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['To measure serum concentrations of progesterone, estradiol and 5α- and 5β-reduced progesterone metabolites in the follicular and luteal phases of the menstrual cycle in women with latent acute intermittent porphyria and manifest acute intermittent porphyria in comparison with healthy control women.', 'A descriptive study with repeated measurements during a complete, ovulatory menstrual cycle.', 'University hospital out-patient clinic.', 'Thirty-two women with DNA-diagnosed acute intermittent porphyria and 20 healthy control women.', 'Blood samples for serum progesterone, estradiol, allopregnanolone and pregnanolone were drawn on predefined menstrual cycle days, twice in the follicular phase and three times in the luteal phase. Serum levels of estradiol and progesterone were analysed with commercial kits. Allopregnanolone and pregnanolone levels were analysed with radioimmunoassay following diethylether extraction and celite column chromatography.', 'Changes in serum levels of progesterone, estradiol, allopregnanolone and pregnanolone throughout the menstrual cycle.', 'Women with acute intermittent porphyria displayed lower serum concentrations of allopregnanolone in comparison with healthy control women, the difference being most prominent in the luteal phase (p < 0.001). Levels of pregnanolone did not differ significantly between groups. No significant difference was found between women with latent acute intermittent porphyria and manifest acute intermittent porphyria.'] |
['High levels of thymidine kinase 1 (TK1) and thymidine phosphorylase (TYMP) are key molecular targets by thymidine therapeutics in cancer treatment. The dual roles of TYMP as a tumor growth factor and a key activation enzyme of anticancer metabolites resulted in a mixed outcome in cancer patients. In this study, we investigated the roles of TK1 and TYMP on a thymidine quinoxaline conjugate to evaluate an alternative to circumvent the contradictive role of TYMP.', 'TK1 and TYMP levels in multiple liver cell lines were assessed along with the cytotoxicity of the thymidine conjugate. Cellular accumulation of the thymidine conjugate was determined with organelle-specific dyes. The impacts of TK1 and TYMP were evaluated with siRNA/shRNA suppression and pseudoviral overexpression. Immunohistochemical analysis was performed on both normal and tumor tissues. In vivo study was carried out with a subcutaneous liver tumor model.', 'We found that the thymidine conjugate had varied activities in liver cancer cells with different levels of TK1 and TYMP. The conjugate mainly accumulated at endothelial reticulum and was consistent with cytosolic pathways. TK1 was responsible for the cytotoxicity yet high levels of TYMP counteracted such activities. Levels of TYMP and TK1 in the liver tumor tissues were significantly higher than those of normal liver tissues. Induced TK1 overexpression decreased the selectivity of dT-QX due to the concurring cytotoxicity in normal cells. In contrast, shRNA suppression of TYMP significantly enhanced the selective of the conjugate in vitro and reduced the tumor growth in vivo.'] |
['The Ca2+ -paradox is an important phenomenon to study cell injury induced by Ca2+ -overload in myocardium. Although intracellular Ca2+ -overload acts as a trigger and modulator of cell death due to apoptosis under various pathophysiological conditions, the presence of apoptosis in hearts subjected to Ca2+ -paradox has not been demonstrated. Since taurine attenuates the changes in cardiac function due to Ca2+ -paradox, this study investigated the occurrence and mechanisms of apoptosis in Ca2+ -paradoxic hearts treated in the absence and presence of taurine.', 'Ca2+ -paradox was induced by perfusing the isolated rat heart with Ca2+ -free medium for 5 min followed by reperfusion with Ca2+ -containing medium for 30 min. Apoptosis related signal transduction mechanisms were determined in Ca2+ -paradoxic hearts perfused with or without 10 mM taurine.', 'Marked alterations in cardiac function and the presence of apoptosis were seen in Ca2+ -paradoxic hearts reperfused for 30 min. Unlike the total protein contents in hearts subjected to Ca2+ -paradox, the contents of phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase (ERK)1, ERK2 and c-jun amino-terminal kinase were increased by 125 +/- 8.6%, 296 +/- 14.3%, 213 +/- 8.5% and 133 +/- 4.2%, respectively vs. control. Caspase-3 and phosphorylated Bcl-2 contents were also increased by 193 +/- 10.2% and 134 +/- 5.0% vs. control whereas phosphorylated Bad and the ratio of Bcl-2/Bad were depressed by 32 +/- 10.8% and 0.23 +/- 0.5% vs. control in Ca2+ -paradoxic hearts. The apoptosis as seen in Ca2+ -paradoxic hearts reperfused for 30 min was not evident in hearts at 10 min Ca2+ -repletion but was similar to hearts subjected to 60 min Ca2+ -repletion. These changes in the apoptotic pathway in cardiomyocytes subjected to Ca2+ -paradox were prevented by taurine. Furthermore, taurine attenuated the KCl- or ATP-induced increase in intracellular concentration of Ca2+ in cardiomyocytes.'] |
['Agave, which is well known for tequila and other liquor production in Mexico, has recently gained attention because of its attractive potential to launch sustainable bioenergy feedstock solutions for semi-arid and arid lands. It was previously found that agave cell walls contain low lignin and relatively diverse non-cellulosic polysaccharides, suggesting unique recalcitrant features when compared to conventional C4 and C3 plants.', "Here, we report sugar release data from fungal enzymatic hydrolysis of non-pretreated and hydrothermally pretreated biomass that shows agave to be much less recalcitrant to deconstruction than poplar or switchgrass. In fact, non-pretreated agave has a sugar release five to eight times greater than that of poplar wood and switchgrass . Meanwhile, state of the art techniques including glycome profiling, nuclear magnetic resonance (NMR), Simon's Stain, confocal laser scanning microscopy and so forth, were applied to measure interactions of non-cellulosic wall components, cell wall hydrophilicity, and enzyme accessibility to identify key structural features that make agave cell walls less resistant to biological deconstruction when compared to poplar and switchgrass."] |
['Most of our knowledge about how antiretrovirals and host immune responses influence the HIV-1 protease gene is derived from studies of subtype B virus. We investigated the effect of protease resistance-associated mutations (PRAMs) and population-based HLA haplotype frequencies on polymorphisms found in CRF01_AE pro.', 'We used all CRF01_AE protease sequences retrieved from the LANL database and obtained regional HLA frequencies from the dbMHC database. Polymorphisms and major PRAMs in the sequences were identified using the Stanford Resistance Database, and we performed phylogenetic and selection analyses using HyPhy. HLA binding affinities were estimated using the Immune Epitope Database and Analysis.', 'Overall, 99% of CRF01_AE sequences had at least 1 polymorphism and 10% had at least 1 major PRAM. Three polymorphisms (L10 V, K20RMI and I62 V) were associated with the presence of a major PRAM (P < 0.05). Compared to the subtype B consensus, six additional polymorphisms (I13 V, E35D, M36I, R41K, H69K, L89M) were identified in the CRF01_AE consensus; all but L89M were located within epitopes recognized by HLA class I alleles. Of the predominant HLA haplotypes in the Asian regions of CRF01_AE origin, 80% were positively associated with the observed polymorphisms, and estimated HLA binding affinity was estimated to decrease 19-40 fold with the observed polymorphisms at positions 35, 36 and 41.'] |
['The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment.', 'Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely.', 'Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3-132 months). A multivariate analysis identified that low serum albumin level (P = 0.011), advanced UICC stage (P < 0.001), and high carcinoembryonic antigen (CEA) level (P < 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (P < 0.001), advanced UICC stage (P < 0.001), and high CEA level (P < 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories.'] |
['Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures.', 'We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity.'] |
['To investigate the action of prostaglandin E1 on hepatic encephalopathy.', 'Prospective, randomised, controlled animal study.', 'University animal laboratory.', 'Male Wistar rats.', 'After passive avoidance learning, acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 min. Then memory retention was evaluated 48 h later. The effects of prostaglandin E1 on memory retention were examined in animals treated with the agent systemically (intravenous injections with prostaglandin E1 twice before and after surgery, 20 microg/kg each time) and animals treated with the agent topically (intracerebroventricular injection with prostaglandin E1, 0.1 microg/h for 48 h beginning at liver ischaemia).', 'Marked damage was found on plasma analysis in animals subjected to liver ischaemia, and the memory retention was also impaired. Intravenous administration of prostaglandin E1 improved both the liver injury and memory retention. However, intracerebroventricular administration of prostaglandin E1 alleviated neither.'] |
['We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression.', 'Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival.', 'Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016).'] |
['Human neonates are highly susceptible to a wide range of infections, which has been attributed to deficiencies in their innate and adaptive immunity. In contrast to the well-documented immaturity in neonatal adaptive immunity, deficiencies in their innate immunity are less defined. This study examined the inflammatory response of neonatal monocytes to bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) stimulation and discriminated the underlying Toll-like receptor (TLR)-mediated signal transduction pathways.', 'Cord blood from 30 healthy newborns of full-term elective cesarean sections and peripheral blood from 25 healthy adult volunteers were collected. Ex vivo production of inflammatory cytokines was assessed by cytometric bead array, and expression of CD14, TLR4, TLR2, phosphorylated NF-κB p65 and p38 on monocytes were detected by FACScan analysis.', 'Neonatal whole blood showed significantly decreased ex vivo TNF-α and IL-1β production in response to stimulation with the TLR4 agonist LPS, but not the TLR2 agonist PGN, when compared with adult whole blood. Consistent with the diminished inflammatory cytokine response to LPS stimulation, neonatal monocytes exhibited substantially impaired TLR-mediated signal transduction pathways characterized by down-regulated expression of CD14 and TLR4, and suppressed phosphorylation of NF-κB p65 at Ser536 and p38 following LPS stimulation. In addition, neonates had a significantly lower percentage of TLR4(+)/CD14(+) monocytes than adults.'] |
['Rheumatoid arthritis (RA), a condition with a strong genetic etiology, is associated with excess cardiovascular disease (CVD). Dyslipidemia in RA may be driven by inflammation and genetic factors. Apolipoprotein E (ApoE) is important for the regulation of lipid levels and CVD risk and immune function in the general population. We compared the frequency of 2 ApoE single-nucleotide polymorphisms (SNP) in patients with RA and controls, and studied the relationship of ApoE genotypes with lipids and inflammation in RA.', 'A total of 387 patients with well-characterized RA and 420 non-RA controls were studied. Two ApoE SNP, rs7412 (ApoE2) and rs429358 (ApoE4), were identified.', 'Genotypic (p = 0.908) and allelic (p = 0.894) frequencies did not differ between RA and controls. Within RA, the E2 allele was associated with the lowest and E4 allele with the highest levels of total cholesterol (p = 0.007), low-density lipoproteins (p = 0.004), and apolipoprotein B (p = 0.009). The E4 allele was also associated with lower C-reactive protein (p = 0.007), erythrocyte sedimentation rate (p = 0.001), and Disease Activity Score (p = 0.015) compared to the E3 allele. E2 or E4 alleles were not associated with CVD in RA, although a trend was observed (p = 0.074).'] |
['Ethanol (EtOH) decreases muscle protein synthesis, and this is associated with reduced mammalian target of rapamycin complex (mTORC)1 and increased mTORC2 activities. In contrast, phospholipase D (PLD) and its metabolite phosphatidic acid (PA) positively regulate mTORC1 signaling, whereas their role in mTORC2 function is less well defined. Herein, we examine the role that PLD and PA play in EtOH-mediated mTOR signaling.', 'C2C12 myoblasts were incubated with EtOH for 18 to 24\xa0hours. For PA experiments, cells were pretreated with the drug for 25\xa0minutes followed by 50-minute incubation with PA in the presence or absence of EtOH. The phosphorylation state of various proteins was assessed by immunoblotting. Protein-protein interactions were determined by immunoprecipitation and immunoblotting. PLD activity was measured using the Amplex Red PLD assay kit. PA concentrations were determined with a total PA assay kit.', 'PA levels and PLD activity increased in C2C12 myocytes exposed to EtOH (100\xa0mM). Increased PLD activity was blocked by inhibitors of AMP-activated protein kinase (AMPK) (compound C) and phosphoinositide 3-kinase (PI3K) (wortmannin). Likewise, suppression of PLD activity with CAY10594 prevented EtOH-induced Akt (S473) phosphorylation. PLD inhibition also enhanced the binding of Rictor to mSin1 and the negative regulatory proteins Deptor and 14-3-3. Addition of PA to myocytes decreased Akt phosphorylation, but changes in mTORC2 activity were not associated with altered binding of complex members and 14-3-3. PA increased S6K1 phosphorylation, with the associated increase in mTORC1 activity being regulated by reduced phosphorylation of AMPKα (T172) and its target tuberous sclerosis protein complex (TSC)2 (S1387). This resulted in increased Rheb and RagA/RagC GTPase interactions with mTOR, as well as suppression of mTORC2.'] |
['Although the predictive and prognostic value of thymidylate synthase (TS) expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.', "251 patients diagnosed with stage III colon carcinoma treated with surgery followed by 5-FU based adjuvant therapy were selected. The variable number of tandem repeats (VNTR) and the single nucleotide polymorphism (SNP) in the 5'untranslated region of the TS gene were genotyped.", 'There was a positive association between tumor T stage and the VNTR genotypes (p = 0.05). In both univariate and multivariate survival analysis no effects of the studied polymorphisms on survival were found. However, there was an association between both polymorphisms and age. Among patients younger than 60 years, the patients homozygous for 2R seemed to have a better overall survival, whereas among the patients older than 67 this longer survival was seen by the carriers of other genotypes.'] |
['The retention of plasma low-density lipoprotein (LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Whether or not C-reactive protein (CRP) can directly affect the transcytosis of LDL is not clear. Here we have examined the effect of CRP on transcytosis of LDL across endothelial cells and have explored the underlying mechanisms.', 'Effects of CRP on transcytosis of FITC-labelled LDL were examined with human umbilical vein endothelial cells and venous rings in vitro and, in vivo, ApoE(-/-) mice. Laser scanning confocal microscopy, immunohistochemistry and Oil Red O staining were used to assay LDL.', 'CRP increased transcytosis of LDL. An NADPH oxidase inhibitor, diphenylene iodonium, and the reducing agent, dithiothreitol partly or completely blocked CRP-stimulated increase of LDL transcytosis. The PKC inhibitor, bisindolylmaleimide I and the Src kinase inhibitor, PP2, blocked the trafficking of the molecules responsible for transcytosis. Confocal imaging analysis revealed that CRP stimulated LDL uptake by endothelial cells and vessel walls. In ApoE(-/-) mice, CRP significantly promoted early changes of atherosclerosis, which were blocked by inhibitors of transcytosis.'] |
['Expression of disaccharidase sucrase-isomaltase (SI) is significantly enhanced during neoplastic transformation of colonic epithelium. Our study was designed to determine whether expression of SI within primary tumors was significantly associated with survival in patients with colorectal carcinoma (CRC).', 'SI expression was analyzed by immunohistochemistry in paraffin sections from 182 Stage I to III CRC that had been resected for cure at the New England Deaconess Hospital between 1965 and 1977. Expression was scored as absent or present in 1 to 50 percent or more than 50 percent of tumor cells. Associations were explored among SI expression, other clinical or pathologic variables, and overall survival. The data set is mature, with 91 (56 percent) patients who had died of CRC at a median follow-up of 96 months.', 'Fifty-five percent of primary CRC expressed SI. When the multivariate Cox analysis was performed, nodal status, T stage, primary site, grade, and SI expression were independent covariates. SI expression was not associated with the expression of other clinicopathologic variables but increased the risk of death from colorectal carcinoma by 1.83-fold.'] |
['In sepsis, the reduced systemic vascular resistance (SVR) can lead to a compensatory increase in cardiac output (CO). This may mimic a normal cardiac function although there is already a sepsis-induced myocardial depression. On a cohort of patients with septic multi-organ dysfunction syndrome, we have recently developed a method to correlate the actual CO to the afterload (estimated by SVR) and introduced the parameter "afterload-related cardiac performance" (ACP), which indicates if the rise of CO is adequate for the particular SVR. In this present study it was to be investigated, if ACP can reveal septic cardiomyopathy in patients with community-acquired sepsis in the early state soon after admission to the emergency department (ED), and if there is a prognostic relevance of septic cardiomyopathy defined by ACP. Results were compared to cardiac index (CI) and cardiac power index (CPI).', 'Adults presenting at the ED with sepsis were included. ACP, CI and CPI were calculated at the time of admission, after 24, and 72 h. They were correlated to severity of disease and the prognostic values were analyzed.', 'A total of 141 patients were included. Only ACP was significantly influenced by severity of sepsis, whereas CI and CPI were not. ACP was the only hemodynamic parameter predicting mortality: nonsurvivors had lower ACP values at the time of admission to the ED (66.9 vs. 88.9 %, p < 0.05) and ACP predicted non-survival with an AUC value of 0.72, p = 0.003. Cardiac impairment defined by an ACP value of 80 % or below determined worse prognosis.'] |
['Over 70% of smokers visit a physician annually, and physicians are well-positioned to assist patients in smoking cessation. Residency offers the ideal setting to train physicians in best practices for treatment of nicotine dependence. We hypothesized that experiential learning during a smoking cessation medical clinic (SCMC) rotation would be associated with an improvement in smoking cessation practice of internal medicine (IM) interns in outpatient primary care and inpatient settings.', "This was a prospective study performed at a large university-affiliated hospital. Forty IM interns rotated through SCMC. After a lecture on nicotine addiction and treatment, interns treated SCMC patients under direct supervision of an attending pulmonologist. Interns' smoking cessation practices before and after SCMC rotation were evaluated through chart review over 1 year. Upon study completion, a survey to assess confidence was administered. Paired t tests measured changes in rates of identifying smokers, offering pharmacological treatment and counseling.", "A total of 5,622 outpatient and 683 inpatient charts of interns' encounters with patients were reviewed. Following SCMC rotation, there was an increase in identifying active smokers (7.1% versus 18.7%), prescribing therapy for smoking cessation (6.5% versus 18.0%), and providing counseling (30.9% versus 42.3%) to outpatients. For inpatients, there was an increase in nicotine replacement during admission (12.9% versus 37.4%) and prescription of therapy upon discharge (5.7% versus 16.1%). Interns reported confidence in providing appropriate counseling and treatment."] |
['Cenicriviroc is a potent antagonist of the chemokine coreceptors 5 and 2 (CCR5/CCR2) and blocks HIV-1 entry. The CCR5 inhibitor maraviroc has been shown in tissue culture to be able to repel cell-free virions from the cell surface into extracellular space. We hypothesized that cenicriviroc might exhibit a similar effect, and tested this using clinical samples from the Phase IIb study 652-2-202, by measuring rates of intracellular DNA decline. We also monitored viral RNA levels in culture fluids.', 'We infected PM-1 cells with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of cenicriviroc (20 nM) or maraviroc (50 nM) or controls. Viral load levels and p24 were measured by ELISA, quantitative PCR and quantitative real-time reverse transcription PCR at 4 h post-infection. Frozen PBMC DNA samples from 30 patients with virological success in the Phase IIb study were studied, as were early and late reverse transcript levels. Docking studies compared binding between cenicriviroc/CCR5 and maraviroc/CCR5.', 'Unlike maraviroc, cenicriviroc did not cause an increase in the amount of virus present in culture fluids at 4 h compared with baseline. The use of cenicriviroc did, however, result in lower levels of intracellular viral DNA after 4 h. Structural modelling indicates that cenicriviroc binds more deeply than maraviroc to the hydrophobic pocket of CCR5, providing an explanation for the absence of viral rebound with cenicriviroc.'] |
['Laparoscopic adrenalectomy (LA) has become the established procedure for adrenal masses less than 6 cm. The role of LA for large adrenal masses is well defined to a lesser extent.', 'Thirty-six LAs were performed in 32 patients (including four patients with single stage bilateral adrenalectomies) over a period of 3 years, from May 2002 to 2005. Patients were divided into two groups based on the tumour size, i.e. masses less than 6 cm (group I) and masses 6 cm or more (group II).The results with respect to mean (95% confidence interval) operative time, blood loss, postoperative course and complications were compared.', "Group II included 11 LAs performed in 10 patients including one bilateral LA for bilateral phaeochromocytomas in multiple endocrine neoplasia 2A. The mean size (+/-standard deviation) of masses was 8 cm (+/-1.47). In comparison, 22 patients in group I underwent 25 adrenalectomies (including three bilateral single stage procedures for Cushing's syndrome). The mean size of masses was 4.1 cm (+/-1.27). There were eight and six phaeochromocytomas in groups I and II, respectively. By comparing groups I and II, only minimal increase in blood loss and operating time was noted with no significant difference in hospital stay and morbidity. Two cases required conversion to hand assistance towards the end of the procedure in view of their large size."] |
['In patients suffering from major depressive disorders (MDD), improvements in MDD are related to increased activation of brain-derived neurotrophic factor (BDNF), an endogenous protein that facilitates neural functioning. To treat patients suffering from severe MDD, electroconvulsive therapy (ECT) is considered an efficacious and safe intervention, though the impact of ECT on plasma BDNF levels has thus far barely been investigated. The aim of the present study was therefore to assess plasma BDNF levels and depression of patients suffering from severe MDD treated with additional ECT compared to patients treated with citalopram only.', 'A total of 40 patients (mean age: M\xa0=\xa031.45 years; females 30%) suffering from MDD and all receiving 40\xa0mg/d citalopram were assigned either to a control group (N\xa0=\xa020), or to a target group (N\xa0=\xa020) undergoing additional 12 sessions of ECT. Plasma BDNF and symptom severity were assessed at baseline and four weeks later.', 'Plasma BDNF increased in both groups over time, though the significant Time by Group-interaction revealed an increase of 101% in the target group as compared to the control group. Symptom severity significantly decreased in both groups over time, though without being related to plasma BDNF levels.'] |
['Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization.', 'Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11.', 'Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables.'] |
['To test the utility of zinc protoporphyrin to heme ratio (ZnPP/H) as an indicator of iron status in premature infants and to evaluate the effect of oral iron supplements on oxidative injury. We hypothesized that iron sulfate supplementation would decrease the ZnPP/H in preterm infants.', 'Infants eligible for this prospective study were: hospitalized, 24 to 32 weeks of gestation, 7 to 60 days old, feeding > or = 70 mL/kg/d, with a ZnPP/H > or = the mean for age. Iron dose was determined by the ZnPP/H. Iron status and oxidative injury were evaluated at study entry and completion. Concurrent control subjects met entry criteria but were not enrolled and were not treated with iron during the study interval. Statistical evaluation included repeated measures analysis of variance and Z-score conversions.', 'Entry ZnPP/H of iron-treated subjects (n = 16) and control subjects (n = 16) were not different. The ZnPP/H of iron-treated infants was lower at study end (P < .05) but did not change in control infants. Iron treatment (3 to 12 mg/kg/day) was not associated with changes in conventional measures of iron status nor in measures of oxidative injury.'] |
['MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0) of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 controls.', 'Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis.'] |
['The purpose of this report was to review the initial use and feasibility of continuous renal replacement therapy (CRRT) among combat casualties in a war zone. Although rapid evacuation to more advanced levels of care has emerged as the standard approach, life-threatening sequelae of acute kidney injury (AKI) can preclude safe patient evacuation. For the first time in US combat casualty care, a sustained, intensivist-led CRRT program was initiated during 2010 at an Air Force theater hospital.', 'A prospective study of consecutive US service members (USSMs) who developed combat-related renal failure and underwent CRRT at the Craig Joint Theater Hospital was undertaken. Baseline patient characteristics, indications for CRRT, laboratory values, and outcomes were evaluated.', 'Nine USSMs were treated during 14-months. All were male, with a mean (SD) age of 28 (7) years and mean (SD) Injury Severity Score (ISS) of 34 (12). The dominant mechanism was blast injury (8 of 9), followed by gunshot wound (1 of 9). Most patients were Acute Kidney Injury Network (AKIN) 3 and all developed critical hyperkalemia (mean [SD], peak K⁺ 6.4 [0.4]). The peak plasma creatinine ranged from 1.4 mg/dL to 4.2 mg/dL (mean [SD], 3.3 [0.9] mg/dL). Patients had a mean (SD) of 17.6 [8.1] hours of CRRT before evacuation to higher echelons of care. All USSMs survived to achieve safe evacuation from the combat zone to the regional trauma center in Landstuhl, Germany (Landstuhl Regional Medical Center). Three patients died of multiorgan failure at Landstuhl Regional Medical Center. Six patients survived to undergo additional treatment in the United States.'] |
['Chronic constipation (CC) is common and there is a need for more effective and better-tolerated agents that normalize bowel function without affecting secretion. Prucalopride is a novel, selective serotonin(4) receptor agonist with enterokinetic properties.', 'Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre.', "After 4-weeks' run in, patients were randomized to 4 weeks' once daily, double-blind treatment with either prucalopride 4 mg (n = 27) or placebo (n = 26). A 50% dose reduction after 2 weeks' treatment was possible for patients with an excessive gastrointestinal response to the study medication (severe cramps, abdominal pain, and diarrhea). Patients assessed efficacy using a visual analogue scale (VAS) and recorded bowel function in daily diaries. The investigator assessed efficacy and total gut transit time (marker study).", 'Patient VAS assessment demonstrated that prucalopride was significantly more effective than placebo in softening stools, and decreasing straining and time to first stool. Prucalopride also had a positive effect on stool frequency, feeling of complete evacuation and total gut transit time, although these differences were not statistically significant compared with placebo. The most common adverse events were gastrointestinal symptoms and headache; most were mild to moderate. There were no clinically relevant effects on cardiovascular or laboratory parameters.'] |
['Diverticular disease and cardiovascular disease share several risk factors. Inflammation associated with diverticular disease could predispose to cardiovascular disease. We assessed the association between a diagnosis of diverticular disease and subsequent arterial and venous thromboembolic events, adjusting for related comorbidities to explore a possible causal relationship.', 'We identified 77,065 incident cases of diverticular disease from 1980-2011 from Danish nationwide medical registries; these were matched for age and sex with 302,572 population comparison cohort members. Individuals with a history of cardiovascular disease were excluded. We used Cox proportional hazards regression to compute incidence rate ratios, comparing the incidence of acute myocardial infarction, stroke, venous thromboembolism, and subarachnoid hemorrhage in patients with diverticular disease with those of the population cohort members, adjusting for age, sex, obesity, diabetes, hyperlipidemia, chronic obstructive pulmonary disease, connective tissue disease, renal disease, and treatments and medications.', 'The adjusted incidence rate ratios for patients with diverticular disease, compared with population cohort members, were 1.11 (95% confidence interval [CI], 1.07-1.14) for acute myocardial infarction, 1.11 (95% CI, 1.08-1.15) for overall stroke, 1.36 (95% CI, 1.30-1.43) for overall venous thromboembolism, and 1.27 (95% CI, 1.09-1.48) for subarachnoid hemorrhage. The relative risk of each event remained increased after we adjusted for changes in aspirin use or for endoscopy or colorectal surgery after the diagnosis of diverticular disease. These findings also held after excluding the first year of follow-up and limiting the analysis to patients with diverticulitis.'] |
['Hypoglycaemic sulphonylureas are thought to stimulate insulin release by binding to a sulphonylurea receptor, closing K(ATP) channels and inducing electrical activity. However, the fact that these drugs stimulate insulin release at high glucose concentrations where K(ATP) channels are closed suggests additional ionic actions. The aim of this study was to test the hypothesis that sulphonylureas influence the current of the glucose- and volume-regulated anion channel.', 'Electrical and ion-channel activity were recorded in isolated rat beta cells using the patch-clamp technique. (86)Rb(+) efflux was measured using intact islets. Beta cell volume was measured using a video-imaging technique.', "In the absence of glucose, tolbutamide (100 micromol/l) transiently depolarised the cells. In the presence of glucose (5 mmol/l), tolbutamide evoked a sustained period of electrical activity, whilst at 10 mmol/l glucose, the drug evoked a pronounced 'silent' depolarisation. In the absence of glucose, tolbutamide inhibited (86)Rb(+) efflux. However, at 10 mmol/l glucose, tolbutamide induced a transient stimulation of efflux. Tolbutamide potentiated the whole-cell volume-regulated anion conductance in a glucose-dependent manner with an EC(50) of 85 micromol/l. In single channel recordings, tolbutamide increased the channel-open probability. Tolbutamide caused beta cell swelling in the presence of glucose, but not in its absence."] |
['The objective of the study was to evaluate microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation in the p53 gene in relation to response and patient survival to a cisplatin-based neoadjuvant chemotherapy in gastric cancer.', 'Fifty-three pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for mutations by denaturing high-pressure liquid chromatography and sequencing. p53 protein expression was evaluated by immunohistochemistry. Patients were treated with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The median follow-up of the patients was 45.6 months.', 'p53 mutations were identified in 19 of the 53 (36%) analyzed tumors. No significant association with response or survival was found for p53 mutation or for p53 protein expression. MSI (either high-grade MSI or low-grade MSI) did not show a correlation with response. With respect to LOH, LOH at chromosome 17p13 showed a significant association with therapy response (P = 0.022) but did not reach statistical significance in terms of patient survival. The global LOH rate, expressed as fractional allelic loss (FAL), was assessed, and tumors were classified into tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A statistically significant association of FAL with therapy response was found (P = 0.003), with a high FAL being related to therapy response. The sensitivity, specificity, positive predictive value, and negative predictive value for FAL > 0.5 were 45%, 93%, 82%, and 72%, respectively.'] |
['Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells.', 'BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed.', 'Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043).'] |
['Cystatin C, a novel endogenous marker of glomerular filtration rate, has been reported as more sensitive to detect renal insufficiency than creatinine. The purpose of the present study was to examine the clinical significance of serum cystatin C level in patients with mild to moderate heart failure.', 'Serum levels of cystatin C were measured by an enzyme immunoassay in 140 patients with heart failure and 64 control subjects without heart failure. Patients were prospectively followed during a median follow-up period of 480 days, with the end points of cardiac death and progressive heart failure requiring rehospitalization. Serum levels of cystatin C were higher in patients with heart failure than in control subjects (1.14 +/- 0.60 ng/mL versus 0.72 +/- 0.14 ng/mL, P < .001). The Cox multivariate proportional hazard analysis revealed that a change of 1 standard deviation (SD) in cystatin C level was the one of independent predictor for cardiac events (hazard ratio, 1.94; 95% confidence interval, 1.29-6.64; P < .01). The cardiac event rate was markedly higher in patients with elevated cystatin C level (> or =1.0 ng/mL) than in those with normal level (< or =1.0 ng/mL) (38.7% versus 10.3%, P < 0.001). Furthermore in patients with normal creatinine levels (n = 91), the cardiac event rate was similarly higher in patients with elevated cystatin C than in those with normal levels (29.2% versus 7.5%, P = .002).'] |
["Building on the Conservation of Resources theory, this paper examined the unique and interactive associations of negative and positive work-to-family spillover (NWFS and PWFS, respectively) at the individual and organizational level with hotel managers' work exhaustion and satisfaction, beyond job demands and supervisors' leadership style.", "Guided by the levels of analysis framework, we first tested the unique associations of NWFS and PWFS with emotional exhaustion and job satisfaction at the individual level (571 hotel managers), beyond job demands supervisors' leadership style. Second, using multilevel modeling, we tested the climate effects of NWFS and PWFS on emotional exhaustion and job satisfaction aggregated at the organizational level (41 hotels). Third, we examined the role of the organizational climate of PWFS in the associations of individual-level NWFS with emotional exhaustion and job satisfaction.", "Beyond the effects of psychological job demands and supervisor's transformational leadership, at the individual level, hotel managers who experienced higher NWFS than other managers reported more exhaustion and lower job satisfaction, whereas those with higher PWFS reported less exhaustion and higher satisfaction. At the organizational level, working in hotels where the average level of NWFS was higher than other hotels was associated with feeling more exhaustion of the individual members; working in hotels with higher PWFS was associated with feeling less exhaustion. The negative link between individual-level NWFS and job satisfaction was buffered when organization-level PWFS was higher, compared to when it was lower."] |
["It has been proposed that multisite atrial pacing (MSAp) restores atrial electrical activation and prevents atrial fibrillation recurrence; however, single-site Bachmann's bundle pacing (BBp) has also been reported as providing effective atrial resynchronization. Coronary sinus pacing (CSp) leads to reversed impulse propagation within the atria.", 'Acute echocardiographic examination was performed in 15 healthy subjects, and in 25 patients with sinus node dysfunction and recurrent atrial fibrillation during MSAp (atrial leads in the BB area and CS ostium), and single-site BBp and CSp. Regional atrial synchrony was assessed by tissue Doppler echocardiography. Pacing mode had no effect on stroke volume. CSp resulted in right atrial filling diminution, shortened mechanical atrioventricular delay in the right heart and diminished right ventricular inflow. The magnitude of reversion of the physiological right-to-left atrial contraction sequence was most prominent during CSp (15+/-11, 12+/-23, 3+/-21, 42+/-23 ms; control, MSAp, BBp, CSp respectively, P<0.0001). BBp provided the best atrial contraction synchrony, and had a comparable effect on global cardiac function to MSAp.'] |
['Early repolarization (ER) is associated with increased risk of sudden cardiac death and ventricular fibrillation (VF) in patients with/without structural heart disease. In this trial we examined the short- and long-term prognostic value of ER on admission electrocardiogram (ECG) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).', 'Consecutive 521 patients with acute STEMI who underwent primary PCI were enrolled prospectively. Twelve-lead ECGs obtained during the initial diagnosis were scanned and stored digitally. The leads showing the typical ST segment elevation due to the acute infarction were excluded and the remaining ECG leads were included in the analysis for the presence of ER.', 'The study group included 61 STEMI patients (55 male; mean age 57.6±12.6 years) with ER and 460 STEMI patients (378 male; mean age 57.1±12.5) without ER on ECG. In the ER group, 14 patients (22.9%) had notching, 10 patients (16.4%) had slurring, and 37 patients (60.7%) had only J-point elevation. When analyzing regional leads, ER was observed mostly in inferior leads (n=40, 65.6%). During the hospitalization period, ventricular tachycardia or VF occurred more frequently in the ER group (19.6% vs. 10.9%; p=0.04) and 6 patients (6.9%) from the ER group and 14 patients (3%) from the control group died (p=0.01). During a follow-up period of 21.1±10.2 months, mortality was significantly higher in the ER group (12.7% vs. 4.2%; p=0.01). When total mortality rates were considered, highest mortality was observed in patients with notching pattern (5/14 subjects; 35.7%) when compared to patients with slurring (3/10 subjects; 30%), patients with only J-point elevation patterns (5/37subjects; 13.5%) and the control group (33/460 subjects; 7.1%). Presence of notching and slurring pattern on admission ECG was found as independent predictors of long-term mortality; whereas presence of only J-point elevation was not.'] |
['The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown.', 'From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665-2028).', 'The eGFR slope was less in Group 1 (-0.081 mL/min/month) compared with Group 0 (-0.183 mL/min/month; P = 0.03) or Group 2 (-0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (-0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P = 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient (n = 99).'] |
['To investigate the direct effects of dexmedetomidine (DEX) on isolated human internal mammary artery (IMA).', 'In vitro experimental study.', 'Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Gulhane School of Medicine, Ankara, Turkey.', 'IMA segments were obtained from 18 patients undergoing coronary artery bypass surgery.', 'The response in IMA was recorded isometrically by a force displacement transducer in isolated organ baths. DEX-induced contractions were tested in the presence of the alpha2-adrenoceptor antagonist yohimbine (10(-7) mol/L) and the alpha1-adrenoceptor antagonist prazosin (10(-8) M). The effect of DEX (10(-7), 10(-6), and 10(-5) mol/L) on phenylephrine (10(-9)-3 x 10(-4) mol/L)-induced contactions was also tested.', 'DEX (10(-9) mol/L-3 x 10(-5) mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10(-9) mol/L-3 x 10(-7) mol/L) was attenuated by yohimbine (10(-7) mol/L), whereas prazosin (10(-8) mol/L) attenuated the contractions at higher concentrations of DEX (10(-6) mol/L-3 x 10(-5) mol/L). Incubation of IMA segments with high concentrations of DEX (10(-6) mol/L and 10(-5) mol/L) caused an inhibition of phenylephrine (10(-9) mol/L-3 x 10(-4) mol/L)-induced contraction.'] |
['The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis.', 'Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD).', 'Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product.', 'Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function.'] |
['Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque.', 'In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects.'] |
['We recently showed that IGFBP2 is overexpressed in primary lung cancer tissues. This study aims to determine whether IGFBP2 is elevated in blood samples of lung cancer patients and whether its level is associated with clinical outcomes.', "Plasma IGFBP2 levels were determined blindly by enzyme-linked immunosorbent assay in 80 lung cancer patients and 80 case-matched healthy controls for comparison. We analyzed blood samples for IGFBP2 levels from an additional 84 patients with lung cancer and then tested for associations between blood IGFBP2 levels and clinical parameters in all 164 lung cancer patients. All statistical tests were two-sided and differences with p<0.05 were considered significant. The mean plasma concentration of IGFBP2 in lung cancer patients was significantly higher than that in healthy controls (388.12 ± 261.00 ng/ml vs 219.30 ± 172.84 ng/ml, p<0.001). IGFBP2 was increased in all types of lung cancer, including adenocarcinoma, squamous cell cancer, and small-cell cancer, regardless of patients' age, sex, or smoking status. IGFBP2 levels were mildly but significantly associated with tumor size and were significantly higher in stage IV than stage I or III disease. A multivariate analysis showed that lung cancer patients whose blood IGFBP2 was higher than 160.9 ng/ml had a poor survival outcome, with a hazard ratio of 8.76 (95% CI 1.12-68.34, p=0.038 after adjustment for tumor size, pathology, and stage). The median survival time for patients with blood IGFBP2 >160.9 ng/ml is 15.1 months; whereas median survival time was 128.2 months for the patients whose blood IGFBP2 was ≤ 160.9 ng/ml (p =0.0002)."] |
['We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma.', 'A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression.', 'There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R(2) = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R(2) = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R(2) = 0.350, P < 0.001) and SAP MD (R(2) = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness.'] |
['To study the inhibitory effects of hyaluronan (HA) on the production of matrix metalloproteinase-1 (MMP-1) by rheumatoid synovial fibroblasts (RSF) stimulated by proinflammatory cytokines, tumor necrosis factor-a (TNF-a), and interleukin-1beta (IL-1beta).', 'HA of various sizes at various concentrations was added to monolayer cultures of RSF in the presence of TNF-a or IL-1beta, with or without pretreatment with a monoclonal antibody against CD44, OS/37. Concentrations of MMP-1 in cell lysates and conditioned media and of CD44 on RSF were assayed by immunoblotting. MMP-1 expression was analyzed by reverse transcriptase-polymerase chain reaction. Binding of HA to RSF was evaluated by confocal microscopy using fluorescein-conjugated HA and OS/37.', 'Treatment with HA (0.3 approximately 3.0 mg/ml) resulted in a significant decrease in the production of MMP-1 induced by TNF-a and IL-1beta, in a dose-dependent manner. HA of 250 approximately 2300 kDa at 3 mg/ml was found to suppress the induction of MMP-1 by TNF-a. HA decreased the cytokine-induced MMP-1 synthesis in RSF at mRNA and protein levels. The monoclonal antibody, which showed abundant expression of CD44 on RSF by immunofluorescein cytochemistry, partially blocked the binding of fluorescein-conjugated HA to RSF. Pretreatment with OS/37 reversed the inhibition of MMP-1 production in TNF-a or IL-1beta-stimulated RSF caused by HA.'] |
['Among patients admitted for acute decompensated heart failure (ADHF), half are aged 75 years or over. The high prevalence of co-morbidities and functional impairments in this age group may affect patient outcomes.', 'To assess the association between co-morbidities, functional status and in-hospital mortality in patients with ADHF aged ≥75 years.', 'A prospective, multicentre cohort study.', 'Five French hospitals.', 'Five hundred and fifty-five patients aged ≥75 years admitted to the emergency department with ADHF.', 'Baseline clinical data and co-morbidities were recorded at admission. Functional status and cognition were assessed using the Katz index and Mini-Mental Status Examination score, respectively. The primary outcome was in-hospital mortality.', 'We found high prevalences of co-morbidities and functional impairments including hypertension (74.0%), atrial fibrillation (40.2%), prior acute coronary syndrome (32.3%) and diabetes (18.2%). The average creatinine clearance was 56.3 ml/min/1.73 m(2) (interquartile range, 39.2-77.0). In-hospital mortality was 67/555 (12.1%; 95% confidence interval, 9.4-14.8). In multivariate analysis, in-hospital mortality showed a statistically positive association with prior loss of self-sufficiency (Odds ratio [OR]: 5.85 [2.25-12.19]), hyperglycaemia (OR: 1.80 [1.26-2.54] per 1 SD increase), prior cerebral ischaemic event (OR: 3.56 [1.51-8.44]) and troponin I elevation above upper limit of normal (OR: 2.81 [1.37-5.77]). In addition, systolic blood pressure (OR: 0.98 [0.97-0.99] per 1 mmHg increase) and creatinine clearance (OR: 0.72 [0.51-1.00] per 1 SD increase) were negatively associated with in-hospital mortality.'] |
['Considering the existence of a large number of liver cell degeneration and necrosis in fibrotic liver, liver function was damaged severely and could not effectively regenerate after partial hepatectomy (PHx). The aim of this study was to investigate whether decorin (DCN) could promote the liver regeneration after PHx in fibrotic mice.', 'Forty mice (5-week-old, Balb/c) were injected with CCl4 intraperitoneally and liver fibrosis model was established after 5 weeks. The survival mice were randomly divided into two groups: control group and DCN group. Then, we performed 70% PHx on all these mice and injected DCN or phosphate-buffered saline plus normal saline (NS) to each group, respectively, after surgery. Liver body weight ratio (LBR), quantitative real-time polymerase chain reaction, and immunohistochemistry were used to analyze liver regeneration and fibrosis degree in both groups, and to find out whether exogenous protein DCN could promote the regeneration of fibrosis liver after PHx.', 'Expressions of a-smooth muscle actin (SMA) mRNA and LBR had significant increases in the DCN group at postoperative Day 3 (POD 3, P < 0.05). The protein expressions of CD31, a-SMA, and tumor necrosis factor (TNF)-a were higher in the DCN group than those in the control group by immunohistochemistry at POD 3 (P < 0.05).'] |
['UBQLN2 mutations have recently been associated with familial forms of amyotrophic lateral sclerosis (ALS) and ALS-dementia. UBQLN2 encodes for ubiquilin-2, a member of the ubiquitin-like protein family which facilitates delivery of ubiquitinated proteins to the proteasome for degradation. To study the potential role of ubiquilin-2 in ALS, we used recombinant adeno-associated viral (rAAV) vectors to express UBQLN2 and three of the identified ALS-linked mutants (P497H, P497S, and P506T) in primary neuroglial cultures and in developing neonatal mouse brains.', 'In primary cultures rAAV2/8-mediated expression of UBQLN2 mutants resulted in inclusion bodies and insoluble aggregates. Intracerebroventricular injection of FVB mice at post-natal day 0 with rAAV2/8 expressing wild type or mutant UBQLN2 resulted in widespread, sustained expression of ubiquilin-2 in brain. In contrast to wild type, mutant UBQLN2 expression induced significant pathology with large neuronal, cytoplasmic inclusions and ubiquilin-2-positive aggregates in surrounding neuropil. Ubiquilin-2 inclusions co-localized with ubiquitin, p62/SQSTM, optineurin, and occasionally TDP-43, but were negative for α-synuclein, neurofilament, tau, and FUS. Mutant UBLQN2 expression also resulted in Thioflavin-S-positive inclusions/aggregates. Mice expressing mutant forms of UBQLN2 variably developed a motor phenotype at 3-4 months, including nonspecific clasping and rotarod deficits.'] |
['Orotate phosphoribosyl-transferase (OPRT) is the initial enzyme of the 5-fluorouracil (5-FU) metabolic pathway, converting 5-FU into 5-fluorouridinemonophosphate, which is the most important mechanism of 5-FU activation. We therefore investigated whether overexpression of the OPRT gene enhances sensitivity to 5-FU.', 'An expression vector of the OPRT gene (pTARGET-OPRT) was transfected into two gastric cancer cell lines, TMK-1 and MKN-45, with low baseline expression levels of OPRT. The sensitivity to and anti-tumor activity of 5-FU were then investigated in vitro and in vivo in these two transfected clones (TMK-OPRT and MKN-OPRT).', 'Although cell growth was unaltered compared to parent cells, overexpression of the OPRT gene was confirmed by Western blotting in both the TMK-OPRT and MKN-OPRT cells. OPRT enzyme activity increased 38-fold in TMK-OPRT cells and 8.0 fold in MKN-OPRT cells compared to their parent cells. Interestingly, although the sensitivity to Adriamycin, cis-platinum, mitomycin C and paclitaxel was unaltered in the transfected clones, the sensitivity to 5-FU was increased 14.2- and 6.0-fold in TMK-OPRT and MKN-OPRT cells, respectively, compared to their parent cells. Moreover, enhanced sensitivity was also confirmed in the in vivo study.'] |
['The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown. AIM, DESIGN AND METHODS: The objective of this study was to investigate this relationship and evaluate the ability of HbA1c levels to predict carotid atherosclerosis in a Chinese population. This was a cross-sectional study, which included 541 subjects without known diabetes (Taiwan Lifestyle Study). About 67 (9·2%) subjects were newly diagnosed with diabetes during the study. Carotid intima-media thickness (IMT) and the presence of carotid plaques were determined using ultrasonography.', 'The HbA1c level in all subjects was positively correlated with carotid IMT (β = 0·018, P = 0·03) after being adjusted for age, gender, smoking, low-density lipoprotein cholesterol level, hypertension and body mass index. HbA1c level was higher in subjects with plaques in carotid arteries (P = 0·01). There was a positive and linear relationship between HbA1c levels and the probability of having plaques, thickened carotid IMT or both (P for all comparisons, <0·05). The ability of HbA1c levels to predict thickened carotid IMT or the presence of plaques was only modest {the optimal cutoff of HbA1c level [5·7%] was determined from the receiver operating characteristic (ROC) curve (sensitivity = 67%, specificity = 61%) and the area under the ROC curve [0·666]}.'] |
["During human pregnancy, the uterine lining is highly populated with killer-immunoglobulin-like receptor (KIR)-expressing NK cells that recognize HLA-C molecules on trophoblast cells. The goal of this study was to analyze the KIR gene contents and frequencies in a N. American cohort of women with RPL of unknown etiology to evaluate whether there is a genetic susceptibility to RPL based on a woman's KIR repertoire and her HLA-C group, as well as the HLA-C group of the partner.", 'The frequencies of KIR and HLA-C1 and HLA-C2 genes were evaluated in 139 Caucasian women with RPL; HLA-C1, and HLA-C2 group genes were analyzed in their partners (n\xa0=\xa042). The gene frequencies were compared with data reported from corresponding populations.', 'Overall, the frequencies of HLA-C groups and KIR genes and genotypes in RPL cohort resembled the frequencies for US Caucasians. The HLA-C1 and HLA-C2 group distribution was significantly different between women with or without KIR2DS1. Women positive for KIR2DS1 (45.3% of the study cohort) had an increased frequency of its ligand, HLA-C2 (0.5159 versus 0.3684 in KIR2DS1 negative women, P\xa0=\xa00.014).'] |
['Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach.', 'Anterior cingulate cortical tissues (gray\xa0+\xa0white matter) were manually-delineated in 1.5\xa0T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis.', 'As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes.'] |
['Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response.', 'Eighteen obese [body mass index (BMI) 30.0-40.0 kg · m(-2)] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed.', 'Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics.'] |
['Along with the increasing prevalence of obesity and related diseases, particularly atherosclerotic diseases, metabolic syndrome (MetS) is now a common and major public health issue in many countries around the world. Adiponectin, a protein secreted by the adipose tissue, has become recognized as a key player in the development of MetS. These days, not only MetS but also borderline metabolic/physiological abnormalities, such as impaired fasting glucose, high normal blood pressure and high normal plasma cholesterol, have been reported to be risk factors for atherosclerotic disease. Therefore, we undertook this study to determine the relationship between adiponectin and borderline metabolic/physiological abnormalities, as well as MetS.', 'A cross-sectional study performed from April 2007 to November 2009.', 'In 16\u2009892 Japanese adults (10\u2009008 men and 6884 women), we examined the relationship between the serum adiponectin concentration and borderline metabolic/physiological abnormalities or MetS by a questionnaire survey about medical treatment, body size measurement and measurement of laboratory parameters including the serum adiponectin concentration.', 'Adiponectin showed a significant negative correlation with the number of MetS components. In subjects without overt diabetes mellitus, hypertension or dyslipidemia, the adiponectin concentration also showed a significant negative correlation with the number of borderline metabolic abnormalities.'] |
['Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms.', 'This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes.', 'An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported.', 'From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3); deoxyribonuclease I-like 3 (DNASE1L3); IL-1β (IL1B); alkaline phosphatase, tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P < .0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV1; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma.'] |
['Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated.', 'Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins.'] |
['Intestinal perforation in extremely premature infants is an important cause of death. The aim of the study was to identify fetal heart rate patterns, which were associated with intestinal perforation.', "A retrospective cohort study was performed in 92 women who delivered at 22-27 weeks' gestation at a tertiary center in Miyazaki. They delivered 74 singletons, 17 twins and one triplet. Intrapartum fetal heart rate monitoring charts of at least 2-h were examined. Intestinal perforation was diagnosed by the clinical manifestations and operative findings. Multiple logistic regression analysis was used to compare between intestinal perforation group and non-perforation group.", 'Of the 111 neonates, 17 had intestinal perforation. Severe variable deceleration (p < 0.05), prematurity (p < 0.05), postnatal corticosteroid (p < 0.05), intraventricular hemorrhage of grade III or IV (p < 0.01) and poor survival (p < 0.05) were more frequent in infants with perforation than in the 94 without perforation. Multivariate analysis adjusted for the other risk factors revealed that only severe variable deceleration remained as a risk factor: (odds ratio 3.7; 95% CI 1.1-12.1; p = 0.03).'] |
['Deficiencies in serotonin function have been associated with irritability and aggression but enhancing serotonin has also been shown to promote social status and affiliative behaviour in non-human primates and more recently in humans.', 'To investigate the effects of citalopram, a selective serotonin reuptake inhibitor (SSRI), on social behaviour with a flatmate and a stranger.', 'Ten pairs of healthy volunteers took part in a randomized double-blind crossover study of 2 weeks treatment with citalopram (20 mg/day) and placebo with a 2-week washout period. In each pair, one person (subject) took the tablets and the other (flatmate) received no treatment. On the last day of each treatment period, the subjects socially interacted with a confederate behaving as a responsive person in a stranger-dyadic social interaction paradigm. After the interaction, subjects played the Mixed-motive game, which measures cooperative behaviour and communication, with the confederate. The flatmates evaluated the social behaviour of the subjects before and at the end of the treatment periods.', 'On citalopram, the subjects were rated as significantly less submissive by their flatmates and they showed a dominant pattern of eye contact in the stranger-dyadic social interaction paradigm. They also reduced the number of points they awarded themselves and sent more cooperative messages during the game.'] |
['Regulatory macrophages play an important role in wound healing and gut homeostasis and have antiinflammatory properties. Induction of this cell type (Mψ(ind) ) by the anti-tumor necrosis factor (TNF) antibodies, infliximab and adalimumab, has recently been shown in vitro. Also, the superiority of infliximab/azathioprine combination therapy over infliximab or azathioprine monotherapy has recently been established, but the mechanism behind this remains unclear. The aim of this study was to examine the induction of regulatory macrophages in patients with and without mucosal healing in response to infliximab. In addition, we studied the effect of infliximab/azathioprine combination treatment on the differentiation and function of regulatory macrophages.', 'Inflammatory bowel disease (IBD) patients (n = 10) underwent endoscopy before and after first infliximab treatment. Immunohistochemical staining of CD68 and CD206 was performed in all patients. Mixed lymphocyte reactions (MLRs) were treated with infliximab, azathioprine, or both. Macrophage phenotype was evaluated by flow cytometry and inhibition of T-cell proliferation was measured in a secondary MLR containing macrophages and third-party lymphocytes.', 'A significant induction of regulatory macrophages was observed in patients with mucosal healing after treatment with infliximab; this induction was absent in patients without mucosal healing. In addition, Mψ(ind) have the ability to induce wound healing in an in vitro model, further suggesting a key role for infliximab-induced macrophages in mucosal healing. Upon infliximab/azathioprine combination treatment, an increased number of regulatory macrophages was observed. These macrophages also displayed stronger immunosuppressive properties than macrophages induced by infliximab monotherapy.'] |
['First-generation, E1-deleted (deltaE1) adenovirus vectors currently used in cardiovascular gene therapy trials are limited by tissue inflammation, mainly due to immune responses to viral gene products. Recently, helper-dependent (HD; also referred to as "gutless") adenovirus vectors devoid of all viral coding sequences have been shown to cause low inflammation when injected intravenously or into skeletal muscles. However, HD vectors have not been evaluated in cardiovascular tissues.', 'HD and deltaE1 vectors containing a cytomegalovirus-driven expression cassette for the green fluorescent protein (GFP) gene were administered intramyocardially to adult rats (n = 54). GFP expression was measured by ELISA at varying time intervals after gene transfer. HD and deltaE1 vectors were equally efficient at transducing the myocardium. Tissue inflammation was assessed by immunostaining for leukocytes and quantitative real-time RT-PCR for cytokine mRNA expression. Monocyte/macrophages, CD4(+) and CD8(+) lymphocytes infiltrating the myocardium were less abundant with HD than deltaE1 vectors. Transcripts levels for pro-inflammatory cytokines such as IL-1beta, tumor necrosis factor-alpha, and RANTES were decreased with HD vectors. However, both vectors were associated with a decline in GFP expression over time, although low-level expression was occasionally detectable 10 weeks after HD vector administration. The two vectors transduced endothelial cells in rat arteries (n = 11) with comparable efficiencies. Vascular GFP expression was not detectable at 10 weeks.'] |
['The objective of this study was to quantify microglial and astrocytic cell responses after focal 125I irradiation of normal brain and to determine the effects of an intravenous infusion of alpha-difluoromethylornithine (DFMO) on those responses.', 'Adult beagle dogs were irradiated using high activity 125I sources. Saline or DFMO (75 mg/kg/day) was infused for 18 days, and 1 to 10 weeks later brain tissues were collected. Immunohistochemical stains were used to label phagocytes and amoeboid microglia (lectin RCA-1), astrocytes (GFAP), and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cell densities (cells/mm2) and BrdU labeling indices were quantified.', 'In dogs infused with saline, increases in phagocytes and amoeboid microglia were observed at 1-2 weeks and 4 weeks, respectively. The labeling indices for phagocytes and amoeboid microglia peaked at 4 weeks with maximum values of 4.8 and 13.4%, respectively. Astrocyte cell numbers increased from 2-6 weeks following irradiation; increased labeling indices were observed after 2 weeks. An infusion of DFMO significantly suppressed BrdU labeling and delayed the increase in cell numbers for phagocytes and amoeboid microglia. In both treatment groups, the proportion of total BrdU labeling accounted for by phagocytes was maximum 1 week after irradiation and then decreased. The proportion of total BrdU labeling accounted for by amoeboid microglia and astrocytes was zero for 2 weeks and then increased.'] |
['Nephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress.', 'The patient cohort comprised 23 cystinosis patients (16 males) aged <18\xa0years (mean age 8.0\u2009±\u20093.6\xa0years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25\xa0mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient.', 'Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2) \xa0nmol/mL, respectively (p\u2009<\u20090.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1\u2009±\u20090.5 vs. 0.9\u2009±\u20090.5\xa0mg/dL, respectively; p\u2009<\u20090.0001), creatinine clearance (69.7\u2009±\u200932.2 vs. T1 = 78.5\u2009±\u200933.9\xa0mL/min/1.73 m(2), respectively; p\u2009=\u20090.006), and cystatin c level (1.33\u2009±\u20090.53 vs. 1.15\u2009±\u20090.54\xa0mg/l, respectively; p\u2009=\u20090.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3\xa0months (T -3) before NAC initiation and at 3 (T +3) and 6\xa0months (T +6) after NAC had been withdrawn were also evaluated.'] |
['Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics.', 'Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-β) by ELISA.', 'Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-β. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation.'] |
['Cisplatin is a widely used anti-cancer drug in the treatment of a wide range of tumors; however, its application is limited by nephrotoxicity, which is affected by oxidative stress. We have reported that molecular hydrogen (H(2)) acts as an efficient antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that hydrogen efficiently mitigates the side effects of cisplatin by reducing oxidative stress.', 'Mice were administered cisplatin followed by inhaling hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) in water) is applicable by examining oxidative stress, mortality, and body-weight loss. Nephrotoxicity was assessed by morphological changes, serum creatinine and blood urea nitrogen (BUN) levels.', 'Inhalation of hydrogen gas improved mortality and body-weight loss caused by cisplatin, and alleviated nephrotoxicity. Hydrogen was detected in blood when hydrogen water was placed in the stomach of a rat. Consuming hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels. Despite its protective effects against cisplatin-induced toxicity, hydrogen did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo.'] |
['Chronic hepatitis C (CHC) patients selected for entry into treatment trials have been reported to have impaired health-related quality of life (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC patients may have been underestimated because of the exclusion of patients with comorbid illness. The aim of this study was to assess HRQOL in an unselected group of CHC patients and to identify factors associated with impairment in HRQOL.', 'A total of 220 consecutive eligible CHC patients were enrolled from a hepatology clinic. HRQOL was assessed by the short form 36 (SF-36) and comorbid illnesses were assessed by an interview.', 'CHC patients had significantly lower SF-36 scores in all subscales and in the summary scales when compared to those of the healthy general population in the United States (p < 0.001). Compared to CHC patients entering treatment trials, our patients had lower SF-36 scores on five subscales (p < 0.001). The presence of comorbid illness was the most important predictor of HRQOL in CHC patients. However, CHC alone resulted in significantly lower SF-36 scores in all subscales and summary scales (p < or = 0.003) compared to those of the healthy U.S. population. There was no correlation between SF-36 scores and history of i.v. drug use or dependence. alcohol dependence. and serum aminotransferase levels.'] |
['How cells decipher the duration of an external signal into different transcriptional outcomes is poorly understood. The hormone gastrin can promote a variety of cellular responses including proliferation, differentiation, migration and anti-apoptosis. While gastrin in normal concentrations has important physiological functions in the gastrointestine, prolonged high levels of gastrin (hypergastrinemia) is related to pathophysiological processes.', 'We have used genome-wide microarray time series analysis and molecular studies to identify genes that are affected by the duration of gastrin treatment in adenocarcinoma cells. Among 403 genes differentially regulated in transiently (gastrin removed after 1 h) versus sustained (gastrin present for 14 h) treated cells, 259 genes upregulated by sustained gastrin treatment compared to untreated controls were expressed at lower levels in the transient mode. The difference was subtle for early genes like Junb and c-Fos, but substantial for delayed and late genes. Inhibition of protein synthesis by cycloheximide was used to distinguish between primary and secondary gastrin regulated genes. The majority of gastrin upregulated genes lower expressed in transiently treated cells were primary genes induced independently of de novo protein synthesis. This indicates that the duration effect of gastrin treatment is mainly mediated via post-translational signalling events, while a smaller fraction of the differentially expressed genes are regulated downstream of primary transcriptional events. Indeed, sustained gastrin treatment specifically induced prolonged ERK1/2 activation and elevated levels of the AP-1 subunit protein JUNB. Enrichment analyses of the differentially expressed genes suggested that endoplasmic reticulum (ER) stress and survival is affected by the duration of gastrin treatment. Sustained treatment exerted an anti-apoptotic effect on serum starvation-induced apoptosis via a PKC-dependent mechanism. In accordance with this, only sustained treatment induced anti-apoptotic genes like Clu, Selm and Mcl1, while the pro-apoptotic gene Casp2 was more highly expressed in transiently treated cells. Knockdown studies showed that JUNB is involved in sustained gastrin induced expression of the UPR/ER stress related genes Atf4, Herpud1 and Chac1.'] |
['To determine whether predictors of fat intake behavior were the same for normal-weight and obese WIC mothers when applying the PRECEDE-PROCEED model and to identify predictors for each group.', 'Proportional stratified convenience sampling.', 'Five hundred eighty-one nonpregnant, black and white normal-weight (n = 180) or obese (n = 401) women.', 'The Special Supplemental Nutrition Program for Women, Infants and Children in six counties in southern Wisconsin.', 'The independent variables were predisposing, enabling, and reinforcing factors. Predisposing factors included beliefs in diet and health, beliefs in diet and body shape, health concerns in food choice, health concerns in nutrition, and eating habits. Enabling factors were cost of food, availability of time to prepare food, and accessibility to purchase food. Reinforcing factors were weight control intentions, sensory appeal, and mood. The dependent variable was fat intake behavior. Structural equation modeling was performed.', 'When controlling for covariates, certain factors affectingfat intake behavior differed between the normal-weight and the obese groups. For the normal-weight group, only reinforcing factors were positively associated with fat intake behavior For the obese group, reinforcing and enabling, but not predisposing, factors were positively associated with fat intake behavior.'] |
['The aim of this research was to compare the risk of all-cause mortality and mortality from all cancers combined, lung cancer, respiratory diseases, cardiovascular diseases and diabetes mellitus between normal-weight smokers and overweight or obese ex-smokers.', 'Data were from 1997 to 2004 National Health Interview Survey (with response rates ranging from 70% to 80%) which were linked to records in the National Death Index. Mortality follow-up was through 31 December 2006. The sample was limited to normal-weight smokers and overweight/obese ex-smokers 25\u2005years of age and older (n=52,819). HR from Cox regression was computed to represent mortality effect.', 'Results showed that in both women and men, normal-weight smokers, relative to overweight or obese ex-smokers, had a higher risk of mortality from all causes combined, all cancers combined, lung cancer, cardiovascular and respiratory diseases. Among women, there was no difference in mortality risk from diabetes mellitus between normal-weight smokers and overweight or obese ex-smokers. Among men, there was some evidence that the risk of mortality was higher in obese ex-smokers than normal-weight smokers.'] |
['There is growing evidence that DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). In order to bind to DNA many mutagens require metabolic activation by cytochrome P450 (CYP) 1A1 or CYP1A2. The objective of this study was to determine the effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and whether smoking interacts with genotype to modify risk.', 'Subjects (n = 873) with a first acute non-fatal MI and population based controls (n = 932) living in Costa Rica, matched for age, sex, and area of residence, were genotyped for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)-PCR, and smoking status was determined by questionnaire.', 'After adjusting for matching variables and potential confounders, no association was observed between CYP1A1 genotype and risk of MI. Compared to individuals with the high inducibility CYP1A2*1A/*1A genotype, the adjusted odds ratio and 95% confidence intervals for risk of MI were 1.19 (0.97 to 1.47) for the *1A/*1F genotype and 1.55 (1.10 to 2.18) for the *1F/*1F genotype. No significant interactions were observed between smoking and either CYP1A1 or CYP1A2 genotype.'] |
['To identify the reasons why those offered a place on diabetes education programmes declined the opportunity.', 'It is well established that diabetes education is critical to optimum diabetes care; it improves metabolic control, prevents complications, improves quality of life and empowers people to make informed choices to manage their condition. Despite the significant clinical and personal rewards offered by diabetes education, programmes are underused, with a significant proportion of patients choosing not to attend.', 'A systematic search of the following databases was conducted for the period from 2005-2015: Medline; EMBASE; Scopus; CINAHL; and PsycINFO. Studies that met the inclusion criteria focusing on patient-reported reasons for non-attendance at structured diabetes education were selected.', 'A total of 12 studies spanning quantitative and qualitative methodologies were included. The selected studies were published in Europe, USA, Pakistan, Canada and India, with a total sample size of 2260 people. Two broad categories of non-attender were identified: 1) those who could not attend for logistical, medical or financial reasons (e.g. timing, costs or existing comorbidities) and 2) those who would not attend because they perceived no benefit from doing so, felt they had sufficient knowledge already or had emotional and cultural reasons (e.g. no perceived problem, denial or negative feelings towards education). Diabetes education was declined for many reasons, and the range of expressed reasons was more diverse and complex than anticipated.'] |
["Migration of colonic lamina propria fibroblasts (CLPF) plays an important role during mucosal wound healing as well as fibrosis and fistula formation in Crohn's disease (CD). Recently, we showed that the migratory potential of CD-CLPF was significantly reduced compared to control CLPF. Fistula-derived CD-CLPF migrated less and fibrosis-CLPF more than CLPF from inflamed CD mucosa. These changes in migratory behavior were associated with changes in production of the migration-inducing fibronectin (FN) isoforms ED-A and ED-B. A permanent reduction of the migratory potential of CLPF was mediated by IFN-gamma and tumor necrosis factor (TNF) modulate FN isofom expression in CLPF and thereby might regulate CLPF migration.", 'Control CLPF were incubated for 72 h with IFN-gamma, TNF, IFN-gamma plus TNF, or TGF-beta1. Messenger RNA (mRNA) was isolated and expression of FN and isoforms ED-A and ED-B was quantified by real-time polymerase chain reaction. FN, ED-A, and ED-B were investigated by Western blotting. FN receptor integrin alpha5beta1 was analyzed by FACS.', 'No difference was found for the surface display of integrin alpha5beta1 between stimulated and non-stimulated cells. In TGF-beta1 incubated CLPF mRNA amount of FN and isoforms ED-A and ED-B was slightly increased. IFN-gamma only decreased FN in CLPF, TNF significantly reduced FN-mRNA by 40%, FN ED-A mRNA by 25%, and ED-B mRNA by 50%. The TNF-mediated mRNA downregulation resulted in a decreased protein amount as revealed by Western blotting.'] |
['To survey patient opinions on prostate cancer (PCa) screening in light of the United States Preventive Services Task Force recommendation against its use.', 'We conducted a survey of all-comers to urology and primary care clinics. Participants provided demographic information and responded to a 5-item questionnaire regarding their opinions on screening before and after reading opposing position statements.', 'The overall response rate was 48%. After excluding incomplete questionnaires, 54 surveys were available for analysis. Patients were predominantly white, middle-aged and older, college-educated men with middle-to-upper-middle-class incomes who were seen at urology clinics. Patients rated their "pre" level of understanding of screening recommendations as good or very good (52%), okay (30%), and poor (19%). After reading the information sheets, good or very good understanding of screening recommendations improved (65%; P\xa0= .05), and agreement with the importance of screening remained high (80%). However, nearly 20% of patients expressed a more neutral or less favorable attitude toward the risk-benefit ratio of screening (P\xa0= .09). Agreement that men should undergo screening, that screening helps detect cancer, and that screening saves lives remained high, regardless of the exposure.'] |
['Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]).', 'Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined.', 'LPS increased maternal serum IL-6 (50 +/- 25 to 3444 +/- 584 pg/mL) and IL-10 (40 +/- 20 to 958 +/- 339 pg/mL) and amniotic fluid IL-6 (59 +/- 25 to 891 +/- 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS.'] |
['Management of unicompartmental knee osteoarthritis in middle-aged patients is a challenging problem. Despite its functional advantages, UKA still raises questions concerning implant survivorship and an increased revision risk for aseptic loosening mainly due to polyethylene wear. The main purpose of the present study was to investigate whether using the minimum thickness of an all-poly tibial UKA in patients under 60 years of age increases the revision rate for aseptic loosening. The secondary purposes were to compare implant survivorship with data reported in literature and to prospectively evaluate the clinical outcome in this selected group of patients.', 'Thirty-three consecutive patients under 60 years of age at the time of surgery with isolated medial compartment osteoarthritis underwent a unilateral medial UKA from 2002 to 2005 and were prospectively followed. A Kaplan-Meier analysis was performed to determine the 8-year implant survivorship with revision for any reason as endpoint. KSS, WOMAC, Tegner-Lysholm, Tegner and VAS scores were prospectively evaluated at 3- to 8-year follow-up. Weight-bearing radiographs were collected pre-operatively and at 3- to 8-year follow-up to prospectively evaluate hip-knee-ankle angle (HKA), femoro-tibial angle (FTA), tibial plateau angle and posterior tibial slope.', "The 8-year Kaplan-Meier survivorship with revision for any reason as endpoint was 83 %. Five failures were reported, and in 3 patients' aseptic loosening of the tibial component was the reason for failure. All clinical scores significantly improved at 3-year follow-up, and no further modification was demonstrated up to 8-year follow-up. HKA, FTA and TPA had a significant difference at 3-year follow-up with respect to pre-operative values (p < 0.01) and no further difference at 8-year follow-up was found."] |
['To determine the severity of emesis caused by ultra-high-dose cisplatin-carboplatin chemotherapy and to compare the antiemetic efficacy of an ondansetron regimen and a metoclopramide regimen.', 'Forty consecutive patients with stage III or IV epithelial ovarian cancer or advanced or recurrent endometrial cancer were treated with ultra-high-dose cisplatin-carboplatin chemotherapy. No patient had received prior chemotherapy. Chemotherapy consisted of intravenous (IV) cisplatin 70 mg/m2 and IV carboplatin 100 mg/m2 administered on days 1 and 8 every 28 days for five cycles, representing a total monthly organoplatin dose of 207 mg/m2. Patients were randomized to receive metoclopramide, diphenhydramine, prochlorperazine, and lorazepam; or ondansetron, dexamethasone, prochlorperazine, and lorazepam. Patients were blinded and there was no crossover. The metoclopramide dose was 2 mg/kg IV every 2 hours x 3, and the ondansetron dose was 0.15 mg/kg IV every 4 hours x 3.', 'All 40 patients developed vomiting; 21 (52%) developed severe vomiting and seven (17%) required home IV therapy (grade 4). Eight patients (40%) receiving the metoclopramide regimen developed severe vomiting, compared to 13 (65%) in the ondansetron group (P = .50). Two patients (10%) in the metoclopramide group developed grade 4 vomiting, compared to five (25%) in the ondansetron group (P = .45). Except for sedation and amnesia, there were no significant side effects associated with either regimen.'] |
['Reflux of bile to the oesophagus has been shown to be of importance in the development of gastro-oesophageal reflux disease. This study aims to assess oesophageal motility patterns in relation to acid and bile reflux to the oesophagus.', 'Forty-nine subjects with and without reflux disease underwent 24-hour ambulatory recordings of oesophageal pH, bile and 3-channel manometry. Gastroscopy was performed to assess severity of oesophagitis. The percentage of effective peristaltic contractions (oesophageal contractions with a peristaltic pattern and a pressure >30 mm Hg) were correlated to the degree of acid and bile reflux. Ten subjects were re-evaluated within 2 years post-fundoplication.', 'Acid and bile reflux were associated with fewer effective contractions (R(2) = 0.07, p = 0.06 and R(2) = 0.21, p = 0.008, respectively). However, in a multivariate model including acid, bile, age and gender dependency, only bile could show a systematic effect on the variation in percentage of effective peristaltic contractions (R(2) = 0.22, p = 0.001). One year after laparoscopic fundoplication, 24-hour oesophageal motility was unchanged.'] |
['To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts.', 'In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage).', 'One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10).'] |
['The study explores the role of acid-sensitive ion channel 3 (ASIC3) in the cerebrospinal fluid (CSF)-contacting nucleus of the parenchyma of rat brain, in inflammatory pain.', "We injected rats subcutaneously with complete Freund's adjuvant (CFA) into the plantar surface of the left hind paw. We then measured the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT). After horseradish peroxidase-conjugated toxin subunit B (CB-HRP) retrograde tracing of one of the rats' lateral ventricles, we used immunohistochemistry, to observe the distribution and expression of ASIC3 in CSF-contacting nucleus with double labeling of CB-HRP and ASIC3. We injected a selective ASIC3 antagonist, APETx2, into one of the rat's lateral ventricles, to test for inhibition of ASIC3 activation and the effects on heat and mechanical hyperalgesia, in response to inflammation.", 'The CSF-contacting nucleus is always located in a specific region of parenchyma in rat brain, consistent with previous findings. The CSF-contacting nucleus has ASIC3, which increased significantly in persistent inflammation following injection of CFA. The intracerebroventricular injection (ICV) administration of specific ASIC3 antagonist APETx2 suppressed the heat and mechanical hyperalgesia following CFA injection.'] |
['We have previously shown that angiotensin II type 2 receptor (AT(2)R) stimulation causes endothelium-dependent vasodilation that does not desensitize after chronic angiotensin II type 1 receptor (AT1R) blockade, suggesting a role for AT2R in antihypertensive treatment.', 'We recorded mean arterial pressure (MAP) and investigated AT2R by Western blot analysis, immunohistochemistry, and function in isolated mesenteric resistance arteries (205 microm in diameter) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) receiving the following for 4 weeks in drinking water: placebo, AT1R blockade (candesartan; 2 mg/kg per day), ACE inhibitor (perindopril; 3 mg/kg per day), nonselective vasodilator (hydralazine; 16 or 24 mg/kg per day), or candesartan plus hydralazine (16 mg/kg per day). In precontracted isolated arteries, AT2R stimulation (angiotensin II in the presence of candesartan) caused vasodilation in WKY rats (MAP=118 mm Hg) and vasoconstriction in SHR (MAP=183 mm Hg). In SHR treated with candesartan (MAP=146 mm Hg) or hydralazine (16 mg/kg per day; MAP=145 mm Hg), AT2R-induced contraction was reduced by 50%. In SHR treated with perindopril (MAP=125 mm Hg), AT2R stimulation induced vasodilation. In SHR treated with hydralazine (24 mg/kg per day; MAP=105 mm Hg) and in SHR treated with hydralazine (16 mg/kg per day) plus candesartan (MAP=102 mm Hg), an AT2R-mediated vasodilation was restored. Immunochemistry and Western blot analysis showed that AT2R expression, lower in SHR than in WKY rats, was restored to normal levels by treatments reducing arterial pressure in SHR.'] |
['Bradyrhizobium japonicum USDA110, a soybean symbiont, is capable of accumulating a large amount of poly-β-hydroxybutyrate (PHB) as an intracellular carbon storage polymer during free-living growth. Within the genome of USDA110, there are a number of genes annotated as paralogs of proteins involved in PHB metabolism, including its biosynthesis, degradation, and stabilization of its granules. They include two phbA paralogs encoding 3-ketoacyl-CoA thiolase, two phbB paralogs encoding acetoacetylCoA reductase, five phbC paralogs encoding PHB synthase, two phaZ paralogs encoding PHB depolymerase, at least four phaP phasin paralogs for stabilization of PHB granules, and one phaR encoding a putative transcriptional repressor to control phaP expression.', 'Quantitative reverse-transcriptase PCR analyses of RNA samples prepared from cells grown using three different media revealed that PHB accumulation was related neither to redundancy nor expression levels of the phbA, phbB, phbC, and phaZ paralogs for PHB-synthesis and degradation. On the other hand, at least three of the phaP paralogs, involved in the growth and stabilization of PHB granules, were induced under PHB accumulating conditions. Moreover, the most prominently induced phasin exhibited the highest affinity to PHB in vitro; it was able to displace PhaR previously bound to PHB.'] |
['The ability to consult effectively is key to the delivery of quality patient care. External peer review of consultations has been available to general medical practitioners (GPs) in the west of Scotland for several years. Pharmacists are expected to provide increasingly complex advice for patients. This study describes the development and first steps in the evaluation of a generic tool to be used to inform feedback about both GP and pharmacist consultations with patients.', "The tool was developed by a small group of GPs and tested for validity using a content validity inventory. An item correlation pilot (ICP) was carried out. Three experienced reviewers reviewed and scored three consultations in each of six GP tapes, a further three reviewers reviewed and scored three consultations in each of four pharmacists' tapes. The results underwent statistical analysis.", 'Pharmacists do not examine patients and so two similar instruments were developed, whereby two questions pertinent to patient examination were omitted from the pharmacist instrument. The content validity inventory demonstrated aspects of face validity and content validity of instruments. Statistical analysis of GP tapes suggested that the instrument could discriminate between GP consultations. Skills demonstrated by pharmacists were given lower scores, were less consistent than the GPs and the instrument did not discriminate between those performing at different levels.'] |
['To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis.', '28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n = 19) or the stented group (n = 9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm(2)) was applied to activate the drug (n = 10). Control arteries (n = 9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis.', 'Intracoronary PDT significantly reduced intimal thickness in both BI and stented arteries (about 65%: 0.22 (SEM 0.05) mm v 0.62 (0.05) mm, p < 0.01; and about 26%: 0.40 (0.04) mm v 0.54 (0.04) mm, p < 0.01, respectively). PDT increased luminal area by <or= 60% and 50% within BI and stented arteries (3.43 (0.27) mm(2)v 5.51 (0.52) mm(2), p < 0.05; 4.0 (0.02) mm(2)v 6.0 (0.16) mm(2), p < 0.01), respectively. Complete re-endothelialisation was observed by immunohistochemical and gross histological analyses in all PDT and control arteries. There were no cases of aneurysm formation or thrombosis.'] |
['Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2.', 'Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001) at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter.'] |
['The biological response to antiplatelet drugs has repeatedly been shown to predict the recurrence of major adverse cardiovascular events (MACEs). However, most studies involved coronary artery disease patients with recent vessel injury shortly after the initiation of antiplatelet therapy. Data on stable cardiovascular patients are scarce, and the added predictive value of specific assays (the vasodilator phosphoprotein assay for the clopidogrel response and serum thromboxane B2 for the aspirin response) and aggregation-based assays relative to common predictors has rarely been addressed.', 'Stable cardiovascular outpatients participating in the Antiplatelet Drug Resistances and Ischemic Events (ADRIE) study (n=771) were tested twice, at 2 separate visits, with specific and aggregation-based assays. Follow-up lasted 3 years, and <1% of patients were lost to follow-up. MACEs were adjudicated by an independent committee. Multivariate survival analyses included relevant variables identified in univariate analysis and platelet function test results. The C-index was used to express the prognostic value of various multivariate models. MACEs, the primary end point, occurred in 16% of patients. Hypertension, smoking, older age, and elevated low-density lipoprotein cholesterol were predictive of MACE recurrence, with a C-index of 0.63 (P<0.001). Neither the specific nor the aggregation-based assays added significant predictive value for the primary end point.'] |
['We previously demonstrated that dihydrotestosterone (DHT) enhances transforming growth factor-beta (TGF-beta) -induced apoptosis in human prostate cancer cells (Endocrinology 2001;142:2419-2426).', 'In this study, the ability of the apoptosis suppressor bcl-2 to directly antagonize the combined apoptotic effect of TGF-beta and DHT in the androgen-sensitive LNCaP TbetaRII prostate cancer cells was examined. The previously cloned TGF-RbetaII receptor LNCaP cells, responsive to both TGF-beta and androgens, were engineered to overexpress the bcl-2 oncoprotein and the profile of apoptosis induction was analyzed in response to TGF-beta alone (5.0 ng/ml) or in combination with DHT (1 nM).', 'Biological characterization of cloned LNCaP TbetaRII hygromycin/bcl-2 transfectants demonstrated that bcl-2 overexpression resulted in a significant inhibition of the combined TGF-beta and DHT apoptotic effect in prostate cancer cells (P < 0.01). Furthermore, molecular analysis indicated that this antagonistic effect of bcl-2 on apoptosis was due to partial suppression of TGF-beta and DHT-mediated induction of caspase-1 expression and activation in LNCaP TbetaRII-hygro/bcl-2 transfectants. These results support a potential bcl-2 interference with the TGF-beta and androgen apoptotic signaling in prostate cancer cells by means of an antagonistic effect on caspase-1 activation.'] |
['Although evidence has shown that ischemic heart disease (IHD) in vascular surgery patients has a negative impact on the prognosis after surgery, it is unclear whether directed treatment of IHD may influence cause-specific and overall mortality. The objective of this study was to determine the prognostic implication of coronary revascularization (CR) on overall and cause-specific mortality in vascular surgery patients.', 'Patients undergoing surgery for abdominal aortic aneurysm, carotid artery stenosis, or peripheral artery disease in a university hospital in The Netherlands between January 2003 and December 2011 were retrospectively included. Survival estimates were obtained by Kaplan-Meier and Cox regression analysis.', 'A total of 1104 patients were included. Adjusted survival analyses showed that IHD significantly increased the risk of overall mortality (hazard ratio [HR], 1.50; 95% confidence interval, 1.21-1.87) and cardiovascular death (HR, 1.93; 95% confidence interval, 1.35-2.76). Compared with those without CR, patients previously undergoing CR had similar overall mortality (HR, 1.38 vs 1.62; P = .274) and cardiovascular mortality (HR, 1.83 vs 2.02; P = .656). Nonrevascularized IHD patients were more likely to die of IHD (6.9% vs 35.7%), whereas revascularized IHD patients more frequently died of cardiovascular causes unrelated to IHD (39.1% vs 64.3%; P = .018).'] |
['Nitrovasodilators have been proposed for the treatment of portal hypertension alone or in combination with beta-blockers. In addition to their vasodilatory properties, nitric oxide (NO) donors may exert direct antifibrogenic properties. We evaluated the effect of nitroglycerin (NTG) and S-nitroso-N-acetyl penicillamine (SNAP) on the mitogenic and chemotactic properties of platelet-derived growth factor (PDGF)-BB and the modulation of the relative intracellular signaling pathways in fully activated human hepatic stellate cells (HSCs), a cell type that plays an active role in liver fibrogenesis and portal hypertension.', "Both NTG and SNAP induced a dose-dependent decrease in PDGF-induced DNA synthesis and cell migration, which was associated with a decrease in PDGF-induced intracellular Ca(2+) increase and extracellular signal-regulated kinase (ERK) activity. These effects were not related to activation of the classic soluble guanylate cyclase (sGC)/guanosine 3',5'-cyclic monophosphate pathway; accordingly, Western blot analysis of HSC lysates revealed the absence of the alpha(1)beta(1) ubiquitous subunits of sGC, whereas they were detectable in quiescent HSCs, freshly isolated from normal human liver. Conversely, both NTG and SNAP induced a more than 10-20-fold increase in prostaglandin E(2) in cell supernatants within 1 minute, associated with an increase in intracellular adenosine 3',5'-cyclic monophosphate levels. Accordingly, the inhibitory effects of NO donors on PDGF action and signaling were eliminated after preincubation with ibuprofen."] |
['In metastasis research, modern microscopic techniques shed a new light on the mechanisms of metastatic tumor cell arrest in the microcirculation of potential metastasis target organs. In this study, we differentiated the contribution of mechanical cell arrest, determined as lumen occlusion of liver sinusoids by tumor cells, and specific cell adhesion mediated by integrins for the arrest of human colon cancer cells in rat livers.', 'Using in vivo microscopy, the diameters of liver sinusoids of two different rat strains (CD, 250-300 g and RNU, 80-120 g) were determined. Cells (HT-29LMM) were intracardially injected, and the numbers of arrested cells and the rates of sinusoid occluding cells were determined.', 'Mean sinusoid diameter in CD rats was 6.98 +/- 1.42 microm compared to 5.14 +/- 1.11 microm in RNU rats (p < 0.001). The numbers of arrested tumor cells and the rates of extravasated tumor cells did not differ between the two rat strains. Nevertheless, 5 and 30 min after cell injection, 35 +/- 15% and 19 +/- 8% of arrested cells, respectively, appeared lumen occluding in RNU rats and 9 +/- 6% and 3 +/- 3%, respectively, in CD rats (p < 0.05). Despite the higher rates of lumen occlusive cells in RNU rats, inhibition of beta-1 or beta-4 integrins significantly impaired cell arrest by 30-60% in both strains.'] |
['Clinical and prognostic consequences of enhanced central chemosensitivity in the contemporary optimally treated patients with chronic heart failure (CHF) are unknown.', 'We studied central chemosensitivity (defined as the ventilatory response to hypercapnia assessed by the rebreathing method, HCVR [L/min/mmHg]) in 161 CHF patients (mean left ventricular ejection fraction [LVEF]: 31±6%, all receiving a combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker) and 55 sex-, age-matched healthy controls. HCVR did not differ between CHF patients and controls (median: 0.63 vs 0.57 L/min/mmHg, P=0.76). When the CHF patients were divided into tertiles according to their HCVR values, there were no significant differences in clinical characteristics, (except for ischaemic aetiology, more frequent in those with the highest HCVR), results of the cardiopulmonary exercise testing and indices of heart rate variability. During the follow up (median: 28 months, range: 1-48 months, ≥15 months in all survivors) 21 patients died. HCVR was not related to survival in the Cox-proportional hazards analysis.'] |
['The step-wise approach to catheter ablation for persistent atrial fibrillation (AF) requires considerable substrate modification targeting at complex fractionated atrial electrograms (CFAEs) in addition to pulmonary vein (PV) isolation. An alternative strategy that minimizes the amount of ablation would be desirable. The aim of this study was to investigate whether the use of pre-procedural amiodarone affects: (i) the amount of ablation required to achieve procedural success, and (ii) long-term outcomes.', 'We studied 121 consecutive patients with persistent AF who underwent catheter ablation. The patients were divided into two groups: Group 1, amiodarone (n = 31); Group 2, other antiarrhythmic drugs or rate control (n = 90). All the patients underwent a step-wise ablation procedure beginning with PV isolation, then proceeding with ablation of the CFAEs and linear lesions until sinus rhythm was achieved. Mean left atrial cycle length of AF (AFCL) was recorded at each step. The number of CFAE ablation sites was recorded. The number of CFAE sites in Group 1 was significantly less than that in Group 2 (P = 0.0121). The AFCLs after each step in Group 1 were significantly longer than those in Group 2. The procedure time and the radiofrequency time of CFAE ablation in Group 1 were significantly shorter than that in Group 2 (P = 0.0276 and P = 0.0458, respectively). There was no significant difference between the two groups in early and long-term outcomes.'] |
['There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients receiving dual antiplatelet therapy (DAPT). Peripheral endothelial dysfunction has recently been reported to predict adverse cardiovascular events. We hypothesized that CYP2C19 loss-of-function (LOF) allele carriers with peripheral endothelial dysfunction had worse prognosis. The aim of this study was to evaluate an additive effect of peripheral endothelial dysfunction on clinical outcome following percutaneous coronary intervention (PCI) in patients with a CYP2C19 variant.', 'We enrolled 434 patients on DAPT following PCI. CYP2C19 genotype was examined, and we divided patients into two groups: carriers, who had at least one CYP2C19 LOF allele, and non-carriers. Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low and high RHI. Thus, subjects were divided into four groups, and clinical events were followed up.', 'A total of 55 patients had a cardiovascular event. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers with low RHI (log-rank test: p=0.007). Multivariate Cox proportional hazards analysis identified both CYP2C19 LOF allele possession (hazard ratio (HR): 1.94; 95% confidence interval (CI): 1.1-3.69; p=0.045) and low RHI (HR: 2.15; 95% CI: 1.22-3.78; p=0.008) as independent and significant predictors of future cardiovascular events.'] |
['Identification of a novel topoisomerase I inhibitor which shows superior efficacy and less individual variation than irinotecan hydrochloride (CPT-11).', 'A novel camptothecin analog that is effective against breast cancer resistance protein (BCRP)-positive cells was screened, and a water soluble prodrug was generated. Antitumor activity of the prodrug was examined in BCRP-positive and -negative xenografts both as a single agent and in combination with other anti-cancer drugs.', 'A novel camptothecin analog, CH0793076, was discovered. Because CH0793076 was found to be highly lipophilic, a water soluble prodrug (TP300) was generated. TP300 is stable in an acidic solution but is rapidly converted to CH0793076 under physiological pH conditions such as in sera. This efficient prodrug activation would minimize interpatient differences in pharmacokinetic and toxicity profiles. Unlike CPT-11, TP300 does not exhibit cholinergic interaction or cause acute diarrhea at effective doses. In mouse xenograft models, TP300 showed antitumor activity against both BCRP-positive and -negative xenografts, whereas CPT-11 was less active against BCRP-positive xenografts. In addition, the effective dose range (MTD/ED(50)) for TP300 was wider than for CPT-11 and TP300 showed additive or synergistic antitumor effects in combination with other anti-cancer drugs such as capecitabine, oxaliplatin, cisplatin, bevacizumab and cetuximab.'] |
['Despite the potential benefits of total quality management (TQM), many healthcare organisations encountered difficulties in its implementation. The purpose of this paper is to explore the barriers to successful implementation of TQM in healthcare organisations of Iran.', 'This study involved a mixed research design. In-depth interviews were conducted with TQM practitioners to explore TQM implementation obstacles in Iranian healthcare organisations. In addition, this study involved survey-based research on the obstacles associated with successful TQM transformation.', "TQM implementation and its impact depend on the ability of managers to adopt and adapt its values and concepts in professional healthcare organisations. Unsuccessful TQM efforts in Iranian healthcare organisations can be attributed to the non-holistic approach adopted in its implementation, inadequate knowledge of managers' about TQM implementation, frequent top management turnover, poor planning, vague and short-termed improvement goals, lack of consistent managers' and employees' commitment to and involvement in TQM implementation, lack of a corporate quality culture, lack of team orientation, lack of continuous education and training and lack of customer focus. Human resource problems, cultural and strategic problems were the most important obstacles to TQM successful implementation, respectively."] |
['To evaluate diffusion tensor imaging (DTI) indices of (i) cortical tubers and (ii) normal-appearing subcortical white matter adjacent to cortical tubers within the epileptogenic zone and non-epileptogenic zone.', 'Twelve children with tuberous sclerosis complex underwent MRI, DTI and magnetoencephalography (MEG). Regions of interest (ROIs) were placed within cortical tubers and normal-appearing subcortical white matter adjacent to cortical tubers within MEG identified epileptogenic zone and non-epileptogenic zone. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (lambda(parallel)) and radial diffusivity (lambda(perpendicular)) were calculated.', '26 out of 104 cortical tubers were in the epileptogenic zone. FA of cortical tubers in the epileptogenic zone was significantly lower than non-epileptogenic zone (p=0.015). There were no significant differences between MD (p=0.896), lambda(parallel) (p=0.672) and lambda(perpendicular) (p=0.651) of cortical tubers in the epileptogenic and non-epileptogenic zone. In normal-appearing subcortical white matter within the epileptogenic zone, FA was lower (p=0.001) and lambda(perpendicular) (p=0.011) was higher than non-epileptogenic zone. There were no significant differences between MD (p=0.110) and lambda(parallel) (p=0.735) of normal-appearing subcortical white matter within the epileptogenic and non-epileptogenic zone.'] |
['Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals.', 'The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression and behaviour in a manner conducive to healing.', 'Skin samples were harvested from the lateral thoracic wall of two healthy thoroughbred horses.', 'Equine dermal cells were isolated using a skin explant method and their phenotype assessed by immunofluorescence. Cells were treated with recombinant proteins, with or without inflammatory stimuli. Gene expression was examined using standard and quantitative reverse transcriptase PCR. Cell behaviour was evaluated in a scratch assay.', 'Cultured cells were half vimentin(+ve) fibroblasts and half alpha smooth muscle actin(+ve) and vimentin(+ve) myofibroblasts. VEGF-E increased basal expression of IL-10 mRNA, whereas VEGF-A and collagenase-1 mRNA expression was increased by ovIL-10. In cells exposed to inflammatory stimulus, both treatments dampened tumour necrosis factor mRNA expression, and ovIL-10 exacerbated expression of monocyte chemoattractant protein. Neither viral protein influenced cell migration greatly.'] |
['CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and/or deafness) syndrome is a genetic disorder with prominent otolaryngologic features including choanal atresia and inner ear malformations. Recent experience with venous malformations during cochlear implant surgery prompted this study to define the spectrum of venous abnormalities in CHARGE and their surgical implications in otology.', 'Retrospective review of medical and radiologic records from databases of patients with CHARGE syndrome from three tertiary care academic medical centers.', 'Eighteen patients with CHARGE for whom temporal bone CT scans were available were included in the review.', 'Venous anomalies of the temporal bone were present in 10 of 18 (56%) patients. The most common were large emissary veins (n = 5). In two of these cases, these veins were associated with an ipsilateral a hypoplastic sigmoid sinus or jugular foramen. Other abnormalities included an aberrant petrosal sinus, venous lakes in proximity to the lateral venous sinus, condylar canal veins, and jugular bulb abnormalities, including a high riding bulb obscuring the round window niche and a dehiscent jugular bulb. In four of six patients undergoing cochlear implantation, the course of the aberrant vessel necessitated a change in the surgical approach, either during mastoidectomy or placement of the cochleostomy.'] |
['Recently we reported a close association between lymphonodular hyperplasia (LNH) of the bulb of the duodenum and increased densities of intraepithelial gammadelta+ T-cells in subjects with untreated food allergies. In this study we sought to determine whether children with LNH of the terminal ileum (TI) show a similar correlation.', "The mucosal specimens taken by colonoscopy from the TIs of 22 children with LNH of the TI without colitis, 13 with right-sided colitis or pancolitis, nine with left-sided colitis, eight with Crohn's disease, and three endoscopically healthy subjects were studied for T-cell subsets with monoclonal antibodies using a three-layer peroxidase staining method.", "LNH of the TI was found in 32 of the 55 subjects (58%). In 22 it was the only endoscopic finding, but in nine of 13 subjects (69%) it was related to right-sided colitis or pancolitis. In patients with left-sided colitis or Crohn's disease it was diagnosed only rarely. In the whole study population, LNH of the of the TI showed a significant association with the increment in the density of gammadelta+ T-cells. The subjects with LNH of the TI and colitis starting from the cecum showed the highest values, discriminating them statistically from any other study group. Accordingly their gammadelta+/CD3+ ratio was high. Even in the subjects with LNH of the TI without colitis, the increment in gammadelta+ T-cells was significant as compared with the subjects with left-sided colitis. Upregulations of D-related expression on the mucosa of the TI were similar regardless of the presence of LNH or colitis or an increment in gammadelta+ T-cells."] |
['Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model.', 'OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P < 0.05.', 'Subchondral bone area/tissue area, trabecular thickness and polar moment of inertia were diminished in OPOA knees compared with control or OA knees (P < 0.05). A decrease of plate thickness, ALP expression and OPG/RANKL ratio as well as an increased fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score.'] |
['Tumors of the parotid gland in children are rare and very little data has been published regarding the incidence of these tumors. We present a nationwide survey on this topic.', 'Data regarding benign and malignant tumors in the parotid gland in children from January 1st, 1990 to December 31st, 2005 in Denmark was collected retrospectively from nationwide registries. This generated 61 patients for inclusion in this study.', '85% of the tumors were benign and the malignant tumors made up the last 15%. The most common of the malignant tumors was the acinic cell carcinoma (n=4) followed by the mucoepidermoid carcinoma (n=3) and adenoid cystic carcinoma (n=2). The overall female-to-male ratio was 1.18, with a ratio of 1.08 and 2.0 in the benign and malignant groups, respectively. At the end of follow-up (August 1st, 2014) two patients had died, one with adenoid cystic carcinoma and one with mucoepidermoid carcinoma. Both patients had perineural invasion and involved resection margins at presentation. The incidence was 0.12 and 0.53 per 100,000 children of the malignant and benign tumors, respectively.'] |
['Whether hyperuricemia and microalbuminuria are separately associated with prehypertension among Chinese Han women is controversial.', 'Information was collected from physical examinations, personal interviews, and blood and urine samples. Associations of hyperuricemia and microalbuminuria with hypertension and prehypertension were analyzed by using multivariate nonconditional logistic regression models in 1,773 women aged ≥30 years.', 'Both average systolic and diastolic blood pressure increased with uric acid and urinary albumin-to-creatinine ratio levels (all trend P values<0.001). When subjects with microalbuminuria or using antihypertensive medication were excluded, individuals with a uric acid level in the 2(nd), 3(rd), and 4(th) quartiles of uric acid were more likely to have prehypertension than those with a uric acid level in the lowest quartile [odds ratio (OR)=1.50, 95% confidence interval (CI) 1.02-2.19; OR=1.69, 95% CI 1.12-2.56; OR=2.67, 95% CI 1.57-4.53). After exclusion of subjects with diabetes or hyperuricemia or using antihypertensive medication, compared with normotensives, individuals with high blood pressure status of prehypertension were more likely to have microalbuminuria (OR=1.83, 95% CI 1.12-2.99). Additionally, microalbuminuria was positively associated with blood pressure levels (trend P value<0.001).'] |
['To determine if automated perimetry detects visual field defects before manual Goldmann perimetry.', "Subjects with ocular hypertension without field loss on detailed manual perimetry were followed prospectively with annual automated and manual perimetry. Subjects with field loss on manual perimetry were age-matched post hoc to subjects who did not have field loss. The automated fields 1 year before the development of field loss on manual perimetry were compared between the two groups. Subjects were recruited from ophthalmologists' offices, eye clinics, and a population-based glaucoma survey in the Baltimore area. Abnormal results detected on the Humphrey Field Analyzer were defined using the glaucoma hemifield test, mean defect, and corrected-pattern standard deviation.", 'Forty subjects who had field loss during 8 years of follow-up were compared with 145 control subjects with ocular hypertension who did not have defects. Seventy-five percent of converters had abnormal results of the glaucoma hemifield test 1 year before field loss on manual perimetry, whereas 22% of controls had abnormal results of the glaucoma hemifield test (odds ratio, 13.4). The odds ratio of field loss developing on manual perimetry within 12 months was 3.3 for those with borderline results of the glaucoma hemifield test relative to the control subjects. The odds ratio was 6.0 for corrected-pattern standard deviation (P < 0.05) and 3.9 for mean deviation (P < 0.05).'] |
["This study estimated changes in the age- and sex-specific prevalence of Paget's disease of bone in six European towns over a 20-year period. Declines in prevalence were observed in this disorder, occurring among both men and women.", "To estimate secular changes in the age-and sex-specific prevalence of Paget's disease of bone in Europe, we conducted a second radiographic survey using identical sampling and methods in six European towns where a baseline study was performed in 1978-1979. In addition to these towns, the survey was carried out in two Hungarian centers not included in the initial study.", 'In each center, a sample of abdominal radiographs of people >or=55 years of age was taken from stored films within the radiology department of the principal general hospital. Radiographs showing the entire pelvis, sacrum, femoral heads, and lumbar vertebrae were studied for the period of 2000-2001. The films were evaluated by a trained observer and a consultant radiologist.', "A total of 6935 radiographs (3512 women and 3423 men) were assessed in the eight towns. The overall age- and sex-standardized prevalence rate of Paget's disease was 0.3% with a male/female ratio of 1.5. Prevalence increased with age among men and women rising to 0.8% of men and 0.9% of women >/=85 years of age. The differences in prevalence rate among the European centers were relatively small, especially in women. There was a decline in rates between 1978/79 and 2000/01."] |
['A previous study has argued that mycophenolate mofetil (MMF) is associated with a reduced incidence of death with function when compared to azathioprine (AZA) in cadaveric renal transplantation. This study was designed to verify this result because methodological issues bring these findings into question.', 'The data used in this study was derived from records of renal transplants performed in 1995 and 1996 as recorded in the UNOS Scientific Renal Transplant Registry and supplied by the United States Renal Data System (USRDS). Univariate and multivariate survival analysis was used to compare rates of death with function. Covariate characteristics of the donor, recipient, procedures, early outcomes and the transplant centre were considered.', '12,251 recipients of cadaveric renal transplants were identified as having received either MMF or AZA, but not both. The relative risk of death with function calculated by the Kaplan-Meier method was 21% less for MMF patients (P=0.005). MMF had from 21% (P=0.008) to 24% (P=0.001) reductions in relative risk by multivariate methods.'] |
['Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.', 'MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.', 'Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.'] |
['SIRT6 belongs to the NAD+-dependent class III deacetylase sirtuin family. Accumulating evidences have supported the critical role of SIRT6 in the proliferation, differentiation, cell cycle progression and apoptosis of cancer cells. The present study aims to determine the expression of SIRT6 in human ovarian cancer tissues and further investigate its the biological effect in ovarian cancer.', 'Real time PCR and western blot were performed to examine the mRNA and protein levels SIRT6 in human ovarian cancer tissues and normal tissues. The proliferation of ovarian cancer cells was determined using MTT methods. Small interfering RNA (siRNA) technology was used to down-regulate the expression of SIRT6 and Notch 3.', 'We found that the SIRT6 expression was significantly reduced in human ovarian cancer tissues compared to the normal tissues. Furthermore, our data showed that overexpression of SIRT6 inhibited the proliferation of ovarian cancer cells SKOV3 and OVCAR3. By contrast, down-regulation of SIRT6 enhanced ovarian cancer cells growth. In addition, our study showed that SIRT6 suppressed the expression of Notch 3 both at the mRNA and protein levels in ovarian cancer cells.'] |
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