text
stringlengths 1.03k
99.1k
|
|---|
['The present study was designed to investigate the role of X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) polymorphisms in apoptosis and the risk of ulcerative colitis (UC).', 'Blood samples from 384 unrelated subject (age range 18-65\xa0years; 171 with UC, 213 healthy controls) were collected after colonoscopy. Genomic DNA was isolated and genotyped for XRCC1 Arg399Gln and APE1 Asp148Glu using a confronting two-pair primers polymerase chain reaction. Apoptosis and intracellular reactive oxygen species (ROS) levels in peripheral blood mononuclear cells were measured using annexin-V and H(2)DCFDA assay, respectively.', 'The frequency of genotype Arg399Gln (heterozygous) of XRCC1 gene was significantly higher in patients with UC than the controls (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.13-2.64; p\xa0=\xa00.01). Similarly the genotypic frequency of APE1 Asp148Glu showed statistically significant incidence among UC subjects (OR 1.54; 95% CI 1.02-2.33; p\xa0=\xa00.04). Polymorphism in XRCC1 Arg399Gln and APE1 Asp148Glu together considerably increased the risk of UC (OR 2.303; 95% CI 1.43-3.69; p\xa0=\xa00.0007). ROS levels were high in UC subjects compared with controls (p\xa0=\xa00.01).'] |
['Bone morphogenetic proteins (BMPs) regulate essential processes during organogenesis, and a functional understanding of these secreted proteins depends on identification of their target cells. In this study, we generate a transgenic reporter for organogenesis studies that we use to define BMP pathway activation in the developing kidney.', 'Mouse strains reporting on BMP pathway activation were generated by transgenically expressing beta-galactosidase under the control of BMP responsive elements from Id1. Reporter expression corresponds well with immunoassays for pathway activation in all organs studied, validating the model. Using these reporters we have generated a detailed map of cellular targets of BMP signaling in the developing kidney. We find that SMAD dependent BMP signaling is active in collecting duct trunks, but not tips. Furthermore, glomerular endothelial cells, and proximal nephron tubules from the renal vesicle stage onward show pathway activation. Surprisingly, little activation is detected in the nephrogenic zone of the kidney, and in organ culture BMP treatment fails to activate SMAD dependent BMP signaling in nephron progenitor cells. In contrast, signaling is efficiently induced in collecting duct tips.'] |
['National registry cohort study.', 'The aim of this study was to investigate the effect of surgical stabilization on survival of spinal fractures related to ankylosing spondylitis (AS).', 'Spinal fractures related to AS are associated with considerable morbidity and mortality. Multiple studies suggest a beneficial effect of surgical stabilization in these patients.', 'In the Swedish patient registry, all patients treated in an inpatient facility are registered with diagnosis and treatment codes. The Swedish mortality registry collects date and cause of death for all fatalities. Registry extracts of all patients with AS and spinal fractures including date of death and treatment were prepared and analyzed for epidemiological purposes.', 'Seventeen thousand two hundred ninety-seven individual patients with AS were admitted to treatment facilities in Sweden between 1987 and 2011. Nine hundred ninety patients with AS (age 66\u200a±\u200a14 years) had 1131 spinal fractures, of which 534 affected cervical, 352 thoracic, and 245 lumbar vertebrae. Thirteen percent had multiple levels of injuries during the observed period. Surgically treated patients had a greater survival than those treated nonsurgically [hazard ratio (HR) 0.79, P\u200a=\u200a0.029]. Spinal cord injury was the major factor contributing to mortality in this cohort (HR 1.55, P\u200a<\u200a0.001). The proportion of surgically treated spinal fractures increased linearly during the last decades (r\u200a=\u200a0.92, P\u200a<\u200a0.001) and was 64% throughout the observed years.'] |
['Mice bearing the autosomal recessive mutation wst express a disease syndrome of immunodeficiency, neurologic dysfunction, increased sensitivity to the killing effects of ionizing radiation, and dramatic weight loss that begins at 21 days of age and progresses until death at 28-32 days of age. Because of the reported association between abnormal liver status and weight loss, we designed experiments to examine expression of a variety of liver-specific genes in wst/wst mice relative to littermates (wst/.) and parental strain (BCF1) controls.', 'Animals were individually weighed from ages 21-28 days to determine relative weight comparisons between wst/wst mice and controls. Dot blot hybridizations were set up to quantitate the accumulation of transcripts specific for alpha-fetoprotein, albumin and other liver-specific gene products.', 'These results showed a 67% reduction in albumin mRNA expression in livers derived from wst/wst mice relative to both controls. Expression of alpha-fetoprotein, as well as a variety of other liver-specific genes [secretory component (SC), metallothionein (MT-2), cytochrome P1-450 (Cyt P1-450), transferrin receptor (Tf Rec), tumor necrosis factor (TNF), and immune-associated antigen (Ia)], was unaffected.'] |
['Leukotriene B4 (LTB4) recruits and activates neutrophils. Accordingly, this leukotriene is involved in innate defense actions.', 'To examine if nasal LTB4 can produce neutrophil activity and to explore whether or not LTB4 can condition neutrophils to exert virucidal effects in vitro and in vivo.', '1. Twenty-three healthy subjects received nasal LTB4 in a randomized and sham-controlled design. Symptoms were scored and nasal lavages carried out. Myeloperoxidase (MPO) and α-defensins were monitored as indices of neutrophil activity. IL-8, eosinophil cationic protein (ECP) and α(2)-macroglobulin were measured as indices of pro-inflammatory cytokine production, eosinophil activity, and plasma exudation. 2. Supernatants from neutrophils activated by LTB4 in vitro were assayed for virucidal activity against respiratory viruses. 3. In 38 healthy individuals, nasal inoculation with human rhinovirus-16 (HRV-16) was performed. In a preliminary study, intervention with LTB4 was given in a randomized and controlled design. Symptoms, virus replication, and antibody-titres were monitored.', '1. LTB4 produced statistically significant increases in MPO and α-defensins, whereas IL-8, ECP, and α(2)-macroglobulin were unaffected. 2. The supernatants efficiently killed human coronavirus, respiratory syncytial virus, and influenza B virus. 3. HRV-16 replication was lower in subjects receiving LTB4, but this difference failed to reach statistical significance. Common cold symptoms and incidence of seroconversion were unaffected.'] |
['Insulin resistance associated with obesity and diabetes is ameliorated by specific overexpression of GLUT4 in skeletal muscle. The molecular mechanisms regulating skeletal muscle GLUT4 expression remain to be elucidated. The purpose of this study was to examine these mechanisms.', 'Here, we report that AMP-activated protein kinase (AMPK) regulates GLUT4 transcription through the histone deacetylase (HDAC)5 transcriptional repressor. Overexpression of HDAC5 represses GLUT4 reporter gene expression, and HDAC inhibition in human primary myotubes increases endogenous GLUT4 gene expression. In vitro kinase assays, site-directed mutagenesis, and site-specific phospho-antibodies establish AMPK as an HDAC5 kinase that targets S259 and S498. Constitutively active but not dominant-negative AMPK and 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) treatment in human primary myotubes results in HDAC5 phosphorylation at S259 and S498, association with 14-3-3 isoforms, and H3 acetylation. This reduces HDAC5 association with the GLUT4 promoter, as assessed through chromatin immunoprecipitation assays and HDAC5 nuclear export, concomitant with increases in GLUT4 gene expression. Gene reporter assays also confirm that the HDAC5 S259 and S498 sites are required for AICAR induction of GLUT4 transcription.'] |
['To investigate whether the expression of apoptosis and cell proliferation related proteins is related to the macroscopic form of colorectal neoplasia.', "The extent of apoptosis, using the 3' end DNA labelling method, and the immunohistochemical expression of cell proliferation (Ki-67) and apoptosis related proteins (Bcl-2, Bak, and p53) were investigated in 64 colorectal adenomas and 22 early carcinomas extending no further than the upper submucosal region. The specimens were classified into three types of macroscopic form (polypoid, flat, and depressed).", 'The Ki-67 labelling index and the Bak score did not differ significantly among each macroscopic form. In contrast, the apoptotic index and the Bcl-2 score changed significantly according to the macroscopic forms. Compared with polypoid and flat tumours, depressed tumours had a significantly lower apoptotic index (2.84, 2.28, and 1.44, respectively) and a significantly lower Bcl-2 score (3.18, 2.70, and 1.64, respectively). The proliferation/apoptosis ratio was significantly lower in polypoid tumours than in the other two macroscopic forms. The Bcl-2 score became significantly lower as the tumours flattened or took on a depressed form. Immunohistochemical p53 overexpression did not correlate with the macroscopic forms.'] |
['The epidermal growth factor receptor- (EGFR) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is associated with tumorigenesis and progression. The aims of the present study were to determine the expression patterns of Akt pathway parameters PI3K, phosphatase and tensin homolog (PTEN), phosphor-Akt (p-Akt) and their combination, for their possible prognostic value in renal cell carcinoma (RCC). PTEN dephosphorylates the liquid product of PI3K.', 'Tumor samples from 176 RCC patients were investigated for PTEN, p-Akt and PI3K expression by immunohistochemistry. Expression levels were correlated to clinical variables and postoperative outcome by uni- and multivariate statistical analysis.', 'The various expression levels within the tumor samples were independent of histological grade and tumor stage, due to different levels of activation of the PI3K/p-Akt pathway. The activation of PI3K protein was found to be significantly associated with reduced survival times (p = 0.0304, multivariate analysis). Analysis of combined biomarker expressions showed that decreased long-term survival was correlated with PTEN low/p-Akt high expression (p < 0.05).'] |
['In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress.', 'Female Wistar rats weighing 100-140g were administered vehicle (C), dihydrotestosterone (DHT) or dihydrotestosterone plus vitamin D3 (DHT+D) (n=10 per group). On the 10th week, acetylcholine (Ach) induced relaxation ability of the isolated thoracic aorta rings was determined. In order to examine the possible role of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) pathways in the impaired endothelial function, immunohistochemical labeling of aortas with anti-eNOS and anti-COX-2 antibodies was performed. Leukocyte smears, aorta and ovary tissue sections were also immunostained with anti-nitrotyrosine antibody to determine nitrative stress.', 'Relaxation ability of aorta was reduced in group DHT, and vitamin D3 partly restored Ach induced relaxation. eNOS labeling was significantly lower in DHT rats compared to the other two groups, however COX-2 staining showed an increment. Nitrative stress showed a significant increase in response to dihydrotestosterone, while vitamin D3 treatment, in case of the ovaries, was able to reverse this effect.'] |
['Sepsis is one of the most troublesome problems in critically ill patients and often accompanied with multiple organ dysfunction and high mortality. Gut injury or dysfunction may contribute to the pathogenesis of sepsis. Neutrophil extracellular traps (NETs) do not only kill microorganisms but also damage host cells during inflammatory response to infection. The aim of this study was to investigate whether NETs are capable of promoting the impairment of the gut in a rat model of lipopolysaccharide (LPS)-induced sepsis.', 'The sepsis model was induced in rats by intraperitoneal injection of LPS (10\xa0mg/kg). All rats were divided into three groups as follows: 1) control group; 2) LPS group; and 3) LPS\xa0+\xa0DNase I group. The DNase I solution (10\xa0mg/kg) was injected intravenously to disrupt NETs 30\xa0min after the LPS treatment. The animals were sacrificed at 3\xa0h and 24\xa0h after LPS or saline challenge. The intestinal cell apoptosis was examined by detecting the level of cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. The length and morphology of Villi were assessed histologically through hematoxylin and eosin stain. The levels of tumor necrosis factor-alpha and interleukin-10 in serum and intestine were detected by enzyme-linked immunosorbent assay. Intestinal injury was evaluated with Chiu scoring system.', 'A large number of neutrophils infiltrated were activated to release NETs in the intestine of LPS-induced septic rats. The disruption of NETs reduced the acute systemic inflammatory response and apoptosis of intestinal epithelial cells and alleviated histologic pathogenesis. Removal of NETs provided a beneficial effect on intestinal injury.'] |
['To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility.', 'Isometric tension recordings were performed under physiologic conditions on isolated myometrial strips taken from low-risk term pregnant women undergoing elective cesarean section. Cumulative effects of natural progesterone (10 (-11) to 10 (-5) mol/L) on oxytocin-induced myometrial contractility were evaluated. Contractile activity following ritodrine exposure was also investigated in myometrium pretreated with natural progesterone.', 'Natural progesterone alone exerted a concentration-dependent relaxant effect on myometrial contractions. The concentration-response curve for ritodrine from natural progesterone pretreated myometrium was shifted to the left with a significant reduction ( P < .01) of 50% of the maximal response, contraction amplitude ( P < .05), and frequency ( P < .05). However, there was no significant difference in the mean maximal inhibition achieved ( P = .95).'] |
['This study aims to investigate whether variations in RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of age-related macular degeneration (AMD) in Chinese population.', 'A total of 119 Chinese patients with AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot.', 'Rs10483810 in RAD51 was significantly associated with advanced AMD (P=0.045). Compared with the wild-type genotype GG, the odds ratio for the risk of advanced AMD was 4.92 (95% confidence interval: 1.04-23.36) for the heterozygous TG genotype. Moreover, the GT genotype at rs10483810 confers significantly increased risk of bilateral AMD compared to unilateral AMD (OR=12.04, 95% CI: 2.50-57.69, P=0.002). Rs13278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and rs9542236 in B3GALTL were not found to be associated with AMD (all P>0.05).'] |
['Nicotinic acetylcholine receptor α1 (nAChRα1) was recently identified as a functional cell receptor for urokinase, a potent atherogenic molecule. Here, we test the hypothesis that nAChRα1 plays a role in the pathogenesis of atherosclerosis.', 'Apolipoprotein E-deficient mice were initially fed a Western diet for 8 wks. Plasmid DNA encoding scramble RNA (pscr) or siRNA (psir2) for nAChRα1 was injected into the mice (n=16) using an aortic hydrodynamic gene transfer protocol. Four mice from each group were sacrificed 7 days after the DNA injection to confirm the nAChRα1 gene silencing. The remaining mice continued on a Western diet for an additional 16 wks.', 'The nAChRα1 was up-regulated in aortic atherosclerotic lesions. A 78% knockdown of the nAChRα1 gene resulted in remarkably less severe aortic plaque growth and neovascularization at 16 wks (both P<0.05). In addition, significantly fewer macrophages (60% less) and myofibroblasts (80% less) presented in the atherosclerotic lesion of the psir2-treated mice. The protective mechanisms of the nAChRα1 knockdown may involve up-regulating interferon-γ/Y box protein-1 activity and down-regulating transforming growth factor-β expression.'] |
['Recurrent hypoglycemia induces hypoglycemia-associated autonomic failure (HAAF), characterized by deterioration in counterregulatory responses. Endogenous opioids may mediate the development of HAAF, and blockade of opioid receptors with naloxone prevented HAAF in nondiabetic subjects.', 'We hypothesized that opioid receptor blockade with naloxone during antecedent hypoglycemia in patients with type 1 diabetes mellitus (T1DM) would prevent the development of HAAF.', 'Eight subjects with T1DM (three women, aged 34 ± 7.4 yr, hemoglobin A1c 7.3 ± 1.1%) were studied on 2 consecutive days on three separate occasions. Day 1 consisted of: 1) two 90-min hypoglycemic clamps (60 mg/dl, N-); 2) two 90-min hypoglycemic clamps (60 mg/dl) with concomitant naloxone infusion (N+); or 3) two 90-min euglycemic clamps (90 mg/dl) with concomitant naloxone infusion (control). Day 2 consisted of hyperinsulinemic stepped hypoglycemic clamps (90, 80, 70, and 60 mg/dl plasma glucose steps).', 'Day 2 hypoglycemia counterregulatory hormonal response and glucose turnover [(3-(3)H)-glucose] as indicators of recovery from hypoglycemia.', 'Antecedent hypoglycemia in N- group resulted in a markedly decreased epinephrine response and a lower rate of endogenous glucose production (EGP) during subsequent hypoglycemia compared with control (75 ± 17 vs. 187 ± 21 pg/ml, P < 0.05 and 0.8 ± 0.1 vs. 1.4 ± 0.2 mg/kg · min, P < 0.05, respectively). In contrast, in the N+ studies, plasma epinephrine was 164 ± 18 pg/ml and EGP was 1.3 ± 0.2 mg/kg · min during subsequent hypoglycemia, both levels similar to those seen in control studies (P = NS vs. control). Plasma glucagon did not increase with hypoglycemia.'] |
["Late night salivary cortisol (LNSC) is useful for diagnosing hypercortisolism and monitoring patients with Cushing's disease (CD) following pituitary surgery. It may also be a better index of cortisol secretion than serum cortisol or urinary free cortisol (UFC). No data regarding the role of LNSC in the early monitoring of patients with CD receiving drug therapy has been published. We investigated the value of LNSC in monitoring the short-term efficacy of pasireotide.", 'Seven patients who were enrolled in a phase II study investigating the efficacy of pasireotide in CD (CSOM230B2208) were included in this analysis. Patients self-administered subcutaneous pasireotide 600 μg bid for 15 days. LNSC and UFC levels were assessed at baseline and day 15.', 'At baseline, all patients had elevated LNSC which was correlated significantly with UFC levels (r = 0.97, P = .0002). At day 15, LNSC was reduced in six patients. LNSC decreases were observed from day 1 (-20%) and persisted until day 15 (overall mean reduction from baseline -51%), with the greatest decrease on day 5 (-58%). At day 15, UFC levels were decreased in all patients and normalized in one that restored also salivary cortisol rhythm.'] |
['To examine uveal melanoma cell lines for the expression of human melanoma proteoglycan (NG2) using monoclonal antibody (mAb) 9.2.27 and subsequently to assess the in vitro specificity and cytotoxicity of mAb 9.2.27 conjugated to the alpha-particle-emitting radioisotope 213bismuth (213Bi-9.2.27) for uveal melanoma cells.', 'Immunocytochemistry and flow cytometry were used to examine OCM-1, OCM-3, OCM-8, OMM-1, Mel202 and 92-1 melanoma cell lines for NG2 expression. Melanoma cells were treated with test (213Bi-9.2.27) or control (213Bi-A2) alpha-immunoconjugates (AICs). The specific cytotoxicity of 213Bi-9.2.27 AIC was evaluated using an MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfenyl)-2H-tetrazolium, inner salt) assay. Cell death was also assessed using TUNEL.', 'OCM-1, OCM-8, OMM-1, and Mel202 cells strongly expressed NG2. OCM-3 cells showed moderate expression and 92-1 cells were NG2-negative. 213Bi-9.2.27 specifically killed NG2-positive OCM-1, OCM-8, and OMM-1 cells in a concentration-dependent manner. D0 values for 37% cell survival of NG2-positive OCM-1, OCM-8, and OMM-1 cells were 5.8, 5.0, and 5.6 microCi, respectively, and the value was 43.4 muCi for NG2-negative 92-1 cells.'] |
['The upper limit of vulnerability is the stimulus strength above which electrical stimulation cannot induce ventricular fibrillation even when the stimulus occurs during the vulnerable period of the cardiac cycle. The purpose of this study was to test the hypothesis that the upper limit of vulnerability can accurately predict the defibrillation threshold in patients undergoing implantable cardioverter-defibrillator (ICD) implantation using nonthoracotomy lead systems.', 'We studied 77 patients at the time of ICD implantation. Multiple endocardial-endocardial and endocardial-subcutaneous shock pathways were used. Two different protocols were used to test the upper limit of vulnerability. In protocol 1 (n = 17), the upper limit of vulnerability was tested with two shocks on the peak or the up-slope of the T wave of paced rhythm. The shocks were given randomly either at the peak and 20 milliseconds before the peak of T wave (n = 7) or at 20 and 40 milliseconds before the peak of T wave (n = 10). In protocol 2 (n = 60), the upper limit of vulnerability was tested with three shocks delivered at 0, 20, and 40 milliseconds before the peak of the T wave. The weakest shock that failed to induce ventricular fibrillation by a 5-J step-down or step-up method was defined as the upper limit of vulnerability. The defibrillation threshold was also determined by a 5-J step-down or step-up method. In protocol 1, the upper limit of vulnerability (9 +/- 6 J) was significantly lower than the defibrillation threshold (13 +/- 7 J) with a correlation coefficient of .87 and P < .001. In protocol 2, the upper limit of vulnerability (13 +/- 6 J) was not significantly different from the defibrillation threshold (13 +/- 6 J) with a correlation coefficient of .85 and P < .001. In 45 of the 60 patients, the upper limit of vulnerability was < or = 15 J; all had a defibrillation threshold of < or = 20 J. In 51 of the 60 patients, the upper limit of vulnerability was within 5 J of the defibrillation threshold. The upper limit of vulnerability overestimated the defibrillation threshold by > 10 J in 8 patients and underestimated the defibrillation threshold by > 10 J in only 1 patient. The overestimation and underestimation occurred only in patients with the upper limit of vulnerability > 15 J.'] |
['The stomach-derived hormone ghrelin drives higher-order feeding processes related to food reward and food seeking via central nervous system signaling at its receptor (GHSR1A). The specific nuclei mediating these effects are only partially understood. Here, we use a rat model to examine whether ghrelin signaling in the ventral subregion of the hippocampus (VHPC), a brain substrate of recent interest in energy balance control, affects learned and motivational aspects of feeding behavior.', 'The effects of VHPC ghrelin administration were examined on feeding-relevant behavioral paradigms, including meal pattern analysis, operant lever pressing for sucrose, and conditioned stimulus-induced feeding. The intracellular signaling and downstream neuronal pathways stimulated by VHPC GHSR1A activation were assessed with immunoblot analysis and behavioral pharmacology.', 'Ghrelin delivery to the VHPC but not the dorsal hippocampus increased food intake primarily by increasing meal frequency. Intra-VHPC ghrelin delivery also increased willingness to work for sucrose and increased spontaneous meal initiation in nondeprived rats after the presentation of a conditioned stimulus that previously signaled meal access when the rats were food-restricted. The food intake enhancing effects of VHPC ghrelin were blocked by co-administration of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002). Immunoblot analyses provided complementary support for ghrelin activated PI3K-Akt signaling in the VHPC and revealed that this activation is blunted with high-fat diet consumption. Other immunoblot results show that VHPC GHSR1A signaling activates downstream dopaminergic activity in the nucleus accumbens.'] |
['To evaluate the influence of the severity of regional myocardial dysfunction and of the length of follow-up on the identification of myocardial viability with rest-redistribution Tl single photon emission computed tomography (SPECT) and low-dose dobutamine echocardiography (LDDE).', 'Twenty-six patients with chronic coronary artery disease and wall motion abnormalities, candidates for revascularization, were included in this study. All patients underwent, in the same week, Tl SPECT and LDDE for pre-revascularization evaluation of myocardial viability. Reversibility of regional dysfunction was assessed by two-dimensional echocardiography, 40+/-20 days (early follow-up) and 12+/-5 months (late follow-up) after revascularization.', 'In a/dyskinetic segments, Tl SPECT showed similar values of sensitivity (78% vs. 71%, P=NS) and slightly higher values of specificity (43% vs. 18%, P<0.01) compared to hypokinetic segments, in predicting functional recovery at early follow-up. No significant changes were observed in the diagnostic accuracy of Tl SPECT at late follow-up. On the contrary, LDDE provided significantly lower values of sensitivity (56% vs. 94%, P<0.05) and higher values of specificity (73% vs. 9%, P<0.01) in a/dyskinetic compared to hypokinetic segments. Specificity of LDDE in a/dyskinetic segments significantly increased from early (73%) to late follow-up (95%; P<0.05). Similarly, positive predictive value in a/dyskinetic segments significantly increased from early (69%) to late follow-up (96%; P<0.05).'] |
['Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17beta-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an antagonistic role for E2 in this process, although no molecular mechanism has been proposed for this phenomenon.', 'E2 attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF) expression as assessed by Northern blot, immunocytochemical analyses, and transient transfection assays using ANF promoter deletion fragments. Both the antihypertrophic effects and ANF induction could be blocked by the estrogen receptor antagonist ICI 182,780, which demonstrates a genomic, estrogen receptor-dependent pathway. To mimic E2-induced autocrine/paracrine effects through stimulation of the guanylyl cyclase A receptor (ANF receptor), cardiomyocytes were stimulated with phenylephrine or endothelin-1 in the presence of exogenous ANF or 8-bromo-cyclic guanosine monophosphate (cGMP), both of which attenuated agonist-induced hypertrophy. Both estrogen and ANF increased cGMP activity. The antihypertrophic effect of ANF could be reduced with extracellular ANF antibodies in a dose-dependent manner. cGMP-dependent protein kinase mediates the antihypertrophic effects of E2, so cardiomyocytes were agonist stimulated in the presence of the cGMP-dependent protein kinase blocker KT-5823. KT-5823 not only reversed the antihypertrophic properties of E2, ANF, or 8-bromo-cGMP, but also evoked potentiation of hypertrophy.'] |
['This study sought to describe the prevalence of supplement use by those with diabetes mellitus receiving care at an academic outpatient diabetes care center and to identify any association of supplement use with glycemic control.', 'This study is based on a retrospective audit of provider-verified and patient-self-reported medication and supplement use by adults with diabetes at the University of Washington Diabetes Care Center during four 2-week periods from fall 2006 through summer 2007 (1 period per season).', 'Verified medication and supplement histories for 459 adults demonstrated a per-person average use of 7 ± 4.1 prescription medicines and 0.4 ± 0.9 over-the-counter medicines daily, with 55% using some form of vitamin, mineral, or nonvitamin-nonmineral supplement on a daily basis. The rate of nonvitamin-nonmineral use was nearly twice that for type 2 diabetes mellitus as for type 1 diabetes mellitus (39.3% vs 20.3%), and A1c was lower in those using any supplement compared to those not using supplements. Vitamin use was associated with reduced A1c; however, this relationship did not hold at A1c < 7.0%.'] |
['In epithelial cells, protein sorting mechanisms regulate localization of plasma membrane proteins that generate and maintain cell polarity. The clathrin-adaptor protein (AP) complex AP-1B is expressed specifically in polarized epithelial cells, where it regulates basolateral sorting of membrane proteins. However, little is known about its physiological significance.', 'We analyzed the intestinal epithelia of mice deficient in Ap1m2 (Ap1m2(-/-) mice), which encodes the AP-1B μ1B subunit, and compared it with 129/B6/CD1 littermates (controls). Notch signaling was inhibited by intraperitoneal injection of dibenzazepine, and β-catenin signaling was inhibited by injection of IWR1. Intestinal tissue samples were collected and analyzed by immunofluorescence analysis.', 'Ap1m2(-/-) mice developed intestinal epithelial cell hyperplasia. The polarity of intestinal epithelial cells was disrupted, as indicated by the appearance of ectopic microvilli-like structures on the lateral plasma membrane and mislocalization of basolateral membrane proteins, including the low-density lipoprotein receptor and E-cadherin. The E-cadherin-β-catenin complex therefore was disrupted at the adherens junction, resulting in nuclear translocation of β-catenin. This resulted in up-regulation of genes regulated by β-catenin/transcription factor 4 (Tcf4) complex, and increased the proliferation of intestinal epithelial cells.'] |
['Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings.', 'Anesthetized pigs underwent (11)C-palmitate PET imaging during fasting (n = 3) or euglycemic hyperinsulinemia (n = 3). Metabolic products of FAs were measured in arterial, portal, and hepatic venous blood. The imaging methodology then was tested in 15 human subjects (8 obese subjects); plasma (11)C-palmitate kinetic analyses were used to quantify systemic and visceral lipolysis.', 'In pigs, PET-derived and corresponding measured FA fluxes (FA uptake, esterification, and triglyceride FA release) did not differ and were correlated with each other. In human beings, obese subjects had increased hepatic FA oxidation compared with controls (mean +/- standard error of the mean, 0.16 +/- 0.01 vs 0.08 +/- 0.01 micromol/min/mL; P = .0007); FA uptake and esterification rates did not differ between obese subjects and controls. Liver FA oxidation correlated with plasma insulin levels (r = 0.61, P = .016), adipose tissue (r = 0.58, P = .024), and systemic insulin resistance (r = 0.62, P = .015). Hepatic FA esterification correlated with the systemic release of FA into plasma (r = 0.71, P = .003).'] |
['It has been proposed that dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEAS) exert neuroprotective effects in the brain, yet evidence of associations between the endogenous levels of these steroids and measures of cognitive function is lacking.', 'The objective of the study was to investigate whether circulating levels of DHEAS independently contribute to aspects of cognitive function in women in the community.', 'This was a community-based, cross-sectional study.', 'Two hundred ninety-five women, aged 21-77 yr, were recruited from a community-based data set and participated between September 2003 and December 2004. Women were excluded if they reported any health condition that might potentially adversely affect cognitive function.', 'The individual scores of a comprehensive battery of tests of cognitive function and the serum level of DHEAS (square root transformed) were measured.', 'In the multiple linear regression analysis, the DHEAS term made a significant independent positive contribution to the Controlled Oral Word Association Test score, a measure of executive function. In addition, women with a DHEAS level in the highest tertile who also had more than 12 yr of education performed better on both Digit Span Forward and Digit Span Backward tests, which are tests of simple concentration and working memory, respectively.'] |
['Little apoptosis has been observed in rheumatoid arthritis (RA) synovial tissues. Tumor necrosis factor alpha (TNFalpha) is expressed in the joints of patients with RA, yet RA synovial fibroblasts are relatively resistant to apoptosis induced by TNFalpha. Recently, we demonstrated that FLIP is highly expressed in the RA joint. These studies were performed to determine if TNFalpha-induced NF-kappaB controls the expression of FLIP long (FLIP(L)) and FLIP short (FLIP(S)) in RA synovial fibroblasts and to determine the role of FLIP in the control of TNFalpha-induced apoptosis.', 'RA synovial fibroblasts were isolated from RA synovial tissues and used between passages 3 and 9. RA synovial or control fibroblasts were sham infected or infected with a control adenovirus vector or one expressing the super-repressor IkappaBalpha (srIkappaBalpha). The cells were stimulated with TNFalpha or a control vehicle, and expression of FLIP(L) and FLIP(S) was determined by isoform-specific real-time polymerase chain reaction and Western blot analysis. Cell viability was determined by XTT cleavage, and apoptosis was determined by annexin V staining, DNA fragmentation, and activation of caspases 8 and 3.', 'TNFalpha induced the expression of both isoforms of FLIP messenger RNA (mRNA) in RA synovial fibroblasts; however, FLIP(L) was the dominant isoform detected by Western blot analysis. In control fibroblasts, TNFalpha induced the expression of FLIP(L) and FLIP(S) mRNA and protein. The TNFalpha-induced, but not the basal, expression of FLIP was regulated by NF-kappaB. When NF-kappaB activation was suppressed by the expression of srIkappaBalpha, TNFalpha-mediated apoptosis was induced. TNFalpha-induced apoptotic cell death was mediated by caspase 8 activation and was prevented by the ectopic expression of FLIP(L) or the caspase 8 inhibitor CrmA.'] |
['Hydrogen sulfide (H(2) S) is one of two volatile sulfur compounds that are known to be the main cause of oral malodor; the other is methyl mercaptan. Other known volatiles existing in mouth air do not contribute significantly to oral malodor originating in the oral cavity. Hydrogen sulfide is also known to be an etiological factor in periodontal disease. However, the effects of H(2) S on alveolar bone remain unclear. The objectives of this study were to determine the apoptotic effects of H(2) S on osteoblasts and to verify the apoptotic molecular pathways.', 'A clonal murine calvaria cell line was incubated with 50 ng/mL of H(2) S. To detect apoptosis, the cells were analysed by flow cytometry and ELISA. Mitochondrial membrane depolarization was assessed using flow cytometry as well. ELISA was used to evaluate the release of cytochrome c into the cytosol and to assess Fas ligand, p53, tumor necrosis factor α, interleukin IL1-α IL-β, IL-2, IL-4, IL-10, interferon-γ, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor. Caspase-3, -8 and -9 activities were estimated. Expression of BAX and Bcl-2 was assessed by real-time quantitative RT-PCR. DNA fragmentation was detected by single-cell gel electrophoresis. Fas receptors were evaluated by western blotting.', 'After H(2) S incubation, apoptotic levels increased significantly in a time-dependent manner. Mitochondrial membrane depolarization, the release of cytochrome c, p53 and caspase-3, -8 and -9 and DNA fragmentation were all significantly greater. BAX gene activity was upregulated, whereas Bcl-2 remained low. Fas ligand/Fas receptor, tumor necrosis factor α and other cytokines were not increased to a significant degree.'] |
['The prognostic significance of atrial fibrillation (AF) in chronic heart failure (CHF) remains poorly understood.', 'Death and rehospitalizaion for CHF exacerbation for 427 consecutive patients hospitalized from 1996 to 2002 were retrospectively analyzed in relation to cardiac rhythm: sinus rhythm (SR; n=239) or AF (n=188). The AF group was classified according to an Intervention (n=57) or Non-Intervention (n=131) group for defibrillating AF. During the follow-up of 34+/-23 months, there was no significant difference of mortality or morbidity between the SR and AF groups, or between the Intervention and Non-Intervention groups, respectively. However, the Non-Intervention group consisted of 28 patients with paroxysmal AF (PAF), which spontaneously converted to SR during hospitalization, and 103 with chronic AF (CAF). The rehospitalization for CHF exacerbation was significantly higher in PAF than that in CAF and SR (p=0.00005 and 0.002, respectively). Multivariate Cox analysis demonstrated that, PAF, but not CAF, was a predictor of readmission (relative risk 2.30, p=0.004, 95% confidence interval 1.30 to 4.05).'] |
['To test the hypothesis that oxidative stress is increased in patients with rheumatoid arthritis (RA) due to increased inflammation and contributes to the pathogenesis of atherosclerosis.', 'The independent association between urinary F₂-isoprostane excretion, a measure of oxidative stress, and RA was tested using multiple linear regression models in 169 patients with RA and 92 control subjects, frequency matched for age, race, and sex. The relationship between F₂-isoprostane excretion and coronary calcium, a marker of atherosclerosis, was examined in multivariable proportional odds logistic regression models that also assessed the interactions between oxidative stress and low-density lipoprotein and high-density lipoprotein (HDL) cholesterol.', 'F₂-isoprostane excretion was significantly higher in patients with RA (median 2.75 [interquartile range (IQR) 1.60-4.06] ng/mg creatinine) than in control subjects (median 1.86 [IQR 1.25-2.62] ng/mg creatinine; adjusted P = 0.006). In patients with RA, F₂-isoprostanes were positively correlated with body mass index (P < 0.001), but not with disease activity or mediators of inflammation such as the Disease Activity Score in 28 joints or serum tumor necrosis factor α, interleukin-6, and C-reactive protein concentrations in adjusted multivariable models (P > 0.05 for all). In patients with RA, F₂-isoprostanes significantly modified the effect of HDL cholesterol on coronary calcification (P = 0.02 for interaction) after adjustment for age, sex, and race. As F₂-isoprostane levels increased, HDL lost its protective effect against coronary calcification.'] |
['Medline, Embase and the Chinese Biomedical Literature databases were searched with no language restrictions.', 'Studies evaluating the diagnostic efficacy of ultrasonography in detecting TMJ disc displacement in participants with any symptoms or clinical signs related to temporomandibular disorders (TMD), with use of MRI as the gold standard, were included.', 'Study selection, data abstraction and risk of bias assessment were carried out independently by two reviewers. A meta-analysis was conducted.', 'Fifteen studies (14 cohort studies and one case control) were included in this review; six studies had a low risk of bias, six studies an unclear risk and three studies a high risk. Meta-regression indicated that the detected results were not influenced by the types of ultrasonography, image dimensions, types of transducer and ultrasonic image of the disc (P= .05). The Q* values (the point where sensitivity equals specificity on the summary reviewer operator characteristics curve) of ultrasonography for the closed- and open-mouth positions were 0.79 and 0.91, respectively. The diagnostic efficacy of disc displacement with reduction had a sensitivity of 0.76, a specificity of 0.82, a positive likelihood ratio of 3.80, a negative likelihood ratio of 0.36, a diagnostic odds ratio of 10.95, an area under the curve of 0.83 and a Q* of 0.76. The diagnostic efficacy of disc displacement without reduction had a sensitivity of 0.79, a specificity of 0.91, a positive likelihood ratio of 80.5, a negative likelihood ratio of 0.25, diagnostic odds ratio of 36.80, an area under the curve of 0.97 and a Q* of 0.92.'] |
['Hypertension (HTN) is associated with coronary artery calcification (CAC). We hypothesized that preexisting CAC is associated with the development of HTN.', "This study included 483 normotensive subjects (mean age 54 years, 83% males) who underwent a baseline evaluation of their CAC score with ungated dual-section computed tomography during 2001-2002 and returned for at least the first annual follow-up. All subjects underwent an annual examination and were followed for a mean period of 6.6 ± 3.2 years to identify newly developed HTN. Data on the patient's medical history, physical examination and laboratory evaluations were collected.", 'During the follow-up, 104 subjects developed HTN. The rate of newly developed HTN was significantly higher among those with CAC (60 of 223 subjects; 27%) than among those without CAC (44 of 260; 17%) (P < 0.01). The presence of CAC predicted the development of HTN with a hazard ratio of 1.73 (95% confidence interval, 1.17-2.56; P < 0.01). After adjustment for age, sex, body mass index, smoking, baseline systolic blood pressure, and levels of glucose, triglycerides, and low-density lipoprotein cholesterol, the presence of CAC still predicted the development of HTN with a hazard ratio of 1.63 (95% confidence interval, 1.02-2.60; P = 0.04).'] |
['Chromosomes reorganize in early meiotic prophase to form the so-called telomere bouquet. In fission yeast, telomeres localize to the nuclear periphery via interaction of the telomeric protein Rap1 with the membrane protein Bqt4. During meiotic prophase, the meiotic proteins Bqt1-2 bind Rap1 and tether to the spindle pole body to form the bouquet. Although it is known that this polarized chromosomal arrangement plays a crucial role in meiotic progression, the molecular mechanisms of telomere bouquet regulation are poorly understood.', 'Here, we detected high levels of Rap1 phospho-modification throughout meiotic prophase, and identified a maximum of 35 phosphorylation sites. Concomitant phosphomimetic mutation of the modification sites suggests that Rap1 hyper-phosphorylation does not directly regulate telomere bouquet formation or dissociation. Despite the negative charge conferred by its highly phosphorylated state, Rap1 maintains interactions with its binding partners. Interestingly, mutations that change the charge of negatively charged residues within the Bqt1-2 binding site of Rap1 abolished the affinity to the Bqt1-2 complex, suggesting that the intrinsic negative charge of Rap1 is crucial for telomere bouquet formation.'] |
["To evaluate whether socioeconomic status (SES) has a role in obstructive sleep apnea syndrome (OSAS) patients' decision to accept continuous positive airway pressure (CPAP) treatment.", 'Cross-sectional study; patients were recruited between March 2007 and December 2007.', 'University-affiliated sleep laboratory.', '162 consecutive newly diagnosed (polysomnographically) adult OSAS patients who required CPAP underwent attendant titration and a 2-week adaptation period.', '40% (n = 65) of patients who required CPAP therapy accepted this treatment. Patients accepting CPAP were older, had higher apnea-hypopnea index (AHI) and higher income level, and were more likely to sleep in a separate room than patients declining CPAP treatment. More patients who accepted treatment also reported receiving positive information about CPAP treatment from family or friends. Multiple logistic regression (after adjusting for age, body mass index, Epworth Sleepiness Scale, and AHI) revealed that CPAP purchase is determined by: each increased income level category (OR, 95% CI) (2.4; 1.2-4.6), age + 1 year (1.07; 1.01-1.1), AHI ( > or = 35 vs. < 35 events/hr) (4.2, 1.4-12.0), family and/or friends with positive experience of CPAP (2.9, 1.1-7.5), and partner sleeps separately (4.3, 1.4-13.3).'] |
['The parasympathetic nervous system (PNS), via neurotransmitter acetylcholine (ACh), modulates fibrogenesis in animal models. However, the role of ACh in human hepatic fibrogenesis is unclear.', 'We aimed to determine the fibrogenic responses of human hepatic stellate cells (hHSC) to ACh and the relevance of the PNS in hepatic fibrosis in patients with non-alcoholic steatohepatitis (NASH).', 'Primary hHSC were analyzed for synthesis of endogenous ACh and acetylcholinesterase and gene expression of choline acetyltransferase and muscarinic ACh receptors (mAChR). Cell proliferation and fibrogenic markers were analyzed in hHSC exposed to ACh, atropine, mecamylamine, methoctramine, and 4-diphenylacetoxy-N-methylpiperidine methiodide. mAChR expression was analyzed in human NASH scored for fibrosis.', 'We observed that hHSC synthesize ACh and acetylcholinesterase and express choline acetyltransferase and M1-M5 mAChR. We also show that M2 was increased during NASH progression, while both M2 and M3 were found upregulated in activated hHSC. Furthermore, endogenous ACh is required for hHSC basal growth. Exogenous ACh resulted in hHSC hyperproliferation via mAChR and phosphoinositide 3-kinase and Mitogen-activated protein kinase kinase (MEK) signaling pathways, as well as increased fibrogenic markers.'] |
['Subjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis.', 'We studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder).', 'In patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis.'] |
['Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. Here we addressed the impact of epigenetic alterations and cellular context on functional and transcriptional reprogramming of hepatocellular carcinoma (HCC) cells. Our strategy employed a 3-day treatment of established and primary human HCC-derived cell lines grown as a monolayer at various cell densities with the DNMT1 inhibitor zebularine (ZEB) followed by a 3D culture to identify cells endowed with self-renewal potential. Differences in self-renewal, gene expression, tumorigenicity, and metastatic potential of spheres at generations G1-G5 were examined. Transient ZEB exposure produced differential cell density-dependent responses. In cells grown at low density, ZEB caused a remarkable increase in self-renewal and tumorigenicity associated with long-lasting gene expression changes characterized by a stable overexpression of cancer stem cell-related and key epithelial-mesenchymal transition genes. These effects persisted after restoration of DNMT1 expression. In contrast, at high cell density, ZEB caused a gradual decrease in self-renewal and tumorigenicty, and up-regulation of apoptosis- and differentiation-related genes. A permanent reduction of DNMT1 protein using short hairpin RNA (shRNA)-mediated DNMT1 silencing rendered HCC cells insensitive both to cell density and ZEB effects. Similarly, WRL68 and HepG2 hepatoblastoma cells expressing low DNMT1 basal levels also possessed a high self-renewal, irrespective of cell density or ZEB exposure. Spheres formed by low-density cells treated with ZEB or shDNMT1 displayed a high molecular similarity which was sustained through consecutive generations, confirming the essential role of DNMT1 depletion in the enhancement of cancer stem cell properties.'] |
['Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, the main pharmacologically active component of Salvia miltiorrhiza. The aim of this study was to investigate the effect of STS on concanavalin A (ConA)-induced hepatitis (CIH) in mice, an experimental model of immune-mediated liver injury.', 'C57BL/6 mice pretreated with STS released much less alanine transaminase into plasma in response to ConA challenge and had reduced inflammatory infiltration and hepatocyte apoptosis in the liver compared with control mice pretreated with vehicle solutions. Thus, STS protected mice from CIH. In STS-pretreated mice induced with CIH, we found abrogated tumor necrosis factor-alpha and interferon (IFN)-gamma production. Moreover, mRNA expressions of IFN-inducible protein-10 and macrophage inflammatory protein-1alpha in these mice were decreased. The mechanism of anti-inflammatory effects of STS may be attributed to its modulation of crucial inflammatory signaling pathways, including NF-kappaB and IFN-gamma/STAT1.'] |
['Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. It is unknown whether renal tight junction (TJ) proteins expression and localization are modified in CP-induced nephrotoxicity.', 'To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity.', 'Male Wistar rats (n\u2009=\u20095/group) were injected with saline solution (V group), and the other group (CP group) was injected with a single dose of saline solution and CP (7.5\u2009mg/kg i.p.). Rats were sacrificed 72\u2009h after CP injection and blood, and 24-h urine samples were collected. Several plasma and urinary injury biomarkers as well as renal histopathology lesions, oxidative and nitrosative stress markers were evaluated, and protein levels of ocludin, claudin-2, claudin-5, ZO-1 were measured by Western blot. Statistically significant changes noted with different p\u2009<\u20090.05 versus V.', 'Nephrotoxicity was evident by histological alterations, glycosuria, decrease in creatinine clearance, increase in fractional excretion of sodium, serum creatinine and kidney injury molecule-1. These changes were associated with oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and protein kinase Cβ2 and decreased renal expression of nuclear factor-erythroid-2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it was found that CP-induced renal damage was associated with decreased renal expression of occludin and claudin-2.'] |
['To assess the effect of preoperative high dose methylprednisolone on stress response and outcome.', 'Randomised, placebo-controlled, double-blind study.', 'University hospital, Germany.', '20 patients listed for abdominal surgery of whom 10 had major intra-abdominal interventions and 10 had incisional hernias repaired.', 'Methylprednisolone 30 mg/kg (100 ml) was given by slow intravenous infusion 90-60 minutes before operation. The control group received the same volume of sodium chloride.', 'Speed of convalescence, degree of fatigue, amount of pain, consumption of analgesics, breathing capacity, and hospital stay, as well as humoral and cellular mediators of the stress response.', 'Methylprednisolone significantly improved criteria of postoperative recovery, fatigue by 47%, (day 1), convalescence by about 45% (days 1-3), and breathing capacity (FEV1) between 47% and 29% (days 5, 7) (p < 0.05, ANOVA), and led to a significant reduction of median hospital stay of 4.5 days. C-reactive protein concentration was significantly decreased (by 46% on day 3) and T-cell activation was suppressed (day 1).'] |
['To determine whether the receptor for advanced glycation end-products (RAGE) plays a role in early brain injury from intracerebral hemorrhage (ICH), RAGE expression and activation after injury were examined in a rat model of ICH with or without administration of a RAGE-specific antagonist (FPS-ZM1).', 'Autologous arterial blood was injected into the basal ganglia of rats to induce ICH. The motor function of the rats was examined, and water content was detected after euthanization. Blood-brain barrier permeability was determined by Evans blue staining and colloidal gold nanoparticle tracers. Nerve fiber injury in white matter was determined by diffusion tensor imaging analysis, and the expression of target genes was analyzed by Western blotting and quantitative reverse transcription polymerase chain reaction. FPS-ZM1 was administered by intraperitoneal injection.', 'Expression of RAGE and its ligand high-mobility group protein B1 were increased at 12 hours after ICH, along with blood-brain barrier permeability and perihematomal nerve fiber injury. RAGE and nuclear factor-κB p65 upregulation were also observed when FeCl2 was infused into the basal ganglia at 24 hours. FPS-ZM1 administration resulted in significant improvements of blood-brain barrier damage, brain edema, motor dysfunction, and nerve fiber injury, and the expression of RAGE, nuclear factor-κB p65, proinflammatory mediators interleukin 1β, interleukin-6, interleukin-8R, cyclooxygenase-2, inducible nitric oxide synthase, and matrix metallopeptidase-9 was attenuated. Moreover, decreases in claudin-5 and occludin expression were partially recovered. FPS-ZM1 also reversed FeCl2-induced RAGE and nuclear factor-κB p65 upregulation.'] |
['Acetaminophen (APAP) overdose is a frequent cause of drug-induced liver injury and the most frequent cause of acute liver failure in the Western world. Previous studies with mouse models have revealed that impairment of mitochondrial respiration is an early event in the pathogenesis, but the exact mechanisms have remained unclear, and therapeutic approaches to specifically target mitochondria have been insufficiently explored. Here, we found that the reactive oxidative metabolite of APAP, N-acetyl-p-benzoquinoneimine (NAPQI), caused the selective inhibition of mitochondrial complex II activity by >90% in both mouse hepatic mitochondria and yeast-derived complexes reconstituted into nanoscale model membranes, as well as the decrease of succinate-driven adenosine triphosphate (ATP) biosynthesis rates. Based on these findings, we hypothesized that methylene blue (MB), a mitochondria-permeant redox-active compound that can act as an alternative electron carrier, protects against APAP-induced hepatocyte injury. We found that MB (<3 µM) readily accepted electrons from NAPQI-altered, succinate-energized complex II and transferred them to cytochrome c, restoring ATP biosynthesis rates. In cultured mouse hepatocytes, MB prevented the mitochondrial permeability transition and loss of intracellular ATP without interfering with APAP bioactivation. In male C57BL/6J mice treated with APAP (450 mg/kg, intraperitoneally [IP]), MB (10 mg/kg, IP, administered 90 minutes post-APAP) protected against hepatotoxicity, whereas mice treated with APAP alone developed massive centrilobular necrosis and increased serum alanine aminotransferase activity. APAP treatment inhibited complex II activity ex vivo, but did not alter the protein expression levels of subunits SdhA or SdhC after 4 hours.'] |
["Data regarding the prevalence and types of drug-related problems (DRPs) among neurology inpatients is sparse. The objective of this study was to characterise the types of DRPs seen among neurology inpatients and furthermore to study factors affecting the acceptance of clinical pharmacologists' and pharmacists' recommendations for improving drug safety.", "1,263 consecutive inpatient cases in a Swiss university hospital neurology unit were assessed for the presence of DRPs over 12 months. Treating neurologists' acceptance of the resulting recommendations was also recorded. Primary outcome measures were types of DRP, recommendations made by clinical pharmacologists and number of recommendations accepted. Factors potentially associated with acceptance were studied using univariate and multivariate generalised estimating equation modelling.", 'Twenty-nine percent of cases demonstrated one or more DRPs. DRPs were the cause of admission in 10 cases (0.8%). In\xa0total 494 DRPs were identified and 467 recommendations given, of which 62% were accepted. Factors associated with an increased likelihood of acceptance were prescriptions involving regularly administered drugs (odds ratio [OR] 2.57 95% confidence interval [CI] 1.73-3.80), adverse drug events (OR 2.5; 95% CI 1.29-5.06), known drug side-effect (OR 1.85; 95% CI 1.06-3.22), high-risk drug-drug interactions (OR 3.22; 95% CI 1.07-9.69) and interventions involving changing a drug (OR 2.71; 95% CI 1.17-6.25).'] |
['Decreased total antioxidant capacity (TAC) has been reported in different neoplasms, including lung cancer. However, no study concerning the relationship between endogenous antioxidants, lifestyle factors, and TAC has been conducted among lung cancer patients. The purpose of the study was to investigate the associations between endogenous antioxidants, severity of disease, lifestyle factors, and TAC in lung cancer patients.', "The study was conducted among 59 lung cancer patients. The levels of total antioxidant status (ATBS method), endogenous antioxidants, and C-reactive protein were measured in patients' sera automatically. Dietary habits of the subjects were evaluated based on the Food Frequency Questionnaire (FFQ) on the day of admission to hospital.", 'We found a positive correlation between serum albumin, uric acid (UA), and TAC and a negative correlation between CRP and TAC. Moreover, TAC was significantly positively associated with disease stage. We did not find any significant relationship between the frequency of selected food consumption and TAC in lung cancer patients, except for a positive correlation between the frequency of refined cereal products consumption and TAC level. Smoking status did not correlate with TAC.'] |
['Pre-operative electrocardiographic (ECG) screening before subcutaneous implantable cardioverter-defibrillator (SICD) implantation is essential to prevent T-wave oversensing and inappropriate shocks. The failure rate of ECG screening was reported to be up to 8% when only two body positions were tested.', 'Three subcutaneous ECG vectors represented by lead I, II and III were obtained in standing, supine, sitting and squatting positions. A patient qualified if the ECG in any same lead passed in all four positions. We report a 31-year-old man with idiopathic ventricular fibrillation who failed ECG screening for SICD implantation with the conventional left parasternal electrode (LPS) configuration in all three subcutaneous ECG vectors. Right parasternal electrode (RPS) configuration with left arm and right arm ECG electrodes positioned 1cm lateral to right sternal border was attempted for screening.', 'The amplitude of the QRS complex was significantly larger in the RPS compared to the LPS configuration in lead III and the patient passed the ECG screening in four body positions. He underwent successful SICD implantation with RPS approach with appropriate sensing both during the procedure and exercise treadmill test four weeks later. Ventricular fibrillation was successfully converted with 65J standard polarity shock during the procedure and no ICD shock was experienced by the patient on six-month follow-up.'] |
['Platelet-derived growth factor (PDGF)-B regulates mesangial cell and vessel development during embryogenesis, and contributes to the pathogenesis of adult renal and vascular diseases. Endothelial cell PDGF-B exerts paracrine effects on mesangial cells, but its regulation is not well defined. We examined the impact of hypoxia on PDGF-B-mediated interactions between glomerular endothelial and mesangial cells, a condition of potential relevance in developing, and diseased adult, kidneys.', 'Glomerular endothelial or mesangial cells were subjected to hypoxia and responses compared to normoxic cells. Endothelial PDGF-B was studied by Northern and Western analysis. Mesangial proliferative responses to PDGF-B were assessed by (3)H-thymidine incorporation, and migration by a modified Boyden chamber assay. Hypoxia-induced changes in receptor specific binding capacity were studied by saturation binding assays.', 'Hypoxia stimulated increases in endothelial PDGF-B mRNA and protein. In normoxic mesangial cells, PDGF-B stimulated dose-dependent proliferation, but the proliferative response of hypoxic cells was two to three times greater. Exogenous PDGF-B also caused prompter migration in hypoxic mesangial cells. Mesangial cells were treated with endothelial cell-conditioned medium. More cells migrated when hypoxic cells were stimulated with hypoxic conditioned medium, than when normoxic cells were stimulated with normoxic conditioned medium. Preincubating conditioned medium with PDGF-B neutralizing antibody greatly decreased the chemoattractant activity. Binding studies demonstrated increased specific binding capacity in hypoxic cells.'] |
['Fifteen percent to 20% of human neuroblastomas show amplification of the MYCN oncogene physiologically located at chromosome 2p24-25, indicating an aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively. We now asked if the amplicon structure is an invariable attribute of an individual tumor or if the coamplification pattern could change during progress or in case of recurrent disease.', 'We used a previously described multiplex PCR approach to analyze the coamplification status of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of initial diagnosis and in consecutive tissue specimens at later time points after initial treatment or from relapsing disease. The MYCN copy number per haploid genome (Mcn/hg) in these specimens was determined in a separate duplex PCR.', 'In 32 of the 33 investigated tumors, the amplicon structure showed no changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a decrease after initial treatment (n = 23), whereas we found a significant increase in recurrent disease (n = 10).'] |
['Macrophage inhibitory cytokine-1 (MIC-1) belongs to the bone morphogenic protein/transforming growth factor-beta (BMP/TGF-beta) superfamily. Serum MIC-1 concentrations are elevated in patients with advanced prostate cancer. The effects of MIC-1 on prostate cancer bone metastases are unknown.', 'In vitro effects of MIC-1 on osteoblast differentiation and activity were analyzed with alkaline phosphatase and mineralization assays; osteoclast numbers were counted microscopically. MIC-1 effects on TLR9 expression were studied with Western blotting. Human Du-145 prostate cancer cells were stably transfected with a cDNA encoding for mature MIC-1 or with an empty vector. The in vivo growth characteristics of the characterized cells were studied with the intra-tibial model of bone metastasis. Tumor associated bone changes were viewed with X-rays, histology, and histomorphometry. Bone formation was assayed by measuring serum PINP.', 'MIC-1 induced osteoblast differentiation and activity and osteoclast formation in vitro. These effects were independent of TLR9 expression, which was promoted by MIC-1. Both MIC-1 and control tumors induced mixed sclerotic/lytic bone lesions, but MIC-1 increased the osteolytic component of tumors. Osteoclast formation at the tumor-bone interface was significantly higher in the MIC-1 tumors, whereas bone formation was significantly higher in the control mice. At sacrifice, the mice bearing MIC-1 tumors were significantly lighter with significantly smaller tumors.'] |
['Several studies have associated depressive symptoms with an increased risk for cardiac events after the onset of acute myocardial infarction (AMI). The aim of the present study is to investigate the impact of the depressive symptoms on prognosis of the elderly patients with AMI.', 'Depression was assessed in consecutive patients with AMI (n = 1042; mean age 63 +/- 11 years) using the Zung Self-Rating Depression Scale (SDS). Patient with a score > or = 40 was classified as having depressive symptoms. Cardiac events (cardiac death, nonfatal re-MI, coronary angioplasty or bypass surgery, readmission for heart failure, unstable angina, or uncontrolled arrhythmia) were examined during 12 months follow-up period.', 'Depressive symptoms were observed in 438 patients (42.0%). Prevalence of depression was not dependent of age (P = 0.60) and gender (P = 0.91). The rate of cardiac events was 31.2% per year in patients with depressive symptoms whereas 23.9% per year in patients without depressive symptoms. Multiple logistic regression analyses showed that depression was significantly associated with 1-year cardiac events (odds ratio 1.41, 95% CI 1.03 to 1.92, P = 0.03) after controlling for age, gender, severity of myocardial infarction, coronary risk factors, e.g. hypertension, diabetes mellitus and smoking habits. Depression was a significant risk factor for the cardiac events (log rank, P = 0.02) in the elderly patients (> or = 65 years old, 501 patients). However, the association of depression with cardiac events in the young patients (< 65 years old, 541 patients) was not statistically significant (P = 0.11).'] |
['In patients with eosinophilic esophagitis (EoE), eosinophils accumulate and release granule proteins onto esophageal epithelium. However, little is understood about the mechanism of eosinophil degranulation.', 'To determine and quantify eosinophil degranulation patterns, we studied esophageal biopsy specimens from both the proximal and distal esophagi of 9 randomly selected patients with EoE.', 'The specimens were fixed in glutaraldehyde, embedded, sectioned, and imaged by means of transmission electron microscopy. Eosinophils and their granules were identified by their distinctive morphology, and all eosinophils and granules were imaged. A total of 1672 images from 18 esophageal specimens were evaluated and graded. Eosinophils were categorized based on membrane integrity and by cytoplasmic vesiculation as evidence of piecemeal degranulation. Granules were categorized based on reversal of staining (eosinophil granule core lightening) and localization within and outside the cells.', 'The results revealed that greater than 98% of eosinophils infiltrating the esophagus in patients with EoE demonstrate morphologic abnormalities ranging from granule changes with reversal of staining to marked cytoplasmic vesiculation to loss of cellular membrane integrity with cytolytic disruption and release of intact membrane-bound granules into the tissues. Approximately 81% of eosinophils showed membrane disruption. Extracellular granules were abundant in at least 70% of the images, and approximately 50% of these granules showed reversal of staining. On the basis of the prominence of tubulovesicular development, piecemeal degranulation appears closely related to the other morphologic changes seen in patients with EoE.'] |
['Laparoscopic surgery usually requires a pneumoperitoneum by insufflating the abdominal cavity with carbon dioxide (CO2). Increased intraabdominal pressure causes diaphragmatic displacement resulting in compressed lung areas, which leads to formation of atelectasis, especially during mechanical ventilation. Application of positive end-expiratory pressure (PEEP) can maintain pulmonary gas exchange. The objective of this study was to investigate the effect of abdominal gas insufflation on arterial oxygenation during mechanical ventilation with and without PEEP in rats.', 'In experiment 1, two groups of six rats were continuously insufflated with CO2 at 12 mmHg for 180 min. Group 1 was ventilated with 8 cm H2O PEEP and group 2 had 0 cm H2O PEEP. Group 3 served as a control. This group had abdominal wall lifting and was ventilated with 0 cmH2O PEEP. In experiment 2, two groups of six rats had abdominal CO2 insufflation and were ventilated with or without PEEP during 180 min (group 4 and 5). In this experiment, abdomens were desufflated in both groups for 5 min at 60 and 120 min. Blood pressure monitoring and measurement of arterial pO2 was performed by placement of an indwelling carotid artery catheter in both experiments.', 'In both experiments, paO2 values decreased significantly in insufflation groups that were ventilated with 0 cmH2O PEEP (groups 2 and 5). Insufflation groups ventilated with 8 cmH2O PEEP had paO2 values comparable to these of control group. There were no significant differences in mean arterial pressure between insufflation groups ventilated with or without PEEP.'] |
['Cerebral hyperperfusion syndrome after carotid endarterectomy (CEA) is a rare but potentially devastating complication. The purpose of the present study, which was not a randomized controlled trial but a case cohort study with historical control, was to determine whether pretreatment with a novel free radical scavenger, edaravone, could prevent occurrence of cerebral hyperperfusion after CEA.', 'Fifty patients with ipsilateral internal carotid artery stenosis (>/=70%) underwent CEA with administration of edaravone before internal carotid artery clamping. Preoperative cerebral blood flow and cerebrovascular reactivity (CVR) to acetazolamide were assessed with single-photon emission computed tomography (SPECT). Cerebral blood flow also was measured immediately after CEA and on the 3rd postoperative day.', 'Cerebral hyperperfusion (cerebral blood flow increase >/=100% compared with preoperative values) was revealed by SPECT performed immediately after CEA in only one patient (2%), who also exhibited reduced preoperative CVR. The incidence of post-CEA hyperperfusion as revealed by SPECT in the control group (51 CEA patients without administration of edaravone) was significantly higher (16%) (P = 0.0310, control versus treatment group). In addition, in a subgroup of patients with reduced preoperative CVR, the incidence of post-CEA hyperperfusion as revealed by SPECT in the edaravone group (7%) was significantly lower than that in the control group (67%) (P = 0.0029). Logistic regression analysis demonstrated that reduced preoperative CVR and absence of pretreatment with edaravone were significant independent predictors of post-CEA hyperperfusion as revealed by SPECT.'] |
['This study assessed the role of adrenergic signal transmission in the control of renal erythropoietin (EPO) production in humans.', 'Forty-six healthy male volunteers underwent a hemorrhage of 750 ml. After phlebotomy, they received (intravenously for 6 hours in a parallel, randomized, placebo-controlled and single-blind design) either placebo (0.9% sodium chloride), or the beta 2-adrenergic receptor agonist fenoterol (1.5 microgram/min), or the beta 1-adrenergic receptor agonist dobutamine (5 micrograms/kg/min), or the nonselective beta-adrenergic receptor antagonist propranolol (loading dose of 0.14 mg/kg over 20 minutes, followed by 0.63 micrograms/kg/min).', 'The AUCEPO(0-48 hr)fenoterol was 37% higher (p < 0.03) than AUCEPO(0-48 hr)placebo, whereas AUCEPO(0-48 hr)dobutamine and AUCEPO(0-48 hr)propranolol were comparable with placebo. Creatinine clearance was significantly increased during dobutamine treatment. Urinary cyclic adenosine monophosphate excretion was increased only by fenoterol treatment, whereas serum potassium levels were decreased. Plasma renin activity was significantly increased during dobutamine and fenoterol infusion.'] |
['Conventional electrocardiogram (ECG)-based diagnosis of left bundle branch block (LBBB) in patients with left ventricular hypertrophy (LVH) is ambiguous. Left ventricular hypertrophy is often seen in patients with severe aortic stenosis in which a transcatheter aortic valve implantation (TAVI) frequently results in a LBBB due to the mechanical interaction of the artificial valve and the conduction system. In this feasibility study, we propose and evaluate the sensitivity of a new electrocardiographic imaging tool; the cardiac isochrone positioning system (CIPS), visualizing the cardiac activation to detect interventricular conduction patterns pre- and post-TAVI.', 'The CIPS translates standard 12-lead ECG into ventricular isochrones, representing the activation sequence. It requires a patient-specific model integrating heart, lungs, and other thoracic structures derived from multi-slice computed tomography. The fastest route-based algorithm was used to estimate the activation isochrones and the results were compared with standard ECG analysis. In 10 patients the CIPS was used to analyse 20 ECGs, 10 pre- and 10 post-TAVI. In 11 cases the CIPS results were in agreement with the ECG-based diagnosis. In two cases there was partial agreement and in seven cases there was disagreement. In four of these cases, the clinical history of the patients favoured interpretation as assessed by CIPS, for the remaining three, it is unknown which method correctly classified the activation.'] |
['FUS (TLS) and EWS (EWSR1) belong to the FET-protein family of RNA and DNA binding proteins. FUS and EWS are structurally and functionally related and participate in transcriptional regulation and RNA processing. FUS and EWS are identified in translocation generated cancer fusion proteins and involved in the human neurological diseases amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.', 'To determine the gene regulatory functions of FUS and EWS at the level of chromatin, we have performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Our results show that FUS and EWS bind to a subset of actively transcribed genes, that binding often is downstream the poly(A)-signal, and that binding overlaps with RNA polymerase II. Functional examinations of selected target genes identified that FUS and EWS can regulate gene expression at different levels. Gene Ontology analyses showed that FUS and EWS target genes preferentially encode proteins involved in regulatory processes at the RNA level.'] |
['To assess the use of antihypertensive drugs and blood pressure (BP) levels in relation to current guidelines for BP control in patients with chronic renal failure (CRF).', 'A cross-sectional survey was carried out in six renal outpatient clinics in Oslo and the surrounding area. The hospital records of all renal patients not yet in need of renal replacement therapy and with serum creatinine>or=200 micromol/l who attended consultations with nephrologists regularly (at least every third month) were reviewed.', 'Of the 351 patients, 97% had hypertension. the majority of patients (96%) were receiving antihypertensive therapy. The average number of antihypertensive drugs being taken was 2.7+/-1.3 (median 3), but it varied with the cause of CRF. The drugs most frequently prescribed as monotherapy were angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, which were used by 32%; 51% of patients were using three or more antihypertensive drugs. Loop diuretics were prescribed as monotherapy in 25% of cases and in combination with two or more other drugs in 87%. Age and serum creatinine levels influenced the choice of antihypertensive therapy. The target BP of <130/80 mmHg was obtained in 13% of patients, and lack of optimal BP control was mainly due to systolic hypertension. A total of 38% of patients had a BP of <140/90 mmHg, while 58% failed to achieve a systolic BP of <140 mmHg.'] |
['The development of target-specific local anesthetic blocks has enabled pain physicians to explore the anatomical source of chronic spinal pain. However, such blocks rely on subjective responses and may be subject to the placebo effect. Comparative local anesthetic blocks have been advocated as a means of identifying true-positive cases and excluding placebo responders. This paradigm employs two local anesthetics with different durations of action; only patients who obtain reproducible relief and correctly identify the longer-acting agent are considered positive.', 'Our objective was to evaluate the reliability of comparative blocks of the medial branches of the cervical dorsal rami in the diagnosis of cervical zygapophysial joint pain.', 'We compared comparative blocks and the criterion-standard of randomized, double-blind, placebo-controlled blocks.', 'The study was conducted at a tertiary referral center.', "We studied the first 50 consecutive patients referred for assessment of chronic neck pain (> 3 months' duration) after a motor vehicle accident, who completed a series of placebo-controlled blocks after an initial positive response. Patients were 41 +/- 11 years (mean +/- SD) old with a male/female ratio of 1:2.", 'Patients underwent three blocks using three different agents-lignocaine, bupivacaine, and normal saline--administered on separate occasions, in random order and under double-blind conditions. The diagnostic decision based on comparative blocks alone was compared with that based on placebo-controlled blocks.', 'Comparative blocks were found to have a specificity of 88%, but only marginal sensitivity (54%). Although comparative blocks result in few false-positive diagnoses, their liability is that they result in a high proportion of false-negative diagnoses. Expanding the comparative blocks diagnostic criteria to include all patients with reproducible relief, irrespective of duration, increases sensitivity to 100% but lowers specificity to 65%.'] |
['To determine whether the nucleic acid amplification (NAA) test on specimens collected by bronchoscopy improves the diagnostic accuracy of pulmonary tuberculosis (PTB) in sputum-negative patients.', 'Bronchoscopy was performed among smear-negative PTB suspects to collect respiratory specimens to assess the efficacy and accuracy of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test in the diagnosis of PTB.', 'In 105 PTB suspects, 80 were finally excluded, of whom two were false-AMTD-positive. PTB (n = 25) was diagnosed in 10 patients culture-positive for Mycobacterium Tuberculosis (7/105 bronchial wash/bronchoalveolar lavage [BW/BAL] specimens, 6/315 expectorated sputum specimens [2 positive in 2 patients; 1 positive in 2 patients], and one with both), and in 15 patients with improvement after anti-tuberculosis treatment. Among the 25 PTB patients, 20 were AMTD-positive, of whom four were culture-positive. Three AMTD-negative patients were culture-positive. The sensitivity and specificity of AMTD were respectively 80.0% and 97.5%. The diagnostic yield was higher in respiratory specimens obtained at bronchoscopy and measured by AMTD than in conventional sputum or BW/BAL culture.'] |
['Venous thromboembolic disease (VTD) is a recently recognized complication of thalidomide in combination therapy for patients with multiple myeloma (MM). The authors assessed the frequency of VTD and its risk factors in 612 consecutive patients with plasma cell dyscrasia (PCD) who were evaluated and followed from 1991 to 2001.', 'In the current study, 404 patients were diagnosed with multiple myeloma (MM), 174 with monoclonal gammopathy of undetermined significance (MGUS), and 34 with other forms (excluding amyloidosis). Univariable correlates of VTD were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis.', 'The authors identified several univariable correlates of VTD in patients with MGUS, including a family and medical history of VTD, immobility, low serum albumin level, and high leukocyte count. Patients with MGUS with immunoglobulin (Ig) G monoclonal immunoglobulin were found to be less prone to develop VTD. In patients with MM, a family and medical history of VTD and the presence of a hypercoagulable state were factors identified in univariable analysis to be associated with an increased risk of VTD. In patients with MM, for each unit increase in serum albumin, the risk of VTD was lower. The type of the treatment regimen did not appear to correlate with the development of VTD.'] |
['Infantile hemangiomas (IHs) are the most common tumor of infancy, yet there are no Food and Drug Administration-approved therapeutics to date. Recently, the nonselective β-adrenergic-blocker propranolol has been shown to be a safe and effective means of treating IHs, although its mechanism has yet to be elucidated. We have previously demonstrated that propranolol induces early and incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize that propranolol promotes dysregulated adipogenesis via the improper regulation of adipogenic genes.', 'Hemangioma stem cells (HemSCs) isolated from resected IH specimens were treated with adipogenic medium for 1 or 4 days in either propranolol or vehicle. Cell death was measured by the incorporation of annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by visualizing lipid droplet formation by Oil Red O staining. Proadipogenic genes C/EBPα, C/EBPβ, C/EBPδ, PPARδ, PPARγ, RXRα, and RXRγ were analyzed by quantitative reverse transcription and polymerase chain reaction.', 'Hemangioma stem cells treated with propranolol increased lipid droplet formation compared to vehicle-treated cells indicating increased adipogenesis. Cell death as measured by FACS analysis indicated that the propranolol-treated cells died due to necrosis and not apoptosis. During adipogenesis, transcript levels of PPARδ, PPARγ, C/EBPβ, and C/EBPδ were significantly increased (P<0.01) in propranolol-treated cells relative to control cells. In contrast, RXRα and RXRγ levels were significantly decreased (P<0.05), and C/EBPα, a gene required for terminal adipocyte differentiation, was strongly suppressed by propranolol when compared to vehicle-treated cells (P<0.01).'] |
['The consensus statements for eosinophilic oesophagitis recommend that ambulatory pH monitoring is one means of determining if gastro-oesophageal reflux is the cause of oesophageal eosinophilia and should guide pharmacological therapy.', 'To evaluate prospectively the accuracy of pH monitoring as a predictor of endoscopic, histological and symptomatic response in patients with oesophageal eosinophilia.', 'We conducted a prospective trial in which patients with oesophageal eosinophilic infiltration with ≥15 eos/hpf underwent a 24-h pH study and were placed in one of two treatment arms for 6 weeks based on positive or negative results. Patients with abnormal acid exposure were treated with esomeprazole 40 mg twice daily and others were treated with oral viscous budesonide 1 g twice daily. Response to treatment was assessed by oesophageal histology (<5 eos/hpf) and symptoms.', 'A total of 51 patients were enrolled in the study. The average patient age was 39 years and 31 patients (61%) were male. The average number of eosinophils per hpf, prior to study enrolment was 41.2 (range 15-140, s.d. 27.7). Nineteen (37%) had positive pH studies and 32 (63%) had negative pH studies. Eighteen patients completed treatment with esomeprazole. Only eleven (61%) had histological response and, of these eleven, five (46%) had symptomatic improvement. A total of 28 patients with normal acid exposure completed treatment with budesonide. Only 16 (57%) had histological and 11 (69%) had symptomatic improvement.'] |
['To investigate the relation between patient survival and incrementally increasing percentages of fluorescence in situ hybridization-determined complete loss of chromosome 3 (monosomy 3) and gain of chromosome 8q in primary uveal melanoma cells.', 'Clinicopathological factors were related to disease-free survival. Fluorescence in situ hybridization was performed using probes on chromosomes 1, 3, 6, and 8. The percentages of UM cells with monosomy 3 or chromosome 8q gain were classified in groups with incrementally increasing percentages and related to disease-free survival. Correlations between clinical factors and cytogenetic aberrations were also analyzed.', 'Two-hundred twenty choroidal and ciliary body melanomas were analyzed. The following proved to be significant predictors of survival in univariate analysis: older patient age (P = 0.003); large tumor diameter (P < 0.001); mixed cell type (P = 0.001); presence of closed microvascular loops (P < 0.001); loss of chromosome 1p (P = 0.006); monosomy 3 (P < 0.001); gain of 6p (P < 0.001); and gain of chromosome 8q (P < 0.001). Multivariate Cox analysis displayed monosomy 3 (Hazard ratio [HR] 2.83, P = 0.002) and gain of chromosome 8q (HR 3.13, P = 0.002) as the most important independent prognostic factors of poor survival, followed by older patient age (HR 1.02, P = 0.017). Increasing percentages of monosomy 3 and gain of chromosome 8q in tumor cells showed a correlation with worse prognosis (Log-rank test 49.9 and 40.4, both P < 0.001) and increased number of additional copies of 8q correlated with shorter disease-free interval (Log-rank test 45.7, P < 0.001).'] |
['Blockade of the mineralocorticoid receptor (MR) in patients with chronic kidney disease (CKD) improves surrogate cardiovascular outcomes, such as left ventricular mass. Animal models of renal disease support a pathological role of mineralocorticoids, in the context of a high sodium intake. We aimed to assess the regulation of mineralocorticoid biosynthesis in patients with CKD.', 'Seventy patients with CKD stages 3/4 and 30 patients with essential hypertension (EH) were recruited. Patients underwent detailed clinical phenotyping, drug history and biochemical assessment. Patients completed a 24-h urine collection for measurement of urinary tetrahydroaldosterone (THALDO) and tetrahydrocorticosterone (THDOC) excretion rates (measured using gas chromatography-mass spectrometry) and urinary electrolytes. The factors which correlated significantly with THALDO and THDOC excretion were entered into linear regression models.', 'Patients with EH and CKD were well matched with no significant differences in gender, age or weight. The mean estimated glomerular filtration rate (eGFR) in CKD patients was 38.6/min/1.73 m(2). The mean urinary excretion rates of THALDO, THDOC and 24-h urinary sodium (24-h USod) were not significantly different between CKD and EH patients. The level of renal function did not correlate with THALDO or THDOC excretion. In patients with CKD, 24-h USodium (r = 0.614, P < 0.001) and 24-h UPotassium (r = 0.538, P < 0.001) were positively correlated with THALDO excretion. On multivariate linear regression analysis, 24-h USod was the strongest independent predictor (P = 0.004) of THALDO and THDOC excretion in CKD. In patients with EH, no relationship was seen between mineralocorticoid excretion and 24-h urinary sodium excretion.'] |
['To examine factors related to long-term psychological functioning in political ex-prisoners who had been subjected to systematic torture.', 'The psychological status of 55 tortured political activists, 55 nontortured political activists, and 55 subjects with no history of torture or political activism was assessed using Structured Clinical Interview for DSM-III for psychiatric assessment, Semi-structured Interview for Survivors of Torture, and other self-rated and assessor-rated measures of anxiety, depression, and posttraumatic stress disorder (PTSD). Correlational and multiple regression analyses were used to assess the independent effects of precaptivity, captivity, and postcaptivity variables as predictors of long-term psychological status among the torture survivors.', 'Istanbul, Turkey.', 'Number of lifetime and current PTSD symptoms, and scores on the Beck Depression Inventory, Hamilton Depression Rating, Hamilton Anxiety Scale, and State-Trait Anxiety Inventory.', 'Effect of captivity experience on various life areas (eg, family and social, economic, and employment status) and other postcaptivity psychosocial stressors were associated with PTSD symptoms, anxiety, and depression. Perceived severity of torture was related to PTSD symptoms but not to anxiety or depression. Lack of social support predicted anxiety and depression but not PTSD. Family history of psychiatric illness correlated with higher scores on most measures. Impact of captivity experience on family was the strongest predictor of PTSD symptoms.'] |
['The US Environmental Protection Agency voluntary phased-out residential use of chlorpyrifos in 2001. In contrast, in Costa Rica, chlorpyrifos-treated bags are increasingly used to protect banana and plantain fruits from insects and to fulfill product standards, even in populated areas.', "To evaluate children's exposure to chlorpyrifos in villages situated nearby banana plantations and plantain farms in Costa Rica.", 'The study targeted two villages with use of chlorpyrifos-treated bags in nearby banana plantations and plantain farms and one village with mainly organic production. For 140 children from these villages, mostly indigenous Ngäbe and Bribri, parent-interviews and urine samples (n=207) were obtained. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) levels were measured as a biomarker for chlorpyrifos exposure. In the banana and plantain village also environmental contamination to chlorpyrifos was explored.', 'Children from the banana and plantain villages had statistically significant higher urinary TCPy concentrations than children from the referent village; 2.6 and 2.2 versus 1.3μg/g creatinine, respectively. Chlorpyrifos was detected in 30% of the environmental samples as well as in 92% of the hand/foot wash samples. For more than half of the children their estimated intake exceeded the US EPA chronic population adjusted dose. For some, the acute population adjusted dose and the chronic reference dose were also exceeded.'] |
['Cognitive impairment is a common finding in end-stage renal disease patients on chronic hemodialysis, but data on the associated factors are still scanty.', 'The present study evaluated the association between cognitive function and left ventricular systolic function in hemodialysis patients.', 'We enrolled 72 patients admitted to the Hemodialysis Unit of the Catholic University, Rome. Cognitive performance was evaluated using the Mini Mental State Examination (MMSE); a cutoff of 24 was used to diagnose cognitive impairment. Left ventricular ejection fraction (LVEF) was assessed by echocardiography. Multivariable linear and logistic regressions were adopted to assess the adjusted association between cognitive performance and LVEF. Also, linear discriminant analysis was performed to ascertain the cutoff level of LVEF which best predicted cognitive impairment.', 'Cognitive impairment was found in 37 (51 %) patients. According to linear regression, MMSE was independently associated with LVEF (B = 0.06; 95 % CI = 0.01-0.12; P = 0.040). Logistic regression confirmed the inverse association between LVEF and cognitive impairment (OR = 0.87; 95 % CI = 0.78-0.98; P = 0.022). In linear discriminant analysis, the LVEF cutoff level that best predicted cognitive impairment was ≤51 %.'] |
['Mimetic peptides of apolipoprotein A-I (apoA-I) present a new strategy for promoting the biological activity of high density lipoproteins (HDL). This study aimed to compare the anti-inflammatory effects of ETC-642, a new apoA-I mimetic peptide, with discoidal reconstituted HDL (rHDL).', 'New Zealand White rabbits (n=42) received daily infusions of saline, rHDL or discoidal complexes of an amphipathic peptide, ETC-642 (1-30 mg/kg), prior to insertion of non-occlusive carotid collars. Human coronary artery endothelial cells (HCAECs) were pre-incubated with ETC-642 or rHDL before TNF-α stimulation. Monocyte adhesion was investigated by pre-incubating HCAECs with rHDL or ETC-642, stimulating with TNF-α and incubating with THP-1 monocytes.', 'Infusion of ETC-642 resulted in dose-dependent reductions of collar-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the artery wall (p<0.05). Pre-incubation of HCAECs with ETC-642 and rHDL reduced TNF-α-induced THP-1 monocyte adhesion (p<0.01). Furthermore, ETC-642 and rHDL treatment reduced TNF-α induced mRNA levels of inflammatory markers VCAM-1, fractalkine, MCP-1 and the p65 subunit of NF-κB (p<0.05).'] |
['We describe the phenotype consistent with axonal Charcot-Marie-Tooth disease type 2 (CMT2) in 4 families with a c.197G>T (p.(Gly66Val)) variant in CHCHD10.', 'We sequenced the CHCHD10 gene in a cohort of 107 families with CMT2 of unknown etiology. The patients were characterized by clinical examination and electroneuromyography. Muscle MRI and biopsy of the muscle or nerve were performed in selected cases. Neuropathologic autopsy was performed in 1 case.', 'The c.197G>T variant in CHCHD10 was found in 6 families, 4 of which included multiple individuals available for detailed clinical study. Variants in this gene have recently been associated with amyotrophic lateral sclerosis-frontotemporal dementia, mitochondrial myopathy, or spinal muscular atrophy Jokela type (SMAJ), but not with CMT2. Our patients had a late-onset distal axonal neuropathy with motor predominance, progressing to involve sensory nerves. Neurophysiologic and neuropathologic studies confirmed the diagnosis of sensorimotor axonal neuropathy with no loss of anterior horn neurons. Muscle biopsies showed occasional cytochrome c oxidase-negative fibers, combined with small amounts of mitochondrial DNA deletions.'] |
['There is scarce information in the literature about a possible association between atopy and certain clinical manifestations of NSAID sensitivity.', '(1) To evaluate the prevalence of atopy in patients proved to be sensitive to cyclooxygenase inhibitors. (2) To assess cross-reactivity to two alternative NSAIDs, paracetamol (acetaminophen) and nimesulide.', 'NSAID-sensitive patients attending an allergy clinic and unselected controls were prick tested with inhalant allergens. Oral challenges with NSAIDs were carried out by the single-blinded (SBOC) method. Clinical data about personal and family history of allergic and atopic diseases were obtained by a careful review of the medical records and by direct questioning by experienced allergists.', 'Fifty patients had positive SBOCs to the suspected NSAID and only these were studied. A personal history of atopic diseases was present in 41 patients (82%) and 7 controls (14.5%), and a family history in 24 patients (48%) and 6 controls (12.5%). Prick skin tests with aeroallergens were positive in 39 of 45 patients tested (86.6%) and in 14 of 48 controls (29.1%), (P = .0001). Skin test positivity rates were higher in patients with cutaneous challenge reactions who responded to only one NSAID (single reactors) in comparison to cross-reactors (P = .04). The most frequent clinical manifestations of NSAID sensitivity were (1) cutaneous (angioedema, urticaria) in 34 patients, (2) blended (cutaneous plus respiratory) in 12, (3) respiratory in 3, and (4) anaphylactoid in 1. Aspirin, pyrazolone, paracetamol, and ibuprofen were the drugs more frequently implicated in these reactions. Cross-sensitivity with paracetamol and nimesulide were 32% and 25%, respectively.'] |
['Ezrin is highly expressed in skin cancer and promotes tumor metastasis. Ezrin serves as a promising target for anti-metastasis therapy. The aim of this study is to determine if the flavonoid bacailein inhibits the metastasis of skin cancer cells through Ezrin.', 'Cells from a cutaneous squamous carcinoma cell line, A431, were treated with baicalein at 0-60 μM to establish the non-cytotoxic concentration (NCC) range for baicalein. Following treatment with baicalein within this range, total Ezrin protein (both phosphorylated and unphosphorylated forms) and phosphorylated-Ezrin (phos-Ezrin) were detected by western blotting, and Ezrin RNA was detected in A431 cells using reverse transcription-polymerase chain reaction (RT-PCR). Thereafter, the motility and invasiveness of A431 cells following baicalein treatment were determined using wound-healing and Boyden chamber invasion assays. Short-interfering RNA (si-RNA) specifically targeting Ezrin was transfected into A431 cells, and a si-RNA Ezrin-A431 cell line was established by G418 selection. This stable cell line was transiently transfected with Ezrin and mutant Ezrin plasmids, and its motility and invasiveness was subsequently determined to clarify whether bacailein inhibits these processes through Ezrin.', 'We determined the range of NCCs for baicalein to be 2.5-40 μM in A431 cells. Baicalein displayed a dose- and time-dependent inhibition of expressions of total Ezrin and phos-Ezrin within this range NCCs. In addition, it exerted this inhibitory effect through the reduction of Ezrin RNA transcript. Baicalein also inhibited the motility and invasiveness of A431 skin carcinoma cells within the range of NCCs, in a dose- and time-dependent manner. A431 cell motility and invasiveness were inhibited by 73% and 80% respectively when cells were treated with 20 μM baicalein. However, the motility and invasiveness of A431 cells containing the Ezrin mutant were not effectively inhibited by baicalein.'] |
['For a variety of reasons, many patients abruptly discontinue statin therapy. The present analysis was conducted to determine whether the risk of cardiovascular outcomes increases after withdrawal of statin therapy in a stable cardiac population.', 'In the Treating to New Target (TNT) study, 2 doses of atorvastatin (10 and 80 mg once daily) are being used in a double-blind parallel-group design. Of the 18,468 patients screened for study participation, 16,619 entered a dietary lead-in/drug-washout period, and of these, 15,432 eligible participants began treatment with atorvastatin 10 mg/d on an open-label basis. Of the subjects who entered the dietary lead-in/drug-washout period, 57% were receiving prior statin therapy. During the 6-week drug-washout period, there were 24 primary events (defined as coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke); throughout the subsequent 8-week open-label period, there were 31 primary events. This equated to monthly Kaplan-Meier event rates of 0.20% during washout and 0.26% in the open-label phase. Event rates were therefore similar during the 2 phases.'] |
['Previous research has reported no effect of exercise modality (aerobic vs. resistance) on energy intake (EI). However, the relatively low energy cost of resistance training, the absence of total energy expenditure (TEE) measurements and the short duration of these studies justify further investigation.', 'To evaluate the effects of exercise modality on EI, TEE, non-exercise activity thermogenesis (NEAT) and post-exercise energy compensation (PEEC) measured acutely, as well as for 10 and 34 h following exercise.', 'Eight men and 8 women participated in three randomized crossover sessions: aerobic-based exercise, resistance-based exercise, and sedentary control. Exercise energy expenditure (ExEE) was continuously measured (indirect calorimetry) throughout the exercise sessions, which were designed to produce an isocaloric ExEE of 4 kcal/kg body weight. TEE and EI were monitored for 34 h post-exercise with biaxial accelerometers and a validated food menu, respectively.', 'There were no differences in EI between exercise modalities acutely, as well as 10 and 34 h following exercise. However, a modality by sex interaction was noted for acute EI. Men ate more after the resistance than after the aerobic session (1567±469; 1255±409 kcal, respectively; P=0.034), while no differences were seen in women (568±237; 648±270 kcal, respectively; P=NS). No differences in TEE, NEAT and PEEC were found 10h and 34 h post-exercise, while a positive correlation (r=0.897; P<0.01) was found between both modalities across participants for PEEC.'] |
['The majority of patients with non-alcoholic fatty liver disease (NAFLD) have simple steatosis. A minority, however, present with non-alcoholic steatohepatitis (NASH), a condition that can lead to advanced fibrosis and cirrhosis. The frequencies of NASH and fibrosis among patients with NAFLD and sustained elevation of liver function tests (LFT) are uncertain. Our aim was to estimate these frequencies. We characterize a population with NAFLD, with special emphasis on insulin resistance and the metabolic syndrome, and study possible predictors for different stages of the disease.', 'All referred patients with sustained elevation of LFT, radiological evidence or clinical suspicion of fatty liver, and absence of other liver disease, were invited to participate in our study in the period June 2002 to December 2004.', 'Of 129 patients who met the inclusion criteria, 88 underwent liver biopsy. NAFLD was verified in 83 of them. Among these patients, 59 (71%) had the metabolic syndrome, 41 (49%) had NASH and 36 (43%) had fibrosis. Abnormal glucose tolerance (T2DM or impaired glucose tolerance) was the only independent risk factor for NASH (OR: 3.14; 95% CI: 1.20-8.23). Independent predictors for fibrosis were abnormal glucose tolerance (OR: 3.83; 95% CI: 1.29-11.40) and body mass index (OR: 1.20; 95% CI: 1.06-1.36) per kg/m2.'] |
['Previous studies have demonstrated that positive blood culture could contribute to poorer outcomes in patients with pneumonia. However, the impact of positive blood culture on the outcomes of patients with sepsis-induced acute respiratory distress syndrome (ARDS) has not been evaluated.', 'An observational study that prospectively screened 4861 patients admitted to medical or surgical intensive care units (ICUs) of a tertiary referral centre was performed.', 'Among 4861 admitted patients, 146 diagnosed with sepsis-induced ARDS were enrolled (mean age: 66.1 years). Lower PaO2 /FiO2 , decreased respiratory system compliance, and higher lung injury scores (LIS) on the day of ARDS diagnosis were associated with positive blood cultures (n = 68) rather than negative blood cultures (n = 78). There was no relationship between positive blood culture and in-hospital mortality. Kaplan-Meier estimates also revealed that positive blood culture was not associated with 60-day mortality but with an increased length of stay in the hospital and in the ICU (P = 0.007 and P = 0.016, respectively). Using multivariate logistic regression, higher LIS was independently associated with positive blood culture. In addition, chronic pulmonary disease, lower platelet count, higher LIS, and the development of shock on the diagnosis of ARDS, were independent risk factors for in-hospital mortality.'] |
['Although the repositioning maneuvers are usually very effective in patients with BPPV, some patients still complain residual dizziness. Danhong injection (DHI), a traditional Chinese medicine, can effectively dilate blood vessels and improve microcirculation, and has been proven to be effective in improving cervical vertigo and posterior circulation ischemic vertigo. The aim of this study was to evaluate the effects of DHI on residual dizziness after successful repositioning treatment in patients with BPPV.', 'Eighty-six patients with BPPV were randomized into two treatment groups, DHI group and non DHI group. The DHI group received the same repositioning treatment as the non-DHI group, with the addition of DHI therapy. The durations of residual dizziness of DHI group and non-DHI group were compared. In addition, the scores of the dizziness handicap inventory of these two groups were calculated.', 'The durations of residual dizziness of DHI group were shorter than that of non-DHI group. There were no significant differences in the scores of dizziness handicap inventory in the first week between these two groups, and there were much significant differences in the second, the fourth, the sixth and eighth weeks.'] |
['Introduction of the yellow obese gene (A(y)) into mice (KKAy) results in obesity and diabetes by 5 weeks of age.', 'Using this model of type 2 diabetes, we evaluated male and female 6- to 8-month-old wild-type (WT, n=10) and KKAy (n=22) mice subjected to myocardial infarction (MI) and sacrificed at day (d) 7.', 'Despite similar infarct sizes (50% ± 4% for WT and 49% ± 2% for KKAy, P=not significant), the 7d post-MI survival was 70% (n=7/10) in WT mice and 45% (n=10/22) in KKAy mice (P<.05). Plasma glucose levels were 1.4-fold increased in KKAy mice at baseline compared to WT (P<.05). Glucose levels did not change in WT mice but decreased 38% in KKAy post-MI (P<.05). End-diastolic and end-systolic dimensions post-MI were smaller and fractional shortening improved in the KKAy (5% ± 1% in WT and 10% ± 2% in KKAy, P<.05 for all). The improved cardiac function in KKAy was accompanied by reduced macrophage numbers and collagen I and III levels (both P<.05). Griffonia (Bandeiraea) simplicifolia lectin-I staining for vessel density demonstrated fewer vessels in KKAy infarcts (5.9% ± 0.5%) compared to WT infarcts (7.3% ± 0.1%, P<.05).'] |
['"Chimney" techniques used to extend landing zones for endovascular aortic repair (chEVAR) have been increasingly reported; however, concerns about durability and patency remain. The purpose of this analysis was to examine midterm outcomes of chEVAR.', 'All patients at the University of Florida treated with chEVAR were reviewed. Major adverse events (MAEs) were recorded and defined as any chimney stent thrombosis, type Ia endoleak in follow-up, reintervention, 30-day/in-hospital death, or ≥25% decrease in estimated glomerular filtration rate after discharge. Primary end points included chimney stent patency and freedom from MAE. Secondary end points included complications and long-term survival.', 'From 2008 to 2012, 41 patients (age\xa0± standard deviation, 73\xa0± 8\xa0years; male, 66% [n\xa0= 27]) were treated with a total of 76 chimney stents (renal, n\xa0= 51; superior mesenteric artery, n\xa0= 16; celiac artery, n\xa0= 9) for a variety of indications: juxtarenal, 42% (n\xa0= 17, one rupture), suprarenal, 17% (n\xa0= 7), and thoracoabdominal aneurysm, 17% (n\xa0=\xa07); aortic anastomotic pseudoaneurysm, 15% (n\xa0= 6; three ruptures); type Ia endoleak after EVAR, 7% (n\xa0= 3); and atheromatous disease, 2% (n\xa0= 1). Two patients had a single target vessel abandoned because of cannulation failure, and\xa0one had a type Ia endoleak at case completion (technical success, 93%). Intraoperative complications occurred in seven patients (17%), including graft maldeployment with unplanned mesenteric chimney (n\xa0= 2) and access vessel injury requiring repair (n\xa0= 5). Major postoperative complications developed in 20% (n\xa0= 8). The 30-day mortality and in-hospital mortality were 5% (n\xa0= 2) and 7% (n\xa0= 3), respectively. At median follow-up of 18.2\xa0months (range, 1.4-41.5\xa0months), 28 of 33 patients (85%) with available postoperative imaging experienced stabilization or reduction of abdominal aortic aneurysm sac diameters. Nine patients (32%) developed endoleak at some point during follow-up (type Ia, 7% [n\xa0= 3]; type II, 10% [n\xa0= 4]; indeterminate, 7% [n\xa0= 3]), and one patient underwent open, surgical conversion. The estimated probability of freedom from reintervention (±standard error mean) was 96%\xa0± 4% at both 1\xa0year and 3\xa0years. Primary patency of all chimney stents was 88%\xa0± 5% and 85%\xa0± 5% at 1\xa0year and 3\xa0years, respectively. Corresponding freedom from MAEs was 83%\xa0± 7% and 57%\xa0± 10% at 1\xa0year and 3\xa0years. The actuarial estimated survival for all patients at 1\xa0year and 5\xa0years was 85%\xa0± 6% and 65%\xa0± 8%, respectively.'] |
['Optimal training intensity and the adequate exercise level for physical fitness is one of the most important interests of coaches and sports physiologists. The aim of this study was to investigate the validity of the Narita et al target heart rate equation for the adequate exercise training level in sedentary young boys.', 'Forty two sedentary young boys (19.07±1.16 years) undertook a blood lactate transition threshold maximal treadmill test to volitional exhaustion with continuous respiratory gas measurements according to the Craig method. The anaerobic threshold (AT) of the participants then was calculated using the Narita target heart rate equation.', "Hopkin's spreadsheet to obtain confidence limit and the chance of the true difference between gas measurements and Narita target heart rate equation revealed that the Narita equation most likely underestimates the measured anaerobic threshold in sedentary young boys (168.76±15 vs. 130.08±14.36) (Difference ±90% confidence limit: 38.1±18). Intraclass correlation coefficient (ICC) showed a poor agreement between the criterion method and Narita equation (ICC= 0.03)."] |
['To compare the difference of the dose distribution in clinical target volume and organ at risk (OAR) between coplanar decile field intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for postoperative radiotherapy of cervical cancer.', 'Ten postoperative patients with cervical cancer were selected randomly to undergo CT scan and planning target volume (PTV) and OAR contouring. 3D-CRT and coplanar decile IMRT planning was performed for each patient with a prescribed dose of 50 Gy. The homogeneity index (HI), conformity index (CI), maximum dose, minimum dose, mean dose of PTV, and irradiated volume of OARs were calculated and the results were compared.', '5-field IMRT, 7-field IMRT and 9-field IMRT plans had a significant better conformity index (CI) of PTV compared with 3D-CRT (P<0.05) . Compared with 3D-CRT plans , V30, V40, and V50 of the bladder, V50 of the small bowel, and V30, V40, and V50 of the rectum in the coplanar decile IMRT plans were all significantly reduced (P<0.05) but showed no significant differences among the IMRT plans (P>0.05).'] |
['Epinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the alpha-adrenoceptor, and it is known that the alpha2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor.', 'Twenty adult patients, scheduled for spinal anesthesia, were allocated to the control group ( n = 10) or epinephrine group ( n = 10). Patients in the control group received 14 mg of tetracaine, whereas the epinephrine group received 14 mg of tetracaine and 0.2 mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5 mg x kg(-1) by infusion for the initial dose, then continuously at 2 mg x kg(-1) x h(-1) in both groups. BIS scores were recorded before subarachnoid block, and then every 5 min for 90 min after subarachnoid block.', 'There were significant differences in the BIS score between the two groups at 45-55 min and at 60-70 min after subarachnoid block.'] |
['Acknowledging that eosinophilic esophagitis (EoE) is a disease with variable involvement throughout the oesophagus, studies have suggested a minimum of five biopsies to diagnose EoE. Although it is accepted that furrows and exudates appear to represent areas of inflammation, no research to date has looked specifically at EoE endoscopic findings to see if eosinophilic infiltrate correlates with specific endoscopic findings.', 'To evaluate the distribution of eosinophils in EoE and determine whether endoscopic appearances predict the degree of eosinophilia at various locations of the oesophagus.', 'We performed a prospective cross sectional study of EoE (treated and untreated) patients to study the distribution of eosinophils according to endoscopic findings. The oesophagus of 10 EoE patients were biopsied up to 32 times in a circumferential manner. The mucosal changes were documented at the site of each biopsy. Histological determination of eosinophil counts and related histopathology of the oesophagus were then correlated with endoscopic findings. Similar biopsy assessments were made in treated (resolved) EoE patients (n\xa0=\xa06) to determine the permanence of specific endoscopic appearances.', 'A total of 16 patients were biopsied (10 EoE, 6 treated EoE). A total of 432 biopsies were obtained in all with 294 biopsies from 10 EoE subjects. Eosinophil density was increased distally in the majority of EoE patients. Biopsies performed in areas of exudates and furrows demonstrated higher eosinophil counts. Lines and normal-appearing oesophagi in EoE subjects were not commonly associated with elevated eosinophil counts (>15\xa0eos/HPF). Rings alone without associated furrows or plaques did not demonstrate elevated eosinophil counts and were seen in resolved EoE (Rx-EoE) as well as in active EoE patients.'] |
['To establish the human colorectal cancer cell model SW620/PAR4D with inducible suppression of proteinase activated receptor 4 (PAR4) expression, and investigate the role PAR4 plays in the proliferation and migration of cancer cells.', 'A human colorectal cancer cell line with tetracycline-inducible expression regulatory system, namely SW620/Tet-on, was established; inducible expression lentiviral vector with artificial microRNA targeting PAR4, pLVX-Tight-Puro-PAR4-miR, was constructed and transfected into SW620/Tet-on to make an inducible PAR4-suppressed cell model SW620/PAR4D. Western blotting was used to confirm the suppression of PAR4 expression after the doxycycline (DOX) treatment. CCK-8 assay was used to evaluate the impact of suppressed PAR4 expression on cell proliferation, and wound-healing assay was used to analyze the migration of the cells.', 'The SW620/PAR4D cell model was established successfully. Suppression of PAR4 expression by DOX treatment had no significant impact on the growth/proliferation of SW620/PAR4D cells, but markedly inhibited the cell migration.'] |
['We have identified a novel cancer/testis antigen, TRAG-3, (Taxol Resistance Associated Gene-3) that was initially discovered in search for new genes involved in drug resistance by differential display. Early study of TRAG-3 revealed minimal to absent expression in various normal tissues and over-expression in many carcinoma cell lines including several melanoma lines.', 'Northern and RT-PCR technologies were used to evaluate TRAG-3 expression in numerous cell lines and tumor tissue.', 'Analysis of a wider panel of normal tissues, 32 melanoma cell lines and 4 malignant melanomas demonstrates TRAG-3 expression in 25 of the 32 melanoma cell lines (78%) and four of four of the malignant melanoma tumors (100%). Of the additional eight normal tissues screened, expression was present in normal testis but absent in all other tissues. RT-PCR evaluation of TRAG-3 reveals two transcripts in many carcinoma cell lines with sequencing of these products demonstrating the 799 bp TRAG-3 transcript and a second alternatively spliced transcript, TRAG-3long TRAG-3 maps to band Xq28 within a MAGE gene complex, however sequence analysis demonstrates that TRAG-3 is not homologous to other known cancer/testis antigens.'] |
['Red cell distribution width (RDW) is a variability of red cell sizes and has been associated with outcomes in many clinical settings. Its prognostic value in intensive care unit (ICU) has been reported but requires confirmation. The study aimed to investigate the role of RDW in predicting hospital mortality in critically ill patients.', 'This is a retrospective study conducted in a 24-bed ICU of a tertiary teaching hospital. Data on demographic characteristics and laboratory measurements were collected from medical information database. Baseline variables were compared between survivors and nonsurvivors. The primary endpoint was hospital mortality; and ICU length of stays (LOS) were compared between patients with RDW >14.8% and ≤14.8%. The predictive value of RDW was also measured using receiver operating characteristic (ROC) curves. Two-sided P<0.05 was considered to be statistically significant.', 'A total of 1,539 patients were enrolled during study period, including 1,084 survivors and 455 nonsurvivors. In univariate analysis, variables such as age, sex, primary diagnosis, C-reactive protein (CRP), RDW and albumin were significantly associated with hospital mortality. RDW remained significantly associated with mortality after adjustment for sex, age, Charlson index albumin and CRP, with an odds ratio of 1.1 (95% CI: 1.03-1.16). Diagnostic performance of RDW in predicting mortality appeared to be suboptimal (AU-ROC: 0.62). Changes in RDW during a short follow up period were not associated with mortality.'] |
['Thymidylate synthase (TYMS) expression in lung cancer tissue affects the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is primarily assessed using immunohistochemistry (IHC), but this method is not suitable for accurate quantitative analysis. It is not known whether the analysis of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a useful method for assessment of TYMS expression.', 'The participants were patients with chemo-naïve advanced NSCLC treated with PMT plus carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was evaluated in 40 patients by gene copy number and protein expression using FISH and IHC. Therapeutic efficacy was evaluated by investigating the response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).', 'TYMS gene amplification was detected in 8 patients (32 %) among 25 patients who could be evaluated for TYMS gene copy number. There were no patients with complete or partial response in the TYMS amplified group. RR and DCR were lower in the TYMS amplified group compared with the TYMS unamplified group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS were reduced in the TYMS amplified group. The analysis of TYMS gene copy number had higher sensitivity and specificity compared with TYMS protein expression (76.2 versus 50.0 %, 75.0 versus 66.7 %).'] |
['To assess the usefulness of transcranial Doppler CO2 reactivity (CO2R) for prediction of ipsilateral ischemic stroke in carotid artery stenosis and occlusion with a meta-analysis of prospective studies based on individual patient data.', 'We searched Medline, Biosis Previews, Science Citation Index, The Cochrane Library, and EMBASE for studies in which patients with severe carotid artery stenosis or occlusion underwent Doppler CO2R testing (inhalation of CO2 or breath-holding) and were prospectively followed for ipsilateral ischemic stroke. Individual data from 754 patients from 9 studies were included. We used percentage cerebral blood flow velocity increase (pCi) during hypercapnia as the primary CO2R measure, and defined impaired reactivity as pCi <20% increase.', 'In a multiple regression model, impaired CO2R was independently associated with an increased risk of ipsilateral ischemic stroke (hazard ratio [HR] 3.69; confidence interval [CI] 2.01, 6.77; p < 0.0001). Risk prediction was similar for recently symptomatic vs asymptomatic patients. Using continuous values of pCi, a significant association between decreasing pCi and increasing risk of ipsilateral stroke was found: HR of 1.64 (95% CI 1.33, 2.02; p < 0.0001) per 10% decrease in pCi. For patients with asymptomatic internal carotid artery stenosis only (n = 330), a comparable stroke risk prediction was found: increasing HR 1.95 (95% CI 1.26, 3.04; p = 0.003) per 10% decrease in pCi.'] |
['We hypothesized that deregulated corepressor actions, with associated histone deacetylation activity, epigenetically suppressed vitamin D receptor (VDR) responsiveness and drives resistance towards 1alpha,25-dihydroxyvitamin D(3).', 'Profiling, transcriptional, and proliferation assays were undertaken in 1alpha,25(OH)(2)D(3)-sensitive MCF-12A nonmalignant breast epithelial cells, a panel of breast cancer cell lines, and a cohort of primary breast cancer tumors (n = 21).', "Elevated NCoR1 mRNA levels correlated with suppressed regulation of VDR target genes and the ability of cells to undergo arrest in G(1) of the cell cycle. A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor alpha-negative (n = 7) tumors. 1alpha,25(OH)(2)D(3) resistance in cancer cell lines was targeted by cotreatments with either 1alpha,25(OH)(2)D(3) or a metabolically stable analogue (RO-26-2198) in combination with either trichostatin A (TSA; histone deacetylation inhibitor) or 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor). Combinations of vitamin D(3) compounds with TSA restored VDR antiproliferative signaling (target gene regulation, cell cycle arrest, and antiproliferative effects in liquid culture) to levels which were indistinguishable from MCF-12A cells."] |
['Uveal melanoma (UM) cells and neurohormone-producing cells both originate from the neural crest. Somatostatin receptors subtype 2 (SSTR2) are over-expressed in several tumors, often from neuroendocrine origin, and synthetic antagonists like octreotide and octreotate are being used as diagnostic or therapeutic agents. We investigated the SSTR2 expression in UM, and determined whether this expression was related to prognosis of the disease.', 'UM cell lines and fresh primary UM samples were tested for SSTR2 expression by autoradiography (AR) using 125I-Tyr3-octreotate. Furthermore, UM cell lines were analyzed for SSTR2 mRNA expression with quantitative real-time RT-PCR.', 'Using AR, cell-surface SSTR2 expression was demonstrated in two UM metastatic cell lines, but no expression was detected in three cell lines derived from primary UM. However, all primary and metastatic UM cell lines showed mRNA expression levels for SSTR2 using quantitative real-time RT-PCR. Only three of 14 primary UM demonstrated moderate SSTR2 expression, and this expression was not significantly associated with tumor-free survival or any tested prognostic factor.'] |
['Interstitial cells of Cajal (ICC) are distributed with smooth muscle throughout the gastrointestinal tract and are involved in regulating motility. ICC were recently discovered in the wall of the human gallbladder. This study sought to determine whether ICC are present in human bile ducts.', 'Biliary tract samples were obtained from several sources: surgical specimens (n = 16, 11 women, mean age 61 years); archival post-mortem specimen (n = 1, 86 years, man); and cadavers (n = 2, 68 and 80 years, men). Paraffin-embedded sections (3 microm) from the gallbladder (fundus, body and neck) and both extrahepatic and intrahepatic bile ducts were investigated. A double immunofluorescence protocol using polyclonal and monoclonal c-kit antibodies and mast cell tryptase was used to distinguish c-kit-positive cells with typical ICC morphology from c-kit-positive mast cells. Small bowel samples were used as positive controls. ICC in the gallbladder were confirmed by ultrastructural study.', 'c-kit-positive cells with characteristic ICC morphology were identified in the subepithelial and muscular layers of the gallbladder and extrahepatic bile ducts. They were most prominent within the muscle layer of the extrahepatic bile ducts where they were organized into loosely arranged laminae running parallel to circular smooth muscle fibers. ICC were not found in intrahepatic bile ducts.'] |
['The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based) approaches alone have failed to resolve. One notable example concerns the rhinoceroses, a group for which several contradictory phylogenies were proposed on the basis of morphology, then apparently resolved using mitochondrial DNA fragments.', 'In this study we report the first complete mitochondrial genome sequences of the extinct ice-age woolly rhinoceros (Coelodonta antiquitatis), and the threatened Javan (Rhinoceros sondaicus), Sumatran (Dicerorhinus sumatrensis), and black (Diceros bicornis) rhinoceroses. In combination with the previously published mitochondrial genomes of the white (Ceratotherium simum) and Indian (Rhinoceros unicornis) rhinoceroses, this data set putatively enables reconstruction of the rhinoceros phylogeny. While the six species cluster into three strongly supported sister-pairings: (i) The black/white, (ii) the woolly/Sumatran, and (iii) the Javan/Indian, resolution of the higher-level relationships has no statistical support. The phylogenetic signal from individual genes is highly diffuse, with mixed topological support from different genes. Furthermore, the choice of outgroup (horse vs tapir) has considerable effect on reconstruction of the phylogeny. The lack of resolution is suggestive of a hard polytomy at the base of crown-group Rhinocerotidae, and this is supported by an investigation of the relative branch lengths.'] |
['Endovascular therapy is an alternative for the treatment of AIS resulting from large intracranial arterial occlusions that depends on the use of iodinated RCM. The risk of RCM-mediated AKI following endovascular therapy for AIS may be different from that following coronary interventions because patients may not have identical risk factors.', 'All consecutive patients with large-vessel AIS undergoing endovascular therapy were prospectively recorded. We recorded the baseline kidney function, and RCM-AKI was assessed according to the AKIN criteria at 48 hours after RCM administration. We compared the rate of RCM-AKI 48 hours after the procedure and sought to determine whether any preexisting factors increased the risk of RCM-AKI.', 'We identified 99 patients meeting inclusion criteria. The average volume of contrast was 189 ± 71 mL, and the average creatinine change was -4.6% at 48 hours postangiography. There were 3 patients with RCM-AKI. Although all 3 patients died as a result of their strokes, return to baseline creatinine levels occurred before death. There was a trend toward higher rates of premorbid diabetes mellitus, chronic renal insufficiency, preadmission statin and NSAID use, and a higher serum creatinine level on admission for the RCM-AKI group. The volume of procedural contrast was similar between groups (those with and those without RCM-AKI) (P = .5).'] |
['To determine whether obstetric handoff quality differs morning versus evening, weekend versus weekday, or based on provider type.', 'Using the American College of Obstetricians and Gynecologists (ACOG) handoff guidelines, we developed an observational tool to assess whether handoffs included its 8 recommended elements. We observed handoffs between attending obstetricians, Obstetrics and Gynecology residents, labor and delivery nurses, and certified nurse midwives. Observation times included a balance of morning, evening, weekdays, and weekends. Participants were blinded to the study objectives. We defined high-quality handoffs as those that included 7 of the 8 recommended ACOG elements.', 'A total of 425 inpatient handoffs were observed: 233 (55%) were morning handoffs and 189 (45%) were evening; 251 (59%) were on weekdays and 171 (41%) on weekends. Of the handoffs observed, 201 (48%) were presented by residents, 139 (33%) by nurses, 56 (13%) by attending obstetricians, and 26 (6%) by midwives. Only 169 (40%) of all handoffs met criteria for high quality. A greater percentage of all morning handoffs met criteria as compared to evening handoffs (45% vs. 34%, p < 0.05). There was no significant difference between the overall percentage of weekday and weekend handoffs meeting criteria (39% vs. 42%, p = 0.48). Residents had a higher percentage of high-quality handoffs as compared to nurses (55% vs. 32%, p < 0.001).'] |
['Hippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis.', 'Magnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor.', 'BHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI.'] |
['Glioblastoma multiforme (GBM) is an incurable malignant glioma which is very resistant to radiation and alkylating agent-based chemotherapy. Necrosis is a hallmark for GBM and the layer surrounding necrotic area is packed with cells which are now believed to be those migrating out of the necrotic area. Oxidative stress is a condition that GBM cells encounter in the necrotic zone, which is one of the stressful conditions that GBM cells need to resist in order to survive. Our previous studies revealed that low PAX6 expression is a favorable molecular trait for survival acquired by GBM cells because PAX6 could suppress cell invasion and tumorigenicity. Since detachment of cells from GBM is an early event for cell migration and subsequent invasion, we examined whether PAX6 is involved in cell survival after detachment.', 'PAX6 over-expression was achieved in glioma cells transiently (by adenoviral-mediated transient over-expression) or stably (by the establishment of stable cell lines after transfection). The effect of PAX6 over-expression on the survival and growth of glioma cells after detachment from the culture was determined.', 'Our data revealed that GBM cells (with their low PAX6 levels) survived the detachment procedure well. However, PAX6 over-expression attenuated GBM cell recovery of growth after detachment-induced stress. Importantly, intracellular reactive oxygen species (ROS) levels increased following cell detachment and that PAX6 over-expressing cells retained higher level of ROS than control cells. This may be partially responsible for the impaired growth rate after cell detachment. Addition of anti-oxidant improved the cell viability of PAX6 over-expressing cells, but did not restore their ability to proliferate.'] |
['A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis.', 'Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization.', 'Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker.'] |
['A primary objective was to evaluate whether addition of enteral iron supplementation will facilitate a systemic erythropoietic effect when feeding erythropoietin (Epo) to suckling rats. A secondary objective was to confirm that iron does not alter the previous finding that enteral Epo exerts local trophic effects on the small intestine.', "Four-day-old Sprague-Dawley rats underwent gastrostomy and were fed a cow's milk-based rat milk substitute for 8 days. We studied rats fed rat milk substitute alone (control), enteral Epo 425 U x kg(-1) x day(-1), and enteral Epo 1700 U x kg(-1) x day(-1), and the effects of oral iron sulfate (Fe) therapy (6 mg x kg(-1) x day(-1)). Blood was collected to measure hemoglobin (Hb), reticulocytes, red cell indices, and zinc protoporphyrin/heme. To confirm previous work describing trophic effects of enteral Epo on the intestine, duodenal villous height was measured.", 'Hb levels in control (84 +/- 1 g/L) were similar to Epo 425 (87 +/- 1 g/L). Hb levels in control+Fe (97 +/- 1 g/L), Epo 425+Fe (97 +/- 1 g/L), and Epo 1700 (94 +/- 1 g/L) were higher than control, P < 0.001, but mean Hb level in Epo 1700+Fe was higher (105 +/- 1 g/L) than the other groups, P < 0.003. Mean cell volume was higher in rats receiving iron supplementation, compared with those without iron, P < 0.005. Duodenal villous height was taller in Epo 1700+Fe compared with control + Fe, P < 0.01.'] |
['Low birth weight has been associated with metabolic and vascular diseases, but the precise mechanism is debated. Adiponectin is one of the key molecules in metabolic disease, and a decrease in level precedes the onset of type 2 diabetes and development of atherosclerosis. Our aim is to examine whether low birth weight is associated with adiponectin concentration in adult.', 'We conducted a population-based cross-sectional study of 2277 subjects (1661 men and 616 women) aged 35 to 66 years who had their self-reported birth weights and adiponectin concentrations measured as adults.', 'After adjusting for potential confounders, including age, sex, current body mass index (BMI), smoking status, alcohol consumption, and exercise, geometric mean adiponectin levels were 6.63, 6.45, 6.86, 7.05, 6.75, and 7.22 microg/mL for subjects with birth weights less than 2500, 2500 to less than 2800, 2800 to less than 3000, 3000 to less than 3200, 3200 to less than 3500, and greater than 3500 g, respectively. A positive association was found between birth weight and adiponectin concentration (trend p = 0.002). Stratified by current BMI of 25 kg/m2, a positive association was not observed for subjects with a BMI less than 25 kg/m2, but was pronounced in those with a BMI of 25 kg/m2 or greater.'] |
['This study presents fungi and their characteristics identified from burn patients at a major Chinese burn centre.', 'All burns patients admitted to our Burn Research Institute from 2003 to 2006 inclusive were included in this study. Once fungal infection was suspected clinically, samples including wound tissue, blood, urine, stool and sputum were harvested for the culture of yeast. The sensitivities of the identified yeast were determined and the positive samples and cases were analysed.', 'Out of a total of 3909 cases, 467 patients were clinically suspected of fungal infection, of which 1970 samples were taken for yeast culture. A total of 38 samples and 36 patients tested positive. The three most positive samples were urine, blood and catheter. Candida tropicalis was identified as the most common yeast type (42.1%), followed by Candida albicans (31.6%), Candida famata (T. Famata) (10.5%) and Candida glabrata (T. Glabrata) (7.9%). Except for C. galbrata, most of the yeast strains found in the study were sensitive to the routine antimycotic agents. There were eight deaths in the 36 positive patients. As much as 83.3% of the positive cases suffered burns of more than 50% total body surface area (TBSA) and half of the positive cases were greater than 80% TBSA. A total of 78.95% of the positive samples were taken from patients after 2 weeks post-burn injury.'] |
['Mesenchymal stem cells (MSCs) have the ability to migrate to lesion sites and undergo differentiation into functional tissues. Although this function may be important for tissue regeneration after radiation therapy, the influence of ionizing radiation (IR) on cellular survival and the functional aspects of differentiation and stem cell characteristics of MSCs have remained largely unknown.', 'Radiation sensitivity of human primary MSCs from healthy volunteers and primary human fibroblast cells was examined, and cellular morphology, cell cycle effects, apoptosis, and differentiation potential after exposure to IR were assessed. Stem cell gene expression patterns after exposure to IR were studied using gene arrays.', 'MSCs were not more radiosensitive than human primary fibroblasts, whereas there were considerable differences regarding radiation sensitivity within individual MSCs. Cellular morphology, cytoskeletal architecture, and cell motility were not markedly altered by IR. Even after high radiation doses up to 10 Gy, MSCs maintained their differentiation potential. Compared to primary fibroblast cells, MSCs did not show an increase in irradiation-induced apoptosis. Gene expression analyses revealed an upregulation of various genes involved in DNA damage response and DNA repair, but expression of established MSC surface markers appeared only marginally influenced by IR.'] |
['We have observed prolonged survival in patients undergoing vaccine reinduction after resection of recurrent metastatic melanoma and adjuvant polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that reinduction with a more intensive vaccine regimen would re-stimulate specific immune responses that were correlated with survival after recurrence.', 'From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent disease was treated with or without vaccine reinduction. Reinduction regimen entailed an increased vaccine frequency and coadministration of two doses of bacille Calmette-Guérin (BCG). PACV Delayed-type hypersensitivity (DTH) responses were prospectively recorded. Survival was defined as the interval from recurrence to death.', 'Ninety-four patients underwent reinduction immunotherapy. DTH responses to PACV before recurrence increased significantly after reinduction therapy (P =.0001). The median survival time was 37 months for reinduced patients and 17 months for other patients. On multivariate analysis, reinduction status remained a significant prognostic variable (P =.0277). In the reinduction group, there was a significant correlation between PACV DTH responses and survival (P =.0178).'] |
['A decline in cognitive test scores in elderly persons can signal the beginning of a descent into dementia or may indicate only a short-term cognitive disturbance. It would be clinically useful to distinguish between the two outcomes and to identify characteristics of each.', 'Four hundred thirty-seven community-dwelling elderly persons were given the Mini-Mental State Examination (MMSE) annually for an average of 7 years. A low score between baseline and final MMSE was identified. A low score 3 or more points lower than baseline score indicated cognitive decline. This decline was called persistent if the final MMSE score was also at least 3 points lower than baseline MMSE score; otherwise, the decline was considered transient.', 'Twenty participants (4.6%) experienced a persistent cognitive decline, 67 participants (15.3%) experienced a transient cognitive decline. Presence of the apolipoprotein epsilon4 allele was significantly associated with persistent cognitive decline (age-adjusted odd ratio [OR] = 11.46, p < .0001) but not with transient cognitive decline (age-adjusted OR = 1.53, p = .219). Incorrect answers on the orientation part of the MMSE at the time of cognitive decline was associated with persistent decline compared to transient decline (age-adjusted OR = 3.58, p = .058).'] |
['The magnitude and longevity of synaptic activity-induced changes in synaptic efficacy is quantified by measuring evoked responses whose potentiation requires gene transcription to persist for more than 2-3 hours. While miniature EPSCs (mEPSCs) are also increased in amplitude and/or frequency during long-term potentiation (LTP), it is not known how long such changes persist or whether gene transcription is required.', 'We use whole-cell patch clamp recordings from dissociated hippocampal cultures to characterise for the first time the persistence and transcription dependency of mEPSC upregulation during synaptic potentiation. The persistence of recurrent action potential bursting in these cultures is transcription-, translation- and NMDA receptor-dependent thus providing an accessible model for long-lasting plasticity. Blockade of GABAA-receptors with bicuculline for 15 minutes induced action potential bursting in all neurons and was maintained in 50-60% of neurons for more than 6 hours. Throughout this period, the frequency but neither the amplitude of mEPSCs nor whole-cell AMPA currents was markedly increased. The transcription blocker actinomycin D abrogated, within 2 hours of burst induction, both action potential bursting and the increase in mEPSCs. Reversible blockade of action potentials during, but not after this 2 hour transcription period suppressed the increase in mEPSC frequency and the recovery of burst activity at a time point 6 hours after induction.'] |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.