. Surprisingly, unlike the case for other p53 target promoters, p53-mediated transactivation of FLT1-T constructs or expression of the endogenous FLT1 gene, as well as binding of p53 and ER at the promoter constructs, was inducible by doxorubicin but not by 5-fluorouracil. Furthermore, ER activity at FLT1-T was differentially affected by ER ligands, compared to a control TFF1/pS2 ER target promoter. The p53-related transcription factors (TFs) p73 and p63 had no effect on FLT1 transactivation.']
['To compare ropivacaine blood concentrations obtained after a continuous lumbar plexus block performed either by the anterior three-in-one femoral (FEM) technique or the posterior (psoas compartment; PSOAS) technique.', 'As a substudy of a larger clinical trial, 24 patients were randomly allocated to receive a bolus of 30 mL of ropivacaine 0.5% plus epinephrine 1:200,000 followed by an infusion of ropivacaine 0.2% at 12 mL.hr(-1) for 48 hr via one of the two continuous lumbar plexus block techniques. Plasma ropivacaine concentrations, up to 48 hr, were measured by high performance liquid chromatography.', 'Mean plasma ropivacaine concentrations were higher in the PSOAS group at 15, 30, and 60 min (two-way analysis of variance, P < 0.0001) but areas under the curve were similar for both groups (FEM 452.4 +/- 253.6 mg.hr(-1).L(-1), PSOAS 433.4 +/- 99.0 mg.hr(-1).L(-1)). Mean maximal plasma concentrations were observed at 48 hr and were comparable for the two techniques (FEM 2630.9 +/- 1470.3 ng.L(-1), PSOAS 2325.1 +/- 604.2 ng.mL(-1)). There was no correlation between blood concentrations at 48 hr and body weight (r2 = 0.085, P = 0.21). One patient in the FEM group achieved a concentration of 6201 ng.mL(-1) at 48 hr.']
['The myeloproliferative neoplasms, essential thrombocytosis, polycythemia vera and primary myelofibrosis, share the same acquired genetic lesion, but the concept of JAK2 V617F serving as the sole lesion responsible for these neoplasms is under question, and there has been interest in identifying additional mutations that may contribute to disease pathogenesis. Because ASXL1 lesions have been increasingly identified in myeloid neoplasms, we examined the relationships of ASXL1 mutation or deletion to both clinical phenotype and associated molecular features in 166 patients with myeloproliferative neoplasms.', 'Exon 12 of ASXL1 was amplified from neutrophil genomic DNA and bidirectionally sequenced in 77 patients with myelofibrosis (including patients with primary and post-essential thrombocytosis or post-polycythemia myelofibrosis), 42 patients with polycythemia vera, 41 with essential thrombocytosis and 6 with post-myelofibrosis acute myeloid leukemia. Pyrosequencing assays were designed to determine the allele percentages of JAK2 V617F (G5073770T), ASXL1 2475dupA, and ASXL1 2846_2847del in neutrophil genomic DNA samples. Clinical and laboratory characteristics of patients with wild-type and ASXL1 mutations were then compared.', 'We identified nonsense mutations or hemizygous deletion of ASXL1 in 36% of the patients with myelofibrosis, but very rarely among those with polycythemia vera or essential thrombocytosis. Among the patients with myelofibrosis, those with ASXL1 lesions were not distinguished from their wild-type counterparts with regard to JAK2 V617F status, exposure to chemotherapy or evolution to leukemia. Myelofibrosis patients with ASXL1 lesions were more likely to have received anemia-directed therapy compared to those without lesions [15/26 (58%) versus 11/39 (23%); P=0.02]. Using serial banked samples and quantitative ASXL1 mutant allele burden assays, we observed the acquisition and accumulation of ASXL1 mutations over time in two patients with post-essential thrombocytosis myelofibrosis.']
['Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT).', "The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3\u2005months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention.", 'Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates.']
['Anesthetic postconditioning is a cellular protective approach whereby exposure to a volatile anesthetic renders a tissue more resistant to subsequent ischemic/reperfusion event. Sevoflurane postconditioning (SPostC) has been shown to exert cardioprotection against ischemia/reperfusion injury, but the underlying mechanism is unclear. We hypothesized that SPostC protects cardiomyocytes against hypoxia/reoxygenation (H/R) injury by maintaining/restoring mitochondrial morphological integrity, a critical determinant of cell fate.', 'Primary cultures of neonatal rat cardiomyocytes (NCMs) were subjected to H/R injury (3 h of hypoxia followed by 3 h reoxygenation). Intervention with SPostC (2.4% sevoflurane) was administered for 15 min upon the onset of reoxygenation. Cell viability, Lactate dehydrogenase (LDH) level, cell death, mitochondrial morphology, mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening were assessed after intervention. Mitochondrial fusion and fission regulating proteins (Drp1, Fis1, Mfn1, Mfn2 and Opa1) were assessed by immunofluorescence staining and western blotting was performed to determine the level of protein expression.', 'Cardiomyocyte H/R injury resulted in significant increases in LDH release and cell death that were concomitant with reduced cell viability and reduced mitochondrial interconnectivity (mean area/perimeter ratio) and mitochondrial elongation, and with reduced mitochondrial membrane potential and increased mPTP opening. All the above changes were significantly attenuated by SPostC. Furthermore, H/R resulted in significant reductions in mitochondrial fusion proteins Mfn1, Mfn2 and Opa1 and significant enhancement of fission proteins Drp1 and Fis1. SPostC significantly enhanced Mfn2 and Opa1 and reduced Drp1, without significant impact on Mfn1 and Fis1.']
['The mechanical properties of three materials (No. 2 polypropylene, No. 5 polybutilate-coated multifilament polyester and 18, 27 and 36 kg test monofilament nylon leader material) commonly used for extra-capsular stabilisation of the stifle in dogs with cranial cruciate ligament insufficiency were determined. The ability of No. 5 polybutilate-coated multifilament polyester and 36 kg test monofilament nylon leader material, when placed as extra-capsular sutures, to mitigate cranial drawer was evaluated in hindlimbs of cadavers.', 'An in vitro mechanical study.', 'Seven pairs of hindlimbs harvested from adult greyhound dogs recently euthanased for other reasons.', 'Samples of each material, including samples of 27 kg test leader material that had been sterilised by one of three methods (ethylene oxide, one or five cycles in an auto-clave), were loaded to determine tensile and stress relaxation properties. The effect of cyclic loading on a No. 5 polybutilate-coated multifilament polyester and 36 kg test leader material was also determined. Using the harvested hindlimbs, cranial drawer was measured before and after transection of the cranial cruciate ligament and on the first and twelfth cycle following extra-capsular stabilisation with either No. 5 polybutilate-coated multifilament suture or 36 kg test leader material.', 'Leader material was found to have the most suitable mechanical characteristics for use as extracapsular stabilisation of the cranial cruciate ligament deficient stifle. Of the sterilisation methods, ethylene oxide was found to have the least detrimental effects on the handling and material characteristics of the leader material. Stifles stabilised with 36 kg test leader material had significantly less drawer than those stabilised with No. 5 polybutilate-coated multifilament polyester suture.']
['TH2-dependent diseases vary in severity according to genotype, but relevant gene polymorphisms remain largely unknown. The integrin CD11a is a critical determinant of allergic responses, and allelic variants of this gene might influence allergic phenotypes.', 'We sought to determine major CD11a allelic variants in mice and human subjects and their importance to allergic disease expression.', "We sequenced mouse CD11a alleles from C57BL/6 and BALB/c strains to identify major polymorphisms; human CD11a single nucleotide polymorphisms were compared with allergic disease phenotypes as part of the international HapMap project. Mice on a BALB/c or C57BL/6 background and congenic for the other strain's CD11a allele were created to determine the importance of mouse CD11a polymorphisms in vivo and in vitro.", 'Compared with the C57BL/6 allele, the BALB/c CD11a allele contained a nonsynonymous change from asparagine to aspartic acid within the metal ion binding domain. In general, the BALB/c CD11a allele enhanced and the C57BL/6 CD11a allele suppressed TH2 cell-dependent disease caused by the parasite Leishmania major and allergic lung disease caused by the fungus Aspergillus niger. Relative to the C57BL/6 CD11a allele, the BALB/c CD11a allele conferred both greater T-cell adhesion to CD54 in vitro and enhanced TH2 cell homing to lungs in vivo. We further identified a human CD11a polymorphism that significantly associated with atopic disease and relevant allergic indices.']
['Polyamines spermidine and spermine and their precursor putrescine are necessary for cell growth. Polyamine content is high in rapidly growing malignant cells, due to enhanced putrescine synthesis by ornithine decarboxylase (ODC), and increased uptake. In contrast to other cells of the body, colon cancer cells are exposed to high putrescine concentrations from the lumen.', 'To investigate the utilization of luminal putrescine in colon cancer, we studied the effect of a potent mitogen, epidermal growth factor (EGF), on the activity of the enzyme responsible for putrescine conversion, S-adenosylmethionine decarboxylase (SAMDC), in Caco-2 cells.', 'Cell counts, ODC and SAMDC activities and intracellular polyamines were evaluated in the presence and absence of exogenous putrescine in concentrations resembling those normally present in the colonic lumen.', 'ODC and SAMDC activity and putrescine uptake were strongly stimulated by EGF. Both synthesized and absorbed putrescine was rapidly converted to spermidine and spermine after EGF. Conversion pattern was identical in the cells stimulated with EGF only and EGF plus exogenous putrescine, indicating that, if stimulated to proliferate, colon cancer cells utilize the entire available putrescine pool. SAMDC inhibitor, methylglyoxal-bis-guanylhydrazone, induced growth arrest which was not reversed by exogenous putrescine, but only by high concentrations of spermidine.']
['In the past few decades, the use of natural compounds, such as flavonoids, as anti-inflammatory agents has gained much attention. Our current study focuses on the preventive effects of quercetin, apigenin, and luteolin on cytokine-induced beta-cell damage.', 'Pancreatic beta-cells or islets were treated with cytokine mixtures in the presence or absence of flavonoids and the inhibitory effect of flavonoids against cytokine toxicity was determined.', 'Treatment of RINm5F (RIN) rat insulinoma cells with interleukin 1beta (IL-1beta) and interferon gamma (IFN-gamma) induced cell damage. Quercetin, apigenin, and luteolin completely protected against IL-1beta- and IFN-gamma-mediated cytotoxicity in RIN cells. Incubation with quercetin, apigenin, and luteolin resulted in a significant reduction in IL-1beta- and IFN-gamma-induced nitric oxide production, a finding that correlated well with reduced levels of the inducible form of NO synthase messenger RNA and protein. The molecular mechanism by which quercetin, apigenin, and luteolin inhibited inducible NO synthase gene expression appeared to involve the inhibition of nuclear factor kappaB (NF-kappaB) activation. The IL-1beta- and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity, p50 and p65 subunit levels in nucleus, and IkappaB alpha degradation in cytosol compared with unstimulated cells. Quercetin, apigenin, and luteolin also prevented IL-1beta- and IFN-gamma-mediated inhibition of insulin secretion.']
['Electroacupuncture (EA) may offer an effective alternative approach for the treatment of obesity. EA mobilizes energy stores, but its effect on hepatic lipid metabolism is unknown, and the underlying mechanisms remain unclear.', 'To examine the effect of EA on hepatic lipid accumulation in diet-induced obese (DIO) rats, and to explore potential underlying mechanisms.', 'Male Sprague-Dawley rats were fed a normal diet (control group, n=10) or a high-fat diet (HFD) for 12\u2005weeks to induce obesity. Those exhibiting diet-induced obesity were subdivided into two groups, one receiving EA (DIO+EA group, n=10) and one left untreated (DIO group, n=10) and observed for a further 4\u2005weeks. Body, liver and fat pad weight were measured, and liver injury was assessed histologically as well as by measuring serum values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic triglyceride (TG) and total cholesterol were quantified by enzymatic colorimetric methods. Expression of liver AMP-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC), and carnitine palmitoyltransferase (CPT-1) was measured by Western blotting.', 'EA treatment led to a reduction in body, liver and fat pad weight in DIO rats. This was accompanied by decreases in hepatic TG and total cholesterol values, fatty droplet accumulation, and serum concentrations of ALT and AST. Furthermore, EA treatment restored phosphorylation levels of AMPK (Thr(172)) and ACC (Ser(79)) inhibited by HFD, and increased CPT-1 expression.']
['The increase in multiple antimicrobial-resistant bacteria seriously threatens global public health. Novel effective strategies are urgently needed. l-Serine was reported as the most effective amino acid inhibitor against bacterial growth and can sensitize Escherichia coli cells to gentamicin. It is currently unknown whether l-serine affects other type of antibiotics such as β-lactams and fluoroquinolones.', 'Using E. coli, we studied the combination of l-serine with diverse antibiotics against laboratory and clinical E. coli cultures and persisters. The intracellular NAD(+)/NADH level and ROS were determined using kits. Total cellular iron was determined by using a colorimetric ferrozine-based assay.', 'Exogenous l-serine sensitized E. coli ATCC 25922 and clinically isolated fluoroquinolone-resistant E. coli to fluoroquinolones. This potentiation is independent of growth phase. Addition of serine increases the production of NADH. The underlying mechanism of this strategy is that the combination of serine with ofloxacin or moxifloxacin increases the NAD(+)/NADH ratio, disrupts the Fe-S clusters and increases the production of endogenous reactive oxygen species. Furthermore, we used a serine and ofloxacin or moxifloxacin combination in vitro to combat bacterial persister cells, compared with antibiotic treatment alone; combinational treatments of persister cells with antibiotics and l-serine resulted in a significantly greater decrease in cell viability.']
['Although circulating tumour DNA has been detected in patients with different types of cancer, little is known of free RNA in cancer patients.', 'We investigated the presence of RNA from epithelial tumours in plasma from patients with colorectal carcinomas, and its correlation with tumour characteristics and circulating tumour cells.', 'beta-actin mRNA was analysed to assess the viability of plasma RNA in samples from 53 patients with colonic cancer and 25 controls. Subsequently, nested primers were used to detect the presence of cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) RNA in the same samples. Nine clinicopathological parameters were studied to correlate the molecular and clinical parameters. Additionally, we investigated for micrometastases in blood in 18 of these patients and in 10 of the controls samples.', 'All samples had detectable quantities of beta-actin RNA. In the controls, one case (4%) was positive for CEA and five (20%) for CK19 RNA; of the 53 patients, 17 cases (32%) were positive for CEA and 39 (73.6%) for CK19 RNA. This was statistically significant (p=0.000001). Advanced stages (p=0.03) and soluble CEA status (p=0.03) were associated with the presence of CEA, CK19, or both RNAs in plasma. Lymph node metastases (p=0.06) and vascular invasion (p=0.07) were almost significant. On the basis of these results, we examined the possible presence of micrometastases in blood in several of these patients. The presence of plasma tumour RNA was found to be associated with circulating tumour cells in blood (p=0.04).']
['To analyze the incidence of primary immunodeficiencies (PIDs), to reveal the specific features of the course of this condition at the present stage, and to estimate the quality of health care to patients with PIDs.', 'An open-label prospective trial was performed in 94 patients with different forms of PIDs (63 with selective immunoglobulin A (IgA) deficiency and 31 with other more severe primary immunodeficiencies) who had been permanent residents in the Perm Territory in the period 1990 to 2012.', 'The registered PID cases were noted to be lower than the estimated ones. Over 22 years of follow-ups, the death rates for this group of patients with these diseases were 11%, and the disability rates were 27%. In severe PIDs (exclusive of selective IgA deficiency), these rates were as high as 35.5 and 96%, respectively. The rate of untimely diagnosis of severe PIDs was high (43%). Molecular genetic studies were conducted in only one tenth of the patents with this disease. PID treatment generally complied with the accepted medical standards. However, all patients with X-linked agammaglobulinemia were observed to have periodic irregularities of replacement therapy with intravenous immunoglobulins, which was a cause of death in 2 patients. Adult patients with common variable immune deficiency received no adequate replacement therapy. Timely diagnosis and adequate therapy could not only preserve the life of many patients with severe PIDs (64.5% survived), but could achieve its relatively satisfactory quality.']
['Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA).', 'To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA.', 'This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment).', 'Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated.']
['Impulsive forces in the knee joint have been suspected to be a co-factor in the development and progression of knee osteoarthritis. We thus evaluated the impulsive sagittal ground reaction forces (iGRF), shock waves and lower extremity joint kinematics at heel strike during walking in knee osteoarthritis (OA) patients and compared them to those in healthy subjects.', 'We studied 9 OA patients and 10 healthy subjects using three-dimensional gait analyses concentrated on the heel strike. Impulse GRF (iGRF) was measured together with peak accelerations (PA) at the tibial tuberosity and sacrum. Sagittal lower extremity joint angles at heel strike were extracted from the gait analyses. As OA is painful and pain might alter movement strategies, the patient group was also evaluated following pain relief by intraarticular lidocaine injections.', 'The two groups showed similar iGRF, similar tibial and sacral PA, and similar joint angles at heel strike. Following pain relief, the OA patients struck the ground with more extended hip and knee joints and lower tibial PA compared to the painful condition. Although such changes occurred after pain relief, all parameters were within their normal ranges.']
['The significance of immunoglobulin (Ig) M antibody to hepatitis C virus (HCV) core antigen was studied in 60 patients with HCV infection after orthotopic liver transplantation (OLT) diagnosed by polymerase chain reaction.', "Patients were followed up for a mean of 28 months after transplantation. Sera collected three months before transplantation, and one and 12 months after transplantation were analysed for anti-HCV core IgM (HCV-IgM EIA 2.0 assay). After OLT protocol biopsies, procedures were performed routinely every six months. Semiquantitative histopathological assessment of allograft hepatitis was performed using Knodell's score. The results were correlated with clinical features, liver histology findings, and virological features, such as genotype and viraemic levels assessed by a branched DNA assay.", 'One year after liver transplantation, 29/60 (48%) patients had chronic hepatitis on graft biopsy. The presence of anti-HCV core IgM one month (p=0.004) and 12 months (p=0.003) after OLT was positively correlated with recurrence of chronic hepatitis. The positive predictive value of anti-HCV core IgM detected one month after transplantation was 0.88. A significant relationship was observed between severity of graft disease and presence of anti-HCV core IgM 12 months after transplantation. The mean Knodell score was 8.9 in anti-HCV core IgM positive patients compared with 3.6 in those who were anti-HCV core IgM negative (p=0.001). The presence of IgM anti-HCV did not correlate with serum HCV RNA level or HCV genotype.']
['The influence of interleukin-10 (IL-10) gene promoter polymorphisms on the mode and sequel of HBeAg seroconversion (a favorable event usually) in patients with chronic Hepatitis B virus (HBV) infection has not been clarified.', 'IL-10 genotyping and haplotype analyses of 340 HBsAg carriers and 100 volunteers with self-limiting HBV infection from southern China, a high prevalent area of HBV were performed according to the single nucleotide polymorphisms in its promoter (-1,082, -819 and -592) using a competitively differentiated PCR.', 'High-producer genotype (GG at -1,082) or haplotype (GCC) was rarely found in patients from southern China (<1%). Intermediate-producer haplotype (ACC) was closely associated with chronic liver disease (P=0.004); compared with this, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with asymptomatic carriers (P=0.035 and 0.035). Intermediate-producer genotype (AC at -592) and haplotype (ACC) were closely associated with covert seroconversion of HBeAg (P=0.0086 and 0.0013) and progressive sequel after HBeAg seroconversion (P=0.013 and 0.0008), while, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with overt seroconversion of HBeAg (P=0.0023 and 0.0061) and silent sequel after HBeAg seroconversion (P=0.0009 and 0.001).']
['To date, most studies aimed at discovering genetic factors influencing treatment response in asthma have focused on biologic candidate genes. Genome-wide association studies (GWAS) can rapidly identify novel pharmacogenetic loci.', 'To investigate if GWAS can identify novel pharmacogenetic loci in asthma.', 'Using phenotypic and GWAS genotype data available through the NHLBI-funded Single-nucleotide polymorphism Health association-Asthma Resource Project, we analyzed differences in FEV(1) in response to inhaled corticosteroids in 418 white subjects with asthma. Of the 444,088 single nucleotide polymorphisms (SNPs) analyzed, the lowest 50 SNPs by P value were genotyped in an independent clinical trial population of 407 subjects with asthma.', 'The lowest P value for the GWAS analysis was 2.09 × 10(-6). Of the 47 SNPs successfully genotyped in the replication population, three were associated under the same genetic model in the same direction, including two of the top four SNPs ranked by P value. Combined P values for these SNPs were 1.06 × 10(-5) for rs3127412 and 6.13 × 10(-6) for rs6456042. Although these two were not located within a gene, they were tightly correlated with three variants mapping to potentially functional regions within the T gene. After genotyping, each T gene variant was also associated with lung function response to inhaled corticosteroids in each of the trials associated with rs3127412 and rs6456042 in the initial GWAS analysis. On average, there was a twofold to threefold difference in FEV(1) response for those subjects homozygous for the wild-type versus mutant alleles for each T gene SNP.']
['We have previously found an increased mast cell density in tendon biopsies from patients with patellar tendinopathy compared to controls. This study examined the influence of mast cells on basic tenocyte functions, including production of the inflammatory mediator prostaglandin E2 (PGE2), extracellular matrix remodeling and matrix metalloproteinase (MMP) gene transcription, and collagen synthesis.', 'Primary human tenocytes were stimulated with an established human mast cell line (HMC-1). Extracellular matrix remodeling was studied by culturing tenocytes in a three-dimensional collagen lattice. Survival/proliferation was assessed with the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. Levels of mRNA for COX-2, COL1A1, MMP1, and MMP7 were determined by quantitative real-time polymerase chain reaction (qPCR). Cox-2 protein level was assessed by Western blot analysis and type I procollagen was detected by immunofluorescent staining. PGE2 levels were determined using an enzyme-linked immunosorbent assay (ELISA).', 'Mast cells stimulated tenocytes to produce increased levels of COX-2 and the pro-inflammatory mediator PGE2, which in turn decreased COL1A1 mRNA expression. Additionally, mast cells reduced the type I procollagen protein levels produced by tenocytes. Transforming growth factor beta 1 (TGF-β1) was responsible for the induction of Cox-2 and PGE2 by tenocytes. Mast cells increased MMP1 and MMP7 transcription and increased the contraction of a three-dimensional collagen lattice by tenocytes, a phenomenon which was blocked by a pan-MMP inhibitor (Batimastat).']
['Obstructive sleep apnea syndrome is associated with cardiovascular diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor of cardiovascular thromboembolic events. The aim of the present study is to investigate the association between the MPV and disease severity in patients with obstructive sleep apnea syndrome.', 'We prospectively included 194 obstructive sleep apnea syndrome patients without cardiovascular disease (mean age 56.5±12.5 years) who were undergoing sleep tests. An overnight full laboratory polisomnography examination was conducted on each patient. The patients were divided into 3 groups according to the apnea-hypopnea index (AHI): (1) AHIlow group: 5≤AHI<15, (2) AHImid group: 15<AHI≤30, and (3) AHIhigh group: AHI>30.', 'The highest MPV values were found in the AHIhigh group compared with other groups (p<0.05 for all). Multiple linear regression analysis indicated that the MPV was associated with the AHI (β=0.500, p<0.001) and the high sensitivity C-reactive protein (hs-CRP) level (β=0.194, p=0.010).']
['Lumen geometry has long been suspected as a risk factor for atherosclerosis by virtue of its influence on blood flow disturbances. Confirmation of this geometric risk hypothesis has, however, proved challenging owing to possible effects of wall thickening on geometry and unproven links between candidate geometric variables and disturbed flow. The purpose of this study was to overcome these challenges.', 'The study relied on imaging and risk factor data from progressively refined subsets of the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study. Group 1 (n=467) included only nonstenotic cases having sufficient quality angiography for 3-dimensional analysis. Group 2 (n=346) excluded cases from group 1 having common and internal carotid artery wall thickness above previously identified thresholds for inward remodeling. Group 3 (n=294) excluded cases from group 2 having lumen irregularities and thus was least likely to include lumen geometries influenced by wall thickening.', 'Multiple linear regressions showed that for group 3, bifurcation flare and proximal curvature were independent predictors of internal carotid artery wall thickness, consistent with their previously demonstrated roles in predicting disturbed flow. For the broadest group 1, flare was an independent predictor of internal carotid artery wall thickness but with a sign change in regression coefficient reflecting effects of wall thickening on lumen geometry.']
['This is the first study of the effect of epidermal growth factor (EGF) on marmoset monkey oocytes matured in vitro.', 'We have evaluated the effects of 10 ng/ml EGF in combination with 1 or 10 IU/ml of gonadotrophins (FSH/hCG 1:1 ratio) during in vitro maturation (IVM) of marmoset oocytes. Immature cumulus-oocyte complexes (COCs) were retrieved from ovarian antral follicles of unprimed monkeys. COCs from six animals (n= 268) used in this study were randomly distributed among four experimental groups: (A) 1 FSH +1 hCG; (B) 10 FSH +10 hCG; (C) 1 FSH +1 hCG + EGF; and (D) 10 FSH +10 hCG + EGF (where 1 and 10 are concentrations, IU/ml). After IVM, oocytes were fertilized in vitro and embryos were allowed to progress up to 87-88 h.', 'the highest rate of total and radial cumulus expansion was observed in Group A, with the lowest in Group B (P < 0.05). Neither maturation nor fertilization rate were affected by gonadotrophin concentration or presence of EGF. Addition of EGF increased degeneration and decreased first cleavage rate, which was significantly lower in Group C than Group A (P < 0.005). Interestingly, in the EGF groups some embryos cleaved faster than without EGF.']
['Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiological process of acute conditions. The aim of the study was to evaluate the effect of mast cell stimulation on the early development of multiple organ dysfunction (MODS) in acute pancreatitis (AP).', 'AP was induced by the intraductal infusion of 5% sodium taurodeoxycholate in the rat. Tissue endothelial barrier dysfunction (TEBD) was measured by plasma exudation of radiolabeled albumin. Activation of mast cells was estimated by measuring the release of histamine. Mast cell stimulation was achieved with compound 48/80 (C48/80) administered intravenously (i.v.) or intraperitoneally (i.p.) in different doses either as pretreatment (30 min prior to induction of AP) or treatment immediately after induction of AP.', 'Administration of C48/80 both i.p. and i.v. demonstrated the same effects. A single pretreatment dose of C48/80 (0.5 mg/kg) significantly reduced AP-induced TEBD in the pancreas and gut. Administration of C48/80 immediately after sham operation or induction of AP resulted in a significant increase in pancreatic and intestinal TEBD (p < 0.05 vs. AP+saline). Plasma levels of histamine increased with increasing doses of C48/80.']
['Neuropathologic studies suggest an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages. We examined the prevalence and associated risk factors for infarcts detected by diffusion-weighted imaging (DWI).', 'We performed retrospective analysis of MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts. We also examined the association between DWI lesions and demographic variables, conventional vascular risk factors, and radiographic markers of CAA severity such as number of hemorrhages on gradient-echo MRI and volume of T2-hyperintense white matter lesions.', 'Twelve of 78 subjects with CAA (15%) had a total of 17 DWI-hyperintense lesions consistent with subacute cerebral infarctions vs 0 of 55 subjects with AD/MCI (p = 0.001). The DWI lesions were located primarily in cortex and subcortical white matter. CAA subjects with DWI lesions had a higher median number of total hemorrhages (22 vs 4, p = 0.025) and no difference in white matter hyperintensity volume or conventional vascular risk factors compared to subjects with CAA without lesions.']
['Mesenchymal stem cells are promising candidates in regenerative cell therapy. Conventional culture methods involve the use of animal substances, specifically fetal bovine serum as growth supplement. Since the use of animal-derived products is undesirable for human applications, platelet lysates produced from human platelets are an attractive alternative. This is especially true if platelet lysates from already approved transfusion units at blood banks can be utilized. The purpose of this study was to produce human platelet lysates from expired, blood bank-approved platelet concentrates and evaluate their use as growth supplement in the culture of mesenchymal stem cells.', 'In this study, bone marrow-derived mesenchymal stem cells were cultured with one of three culture supplements; fetal bovine serum, lysates from freshly prepared human platelet concentrates, or lysates from expired human platelet concentrates. The effects of these platelet-derived culture supplements on basic mesenchymal stem cell characteristics were evaluated. All cultures maintained the typical mesenchymal stem cell surface marker expression, trilineage differentiation potential, and the ability to suppress in vitro immune responses. However, mesenchymal stem cells supplemented with platelet lysates proliferated faster than traditionally cultured cells and increased the expression of the osteogenic marker gene RUNX-2; yet no difference between the use of fresh and expired platelet concentrates was observed.']
['The purpose of this study was to investigate the distribution of the A986S and R990G polymorphisms of the calcium-sensing receptor (CASR) gene in the Chinese population and whether there is an association between genetic variants and the risk of developing primary hyperparathyroidism (PHPT) and its associated clinical phenotypes.', 'A total of 164 Chinese Han PHPT patients (M/F: 51/113) and 230 healthy controls (M/F: 50/180) were enrolled. The common clinical parameters of PHPT patients including biochemical markers, bone mineral density (BMD), kidney stone occurrence, and pathology results were analyzed. Genotyping was conducted for both the patients and controls, and it was carried out using standard procedures.', 'The R990G variant was more frequently present than the A986S variant in this group of Chinese PHPT patients. The R allele increased the risk of PHPT (odds ratio=1.134, 95% CI: 1.008, 1.277, and P=0.036). Patients with either the RR or RG genotype had lower blood calcium levels and higher alkaline phosphate levels than patients with the GG genotype. The lumbar BMD T-score was -2.20 (-2.63, -0.32) in patients with the GG genotype, and it was significantly lower in patients with the RR+RG genotype (-2.53 (-3.70, -1.72) P=0.036). Patients with the R allele had a significantly higher incidence of hyperplasia (25.0%) and carcinomas (7.1%) than those with the GG genotype (5.3 and 0% respectively; P=0.025). The prevalence of osteoporosis and parathyroid carcinomas was higher in Chinese PHPT patients with the R allele.']
['Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity. However, the contribution of rapid weight gain during specific infancy periods is not clear.', 'We aimed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls.', 'A total of 2715 girls from a prospective UK birth cohort study participated in the study.', 'Routinely measured weights and lengths at ages 2, 9, and 19 months were extracted from the local child health computer database. Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr, and age at menarche was assessed by questionnaire (categorized into three groups: <12.0, 12.0-13.0, and >13.0 yr).', 'Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche. Each +1 unit gain in weight sd score between 0 and 9 months was associated with an odds ratio (95% confidence interval) = 1.48 (1.27-1.60) for overweight (body mass index > 85th centile) at 10 yr, and 1.34 (1.21-1.49) for menarche at less than 12 yr. In contrast, subsequent weight gain between 9 and 19 months was not associated with later adiposity or age at menarche.']
['To investigate the relationship of the inflammatory parameters--leukocyte count and fibrinogen level--to the intima-media thickness (IMT) of the common carotid artery and the common femoral artery, as well as to a variety of risk factors within the metabolic syndrome in a risk population for diabetes.', 'A total of 597 subjects were analyzed from the Risk factors in Impaired glucose tolerance for Atherosclerosis and Diabetes (RIAD) study, who were at risk for the development of type 2 diabetes. IMT of the common carotid and common femoral artery was determined by B-mode ultrasound. Leukocyte count and fibrinogen level, as well as various risk factors for atherosclerosis, were measured by established methods.', 'In univariate analysis, leukocyte count and fibrinogen level correlated significantly to carotid and femoral IMT. Leukocyte count was significantly correlated to body mass index, waist to hip ratio, blood pressure, plasma triglycerides, high-density lipoprotein cholesterol (inversely), fasting and postprandial plasma glucose, insulin and proinsulin, PAI(active), tPA and microalbuminuria, as well as to smoking and physical activity (inversely). Fibrinogen level was significantly correlated with body mass index, systolic blood pressure, plasma triglycerides, fasting plasma glucose, HbA1c, PAI(active), tPA and von Willebrandt factor, as well as with smoking and low physical activity. In multivariate analysis, leukocyte count was an independent determinant of the maximal carotid IMT and fibrinogen level of femoral IMT.']
['Esophageal perforation caused by endoscopic submucosal dissection (ESD) induces serious pneumomediastinum. In the absence of endoscopically detected perforation, postprocedural pneumomediastinum may occur. The aim of this study was to evaluate the association between the clinical factors/courses and pneumomediastinum revealed by chest computed tomography (CT) with special reference to an exposed muscle layer during esophageal ESD.', 'A total of 58 patients undergoing ESD for esophageal neoplasms between February 2003 and June 2007 also underwent both chest radiography and chest CT within 1 hour after ESD. We studied the association between findings on CT scan and tumor-related and technical factors of esophageal ESD by uni- and multivariate analyses. We also analyzed the clinical factors/courses experienced by all patients.', 'Pneumomediastinum was detected in 18 / 58 patients (31 %) by chest CT compared with only 1 / 58 patients (1.7 %) by chest radiography. ESD-induced exposure of the muscular layer (32 patients) was the only significant factor for pneumomediastinum (18 / 32; P < 0.0001). Clinical factors such as fever, white blood cell count, and C-reactive protein were significantly increased in the group positive for both endoscopically exposed muscular layer and pneumomediastinum (+/+, n = 18) compared with the (-/-) group (n = 26) in the early phase (day 1) after ESD. However, these factors did not affect the length of the fasting period or the length of hospital stay.']
['Oncogenesis is a multistep process, resulting from the accumulations of multiple mutations. Of these mutations, self-sufficiency in growth signals, i.e., disruption of cell growth regulation, is the first episode. Nonetheless, the genes associated with cell growth dysregulation have seldom been systematically evaluated in either urothelial carcinomas of upper urinary tract (UTUC) or urothelial carcinomas of urinary baldder (UBUC). By data mining a published transcriptomic dataset of UBUCs (GSE31684), we identified the NDN gene as one of the most significant of those associated with the regulation of cell growth and found this gene is associated with advanced tumor status and metastatic disease (GO:0001558). Accordingly, we analyzed NDN transcript and protein expression with their clinicopathological significance.', 'We used real time RT-PCR to detect NDN transcript levels in 27 UTUCs and 27 UBUCs, respectively. Immunohistochemical study was performed to determine NDN protein (a.k.a. Necdin) expression evaluated by H-score method in 340 UTUCs and 295 UBUCs. NDN expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS).', 'NDN transcriptional level was significantly higher in UCs of both sites with stepwise more advanced pT statuses. Through immunohistochemistry, we found NDN protein expression was significantly associated with adverse clinicopathological parameters, e.g., advanced pT status, nodal metastasis, high grade histological patterns, and frequent mitotses (all P<0.05). In univariate analysis, NDN overexpression not only predicted worse DSS and MeFS in both the UTUC and UBUC groups, it also served as an independent prognostic factor for DSS and MeFS in multivariate analysis (all P<0.05).']
['Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. Metastatic RCC is difficult to treat. The 5-year survival rate for metastatic RCC is ≤10%. Recently, microRNAs (miRNAs) have been shown to have a role in cancer metastasis and potential as prognostic biomarkers in cancer.', 'We performed a miRNA microarray to identify a miRNA signature characteristic of metastatic compared with primary RCCs. We validated our results by quantitative real-time PCR. We performed experimental and bioinformatic analyses to explore the involvement of miR-215 in RCC progression and metastasis.', 'We identified 65 miRNAs that were significantly altered in metastatic compared with primary RCCs. We validated our results by examining the expression of miR-10b, miR-126, miR-196a, miR-204 and miR-215, in two independent cohorts of patients. We showed that overexpression of miR-215 decreased cellular migration and invasion in an RCC cell line model. In addition, through gene expression profiling, we identified direct and indirect targets of miR-215 that can contribute to tumour metastasis.']
['Obesity-associated hypertension is likely to be due to multiple mechanisms. Identification of the renin-angiotensin system (RAS) within adipose tissue does, however, suggest a potential causal role for it in obesity-associated hypertension. Obese patients are often hyperinsulinemic, but mechanisms underlying insulin upregulation of the RAS in adipose tissue are unclear. Tumor necrosis factor-alpha (TNF-alpha), an inducer of angiotensinogen in hepatocytes, is elevated in hyperinsulinemic, obese individuals and may provide a link in mediating insulin upregulation of the RAS in adipose tissue. Furthermore, thiazolidinediones lower blood pressure in vivo, and downregulation of the RAS in adipose tissue may contribute to this effect. We therefore examined the effect of rosiglitazone (RSG) on the insulin-mediated upregulation of the RAS.', 'Sera were obtained from the arterial circulation and from venous blood by draining subcutaneous abdominal adipose tissue. Isolated human abdominal subcutaneous adipocytes (n=12) were treated with insulin (1 to 1000 nmol/L), insulin in combination with RSG (10 nmol/L), and RSG (10 nmol/L) alone to determine angiotensinogen expression and angiotensin II, bradykinin, and TNF-alpha secretion. Subcutaneous adipocytes were also treated with TNF-alpha (10 to 100 ng/mL) to examine the direct effect on angiotensinogen expression and angiotensin II secretion. The findings showed that the arteriovenous difference in angiotensin II levels was significant (>23%; P<0.001). Insulin increased TNF-alpha secretion in a concentration-dependent manner (P<0.01), whereas RSG (10 nmol/L) significantly reduced the insulin-mediated rise in TNF-alpha (P<0.001), as well as angiotensin and angiotensin II. TNF-alpha also increased angiotensinogen and angiotensin II in isolated adipocytes.']
['Immunosuppressant therapy is thought to be a major contributor to post-transplant bone disease. Histological data and serum parameters suggest that Cyclosporin A (CsA) treatment causes osteopenia as a result of an altered bone turnover, but the pathogenic mechanisms of this process remain unclear. We investigate if CsA affects cell turnover and extracellular matrix (ECM) synthesis and degradation in MC3T3-E1 osteoblasts, as a surrogate model for in vivo events.', 'Cells were exposed to increasing doses of CsA (0, 0.5, 1 and 5 microg/ml). Proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation, viability by Trypan Blue exclusion and apoptosis by ELISA. Type I collagen was measured by ELISA and reverse transcription-polymerase chain reaction (RT-PCR), matrix metalloproteinases (MMP) by zymography and RT-PCR, and tissue inhibitors of MMP (TIMP) by reverse zymography.', 'CsA exposure for 48 h decreased osteoblast number in a dose-dependent manner in the absence of apoptosis or cytotoxicity. CsA at a dose of 5 microg/ml for 72 h caused decreased collagen type I mRNA expression and protein accumulation. While MMP-2 remained unaffected, MMP-9 activity increased. TIMP-1 activity was unaffected, while a dose-dependent increase of TIMP-2 was observed.']
['The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a widely used risk assessment tool in patients with severe aortic stenosis to determine operability and to select patients for alternative therapies such as transcatheter aortic valve implantation. The objective of this study was to determine the accuracy of the EuroSCORE in predicting mortality following aortic valve replacement (AVR).', 'The logistic EuroSCORE was determined for all consecutive patients that underwent conventional AVR between 1995 and 2005 at our institution. Provincial Vital Statistics were used to determine all-cause mortality. The accuracy of the prognostic risk prediction provided by logistic EuroSCORE was assessed by comparing observed and expected operative mortality.', 'During the study period, a total of 1,421 patients underwent AVR including 237 patients (16.7%) that had a logistic EuroSCORE > 20. Among these patients, the mean predicted operative mortality was 38.7% (SD = 18.1). The actual mortality of these patients was significantly lower than that predicted by EuroSCORE (11.4% vs. 38.7%, observed/expected ratio 0.29, 95% CI 0.15-0.52, P < 0.05). The EuroSCORE overestimated mortality within all strata of predicted risk. Although medium-term mortality is significantly higher among patients with EuroSCORE > 20 (log rank P = 0.0001), approximately 60% are alive at five years.']
['Dual blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has higher antiproteinuric effects than single blockade in adults. In children, little is known on dual blockade of the renin-angiotensin system. The study investigates whether adding an ARB to proteinuric children already on ACEI reduces proteinuria.', 'A total of 10 children (median age 13.3 years) with chronic kidney disease and persistent proteinuria despite maximal dose of ACEI were included. Losartan was given at an initial dose 0.8 mg/kg/day. Proteinuria, blood pressure (BP) and renal function (glomerular filtration rate) were measured.', 'Mean proteinuria decreased from 484 +/- 290 mg/mmol creatinine to 223 +/- 197 after 1-3 months of losartan treatment and remained stable at 234 +/- 153, 224 +/- 177 and 195 +/- 133 after 3-6, 6-12 months and at the last follow-up check (median 1.9 years, p < 0.05 for all visits vs. before treatment). The median percentage decrease in proteinuria was 66, 56, 44 and 66% during the study periods. No significant change in BP, glomerular filtration rate or serum potassium was observed. One child complained of rash, which led to discontinuation of losartan.']
['To explore the effect of PI3K p85alpha gene silencing on the 5-fluorouracil (5-FU)-induced apoptosis of colorectal cancer cells.', 'The PI3K p85alpha/RNAi transfected cells (PI3K p85alpha/RNAi-LoVo) were cultured in RPMI 1640 supplemented with 10% fetal calf serum and 500 microg/ml G418. The 50% inhibitory concentration (IC50) values of 5-FU (0.000625, 0.00125, 0.005, 0.01, 0.02, 0.04, 0.08, 0.16, 0.32 micromol/ml) were evaluated by MTT assay. Mitochondrial membrane potential was detected by JC-1 fluorescence, and Western blotting was used to analyze the expression of apoptotic proteins Bcl-6 and Bim.', 'Compared with the untransfected LoVo cells, PI3K p85alpha/RNAi-LoVo showed obviously decreased IC(50) of 5-FU (P=0.000). The mitochondrial membrane potential of PI3K p85alpha/RNAi-LoVo cells was significantly lower than that of LoVo cells, suggesting that silencing PI3K p85alpha expression increased the sensitivity of LoVo cells to 5-FU. The expression of apoptotic protein Bcl-6 and Bim were significantly higher in PI3K p85alpha/RNAi-LoVo cells treated with 5-FU than LoVo cells (P=0.000).']
["Debate that Helicobacter pylori might play a causative role in gastric carcinogenesis still exists in spite of the World Health Organization's definition of H. pylori as a class I carcinogen. In order to define the exact role of H. pylori infection in gastric carcinogenesis, we established a mice model of H. pylori infection.", 'One hundred and forty-four female C57BL/6 mice were divided into nine groups according to N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the 50th or 80th week after treatment, and their histopathological changes were evaluated according to group.', 'The incidence of gastric adenocarcinoma at the 50th week was 80% in mice treated with both MNU 240 microg/L and H. pylori infection, whereas the incidence was only 27% in mice treated with only MNU 240 microg/L. Although H. pylori caused marked expansion of the proliferative zone at the surface epithelium, H. pylori infection alone caused only chronic atrophic gastritis without any evidence of carcinomas until 80 weeks. The combination of MNU and H. pylori infection also resulted in a significantly higher incidence of gastric adenoma and adenocarcinoma. Significantly higher expressions of proliferating cell nuclear antigen were noted in the gastric mucosa infected with H. pylori compared to controls.']
['The purpose of this study was to determine whether body mass index (BMI, kg body weight/height (in m2) is related to survival in recipients of allogeneic stem cell transplantation (ASCT).', 'Since 1977, 544 adult patients (age ranging from 18 to 64 years) diagnosed with hematologic malignancies; 172 acute myeloid leukemia, 83 acute lymphocytic leukemia, 190 chronic myeloid leukemia and 99 others, underwent myeloablative conditioning and ASCT. Low BMI (<20) was seen in 88 patients, normal BMI (20-25) in 290 and high BMI (>25) in 166 patients. The donors were 348 HLA-identical siblings, 157 matched unrelated donors and 39 HLA major mismatched donors. We assessed BMI as a risk-factor controlling for other risk-factors regarding transplant-related mortality, survival and relapse-free survival using the Cox regression model.', 'Patients with a low BMI more often had ALL, were younger, were more often conditioned with total body irradiation and more often received monotherapy as immunosuppression against graft-versus-host disease. BMI had no effect on engraftment, transfusions and acute or chronic GVHD. Patients with BMI <20 had a higher incidence of a-streptococcal septicemia (p=0.005) than did patients with BMI > or = 20, but both groups had a similar incidence of overall bacteremia. Five-year survival was 36% in those with low BMI, 47% in those with normal BMI and 55% in those with high BMI. In multivariate analysis, death was associated with BMI <20 (p=0.023). Other significant factors adjusted for were: diagnosis of acute lymphoblastic leukemia, donors other than HLA-identical siblings, disease stage beyond first complete remission or 1st chronic phase, transplantation before 1993 and total body irradiation vs. busulfan conditioning.']
['The efficacy of carotid endarterectomy (CEA) in symptomatic patients with > 70% stenosis is accepted. The stroke risk of asymptomatic patients may not justify surgical intervention. The aim of this study is to use natural history data from a single unit to identify asymptomatic patients who would benefit from CEA.', 'Five hundred and sixty-four patients attending for duplex ultrasound assessment of the internal carotid artery between 1986 and 1993 were retrospectively identified as focally asymptomatic with > 40% ipsilateral stenosis. Patients were traced using hospital records, family practitioner databases and the Office of Population of Census and Surveys. The number of strokes, transient ischaemic attacks and cause of death were determined. Exclusions were 15 (2.7%) asymptomatic occlusions and 49 patients (8.7%) who underwent surgery for asymptomatic disease.', 'Thirteen patients (2.6%) were not traced, leaving 487 study patients. The average follow-up was 41 months (range, 1-120 months). Mean presentation age was 69 years (S.D. 8.9), and the male to female ratio was 3:2. One hundred and fifty-six (32%) patients died. Forty-three patients suffered strokes, of whom two had bilateral strokes. In total there were 16 (i/p) strokes, 25 (c/l) strokes and four strokes undetermined. The average yearly stroke rate was 2.74 per 100 person years and the (i/p) rate 1.02 per hundred person years. There was no effect of age, sex or degree of stenosis on stroke. The presence of bilateral disease did increase the risk of stroke (rel risk 2.35, p = 0.029) but not ipsilateral stroke (rel risk 1.6, p = 0.39). Patients with unilateral asymptomatic carotid disease had an all stroke rate of less than 5% in the first year after presentation and this was unaffected by degree of stenosis. In patients with bilateral disease the stroke rate in the first year after presentation increased with degree of stenosis to a stroke rate of 9.6 per 100 person years in patients with > 90% contralateral stenosis.']
['The biological processes and molecular mechanisms underlying miR-107 remain unclear in gastric cancer(GC). In this study, we aimed to investigate the expression, biological functions and mechanisms of miR-107 in GC.', 'Quantitative real-time RT-PCR was used to test miR-107 expression. MTT and colony formation assays were conducted to explore the potential function of miR-107 in human GC cell line SGC7901. The target gene was determined by bioinformatic algorithms, dual luciferase reporter assay, RT-PCR and Western blot.', "Expression of miR-107 was significantly elevated in GC cell line than that in gastric epithelial cell line(p\u2009=\u20090.012). We found that miR-107 inhibitor transfection significantly decreased the proliferation of GC cell line, and clone formation rate of miR-107 inhibitor transfected group was significantly lower than that of control group. Luciferase assays using a reporter carrying a putative miR-107 target site in the 3'untranslated region (3'-UTR) of cyclin dependent kinase 8 (CDK8) revealed that miR-107 directly targets CDK8. The expression level of CDK8 mRNA and protein in miR-107 inhibitor transfected GC cell line was significantly decreased compared with control group."]
['To prospectively compare two local anaesthetic techniques for prostatic biopsies, which are usually taken with no anaesthesia; because multiple biopsy techniques are becoming more common and there is an increasing need for analgesia/anaesthesia during the procedure.', 'The study group comprised 86 consecutive men (median age 67.7 years) undergoing prostatic biopsy because of either an abnormality of prostate specific antigen level or digital rectal examination. They were randomized into four groups; men in group 1 received 10 mL of 1% lignocaine infiltrated into the periprostatic nerve plexus bilaterally; men in group 2 received 11 mL of 2% lignocaine gel rectally; men in groups 3 and 4 were recruited as controls, and given either plain gel rectally or an injection with saline into the periprostatic nerve plexus. Sextant prostate biopsies were taken in all cases using a standardized protocol. Immediately after the procedure patients were asked to indicate the degree of pain on a 10-cm visual analogue scale.', 'Men in group 1 had significantly less pain than the others (P < 0.001). There was no statistically significant difference in pain between men who received plain gel rectally or saline injection (P = 0.35). The rectal instillation of 2% lignocaine gel did not reduce pain significantly (P = 0.186) compared with the controls.']
['To ascertain whether use of non-benzodiazepine sedative-hypnotics is associated with risk of falls and compare this to risk of falls associated with use of benzodiazepines.', 'Among 4450 community-dwelling men, aged 71 years and older, enrolled in the population-based prospective cohort study, Osteoporotic Fractures in Men (MrOS), use of nonbenzodiazepine sedative-hypnotics and benzodiazepines was assessed by interview and verified from medication containers at the third annual visit of the MrOS study. Falls in the subsequent one-year period were ascertained by tri-annual questionnaires and a computerized dictionary used to categorize type of medication.', 'In age-adjusted models, non-benzodiazepine sedative hypnotic use was associated with an increased risk of any falls (one or more falls) (RR 1.44, 95% CI 1.15, 1.81) and recurrent falls (2 or more falls) (RR 1.51, 95% CI 1.07, 2.14). Use of benzodiazepines was associated with a similar increase in age-adjusted risk of falling. Depressive symptoms, inability to stand from a chair, and instrumental activities of daily living (IADL) impairment modestly attenuated these associations. The association between non-benzodiazepine sedative-hypnotic use and falls was most pronounced among men without a history of falls in the previous year: in a multivariable model controlling for multiple potential confounders, the RR of any falls was 1.74 (95% CI 1.13, 2.68) in this subgroup.']
['Type 1 autoimmune pancreatitis (AIP) is clinically characterized by a response to steroid therapy. Despite having a favorable prognosis, AIP has a high relapse rate and factors predicting relapse in AIP patients treated with steroids have not yet been established.', 'A retrospective chart review was conducted of 32 newly diagnosed type 1 AIP patients who had undergone enhanced computed tomography (CT) pre- and post-steroid therapy.', 'Ten patients experienced relapse. Pancreatic volume was reduced significantly in all patients (pre-treatment volume, 88.5\u2009±\u200932.9\xa0cm(3) vs. post-treatment volume, 45.4\u2009±\u200921.1\xa0cm(3); P\u2009<\u20090.001), although the pre-treatment pancreatic volume did not differ between the relapse and non-relapse groups (92.6\u2009±\u200910.5\xa0cm(3) vs. 86.6\u2009±\u20097.1\xa0cm(3), P\u2009=\u20090.401). However, the post-treatment pancreatic volume was significantly greater in the relapse group than that in the non-relapse group (56.9\u2009±\u20096.3\xa0cm(3) vs. 40.2\u2009±\u20094.2\xa0cm(3), P\u2009=\u20090.008). Similarly, the percent reduction in pancreatic volume was significantly smaller in the relapse group than that in the non-relapse group (36.6\u2009±\u20094.7\xa0% vs. 52.1\u2009±\u20093.2\xa0%, P\u2009=\u20090.002). Multivariate analysis identified post-treatment pancreatic volume (HR, 1.04, 95\xa0% CI: 1.01-1.08, P\u2009=\u20090.010) and percent reduction in pancreatic volume (HR, 0.87, 95\xa0% CI: 0.79-0.94, P\u2009<\u20090.001) as predictive factors for relapse of type 1 AIP. A post-treatment pancreatic volume of 50\xa0cm(3)\u2009<\u2009(P\u2009=\u20090.009) and a percent reduction in the pancreatic volume of <35\xa0% (P\u2009=\u20090.004) had a significantly high relapse rate. These data suggest that early pancreatic volume changes after steroid therapy may be a useful prognostic value, because type 1 AIP patients with a high post-treatment pancreatic volume or low pancreatic volume reduction showed significant relapse.']
['With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in patients with advanced non-small cell lung cancer (NSCLC), its acquired resistance has become a major clinical problem. Recent studies revealed that miR-21 was involved into the resistance of cytotoxic agents. The aim of this study was to investigate its role in the acquired resistance of NSCLC to EGFR-TKI.', 'EGFR-TKI-sensitive human lung adenocarcinoma cell line PC9 and the acquired resistant cell line, PC9R, were used. Lentiviral vectors were used to infect PC9 or PC9R to regulate the miR-21 expression. The expression of targeted proteins PTEN and PDCD4 was controlled by RNA interference. MicroRNA array, RT-PCR and TaqMan MicroRNA Assays were used to detect miR-21 expression. The MTT and Annexin V assays were used to determine proliferation and apoptosis. Western Blot and immunohistochemistry were used to analyze target protein expression (PTEN, PDCD4, Akt, p-Akt). We also constructed PC9R xenograft tumor model to observe the relationship between miR-21 and EGFR-TKI resistance in vivo and validated it in the clinical serum specimens of NSCLC patients treated with EGFR-TKI.', 'MiR-21 was overexpressed in the EGFR-TKI resistant cell line PC9R relative to PC9. The level of miR-21 was reversely correlated with the expression of PTEN and PDCD4 and positive correlated with PI3K/Akt pathway. Inhibiting miR-21 with lentivirus vector induces apoptosis in PC9R cell line and inhibiting miR-21with ASO suppressed tumor growth in nude mice treated with EGFR-TKI. Furthermore, serum miR-21 expression in NSCLC patients treated with EGFR-TKI was significantly higher at the time of acquiring resistance than at baseline (p<0.01).']
['Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology.', 'To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible.', 'We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy.', 'The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results.']
['Impairments in social processes characterize one of the core deficits in autism spectrum disorders (ASD) and accumulating evidence suggests that oxytocin neurotransmission is implicated in mediating social adaptation in ASD. Using a mouse model, CD38, a transmembrane protein expressed in immune cells but also in brain, was found to be critical for social behavior via regulation of oxytocin secretion. This prompted us to both examine CD38 expression in human lymphoblastoid cell lines (LBC) as well as to test association between SNPs across the CD38 gene and ASD.', 'LBC’s were derived from 44 ASD lines and 40 "unaffected" parents. Family-based association (UNPHASED) was examined by genotyping 11 tagging SNPs spanning the CD38 gene identified using HapMap data in 170 trios. An additional SNP (rs3796863) associated in a study by Munesue et al. with ASD was also genotyped.', 'A highly significant reduction in CD38 expression was observed in immortalized lymphocytes derived from ASD subjects compared to their "unaffected" parents (F517.2, P50.00024, df51). Haplotype analysis showed significant association (permutation corrected) between three and seven locus haplotypes and DSM IV ASD in low functioning (IQ < 70) subjects.']
['Severe hypotension deteriorates renal functions and renal hemodynamics especially renal cortical blood flow. Systemic hypotension following high level spinal anesthesia may impair renal functions in spite of the blockade of renal sympathetic nerves that may help prevent vasoconstriction. Fluid loading is clinically applied for preventing hypotension but the effects on the changes of renal functions have not been studied. This study was designed to investigate the effects of fluid loading on systemic hemodynamics, renal hemodynamics and functions especially the blood distribution to renal cortex.', 'A rat model was used in our study. Intravenous normal saline infusion was started in both control group (5 ml/kg/h, 8 rats) and fluid loading group (15 ml/kg/h, 8 rats) 30 min before spinal anesthesia. A high level (above T4) spinal anesthesia was conducted via a preset intrathecal catheter with 0.5% hyperbaric bupivacaine. Blood pressure, heart rate and renal cortical microvascular blood flow (CMBF) were measured via a laser Doppler probe firmly contacted on renal cortex and recorded continuously after spinal anesthesia. Renal functions including glomerular filtration rates (GFR, by inulin clearance), effective renal plasma flow (ERPF, by P-aminohippurate clearance), urine flow rate (UFR) and electrolytes excretion were measured every 30 min after spinal anesthesia.', 'Severe hypotension was notable within 5-10 min after intrathecal anesthesia and recovered with 30 min in both groups but the difference was not significant between groups. In the control group, GFR and ERPF decreased significantly in the first 30 min by 51.9 +/- 19.8% and 44.3 +/- 13.7% respectively (P < 0.05) and recovered after 60 min. Also the deteriorations of UFR and CMBF were significantly longer (over 60 min). In fluid loading group, ERPF, UFR and CMBF could maintain throughout the experiment but only GFR was affected in the first 30 min.']
['The benefit of adjuvant chemotherapy appears to be limited for patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a subgroup of patients with a high recurrence risk. In the current case-control analysis, the authors evaluated whether patients with a high risk of hematogenous metastasis could be identified by means of a thorough histologic and immunohistochemical examination of the resection specimens.', 'A database was built for all patients treated in a general teaching hospital for colorectal carcinoma between 1985 and 1995. From this database, all patients with an Astler Coller B1 or B2 tumor who subsequently had developed hematogenous metastases were taken as cases. For each case, three matched controls (age, Astler Coller, year of diagnosis) without metachronous metastases were selected. The resection specimens of cases and controls were blindly examined by two observers for the following: World Health Organization (WHO) classification; differentiation grade; growth pattern; lymphocytic, fibroblastic, and eosinophilic reaction; angioinvasion; number of lymph nodes examined; expression of E-cadherin, vascular endothelial growth factor and thymidine phosphorylase (TP); P53; microvessel density.', 'Twenty-two cases and 65 controls were included in the analysis. Tumor growth pattern and tumor TP expression both independently contributed to recurrence risk. With these 2 variables, 4 subgroups could be identified with a recurrence risk ranging from 0% to 42%.']
['Elevated serum interleukin-6 (IL-6) levels in patients with intraabdominal sepsis have been associated with increased morbidity and mortality. The authors hypothesized that after surgical intervention a persistent elevation of IL-6 would more accurately reflect the inflammatory state and thus predict the subsequent time to recovery better than the preoperative value alone.', 'Nineteen consecutive children with peritonitis and manifestations of the systemic inflammatory response syndrome were enrolled prospectively. IL-6 levels were determined from pre- and postoperative serum samples (within 12 to 24 hours) by enzyme-linked immunosorbant assay (ELISA). Patient postoperative length of stay (LOS) was recorded.', 'Before surgery, patient serum IL-6 levels ranged from 48 to 132,546 pg/mL. LOS ranged from 4 to 60 days, with subjects falling into 2 groups of < or =11 (n = 14) and > or =25 (n = 5) days. Using an IL-6 level greater than 500 pg/mL to predict a prolonged LOS (>11 days), a persistent elevation of IL-6 postoperatively appears to increase the likelihood of a prolonged LOS.']
['Nitric oxide (NO) biphasically modulates osteoclast function, sperm motility and testosterone production by exerting a positive effect at low concentrations and a negative effect at high concentrations. In this study the effect due to administration of four NO-donors, each releasing an individual amount of NO, was studied on GH secretion from human adenomatous GH-secreting cells.', 'Sodium nitroprusside (SNP), diethylenetriamine NO adduct (DETA/NO), diethylamine/NO complex sodium salt (DEA/NO), and S-nitroso-N-acetylpenicillamine (SNAP) were administered at a concentration of 10-4 M to cells isolated after transsphenoidal adenomectomy from five acromegalic patients.', 'SNP significantly (p < 0.01) increased GH secretion, while the other NO donors inhibited GH secretion in comparision with the amount of GH spontaneously released by unstimulated cells. Each drug showed an individual degree of inhibitory potency: DEA/NO > DETA/NO > SNAP. Nitrite accumulation in the media was measured as a marker of NO released by each individual drug and was found to be different for each drug (DEA/NO > DETA/NO > SNAP > SNP). A negative correlation (R = -0.93; p < 0.05) was found between nitrite release and GH secretion induced by each drug.']
['Coagulopathy plays an important role in sepsis. The aim of this study was to determine whether bone marrow stromal cell (BMSC) administration could attenuate coagulopathy in sepsis.', 'In vitro: endothelial cells were cultured with/without BMSCs for 6\u2009h following LPS stimulation and were collected for thrombomodulin (TM) and endothelial protein C receptor (EPCR) measurements. In vivo: Thirty-six mice were randomized into sham, sepsis, and sepsis\u2009+\u2009BMSC groups (n\u2009=\u200912 each group). Sepsis was induced through cecal ligation and puncture (CLP). BMSC infusion was started at 6\u2009h after CLP. Lung tissues and plasma samples were collected at 24\u2009h after CLP for enzyme-linked immunosorbent assay (ELISA), quantitative real-time RT-PCR, western blot, and immunohistochemistry analysis.', 'In vitro: BMSCs attenuated the decrease in TM and EPCR mRNA and protein expression levels in LPS-stimulated endothelial cells. In vivo: BMSC treatment decreased lung injury and mesenteric perfusion impairment, and ameliorated coagulopathy, as suggested by the reduction in elevated TF, vWF, and TAT circulation levels. BMSC infusion decreased TF mRNA transcription and protein expression levels in lung tissues, and increased TM and EPCR mRNA transcription and expression levels.']
['Hydrogels have been widely studied as tissue engineering scaffolds over the past 2 decades because of their favorable biological properties. Recently, a new biodegradable glycol chitin-based thermoresponsive hydrogel scaffold (GC-TRS) was developed that can be easily applied as a mild viscous solution at room temperature but quickly transforms into a durable hydrogel under physiological conditions. The aim of this study was to investigate the effects of GC-TRS on the proliferation and odontogenic differentiation of colony-forming human dental pulp cells (hDPCs) in the presence of enamel matrix derivative.', 'Glycol chitin was synthesized by N-acetylation of glycol chitosan. The morphology of the thermoresponsive hydrogel scaffold was observed by using scanning electron microscopy. The sol gel phase transition of the aqueous solution of glycol chitin was investigated by using the tilting method and rheometer studies. hDPCs were isolated based on their ability to generate clonogenic adherent cell clusters. The effect of GC-TRS and collagen on cell viability was examined by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of markers for odontogenic/osteogenic differentiation (ie, dentin sialophosphoprotein, dentin matrix protein-1, osteonectin, and osteopontin) was analyzed by performing real-time polymerase chain reaction.', 'GC-TRS exhibited a highly macroporous and well-interconnected porous structure. The polymer solution existed in a mildly viscous sol state, but it transitioned to a gel state and did not flow above approximately 37°C. Rheometer studies showed that the glycol chitin solution exhibited a fast sol gel transition approximately at body temperature. GC-TRS and collagen did not inhibit cell viability until 7 days. Dentin sialophosphoprotein and dentin matrix protein-1 were expressed by cells cultured in GC-TRS at a higher level than that in cells cultured in collagen (P < .05). In both the scaffold groups, dentin sialophosphoprotein, dentin matrix protein-1, and osteopontin messenger RNA was up-regulated significantly in EMD-treated hDPCs when compared with the nontreated cells (P < .05).']
['The main purpose of this study was to evaluate the biocompatibility and bioactivity of a new mineral trioxide aggregate (MTA)-based endodontic sealer, MTA Fillapex (MTA-F; Angelus, Londrina, Brazil), in human cell culture.', 'Human osteoblast-like cells (Saos-2) were exposed for 1, 2, 3, and 7 days to MTA-F, Epiphany SE (EP-SE; SybronEndo, Orange, CA), and zinc oxide-eugenol sealer (ZOE). Unexposed cultures were the control group (CT). The viability of the cells was assessed by MTT assay and the morphology by scanning electron microscopy (SEM). The bioactivity of MTA-F was evaluated by alkaline phosphatase activity (ALP) and the detection of calcium deposits in the culture with alizarin red stain (ARS). Energy-dispersive X-ray spectroscopy (EDS) was used to chemically characterize the hydroxyapatite crystallites (HAP). Saos-2 cells were cultured for 21 days for ARS and SEM/EDS. ARS results were expressed as the number of stained nodules per area. Statistical analysis was performed with analysis of variance and Bonferroni tests (P < .01).', 'MTA-F exposure for 1, 2, and 3 days resulted in increased cytotoxicity. In contrast, viability increased after 7 days of exposure to MTA-F. Exposure to EP-SE and ZOE was cytotoxic at all time points. At day 7, ALP activity increase was significant in the MTA-F group. MTA-F presented the highest percentage of ARS-stained nodules (MTA-F > CT > EP-SE > ZOE). SEM/EDS analysis showed hydroxyapatite crystals only in the MTA-F and CT groups. In the MTA-F group, crystallite morphology and chemical composition were different from CT.']
['The regulatory molecule for cell life span, telomerase, was modified by human telomerase reverse transcriptase (hTERT) gene transfer to investigate its effect on regenerative properties of endothelial progenitor cells (EPCs) in neovascularization.', 'Telomerase activity was enhanced in hTERT-transduced EPCs (Td-TERTs) (1.2-fold versus no transduced EPCs [no-Td] and 1.2-fold versus GFP-transduced EPCs [Td/GFPs] at day 8; 5.2-fold versus no-Td and 4.8-fold versus Td/GFP at day 21, respectively) Mitogenic capacity in Td/TERTs exceeded that in Td/GFPs at day 8 (0.62+/-0.02 versus 0.53+/-0.01, respectively; P<0.01). Vascular endothelial growth factor-induced cell migration in EPCs was markedly enhanced by hTERT overexpression (Td/TERTs versus Td/GFPs, 292+/-12 versus 174+/-6 cells, respectively; P<0.01). hTERT overexpression has rescued EPCs from starvation-induced cell apoptosis, an outcome that was further enhanced in response to vascular endothelial growth factor. The colony appearance of totally differentiated endothelial cells (tdECs) was detected before day 30 only in Td/TERT, whereas no tdEC colonies could be detected in both Td/GFPs and no-Tds. Finally, we investigated in vivo transplantation of heterologous EPCs. Td/TERTs dramatically improved postnatal neovascularization in terms of limb salvage by 4-fold in comparison with that of Td/GFPs; limb perfusion was measured by laser Doppler (0.77+/-0.10 versus 0.47+/-0.06; P=0.02), and capillary density (224+/-78 versus 90+/-40 capillaries/mm2; P<0.01).']
['Recent studies showed that Wnt signaling through the beta-catenin pathway (canonical Wnt signaling) act on mouse dermal papilla cells (DPCs) enabling hair follicles to keep growing.', 'To investigate whether human DPCs respond to canonical Wnt signaling and, if so, to identify target genes of Wnt/beta-catenin pathway.', 'Cultured human DPCs were transiently transfected with the beta-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of beta-catenin signaling by Wnt3a (one of the canonical Wnts). Immunofluorescence staining was also performed to localize beta-catenin in the presence or absence of Wnt3a. Microarray was carried out using Affymetrix gene chips. RT-PCR analysis and immunoblot were employed to verify microarray data. Cyclic AMP (cAMP) levels were measured using EIA assay after Wnt3a and PGE2 treatment in DPCs.', 'Wnt3a significantly stimulated the transcriptional activity of pTopflash but not pFopflash. In line with this, we identified a number of genes that are regulated by Wnt3a. Some of the differently expressed genes including EP2 were confirmed by RT-PCR analysis. Immunoblot further confirmed that EP2 protein is indeed increased by Wnt3a. DPCs pretreated with Wnt3a showed higher responsiveness to PGE2 as measured by cAMP levels.']
['The purpose of this study was to reveal the correlation between the size of the native anterior cruciate ligament (ACL) footprint and the area of commonly used autografts using cadaveric knees.', "Twenty-Four non-paired human cadaver knees were used. The size of the femoral and tibial ACL footprints, length of Blumensaat's line, and the height and area of the lateral wall of the femoral intercondylar notch were photographed and measured with Image J software (National Institution of Health). Simulating an semitendinosus tendon (ST) graft, the ST was cut in half. The bigger half was regarded as the antero-medial (AM) bundle, and the remaining half was regarded as the postero-lateral (PL) bundle. Simulating an semitendinosus and gracilis (ST-G) graft, the bigger half of the ST and G was regarded as the AM bundle, and the smaller half of the ST was regarded as the PL bundle. Each graft diameter was measured, and the graft area was calculated. Simulating a bone-patella tendon-bone (BPTB) graft, a 10-mm wide BPTB graft was harvested and the area calculated.", "The sizes of the native femoral and tibial ACL footprints were 72.3 ± 24.4 and 134.1 ± 32.4 mm(2), respectively. The length of Blumensaat's line, and the height and area of the lateral wall of the femoral intercondylar notch were 29.5 ± 2.5 mm, 17.7 ± 2.3 mm, and 400.9 ± 62.6 mm(2), respectively. The average areas of the ST, ST-G, and BPTB graft were 52.7 ± 6.3, 64.7 ± 7.6, and 37.1 ± 7.5 mm(2). Both the height and the area of the lateral wall of the femoral intercondylar notch were significantly correlated with the femoral size of the ACL footprint (p = 0.007 and 0.008, respectively). However, no significant correlation was observed between ACL footprint size and autograft size. No significant correlation was observed between autograft size and the size of the lateral wall of the femoral intercondylar notch."]
['Ly-1 antibody reactive clone (LYAR) is a nucleolar zinc finger protein that has been implicated in cell growth, self-renewal of embryonic stem cells, and medulloblastoma. To test whether LYAR is critical for cell growth and development, we generated Lyar mutant mice.', 'Mice carrying the mutant Lyar(gt) allele were generated from embryonic stem cells that contained a gene-trap insertion in the Lyar gene. Phenotypic analyses were performed on Lyar mutant mice and mouse embryonic fibroblasts. Lyar(gt/gt) mice were crossed to mice lacking the p53 tumor suppressor protein and Lyar/p53 compound mutants scored for external abnormalities.', 'Lyar(gt/gt) homozygotes are viable, fertile, and indistinguishable from wild type littermates. However, the growth of Lyar(+/gt) and Lyar(gt/gt) mouse embryonic fibroblasts (MEFs) was impaired, coincident with an increase in the steady-state level of p53 and a key p53 effector of growth arrest, p21, suggesting that a cellular stress response is triggered in the absence of a wild type level of LYAR. Remarkably, the majority of Lyar(+/gt) and Lyar(gt/gt) female mice lacking p53 mice failed to survive. The neural tube defect (NTD) exencephaly was observed in ≈26% and ≈61% of female Lyar(+/gt;) p53(-/-) and Lyar(gt/gt;) p53(-/-) embryos, respectively.']
['Angiogenesis is essential for tumor growth and metastasis. It is a complex, dynamic process that is coordinated by several classes of angiogenic factors. One candidate family is the Tie2 tyrosine kinase, whose expression is restricted largely to endothelial cells. Tie2 has three known ligands, angiopoietin (Ang)-1, Ang-2, and Ang-4, that have different functional effects but play a requisite role in embryonic vessel remodeling. Because there are only limited data on the Tie2 pathway in human breast cancer, and our previous data have suggested that breast tumors establish a blood supply by vascular remodeling, we have investigated the expression of Ang-1, Ang-2, Ang-4, and Tie2 in a series of normal and neoplastic human breast tissues.', 'We examined mRNA expression by reverse transcription-PCR in 6 normal and 52 malignant breast tissues and correlated expression with clinicopathological and angiogenic variables. We also examined the effect of physiological levels of estrogen on Ang expression.', 'Ang-1, Ang-2, Ang-4, and Tie2 were detected in 19%, 52%, 35%, and 65%, respectively, of tumor samples. There was a significant reduction in expression of tumor Ang-1 (P = 0.04), Ang-2 (P = 0.01), Ang-4 (P = 0.004), and Tie2 (P = 0.02) compared with that in normal breast tissues. There was a significant relationship in tumors between all Angs and between each ligand and Tie2. In a multivariate analysis, there were significant positive correlations between Ang-4 and estrogen receptor (P = 0.016) and a significant inverse correlation between Ang-1 and thymidine phosphorylase expression (P = 0.01). No significant associations were observed between the other members of the Ang/Tie2 gene family and patient age, tumor size, lymph node status, tumor grade, vascular invasion, tumor vascularity, vascular maturation, thymidine phosphorylase, or vascular endothelial growth factor A expression (P > 0.05 for all). The potential regulation of Ang-4 by estrogen was further investigated in vitro. Addition of physiological concentrations of 17beta-estradiol (1 nM) to hormone-free media caused no significant change in Ang-4 mRNA abundance (P = 0.75) in the estrogen receptor-positive cell line MCF-7 after either 2 or 18 h, despite demonstrating induction for the estrogen response gene pS2.']
["Nonsense-mediated mRNA decay (NMD) is an mRNA quality control mechanism that selectively recognizes and targets for degradation mRNAs containing premature termination codons. Retroviral full-length RNA is presented to the host translation machinery with characteristics rarely observed among host cell mRNAs: a long 3' UTR, retained introns, and multiple open reading frames. As a result, the viral RNA is predicted to be recognized by the host NMD machinery and degraded. In the case of the Rous sarcoma virus (RSV), we identified a stability element (RSE), which resides immediately downstream of the gag termination codon and facilitates NMD evasion.", "We defined key RNA features of the RSE through directed mutagenesis of the virus. These data suggest that the minimal RSE is 155 nucleotides (nts) and functions independently of the nucleotide sequence of the stop codon or the first nucleotide following the stop codon. Further data suggested that the 3'UTRs of the RSV pol and src may also function as stability elements."]
["Fibromyalgia (FM) is a chronic musculoskeletal pain disorder characterized by widespread pain. This study focuses on patients' attributions of illness and of symptom onset.", "Semi-structured interviews were conducted with 56 women to elicit patients' views on what triggered their FM. The transcripts of the interviews were analyzed using a classical indexing technique to identify key themes. Content analysis was performed by two independent coders.", "Primary causal attributions fell into five categories: psychological problems (28 respondents); somatic concerns (N=12); violence/abuse during childhood (N=7), gynaecological/obstetrical problems (N=6), and fatigue (N=3). Patients' attributions were internal and external in the same proportions, more frequently unstable than stable, and more often described uncontrollable than controllable. Participants expressed decrements in self-esteem and feelings such as self-blame or despair; global perceptions of persistent pain and long-lasting problems, evoking chronicity and hopelessness; and low perceived control over their lives as well as beliefs that nothing can be done, thus increasing a feeling of guilt and vulnerability. Patients' narratives emphasized disruptive circumstances surrounding symptom onset."]
['Based on previous observations that infarcts encompassing the insula were linked to unfavorable clinical outcome, we hypothesized that insular damage was directly associated with worsened infarction in ischemic but potentially viable neighboring brain tissue.', 'Using acute diffusion- and perfusion-weighted MRI within the first 12 hours of symptom onset and a follow-up MRI on day 5 or later, we calculated the percentage of mismatch lost (PML) in 61 consecutive patients with ischemic stroke within the middle cerebral artery territory. PML denoted the percentage of mismatch tissue between diffusion-weighted imaging and mean transit time maps that eventually underwent infarction. We explored the relationship between PML and insular location using a regression model.', 'The median PML was 17.7% (interquartile range, 3.5% to 54.2%) in insular and 2.5% (0.0% to 12.7%) in noninsular infarcts (P<0.01). The PML correlated with the volume of abnormal regions on diffusion-weighted imaging (P<0.01), mean transit time (P<0.01), cerebral blood flow maps (P<0.01), and cerebral blood volume maps (P<0.01). A linear regression model with PML as response and with acute MRI volumes, age, and the site of vascular occlusion as covariates showed that insular involvement was an independent predictor of PML (P=0.01). The regression model predicted an approximately 3.2-fold increase in PML with insular involvement.']
['Mean nocturnal baseline impedance (MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden.', 'To assess the predictive value of MNBI on symptomatic outcomes after anti-reflux therapy.', 'In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from six channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal oesophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7 and 9 cm, and 15 and 17 cm respectively. Symptomatic outcomes were measured as changes in global symptom severity (GSS, rated on 100-mm visual analogue scales) on prospective follow-up after medical or surgical anti-reflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes.', "Of 266 patients, 135 (50.8%) were tested off proton pump inhibitor (PPI) therapy and formed the study cohort (52.1 ± 1.1 years, 63.7% F). The 59 with elevated acid exposure time (AET) had lower composite and distal MNBI values than those with physiological AET (P < 0.0001), but similar proximal MNBI (P = 0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r = -0.5, P < 0.001), but not proximal MNBI (Pearson's r = 0, P = 0.72). After prospective follow-up (94 patients were followed up for 3.1 ± 0.2 years), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement."]
['To observe the therapeutic effects of continuous plasma filtration absorption (CPFA) treatment on burn sepsis.', "Thirty burn patients with sepsis hospitalized in Beijing Fengtai You'anmen Hospital from July 2009 to October 2012 were treated by CPFA for twice besides routine treatment. The blood samples were collected at five sites (A, B, C, D, and E, respectively) of blood purification equipment before and after CPFA, before and after hemoabsorption, and before hemofiltration. The plasma levels of TNF-α, IL-1β, IL-6, IL-10, interleukin-1 receptor antagonist (IL-1RA), soluble tumor necrosis factor receptor (sTNFR) I , and sTNFR-II from sites A, C, and E were determined with ELISA before CPFA was performed for the first time, and those from sites B and D were determined with ELISA after CPFA was performed for the first time. Plasma levels of the above-mentioned cytokines from sites A and B were determined with ELISA before CPFA and after CPFA was performed for the second time. The data of plasma levels of IL-1βP3, IL-1RA, sTNFR-I, sTNFR-II, and TNF-α before CPFA and after CPFA was performed for the second time were collected for calculation of the ratios of IL-1RA to IL-1β and sTNFR-I plus sTNFR-II to TNF-α. The expression rate of human leukocyte antigen DR (HLA-DR) on the CD14 positive monocytes, acute physiology and chronic health evaluation (APACHE) II score, body temperature, pulse, respiratory rate, and leukocyte count of patients were evaluated or recorded before CPFA and after CPFA was performed for the second time. Patients'condition was observed. Data were processed with paired t test.", 'The plasma levels of TNF-α, IL-1β, IL-6 and IL-10 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the first time (with t values respectively 7.05, 5.23, 4.73, 2.37, P values below 0.01). After CPFA was performed for the first time, the plasma levels of TNF-α, IL-1β, and IL-6 from site D were significantly lower than those from site C before CPFA was performed for the first time (with t values respectively 5.48, 2. 17, 1.78, P < 0.05 or P <0.01). The plasma levels of all cytokines were close between site B after CPFA was performed for the first time and site E before CPFA was performed for the first time (with t values from 0.04 to 1.05, P values above 0.05). The plasma levels of TNF-α, IL-1β, and IL-6 from site B after CPFA was performed for the second time were significantly lower than those from site A before CPFA was performed for the second time (with t values from 1.87 to 5.93, P <0.05 or P <0.01). The ratios of IL-1RA to IL-1β and sTNFR-I plus sTNFR-II to TNF-α, and expression rate of HLA-DR were increased significantly after CPFA was performed for the second time as compared with those before CPFA (with t values from 3.99 to 7. 80, P values below 0.01). APACHE II score after CPFA was performed for the second time was 11 ± 6, which was lower than that before CPFA (22 ± 7, t =4.63, P <0.01). After CPFA was performed for the second time, body temperature, pulse, and respiratory rate of patients were improved (with t values from 1.95 to 3.55, P values below 0.05) , and the leukocyte count was significantly decreased (t =4.36, P <0.01) as compared with those before CPFA. All patients survived and were discharged with length of stay of (27 ± 31) d, and no adverse effects occurred during CPFA treatment.']
['Experimental and clinical data suggest that morphine possesses unique cardioprotective and antiinflammatory properties. In this clinical investigation, we sought to determine whether the choice of intraoperative opioid (morphine or fentanyl) influences early recovery after cardiac surgery.', 'Ninety patients undergoing cardiac surgery with cardiopulmonary bypass were randomized to receive either morphine (40 mg) or fentanyl (600 mug) as part of a standardized opioid-isoflurane anesthetic. Quality of recovery was assessed using the QoR-40 questionnaire administered preoperatively and daily on postoperative days 1-3. During the first three postoperative days, pain was measured using a 100-mm visual analog scale, and the use of IV and oral pain medications (morphine or acetaminophen/hydrocodone) was quantified. Hemodynamic variables, duration of tracheal intubation, postoperative febrile reactions, organ morbidities, and intensive care unit (ICU) and hospital length of stay were evaluated.', 'Compared with patients given fentanyl, those receiving morphine had higher global QoR-40 scores on postoperative days 1 (173 vs 160, P < 0.0001), 2 (174 vs 164, P < 0.0001), and 3 (177 vs 167, P < 0.001). Differences between the groups were observed in the QoR-40 dimensions of emotional state, physical comfort, and pain (all P < 0.01-0.0001). Postoperative visual analog scale pain scores, use of pain medication in the ICU and surgical ward, and postoperative febrile reactions were reduced significantly in the morphine group (all P < 0.01). No differences between the groups were noted in duration of tracheal intubation, ICU and hospital length of stay, or postoperative complications.']
['Early efforts to predict death following severe burns focused on age and burn size; more recent work incorporated inhalation injury and pneumonia. Gender, co-morbid illness, and co-existent trauma have been implicated in burn mortality but have rarely been incorporated into predictive models.', 'The National Burn Repository (NBR) and the National Trauma Data Bank (NTDB) provided data on 68,661 (54,219 and 14,442, respectively) burn patients that was used to develop and validate, respectively, a predictive model of burn mortality. Logistic regression was used to model the odds of mortality with respect to age, gender, % body surface area burned (BSAB), co-existent trauma, inhalation injury, pneumonia, and co-morbid illness. Performance of the predictive model was assessed using a deviance statistic, receiver operating characteristic (ROC) curves, and the Hosmer-Lemeshow (HL) statistic.', 'The predictive model that demonstrated optimal performance included the variables age, percent total BSAB, inhalation injury, co-existent trauma, and pneumonia. The area under the ROC curve for this model was 0.94 and the HL statistic was 16.0. The inclusion of additional variables, i.e., gender, co-morbid illness, did not improve the performance of the model despite reduction in the model deviance. When the predictive model was applied to the validation data source, the area under the ROC curve was 0.87 and the HL statistic was 10.0, indicating good discrimination and calibration.']
['Sphingosine-1-phosphate (S1P) influences activation, migration and death of immune cells. Further, S1P was proposed to play a major role in the induction and promotion of allergic diseases. However, to date only limited information is available on the role of S1P in food allergy.', 'We aimed to investigate the role of sphingosine-kinase (SphK) 1 and 2, the enzymes responsible for endogenous S1P production, on the induction of food allergy.', 'Human epithelial colorectal CaCo2 cells stimulated in vitro with S1P revealed a decrease of transepithelial resistance and enhanced transport of FITC labeled OVA. We studied the effect of genetic deletion of the enzymes involved in S1P production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (OVA) with concomitant acid-suppression. Wild-type (WT), SphK1(-/-) and SphK2(-/-) mice immunized with OVA alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. SphK1- and SphK2-deficient mice fed with OVA under acid-suppression showed reduced induction of OVA specific IgE and IgG compared to WT mice, but had normal responses when immunized by the intraperitoneal route. Flow cytometric analysis of spleen cells revealed a significantly reduced proportion of CD4(+) effector T-cells in both SphK deficient animals after oral sensitization. This was accompanied by a reduced accumulation of mast cells in the gastric mucosa in SphK-deficient animals compared to WT mice. Furthermore, mouse mast cell protease-1 (mMCP-1) levels, an IgE-mediated anaphylaxis marker, were reliably elevated in allergic WT animals.']
['Melanocyte stem cells (McSCs) are the origin of melanocytes that are periodically refreshed in skin and hair follicle. Previously, we reported that Wnt3a could promote melanogenesis, but the mechanism of McSCs activation remains unclear.', 'We aimed to illustrate the roles of Wnt/ß-catenin signaling pathway during McSC activation.', 'Adenovirus-mediated overexpression of Wnt3a and Wnt10b were used. In vitro experiments were performed on the immortalized melanocyte progenitor cell line iMC23, wheres in vivo experiments were performed in Dct-LacZ mice. Immunofluorescence and western blot were used to determine the protein expression.', 'Wnt3a promotes the differentiation and melanogenesis of iMC23, by activating Wnt/β-catenin signaling pathway. Wnt3a induces hair follicle regeneration and McSC activation. Detailed analysis indicats that Wnt3a activated Wnt/β-catenin signaling pathway, thus promoting the differentiation of McSCs during this process. Wnt10b, another canonical Wnt signaling ligand, induces hair follicle regeneration and McSC activation as well.']
['Obstetric outcome data can be accessed by a variety of different methods in New South Wales, Australia, including Diagnosis-Related Group (DRG) summaries and the Midwives Data Collection (MDC). The accuracy of the reporting of the obstetric complications encompassed by the hypertensive disorders of pregnancy (HDP) has been doubted owing to the inconsistency and confusing coding categories available in both coding systems.', 'To test that there would be no disagreement in coding between DRG coding, MDC coding and a disorder-specific database.', 'A prospective disorder-specific database, namely the Hypertensive Disorders of Pregnancy Database (HDPDB), was maintained for 6 months and diagnoses were compared with the DRG and MDC coding systems. Medical records of all women (n = 230) who received a HDP coding during this period were examined and recoded using the Australasian Society for the Study of Hypertension in Pregnancy diagnostic groupings. The HDPDB was the gold standard for the comparison of coding.', 'Significant coding errors were found in both systems available. Sixty-four percent (P < 0.001) of medical records were incorrectly coded in the DRG coding system and 56% (P < 0.001) were incorrectly coded in the MDC.']
['Metopic synostosis results in trigonocephaly with bitemporal narrowing. Treatment involves differential fronto-orbital advancement, widening of the bitemporal region, and rounding the forehead. The purpose of this article was to implement three-dimensional surgical planning to treat metopic synostosis, including use of intraoperative templates, and to test the accuracy of the results.', 'This is a prospectively analyzed series of retrospective patients with metopic synostosis. Consecutive cases treated by the authors involving a simulated computer-aided planning session were reviewed. Demographic data were tabulated, and three-dimensional quantitative data reviewed. Measurements obtained included bifrontal angle, temporal advancement, and bitemporal distance and widening. Preoperative, simulated, and actual results were compared and analyzed using the t test.', 'Five infants with metopic synostosis treated by this method were included (3 boys, 2 girls). The endocranial bifrontal anglechanged from 111.25° preoperatively to 148.58° postoperatively (P = 0.0001) and simulated 145.62° (compared with actual 148.58) (P = 0.5099). The bitemporal distance preoperative averaged 73.72mm, compared with actual of 89.78mm (P = 0.019), and was simulated to 89.28mm (vs actual 89.78) (P = 0.8815). The surgically planned advancement and expansion were similar compared with actual (P = 0.591, 0.806, and 0.806), respectively.']
['Smoking cessation is the key cancer prevention behaviour for smokers; nonetheless, smokers can still benefit from earlier diagnosis of cancer. However, fewer smokers participate in screening despite their increased risk, which may reflect different beliefs about cancer.', "A UK population-representative sample of ⩾50 year-olds (n=6965) was surveyed using the Awareness and Beliefs about Cancer measure. These analyses examine six items on cancer beliefs (e.g., 'cancer can often be cured'), and four on help-seeking barriers (e.g., 'I would be too embarrassed').", "Smokers were more likely to hold pessimistic cancer beliefs than never-smokers or former-smokers on four of six items. For example, 34% agreed 'a cancer diagnosis is a death sentence', compared with 24% of non/former-smokers (P<0.001). More smokers (18%) than non/former-smokers (11%) would not want to know if they had cancer (P<0.01). The only barrier to symptomatic help-seeking differing by smoking status was 'worry about what the doctor might find' (36% vs 28%, P<0.01). Associations were independent of demographics, self-rated health and cancer experience."]
['Remifentanil preconditioning (RPC) reduces the infarct size in anesthetized rat hearts, and this effect seems to be mediated by all three types of opioid receptors (ORs). Because there is evidence of only kappa- and delta- but not mu-ORs in the rat heart, the authors investigated whether RPC confers cardioprotection via cardiac kappa- and delta-OR as well as via extracardiac mu-OR agonist activity. The authors also investigated the involvement of signaling mechanisms, namely protein kinase C and mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels.', "The hearts of male Sprague-Dawley rats weighing 190-210 g were removed, mounted on a Langendorff apparatus, and perfused retrogradely at 100 cm H2O with Krebs-Ringer's solution. All hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The study consisted of three series of experiments on the effect of ischemic preconditioning or RPC (10, 50, and 100 ng/ml remifentanil) after blockade of OR subtypes (delta-OR antagonist naltrindol, kappa-OR antagonist nor-binaltorphimine, and mu-OR antagonist CTOP). The involvement of protein kinase C or the KATP channel in the cardioprotection of RPC was also investigated using specific blockers in each group. RPC was produced by three cycles of 5-min perfusion of remifentanil in Krebs-Ringer's solution interspersed with a 5-min reperfusion with Krebs solution only. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining.", 'Infarct size as a percentage of the area at risk was significantly reduced after RPC from 51.9 +/- 5.0% (control, n = 8) to 36.2 +/- 10.0% (100 ng/ml RPC, n = 8, P < 0.01). This effect was stopped by pretreatment with naltrindol (52.3 +/- 5.2%) and nor-binaltorphimine (43.5 +/- 6.0%) but not CTOP (37.1 +/- 6.0%). Chelerythrine and GF109203X, both protein kinase C inhibitors, abolished the effects of RPC or ischemic preconditioning on infarct size as a percentage of area at risk. 5-Hydroxydecanoate (a selective mitochondrial KATP channel blocker) also abolished the cardioprotection of RPC and IPC, but HMR-1098 (a selective inhibitor of the sarcolemmal KATP channel) did not.']
['Monocytes and their progeny are abundant constituents of the tumor microenvironment in lymphoproliferative disorders, including chronic lymphocytic leukemia (CLL). Monocyte-derived cells, including nurse-like cells (NLC) in CLL, promote lymphocyte proliferation and survival, confer resistance to chemotherapy, and are associated with more rapid disease progression. Colony-stimulating factor-1 receptor (CSF-1R) regulates the homeostatic survival of tissue-resident macrophages. Therefore, we sought to determine whether CSF-1R is similarly required for NLC survival.', 'CSF-1R expression by NLC was examined by flow cytometry and immunohistochemistry. CSF-1R blocking studies were performed using an antagonistic monoclonal antibody to examine its role in NLC generation and in CLL survival. A rational search strategy was performed to identify a novel tyrosine kinase inhibitor (TKI) targeting CSF-1R. The influence of TKI-mediated CSF-1R inhibition on NLC and CLL viability was examined.', 'We demonstrated that the generation and survival of NLC in CLL is dependent upon CSF-1R signaling. CSF-1R blockade is associated with significant depletion of NLC and consequently inhibits CLL B-cell survival. We found that the JAK2/FLT3 inhibitor pacritinib suppresses CSF-1R signaling, thereby preventing the generation and survival of NLC and impairs CLL B-cell viability.']
['Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.', 'Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.', 'Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations.', 'The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis.']
['Myxomatous mitral valve disease (MMVD) is associated with leaflet thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular mechanisms contributing to MMVD, however, remain poorly understood. We tested the hypothesis that increased transforming growth factor-β (TGF-β) signalling and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene expression in human and mouse mitral valves.', 'Using qRT-PCR, we found that increased expression of TGF-β1 in mitral valves from humans with MMVD (n = 24) was associated with increased expression of connective tissue growth factor (CTGF) and matrix metalloproteinase 2 (MMP2). Increased levels of phospho-SMAD2/3 (western blotting) and expression of SMAD-specific E3 ubiquitin-protein ligases (SMURF) 1 and 2 (qRT-PCR) suggested that TGF-β1 signalling occurred through canonical signalling cascades. Oxidative stress (dihydroethidium staining) was increased in human MMVD tissue and associated with increases in NAD(P)H oxidase catalytic subunits (Nox) 2 and 4, occurring despite increases in superoxide dismutase 1 (SOD1). In mitral valves from SOD1-deficient mice, expression of CTGF, MMP2, Nox2, and Nox4 was significantly increased, suggesting that ROS can independently activate pro-fibrotic and matrix remodelling gene expression patterns. Furthermore, treatment of mouse mitral valve interstitial cells with cell permeable antioxidants attenuated TGF-β1-induced pro-fibrotic and matrix remodelling gene expression in vitro.']
['People exposed to stressful experience are at increased risk of the development of depression. A number of functional imaging studies have found disturbances in the mood-regulating circuit of the stress-exposed depressed patients, although few animal imaging studies have been undertaken addressing the brain functional changes of depression.', 'Two rat models of depression: maternal separation (MS) and chronic unpredictable mild stress (CUMS), imitating early life stress and adult stress respectively, were administered with escitalopram. The differences in functional brain changes were determined by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI).', 'Increased BOLD activation was observed in some brain regions of MS and CUMS animals, such as the bilateral hypothalamus, limbic system, hippocampus and frontal lobe, which were parts of mood-regulating circuit. Furthermore, the MS- and CUMS-induced increases in BOLD activation were partially attenuated by chronic escitalopram treatment.']
['Tobacco smoking is the largest preventable cause of morbidity and premature mortality in the world. Although its medical consequences are well documented, 20-50% of the population even in developed countries remain tobacco smokers. The drugs presently used in smoking cessation have limited efficiency and, therefore, there is a need for alternative and improved treatments. One novel approach in this regard may be provided by immunization against nicotine.', 'The present study in male Wistar rats investigated if active immunization with a novel nicotine immunogen, IP18-KLH, may generate nicotine-selective antibodies and, furthermore, whether this treatment might prevent nicotine from exerting its stimulating effect on the mesolimbic, dopaminergic reward system in the brain.', "Enzyme-linked immunosorbent assay (ELISA) was used to determine the titer of nicotine antibodies in plasma after immunization with IP18-KLH in Freund's adjuvant. Competitive ELISA was used to assess the selectivity of the antibodies. Finally, we used in vivo voltammetry to investigate whether active immunization with IP18-KLH could prevent nicotine-induced dopamine release in the shell of nucleus accumbens (NAC(shell)).", 'The present study shows that active immunization with IP18-KLH generates antibodies that are highly selective for nicotine. Furthermore, immunization with IP18-KLH prevented the nicotine-induced increase in dopamine release in the NAC(shell), a biochemical correlate to the rewarding properties of nicotine.']
['Flaviviruses, which include Dengue (DV) and West Nile (WN), mutate in response to immune system pressure. Identifying escape mutants, variant progeny that replicate in the presence of neutralizing antibodies, is a common way to identify functionally important residues of viral proteins. However, the mutations typically occur at variable positions on the viral surface that are not essential for viral replication. Methods are needed to determine the true targets of the neutralizing antibodies.', 'Stereophysicochemical variability plots (SVPs), 3-D images of protein structures colored according to variability, as determined by our PCPMer program, were used to visualize residues conserved in their physical chemical properties (PCPs) near escape mutant positions. The analysis showed 1) that escape mutations in the flavivirus envelope protein are variable residues by our criteria and 2) two escape mutants found at the same position in many flaviviruses sit above clusters of conserved residues from different regions of the linear sequence. Conservation patterns in T-cell epitopes in the NS3- protease suggest a similar mechanism of immune system evasion.']
['Inhalation injury, especially in combination with cutaneous burns, is the major cause of morbidity and mortality in patients admitted to burn care centers. Either with or without the presence of a cutaneous burn, inhalation injury contributes to high risk for developing severe pulmonary complications. Steroids may reduce a prolonged and destructive inflammatory response to toxic or allergic substances. The objective of this study was to evaluate the effect of early single-shot intravenous steroids on pulmonary complications and mortality in burned or scalded patients with or without inhalation injury.', 'Retrospective analysis of a prospective single center database of patients registered between 1989 and 2011 who were admitted to the intensive care unit of our burn care center after burn or scald injury. Uni-variate statistical analysis was performed comparing two groups (steroid treated vs. non steroid treated patients) with regard to clinical outcome. Main parameters were sepsis, mortality and pulmonary complications such as pneumonia, ALI and ARDS. Multi-variate analysis was used by logistic regression with mortality and pulmonary complications as the dependent variables to identify independent risk factors after burn or scald injuries.', 'A total of 1637 patients with complete data were included in the present analysis. 199 (12.2%) received single-shot intravenous steroids during the prehospital phase of care. In 133 (66.8%) of these patients, inhalation injury was diagnosed via bronchoscopy. Steroid treated patients had sustained a significantly higher severity of burn than non-steroid treated patients (Abbreviated Burn Severity Index 7.1±3 vs. 6.0±2.9; p<0.001). In a multivariate analysis using a logistic regression model early intravenous steroid treatment had no significant effect on pulmonary complications and mortality.']
['The skeleton has been suggested to be involved in energy metabolism through osteocalcin (OC), an osteoblast-specific molecule. The objective of this study was to investigate whether high-impact (HI) exercise stimulating bone formation would lead to changes in glucose and lipid metabolism independent of cardiorespiratory effects and whether OC mediates this association.', 'Prospective intervention study.', 'Fifty men aged 20-32 years were allocated to an intervention group or a control group. The intervention group completed six different types of jumps in sets of five, with the frequency of these exercises gradually increasing over 8 weeks. At baseline and after 8 weeks, glycerol concentrations were measured in fat tissue as a marker of lipolysis using microdialysis. Blood samples were assayed for OC and markers of glucose and lipid metabolism. Physical activity was measured using an accelerometer.', 'After adjustment for confounders at baseline and changes in physical activity during the intervention period, the intervention was associated with a decrease in levels of glucose (P = 0·04), adrenalin (P = 0·03) and OC (P = 0·04) after adjusting for baseline levels and changes in physical activity. No other differences between the groups were significant, although the trends of the metabolic variables favoured the intervention group.']
['Cardiac catheterization shortly before coronary artery bypass grafting or valve surgery has been associated with increased postoperative acute kidney injury. The relationship between catheterization timing and acute kidney injury after proximal aortic surgery remains unknown.', 'Between August 2005 and February 2011, a total of 285 consecutive patients underwent cardiac catheterization before elective proximal aortic surgery with cardiopulmonary bypass at a single institution. The association between timing of catheterization and postoperative acute kidney injury (defined as postoperative increase in serum creatinine ≥ 50% of baseline) was assessed using logistic regression analysis.', 'Of 285 patients, 152 (53%) underwent catheterization on preoperative days 1 to 3 and 133 (47%) underwent catheterization on preoperative day 4 or before. Acute kidney injury occurred in 88 (31%) patients, 3 (1.1%) requiring dialysis. Acute kidney injury occurred in 37 (24%) patients catheterized on preoperative days 1 to 3, and 51 (38%) patients catheterized on preoperative day 4 or before. Catheterization on preoperative days 1 to 3 was not associated with an increased risk of acute kidney injury relative to catheterization on preoperative day 4 or before (unadjusted odds ratio, 0.52; 95% confidence interval, 0.31-0.86; P = .01; adjusted odds ratio, 0.35; 95% confidence interval, 0.17-0.73; P = .005).']
['This study was conducted to investigate the action of human recombinant interleukin 1 as a radioprotector for different mouse normal cells other than bone marrow cells.', 'Semi-continuous injections of tritiated thymidine were administered every 6 h, over 24 h to determine thymidine labeling index. Mice were injected with recombinant human interleukin 1 24 h prior to tritiated thymidine and were compared to control animals that did not receive interleukin 1. Mice were killed 1 h after the last thymidine injection. The 24 h thymidine labeling index for normal tissues and RIF-1 tumor was determined. Labeling indices were also determined 1-14 days after a series of fractionated irradiations with or without pretreatment with a single dose of interleukin 1 administered 24 h prior to the first radiation.', 'The thymidine labeling index of normal tissues was higher following the injection of recombinant human interleukin 1 24 h before radiolabeling. This was found in all normal tissues tested, including the lip and tongue mucosal basal cell layers, crypt cells of the duodenum, alveolar cells of the lung, hepatocytes, and basal skin cells. The thymidine labeling index of RIF-1 fibrosarcoma was not affected by interleukin 1 injection. A single interleukin 1 injection 24 h before the first radiation fraction also increased the thymidine labeling indices of normal tissues after localized fractionated irradiation. The thymidine labeling index of RIF-1 tumor was not increased by interleukin 1 administration except after relatively high radiation doses (20 Gy in five fractions). The ability of interleukin 1 to enhance the thymidine labeling index declined after the first day following the completion of fractionated irradiation.']
["Alzheimer's disease (AD) is a multifactorial, neurodegenerative disease, which is in part caused by an impairment of synaptic function, probably mediated by oligomeric forms of amyloid-beta (Abeta). While the Abeta pathology mainly affects the physiology of neurotransmission, neuronal decline is caused by excitotoxic cell death, which is mediated by the NMDA receptor. A comprehensive therapeutic approach should address both Abeta-induced synaptic deficits, as well as NMDA receptor-mediated neurodegeneration, via one molecular target. This study was designed to test whether calpain could be involved in both pathological pathways, which would offer a promising avenue for new treatments.", 'Application of the specific, water-soluble calpain inhibitor A-705253 was used to inhibit calpain in hippocampal slice cultures. We examined whether inhibition of calpain would prevent Abeta-induced deficits in neurotransmission in CA1, as well as NMDA-induced neuronal cell death.', 'A-705253 dose-dependently prevented excitotoxicity-induced neurodegeneration at low nanomolar concentrations, determined by propidium iodide histochemistry. Inhibition of the NMDA receptor similarly protected from neuronal damage. Caspase staining indicated that calpain inhibition was protective by reducing apoptosis. Electrophysiological analysis revealed that inhibition of calpain by A-705253 also fully prevented Abeta oligomer-induced deficits in neurotransmission. The protective effect of calpain was compared to the clinically available NMDA receptor antagonist memantine, which was also effective in this model.']
['Diets high in fat have been proposed as one cause of obesity, primarily because fat is more energy-dense than other macronutrients. However, the literature on fat consumption and human obesity is inconclusive. This research examines associations between dietary fat intake and obesity in men participating in the Prostate Cancer Prevention Trial.', 'Data in this cross-sectional study are from 15,266 men (55-79 years) who completed questionnaires on usual diet, physical activity, and health-related characteristics. Height and weight were collected by clinic personnel. Obesity was defined as body mass index (BMI) greater than or equal to 30 kg/m2.', 'In this healthy cohort, 23.3% were obese. Younger age, a sedentary lifestyle, lower education, and black race were positively associated with obesity (all P < 0.001). Using two statistical approaches, both total energy and energy from fat, but not total energy from other macronutrients, increased linearly and significantly with increasing BMI. Mean fat intake increased from 691 kcal (31.4% energy) among normal-BMI men to 797 kcal (34.3% energy) among the obese (P for trend <0.001). After controlling for demographic and health-related characteristics in regression models, BMI increased by 0.53 and 0.14 kg/m(2) for every 500 kcal of fat and total energy consumed, respectively. Energy underreporting, based on estimated basal metabolic rate and physical activity, was fourfold higher among obese compared to normal-weight men.']
['Neuropathic pain is caused by neural damage or dysfunction and neuropathic pain-related symptoms are resistant to conventional analgesics. Neuroinflammation due to the cytokine-chemokine network may play a pivotal role in neuropathic pain. We demonstrate that macrophage inflammatory protein-1β (MIP-1β) participates in neuropathic pain.', 'Mice received partial sciatic nerve ligation (PSL), and tactile allodynia and thermal hyperalgesia were assessed by von Frey test and Hargreaves test, respectively. Agents were administered into the region surrounding the sciatic nerve (SCN).', 'Using reverse transcription polymerase chain reaction, the mRNA expressions of MIP-1β and its receptor (CC-chemokine receptor 5; CCR5) in the injured SCN were up-regulated after PSL. MIP-1β immunoreactivity was localized in macrophages and Schwann cells and increased in the injured SCN on day 1. PSL-induced tactile allodynia on days 4 to 7 was prevented by the administration of MIP-1β neutralizing antibody (anti-MIP-1β; on days 0, 3 and 6). PSL-induced up-regulations of inflammatory cytokine-chemokine mRNAs in the injured SCN were suppressed with anti-MIP-1β treatment on day 7. Administration of CCR5 antagonist, D-ala-peptide T-amide (on days 0, 3 and 6) prevented tactile allodynia and thermal hyperalgesia on days 4 to 14. Single administration of recombinant mouse MIP-1β (rmMIP-1β) elicited tactile allodynia. Moreover, rmMIP-1β increased the mRNA expression of inflammatory mediators in the SCN on day 1 after administration.']
['Flexible poles can provide rapid eccentric and concentric muscle contractions. Muscle vibration is associated with a "tonic vibration reflex" that is stimulated by a sequence of rapid muscle stretching, activation of the muscle spindles and stimulation of a response that is similar to the myotatic reflex. Literature studies analyzing the acute cardiovascular responses to different exercises performed with this instrument are lacking. We investigated the acute effects of exercise with flexible poles on the heart period in healthy men.', 'The study was performed on ten young adult males between 18 and 25 years old. We evaluated the heart rate variability in the time and frequency domains. The subjects remained at rest for 10 min. After the rest period, the volunteers performed the exercises with the flexible poles. Immediately after the exercise protocol, the volunteers remained seated at rest for 30 min and their heart rate variability was analyzed.', 'The pNN50 was reduced at 5-10 and 15-20 min after exercise compared to 25-30 min after exercise (p\u200a=\u200a0.0019), the SDNN was increased at 25-30 min after exercise compared to at rest and 0-10 min after exercise (p\u200a=\u200a0.0073) and the RMSSD was increased at 25-30 min after exercise compared to 5-15 min after exercise (p\u200a=\u200a0.0043). The LF in absolute units was increased at 25-30 min after exercise compared to 5-20 min after exercise (p\u200a=\u200a0.0184).']
['Since its first description in the early 1990s, minimally invasive Heller myotomy has become the treatment of choice for esophageal achalasia. We report the experience of a single unit with thoracoscopic Heller myotomy (THM) and laparoscopic Heller myotomy (LHM) and we analyze the short- and long-term surgical outcomes in patients treated by each of the two approaches.', 'We evaluated retrospectively 33 patients who underwent surgical treatment for achalasia. Sixteen patients underwent THM without an antireflux procedure, and 17 patients underwent LHM and partial anterior fundoplication (n = 10) or closure of the angle of His (n = 7).', 'Mean operative time was significantly shorter for LHM than for THM (150 vs 222 min, respectively) (p = 0.0001). Mean hospital stay was significantly shorter after LHM than after THM (2.0 +/- 1.0 vs 5.1 +/- 2.2 days, respectively) (p = 0.0001). Six of 16 patients (37.5%) in the THM group experienced persistent or recurrent dysphagia compared to one of 17 patients (5.8%) in the LHM group (p = 0.04). Heartburn developed in five patients (31.2%) after THM and in one patient (5.8%) after LHM (p = 0.07). Regurgitation developed in four patients (25%) after THM and in one patient (5.8%) after LHM (p = 0.149). Lower esophageal sphincter (LES) basal pressure decreased significantly from 30.1 +/- 5.07 to 15.3 +/- 2.1 after THM and from 32.1 +/- 5.9 to 10.5 +/- 1.7 after LHM (p = 0.0001). Mean esophageal diameter was significantly reduced after LHM compared to THM (from 54.5 +/- 5.7 mm to 27.1 +/- 3.3 mm vs 50.8 +/- 7.6 mm to 37.2 +/- 6.9 mm, respectively) (p = 0.0001).']
['A variant of the human GH receptor (GHR) lacks a 22-amino-acid sequence derived from exon 3 (d3-GHR). It was reported that pediatric patients, born small for gestational age or with idiopathic short stature who were homozygous or heterozygous for this variant responded better to GH treatment than those homozygous for the full-length allele (fl-GHR).', 'The objective was to study the impact of the GHR genotype on the phenotype and growth response in patients with isolated GH deficiency (IGHD) treated with GH.', 'This was a retrospective, multinational, multicenter observational study.', 'Patients with IGHD (n = 107) were recruited.', 'All patients received GH treatment at replacement doses. The GHR genotype (fl-GHR/fl-GHR, fl-GHR/d3-GHR, or d3-GHR/d3-GHR) was determined by PCR amplification.', 'Measures included height sd score, height velocity, height velocity sd score at baseline and 1 yr of GH treatment, and their changes.', 'There was no statistically significant difference of the main outcome measures between patients with the d3-GHR allele (n = 48) and patients who were homozygous for the fl-GHR allele (n = 59). Moreover, the genotype group did not contribute significantly to the growth prediction in multiple linear regression models.']