title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Development and evaluation of a system to assess antimicrobial drug use in farm animals: results of an Austrian study. | The objective of this study was to develop and evaluate a feasible system for the collection of antimicrobial consumption data in farm animals in Austria. An electronic registry of all antibacterial pharmaceuticals approved in Austria for use in farm animals was created, listing product name, marketing authorisation number, active ingredient, package unit, strength, target species (cattle, swine, poultry), route of administration and indication, and allocating the corresponding code of the World Health Organization (WHO) Anatomical Therapeutic Chemical classification system for veterinary medicines to each substance (ATCvet-code). Different units (absolute quantities, animal daily dose, assumed daily product dose) enabled computation of the amounts of antimicrobials as pure substance, the constituents of a veterinary medicinal product, or the number of administrations. Two data collection systems were evaluated: (1) data transfer from the management software of veterinary practices or the Austrian Poultry Health Service; and (2) on-site data collection by manual data input from prescription records into an electronic registry. A total of 14,267 data sets provided by 18 practices were documented during the period January 2008 to March 2010. The total weight of active substances reported amounted to more than 5.4 tonnes for all species studied. The systems proved suitable for routine data acquisition and were considered in a recent national regulation on the surveillance of sale and consumption of veterinary antimicrobial substances. | 25,163,816 | [
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In vitro rescue of FGA deletion by lentiviral transduction of an afibrinogenemic patient's hepatocytes. | Congenital afibrinogenemia is a rare inherited autosomal recessive disorder in which a mutation in one of three genes coding for the fibrinogen polypeptide chains Aα, Bβ and γ results in the absence of a functional coagulation protein. A patient with congenital afibrinogenemia, resulting from an FGA homozygous gene deletion, underwent an orthotopic liver transplant that resulted in complete restoration of normal hemostasis. The patient's explanted liver provided a unique opportunity to further investigate a potential novel treatment modality. To explore a targeted gene therapy approach for patients with congenital afibrinogenemia. At the time of transplant, the patient's FGA-deficient hepatocytes were isolated and transduced with lentiviral vectors encoding the human fibrinogen Aα-chain. FGA-transduced hepatocytes produced fully functional fibrinogen in vitro. Orthotopic liver transplantation is a possible rescue treatment for failure of on-demand fibrinogen replacement therapy. In addition, we provide evidence that hepatocytes homozygous for a large FGA deletion can be genetically modified to restore Aα-chain protein expression and secrete a functional fibrinogen hexamer. | 25,163,824 | [
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Direct role of antibody-secreting B cells in the severity of chronic hepatitis B. | Chronic hepatitis B involves different immune cells. The direct role of antibody-secreting B cells in the severity of chronic hepatitis B unclear. In this study, the number of plaque forming cells [PFC-(IgG, IgM, anti-HBc IgG, and anti-HBc IgM)], liver function tests (LFT) [alkaline phosphatase (ALP), alanine aminotransferase (ALT), and total serum bilirubin (TSB)], the levels of IL-10 in sera and in lymphocyte cultures, the number of CD4(+) and CD8(+) cells were measured in the peripheral blood of patients and in the controls. In addition, the hepatocytotoxic effect of anti-HBc and anti-HBe in vitro was studied. The largest number of PFCs was observed in the peripheral blood of patients with chronic hepatitis B. This was concomitant with a decrease in CD4(+) /CD8(+) ratio versus this ratio in asymptomatic HBV carriers and in healthy volunteers (P < 0.05). An increase in immunoglobulin (IgG and IgM) levels, anti-HBc IgG, and anti-HBc IgM levels and LFTs in peripheral blood of patients with chronic hepatitis B was seen. Anti-HBc induced hepatocytotoxicity in vitro. The expression of mRNA and protein for IL-10 production was observed at a significant level in culture of lymphocytes isolated from patients with chronic hepatitis B. In addition, a high level of IL-10 was found only in the sera of patients with chronic hepatitis B. It is concluded that the antibody-secreting B cells and the antibodies, which are produced, play an important role in the severity of chronic hepatitis B, which was related negatively with CD4(+) /CD8(+) ratio and positively with IL-10 expression. | 25,163,843 | [
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Balanced UTE-SSFP for 19F MR imaging of complex spectra. | A novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout. Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2 )6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE. The proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 μmolPFOB(-1) min(-1/2) (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 μmolPFOB(-1) min(-1/2) ) or Cartesian k-space filling (GRE: 12 μmolPFOB(-1) min(-1/2) ; FSE: 16 μmolPFOB(-1) min(-1/2) ; balanced SSFP: 23 μmolPFOB(-1) min(-1/2) ). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner. A new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra. | 25,163,853 | [
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Anomalous surface fatigue in a nano-layered material. | Nanoscale materials fatigue within a single 7 Å layer of a 2D nano-layered material, muscovite mica, resembles fatigue in macroscopic systems except for two remarkable properties: first, there is an Å-scale precision in the depth of the damage and second, there are sharply defined "magical" stresses, beyond yield, at which the surface remains intact regardless of the number of applications of stress. | 25,163,860 | [
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Applications in education and training: a force behind the development of cognitive science. | This paper reviews 30 years of progress in U.S. cognitive science research related to education and training, as seen from the perspective of a research manager who was personally involved in many of these developments. | 25,163,867 | [
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Preparation of cross-linked enzyme aggregates of trehalose synthase via co-aggregation with polyethyleneimine. | Trehalose synthase (TreS) from Meiothermus ruber was co-aggregated with polyethyleneimine (PEI) and precipitated with polyethylene glycol (PEG), followed by cross-linking with glutaraldehyde to obtain TreS-polyethyleneimine cross-linked enzyme aggregates (termed as CLEAs-PEI-PEG). The TreS solution at 0.5 mg mL(-1) protein concentration, with PEI at a mass ratio of 1:0.8 (enzyme/PEI, w/w) and 25 % (w/v) PEG concentration were found to be most adequate for the co-aggregation of TreS. CLEAs-PEI-PEG was most active with glutaraldehyde at a mass ratio of 1:0.5 (enzyme/glutaraldehyde, w/w) to cross-link the co-aggregates. The CLEAs-PEI-PEG prepared in this work had an optimum pH of 6.5 and optimum temperature of 60 °C. For lower concentrations of enzyme, using PEI could enhance the cross-linking efficiency of TreS. The thermal stability and pH tolerance of CLEAs-PEI-PEG were significantly improved. Scanning electron microscopy revealed that the main structure of CLEAs-PEI-PEG showed scaffolding morphology which was constituted by structured ball-like particles with a size of 1-2.5 μm in diameter. | 25,163,880 | [
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Mass transfer analysis of growth and substance metabolism of NSCs cultured in collagen-based scaffold in vitro. | The aim of this study is to analyze the growth and substance metabolism of neural stem cells (NSCs) cultured in biological collagen-based scaffolds. Mass transfer and metabolism model of glucose, lactic acid, and dissolved oxygen (DO) were established and solved on MATLAB platform to obtain the concentration distributions of DO, glucose, and lactic acid in culture system, respectively. Calculation results showed that the DO influenced their normal growth and metabolism of NSCs mostly in the in vitro culture within collagen-based scaffolds. This study also confirmed that 2-mm thickness of collagen scaffold was capable of in vitro cultivation and growth of NSCs with an inoculating density of 1 × 10(6) cells/mL. | 25,163,884 | [
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Incidence of bowel wall oedema on computed tomography exams and association with diarrhoea in renal cell carcinoma patients treated with sunitinib. | The purpose of this study was to retrospectively assess the incidence of bowel wall oedema on computed tomography (CT) in patients with renal cell carcinoma (RCC) treated with sunitinib, and to investigate its association with diarrhoea. We conducted a retrospective analysis of all RCC patients treated with sunitinib at our hospital between December 2005 and December 2011. The presence or absence of bowel wall oedema on these CT examinations was scored. The presence of diarrhoea preceding, during, or after sunitinib treatment was identified from the patient files and retrospectively graded. For 54 of 87 patients, bowel wall oedema was present on at least one CT examination. Of these 54 patients, the right-sided colonic segment was affected in 87%. Diarrhoea was the most common reported adverse event during treatment, with 58 patients (67%) having grade 1/2 diarrhoea and 9 patients (10%) having grade 3. There was a statistically significant correlation between the incidence of CT-scored bowel oedema and diarrhoea during sunitinib treatment (P = 0.004). This study shows a very high incidence of bowel wall oedema and a strong correlation between the incidence of bowel wall oedema and diarrhoea in patients treated with sunitinib. • Sunitinib is routinely used in patients with advanced renal cell carcinoma. • Diarrhoea is the most common reported adverse event during sunitinib treatment. • Incidence of bowel oedema and diarrhoea during sunitinib treatment is correlated. • Radiologists should avoid misinterpretation of bowel oedema as infectious colitis. | 25,163,900 | [
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TBC1D1 reduces palmitate oxidation by inhibiting β-HAD activity in skeletal muscle. | In skeletal muscle the Rab-GTPase-activating protein TBC1D1 has been implicated in the regulation of fatty acid oxidation by an unknown mechanism. We determined whether TBC1D1 altered fatty acid utilization via changes in protein-mediated fatty acid transport and/or selected enzymes regulating mitochondrial fatty acid oxidation. We also determined the effects of TBC1D1 on glucose transport and oxidation. Electrotransfection of mouse soleus muscles with TBC1D1 cDNA increased TBC1D1 protein after 2 wk (P<0.05), without altering its paralog AS160. TBC1D1 overexpression decreased basal palmitate oxidation (-22%) while blunting 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated palmitate oxidation (-18%). There was a tendency to increase fatty acid esterification (+10 nmol·g(-1)·60 min(-1), P=0.07), which reflected the reduction in fatty acid oxidation (-12 nmol·g(-1)·60 min(-1)). Concomitantly, basal (+21%) and AICAR-stimulated glucose oxidation (+8%) were increased in TBC1D1-transfected muscles relative to their respective controls (P<0.05), independent of changes in GLUT4 and glucose transport. The reductions in TBC1D1-mediated fatty acid oxidation could not be attributed to changes in the transporter FAT/CD36, muscle mitochondrial content, CPT1 expression or the expression and phosphorylation of AS160, acetyl-CoA carboxylase, or AMPK. However, TBC1D1 overexpression reduced β-HAD enzyme activity (-18%, P<0.05). In conclusion, TBC1D1-mediated reduction of muscle fatty acid oxidation appears to occur via inhibition of β-HAD activity. | 25,163,918 | [
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Proportion and factors associated with depressive symptoms among elderly in an urban slum in Bangalore. | Depression among elderly is emerging as an important public health issue in developing countries like India. Published evidence regarding the magnitude and determinants of depression among elderly hailing from urban slum is currently limited. Hence, the current study was conducted to assess magnitude of the problem and identify factors associated with depression among the elderly in an urban slum. A cross-sectional study was done to cover total of 473 elderly persons from an urban slum in Bangalore, India. They were assessed for depression using Center for Epidemiologic Studies Depression scale. The overall prevalence of depression was found to be 37.8 (95% CI = 33.43-42.16). Multivariate analysis revealed that unemployment (self or children) (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.41-4.72), illness of self (OR 2.2; 95% CI 1.45-3.21), female gender (OR 1.9; 95% CI 1.19-2.89), conflicts in family (OR 1.6; 95% CI 1.03-2.43), and marriage of children or grandchildren (OR 1.6; 95% CI 1.02-2.68) as independent risk factors. Depression among elderly is an important health issue of this area. Psychological intervention need to be provided for all elderly persons especially at the time of being diagnosed with any kind of illness. Strategies should be targeted to the females. The stressful life events need to be identified and remedial actions taken. This facility should be made available to them at the primary level of health care. There is a need to include screening of depression in our national health programs. | 25,163,930 | [
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QTL analysis in multiple sorghum populations facilitates the dissection of the genetic and physiological control of tillering. | A QTL model for the genetic control of tillering in sorghum is proposed, presenting new opportunities for sorghum breeders to select germplasm with tillering characteristics appropriate for their target environments. Tillering in sorghum can be associated with either the carbon supply-demand (S/D) balance of the plant or an intrinsic propensity to tiller (PTT). Knowledge of the genetic control of tillering could assist breeders in selecting germplasm with tillering characteristics appropriate for their target environments. The aims of this study were to identify QTL for tillering and component traits associated with the S/D balance or PTT, to develop a framework model for the genetic control of tillering in sorghum. Four mapping populations were grown in a number of experiments in south east Queensland, Australia. The QTL analysis suggested that the contribution of traits associated with either the S/D balance or PTT to the genotypic differences in tillering differed among populations. Thirty-four tillering QTL were identified across the populations, of which 15 were novel to this study. Additionally, half of the tillering QTL co-located with QTL for component traits. A comparison of tillering QTL and candidate gene locations identified numerous coincident QTL and gene locations across populations, including the identification of common non-synonymous SNPs in the parental genotypes of two mapping populations in a sorghum homologue of MAX1, a gene involved in the control of tiller bud outgrowth through the production of strigolactones. Combined with a framework for crop physiological processes that underpin genotypic differences in tillering, the co-location of QTL for tillering and component traits and candidate genes allowed the development of a framework QTL model for the genetic control of tillering in sorghum. | 25,163,934 | [
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Characterization and molecular mapping of stripe rust resistance gene Yr61 in winter wheat cultivar Pindong 34. | We report a new stripe rust resistance gene on chromosome 7AS in wheat and molecular markers useful for transferring it to other wheat genotypes. Several new races of the stripe rust pathogen have established throughout the wheat growing regions of China in recent years. These new races are virulent to most of the designated seedling resistance genes limiting the resistance sources. It is necessary to identify new genes for diversification and for pyramiding different resistance genes in order to achieve more durable resistance. We report here the identification of a new resistance gene, designated as Yr61, in Chinese wheat cultivar Pindong 34. A mapping population of 208 F2 plants and 128 derived F2:3 lines in a cross between Mingxian 169 and Pindong 34 was evaluated for seedling stripe rust response. A genetic map consisting of eight resistance gene analog polymorphism (RGAP), two sequence-tagged site (STS) and four simple sequence repeat (SSR) markers was constructed. Yr61 was located on the short arm of chromosome 7A and flanked by RGAP markers Xwgp5467 and Xwgp5765 about 1.9 and 3.9 cM in distance, which were successfully converted into STS markers STS5467 and STS5765b, respectively. The flanking STS markers could be used for marker-assisted selection of Yr61 in breeding programs. | 25,163,935 | [
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Measured resection versus gap balancing technique for femoral rotational alignment: a prospective study. | To compare the measured resection technique and the gap balancing technique for correction of the femoral rotational alignment. 57 women and 6 men (mean age, 70 years) with end-stage osteoarthritis and <15º malalignment and <10º flexion contracture of the knee underwent primary total knee arthroplasty through the medial approach using the measured resection technique (n=34) or the gap balancing technique (n=29). Femoral rotational alignment was evaluated before and 7 days after surgery using computed tomography by referencing the 2 posterior condyles to the transepicondylar axis. The 2 groups did not differ significantly in terms of correction of the femoral rotational alignment (3.4º ± 1.4º vs. 3.5º ± 3.1º, p=0.817). The measured resection and the gap balancing techniques achieved comparable correction of femoral rotational alignment. | 25,163,946 | [
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Modified Weaver-Dunn procedure versus the use of a synthetic ligament for acromioclavicular joint reconstruction. | PURPOSE. To compare the subjective outcome of acromioclavicular joint (ACJ) reconstruction using the modified Weaver-Dunn procedure versus the Surgilig synthetic ligament. METHODS. 55 patients aged 19 to 72 (mean, 42) years underwent ACJ reconstruction of Rockwood grade 3 (n=38), grade 4 (n=8), and grade 5 (n=9) using the modified Weaver-Dunn procedure (n=31) or the Surgilig synthetic ligament (n=24), based on the surgeon's preference. The mean period from injury to surgical treatment was 39 months. Subjective outcomes were assessed before and after surgery using the Oxford Shoulder score and Nottingham Clavicle score. The time required to return to work and sports was also recorded. RESULTS. After a mean follow-up period of 40 months, the mean Oxford Shoulder scores improved from 28 to 42 in the Weaver-Dunn group (p=0.009), and from 26 to 45 in the Surgilig group (p=0.007), whereas the respective mean Nottingham Clavicle scores improved from 53 to 81 (p=0.047) and from 51 to 93 (p=0.023). The Surgilig group achieved significantly better postoperative Oxford Shoulder score (p=0.008) and Nottingham Clavicle score (p=0.007), and could also return to work (14 vs. 6 weeks, p<0.001) and sports (25 vs. 12 weeks, p<0.001) sooner than the Weaver-Dunn group. Three patients in the Weaver- Dunn group and one patient in the Surgilig group had persistent pain and/or functional deficit with evidence of ACJ dislocation. CONCLUSION. Chronic ACJ reconstruction using the Surgilig synthetic ligament achieved better Oxford Shoulder score and Nottingham Clavicle score and earlier return to work and sports, compared with the modified Weaver-Dunn procedure. | 25,163,955 | [
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Metabolic engineering of 3-hydroxypropionic acid biosynthesis in Escherichia coli. | 3-Hydroxypropionic acid (3-HP) can be produced in microorganisms as a versatile platform chemical. However, owing to the toxicity of the intermediate product 3-hydroxypropionaldehyde (3-HPA), the minimization of 3-HPA accumulation is critical for enhancing the productivity of 3-HP. In this study, we identified a novel aldehyde dehydrogenase, GabD4 from Cupriavidus necator, and found that it possessed the highest enzyme activity toward 3-HPA reported to date. To augment the activity of GabD4, several variants were obtained by site-directed and saturation mutagenesis based on homology modeling. Escherichia coli transformed with the mutant GabD4_E209Q/E269Q showed the highest enzyme activity, which was 1.4-fold higher than that of wild type GabD4, and produced up to 71.9 g L(-1) of 3-HP with a productivity of 1.8 g L(-1) h(-1) . To the best of our knowledge, these are the highest 3-HP titer and productivity values among those reported in the literature. Additionally, our study demonstrates that GabD4 can be a key enzyme for the development of industrial 3-HP-producing microbial strains, and provides further insight into the mechanism of aldehyde dehydrogenase activity. | 25,163,985 | [
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[The influence of an improvement of body contact on regulatory disorders in infancy]. | This study concerns the influence of an improvement of body contact on regulatory disorders in infancy. Two interventions were examined: 1. parent counseling on the subject of body contact; 2. practical training of body contact in connection with exposure. Both methods were supplemented by a video-based parent training. 20 infants with regulatory disorder were assigned to each treatment. Body and eye contact were examined by means of video ratings before and after treatment. In addition, we measured the daily amount of crying, sleeping, feeding, being fussy, and quiet play by means of an infant behavior diary. Both interventions resulted in an improvement of body contact, though only in the group with practical training was this improvement stable after 3 months. Taking all 40 participating infants together, we found significant improvements for "fussiness," "sleep duration," "awake, quiet or playing," and a marginal significant intervention effect for the duration of crying. Both interventions showed that children who had markedly improved in body contact also improved with regard to the regulation problem. Finally, the practical training of body contact was superior to pure counseling respective to the fussiness of the infants and to their gaze contact. Body contact can be improved through specific therapeutic interventions. Video-based parent training in combination with interventions aiming at an improvement of body contact have a positive effect on the regulation problem. | 25,163,993 | [
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MYCN-dependent expression of sulfatase-2 regulates neuroblastoma cell survival. | Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999-6009. ©2014 AACR. | 25,164,011 | [
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Trehalose pretreatment induces salt tolerance in rice (Oryza sativa L.) seedlings: oxidative damage and co-induction of antioxidant defense and glyoxalase systems. | Salinity in the form of abiotic stress adversely effects plant growth, development, and productivity. Various osmoprotectants are involved in regulating plant responses to salinity; however, the precise role of trehalose (Tre) in this process remains to be further elucidated. The present study investigated the regulatory role of Tre in alleviating salt-induced oxidative stress in hydroponically grown rice seedlings. Salt stress (150 and 250 mM NaCl) for 72 h resulted in toxicity symptoms such as stunted growth, severe yellowing, and leaf rolling, particularly at 250 mM NaCl. Histochemical observation of reactive oxygen species (ROS; O2 (∙-) and H2O2) indicated evident oxidative stress in salt-stressed seedlings. In these seedlings, the levels of lipoxygenase (LOX) activity, malondialdehyde (MDA), H2O2, and proline (Pro) increased significantly whereas total chlorophyll (Chl) and relative water content (RWC) decreased. Salt stress caused an imbalance in non-enzymatic antioxidants, i.e., ascorbic acid (AsA) content, AsA/DHA ratio, and GSH/GSSG ratio decreased but glutathione (GSH) content increased significantly. In contrast, Tre pretreatment (10 mM, 48 h) significantly addressed salt-induced toxicity symptoms and dramatically depressed LOX activity, ROS, MDA, and Pro accumulation whereas AsA, GSH, RWC, Chl contents, and redox status improved considerably. Salt stress stimulated the activities of SOD, GPX, APX, MDHAR, DHAR, and GR but decreased the activities of CAT and GST. However, Tre-pretreated salt-stressed seedlings counteracted SOD and MDHAR activities, elevated CAT and GST activities, further enhanced APX and DHAR activities, and maintained GPX and GR activities similar to the seedlings stressed with salt alone. In addition, Tre pretreatment enhanced the activities of methylglyoxal detoxifying enzymes (Gly I and Gly II) more efficiently in salt-stressed seedlings. Our results suggest a role for Tre in protecting against salt-induced oxidative damage attributed to reduced ROS accumulation, elevation of non-enzymatic antioxidants, and co-activation of the antioxidative and glyoxalase systems. | 25,164,029 | [
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Nigella sativa oil reduces aluminium chloride-induced oxidative injury in liver and erythrocytes of rats. | The present study was planned to investigate the protective effects of Nigella sativa oil (NSO) supplementation against aluminium chloride (AlCl3)-induced oxidative damage in liver and erythrocytes of rats. Simultaneously, a preliminary phytochemical study was affected in order to characterize the bioactive components containing in the NSO using chemical assays. The antioxidant capacities of NSO were evaluated by DPPH assay. The results showed that NSO was found to contain large amounts of total phenolics, flavonoids and tannins. Twenty-four rats were equally divided into two groups, in which group A received standard diet, whereas group B treated daily with an oral gavage dose of 2 ml NSO/kg body weight. After 5 weeks pretreatment, both groups were divided again into two subgroups (A and B) of six animals each and treated for other 3 weeks. Therefore, subgroup A1 was served as a control which received standard diet, but subgroup A2 received AlCl3 (34 mg/kg bw mixed with food). Subgroup B1 received both AlCl3 and NSO; however, subgroup B2 received NSO only. Results showed that AlCl3 exhibited an increase in white blood cell counts and a marked decrease in erythrocyte counts and haemoglobin content. Plasma aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase activities and total bilirubin concentration were higher in AlCl3 group than those of the control, while albumin and total protein concentration were significantly lower. Compared to the control, a significant raise of hepatic and erythrocyte malondialdehyde level associated with a decrease in reduced glutathione content, glutathione peroxidase, superoxide dismutase and catalase, activities of AlCl3 treated rats. However, the administration of NSO alone or combined with AlCl3 has improved the status of all parameters studied. It can be concluded that AlCl3 has induced the oxidative stress, altered the biochemical parameters and the hepatic histological profile, but the supplementation of NSO has alleviated such toxicity. | 25,164,035 | [
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Promoter methylation in epithelial-enriched and epithelial-depleted cell populations isolated from breast milk. | Breast cancer is the most frequently diagnosed cancer among Turkish women and both the incidence and associated mortality appear to be increasing. Of particular concern is the percentage of young women diagnosed with breast cancer; roughly 20% of all breast cancer diagnoses in Turkey are in women younger than 40 years. Increased DNA methylation in the promoter region of tumor suppressor genes is a promising molecular biomarker, and human milk provides exfoliated breast epithelial cells appropriate for DNA methylation analyses. Comparisons between DNA methylation patterns in epithelial (epithelial-enriched) and nonepithelial (epithelial-depleted) cell fractions from breast milk have not been reported previously. In the present study, we examined promoter methylation of 3 tumor suppressor genes in epithelial-enriched and epithelial-depleted cell fractions isolated from breast milk of 43 Turkish women. Percentage methylation in the promoter region of Rass association domain family 1 (RASSF1), secreted frizzle related protein 1 (SFRP1), and glutathione-S-transferase class pi 1 was determined by pyrosequencing of the epithelial-enriched and epithelial-depleted cell fractions. Pyrosequencing identified a few subjects with significantly increased methylation in 1 or more genes. There was little correlation between the 2 cell fractions within individuals; only 1 woman had increased methylation for 1 gene (SFRP1) in both her enriched and depleted cell fractions. Methylation was positively associated with age for SFRP1 (epithelial-depleted fraction) and with body mass index for RASSF1 (epithelial-enriched cell fraction), respectively. Overall, results show that the methylation signals vary between different cell types in breast milk and suggest that breast milk can be used to assess DNA methylation patterns associated with increased breast cancer risk. | 25,164,041 | [
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Recent advances in the development of anti-infective prophylactic and/or therapeutic agents based on Toll-Like Receptor (TLRs). | Toll-like receptors (TLRs) are key players in innate immunity. They are able to sense different microorganisms ranging from protozoa to bacteria, fungi or viruses. Innate immune responses can directly influence adaptive immune responses. Therefore, TLRs are considered as relevant targets for therapeutic applications in immune diseases: such as autoimmune disorders, allergy, sepsis, and cancer. We here review the recent patents based on the modulation of the toll-like receptors to develop anti-infective (prophylactic and/or therapeutic) agents. | 25,164,058 | [
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Apoptins: selective anticancer agents. | Therapies that selectively target cancer cells for death have been the center of intense research recently. One potential therapy may involve apoptin proteins, which are able to induce apoptosis in cancer cells leaving normal cells unharmed. Apoptin was originally discovered in the Chicken anemia virus (CAV); however, human gyroviruses (HGyV) have recently been found that also harbor apoptin-like proteins. Although the cancer cell specific activity of these apoptins appears to be well conserved, the precise functions and mechanisms of action are yet to be fully elucidated. Strategies for both delivering apoptin to treat tumors and disseminating the protein inside the tumor body are now being developed, and have shown promise in preclinical animal studies. | 25,164,066 | [
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Capturing of the monoterpene olefin limonene produced in Saccharomyces cerevisiae. | Monoterpene olefins such as limonene are plant compounds with applications as flavouring and fragrance agents, as solvents and potentially also in polymer and fuel chemistry. We engineered baker's yeast Saccharomyces cerevisiae to express a (-)-limonene synthase from Perilla frutescens and a (+)-limonene synthase from Citrus limon. Both proteins were expressed either with their native plastid targeting signal or in a truncated form in which the plastidial sorting signal was removed. The yeast host strain for expression was AE9 K197G, which expresses a mutant Erg20 enzyme. This enzyme catalyses the formation of geranyl diphosphate, which is the precursor for monoterpenes. Several methods were tested to capture limonene produced by the yeast. Extraction from the culture medium by pentane, or by the addition of CaCl2 followed by solid-phase micro-extraction, did not lead to detectable limonene, indicating that limonene is rapidly lost from the culture medium. Volatile terpenes such as limonene may also be trapped in a dodecane phase added to the medium during fermentation. This method resulted in recovery of 0.028 mg/l (+)-limonene and 0.060 mg/l (-)-limonene in strains using the truncated Citrus and Perilla synthases, respectively. Trapping the headspace during culture of the limonene synthase-expressing strains resulted in higher titres, at 0.12 mg/l (+)-limonene and 0.49 mg/l (-)-limonene. These results show that the volatile properties of the olefins produced require specific methods for efficient recovery of these molecules from biotechnological production systems. | 25,164,098 | [
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Fabrication of biodegradable polyurethane microspheres by a facile and green process. | Two different compositions of water-based biodegradable polyurethane (PU) in the form of homogeneous nanoparticles (NPs) were synthesized using biodegradable polyesters as the soft segment. The first PU (PU01) was based on poly(ε-caprolactone) (PCL) diol and the second PU (PU02) was based on 40% PCL diol and 60% polyethylene butylene adipate diol. The PU NP dispersions with different solid contents were sprayed into liquid nitrogen and resuspended in water to generate elastic microspheres (50-60 µm) with different nanoporosities. In vitro degradation analysis revealed that microspheres of PU02 (i.e., PU02 MS) degraded faster than those of PU01 (PU01 MS). Methylene blue was encapsulated during microsphere formation and the release was investigated. Microspheres made from a lower content (10%) of PU02 dispersion (i.e., PU02 MS_10) showed a greater burst release of methylene blue in 6 h, whereas those made from a higher content (30%) of PU01 dispersion (i.e., PU01 MS_30) revealed a prolonged release with a significantly lower burst release. Biocompatibility evaluation using L929 fibroblasts demonstrated that cells were attached and proliferated on microspheres after 24 h. On the other hand, microspheres may further self-assemble into films and scaffolds. Surface modification of microspheres by chitosan may modify the self-assembly behavior of microspheres. Microspheres could be stacked to form scaffolds with different macroporosities. Fibroblasts were successfully seeded and grown in the microsphere-stacked scaffolds. We concluded that the biodegradable and elastic microspheres may be facilely produced from a green and sustainable process with potential applications in drug release and three-dimensional cell culture. | 25,164,115 | [
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The regulatory peptide apelin: a novel inhibitor of renal interstitial fibrosis. | Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is a key event in renal interstitial fibrosis and the progression of chronic kidney disease (CKD). Apelin is a regulatory peptide involved in the regulation of normal renal hemodynamics and tubular functions, but its role in renal fibrosis remains unknown. In this study, we examined the inhibitory effects of apelin on transforming growth factor-β1 (TGF-β1)-induced EMT in HK-2 cells, and evaluated its therapeutic efficacy in mice with complete unilateral ureteral obstruction (UUO). In vitro, apelin inhibited TGF-β1-mediated upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin. Increased levels of phosphorylated Smad-2/3 and decreased levels of Smad7 in TGF-β1-stimulated cells were reversed by apelin co-treatment. In the UUO model, administration of apelin significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin and laminin expression, and markedly suppressed expression of α-SMA, TGF-β1 and its type I receptor, as well as interstitial matrix components. Interestingly, in UUO mice, there was a reduction in the plasma level of apelin, which was compensated by upregulation of APJ expression in the injured kidney. Exogenous supplementation of apelin normalized the level of plasmatic apelin and renal APJ. In conclusion, our study provides the first evidence that apelin is able to ameliorate renal interstitial fibrosis by suppression of tubular EMT through a Smad-dependent mechanism. The apelinergic system itself may promote some compensatory response in the renal fibrotic process. These results suggest that apelin has potential renoprotective effects and may be an effective agent for retarding CKD progression. | 25,164,121 | [
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Factors affecting patient compliance with compressive brace therapy for pectus carinatum. | The aim of this study was to identify factors affecting patient compliance with brace therapy for pectus carinatum. Eighty-six pectus carinatum patients who started brace therapy from August 2008 to November 2011 were included in this study. Patients were divided into two groups: patients who wore the brace for ≥6 months (compliance group) or patients who wore the brace for <6 months (non-compliance group). Factors affecting patient compliance were assessed at the last day of follow-up with a multiple-choice questionnaire. The questionnaire comprised seven items: pain at compression site, skin problems on compression area, confidence in brace treatment, shame, discomfort, initial result of bracing treatment and total number of factors affecting patient compliance. Eighty-six patients completed the survey, including seven (8.1%) female patients and 79 (91.9%) male patients, with a mean age of 12.0 years at the time of treatment (range, 3-20 years). The initial result of the compression period (P <0.001) and total number of factors affecting patient compliance (P <0.05) were significant predictors of patient compliance. An initial successful result of the compression period may increase patient compliance during treatment for pectus carinatum. Additional efforts to decrease pain, skin problems, shame and discomfort, and to give confidence may be beneficial in increasing compliance with bracing treatment. | 25,164,133 | [
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A patent ductus arteriosus complicating cardiopulmonary bypass for combined coronary artery bypass grafting and aortic valve replacement only discovered by computed tomography 3D reconstruction. | We describe the case of a 59-year old male patient undergoing combined coronary artery bypass grafting and aortic valve replacement. Manipulation of the heart during cardiopulmonary bypass significantly decreased venous return. Several measures were necessary to improve venous return to a level at which continuation of the procedure was safe. Based on the initial troubles with venous return, we decided to selectively cross-clamp the aorta. This resulted in a large amount of backflow of oxygenated blood from the left ventricle, necessitating additional vents in the pulmonary artery and directly in the left ventricle. The procedure was continued uneventfully, and postoperative recovery was without significant complications. Postoperative 2D computed tomography did not show any signs of a shunt, but 3D reconstruction showed a small patent ductus arteriosus. | 25,164,136 | [
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Stable graphene-polyoxometalate nanomaterials for application in hybrid supercapacitors. | We report the synthesis of hybrid supercapacitor electrodes by a novel reduction of GO with simultaneous incorporation of polyoxometalate. These hybrids show a 30% increase in specific capacitance and excellent stability after 10,000 cycles. | 25,164,153 | [
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Measures of cardiorespiratory fitness in relation to measures of body size and composition among children. | In the exercise testing measures of cardiorespiratory fitness need to be scaled by body size or composition to enable comparison between individuals. Traditionally used weight-proportional measures are potentially confounded by body adiposity that hampers their interpretation and applicability in the clinical assessment of cardiorespiratory fitness. We aimed to find the most appropriate measure of body size or composition for scaling of measures of cardiorespiratory fitness among children. We assessed body weight and height, maximal workload (W MAX ) and maximal oxygen uptake (VO2 MAX ) using cycle ergometer exercise test with respiratory gas analysis and body lean mass (LM) and fat mass (FM) by dual-energy X-ray absorptiometry and by bioimpedance analysis among 38 children. The data were analysed using Pearson's coefficients for correlation and stepwise linear regression models. Lean mass (r > 0.54) and height (r > 0.51) had stronger positive correlations with absolute W MAX and VO2 MAX than weight (r > 0.30) in girls and boys. None of the measures of body size or composition correlated with LM-proportional W MAX or VO2 MAX in girls or boys. Only LM correlated positively with height-proportional W MAX (r = 0.65) and VO2 MAX (r = 0.71) in boys. FM correlated negatively with weight-proportional W MAX (r < -0.58) and VO2 MAX (r < -0.64) in girls and boys. FM was even stronger determinant of weight-proportional W MAX (β = -0.68) and VO2 MAX (β = -0.61) than exercise performance in multivariate linear regression models. While assessing cardiorespiratory fitness, LM is the most appropriate measure of body size or composition for scaling of W MAX and VO2 MAX, because scaling by body weight introduces confounding by body adiposity. | 25,164,157 | [
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[Practical clinical aspects of oocyte vitrification for fertility preservation]. | Oocyte vitrification is a preservation fertility strategy, which can be performed in women after puberty to preserve gametes before beginning a gonadotoxic anticancer treatment. Based on available literature and our personal data, we aim to provide an overview about the feasibility, the clinical and logistic difficulties of oocyte vitrification in the field of oncofertility: limit age for oocyte cryopreservation, time required and protocols for ovarian controlled stimulation, ovarian response to stimulation, for what hopes of pregnancy? | 25,164,159 | [
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[Salpingo-oophorectomy by laparoendoscopic single-site surgery for everybody]. | To study the adnexectomy by laparoendoscopic single-site surgery with conventional laparoscopic instruments, we standardised the technique of salpingo-oophorectomy. In this prospective study, all patients with adnexectomies from June 2010 to January 2014 were included. Laparoendoscopic single-site adnexectomy with conventional instruments is described step by step in order to make it available for the majority of gynecologic surgeons. Laparoconversions and complications are also noted. We realized 42 bilateral salpingo-oophorectomies, 16 single salpingo-oophorectomy. The average operative time was 45min (15-120) with negligible blood losses. There were no laparoconversions and very few complications. After 15-20 adnexectomies, the procedure took less and less time. Adnexectomy by laparoendoscopic single-site surgery procedure with conventional laparoscopic instruments is easily reproducible with standardized steps and has many advantages. | 25,164,162 | [
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[Setting-up and evaluation of an educational program for the teaching of breast and pelvic examination in undergraduate medical students: the "PRESAGE" simulation center experience of the medicine university of Lille, France]. | To report the setting-up of a new educational program in the teaching of female pelvic and breast examinations and to investigate and compare the views and experience of undergraduate medical students and teachers on the program. Prospective evaluation of the teaching program through completion of a satisfaction questionnaire including items related to the educational value of the session by the students and the teachers. The educational program included an online preparation for the session, 3 workshops on training models (breast examination, pelvic examination, cervical snear procedure) and a video clip. In total, 419 (80.6%) of 520 second study year students (and 15 [50%] of 30 teachers [13 doctors and 17 midwifes] responded to the questionnaire). The students and the teachers were either very satisfied (56.6% and 13.4%, respectively) or satisfied (43.2% and 86.6%, respectively). On average, 89.7% of students wanted more lessons of this type and all teachers felt these useful or very useful training for students. Teaching sessions for pelvic and breast examination, which make combined use of videos and training models, are associated with a high degree of satisfaction from teachers and students in their second student's year. | 25,164,165 | [
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Combining background knowledge and learned topics. | Statistical topic models provide a general data-driven framework for automated discovery of high-level knowledge from large collections of text documents. Although topic models can potentially discover a broad range of themes in a data set, the interpretability of the learned topics is not always ideal. Human-defined concepts, however, tend to be semantically richer due to careful selection of words that define the concepts, but they may not span the themes in a data set exhaustively. In this study, we review a new probabilistic framework for combining a hierarchy of human-defined semantic concepts with a statistical topic model to seek the best of both worlds. Results indicate that this combination leads to systematic improvements in generalization performance as well as enabling new techniques for inferring and visualizing the content of a document. | 25,164,174 | [
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Identifying optimum performance trade-offs using a cognitively bounded rational analysis model of discretionary task interleaving. | We report the results of a dual-task study in which participants performed a tracking and typing task under various experimental conditions. An objective payoff function was used to provide explicit feedback on how participants should trade off performance between the tasks. Results show that participants' dual-task interleaving strategy was sensitive to changes in the difficulty of the tracking task and resulted in differences in overall task performance. To test the hypothesis that people select strategies that maximize payoff, a Cognitively Bounded Rational Analysis model was developed. This analysis evaluated a variety of dual-task interleaving strategies to identify the optimal strategy for maximizing payoff in each condition. The model predicts that the region of optimum performance is different between experimental conditions. The correspondence between human data and the prediction of the optimal strategy is found to be remarkably high across a number of performance measures. This suggests that participants were honing their behavior to maximize payoff. Limitations are discussed. | 25,164,177 | [
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Long working hours may increase risk of coronary heart disease. | To evaluate the association between long working hours and risk of coronary heart disease (CHD) estimated by Framingham risk score (FRS) in Korean adults. This study evaluated adult participants in Korean National Health and Nutrition Examination Survey IV (2007-2009). After inclusion and exclusion criteria were applied, the final sample size for this study model was 8,350. Subjects were asked about working hours and health status. Participants also completed physical examinations and biochemical measurement necessary for estimation of FRS. Multiple logistic regression was conducted to investigate the association between working hours and 10-year risk for CHD estimated by FRS. Compared to those who work 31-40 hr, significantly higher 10-year risk was estimated among subjects working longer hours. As working hours increased, odds ratio (OR) for upper 10 percent of estimated 10-year risk for CHD was increased up to 1.94. Long working hours are significantly related to risk of coronary heart disease. | 25,164,196 | [
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Orientationally ordered colloidal co-dispersions of gold nanorods and cellulose nanocrystals. | Nematic-like and helicoidally orientational self-assemblies of gold nanorods co-dispersed with cellulose nanocrystals to form liquid crystalline phases are developed. Polarization-sensitive extinction spectra and two-photon luminescence imaging are used to characterize orientations and spatial distributions of gold nanorods. Cholesteric-isotropic phase coexistence and continuous domains of single-phase regions are observed and qualitatively discussed on the basis of entropic and electrostatic interactions in co-dispersions of rigid rods of different aspect ratios. Potential applications include biologically compatible plasmonic composite nanomaterials for solar biofuel production and polarization-sensitive plasmonic papers and fabrics. | 25,164,198 | [
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Corpus callosal morphology in youth with bipolar depression. | Recent evidence has demonstrated that corpus callosum maturation follows a similar developmental timeline to cognitive processes. Bipolar disorder (BD) has been associated with disruptions in error processing, response inhibition, and motor functioning, which are mediated by underlying white matter structures, including the corpus callosum. Disruptions in white matter integrity have been demonstrated in BD. However, it is unknown whether alterations in the developmental trajectory of the corpus callosum may contribute to cognitive impairments in the disorder. We assessed the area of the corpus callosum and its subregions (the genu, rostral body, anterior and posterior bodies, isthmus, and splenium) in 14 treatment-naïve adolescents with BD (<21 years of age and in the depressed phase) and 18 healthy adolescent controls. In comparison with healthy controls, participants with BD demonstrated a significantly reduced overall corpus callosum area. We also noted smaller areas in the anterior and posterior mid-body of the corpus callosum in adolescents with BD. Our results suggest that commissural fibers of the corpus callosum are disrupted in early-onset BD. Specific decreases in the anterior and posterior mid-body callosal aspects may contribute to motor organization and inhibition deficits seen in BD. These findings are consistent with the involvement of inter-hemispheric tracts in early-onset BD, which may reflect an early deviation in white matter development. | 25,164,210 | [
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[Long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population]. | To observe the long term trends of blood lipid and glucose change in Guangzhou urban and rural natural population. We cross-sectionally studied individuals 35 to 65 years of age (50% male) from People' Republic of China-United States cardiovascular and cardiopulmonary epidemiology research study using random sampling design in Guangzhou Shipyard and Panyu Dashi Town (Dashi Street and Luopu Street now) in 1983 and 1984 (n = 4 548), 1998 (n = 1 593), 2004 (n = 2 095)and 2011 (n = 1 692). Prevalence of dyslipidemia and pathoglycemia were standardized to the WHO world standard population. Blood lipid and glucose levels were compared in this cohort during the 28 years. (1) The age adjusted mean average levels of blood lipid and glucose and the standardized prevalence rate of dyslipidemia and increased blood glucose as well as cardiovascular risk factors were significantly higher in the urban than in the rural residents and higher in male than in female participants (P < 0.01 or 0.05).(2) The age adjusted mean level of blood total cholesterol (TC), triglyceride (TG), glucose and high density lipoprotein cholesterol (HDL-C) increased from 1983/1984 to 2004 year in both urban and rural residents, and trended to be stable or decreased thereafter.(3) Standardized prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, blood lipid disorder, fasting blood glucose level and diabetes, steadily increased from 1983/1984 to 2004 and this increasing trend was slowed or reversed thereafter, except the prevalence rate of high blood TC. Except for high blood TC, the prevalence of multiple cardiovascular risk factors, such as high blood TG, low HDL-C, higher fasting blood glucose and diabetes, tended to be under control after 2004 in this cohort. Further efforts are warranted to strengthen this positive trend in the natural population. | 25,164,228 | [
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Early prediction of medication refractoriness in children with idiopathic epilepsy based on scalp EEG analysis. | Refractory epilepsy often has deleterious effects on an individual's health and quality of life. Early identification of patients whose seizures are refractory to antiepileptic drugs is important in considering the use of alternative treatments. Although idiopathic epilepsy is regarded as having a significantly lower risk factor of developing refractory epilepsy, still a subset of patients with idiopathic epilepsy might be refractory to medical treatment. In this study, we developed an effective method to predict the refractoriness of idiopathic epilepsy. Sixteen EEG segments from 12 well-controlled patients and 14 EEG segments from 11 refractory patients were analyzed at the time of first EEG recordings before antiepileptic drug treatment. Ten crucial EEG feature descriptors were selected for classification. Three of 10 were related to decorrelation time, and four of 10 were related to relative power of delta/gamma. There were significantly higher values in these seven feature descriptors in the well-controlled group as compared to the refractory group. On the contrary, the remaining three feature descriptors related to spectral edge frequency, kurtosis, and energy of wavelet coefficients demonstrated significantly lower values in the well-controlled group as compared to the refractory group. The analyses yielded a weighted precision rate of 94.2%, and a 93.3% recall rate. Therefore, the developed method is a useful tool in identifying the possibility of developing refractory epilepsy in patients with idiopathic epilepsy. | 25,164,248 | [
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Thermal structural characterization of the acentric layered perovskite LiHSrTa2O7: X-ray and neutron diffraction, SHG and Raman experiments. | The present work concerns the thermal structural characterization of the acentric Ruddlesden-Popper LiHSrTa2O7. A previous study, performed with powder neutron diffraction data, has revealed that at room temperature, LiHSrTa2O7 crystallizes in the Ama2 space group and that the acentric character is mainly due to the unequal distribution of the Li(+) and H(+) cations on their sites. In this new paper, the thermal behaviour has been studied by several techniques: powder X-ray and neutron diffraction, SHG experiments and Raman spectroscopy. All of them have revealed that LiHSrTa2O7 undergoes a reversible structural transition from an orthorhombic to a tetragonal symmetry around 200 °C. This transition is associated with the progressive vanishing of the TaO6 octahedra tilting, becoming completely straight in the high temperature form (S.G. I4/mmm), and with a variation of the Li(+) and H(+) distribution in the interlayer spacing. | 25,164,264 | [
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Responses to static stretching are dependent on stretch intensity and duration. | Information regarding the effects of stretching intensity on the joint torque-angle response is scarce. The present study examined the effects of three static stretching protocols with different intensities and durations on the passive knee extension torque-angle response of seventeen male participants (age ± SD: 23.9 ± 3.6 years, height: 177.0 ± 7.2 cm, BMI: 22.47 ± 1.95 kg · m(2)). The stretching intensity was determined according to the maximal tolerable torque of the first repetition: fifty per cent (P50), seventy-five per cent (P75) and the maximum intensity without pain (P100). Five repetitions were performed for each protocol. The stretch duration of each repetition was 90, 135 and 180 s for P100, P75 and P50, respectively. The rest period between repetitions was 30 s. Passive torque at a given angle, angle, stress relaxation, area under the curve, surface electromyography activity and visual analogue scale score were compared. The significant (P < 0.05) results found were as follows: (i) the P50 and P75 did not increase the angle and passive peak torque outcomes, despite more time under stretch; (ii) only the P100 increased the angle and passive peak torque outcomes; (iii) the perception of stretching intensity mainly changed depending on knee angle changes, and not passive torque; (iv) the P50 induced a higher passive torque decrease; (v) when protocols were compared for the same time under stretch, the torque decrease was similar; (vi) the change in torque-angle curve shape was different depending on the stretching protocol. In conclusion, higher stretch duration seems to be a crucial factor for passive torque decrease and higher stretch intensity for maximum angle increase. | 25,164,268 | [
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Microdissection approaches in tuberculosis research. | Mycobacterium tuberculosis, a globally significant pathogen, results in active or latent tuberculosis. The granuloma is the characteristic lesion that offers insight into host-pathogen interactions in these distinct states. Microdissection provides a way to isolate and consequently investigate specific tissue sections. We review various techniques available and in use. | 25,164,280 | [
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Semantics and metaphysics in informatics: toward an ontology of tasks. | This article clarifies three principles that should guide the development of any cognitive ontology. First, that an adequate cognitive ontology depends essentially on an adequate task ontology; second, that the goal of developing a cognitive ontology is independent of the goal of finding neural implementations of the processes referred to in the ontology; and third, that cognitive ontologies are neutral regarding the metaphysical relationship between cognitive and neural processes. | 25,164,287 | [
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Symbol interdependency in symbolic and embodied cognition. | Whether computational algorithms such as latent semantic analysis (LSA) can both extract meaning from language and advance theories of human cognition has become a topic of debate in cognitive science, whereby accounts of symbolic cognition and embodied cognition are often contrasted. Albeit for different reasons, in both accounts the importance of statistical regularities in linguistic surface structure tends to be underestimated. The current article gives an overview of the symbolic and embodied cognition accounts and shows how meaning induction attributed to a specific statistical process or to activation of embodied representations should be attributed to language itself. Specifically, the performance of LSA can be attributed to the linguistic surface structure, more than special characteristics of the algorithm, and embodiment findings attributed to perceptual simulations can be explained by distributional linguistic information. | 25,164,297 | [
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Dynamical models: an alternative or complement to mechanistic explanations? | While agreeing that dynamical models play a major role in cognitive science, we reject Stepp, Chemero, and Turvey's contention that they constitute an alternative to mechanistic explanations. We review several problems dynamical models face as putative explanations when they are not grounded in mechanisms. Further, we argue that the opposition of dynamical models and mechanisms is a false one and that those dynamical models that characterize the operations of mechanisms overcome these problems. By briefly considering examples involving the generation of action potentials and circadian rhythms, we show how decomposing a mechanism and modeling its dynamics are complementary endeavors. | 25,164,303 | [
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First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation. | The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands. | 25,164,318 | [
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Psychological determinants of erectile dysfunction among middle-aged men. | We describe psychological determinants of erectile dysfunction (ED) among middle-aged men with no identifiable medical risk factors and compare them with a sample of young individuals. Two groups of young (⩽ 30 years, n = 59) and middle-aged men (⩾ 40 years, n = 63) who scored ⩽ 25 on the erectile functioning domain of the International Index of Erectile Functioning were enrolled. Patients were included if they had no metabolic diseases, prostate problems or external genitalia abnormalities. Patients were not included if they were smokers, excessive drinkers or took medications known to cause ED. To assess psychopathology, symptom check list 90-revised (SCL-90-R) was administered. Structural equation modeling was performed to assess the relationship between psychopathology and ED. One in five men had severe ED, and the proportion was not different between the two groups. Middle-aged men had lower scores on different SCL-90-R domains. In both age groups, somatization and interpersonal sensitivity contributed to ED. Among younger individuals, anxiety and psychosis-related domains were also associated with ED. Unique contributors to ED in middle-aged men were depression and additional questions. In conclusion, among middle-aged men, psychological factors significantly contribute to ED when no medical risk factors are present. The pattern and composition of distress depicts distinct features, not seen in young age. | 25,164,317 | [
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Acid-suppressive medication use in acute stroke and hospital-acquired pneumonia. | Pneumonia is a morbid complication of stroke, but evidence-based strategies for its prevention are lacking. Acid-suppressive medications have been associated with increased risk for nosocomial pneumonia in hospitalized patients. It is unclear whether these results can be extrapolated to stroke patients, where other factors strongly modulate pneumonia risk. We investigated the association between acid-suppressive medication and hospital-acquired pneumonia in patients with acute stroke. All patients hospitalized with acute ischemic stroke or intracerebral hemorrhage in a large, urban academic medical center in Boston, Massachusetts from June 2000 to June 2010 who were ≥18 years of age and hospitalized for ≥2 days were eligible for inclusion. Acid-suppressive medication use was defined as any pharmacy charge for a proton-pump inhibitor or histamine-2 receptor antagonist. Multivariate logistic regression was used to control for confounders. The main outcome measure was hospital-acquired pneumonia, defined via International Classification of Diseases, Ninth Revision, Clinical Modification codes. The cohort comprised 1,676 admissions. Acid-suppressive medication was ordered in 1,340 (80%) and hospital-acquired pneumonia occurred in 289 (17.2%). The unadjusted incidence of hospital-acquired pneumonia was higher in the group exposed to acid-suppressive medication compared to those unexposed (20.7% vs 3.6%, odds ratio [OR] = 7.0, 95% confidence interval [CI] = 3.9-12.7). After adjustment, the OR of hospital-acquired pneumonia in the exposed group was 2.3 (95% CI = 1.2-4.6). The association was significant for proton-pump inhibitors (OR = 2.7, 95% CI = 1.4-5.4), but not for histamine-2 receptor antagonists (OR = 1.6, 95% CI = 0.8-3.4). In this large hospital-based cohort of patients presenting with acute stroke, acid-suppressive medication use was associated with increased odds of hospital-acquired pneumonia. | 25,164,323 | [
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Rebuttal to "Life-threatening cardiac tamponade: a rare complication of acupuncture": who framed acupuncture? | A rebuttal to Chun KJ, Lee SG, Son BS, Kim Do H: Life-threatening cardiac tamponade: a rare complication of acupuncture. J Cardiothorac Surg 2014, 9:61. | 25,164,325 | [
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Selective oxidation of glycerol to 1,3-dihydroxyacetone by covalently immobilized glycerol dehydrogenases with higher stability and lower product inhibition. | Glycerol dehydrogenase (GlyDH) catalyzes the regioselective oxidation of glycerol to yield 1,3-dihydroxyacetone (DHA); an important building block in chemical industry. Three recombinant GlyDHs from Geobacillus stearothermophilus, from Citrobacter braakii and from Cellulomonas sp. were stabilized by covalent immobilization. The highest activity recoveries (40-50%) of the insoluble preparations were obtained by immobilizing these enzymes in presence of polyethylene glycol (PEG). Noteworthy, these immobilized preparations were more stable and less inhibited by DHA than their soluble counterparts. In particular, GlyDH from G.stearothermophilus immobilized on agarose activated with both amine and glyoxyl groups and crosslinked with dextran aldehyde was 3.7-fold less inhibited by DHA than its soluble form and retained 100% of its initial activity after 18h of incubation at 65°C and pH 7. This is one of the few examples where the same immobilization protocol has minimized enzyme product inhibition and maximized thermal stability. | 25,164,336 | [
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A novel molecule Me6TREN promotes angiogenesis via enhancing endothelial progenitor cell mobilization and recruitment. | Critical limb ischaemia is the most severe clinical manifestation of peripheral arterial disease. The circulating endothelial progenitor cells (EPCs) play important roles in angiogenesis and ischemic tissue repair. The increase of circulating EPC numbers by using mobilization agents is critical for obtaining a better therapeutic outcome in patients with ischemic disease. Here, we firstly report a novel small molecule, Me6TREN (Me6), can efficiently mobilize EPCs into the blood circulation. Single injection of Me6 induced a long-lasting increase in circulating Flk-1(+) Sca-1(+) EPC numbers. In a mouse hind limb ischemia (HLI) model, local intramuscular transplantation of these Me6-mobilized cells accelerated the blood flow restoration in the ischemic muscles. More importantly, systemic administration of Me6 notably increased the capillary density, arteriole density and regenerative muscle weight in the ischemic tissue of HLI. Mechanistically, we found Me6 reduced stromal cell-derived factor-1α level in bone marrow by up-regulation of matrix metallopeptidase-9 expression, which allowed the dissemination of EPCs into peripheral blood. These data indicate that Me6 may represent a potentially useful therapy for ischemic disease via enhancing autologous EPC recruitment and promote angiogenesis. | 25,164,363 | [
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Palmitate induces ER stress and autophagy in H9c2 cells: implications for apoptosis and adiponectin resistance. | The association between obesity and heart failure is well documented and recent studies have indicated that understanding the physiological role of autophagy will be of great significance. Cardiomyocyte apoptosis is one component of cardiac remodeling which leads to heart failure and in this study we used palmitate-treated H9c2 cells as an in vitro model of lipotoxicity to investigate the role of autophagy in cell death. Temporal analysis revealed that palmitate (100 μM) treatment induced a gradual increase of intracellular lipid accumulation as well as apoptotic cell death. Palmitate induced autophagic flux, determined via increased LC3-II formation and p62 degradation as well as by detecting reduced colocalization of GFP with RFP in cells overexpressing tandem fluorescent GFP/RFP-LC3. The increased level of autophagy indicated by these measures were confirmed using transmission electron microscopy (TEM). Upon inhibiting autophagy using bafilomycin we observed an increased level of palmitate-induced cell death assessed by Annexin V/PI staining, detection of active caspase-3 and MTT cell viability assay. Interestingly, using TEM and p-PERK or p-eIF2α detection we observed increased endoplasmic reticulum (ER) stress in response to palmitate. Autophagy was induced as an adaptive response against ER stress since it was sensitive to ER stress inhibition. Palmitate-induced ER stress also induced adiponectin resistance, assessed via AMPK phosphorylation, via reducing APPL1 expression. This effect was independent of palmitate-induced autophagy. In summary, our data indicate that palmitate induces autophagy subsequent to ER stress and that this confers a prosurvival effect against lipotoxicity-induced cell death. Palmitate-induced ER stress also led to adiponecin resistance. | 25,164,368 | [
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Bariatric surgery for obesity and metabolic conditions in adults. | This review summarizes recent evidence related to the safety, efficacy, and metabolic outcomes of bariatric surgery to guide clinical decision making. Several short term randomized controlled trials have demonstrated the effectiveness of bariatric procedures for inducing weight loss and initial remission of type 2 diabetes. Observational studies have linked bariatric procedures with long term improvements in body weight, type 2 diabetes, survival, cardiovascular events, incident cancer, and quality of life. Perioperative mortality for the average patient is low but varies greatly across subgroups. The incidence of major complications after surgery also varies widely, and emerging data show that some procedures are associated with a greater risk of substance misuse disorders, suicide, and nutritional deficiencies. More research is needed to enable long term outcomes to be compared across various procedures and subpopulations, and to identify those most likely to benefit from surgical intervention. Given uncertainties about the balance between the risks and benefits of bariatric surgery in the long term, the decision to undergo surgery should be based on a high quality shared decision making process. | 25,164,369 | [
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Synthesis and characterisation of zirconium complexes for cell tracking with Zr-89 by positron emission tomography. | The increasing availability of the long half-life positron emitter Zr-89 (half life 78.4 h) suggests that it is a strong candidate for cell labelling and hence cell tracking using positron emission tomography. The aim was to produce a range of neutral ZrL4 lipophilic complexes for cell labelling which could be prepared under radiopharmaceutical conditions. This was achieved when the ligand was oxine, tropolone or ethyl maltol. The complexes can be prepared in high yield from zirconium(iv) precursors in hydrochloric or oxalic acid solution. The oxinate and tropolonate complexes were the most amenable to chromatographic characterisation, and HPLC and ITLC protocols have been established to monitor their radiochemical purity. The radiochemical synthesis and quality control of (89)Zr(oxinate)4 is reported as well as preliminary cell labelling data for the oxinate, tropolonate and ethyl maltolate complexes which indicates that (89)Zr(oxinate)4 is the most promising candidate for further evaluation. | 25,164,373 | [
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Profile of cancer patients' seen at Korle Bu teaching hospital in Ghana (a cancer registry review). | Though cancer has become a major source of morbidity and mortality globally, few countries in Sub Saharan Africa have data on cancer incidence. This study aims to describe the profile of cancers seen at the Korle Bu teaching hospital which is a major referral centre in Ghana for cancers and other health conditions.Data for the study was obtained from the cancer registry of the hospital and covered the period from January 2012 to December 2012. The public health unit actively collects data on all cancer cases presenting to any department/unit of the hospital to feed the cancer registry. A total of 1136 patients with cancer were studied. Their ages ranged from 1 year to 92 years with a mean of 52.3 ± 15.9 years and a median of 54 years. Patients were predominantly female (70.2%) and majority had attained secondary level of education or higher. The most prevalent cancers seen in men were those of prostate, pharynx and colorectal while in the females, the corresponding cancers were breast, cervix and uterus. Breast and prostate cancers were the commonest among females and males respectively who presented with cancer at the Korle Bu teaching hospital in 2012. | 25,164,384 | [
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Are literacy skills associated with young adults' health in Africa? Evidence from Malawi. | This study investigates whether literacy skills are a distinct dimension of education that influences young adults' health in the southeast African context of Malawi. It uses new data from Tsogolo la Thanzi, a study of young adults in southern Malawi, to achieve three aims. The first is descriptive: to demonstrate a direct assessment for measuring literacy in a population-based survey, and show that it captures variability in skills among young adults, including those with comparable levels of educational attainment. The second aim is to identify whether literacy influences young adults' health - net of their educational attainment and other confounding factors. Multivariate analyses reveal that literacy is associated with two measures of physical health: self-rated health and prolonged sickness. Because literacy is a key determinant of health, the third aim is to provide insight into how to measure it: can commonly used indirect approaches to estimating literacy (e.g., based on educational attainment or self-reports), accurately capture its prevalence and relationship with health? In a second set of analyses, bivariate results show whether, and the extent to which, indirect measures of literacy overestimate literacy's prevalence, and multivariate models assess whether indirect estimates of literacy capture its relationship with health. The findings support future efforts to incorporate literacy assessments into population surveys to accurately estimate literacy's prevalence and health benefits, particularly in contexts like Malawi where access to high-quality schools remains limited. | 25,164,414 | [
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Systemic inflammation in the extremely low gestational age newborn following maternal genitourinary infections. | Gestational genitourinary infections are associated with lifelong disabilities, but it is unknown if neonatal inflammation is involved. Mothers of 914 infants born before 28th gestation week reported cervical/vaginal infection (CVI), and/or urine/bladder/kidney infection (UTI), or neither. Inflammation proteins measured in baby's blood on postnatal days 1, 7, and 14 were considered elevated if in the top quartile for gestational age. Logistic regression models adjusting for potential confounders assessed odds ratios. Compared to mothers with neither UTI/CVI, those with CVI were more likely to have infants with elevated CRP, SAA, MPO, IL-1β, IL-6, IL-6R, TNF-α, RANTES, ICAM-3, E-selectin, and VEGF-R2 on day 1; those with UTI were more likely to have infants with elevated MPO, IL-6R, TNF-R1, TNF-R2, and RANTES on day 7. Placental anaerobes and genital mycoplasma were more common in pregnancies with CVI. Gestational UTI/CVI should be targeted for preventing systemic inflammation in the very preterm newborn. | 25,164,433 | [
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An efficacy study on alleviating micronutrient deficiencies through a multiple micronutrient fortified salt in children in South India. | Multiple micronutrient deficiencies are prevalent in India. The study aims to establish the efficacy of multi-micronutrient fortified salt in addressing multiple micronutrient deficiencies among children compared to nutrition education and no intervention in Tamilnadu. The study employed a community based randomized controlled trial designed to study the impact of multiple micronutrient salt (micronutrient group) in comparison with nutrition education (education group) and no intervention (control group) on haemoglobin, serum ferritin, soluble transferrin receptor, body iron stores, serum retinol and urinary iodine outcomes over a period of 8 months. The fortified salt contained iron, iodine, vitamin A, vitamin B12 and folic acid. All the children were dewormed at baseline and at the end of the study just before the biochemical measurements. There was a significant improvement in most biochemical parameters studied in the micronutrient group when compared with the control group whereas this was not seen between the education and control. Over 8 months, in the micronutrient group, hemoglobin increased by 0.52 g/dL, retinol by 8.56 μg/dL, ferritin by 10.8 μg/L, body iron stores by 1.27 mg and the decrease in the prevalence of retinol deficiency was from 51.6% to 28.1%, anaemia from 46.0% to 32.6%, iron deficiency from 66.9% to 51.3% and iron deficiency anaemia from 35.2% to 31.0%, while the prevalence of all these deficiencies increased or the changes were not significant in the other two groups. Multiple micronutrient fortified salt was able to improve iron and vitamin A status, whereas this was not seen in the nutrition education group. | 25,164,452 | [
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Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe. | Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE + EXE). This study estimates the costs of managing adverse events (AEs) during EVE + EXE therapy and single-agent chemotherapy in Western Europe. An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE + EXE or chemotherapies. AE rates for patients receiving EVE + EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€). The EVE + EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE + EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively. The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE + EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment. | 25,164,472 | [
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Photoactive dye-enhanced tissue ablation for endoscopic laser prostatectomy. | Laser light has been widely used as a surgical tool to treat benign prostate hyperplasia (BPH) over 20 years. Recently, application of high laser power up to 200 W was often reported to swiftly remove a large amount of prostatic tissue. The purpose of this study was to validate the feasibility of photoactive dye injection to enhance light absorption and eventually to facilitate tissue vaporization with low laser power. Chicken breast tissue was selected as a target tissue due to minimal optical absorption at the visible wavelength. Four biocompatible photoactive dyes, including amaranth (AR), black dye (BD), hemoglobin powder (HP), and endoscopic marker (EM), were selected and tested in vitro with a customized 532 nm laser system with radiant exposure ranging from 0.9 to 3.9 J/cm(2) . Light absorbance and ablation threshold were measured with UV-Vis spectrometer and Probit analysis, respectively, and compared to feature the function of the injected dyes. Ablation performance with dye-injection was evaluated in light of radiant exposure, dye concentration, and number of injection. Higher light absorption by injected dyes led to lower ablation threshold as well as more efficient tissue removal in the order of AR, BD, HP, and EM. Regardless of the injected dyes, ablation efficiency principally increased with radiant exposure, dye concentration, and number of injection. Among the dyes, AR created the highest ablation rate of 44.2 ± 0.2 µm/pulse due to higher absorbance and lower ablation threshold. High aspect ratios up to 7.1 ± 0.4 entailed saturation behavior in the tissue ablation injected with AR and BD, possibly resulting from plume shielding and increased scattering due to coagulation. Preliminary tests on canine prostate with a hydraulic injection system demonstrated that 80 W with dye injection yielded comparable ablation efficiency to 120 W with no injection, indicating 33% reduced laser power with almost equivalent performance. Due to efficient coupling of optical energy, pre-injection of photoactive dyes promoted the degree of tissue removal during laser irradiation. Further studies will investigate spatial distribution of dyes and optimal injecting pressure to govern the extent of dye-assisted ablation in a predictable manner. In-depth comprehension on photoactive dye-enhanced tissue ablation can help accomplish efficient and safe laser vaporization for BPH with low power application. | 25,164,484 | [
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Development and preliminary validation of a short form of the Beck Depression Inventory for Youth (BDI-Y) in a sample of adolescent cancer survivors. | The aim of this study was to analyze adolescent cancer survivors' responses to the Beck Depression Inventory for Youth (BDI-Y) to determine if a short form of the measure could be developed that would accurately identify survivors with clinically significant levels of depressive symptoms. Two hundred two adolescent survivors (mean age = 15.39 years, SD = 1.93) completed the BDI-Y at a single time point and were divided into two groups: a derivation sample (n = 105) and a replication sample (n = 97). Based on correlations with the total BDI-Y score in the derivation sample, items were selected for inclusion in three potential short forms, with 6, 8, and 11 items, respectively. These short forms were then evaluated against the full BDI-Y scale first in the derivation sample and subsequently in the replication sample (n = 97). Each of the three short forms had high correlations with the total BDI-Y scale (r > 0.95), good internal consistency (α > 0.80), and good overall discrimination compared to a standard BDI-Y cutoff score (AUC > 0.90). The eight-item short form demonstrated notable consistency across the derivation and replication samples, with high sensitivity and specificity using a cutoff score of ≥5, making it a promising tool for clinical screening. Abbreviated versions of the BDI-Y can accurately detect depression in adolescent cancer survivors. An eight-item short form demonstrates strong psychometric properties and potential for use as a screening measure in this population, while the 6- and 11-item short forms may be suited to other applications. | 25,164,512 | [
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Diagnostic criteria for Huntington's disease based on natural history. | Huntington's disease (HD) is currently diagnosed based on the presence of motor signs indicating 99% "diagnostic confidence" for HD. Recent advances in the understanding of HD natural history and neurobiology indicate that disease-related brain changes begin at least 12 to 15 years before the formal diagnosis based on motor onset. Furthermore, subtle motor dysfunction, cognitive changes, and behavioral alterations are often seen before diagnosis made according to the current criteria. As disease-modifying treatments are developed, likely beginning therapy early will be desirable. We therefore suggest that expanded diagnostic criteria for HD should be adapted to better reflect the natural history of the disease, to enable the conduct of clinical trials in premanifest subjects targeting prevention of neurodegeneration, and to facilitate earlier symptomatic treatment. We propose a new set of criteria for HD diagnostic categories in the International Classification of Diseases that reflect our current understanding of HD natural history and pathogenesis. Based on defined criteria, for example, the Diagnostic Confidence Level and the Total Functional Capacity scales of the Unified Huntington's Disease Rating Scale, HD should be divided in the categories "genetically confirmed" with the subcategories "presymptomatic," "prodromal," and "manifest" and "not genetically confirmed" subdivided into "clinically at risk," "clinically prodromal," and "clinically manifest." | 25,164,527 | [
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Self-management support interventions to reduce health care utilisation without compromising outcomes: a systematic review and meta-analysis. | There is increasing interest in the role of 'self-management' interventions to support the management of long-term conditions in health service settings. Self-management may include patient education, support for decision-making, self-monitoring and psychological and social support. Self-management support has potential to improve the efficiency of health services by reducing other forms of utilisation (such as primary care or hospital use), but a shift to self-management may lead to negative outcomes, such as patients who feel more anxious about their health, are less able to cope, or who receive worse quality of care, all of which may impact on their health and quality of life. We sought to determine which models of self-management support are associated with significant reductions in health services utilisation without compromising outcomes among patients with long-term conditions. We used systematic review with meta-analysis. We included randomised controlled trials in patients with long-term conditions which included self-management support interventions and reported measures of service utilisation or costs, as well as measures of health outcomes (standardized disease specific quality of life, generic quality of life, or depression/anxiety).We searched multiple databases (CENTRAL, CINAHL, Econlit, EMBASE, HEED, MEDLINE, NHS EED and PsycINFO) and the reference lists of published reviews. We calculated effects sizes for both outcomes and costs, and presented the results in permutation plots, as well as conventional meta-analyses. We included 184 studies. Self-management support was associated with small but significant improvements in health outcomes, with the best evidence of effectiveness in patients with diabetic, respiratory, cardiovascular and mental health conditions. Only a minority of self-management support interventions reported reductions in health care utilisation in association with decrements in health. Evidence for reductions in utilisation associated with self-management support was strongest in respiratory and cardiovascular problems. Studies at higher risk of bias were more likely to report benefits. Self-management support interventions can reduce health service utilization without compromising patient health outcomes, although effects were generally small, and the evidence was strongest in respiratory and cardiovascular disorders. Further work is needed to determine which components of self-management support are most effective. | 25,164,529 | [
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Radiation knowledge and perception of referral practice among radiologists and radiographers compared with referring clinicians. | To explore if the perception of radiologists and radiographers on referral practice differs from that of referring clinicians, and to see if knowledge of radiation issues and referral guidelines differ between these groups. A questionnaire was handed out to 46 radiologists and 36 radiographers in Norway. Findings were compared to corresponding results from a similar already published study on clinicians. Questions dealt with referrals unlikely to affect treatment as well as respondents' radiation and referral guideline knowledge. Radiographers estimated the highest proportion of referrals most unlikely to affect treatment (median 20 %) in comparison to radiologists (10 %) and clinicians (5 %). Lack of time, compensating for limited clinical examination and patient expectations were rated as more important reasons for such referrals by radiologists than by clinicians. Radiologists and radiographers possessed significantly better radiation knowledge than clinicians, and were more familiar with referral guidelines. The perception of radiologists and radiographers differs from that of clinicians, concerning the use of imaging most unlikely to affect treatment, and the reasons for such referrals. Radiologists and radiographers possess better radiation knowledge than referring clinicians, but all groups have a potential in improving their radiation protection knowledge. • Radiographers estimated the highest proportion of referrals most unlikely to affect treatment. • Radiologists rated "getting the patient discharged" as an important reason for such referrals. • Radiologists and radiographers possess significantly better radiation knowledge than clinicians. | 25,164,546 | [
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Trends in Australian government health expenditure by age: a fiscal incidence analysis. | Australian government health expenditure per capita has grown steadily across the past few decades, but little is known about trends in the age distribution of health expenditure. In this paper, the Australian Bureau of Statistics (ABS) fiscal incidence studies, which track expenditure at the household level between 1984 and 2010, are used to shed light on this topic. The main finding was that spending has shifted focus from the younger half to the older half of the population. This shift is evident in three areas: (1) acute care (hospitals); (2) community health services (doctors); and (3) pharmaceuticals. Together, these areas account for approximately 88% of expenditure. The trend is independent of demographic aging. It is unlikely to reflect changes in population health. Its explanation is open to debate. Growth in expenditure per household has been more than threefold faster for elderly than young households. Across this period, expenditure per household per week has increased by 51% for the young, by 79% for the middle aged and by 179% for the elderly. This age-related growth is most prominent in expenditure on acute care, community health services and pharmaceuticals. WHAT IS KNOWN ABOUT THE TOPIC?: The Productivity Commission has published figures that relate age and Australian heath expenditure. However, there has been no published study of age-related trends in Australian health expenditure. WHAT DOES THIS PAPER ADD?: In addition to tracking age-related trends across 26 years, this paper adds a breakdown of those trends into four categories of expenditure, namely acute care, community health services, pharmaceutical benefits, and other. This breakdown shows that the trends vary by expenditure type. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: The paper shows that forward projections in health expenditure need to take into account age-related trends as well as demographic trends. | 25,164,547 | [
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Quality measurement in breast cancer. | Variation in the quality of breast care affects outcomes. Objective measurement tools are central to this effort. Most quality measures are process measures. Application of these improves quality. Many national organizations are promoting them for purposes ranging from feedback to providers to public reporting and directing payment. Surgeons should evaluate their own practices and should be involved in local, regional and national efforts to assess and improve breast care. | 25,164,555 | [
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Evaluation of two quantitative analysis methods of optical coherence tomography for detection of enamel demineralization and comparison with microhardness. | We aimed to evaluate in the same study two quantitative methods for quantification of incipient caries in human dental enamel by using optical coherence tomography (OCT): the optical attenuation coefficient and the area under the A-scan signal, and to compare their results with those obtained from microhardness analysis. One hundred and sixty samples were obtained from 40 sound human third molars, which had their crowns sectioned. Simulated caries were created by a pH cycling method. OCT measurements were performed on the samples, before and after the induced demineralization. We determined the total optical attenuation coefficient from the OCT signal in each site and evaluated the sensitivity and specificity of this approach to the detection of the demineralization. Also, the areas under the OCT curves (AUC-OCT) and those from sectional microhardness tests (AUC-MH) were compared. Both the analysis of the optical attenuation coefficient and the AUC-OCT were adequate to efficiently distinguish sound and demineralized samples with sensitivity of 0.93 and specificity of 0.96. The AUC-MH and the AUC-OCT data presented linear relationship and correlation of 0.99. Both methods for signal analysis from OCT allowed detection of demineralization with good performance. The AUC-OCT approach enables obtaining a linear relation with the microhardness results, for a quantitative assessment of mineral loss in human teeth. | 25,164,563 | [
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Efficacy of budesonide in collagenous colitis Evaluation of: Miehlke S, Madisch A, Kupcinskas L, et al. Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis. Gastroenterology 2014;146(5):1222-1230 e1222. | Collagenous colitis (CC) is a less common colonic disease with variable prevalence and undulating course. Among the available therapies, budesonide was demonstrated to induce a rapid and sustained remission in many cases, but little is known about the comparative efficacy of other treatments, such as mesalamine. Evaluation of a randomized study assessing the efficacy and safety of budesonide over mesalamine in patients with CC. Data from the study showed that budesonide was significantly superior to placebo and to mesalamine and further supports the recommendation of the current guidelines on the use of budesonide in CC. However, other forms of mesalamine may further be evaluated for this disease. | 25,164,577 | [
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Quality use of medicines within universal health coverage: challenges and opportunities. | Medicines are a major driver of quality, safety, equity, and cost of care in low and middle-income country health systems. Universal health coverage implementers must explicitly address appropriate use of medicines to realize the health benefits of medicines, avoid wasting scarce resources, and sustain the financial viability of universal health coverage schemes. Medicines are major contributors to the health and well-being of individuals and populations when used appropriately, and they waste resources and endanger health when used unnecessarily or incorrectly. Stakeholders need to balance inherently competing objectives in the pharmaceutical sector. Emerging and expanding UHC schemes provide potential levers to balance competing system objectives.To use these levers, sustainable universal coverage programs will require a) information systems that can track medicines utilization, expenditures, and quality of medicines use; b) routine monitoring of indicators of medicines availability, access, affordability, and use; c) policies and programs that facilitate appropriate medicines use by prescribers, dispensers, and patients; d) transparency in setting priorities for medicines coverage under resource constraints; and e) a system perspective to engage diverse actors.As they operationalize paths toward universal health coverage and include targeted medicines coverage policies and programs, systems can build on, and innovate, pharmaceutical policy frameworks and management tools from different countries' settings. Ensuring that medicines which achieve important health outcomes are available, accessible to all, used appropriately, and sustainably affordable is essential for realizing universal health coverage. Stakeholder cooperation and use of information and financing system levers provide opportunities to work toward this goal. | 25,164,588 | [
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Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells. | Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative that was shown to have anti-inflammatory and anticancer activities in various solid tumors. The anticancer effect of nobiletin on nonsolid tumor remains unclear. Herein, the molecular mechanisms by which nobiletin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. The results showed that nobiletin suppressed cell proliferation in various types of AML cell lines. Moreover, nobiletin induced cell-cycle arrest of HL-60 AML cells at the G0/G1 phase by suppressing extracellular signal-regulated kinase (ERK) activity. Furthermore, nobiletin effectively induced apoptosis of HL-60 cells through caspase-8, caspase-9, and caspases-3 activation concomitantly with a marked induction of p38 mitogen-activated protein kinase (MAPK) activation, but without affecting expression levels of Bcl-2, Bax, or Bid. Taken together, our results suggest that nobiletin inhibited HL-60 cell proliferation through inducing cell-cycle arrest and apoptosis and could serve as a potential additional chemotherapeutic agent for treating AML. | 25,164,609 | [
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Heavy lifting at work and risk of ischemic heart disease: protocol for a register-based prospective cohort study. | There are theoretical grounds to suspect that heavy lifting at work is an important risk factor for ischemic heart disease (IHD). However the relationship has not been sufficiently acknowledged by empirical studies. Positive and statistically significant associations have been found in studies that utilize self-reported exposure data. Such studies are, however, prone to reporting bias. All else equal, people with a poor cardiovascular fitness/health may have a higher propensity to perceive their work environment as heavy. The study described in the present protocol aims to investigate the relationship between heavy lifting at work and IHD by use of material and methods that are free from reporting bias. This is a register-based prospective cohort study. Male blue-collar workers in Denmark will be identified and followed through national registers, from 2001-2010, for hospital treatment or death due to IHD. Relative rates of IHD between "workers in occupations likely to involve heavy lifting" and "other blue-collar workers" will be estimated through Poisson regression. Results are expected to be ready in mid-2015. Since this is not a randomized study, it cannot confirm etiological hypotheses. It may, however, confirm that employment in occupations that involve heavy lifting is a predictor for IHD and thereby lend support to the hypothesis of a causal relationship. | 25,164,612 | [
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Does urbanization facilitate individual recognition of humans by house sparrows? | Wild animals living in proximity to humans may benefit from recognizing people individually and adjusting their behaviour to the potential risk or gain expected from each person. Although several urban-dwelling species exhibit such skills, it is unclear whether this is due to pre-existing advanced cognitive abilities of taxa predisposed for city life or arises specifically in urban populations either by selection or through ontogenetic changes facilitated by exposure to humans. To test these alternatives, we studied populations of house sparrows (Passer domesticus) along the urbanization gradient. We manipulated the birds' experience (hostile or not) associated with humans with different faces (masks) and measured their behavioural responses to the proximity of each person. Contrary to our expectations, we found that while rural birds showed less fear of the non-hostile than of the hostile or an unfamiliar person, urban birds made no distinction. These results indicate that house sparrows are less able to recognize individual humans or less willing to behaviourally respond to them in more urbanized habitats with high human population density. We propose several mechanisms that may explain this difference, including reduced pay-off of discrimination due to a low chance of repeated interactions with city people, or a higher likelihood that city people will ignore them. | 25,164,623 | [
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Diaphragmatic hernia in horses: 44 cases (1986-2006). | To present a case series of horses diagnosed with diaphragmatic hernia, and to determine the significance of (1) historical information, examination findings, and laboratory data; and (2) exploratory laparotomy or necropsy findings on short- and long-term outcome. University Referral Hospital. Retrospective study. Forty-four horses/foals admitted between 1986 and 2006 with a diagnosis of diaphragmatic hernia made either at exploratory laparotomy or necropsy. None. Information from the medical records included history, clinical examination findings at presentation, and findings of exploratory laparotomy or necropsy. Logistic regression or the Fisher exact test was used to determine factors associated with survival. Outcome was defined as survival to discharge (short-term survival), and long-term survival was defined as horses alive at least 1-year post surgery. Of the 44 horses, 18 died or were euthanized before surgery. Twenty-six were taken to surgery, 17 were euthanized. Nine horses recovered from anesthesia, 7 of which survived to hospital discharge. Of these, 5 were alive at long-term follow-up. Survival was significantly associated with the age of the horse (≤2 y old) at presentation, presence of normal peritoneal fluid at presentation, amount of compromised viscera at surgery (<50% small intestine), and the size (<10 cm) and location (ventral) of the diaphragmatic tear. This study confirms that size and location of the lesion do play a significant role in prognosis. And, although the prognosis for horses with diaphragmatic hernia is poor, if horses have operable lesions there is a fair prognosis for long-term survival. | 25,164,635 | [
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Phasic dopaminergic activity exerts fast control of cholinergic interneuron firing via sequential NMDA, D2, and D1 receptor activation. | Phasic increases in dopamine (DA) are involved in the detection and selection of relevant sensory stimuli. The DAergic and cholinergic system dynamically interact to gate and potentiate sensory inputs to striatum. Striatal cholinergic interneurons (CINs) respond to relevant sensory stimuli with an initial burst, a firing pause, or a late burst, or a combination of these three components. CIN responses coincide with phasic firing of DAergic neurons in vivo. In particular, the late burst of CINs codes for the anticipated reward. To examine whether DAergic midbrain afferents can evoke the different CIN responses, we recorded from adult olfactory tubercle slices in the mouse ventral striatum. Olfactory inputs to striatal projection neurons were gated by the cholinergic tone. Phasic optogenetic activation of DAergic terminals evoked combinations of initial bursts, pauses, and late bursts in subsets of CINs by distinct receptor pathways. Glutamate release from midbrain afferents evoked an NMDAR-dependent initial burst followed by an afterhyperpolarization-induced pause. Phasic release of DA itself evoked acute changes in CIN firing. In particular, in CINs without an initial burst, phasic DA release evoked a pause through D2-type DA receptor activation. Independently, phasic DA activated a slow depolarizing conductance and the late burst through a D1-type DA receptor pathway. In summary, DAergic neurons elicit transient subsecond firing responses in CINs by sequential activation of NMDA, D2-type, and D1-type receptors. This fast control of striatal cholinergic tone by phasic DA provides a novel dynamic link of two transmitter systems central to the detection and selection of relevant stimuli. | 25,164,653 | [
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Dynamic fidelity control to the central auditory system: synergistic glycine/GABAergic inhibition in the cochlear nucleus. | GABA and glycine are the major inhibitory transmitters that attune neuronal activity in the CNS of mammals. The respective transmitters are mostly spatially separated, that is, synaptic inhibition in the forebrain areas is mediated by GABA, whereas glycine is predominantly used in the brainstem. Accordingly, inhibition in auditory brainstem circuits is largely mediated by glycine, but there are few auditory synapses using both transmitters in maturity. Little is known about physiological advantages of such a two-transmitter inhibitory mechanism. We explored the benefit of engaging both glycine and GABA with inhibition at the endbulb of Held-spherical bushy cell synapse in the auditory brainstem of juvenile Mongolian gerbils. This model synapse enables selective in vivo activation of excitatory and inhibitory neuronal inputs through systemic sound stimulation and precise analysis of the input (endbulb of Held) output (spherical bushy cell) function. The combination of in vivo and slice electrophysiology revealed that the dynamic AP inhibition in spherical bushy cells closely matches the inhibitory conductance profile determined by the glycine-R and GABAA-R. The slow and potent glycinergic component dominates the inhibitory conductance, thereby primarily accounting for its high-pass filter properties. GABAergic transmission enhances the inhibitory strength and shapes its duration in an activity-dependent manner, thus increasing the inhibitory potency to suppress the excitation through the endbulb of Held. Finally, in silico modeling provides a strong link between in vivo and slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances during in vivo-like spontaneous and sound evoked activities. | 25,164,657 | [
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Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab enhances amyloid reduction in APPLondon mice. | Therapeutic approaches for prevention or reduction of amyloidosis are currently a main objective in basic and clinical research on Alzheimer's disease. Among the agents explored in clinical trials are anti-Aβ peptide antibodies and secretase inhibitors. Most anti-Aβ antibodies are considered to act via inhibition of amyloidosis and enhanced clearance of existing amyloid, although secretase inhibitors reduce the de novo production of Aβ. Limited information is currently available on the efficacy and potential advantages of combinatorial antiamyloid treatment. We performed a chronic study in APPLondon transgenic mice that received treatment with anti-Aβ antibody gantenerumab and BACE inhibitor RO5508887, either as mono- or combination treatment. Treatment aimed to evaluate efficacy on amyloid progression, similar to preexisting amyloidosis as present in Alzheimer's disease patients. Mono-treatments with either compound caused a dose-dependent reduction of total brain Aβ and amyloid burden. Combination treatment with both compounds significantly enhanced the antiamyloid effect. The observed combination effect was most pronounced for lowering of amyloid plaque load and plaque number, which suggests effective inhibition of de novo plaque formation. Moreover, significantly enhanced clearance of pre-existing amyloid plaques was observed when gantenerumab was coadministered with RO5508887. BACE inhibition led to a significant time- and dose-dependent decrease in CSF Aβ, which was not observed for gantenerumab treatment. Our results demonstrate that combining these two antiamyloid agents enhances overall efficacy and suggests that combination treatments may be of clinical relevance. | 25,164,658 | [
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Beyond blindsight: properties of visual relearning in cortically blind fields. | Damage to the primary visual cortex (V1) or its immediate afferents results in a dense scotoma, termed cortical blindness (CB). CB subjects have residual visual abilities, or blindsight, which allow them to detect and sometimes discriminate stimuli with high temporal and low spatial frequency content. Recent work showed that with training, discriminations in the blind field can become more reliable, and even reach consciousness. However, the narrow spatiotemporal bandwidth of blindsight limits its functional usefulness in everyday vision. Here, we asked whether visual training can induce recovery outside the spatiotemporal bandwidth of blindsight. Specifically, could human CB subjects learn to discriminate static, nonflickering stimuli? Can such learning transfer to untrained stimuli and tasks, and does double training with moving and static stimuli provide additional advantages relative to static training alone? We found CB subjects capable of relearning static orientation discriminations following single as well as double training. However, double training with complex, moving stimuli in a separate location was necessary to recover complex motion thresholds at locations trained with static stimuli. Subjects trained on static stimuli alone could only discriminate simple motion. Finally, both groups had approximately equivalent, incomplete recovery of fine orientation and direction discrimination thresholds, as well as contrast sensitivity. These results support two conclusions: (1) from a practical perspective, complex moving stimuli and double training may be superior training tools for inducing visual recovery in CB, and (2) the cortically blind visual system can relearn to perform a wider range of visual discriminations than predicted by blindsight alone. | 25,164,661 | [
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Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease. | The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease. | 25,164,669 | [
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Fear conditioning, safety learning, and sleep in humans. | Fear conditioning is considered an animal model of post-traumatic stress disorder. Such models have shown fear conditioning disrupts subsequent rapid eye movement sleep (REM). Here, we provide a translation of these models into humans. Using the fear potentiated startle (FPS) procedure, we examined the effects of fear conditioning and safety signal learning on subsequent REM sleep in healthy adults. We also examined the effects of changes in REM sleep on retention of fear and safety learning. Participants (n = 42 normal controls) spent 3 consecutive nights in the laboratory. The first was an adaptation night. Following the second night, we administered a FPS procedure that included pairing a wrist shock with a threat signal and a safety signal never paired with a shock. The next day, we administered the FPS procedure again, with no wrist shocks to any stimulus, to measure retention of fear and safety. Canonical correlations assessed the relationship between FPS response and REM sleep. Results demonstrated that increased safety signal learning during the initial acquisition phase was associated with increased REM sleep consolidation that night, with 28.4% of the variance in increased REM sleep consolidation from baseline accounted for by safety signal learning. Overnight REM sleep was, in turn, related to overnight retention of fear and safety learning, with 22.5% of the variance in startle retention accounted for by REM sleep. These data suggest that sleep difficulties, specifically REM sleep fragmentation, may play a mechanistic role in post-traumatic stress disorder via an influence on safety signal learning and/or threat-safety discrimination. | 25,164,670 | [
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Fast phasic release properties of dopamine studied with a channel biosensor. | Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation. | 25,164,674 | [
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Necrotizing gastritis associated with Clostridium septicum in a rabbit. | Clostridium septicum is the causative agent of histotoxic infections, including malignant edema and braxy (necrotizing abomasitis) in several animal species. The carcass of a 2-year-old, female New Zealand white rabbit with a history of acute depression and obtundation followed by death was received at the California Animal Health and Food Safety Laboratory System (San Bernardino, California) for necropsy and diagnostic workup. No gross lesions were detected at necropsy. Microscopically, there was moderate to severe, multifocal fibrinonecrotizing, transmural gastritis with numerous intralesional Gram-positive, sporulated rods, and disseminated thrombosis of the brain, lungs, heart, and liver, with occasional intravascular rods. The rods observed within the gastric wall and thrombi in the stomach and lung were positive for C. septicum by immunohistochemical staining. However, this microorganism was not isolated from stomach content. Clostridium septicum should be included in the list of possible etiologies of gastritis in rabbits. | 25,164,682 | [
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Acupuncture decreases matrix metalloproteinase-2 activity in patients with migraine. | To evaluate the effect of acupuncture on the serum matrix metalloproteinase-2 (MMP-2) level and activity in patients with migraine. After baseline testing, eligible patients with migraine according to the criteria of the International Headache Society who volunteered to join the study were included (n=27). The patients received 10 sessions of acupuncture treatment. The points selected were bilateral ST8, ST44, LI4, LI11, LIV3, SP6, GB1, GB14, GB20, GV14, GV20, Yintang, Taiyang and ear Shenmen. Pain was measured using a visual analogue scale (VAS). Short form-36 (SF-36) was used to determine their quality of life. Blood samples were taken before treatment and after the first and last sessions of acupuncture for measurement of MMP-2 concentration and activity. The mean VAS was 85.5±16.6 before acupuncture and was significantly decreased to 39.8±20.6 after 10 sessions of acupuncture (p<0.0001). There was a significant increase in all SF-36 scores after acupuncture compared with values before treatment (p<0.0001). No significant differences were found in MMP-2 concentrations before treatment and after the first and last sessions (p>0.05). However, there were significant changes in MMP-2 activity (p<0.0001). The results of this study showed a clinically relevant decrease in MMP-2 activity in patients with migraine treated with acupuncture. The mechanism underlying the effect of acupuncture in alleviating pain may be associated with a decrease in MMP-2 activity. | 25,164,776 | [
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Visual dysfunction in patients with Parkinson's disease and essential tremor. | The aim of this study was to determine the specificity and sensitivity of the Pelli-Robson and Ishihara diagnostic methods in differing Parkinson's disease from essential tremor compared to DaTSCAN (dopamine transporter scan) findings. The intention was to investigate whether visual dysfunction appears in the early state of Parkinson's disease. Therefore, we included patients with the symptomatology of parkinsonism lasting between 6 and 12 months. The study included 164 patients of which 59 (36.0%) suffered from Parkinson's disease, 51 (31.1%) from essential tremor, and 54 (32.9%) healthy patients which presented the control group. The specificity of Pelli-Robson test in confirming Parkinson's disease was 53% and the sensitivity 81.4%. The specificity of Ishihara test in confirming Parkinson's disease was 88.2%, and sensitivity 55.9%. We found that the colour and contrast dysfunction are present as the earliest symptoms of Parkinson's disease. In this study the Pelli-Robson test is highly sensitive and the Ishihara tables are highly specific in the differential diagnosis between Parkinson's disease and essential tremor, but neither of these methods fulfils the criteria for the validity of a test. We suggest performing both of these methods to evaluate which patients are indicated for DaTSCAN. | 25,164,787 | [
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Distinct biochemical and functional properties of two Rab5 homologs from the rice blast fungus Magnaporthe oryzae. | Rab5 is a key regulator of early endocytosis by promoting early endosomal fusion and motility. In this study, we have unexpectedly found distinct properties of the two Rab5 homologs (MoRab5A and MoRab5B) from Magnaporthe oryzae, a pathogenic fungus in plants whose infection causes rice blast disease. Like mammalian Rab5, MoRab5A and MoRab5B can bind to several Rab5 effectors in a GTP-dependent manner, including EEA1, Rabenosyn-5, and Rabaptin-5. However, MoRab5A shows distinct binding characteristics in the sense that both the wild-type and the GTP hydrolysis-defective constitutively active mutant bind the effectors equally well in GST pull-down assays, suggesting that MoRab5A is defective in GTP hydrolysis and mostly in the GTP-bound conformation in the cell. Indeed, GTP hydrolysis assays indicate that MoRab5A GTPase activity is dramatically lower than MoRab5B and human Rab5 and is insensitive to RabGAP5 stimulation. We have further identified a Pro residue in the switch I region largely responsible for the distinct MoRab5A properties by characterization of MoRab5A and MoRab5B chimeras and mutagenesis. The differences between MoRab5A and MoRab5B extend to their functions in the cell. Although they both target to early endosomes, only MoRab5B closely resembles human Rab5 in promoting early endosome fusion and stimulating fluid phase endocytosis. In contrast, MoRab5A correlates with another related early endosomal Rab, Rab22, in terms of the presence of the switch I Pro residue and the blocked GTPase activity. Our data thus identify MoRab5B as the Rab5 ortholog and suggest that MoRab5A specializes to perform a non-redundant function in endosomal sorting. | 25,164,815 | [
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The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats. | L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats. | 25,164,827 | [
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Severity of cognitive impairment as a prognostic factor for mortality and functional recovery of geriatric patients with hip fracture. | To identify how the severity of dementia influences functional recovery and mortality in elderly patients hospitalized for hip fracture. An observational retrospective study of 1258 patients aged older than 69 years and diagnosed with hip fracture who received care within an orthogeriatrics unit from 2004 to 2008 was carried out. During a 12-month follow-up period, functional recovery and mortality outcomes were measured. Dementia was present in 383 (28.1%) patients: it was mild in 183 (48%), moderate in 102 (26.5%) and severe in 98 (25.5%). Compared with patients with preserved cognitive status, patients with dementia had the following statistically significant differences (means [standard deviation] or percentage): older age (preserved, 82.29 years [6.5 years]; mild, 83.63 years [6.1 years]; moderate, 83.47 years [5.9 years]; severe, 84.46 years [6.1 years]; P < 0.001); lower Barthel Index (89.7 [21.6], 72.7 [24.6], 58.9 [28.6], 38.0 [28.1]; P < 0.001); delirium (11.7%, 25.6%, 37.6%, 44.7%; P < 0.001); less ambulation at 6 months postdischarge (83.9%, 72.8%, 56.9%, 41.7%; P < 0.001); and higher mortality at discharge (4%, 5.7%, 8.2%, 10.6%; P < 0.001) and 12 months after discharge (21.2%, 32.3%, 46.3%, 53.5%; P < 0.001). Patients with severe dementia had lower probability of functional recovery at discharge (OR 0.272, 95% CI 0.140-0.526, P < 0.001) and 6 months after discharge (OR 0.439, 95% CI 0.197-0.979, P = 0.04), as well as a greater probability of dying (HR 1.640, 95% CI 1.020-2.635, P = 0.04). We observed higher 12-month mortality and less functional recovery with increasing severity of dementia. | 25,164,866 | [
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The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation. | It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the "Hobart method") has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial. This is a multicentre, randomised, masked, controlled trial in preterm infants 25-28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017. Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25-28 weeks gestation. Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580. | 25,164,872 | [
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Somatically mutated tumor antigens in the quest for a more efficacious patient-oriented immunotherapy of cancer. | Although cancer immunotherapy shows efficacy with adoptive T cell therapy (ACT) and antibody-based immune checkpoint blockade, efficacious therapeutic vaccination of cancer patients with tumor-associated antigens (TAAs) remains largely unmet. Current cancer vaccines utilize nonmutated shared TAAs that may have suboptimal immunogenicity. Experimental evidence underscores the strong immunogenicity of unique TAAs derived from somatically mutated cancer proteins, whose massive characterization has been precluded until recently by technical limitations. The development of cost-effective, high-throughput DNA sequencing approaches makes now possible the rapid identification of all the somatic mutations contained in a cancer cell genome. This method, combined with robust bioinformatics platforms for T cell epitope prediction and established reverse immunology approaches, provides us with an integrated strategy to identify patient-specific unique TAAs in a relatively short time, compatible with their potential use in the clinic. Hence, it is now for the first time possible to quantitatively define the patient's unique tumor antigenome and exploit it for vaccination, possibly in combination with ACT and/or immune checkpoint blockade to further increase immunotherapy efficacy. | 25,164,877 | [
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Tuftsin-based, EGFR-targeting fusion protein and its enediyne-energized analog show high antitumor efficacy associated with CD47 down-regulation. | Tuftsin (TF) is an immunomodulator tetrapeptide (Thr-Lys-Pro-Arg) that binds to the receptor neuropilin-1 (Nrp1) on the surface of cells. Many reports have described anti-tumor activity of tuftsin to relate with nonspecific activation of the host immune system. Lidamycin (LDM) that displays extremely potent cytotoxicity to cancer cells is composed of an apoprotein (LDP) and an enediyne chromophore (AE). In addition, Ec is an EGFR-targeting oligopeptide. In the present study, LDP was used as protein scaffold and the specific carrier for the highly potent AE. Genetically engineered fusion proteins LDP-TF and Ec-LDP-TF were prepared; then, the enediyne-energized fusion protein Ec-LDM-TF was generated by integration of AE into Ec-LDP-TF. The tuftsin-based fusion proteins LDP-TF and Ec-LDP-TF significantly enhanced the phagocytotic activity of macrophages as compared with LDP (P < 0.05). Ec-LDP-TF effectively bound to tumor cells and macrophages; furthermore, it markedly suppressed the growth of human epidermoid carcinoma A431 xenograft in athymic mice by 84.2 % (P < 0.05) with up-regulated expression of TNF-α and IFN-γ. Ec-LDM-TF further augmented the therapeutic efficacy, inhibiting the growth of A431 xenograft by 90.9 % (P < 0.05); notably, the Ec-LDM-TF caused marked down-regulation of CD47 in A431 cells. Moreover, the best therapeutic effect was recorded in the group of animals treated with the combination of Ec-LDP-TF with Ec-LDM-TF. The results suggest that tuftsin-based, enediyne-energized, and EGFR-targeting fusion proteins exert highly antitumor efficacy with CD47 modulation. Tuftsin-based fusion proteins are potentially useful for treatment of EGFR- and CD47-overexpressing cancers. | 25,164,878 | [
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[Continuous development of laparoscopic surgery for gastrointestinal carcinoma based on process optimization and technical innovation]. | With process optimization and technical innovation, laparoscopic gastrointestinal surgery has evolved dramatically over the last two decades and provided important improvement in the contemporary surgical practice and patients' recovery. With the emergence of many new minimally invasive technologies, including total laparoscopic surgery, single-incision laparoscopic surgery, and natural orifice specimen extraction, patents with gastrointestinal carcinomas may experience less pain and have lower perioperative complications, but the exact efficacy remains to be proven. Large-scale international multi-centre randomized controlled trial data have revealed that laparoscopic colorectal surgery is safe both in terms of short-term perioperative outcomes and long-term oncological efficacy. However, the question whether there is an equivalent oncological outcome compared to the open approach in gastric cancer is still unanswered by now and needs to be proven by future studies. | 25,164,884 | [
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[A meta-analysis on the outcomes and potential benefits of hybrid robotic technique in rectal cancer surgery]. | To assess the efficacy and potential benefits of hybrid robotic technique in rectal cancer surgery. A meta-analysis on the literatures about the hybrid robotic proctectomy from Medline(PubMed), Cochrane, EMBASE, OVID, CNKI, Wanfang database, manually retrieved articles between January 2007 and January 2013 was performed by RevMan 5.2. According to Newcastle-Ottawa Scale, 7 articles were screened. A total of 884 cases (430 robotic cases and 454 laparoscopic cases) were included. Compared to the laparoscopic group, the conversion rate and intraoperative blood loss was reduced and operation time was longer in the robotic group. The number of lymph node harvested, time to first flatus, length of hospital stay and postoperative complication morbidity were not significantly different between the two groups. Potential benefits of robotic surgery include lower conversion rate and less blood loss, however, present evidence supporting the robotic benefits is still limited. | 25,164,895 | [
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Adherence to oral migraine-preventive medications among patients with chronic migraine. | Chronic migraine (CM) is a disabling disorder characterized by ≥15 headache days per month that has been shown to significantly reduce quality of life. Migraine-prevention guidelines recommend preventive medications as the standard of care for patients with frequent migraine. The aim of this study was to assess adherence to 14 commonly prescribed oral migraine-preventive medications (OMPMs) among patients with CM. Retrospective claims analysis of a US claim database (Truven MarketScan® Databases) was queried to identify patients who were at least 18 years old, diagnosed with CM, and initiated an OMPM (antidepressants, beta blockers, or anticonvulsants) between January 1, 2008 and September 30, 2012. Medication possession ratios (MPR) and proportion of days covered (PDC) were calculated for each patient. A cutoff of ≥80% was used to classify adherence. The odds of adherence between OMPMs were compared using logistic regression models. Of the 75,870 patients identified with CM, 8688 met the inclusion/exclusion criteria. Adherence ranged between 26% to 29% at six months and 17% to 20% at 12 months depending on the calculation used to classify adherence (PDC and MPR, respectively). Adherence among the 14 OMPMs was similar except for amitriptyline, nortriptyline, gabapentin, and divalproex, which had significantly lower odds of adherence when compared to topiramate. Adherence to OMPMs is low among the US CM population at six months and worsens by 12 months. | 25,164,920 | [
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Mutations associated with occult hepatitis B in HIV-positive South Africans. | Occult hepatitis B is characterized by the absence of hepatitis B surface antigen (HBsAg) but the presence of HBV DNA. Because diagnosis of hepatitis B virus (HBV) typically includes HBsAg detection, occult HBV remains largely undiagnosed. Occult HBV is associated with increased risk of hepatocellular carcinoma, reactivation to chronic HBV during immune suppression, and transmission during blood transfusion and liver transplant. The mechanisms leading to occult HBV infection are unclear, although viral mutations are likely a significant factor. In this study, sera from 394 HIV-positive South Africans were tested for HBV DNA and HBsAg. For patients with detectable HBV DNA, the overlapping surface and polymerase open reading frames (ORFs) were sequenced. Occult-associated mutations-those mutations found exclusively in individuals with occult HBV infection but not in individuals with chronic HBV infection from the same cohort or GenBank references-were identified. Ninety patients (22.8%) had detectable HBV DNA. Of these, 37 had detectable HBsAg, while 53 lacked detectable surface antigen. The surface and polymerase ORFs were cloned successfully for 19 patients with chronic HBV and 30 patients with occult HBV. In total, 235 occult-associated mutations were identified. Ten occult-associated mutations were identified in more than one patient. Additionally, 15 amino acid positions had two distinct occult-associated mutations at the same residue. Occult-associated mutations were common and present in all regions of the surface and polymerase ORFs. Further study is underway to determine the effects of these mutations on viral replication and surface antigen expression in vitro. | 25,164,924 | [
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The influence of land use change on landslide susceptibility zonation: the Briga catchment test site (Messina, Italy). | The spatial distribution of landslides is influenced by different climatic conditions and environmental settings including topography, morphology, hydrology, lithology, and land use. In this work, we have attempted to evaluate the influence of land use change on landslide susceptibility (LS) for a small study area located in the southern part of the Briga catchment, along the Ionian coast of Sicily (Italy). On October 1, 2009, the area was hit by an intense rainfall event that triggered abundant slope failures and resulted in widespread erosion. After the storm, an inventory map showing the distribution of pre-event and event landslides was prepared for the area. Moreover, two different land use maps were developed: the first was obtained through a semi-automatic classification of digitized aerial photographs acquired in 1954, the second through the combination of supervised classifications of two recent QuickBird images. Exploiting the two land use maps and different land use scenarios, LS zonations were prepared through multivariate statistical analyses. Differences in the susceptibility models were analyzed and quantified to evaluate the effects of land use change on the susceptibility zonation. Susceptibility maps show an increase in the areal percentage and number of slope units classified as unstable related to the increase in bare soils to the detriment of forested areas. | 25,164,982 | [
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Web-based experiments for the study of collective social dynamics in cultural markets. | Social scientists are often interested in understanding how the dynamics of social systems are driven by the behavior of individuals that make up those systems. However, this process is hindered by the difficulty of experimentally studying how individual behavioral tendencies lead to collective social dynamics in large groups of people interacting over time. In this study, we investigate the role of social influence, a process well studied at the individual level, on the puzzling nature of success for cultural products such as books, movies, and music. Using a "multiple-worlds" experimental design, we are able to isolate the causal effect of an individual-level mechanism on collective social outcomes. We employ this design in a Web-based experiment in which 2,930 participants listened to, rated, and downloaded 48 songs by up-and-coming bands. Surprisingly, despite relatively large differences in the demographics, behavior, and preferences of participants, the experimental results at both the individual and collective levels were similar to those found in Salganik, Dodds, and Watts (2006). Further, by comparing results from two distinct pools of participants, we are able to gain new insights into the role of individual behavior on collective outcomes. We conclude with a discussion of the strengths and weaknesses of Web-based experiments to address questions of collective social dynamics. | 25,164,996 | [
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Preserving knee function following osteoarthritis diagnosis: a sustainability theory and social ecology clinical commentary. | To sustain natural systems, there must be an ongoing balance between environmental, social, and economic considerations. A key element of sustainability theory is to identify the most vulnerable surroundings. The most vulnerable knee tissue is the articular cartilage as it is the last line of osteoarthritis (OA) defense. This tissue has a poor capacity for healing. Based on sustainability theory and social ecology concepts we propose that several key factors contribute to knee function preservation. Factors include health history, genetic predisposition, personal behaviors, and socio-environmental factors in addition to local-regional-global physiological system function. Addressing only some of these factors or any one factor in isolation may lead to less than optimal treatment effectiveness. The purpose of this commentary is to introduce a medical, surgical and rehabilitation management approach for patients with knee OA that considers more than physical function improvement. This approach also considers social, emotional, and environmental factors to better ensure patient satisfaction, fulfilled expectations and successful outcomes. A clinical care pathway is presented for a 57-year-old patient with medial compartment knee OA who is contemplating early arthroplasty versus a knee function preservation treatment approach. Early arthroplasty refers to high revision likelihood based on a minimum 15 year prosthesis life-expectancy. | 25,165,013 | [
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Association of elevated radiation dose with mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention. | This study sought to identify clinical and procedural predictors of elevated radiation dose received by patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and to determine if elevated radiation dose was predictive of mortality in this population. Little data exist regarding the impact of excessive radiation burden on clinical outcomes in patients undergoing PCI. The study population included 1,039 patients who underwent PCI for an AMI between January 1, 2007 and December 31, 2008 at an academic tertiary care teaching hospital. Cumulative skin dose (measured in milligray [mGy]) was selected as a measurement of patient radiation burden. Clinical and procedural variables were analyzed in multiple logistic and linear regression models to determine predictors of higher skin dose, and its impact was evaluated on all-cause intermediate-term mortality at two years. Median skin dose was 2120 mGy (IQR 1379-3190 mGy) in the overall population, of which 153 (20.8%) patients received an elevated skin dose (defined as a skin dose>4,000 mGy). Independent predictors of elevated skin dose included male gender, obesity, multivessel intervention, and presentation with a non-ST-elevation MI (NSTEMI) versus an ST-elevation MI (STEMI). Increased skin dose was not predictive of intermediate-term mortality by multivariate analysis in the overall population or in either subgroup of STEMI and NSTEMI. In this contemporary observational study examining patients with AMI undergoing PCI, male gender, obesity, multivessel intervention, and presentation with a NSTEMI were associated with increased radiation exposure. | 25,165,016 | [
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Effective diameter of the aortic annulus prior to transcatheter aortic valve implantation: influence of area-based versus perimeter-based calculation. | In computed tomography (CT) evaluation prior to transcatheter aortic valve implantation area- and perimeter-based calculation of the aortic annulus diameter, the so-called effective annulus diameter (ED), is the preferred parameter for decision making regarding prosthesis sizes. Currently, it is unclear how relevant the differences between the two methods of measurement are and how they are influenced by the cardiac cycle. The aim of this study was to compare area- and perimeter-based measurements in computed tomography derived aortic annulus sizing. A total of 60 patients who underwent evaluation for transcatheter aortic valve implantation were included in this study. All patients received pre-procedural ECG gated CT. The aortic annulus area and perimeter were measured and the derived ED compared using parametric statistics and Bland and Altman analysis. The mean patient age was 80.2 ± 4 years. Systolic aortic annulus area and perimeter were higher compared to diastolic results (mean difference area 12.8 ± 24 mm(2) and perimeter 0.72 ± 1 mm; p = 0.009-0.068). Both the area- and perimeter-based ED had a good agreement within two standard deviations for systolic and diastolic measurements. Effective diameter measurements derived from the area were significantly smaller compared to perimeter-based measurements (mean difference: systolic 0.72 ± 0.3 mm and diastolic 0.81 ± 0.4 mm; p < 0.001). While the area-based ED was significantly influenced by the cardiac cycle with a mean difference of 0.4 ± 0.6 mm (p = 0.009), no significant difference was found for the perimeter-based ED (mean difference: 0.2 ± 0.4; p = 0.07). For patients undergoing CT evaluation prior to transcatheter aortic valve implantation, the perimeter-based effective annulus diameter provides a reliable parameter for annulus sizing without significant affection by the cardiac cycle and therefore facilitates annulus measurements with a single heart phase. However, perimeter-based diameters of the annulus are significantly larger than area-based diameters. | 25,165,022 | [
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Embryonic cerebrospinal fluid in brain development: neural progenitor control. | Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called "embryonic CSF." Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. | 25,165,044 | [
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... |
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