title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Prognostic significance of the peripheral blood absolute monocyte count in patients with locally advanced or metastatic hepatocellular carcinoma receiving systemic chemotherapy. | The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy. Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS). A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was 0.38×10⁹/L. Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009). Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy. | 25,124,630 | [
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Weight and fat distribution in patients taking valproate: a valproate-discordant gender-matched twin and sibling pair study. | Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA-discordant same-sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed. Height, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%. We studied 19 pairs of VPA-discordant, gender-matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within-pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA-user was treated for >11 years there were statistically significant mean within-pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%. This study demonstrated a relationship between long-term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA. | 25,124,647 | [
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Differential Effects of Mental Health Problems Among Truant Youths. | Research indicates at-risk youth are more likely to experience emotional and psychological problems. Young people who are often truant from school represent a group of at-risk youth, but one for which mental health issues are understudied. This study examined heterogeneity of mental health problems among a sample of 300 truant adolescents using latent class analysis (LCA). LCA indicated the sample of truants was best represented by four latent subgroups of youth with low mental health problems; high depression, low mania; high mania, low depression; and high depression and mania. These subgroups were examined in relation to sociodemographic and psychosocial measures at baseline and after truancy offenses. Results indicated general and unique differences in these covariates across the four latent classes. Service and practice implications of better understanding mental health issues of truant youth are discussed. | 25,124,652 | [
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Endometrial signals improve embryo outcome: functional role of vascular endothelial growth factor isoforms on embryo development and implantation in mice. | Does vascular endothelial growth factor (VEGF) have important roles during early embryo development and implantation? VEGF plays key roles during mouse preimplantation embryo development, with beneficial effects on time to cavitation, blastocyst cell number and outgrowth, as well as implantation rate and fetal limb development. Embryo implantation requires synchronized dialog between maternal cells and those of the conceptus. Following ovulation, secretions from endometrial glands increase and accumulate in the uterine lumen. These secretions contain important mediators that support the conceptus during the peri-implantation phase. Previously, we demonstrated a significant reduction of VEGFA in the uterine cavity of women with unexplained infertility. Functional studies demonstrated that VEGF significantly enhanced endometrial epithelial cell adhesive properties and embryo outgrowth. Human endometrial lavages (n = 6) were obtained from women of proven fertility. Four-week old Swiss mice were superovulated and mated with Swiss males to obtain embryos for treatment with VEGF in vitro. Preimplantation embryo development was assessed prior to embryo transfer (n = 19-30/treatment group/output). Recipient F1 female mice (8-12 weeks of age) were mated with vasectomized males to induce pseudopregnancy and embryos were transferred. On Day 14.5 of pregnancy, uterine horns were collected for analysis of implantation rates as well as placental and fetal development (n = 14-19/treatment). Lavage fluid was assessed by western immunoblot analysis to determine the VEGF isoforms present. Mouse embryos were treated with either recombinant human (rh)VEGF, or VEGF isoforms 121 and 165. Preimplantation embryo development was quantified using time-lapse microscopy. Blastocysts were (i) stained for cell number, (ii) transferred to wells coated with fibronectin to examine trophoblast outgrowth or (iii) transferred to pseudo pregnant recipients to analyze implantation rates, placental and fetal development. Western blot analysis revealed the presence of VEGF121 and 165 isoforms in human uterine fluid. Time-lapse microscopy analysis revealed that VEGF (n = 22) and VEGF121 (n = 23) treatment significantly reduced the preimplantation mouse embryo time to cavitation (P < 0.05). VEGF and VEGF165 increased both blastocyst cell number (VEGF n = 27; VEGF165 n = 24: P < 0.001) and outgrowth (n = 15/treatment: 66 h, P < 0.001; 74, 90, 98 and 114 h, P < 0.01) on fibronectin compared with control. Furthermore, rhVEGF improved implantation rates and enhanced fetal limb development (P < 0.05). Due to the nature of this work, embryo development and implantation was only examined in the mouse. The absence or reduction in levels of VEGF during the preimplantation period likely affects key events during embryo development, implantation and placentation. The potential for improvement of clinical IVF outcomes by the addition of VEGF to human embryo culture media needs further investigation. This study was supported by a University of Melbourne Early Career Researcher Grant #601040, the NHMRC (L.A.S., Program grant #494802; Fellowship #1002028; N.J.H., Fellowship # 628927; J.E.; project grant #1047756) and L.A.S., Monash IVF Research and Education Foundation. N.K.B. was supported by an Australian Postgraduate Award. Work at PHI-MIMR Institute was also supported by the Victorian Government's Operational Infrastructure Support Program. There are no conflicts of interest to declare. | 25,124,669 | [
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Daily life evidence of environment-incongruent emotion in schizophrenia. | Researchers have recently hypothesized that negative emotion in positive situations may be one mechanism for understanding emotion dysfunction in schizophrenia. Using ecological momentary assessment, we examined the relationship between emotion experience and environmental context in the daily lives of participants with and without schizophrenia. Participants with (n=47) and without schizophrenia (n=41) were provided a cellular telephone and called four times a day for one week. During each call participants rated their emotion experiences, described their current activities, and rated enjoyment from those activities. In line with previous research, participants with schizophrenia reported higher negative emotion overall relative to participants without schizophrenia, but equivalent levels of positive emotion and activity enjoyment. In line with the environment-incongruent negative emotion hypothesis, participants with schizophrenia evidenced a weaker relationship between reported enjoyment of current activities and current negative emotion compared to participants without schizophrenia. In addition, lower neurocognition predicted this weak relationship between negative emotion and context in the schizophrenia group. These findings provide ecologically valid support for environment-incongruent negative emotion in schizophrenia, and suggest that people with schizophrenia with more impaired neurocognition may have more difficulties regulating negative emotion. | 25,124,684 | [
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Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice. | Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections. | 25,124,689 | [
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Identification and characterization of human Rad51 inhibitors by screening of an existing drug library. | Homologous Recombination (HR) plays an essential role in cellular proliferation and in maintaining genomic stability by repairing DNA double-stranded breaks that appear during replication. Rad51, a key protein of HR in eukaryotes, can have an elevated expression level in tumor cells, which correlates with their resistance to anticancer therapies. Therefore, targeted inhibition of Rad51 through inhibitor may improve the tumor response to these therapies. In order to identify small molecules that inhibit Rad51 activity, we screened the Prestwick Library (1120 molecules) for their effect on the strand exchange reaction catalyzed by Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51, showing IC₅₀ values in the low nanomolar range (400 nM). Biochemical analysis demonstrated that the inhibitory mechanism probably occurs by disrupting the Rad51 association with the single-stranded DNA, which prevents the nucleoprotein filament formation, the first step of the protein activity. Structure Activity Relationship analysis with a number of compounds that shared structure homology with CSB was also performed. The sensitivity of Rad51 inhibition to CSB modifications suggests specific interactions between the molecule and Rad51 nucleofilament. CSB and some of its analogs open up new perspectives in the search for agents capable of potentiating chemo- and radio-therapy treatments for cancer. Moreover, these compounds may be excellent tools to analyze Rad51 cellular functions. Our study also highlights how CSB and its analogs, which are frequently used in colorants, stains and markers, could be responsible of unwanted side effects by perturbing the DNA repair process. | 25,124,703 | [
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Structure and development of 'witches' broom' galls in reproductive organs of Byrsonima sericea (Malpighiaceae) and their effects on host plants. | Galls are anomalies in plant development of parasitic origin that affect the cellular differentiation or growth and represent a remarkable plant-parasite interaction. Byrsonima sericea DC. (Malpighiaceae) is a super host of several different types of gall in both vegetative and reproductive organs. The existence of galls in reproductive organs and their effects on the host plant are seldom described in the literature. In this paper, we present a novel study of galls in plants of the Neotropical region: the 'witches' broom' galls developed in floral structures of B. sericea. The unaffected inflorescences are characterised by a single indeterminate main axis with spirally arranged flower buds. The flower buds developed five unaffected brownish hairy sepals and five pairs of elliptical yellow elaiophores, five yellow fringed petals, 10 stamens and a pistil with superior tricarpellar and trilocular ovary. The affected inflorescences showed changes in architecture, with branches arising from the main axis and flower buds. The flower buds exhibited several morphological and anatomical changes. The sepals, petals and carpels converted into leaf-like structures after differentiation. Stamens exhibited degeneration of the sporogenous tissue and structures containing hyphae and spores. The gynoecium did not develop, forming a central meristematic region, from which emerges the new inflorescence. In this work, we discuss the several changes in development of reproductive structures caused by witches' broom galls and their effects on reproductive success of the host plants. | 25,124,715 | [
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SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. | Methotrexate (MTX) is used for rheumatoid arthritis (RA) treatment showing a wide toxicity profile. This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding for MTX transporters with the occurrence of MTX-related toxicity (overall and gastrointestinal). A total of 233 Portuguese RA patients were genotyped for 23 SNPs. Haplotype analyses were performed and a toxicogenetic risk index (TRI) was created for SNPs that revealed to be statistically significant. Regarding MTX overall toxicity, an increased risk was associated to SLC19A1 rs7499 G carriers (p = 0.017), SLC46A1 rs2239907 GG (p = 0.030) and, SLCO1B1 rs4149056 T carriers (p = 0.040) and TT (p = 0.019). TRI revealed that patients with Index 3 were 18-fold more likely to present an adverse drug reaction when compared to those with Index 1 (p = 0.001). For MTX gastrointestinal toxicity, results demonstrated an increased risk associated with SLC19A1 rs7499 G carriers (p = 0.012) and GG (p = 0.045), SLC19A1 rs1051266 G carriers (p = 0.034), SLC19A1 rs2838956 A carriers (p = 0.049) and, SLCO1B1 rs4149056 T carriers (p = 0.042) and TT (p = 0.025). Haplotype analyses showed association between GGAG haplotype for SLC19A1 rs7499, rs1051266, rs2838956 and rs3788200 with MTX gastrointestinal toxicity (p = 0.029). TRI revealed that patients with Index 4 were 9-fold more likely to present a gastrointestinal disorder when compared to those with Index 1 (p = 0.020). This study demonstrated that SLC19A1, SLC46A1 and SLCO1B1 genotypes may help to identify patients with increased risk of MTX-related overall toxicity and that SLC19A1 and SLCO1B1 genotypes, and SLC19A1 haplotypes may help to identify patients with increased risk of MTX-related gastrointestinal toxicity. | 25,124,723 | [
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TiO2 hollow spheres composed of highly crystalline nanocrystals exhibit superior lithium storage properties. | While the synthesis of TiO2 hollow structures is well-established, in most cases it is particularly difficult to control the crystallization of TiO2 in solution or by calcination. As a result, TiO2 hollow structures do not really exhibit enhanced lithium storage properties. Herein, we report a simple and cost-effective template-assisted method to synthesize anatase TiO2 hollow spheres composed of highly crystalline nanocrystals, in which carbonaceous (C) spheres are chosen as the removable template. The release of gaseous species from the combustion of C spheres may inhibit the growth of TiO2 crystallites so that instead small TiO2 nanocrystals are generated. The small size and high crystallinity of primary TiO2 nanoparticles and the high structural integrity of the hollow spheres gives rise to significant improvements in the cycling stability and rate performance of the TiO2 hollow spheres. | 25,124,735 | [
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Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder. | Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population. | 25,124,743 | [
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Early embryonic specification of vertebrate cranial placodes. | Cranial placodes contribute to many sensory organs and ganglia of the vertebrate head. The olfactory, otic, and lateral line placodes form the sensory receptor cells and neurons of the nose, ear, and lateral line system; the lens placode develops into the lens of the eye; epibranchial, profundal, and trigeminal placodes contribute sensory neurons to cranial nerve ganglia; and the adenohypophyseal placode gives rise to the anterior pituitary, a major endocrine control organ. Despite these differences in fate, all placodes are now known to originate from a common precursor, the preplacodal ectoderm (PPE). The latter is a horseshoe-shaped domain of ectoderm surrounding the anterior neural plate and neural crest and is defined by expression of transcription factor Six1, its cofactor Eya1, and other members of the Six and Eya families. Studies in zebrafish, Xenopus, and chick reveal that the PPE is specified together with other ectodermal territories (epidermis, neural crest, and neural plate) during early embryogenesis. During gastrulation, domains of ventrally (e.g., Dlx3/Dlx5, GATA2/GATA3, AP2, Msx1, FoxI1, and Vent1/Vent2) and dorsally (e.g., Zic1, Sox3, and Geminin) restricted transcription factors are established in response to a gradient of BMP and help to define non-neural and neural competence territories, respectively. At neural plate stages, the PPE is then induced in the non-neural competence territory by signals from the adjacent neural plate and mesoderm including FGF, BMP inhibitors, and Wnt inhibitors. Subsequently, signals from more localized signaling centers induce restricted expression domains of various transcription factors within the PPE, which specify multiplacodal areas and ultimately individual placodes. For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article. | 25,124,756 | [
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Maternal control of the Drosophila dorsal-ventral body axis. | The pathway that generates the dorsal-ventral (DV) axis of the Drosophila embryo has been the subject of intense investigation over the previous three decades. The initial asymmetric signal originates during oogenesis by the movement of the oocyte nucleus to an anterior corner of the oocyte, which establishes DV polarity within the follicle through signaling between Gurken, the Drosophila Transforming Growth Factor (TGF)-α homologue secreted from the oocyte, and the Drosophila Epidermal Growth Factor Receptor (EGFR) that is expressed by the follicular epithelium cells that envelop the oocyte. Follicle cells that are not exposed to Gurken follow a ventral fate and express Pipe, a sulfotransferase that enzymatically modifies components of the inner vitelline membrane layer of the eggshell, thereby transferring DV spatial information from the follicle to the egg. These ventrally sulfated eggshell proteins comprise a localized cue that directs the ventrally restricted formation of the active Spätzle ligand within the perivitelline space between the eggshell and the embryonic membrane. Spätzle activates Toll, a transmembrane receptor in the embryonic membrane. Transmission of the Toll signal into the embryo leads to the formation of a ventral-to-dorsal gradient of the transcription factor Dorsal within the nuclei of the syncytial blastoderm stage embryo. Dorsal controls the spatially specific expression of a large constellation of zygotic target genes, the Dorsal gene regulatory network, along the embryonic DV circumference. This article reviews classic studies and integrates them with the details of more recent work that has advanced our understanding of the complex pathway that establishes Drosophila embryo DV polarity. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. | 25,124,754 | [
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Cell-intrinsic timing in animal development. | In certain instances we can witness cells controlling the sequence of their behaviors as they divide and differentiate. Striking examples occur in the nervous systems of animals where the order of differentiated cell types can be traced to internal changes in their progenitors. Elucidating the molecular mechanisms underlying such cell fate succession has been of interest for its role in generating cell type diversity and proper tissue structure. Another well-studied instance of developmental timing occurs in the larva of the nematode Caenorhabditis elegans, where the heterochronic gene pathway controls the succession of a variety of developmental events. In each case, the identification of molecules involved and the elucidation of their regulatory relationships is ongoing, but some important factors and dynamics have been revealed. In particular, certain homologs of worm heterochronic factors have been shown to work in neural development, alerting us to possible connections among these systems and the possibility of universal components of timing mechanisms. These connections also cause us to consider whether cell-intrinsic timing is more widespread, regardless of whether multiple differentiated cell types are produced in any particular order. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. | 25,124,757 | [
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Developmental programs of lung epithelial progenitors: a balanced progenitor model. | The daunting task of lung epithelium development is to transform a cluster of foregut progenitors into a three-dimensional (3D) tubular network with distinct cell types distributed at their appropriate locations. A complete understanding of lung development needs to address not only how, but also where, different cell types form. We propose that the lung epithelium forms through regulated deployment of three developmental programs: branching morphogenesis to expand progenitors and build a tree-like tubular network, airway differentiation to specify cells for the proximal conducting airways, and alveolar differentiation to specify cells for the peripheral gas exchange region. Each developmental program has its unique morphological features and molecular control mechanisms; their spatiotemporal coordination can be accounted for in a balanced progenitor model where progenitors balance between alternative developmental programs in response to spatiotemporal cues. This model integrates progenitor morphogenesis and differentiation, and provides new insights to lung immaturity in preterm birth and lung evolution. Advanced gene targeting and 3D imaging tools are needed to achieve a comprehensive understanding of lung epithelial progenitors on molecular, cellular, and morphological levels. For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article. | 25,124,755 | [
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Assessment of 5-fluorouracil and 4-nitroquinoline-1-oxide in vivo genotoxicity with Pig-a mutation and micronucleus endpoints. | Genotoxicity assessments were conducted on male Sprague Dawley rats treated with 5-fluorouracil (5-FU) and 4-nitroquinoline-1-oxide (4NQO) as part of an international validation trial of the Pig-a mutant phenotype assay. Rats were orally exposed to 0, 11.5, 23, or 46 mg/kg/day 5-FU for three consecutive days (Days 1-3); blood was sampled on Days -1, 4, 15, 29, and 45. Pig-a mutant phenotype reticulocyte (RET(CD59-)) and mutant phenotype erythrocyte (RBC(CD59-)) frequencies were determined on Days -1, 15, 29, and 45, and percent micronucleated reticulocytes (%MN-RET) were measured on Day 4. Rats were treated with 4NQO for 28 consecutive days by oral gavage, at doses of 1.5, 3, or 6 mg/kg/day. RBC(CD59-) and RET(CD59-) frequencies were determined on Days -1, 15, and 29, and MN-RET were quantified on Day 29. Whereas 5-FU was found to increase %MN-RET, no significant increases were observed for RBC(CD59-) or RET(CD59-) at any of the time points studied. The high dose of 4NQO (6 mg/kg/day) was observed to markedly increase RBC(CD59-) and RET(CD59-) frequencies, and this same dose level caused a weak but significantly elevated increase in MN-RET (approximately twofold). Collectively, the results provide additional support for the combination of Pig-a mutation and MN-RET into acute and 28-day repeat-dose studies. | 25,124,805 | [
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Unexpected positive intraoperative cultures in aseptic revision arthroplasty. | Unexpected positive intraoperative cultures (UPIC) in presumed aseptic revision arthroplasty can be difficult to interpret. The purpose of this retrospective study was to compare the incidence of subsequent periprosthetic joint infection (PJI) in patients who received antibiotic therapy according to an institutional protocol with those who did not and whether they meet Musculoskeletal Infection Society (MSIS) criteria for PJI. In patients who were treated with antibiotic according to institutional criteria, the incidence of PJI after revision was higher in those who did not meet MSIS criteria (22%) than in those that met MSIS criteria (14%; P > 0.71). UPIC in aseptic revision arthroplasty are not uncommon. PJI cannot be excluded in patients that do not meet MSIS definition. | 25,124,809 | [
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Exploring associations between lower urinary tract symptoms (LUTS) and gastrointestinal (GI) problems in women: a study in women with urological and GI problems vs a control population. | To study the prevalence of self-reported lower urinary tract symptoms (LUTS) in women consulting a Gastroenterology clinic with complaints of functional constipation (FC), fecal incontinence (FI) or both, compared with a female control population. Also, to study the influence of FC, FI, or both on self-reported LUTS in women attending a Urology clinic. We present a retrospective study of data collected through a validated self-administered bladder and bowel symptom questionnaire in a tertiary referral hospital from three different female populations: 104 controls, 159 gastroenterological patients and 410 urological patients. Based on the reported bowel symptoms, patients were classified as having FC, FI, a combination of both, or, no FC or FI. LUTS were compared between the control population and the gastroenterological patients, and between urological patients with and without concomitant gastroenterological complaints. Results were corrected for possible confounders through logistic regression analysis. The prevalence of LUTS in the control population was similar to large population-based studies. Nocturia was significantly more prevalent in gastroenterological patients with FI compared with the control population [odds ratio (OR) 9.1]. Female gastroenterological patients with FC more often reported straining to void (OR 10.3), intermittency (OR 5.5), need to immediately re-void (OR 3.7) and feeling of incomplete emptying (OR 10.5) compared with the control population. In urological patients, urgency (94%) and urgency urinary incontinence (UUI, 54% of UI) were reported more often by patients with FI than by patients without gastroenterological complaints (58% and 30% of UI respectively), whereas intermittency (OR 3.6), need to immediately re-void (OR 2.2) and feeling of incomplete emptying (OR 2.2) were reported more often by patients with FC than by patients without gastroenterological complaints. As LUTS are reported significantly more often by female gastroenterological patients than by a control population, and as there is a difference in self-reported LUTS between female urological patients with different concomitant gastroenterological complaints, we suggest that general practitioners, gastroenterologists and urologists should always include the assessment of symptoms of the other pelvic organ system in their patient evaluation. The clinical correlations between bowel symptoms and LUTS may be explained by underlying neurological mechanisms. | 25,124,824 | [
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Skull-stripping with machine learning deformable organisms. | Segmentation methods for medical images may not generalize well to new data sets or new tasks, hampering their utility. We attempt to remedy these issues using deformable organisms to create an easily customizable segmentation plan. We validate our framework by creating a plan to locate the brain in 3D magnetic resonance images of the head (skull-stripping). Our method borrows ideas from artificial life to govern a set of deformable models. We use control processes such as sensing, proactive planning, reactive behavior, and knowledge representation to segment an image. The image may have landmarks and features specific to that dataset; these may be easily incorporated into the plan. In addition, we use a machine learning method to make our segmentation more accurate. Our method had the least Hausdorff distance error, but included slightly less brain voxels (false negatives). It also had the lowest false positive error and performed on par to skull-stripping specific method on other metrics. We tested our method on 838 T1-weighted images, evaluating results using distance and overlap error metrics based on expert gold standard segmentations. We evaluated the results before and after the learning step to quantify its benefit; we also compare our results to three other widely used methods: BSE, BET, and the Hybrid Watershed algorithm. Our framework captures diverse categories of information needed for brain segmentation and will provide a foundation for tackling a wealth of segmentation problems. | 25,124,851 | [
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Plasticity versus specificity in RTK signalling modalities for distinct biological outcomes in motor neurons. | Multiple growth factors are known to control several aspects of neuronal biology, consecutively acting as morphogens to diversify neuronal fates, as guidance cues for axonal growth, and as modulators of survival or death to regulate neuronal numbers. The multiplicity of neuronal types is permitted by the combinatorial usage of growth factor receptors, each of which is expressed in distinct and overlapping subsets of neurons, and by the multitasking role of growth factor receptors, which recruit multiple signalling cascades differentially required for distinct biological outcomes. We have explored signalling robustness in cells where a given receptor tyrosine kinase (RTK) elicits qualitatively distinct outcomes. As the HGF/Met system regulates several biological responses in motor neurons (MN) during neuromuscular development, we have investigated the signalling modalities through which the HGF/Met system impacts on MN biology, and the degree of robustness of each of these functions, when challenged with substitutions of signalling pathways. Using a set of mouse lines carrying signalling mutations that change the Met phosphotyrosine binding preferences, we have asked whether distinct functions of Met in several MN subtypes require specific signalling pathways, and to which extent signalling plasticity allows a pleiotropic system to exert distinct developmental outcomes. The differential ability of signalling mutants to promote muscle migration versus axonal growth allowed us to uncouple an indirect effect of HGF/Met signalling on nerve growth through the regulation of muscle size from a direct regulation of motor growth via the PI3 kinase (PI3K), but not Src kinase, pathway. Furthermore, we found that HGF/Met-triggered expansion of Pea3 expression domain in the spinal cord can be accomplished through several alternative signalling cascades, differentially sensitive to the Pea3 dosage. Finally, we show that the regulation of MN survival by HGF/Met can equally be achieved in vitro and in vivo by alternative signalling cascades involving either PI3K-Akt or Src and Mek pathways. Our findings distinguish MN survival and fate specification, as RTK-triggered responses allowing substitutions of the downstream signalling routes, from nerve growth patterning, which depends on a selective, non-substitutable pathway. | 25,124,859 | [
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Effect of JEZTC, a synthetic compound, on proliferation and phenotype maintenance of rabbit articular chondrocytes in vitro. | Antioxidant may provide anti-arthritic effect that contributes to resolution of inflammation. Gallic acid (GA) and its derivatives were reported to be effective in treatment of arthritis. But GA-suppressed cell proliferation may compromise its effect on chondro-protection. In this study, we synthesized sulfonamido-based gallate-JEZTC and investigated its effect on rabbit articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycan (GAG) synthesis, and cartilage-specific gene expression. Results showed that JEZTC could effectively promote chondrocyte growth and enhance secretion and synthesis of cartilage extracellular matrix (ECM) by upregulating expression levels of aggrecan, collagen II, and Sox9 genes. Expression of collagen I which marked chondrocyte dedifferentiation was effectively downregulated by JEZTC. In addition, hypertrophy that may lead to chondrocyte ossification could not be detected in JEZTC groups. The results indicated JEZTC can well preserve the phenotype of chondrocytes. Range of 2.344 to 9.375 μg/ml is the recommended dose of JEZTC, which showed increased cell proliferation. Especially, JEZTC of 4.688 μg/ml showed the best performance. This study might provide a basis for development of a novel agent for the treatment of symptomatic chondral and osteochondral lesions. | 25,124,868 | [
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Qualitative and quantitative analysis of a group of volatile organic compounds in biological samples by HS-GC/FID: application in practical cases. | A simple and sensitive procedure, using n-propanol as internal standard (IS), was developed and validated for the qualitative and quantitative analysis of a group of 11 volatile organic substances with different physicochemical properties (1-butanol, 2-propanol, acetaldehyde, ethyl acetate, acetone, acetonitrile, chloroform, diethyl ether, methanol, toluene and p-xylene) in whole blood, urine and vitreous humor. Samples were prepared by dilution with an aqueous solution of internal standard followed by Headspace Gas Chromatography with a Flame-ionization Detector (HS GC-FID) analysis. Chromatographic separation was performed using two capillary columns with different polarities (DB-ALC2: 30m×0.320mm×1.2μm and DB-ALC1: 30m×0.320mm×1.8μm), thus providing a change in the retention and elution order of volatiles. This dual column confirmation increases the specificity, since the risk of another substance co-eluting at the same time in both columns is very small. The method was linear from 5 to 1000mg/L for toluene and p-xylene, 50-1000mg/L for chloroform, and 50-2000mg/L for the remaining substances, with correlation coefficients of over 0.99 for all compounds. The limits of detection (LOD) ranged 1 to 10mg/L, while the limits of quantification (LOQ) ranged from 2 to 31mg/L. The intra-day precision (CV<6.4%), intermediate precision (CV<7.0%) and accuracy (relative error ±10%) of the method were in conformity with the criteria normally accepted in bioanalytical method validation. The method developed has been applied to forensic cases, with the advantages that it uses a small sample volume and does not require any extraction procedure as it makes use of a headspace injection technique. | 25,124,884 | [
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Estimation of contaminant subslab concentration in petroleum vapor intrusion. | In this study, the development and partial validation are presented for an analytical approximation method for prediction of subslab contaminant concentrations in PVI. The method involves combining an analytic approximation to soil vapor transport with a piecewise first-order biodegradation model (together called the Analytic Approximation Method, including Biodegradation, AAMB), the result of which calculation provides an estimate of contaminant subslab concentrations, independent of building operation conditions. Comparisons with three-dimensional (3-D) simulations and another PVI screening tool, BioVapor, show that the AAMB is suitable for application in a scenario involving a building with an impermeable foundation surrounded by open ground surface, where the atmosphere is regarded as the primary oxygen source. Predictions from the AAMB can be used to determine the required vertical source-building separation, given a subslab screening concentration, allowing identification of buildings at risk for PVI. This equation shows that the "vertical screening distance" suggested by U.S. EPA is sufficient in most cases, as long as the total petroleum hydrocarbon (TPH) soil gas concentration at the vapor source does not exceed 50-100mg/L. When the TPH soil gas concentration of the vapor source approaches a typical limit, i.e. 400mg/L, the "vertical screening distance" required would be much greater. | 25,124,892 | [
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[The effects of fluid resuscitation on oxygenation index and prognosis in early stage of severe acute pancreatitis]. | To analyze the correlation between fluid equilibrium and oxygen index in patients at early stage (within 2 weeks) of severe acute pancreatitis (SAP), and to discuss the effects of fluid equilibrium after resuscitation on the prognosis. A clinical study was conducted. Ninety-seven patients with SAP admitted into Shengjing Hospital of China Medical University directly or transferred into intensive care unit (ICU) in 24 hours after admission between March 2011 to October 2013 were studied. Finally, 65 patients were enrolled in statistical analysis, and those with termination of treatment prematurely were excluded. The patients received treatment protocol formulated by the same physician in ICU. Patients were divided into improved group and death group according to the outcome. The differences in fluid equilibrium on 1, 2, 3, 7, 14 days after admission of ICU between the two groups were compared. The correlation between fluid equilibrium and oxygen index was analyzed with curve fitting. Among 65 patients enrolled, 53 of them were improved after intensive care and were transferred into ordinary wards. However, 12 patients died in ICU. Patients in the improved group showed delayed positive fluid equilibrium, and some patients even showed negative fluid equilibrium. Patients in death group needed more fluid to achieve fluid equilibrium. There was a significant difference in the need of fluid to reach an equilibrium between improved group and death group [1 day: 1 814.5 (905.2, 2 152.8) mL vs. 3 891.0 (2 524.2, 5 714.5) mL, Z=-3.303, P=0.001; 2 days: 2 469.0 (1 456.0, 3 696.0) mL vs. 6 498.0 (4 617.8, 8 763.5) mL, Z=-4.431, P<0.001; 3 days: 3 234.0 (1 098.0, 4 295.5) mL vs. 9 533.5 (6 748.8, 10 689.0) mL, Z=-4.684, P<0.001; 7 days: 3 234.0 (1 033.0, 5 162.0) mL vs. 13 986.5 (8 045.8, 14 518.0) mL, Z=-4.718, P<0.001; 14 days: 3 234.0 (978.5, 4 924.0) mL vs. 13 436.5 (8 045.8, 14 518.0) mL, Z=-4.769, P<0.001]. There was no correlation between fluid equilibrium and oxygen index in improved patients within 3 days of ICU admission (R² = 0.000, P=0.827), and it fit the logistic curve in a relatively low level after 3 days of ICU admission (R² = 0.036, P<0.001). Early fluid resuscitation could help maintain hemodynamics stability in SAP patients. Those SAP patients who showed a negative equilibrium in early stage showed a better prognosis, and the fluid equilibrium and oxygen index in improved patients fit the logistic curve after 3 days of ICU admission. | 25,124,908 | [
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Small metastasizing choroidal melanomas. | Small choroidal melanomas have a better prognosis than large tumours. However, these small tumours can spread, often late in their course. The aim of the study was to analyse survival and tumour characteristics of six cases of late metastatic diseases after conservative treatment. A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon among 523 patients treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with 106 (Ru/Rh) (15) for uveal melanomas. We have selected patients with small choroidal melanoma (thickness≤3 mm and diameter≤9 mm) (59 patients), who have developed hepatic metastases (six of 59). At the time of diagnosis, median age was 57 years (range, 37-82 years). The mean tumour thickness was 2.9 mm (range 2.5-3 mm), and the mean diameter was 7 mm (5-8 mm). Orange pigment was observed in four cases, subretinal fluid was observed in two cases, and one tumour touched the optic disc. Five patients had proton beam therapy. One patient had beta brachytherapy (106 Ru/106 Rh). Average follow-up was 8.3 years (range 4.2-11.8 years). None of the six patients developed local tumour recurrence. The mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9-14.6 years). The average time from treatment of primary tumour to detection of liver metastasis was 7 years (range 3.9-12 years). The mean survival time from the diagnosis of metastasis was 35.2 months (range 9-101 months). Small melanoma-related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at 15 years in our series. Despite a small tumoral size and an early and effective local treatment, six of 59 small choroidal melanomas have developed metastasis after local treatment. Small tumours represent a significant risk of metastasis. | 25,124,923 | [
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Antimicrobial and antibiofilm potential of biosurfactants isolated from lactobacilli against multi-drug-resistant pathogens. | Biosurfactants (BS) are amphiphilic compounds produced by microbes, either on the cell surface or secreted extracellularly. BS exhibit strong antimicrobial and anti-adhesive properties, making them good candidates for applications used to combat infections. In this study, our goal was to assess the in vitro antimicrobial, anti-adhesive and anti-biofilm abilities of BS produced by Lactobacillus jensenii and Lactobacillus rhamnosus against clinical Multidrug Resistant (MDR) strains of Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus (MRSA). Cell-bound BS from both L. jensenii and L. rhamnosus were extracted and isolated. The surface activities of crude BS samples were evaluated using an oil spreading assay. The antimicrobial, anti-adhesive and anti-biofilm activities of both BS against the above mentioned MDR pathogens were determined. Surface activities for both BS ranged from 6.25 to 25 mg/ml with clear zones observed between 7 and 11 cm. BS of both L. jensenii and L. rhamnosus showed antimicrobial activities against A. baumannii, E. coli and S. aureus at 25-50 mg/ml. Anti-adhesive and anti-biofilm activities were also observed for the aforementioned pathogens between 25 and 50 mg/ml. Finally, analysis by electron microscope indicated that the BS caused membrane damage for A. baumannii and pronounced cell wall damage in S. aureus. Our results indicate that BS isolated from two Lactobacilli strains has antibacterial properties against MDR strains of A. baumannii, E. coli and MRSA. Both BS also displayed anti-adhesive and anti-biofilm abilities against A. baumannii, E. coli and S. aureus. Together, these capabilities may open up possibilities for BS as an alternative therapeutic approach for the prevention and/or treatment of hospital-acquired infections. | 25,124,936 | [
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Predictors in adolescence of ESRD in middle-aged men. | Identification of predictors of end-stage renal disease (ESRD) in adolescence could provide intervention targets and improve understanding of the cause. Register-based nested case-control study. A cohort of all Swedish male residents born from 1952 through 1956 who attended mandatory military conscription examinations in late adolescence was used to identify 534 cases and 5,127 controls matched by birth year, county, and vital status. Erythrocyte sedimentation rate (ESR), proteinuria, blood pressure, and body mass index (BMI) in late adolescence. ESRD (defined here as dialysis therapy, kidney transplantation, surgical procedures creating long-term access for dialysis therapy, or chronic kidney disease stage 5) from 1985 through 2009. Physical working capacity and cognitive function score in late adolescence. Head of household's occupation and household crowding measured as person-per-room ratio from the 1960 census when participants were children. Proteinuria is associated notably with future ESRD, with an adjusted OR of 7.72 (95% CI, 3.94-15.14; P<0.001) for trace or positive dipstick findings. ESR has a dose-dependent association with ESRD with an adjusted OR of 2.07 (95%CI, 1.14-3.75; P=0.02) for ESR >15mm/h. Hypertension is associated strongly with future ESRD with an OR of 3.97 (95%CI, 2.08-7.59; P<0.001) for grade 2 hypertension and higher. Elevated BMI is associated statistically significantly with increased ESRD risk with an OR of 3.53 (95%CI, 2.04-6.11; P<0.001) for BMI ≥30 compared with 18.5-<25kg/m(2). The study was limited to men, with no initial estimation of glomerular filtration rate, and information on smoking was unavailable. ESR, proteinuria, BMI, and blood pressure in late adolescence are independent predictors of ESRD in middle-aged men. This highlights the long natural history and importance of adopting a life-course approach when considering the cause of chronic kidney disease. | 25,124,945 | [
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Dosage individualization in children: integration of pharmacometrics in clinical practice. | Children are in a continuous and dynamically changing state of growth and development. A thorough understanding of developmental pharmacokinetics (PK) and pharmacodynamics (PD) is required to optimize drug therapy in children. Based on recent publications and the experience of our group, we present an outline on integrating pharmacometrics in pediatric clinical practice to develop evidence-based personalized pharmacotherapy. Antibiotics in septic neonates and immunosuppressants in pediatric transplant recipients are provided as proof-of-concept to demonstrate the utility of pharmacometrics in clinical practice. Dosage individualization based on developmental PK-PD model has potential benefits of improving the efficacy and safety of drug therapy in children. The pharmacometric technique should be better developed and used in clinical practice to personalize drug therapy in children in order to decrease variability of drug exposure and associated risks of overdose or underdose. | 25,124,969 | [
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A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS. | Our objective was to compare the phase II and phase III (EMPOWER) studies of dexpramipexole in ALS and evaluate potential EMPOWER responder subgroups and biomarkers based on significant inter-study population differences. In a post hoc analysis, we compared the baseline population characteristics of both dexpramipexole studies and analyzed EMPOWER efficacy outcomes and laboratory measures in subgroups defined by significant inter-study differences. Results showed that, compared with phase II, the proportion of El Escorial criteria (EEC) definite participants decreased (p = 0.005), riluzole use increased (p = 0.002), and mean symptom duration increased (p = 0.037) significantly in EMPOWER. Baseline creatinine (p < 0.001) and on-study creatinine change (p < 0.001) correlated significantly with ALSFRS-R in EMPOWER. In the EMPOWER subgroup defined by EEC-definite ALS, riluzole use, and < median symptom duration (15.3 months), dexpramipexole-treated participants had reduced ALSFRS-R slope decline (p = 0.015), decreased mortality (p = 0.011), and reduced creatinine loss (p = 0.003). In conclusion, significant differences existed between the phase II and EMPOWER study populations in ALS clinical trials of dexpramipexole. In a post hoc analysis of EMPOWER subgroups defined by these differences, potential clinical benefits of dexpramipexole were identified in the subgroup of riluzole-treated, short-symptom duration, EEC-definite ALS participants. Creatinine loss correlated with disease progression and was reduced in dexpramipexole-treated participants, suggesting it as a candidate biomarker. | 25,125,035 | [
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Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease? | An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). Twenty-four patients (mean age, 63.5 ± 9.5 years; mean disease duration, 12 ± 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 ± 28.2% and 34.3 ± 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 ± 47.8% and 10.8 ± 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03). An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related. | 25,125,047 | [
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[Adnexal neoplasms in the context of skin cancer: trichilemmal carcinoma. Apropos of a case]. | The trichilemmal carcinoma is a rare malignant neoplasm, whose origin lies in the annexes of the skin, because of its low prevalence often confused with other dermal tumors, the differential diagnosis is not easy and is usually made by exclusion; in theory, its behavior is slow with little tendency to send both regional lymph node metastasis and systemic. Due to the limited number of cases there is no consensus on the prognosis, although it is generally considered good. The aim of this report is to show a case that, contrary to previous reports, the clinical presentation is aggressive with large soft tissue tumor infiltration around the site of origin in a patient without risk factors for skin cancer. Male patient, 65 years old with cytologic diagnosis of carcinoma in a preprarotideal facial tumor, characteristics at diagnosis were infiltration of the facial skin, ear, and parotid gland. Complete block resection was performed, radical parotiroidectomy and radical neck dissection; the soft tissue defect was covered with a pediculated flap. The evolution was satisfactory it follow-up short though. We evaluated the experience in the literature regarding the prognosis and treatment of these patients. Trichilemmal carcinoma can be fully invasive behavior prognosis is difficult to know and probably depends on the clinical stage at diagnosis. | 25,125,062 | [
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[Intracranial tumor behavior of plasma cell neoplasms. Report of 2 cases and literature review]. | Multiple myeloma is a plasmatic cell neoplasm that is characterized by skeletal destruction, renal failure, anemia and hypercalcemia. The skull plasmacytomas represent less than 1% of the head and neck tumors, they can be the primary lesion or occur as a secondary manifestation of multiple myeloma in 20-30% of the patients, or they can even manifest several years later after the diagnosis of plasmacytoma. Although some of the lesions may be surgically accessible, the aggressive natural behavior will complicate the evolution of the patients. We present two cases of Mexican women with intracranial plasmacytomas, one of them associated with multiple myeloma. The first case was a 24 year-old woman diagnosed with a multiple myeloma with plasmacytic-plasmablastic bone infiltration that was removed in 90%. She presented a local recurrence that required a second intervention for removal. The second case was a 62 year-old female with a malignant intracranial tumor of plasma cells that was totally resected. Both patients received adjuvant treatment based on chemotherapy and radiation therapy with favorable results. The patients died at 5 and 1.5 years respectively due to renal failure secondary to systemic disease. We propose chemotherapy and radiation therapy as an essential part of treatment for this condition, as the aggressive behavior of the neoplasms can complicate the evolution, despite being surgically accessible. | 25,125,061 | [
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[Experience in kidney transplantation without blood transfusion: kidney transplantation transfusion-free in Jehovah's Witnesses. First communication in Mexico]. | Jehovah's Witness refuse blood transfusion, but they accept organ transplantation, albumin, immunoglobulin, vaccines and clotting factors. We present 3 kidney transplants in Jehovah's Witness patients (two male and one female) without blood transfusion, with a mean age of 31.33 years and a mean body mass index of 20.99 kg/m(2). All patients underwent pretransplant peritoneal dialysis for an average of 52.3 months. Two transplants came from living donors and one from a deceased donor with a cold ischemia of 23 hours. The donors were two females and one male, with a mean age of 34.33 years. All patients received pretransplant erythropoietin and iron dextran and an intraoperative cell saver was used. Hemoglobin, hematocrit, red blood cells and serum creatinine levels, as well as the glomerular filtration at 24 months postransplant were stable. All patients received induction with basiliximab and initial immunosuppression with calcineurin inhibitors. One of the patients had a perirenal hematoma as a complication, which required a surgery 20 days post-transplant. At 5, 26 and 36 months postransplant the three patients are alive and with functional grafts. It is possible to perform kidney transplantation without transfusion in Jehovah's Witness, obtaining an acceptable global survival without acute rejection. | 25,125,065 | [
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Combinatorial gene therapy accelerates bone regeneration: non-viral dual delivery of VEGF and BMP2 in a collagen-nanohydroxyapatite scaffold. | Vascularization and bone repair are accelerated by a series of gene-activated scaffolds delivering both an angiogenic and an osteogenic gene. Stem cell-mediated osteogenesis in vitro, in addition to increased vascularization and bone repair by host cells in vivo, is enhanced using all systems while the use of the nanohydroxyapatite vector to deliver both genes markedly enhances bone healing. | 25,125,073 | [
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Prevalence of and risk factors for diabetic macular edema in the United States. | Diabetic macular edema (DME) is a leading cause of vision loss in persons with diabetes mellitus. Although there are national estimates for the prevalence of diabetic retinopathy and its risk factors among persons with diabetes, to our knowledge, no comparable estimates are available for DME specifically. To estimate the prevalence of DME in the US population and to identify associated risk factors. A cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and valid fundus photographs in the 2005 to 2008 National Health and Nutrition Examination Survey. The overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex. Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746, 000 persons in the US 2010 population aged 40 years or older. We identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis showed that the odds of having DME were higher for non-Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19-5.84; P = .02). Elevated levels of glycosylated hemoglobin A1c (OR, 1.47; 95% CI, 1.26-1.71 for each 1%; P < .001) and longer duration of diabetes (OR, 8.51; 95% CI, 3.70-19.54 for ≥ 10 vs <10 years; P < .001) were also associated with DME prevalence. These results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A1c, and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation is even more important for those at higher risk for DME. | 25,125,075 | [
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Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. | Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e., fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (±5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. NAFLD patients had an increased mortality compared with the reference population (hazard ratio [HR] 1.29, confidence interval [CI] 1.04-1.59, P = 0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, P = 0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, P = 0.001), infectious disease (HR 2.71, CI 1.02-7.26, P = 0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, P = 0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, P = 0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, P < 0.001). NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality. | 25,125,077 | [
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Neuroendocrine gene expression reveals a decrease in dopamine D2B receptor with no changes in GnRH system during prepubertal metamorphosis of silvering in wild Japanese eel. | Silvering is a prepubertal metamorphosis preparing the eel to the oceanic reproductive migration. A moderate gonad development occurs during this metamorphosis from the sedentary yellow stage to the migratory silver stage. The aim of this study was to elucidate the molecular aspects of various endocrine parameters of BPG axis at different ovarian developmental stages in wild yellow and silver female Japanese eels. The GSI of the sampled female eels ranged between 0.18 and 2.3%, corresponding to yellow, pre-silver and silver stages. Gonad histology showed changes from previtellogenic oocytes in yellow eels to early vitellogenic oocytes in silver eels. Both serum E2 and T concentrations significantly increased with ovarian development indicating a significant activation of steroidogenesis during silvering. In agreement with previous studies, significant increases in pituitary gonadotropin beta subunits FSH-β and LH-β transcripts were also measured by qPCR, supporting that the activation of pituitary gonadotropin expression is likely responsible for the significant ovarian development observed during silvering. We investigated for the first time the possible brain neuroendocrine mechanisms involved in the activation of the pituitary gonadotropic function during silvering. By analyzing the expression of genes representative of the stimulatory GnRH control and the inhibitory dopaminergic control. The transcript levels of mGnRH and the three GnRH receptors did not change in the brain and pituitary between yellow and silver stages, suggesting that gene expression of the GnRH system is not significantly activated during silvering. The brain transcript levels of tyrosine hydroxylase, limiting enzyme of DA synthesis did not change during silvering, indicating that the DA synthesis activity was maintained. In contrast, a significant decrease in DA-D2B receptor expression in the forebrain and pituitary was observed, with no changes in DA-D2A receptor. The decrease in the pituitary expression of DA-D2BR during silvering would allow a reduced inhibitory effect of DA. We may raise the hypothesis that this regulation of D2BR gene expression is one of the neuroendocrine mechanisms involved in the slight activation of the pituitary gonadotropin and gonadal activity that occur at silvering. | 25,125,083 | [
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Electrodeposition of Co/CoO nanoparticles onto graphene for ORR electrocatalysis: a study based on micro-X-ray absorption spectroscopy and X-ray fluorescence mapping. | Electrodeposition of graphene-supported Co for ORR electrocatalysts from an acetonitrile solution has been studied by a multi-technique approach, combining a suite of spectroscopic methods with electrochemical measurements, allowing a molecular-level understanding of potentiostatic and pulsed-potential plating processes from the organic solvent onto a freestanding graphene film. The formation of the graphene film by the light-scribe approach has been monitored by Raman spectroscopy; the electrodeposition process has been clarified by cyclic voltammetry and the compositional and chemical-state distribution of Co have been investigated ex situ by soft X-ray absorption spectroscopy and fluorescence mapping, showing that both spatial distribution and valence state are homogeneous and independent of the local current density. The deposit consists in micrometric aggregates of Co/CoO nanoparticles with diameter ca. 30 nm (pulsed) and 200 nm (potentiostatic deposition). Potentiostatic deposition allows to obtain better ORR electrocatalytic perfomance in terms of nnumber of transferred electrons, onset/ half-wave potential and current density. | 25,125,109 | [
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Identification and characterization of a pesticide degrading flavobacterium species EMBS0145 by 16S rRNA gene sequencing. | Organophosphates (OPs) like chlorpyrifos, diazinon, or malathion have become most common and indisputably most toxic pest-control agents that adversely affects the human nervous system even at low levels of exposure. Because of their relatively low cost and ability to be applied on a wide range of target insects and crop, organophosphorus pesticides account for a large share of all insecticides used in India, this in turn raises severe health concerns. In this view, the present investigation was aimed to identify novel species of Flavobacterium bacteria which is bestowed with the capacity to degrade pesticides like chlorpyrifos, diazinon or malathion. The bacterium was isolated from agricultural soil collected from Guntur District, Andhra Pradesh, India. The samples were serially diluted and the aliquots were incubated for a suitable time following which the suspected colony was subjected to 16S rRNA gene sequencing. The sequence thus obtained was aligned pairwise against Flavobacterium species, which resulted in identification of novel species of Flavobacterium later which was named as EMBS0145 and sequence was deposited in GenBank with accession number JN794045. | 25,125,136 | [
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Association between TNF-α-308 G/A gene polymorphism and gastric cancer risk: a systematic review and meta-analysis. | Tumor necrosis factor-alpha (TNF-α) has been found to be associated with gastric carcinogenesis, but individually published results have been inconclusive. The aim of this study was to explore the relationship between the TNF-α-308 G/A polymorphism and gastric cancer risk. MEDLINE, EMBASE and the COCHRANE library databases were searched for relevant articles to identify all available data. The odds ratios (ORs) with 95% confidence intervals (95% CIs) from each study were used to assess the association between the TNF-α-308 G/A polymorphism and gastric cancer risk. This meta-analysis included 30 studies (32 datasets) involving 7009 gastric cancer cases and 12,119 control subjects. Overall, a significant association was found between the TNF-α-308 G/A polymorphism and gastric cancer in AA+GA vs. GG (dominant contrast model) (OR=1.20, 95% CI=1.07-1.34, p=0.001). With stratification based on ethnicity, the TNF-α-308 G/A polymorphism was correlated with gastric cancer risk in Caucasians, using the dominant contrast model (OR=0.74, 95% CI=0.57-0.96, p=0.02), but not in East Asians and other ethnic groups. In the comprehensive subgroup analysis, a significant association was also found in recent articles (published after 2005), population-based high-quality studies, hospital-based high-quality studies, studies using the TaqMan method and non-cardia subgroups. However, the TNF-α-308 G/A polymorphism was not associated with specific histological types of gastric cancer risk. The TNF-α-308 G/A polymorphism may contribute to susceptibility to gastric cancer in Caucasians, especially for non-cardia gastric cancer, as most strongly demonstrated in high-quality studies and in studies using the TaqMan genotyping method. Furthermore, we recommend the TaqMan method as the preferred genotyping method in DNA polymorphism studies. | 25,125,137 | [
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Chromosomal rearrangements directly cause underdominant F1 pollen sterility in Mimulus lewisii-Mimulus cardinalis hybrids. | Chromosomal rearrangements can contribute to the evolution of postzygotic reproductive isolation directly, by disrupting meiosis in F1 hybrids, or indirectly, by suppressing recombination among genic incompatibilities. Because direct effects of rearrangements on fertility imply fitness costs during their spread, understanding the mechanism of F1 hybrid sterility is integral to reconstructing the role(s) of rearrangements in speciation. In hybrids between monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all quantitative trait loci (QTLs) for both premating barriers and pollen sterility, suggesting that they may have facilitated speciation in this model system. We used artificial chromosome doubling and comparative mapping to test whether heterozygous rearrangements directly cause underdominant male sterility in M. lewisii-M. cardinalis hybrids. Consistent with a direct chromosomal basis for hybrid sterility, synthetic tetraploid F1 s showed highly restored fertility (83.4% pollen fertility) relative to diploids F1 s (36.0%). Additional mapping with Mimulus parishii-M. cardinalis and M. parishii-M. lewisii hybrids demonstrated that underdominant male sterility is caused by one M. lewisii specific and one M. cardinalis specific reciprocal translocation, but that inversions had no direct effects on fertility. We discuss the importance of translocations as causes of reproductive isolation, and consider models for how underdominant rearrangements spread and fix despite intrinsic fitness costs. | 25,125,144 | [
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NDST1 missense mutations in autosomal recessive intellectual disability. | NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in the clinical features, including both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency. Furthermore, in Drosophila, knockdown of sulfateless, the NDST ortholog, impairs long-term memory, highlighting its function in cognition. Our data confirm NDST1 mutations as a cause of autosomal recessive intellectual disability with a distinctive phenotype, and support an important function of NDST1 in human development. | 25,125,150 | [
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[The Taiwan Nurses Association and professional diplomacy]. | The Taiwan Nurses Association (TWNA) is publishing a special centenary issue to commemorate the 100th anniversary of the association in 2014. For this issue, TWNA invited the author to write a review article that addresses the involvement of the TWNA in professional diplomacy and international exchange over the past century. The author reviews the history of both TWNA and the International Council of Nurses and introduces the contributions of the association in the field of professional diplomacy and the positive contributions of many Taiwan nursing leaders to global healthcare and society. The purpose of the paper is to convey the traditions and experiences of TWNA forward to the next generation. | 25,125,155 | [
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Regulation of structure and function of sarcomeric actin filaments in striated muscle of the nematode Caenorhabditis elegans. | The nematode Caenorhabditis elegans has been used as a valuable system to study structure and function of striated muscle. The body wall muscle of C. elegans is obliquely striated muscle with highly organized sarcomeric assembly of actin, myosin, and other accessory proteins. Genetic and molecular biological studies in C. elegans have identified a number of genes encoding structural and regulatory components for the muscle contractile apparatuses, and many of them have counterparts in mammalian cardiac and skeletal muscles or striated muscles in other invertebrates. Applicability of genetics, cell biology, and biochemistry has made C. elegans an excellent system to study mechanisms of muscle contractility and assembly and maintenance of myofibrils. This review focuses on the regulatory mechanisms of structure and function of actin filaments in the C. elegans body wall muscle. Sarcomeric actin filaments in C. elegans muscle are associated with the troponin-tropomyosin system that regulates the actin-myosin interaction. Proteins that bind to the side and ends of actin filaments support ordered assembly of thin filaments. Furthermore, regulators of actin dynamics play important roles in initial assembly, growth, and maintenance of sarcomeres. The knowledge acquired in C. elegans can serve as bases to understand the basic mechanisms of muscle structure and function. | 25,125,169 | [
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Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes. | It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, nonmuscle myosin II, muscle myosin II, and α-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that nonmuscle myosins II A and B are components of the Z-bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. | 25,125,171 | [
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Expression of myotilin during chicken development. | Several missense mutations in the Z-band protein, myotilin, have been implicated in human muscle diseases such as myofibrillar myopathy, spheroid body myopathy, and distal myopathy. Recently, we have reported the cloning of chicken myotilin cDNA. In this study, we have investigated the expression of myotilin in cross-striated muscles from developing chicken by qRT-PCR and in situ hybridizations. In situ hybridization of embryonic stages shows myotilin gene expression in heart, somites, neural tissue, eyes and otocysts. RT-PCR and qRT-PCR data, together with in situ hybridization results point to a biphasic transcriptional pattern for MYOT gene during early heart development with maximum expression level in the adult. In skeletal muscle, the expression level starts decreasing after embryonic day 20 and declines in the adult skeletal muscles. Western blot assays of myotilin in adult skeletal muscle reveal a decrease in myotilin protein compared with levels in embryonic skeletal muscle. Our results suggest that MYOT gene may undergo transcriptional activation and repression that varies between tissues in developing chicken. We believe this is the first report of the developmental regulation on myotilin expression in non-mammalian species. | 25,125,173 | [
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Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients. | Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption. Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients. | 25,125,218 | [
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Sex steroids as pheromones in mammals: the exceptional role of estradiol. | This article is part of a Special Issue (Chemosignals and Reproduction). Whether from endogenous or exogenous sources, 17β-estradiol (E2) has very powerful influences over mammalian female reproductive physiology and behavior. Given its highly lipophilic nature and low molecular mass, E2 readily enters excretions and can be absorbed from exogenous sources via nasal, cutaneous, and other modes of exposure. Indeed, systemic injection of tritiated estradiol ((3)H-E2) into a male mouse or bat has been shown to produce significant levels of radioactivity in the reproductive tissues and brain of cohabiting female conspecifics. Bioactive E2 and other steroids are naturally found in male mouse urine and other excretions, and males actively direct their urine at proximate females. Very low doses of E2 can mimic the Bruce effect (disruption of peri-implantation pregnancy by novel males), the Vandenbergh effect (early reproductive maturation induced by novel males), and male-induced estrus and ovulation. Males' capacities to induce the Bruce and Vandenbergh effects can both be diminished by manipulations that reduce their urinary E2. Uterine dynamics during the Bruce and Vandenbergh effects are consistent with the actions of E2. Collectively, these data demonstrate a critical role of male-sourced E2 in these major mammalian pheromonal effects. | 25,125,222 | [
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Quantification of the triglyceride fatty acid composition with 3.0 T MRI. | The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero- and first-order phase and rebuild the real part images. Then, using a model of a fat (1)H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene-interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 ± 0.25/0.51 ± 0.21/17.43 ± 0.07, 2.72 ± 0.31/0.94 ± 0.16/17.47 ± 0.08 and 2.53 ± 0.21/0.84 ± 0.14/17.43 ± 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T. | 25,125,224 | [
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The relationship between child maltreatment and substance abuse treatment outcomes among emerging adults and adolescents. | Emerging adulthood is the period of greatest risk for problematic substance use. The primary aim of the current study was to examine the relationship between a broad measure of child maltreatment and several key outcomes for a large clinical sample of emerging adults (n = 858) and adolescents (n = 2,697). The secondary aim was to examine the extent to which the relationship between child maltreatment and treatment outcomes differed between emerging adults and adolescents. Multilevel latent growth curve analyses revealed emerging adults and adolescents who experienced child maltreatment reported significantly greater reductions over time on several treatment outcomes (e.g., substance use, substance-related problems, and emotional problems). Overall, analyses did not support differential relationships between child maltreatment and changes over time in these substance use disorder treatment outcomes for emerging adults and adolescents. The one exception was that although emerging adults with child maltreatment did reduce their HIV risk over time, their improvements were not as great as were the improvements in HIV risk reported by adolescents who had experienced child maltreatment. | 25,125,233 | [
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Incisional negative pressure wound therapy after hemiarthroplasty for femoral neck fractures - reduction of wound complications. | The aim of the study was to evaluate the use of incisional negative pressure wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound secretion, as well as time and material consumption for dressing changes. The study is a prospective randomised evaluation of iNPWT in patients with large surgical wounds after FNF. Patients were randomised either to be treated by iNPWT (group A) or a standard wound dressing (group B). Follow-up included ultrasound measurements of seroma volumes on postoperative days 5 and 10, duration of wound secretion, and time and material spent for wound dressing changes. For comparison of the means, we used the t-test for independent samples, P > 0·05 was considered significant. There were 21 patients randomised in this study. Group A (11 patients, 81·6 ± 5·2 years of age) developed a seroma of 0·257 ± 0·75 cm(3) after 5 days and had a secretion of 0·9 ± 1·0 days, and the total time for dressing changes was 14·8 ± 3·9 minutes, whereas group B (ten patients, 82·6 ± 8·6 years of age) developed a seroma of 3·995 ± 5·01 cm(3) after 5 days and had a secretion of 4·3 ± 2·45 days, and the total time for dressing changes was 42·9 ± 11·0 minutes. All mentioned differences were significant. iNPWT has been used on many different types of traumatic and non-traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas, reduction of total wound secretion days and reduction of needed time for dressing changes. | 25,125,244 | [
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High variability of atmospheric mercury in the summertime boundary layer through the central Arctic Ocean. | The biogeochemical cycles of mercury in the Arctic springtime have been intensively investigated due to mercury being rapidly removed from the atmosphere. However, the behavior of mercury in the Arctic summertime is still poorly understood. Here we report the characteristics of total gaseous mercury (TGM) concentrations through the central Arctic Ocean from July to September, 2012. The TGM concentrations varied considerably (from 0.15 ng/m(3) to 4.58 ng/m(3)), and displayed a normal distribution with an average of 1.23 ± 0.61 ng/m(3). The highest frequency range was 1.0-1.5 ng/m(3), lower than previously reported background values in the Northern Hemisphere. Inhomogeneous distributions were observed over the Arctic Ocean due to the effect of sea ice melt and/or runoff. A lower level of TGM was found in July than in September, potentially because ocean emission was outweighed by chemical loss. | 25,125,264 | [
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Caries experience and use of dental services in rural and urban adults and older adults from central Chile. | To determine whether there is a relationship between the use of dental services and caries experience in adults and older adults from central Chile. A sample of 453 adults, 35-44 years of age, and 438 older adults, 65-74 years of age, was interviewed and examined using World Health Organisation (WHO) methods. Sociodemographic variables were also registered. Caries experience was assessed using the Decayed, Missing and Filled teeth (DMFT) index. Multiple linear regression models were used to determine whether there was an association between the independent variables and caries experience. Caries prevalence was 99.6% for adults [DMFT score = 14.89 (±6.16)] and 99.8% for older adults [DMFT score = 25.68 (±6.49)]. Less than half of the population - 41.7% of adults and 31.5% of older adults - received dental care. Regardless of the age group, there were no differences in the DMFT score between those who received and those who did not receive attention (P > 0.05). When the DMFT findings were analysed in greater detail, people who received dental care and urban participants had more fillings (P < 0.05) than did those who were not provided with attention or lived in rural areas, who, in turn, had more missing teeth (P < 0.05). A higher educational level was associated with a decrease of 1.15 DMFT points (P = 0.003) in the group of older adults. Adults and older adults from the Maule Region showed severe dental damage from caries. Although rurality and use of services do not seem to affect caries experience, they are associated with differences in fillings and missing teeth. | 25,125,265 | [
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Chondroprotective effect of high-dose zoledronic acid: An experimental study in a rabbit model of osteoarthritis. | To address the need to impact the subchondral bone-articular cartilage interaction for the treatment of degenerative osteoarthritis (OA), bisphosphonates may be used as a means to inhibit the subchondral bone resorption. The purpose of the present study is to evaluate the chondroprotective effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits underwent an anterior cruciate ligament transection and were separated into two groups: ZOL group (n=10) received 0.6 mg/kg intravenous injection of ZOL on day 1, 15, and 29 and placebo group (n=8) received saline. The animals were euthanized at 8 weeks. Macroscopically, the ZOL group had significantly milder ulcerations, cartilage softening and fibrillation compared to the placebo group. Microscopically, morphology of the articular cartilage was better in the ZOL treated group compared with the placebo group, without complete disorganization in any section of the ZOL group. Furthermore, the chondrocytes in the ZOL treated group were mainly cloning, indicating cartilage repairing and regeneration process, while in the placebo group hypocellularity predominated. Additionally, subchondral necrosis was evident in some specimens of the placebo group. Zoledronic acid, in a high-dose regimen, proved to be chondroprotective in a well-established animal model of OA. | 25,125,266 | [
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Patient safety training in pediatric emergency medicine: a national survey of program directors. | The Accreditation Council for Graduate Medical Education requires training in patient safety and medical errors but does not provide specification for content or methods. Pediatric emergency medicine (EM) fellowship directors were surveyed to characterize current training of pediatric EM fellows in patient safety and to determine the need for additional training. From June 2013 to August 2013, pediatric EM fellowship directors were surveyed via e-mail. Of the 71 eligible survey respondents, 57 (80.3%) completed surveys. A formal curriculum was present in 24.6% of programs, with a median of 6 hours (range = 1 to 18 hours) dedicated to the curriculum. One program evaluated the efficacy of the curriculum. Nearly 91% of respondents without formal programs identified lack of local faculty expertise or interest as the primary barrier to implementing patient safety curricula. Of programs without formal curricula, 93.6% included at least one component of patient safety training in their fellowship programs. The majority of respondents would implement a standardized patient safety curriculum for pediatric EM if one was available. Despite the importance of patient safety training and requirements to train pediatric EM fellows in patient safety and medical errors, there is a lack of formal curriculum and local faculty expertise. The majority of programs have introduced components of patient safety training and desire a standardized curriculum. | 25,125,275 | [
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Rhythm control in heart failure patients with atrial fibrillation: contemporary challenges including the role of ablation. | Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure. | 25,125,304 | [
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Interventions to reduce haemorrhage during myomectomy for fibroids. | Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life-threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11). To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy. In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials. We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment. The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods. Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.Blood lossWe found significant reductions in blood loss with the following interventions: vaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate-quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to -43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD -243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI -502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to -255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD -26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However, pooling data from these peri-cervical tourniquet RCTs revealed significant heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI -2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.Need for blood transfusion We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs, 121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low-quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.There were insufficient data on the adverse effects and costs of the different interventions. At present there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation and a fibrin sealant patch may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy. | 25,125,317 | [
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Practical aspects of monochromators developed for transmission electron microscopy. | A few practical aspects of monochromators recently developed for transmission electron microscopy are briefly reviewed. The basic structures and properties of four monochromators, a single Wien filter monochromator, a double Wien filter monochromator, an omega-shaped electrostatic monochromator and an alpha-shaped magnetic monochromator, are outlined. The advantages and side effects of these monochromators in spectroscopy and imaging are pointed out. A few properties of the monochromators in imaging, such as spatial or angular chromaticity, are also discussed. | 25,125,333 | [
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Osteoclast inhibition impairs chondrosarcoma growth and bone destruction. | Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. | 25,125,336 | [
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Novel MTCYB mutation in a young patient with recurrent stroke-like episodes and status epilepticus. | The acronym "MELAS" (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) denotes patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Here we report on a girl with repeated stroke-like episodes and status epilepticus, who was diagnosed with MELAS due to a novel mitochondrial cytochrome b gene (MTCYB) mutation (m.15092G>A, which predicts p.G116S). Western blotting and in silico analyses suggested that this mutation could affect the stability of complex III. Cytochrome b is the only mtDNA-encoded subunit of respiratory chain complex III. Mutations in MTCYB have been associated with isolated mitochondrial myopathy and exercise intolerance, and rarely with multisystem and/or central nervous system involvement. If the m.3243A>G and other common MELAS mutations are absent in several tissues, MTCYB should be sequenced from muscle in patients with stroke-like episodes, especially if muscle histology does not support a mitochondrial myopathy and lactic acidosis is absent. | 25,125,337 | [
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Controlled release of therapeutic antibody formats. | The local administration of antibodies can represent in many cases a significant improvement for antibody-based therapies. The benefits of local delivery include high drug concentrations at the target site, the possibility of lower drug dosing and less systemic drug exposure. Currently, the most relevant delivery sites for therapeutic antibodies are the posterior segments of the eye, mucosal surfaces, the articular joints and the central nervous system (CNS). In addition, the oral and pulmonary route may enable non-invasive systemic antibody delivery. However, local antibody delivery to these sites is characterized by short drug residence times and a low compliance of administration. Controlled release (CR) systems can address these limitations and, thereby, enable and improve local delivery applications by achieving long lasting local drug concentrations, improved efficacy-dosing ratios and reduced treatment-associated side effects. The requirements for CR antibody formulations are more complex compared to conventional CR systems for small molecules, and their development poses an enormous technical challenge. Therefore, the review highlights experiences and challenges gathered in the development of the different CR systems for antibodies to date. Additionally, the unmet technological needs encountered in the field are described. This includes a critical evaluation of the limited capability of various CR systems to preserve antibody stability, delivery site specific considerations, as well as the processability of a CR system with a particular focus on drug loading and injectability. We believe that the success of CR and local delivery approaches could create an enormous added value for patients in the future. | 25,125,350 | [
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The caregiver role in thromboprophylaxis management in atrial fibrillation: a literature review. | Atrial fibrillation is a common arrhythmia and a risk factor for adverse events including stroke. People living with atrial fibrillation are commonly elderly and have multiple comorbidities. The role of a caregiver in supporting the individual to manage a chronic and complex condition has received limited attention. This review aims to summarize available information on the caregiver role in atrial fibrillation, specifically in promoting adherence to thromboprophylaxis and evidence for strategies to support and enable the caregiver. A review of electronic databases and search engines was undertaken including Medline, Scopus and CINAHL. The search terms 'atrial fibrillation', 'anticoagulation', 'carer', 'caregiver', 'family support' were used. Dates searched were from January 1990 to November 2012. The review found limited original clinical research studies. The majority of the literature identified in the initial search included review papers and work which recommends the inclusion of the caregiver in the care of patients with atrial fibrillation but limited empirical evidence. Caregivers have an essential role to play in advocacy, family centred care and shared decision-making. This may influence thromboprophylaxis treatment choices and potentially adherence. Assessment of caregiver needs and support should be central to patient assessment and care planning. There is a need for clinical intervention studies which more target and address the caregiver role. | 25,125,352 | [
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Diagnostic and clinical characteristics of early-manifesting females with Duchenne or Becker muscular dystrophy. | Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up to 40% of heterozygous females, but there are few reports of females who exhibit skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance Tracking and Research Network, a multi-site population-based surveillance network for dystrophinopathy, nine symptomatic female heterozygotes with onset of symptoms prior to age 9 years were identified. The median age at diagnosis was 8.3 years, and the median interval from first symptoms to diagnosis was 1.35 years. Of the nine female heterozygotes, four had a positive family history, seven had intellectual disability and five had at least one mental health disorder. Mental health concerns included attention deficit hyperactivity disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The frequency of intellectual and mental health problems in this group is higher than previously reported for affected males and for symptomatic females. These findings may have implications for diagnosis of early manifesting heterozygotes and for their health supervision. | 25,125,379 | [
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Investigation of availability and accessibility of community automated external defibrillators in a territory in Hong Kong. | To evaluate the availability and accessibility of community automated external defibrillators in a territory in Hong Kong. Cross-sectional study. Two public hospitals in New Territories West Cluster in Hong Kong. Information about the locations of community automated external defibrillators was obtained from automated external defibrillator suppliers and through community search. Data on locations of out-of-hospital cardiac arrests from August 2010 to September 2013 were obtained from the local cardiac arrest registry of the emergency departments of two hospitals. Sites of both automated external defibrillators and out-of-hospital cardiac arrests were geographically coded and mapped. The number of out-of-hospital cardiac arrests within 100 m of automated external defibrillators per year and the proportion of out-of-hospital cardiac arrests with accessible automated external defibrillators (100 m) were calculated. The number of community automated external defibrillators per 10,000 population and public access defibrillation rate were also calculated and compared with those in other countries. There were a total of 207 community automated external defibrillators in the territory. The number of automated external defibrillators per 10,000 population was 1.942. All facilities with automated external defibrillators in this territory had more than 0.2 out-of-hospital cardiac arrests per automated external defibrillator per year within 100 m. Among all out-of-hospital cardiac arrests, 25.2% could have an automated external defibrillator reachable within 100 m. The public access defibrillation rate was 0.168%. The number and accessibility of community automated external defibrillators in this territory are comparable to those in other developed countries. The placement site of community automated external defibrillators is cost-effective. However, the public access defibrillation rate is low. | 25,125,422 | [
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[Visits to an emergency department due to head injuries]. | Head injury is a common consequence of accidents and violence. It can result in permanent disability and is one of the leading causes of premature death worldwide. Our aim was to review all visits to Landspitali University Hospital (LUH) from head injuries, to study the incidence, nature and severity of head injuries. A retrospective study on all visits of Reykjavik's inhabitants to LUH for head injuries in the years 2000-2005 and 2008-2009. Data were collected from patient records at LUH. One main diagnosis was used if head injury diagnoses were many. They were categorised into 5 groups; soft tissue injury, eye injury, injury to cranium, intracranial- and cranial nerve injury and multiple trauma. During the study period 35.031 patients presented with head injuries to LUH. Males were 67%. Mean age was 26 years (0-107). The highest rate was among infants and children aged 0-4 years (20.8%), followed by 5-9 years (11,5%) and 20-24 years (9.4%). The annual incidence decreased between the study periods from 4.2% to 3.3%. The annual incidence for admitted head injury patients decreased from 181/year/100.000 inhabitants to 110/year/100.000 inhabitants. Most often injuries were caused by accidents (80,5%) and violence (12.7%). Soft tissue injury was the most common injury (65%), followed by eye injury (15%) and intracranial- and cranial nerve injury (14%). The injuries that most frequently led to hospital admission were intracranial bleeding (90.1%), followed by skull fracture (79.2%). Accidents and violence caused most head injuries and they are more common among men than women. Patients with intracranial haemorrhage were usually admitted. Incidence of hospital visits and admissions because of head injuries in Reykjavik has decreased over the last decade. Key words: Head injury, accident, violence, brain injury, intracranial bleeding. | 25,125,431 | [
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[Giant thymoma - case report]. | Thymomas are usually benign tumors and are most often found in the anterior mediastinum. We report a rare case of a giant tumor in the right hemithorax that originated in the thymus. The tumor was 15x8 cm and histology revealed a type AB thymoma. The tumor was removed and the patient is doing well and is without symptoms two years after the operation. Key words: Thymoma, abdominal pain, giant tumor, mediastinum. | 25,125,432 | [
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Effectiveness of constraint-induced movement therapy on upper-extremity function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials. | To systematically examine the research literature on the effectiveness of constraint-induced movement therapy on improving arm function in children with cerebral palsy, and to assess the association between the study effect size and the characteristics of the patients and intervention protocol. A systematic literature search was conducted in PubMed, PsycINFO, Cochrane, CINAHL, Web of Science, and TRIP Database up to May 2014. Studies employing randomized controlled trial design, children with cerebral palsy, comparing constraint-induced movement therapy with another intervention with a focus on arm function, and upper-extremity measures were included in this review. Methodological quality was evaluated using the Physiotherapy Evidence-based Database (PEDro) scale. The literature search resulted in 27 randomized controlled trial studies with good methodological quality that compared constraint-induced movement therapy with other intervention therapy. Overall, constraint-induced movement therapy provided a medium beneficial effect (d = 0.546; p < 0.001) when compared with conventional therapy. For the subgroup analyses, presence of a dose-equivalent comparison group, intervention location, and time of follow-up were significant factors. Studies examining constraint-induced movement therapy effect without a dose-equivalent comparison group showed a large effect in children with cerebral palsy, but studies with a dose-equivalent group only showed a small effect. Children who received home-based constraint-induced movement therapy had a better improvement in arm function than those who received constraint-induced movement therapy elsewhere. The research literature supports constraint-induced movement therapy as an effective intervention to improve arm function in children with cerebral palsy. | 25,125,440 | [
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A brain-computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex. | Brain-computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). Self-regulation of gamma-power in the SPC is a feasible paradigm for brain-computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking. | 25,125,446 | [
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Closing-in is related to apathy in Alzheimer's disease patients. | Apathy and depression are behavioral manifestations that may occur often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in (CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that apathetic symptoms are related to frontal dysfunctions in AD patients, whereas the cognitive bases of depressive symptoms in AD are still unclear. Recent studies demonstrated that frontal dysfunctions are also involved in the genesis of CI in AD patients. Since frontal dysfunctions are thought to be more strongly related to apathetic than depressive symptoms, here we tested the hypothesis that CI is significantly associated with apathy in AD patients. Forty-four AD patients were enrolled for this study. All patients completed a neuropsychological evaluation of visuo-spatial, frontal/executive, visuo-constructional, and memory skills. Moreover, graphic copying tasks were employed to detect CI, and behavioral scales to assess apathetic and depressive symptoms. CI and apathetic and depressed symptoms occurred in more than half of the present AD sample, but regression models revealed that the number of CI was significantly related to apathy only. The number of CI was also significantly correlated with severity of apathetic but not of depressive symptoms. The present study demonstrated that CI and apathy are correlated with each other in mild to moderate AD, likely because they share common pathogenic mechanisms related to frontal/executive dysfunctions. | 25,125,462 | [
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Tumor-associated macrophages as major players in the tumor microenvironment. | During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy. | 25,125,485 | [
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Public service stress and burnout over 12 months. | Research indicates that workplace stress has the potential to harm employee health with stress and stress-related absence increasing significantly during economic recession and times of organizational change. To explore whether psychosocial hazards and burnout changed over a 12 month period in a public sector organization during a period of severely reduced organizational finances. The Management Standards Indicator Tool (MSIT) and the Maslach Burnout Inventory-General Scale (MBI-GS) were administered to employees of one local government department in July 2011 and July 2012. A total of 128 employees completed the questionnaires in July 2011 (response rate 67%) and 57 in July 2012 (response rate 54%). MSIT factor scores of demands, peer support and role worsened significantly over the period of study. Furthermore, all psychosocial hazards scored worse than the recommended level set by Health and Safety Executive. Two burnout dimensions, 'demands' and 'cynicism', significantly worsened over the 12 month period but professional efficacy increased. The MSIT and MBI-GS appeared to have utility in this comparison. Psychosocial hazards appeared to worsen over the 12 months of the study, as 'demands' and 'cynicism' increased. However, an increase in professional efficacy was also seen, which requires further investigation. | 25,125,489 | [
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Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. | The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD-scid IL2rγ(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT-NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. | 25,125,497 | [
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Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary . BET 1: Do patients with an asymptomatic sub-segmental pulmonary embolism need anticoagulation therapy? | A short cut review was carried out to establish whether therapeutic anticoagulation is required for patients who have an incidental diagnosis of subsegmental pulmonary embolism (PE), which is asymptomatic. 4 studies were relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The evidence suggests that patients with clinically unsuspected PE may have better prognostic outcomes than those with symptomatic presentations, especially if the PE is at the sub-segmental level. The only direct comparison of anti-coagulation versus no anti-coagulation in patients with an asymptomatic, unsuspected PE suggests a survival benefit from anti-coagulation. However, this study included patients with cancer and was not restricted to patients with subsegmental PE. Consequently, the clinical bottom line is that level 1 evidence is required to answer this question. In the meantime decisions must continue to be informed by clinical judgment. | 25,125,517 | [
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Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults. | Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. | 25,125,564 | [
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Comparison between three systems of classification criteria in juvenile systemic lupus erythematous. | The most widely used classification criteria for SLE are those derived and validated in adult patients by the ACR. Alternatives include the Boston weighted (BW) and SLICC criteria. The aim of this study was to compare the performance of BW and SLICC criteria with the 1997 ACR criteria in a JSLE cohort. Cases were JSLE patients and controls were patients with other rheumatic diseases attending a tertiary centre in the past 10 years. Data were retrospectively collected to establish the ACR, BW and SLICC criteria fulfilled at the first visit and within the first year of follow-up. A consensus diagnosis of JSLE established by the same group of highly experienced paediatric rheumatologists was chosen as the standard of reference. One hundred and seventy-three patients were included: 81 JSLE and 92 controls. There was a sharp increase in sensitivity and prevalence of all criteria within the first year of follow-up. The BW criteria had higher sensitivity than the ACR criteria (81.5% vs 58%, P < 0.001) at the first visit, but lower specificity in both periods. SLICC criteria had higher sensitivity (82.7% vs 58%, P < 0.001) at the first visit, but similar specificity in both periods. In this JSLE population, the SLICC criteria performed best in terms of sensitivity and accuracy at the first visit and within the first year of follow-up. | 25,125,590 | [
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Comparative transcriptomic analysis of cultivated limbal epithelium and donor corneal tissue reveals altered wound healing gene expression. | The improved surgical outcomes associated with transplantation of cultivated amniotic membrane expanded limbal epithelium (AMLE) compared to traditional donor methods has led to substantial adoption of this technique for treatment of limbal stem cell deficiency. The mRNA expression profiles of AMLE and CE were assayed using microarrays. Transcripts with a 1.5-fold change in either direction in addition to a Bonferroni adjusted P value < 0.05 were considered to be differentially expressed. Expression changes detected by microarray profiling and important corneal-limbal markers were assessed using quantitative real-time PCR (qRT-PCR) and immunofluorescence staining. A total of 487 probe sets (319 upregulated and 168 downregulated) were found to be differentially expressed between AMLE and CE. Enrichment analysis revealed significant overrepresentation of multiple biological processes (e.g., response to wounding, wound healing, and regulation of cell morphogenesis) within the differentially expressed gene list. The expression of a number of genes that were upregulated (ABCG2, S100A9, ITGA5, TIMP2, FGF5, PDGFC, SEMA3A) and downregulated (KLF4, P63α) in AMLE was confirmed using qRT-PCR. Immunofluorescence confirmed that AMLE cultures were P63α, ABCG2, CK3, CK12, and E-cadherin (E-cad) positive. In this study, we have shown that genes associated with wound healing processes are upregulated in AMLE. These gene expression changes may contribute to corneal restoration and the positive outcomes associated with transplantation. | 25,125,605 | [
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Loss of Raf-1 kinase inhibitory protein delays early-onset severe retinal ciliopathy in Cep290rd16 mouse. | Mutations in the cilia-centrosomal protein of centrosomal protein of 290 kDa (CEP290) result in severe ciliopathies, including autosomal recessive early onset childhood blindness disorder Leber congenital amaurosis (LCA). The Cep290(rd16) (retinal degeneration 16) mouse model of CEP290-LCA exhibits accumulation of CEP290-interacting protein Raf-1 kinase inhibitory protein (RKIP) prior to onset of retinal degeneration (by postnatal day P14). We hypothesized that reducing RKIP levels in the Cep290(rd16) mouse will delay or improve retinal phenotype. We generated double mutant mice by combining the Cep290(rd16) and Rkip(ko) alleles (Cep290(rd16):Rkip(+/ko) and Cep290(rd16):Rkip(ko/ko)). Retinal function was assessed by ERG and retinal morphology and protein trafficking were assessed by histology, transmission electron microscopy (TEM), and immunofluorescence analysis. Cell death was examined by apoptosis. Prior to testing our hypothesis, we examined ERG and retinal morphology of Rkip(ko/ko) mice and did not find any detectable differences compared with wild-type mice. The Cep290(rd16):Rkip(+/ko) mice exhibited similar retinopathy as Cep290(rd16); however, Cep290(rd16): Rkip(ko/ko) double knockout mice demonstrated a substantial improvement (>9-fold) in photoreceptor function and structure at P18 as of Cep290(rd16) mice. We consistently detected transient preservation of photoreceptors at P18 and polarized trafficking of opsins to sensory cilia in the double mutant mice; however, retinal degeneration ensued by P30. Our studies implicate CEP290-RKIP pathway in CEP290-retinal degeneration and suggest that targeting RKIP levels can delay photoreceptor degeneration, assisting in extending the time-window for treating such rapidly progressing blindness disorder. | 25,125,607 | [
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A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease. | Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys) segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family. Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2. | 25,125,609 | [
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Mesothelin expression in pancreatic mucinous cysts. | Mesothelin (MSLN) is a differentiation antigen found to be overexpressed in intraductal papillary mucinous neoplasms (IPMNs) and is a potential treatment target in pancreatic ductal adenocarcinoma. From institutional archives, 114 cases of resected pancreatic mucinous cysts were identified, including IPMN and mucinous cystic neoplasm (MCN). Immunohistochemical analysis of MSLN was performed on representative sections. MSLN was seen more frequently in neoplastic epithelial cells from IPMN (39/52; P < .0005) and MCN (9/14; P < .0001) compared with unremarkable adjacent pancreatic and bile ducts (0/57) and benign foveolar and duodenal epithelium (0/21). When present, MSLN was diffusely expressed in neoplastic epithelium and only focally expressed in adjacent ducts (8/57). No significant difference was seen (P = .26) in MLSN expression between IPMN (79%) and MCN (83%) when only presence or absence was considered. Our findings suggest that MLSN can be used as a marker of neoplastic transformation of epithelial cells in pancreatic mucinous cysts. The findings can help identify neoplastic mucinous epithelium. | 25,125,620 | [
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Aberrations of MYC are a common event in B-cell prolymphocytic leukemia. | B-cell prolymphocytic leukemia (B-PLL) remains a controversial entity, and its molecular pathogenesis is largely unknown. Patients are older, typically having marked lymphocytosis and splenomegaly in the absence of lymphadenopathy. It is defined as a mature B-cell leukemia with more than 55% circulating prolymphocytes. Leukemic mantle cell lymphoma and chronic lymphocytic leukemia in prolymphocytic transformation must be excluded. Case archives were retrospectively reviewed for B-PLL in patients without a previous diagnosis of chronic lymphocytic leukemia or other B-cell neoplasm. We identified six cases of B-PLL with available cytogenetic data, five of which showed evidence of aberrations in MYC. Three cases showed additional signals for the MYC gene by fluorescence in situ hybridization (FISH), and two cases demonstrated t(8;14)MYC/IGH by karyotyping or FISH. High levels of MYC protein expression were detected in all cases tested with MYC aberrations. These results suggest that deregulation of MYC plays an important role in the pathogenesis of B-PLL and expands the spectrum of B-cell neoplasms associated with aberrations of MYC. | 25,125,625 | [
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Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology. | Colorectal carcinomas (CRCs) with a micropapillary pattern and those showing high counts of poorly differentiated clusters (PDCs) are characterized by a higher probability to develop nodal metastases and have a worse prognosis. In light of the morphologic similarity to the micropapillary component, we aimed to verify whether PDCs also display an inverted secretory pattern. The immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of CRCs with PDCs and compared with that observed in CRCs without PDCs. PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs. The altered expression of MUC1 and E-cadherin may account for the aggressive behavior and higher metastatic potential of CRCs with high PDC counts and indicate an epithelial-mesenchymal transition. Our findings suggest that regardless of the morphologic aspect, PDCs and the micropapillary component may reflect the same biological phenomenon in CRCs. Thus, we wonder whether the micropapillary areas should be considered a variant of CRCs or more objectively counted as PDCs to predict prognosis. We also believe that the term PDC better describes the biological phenomena underlying this peculiar morphologic aspect in comparison with the misnomer micropapillary. | 25,125,629 | [
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Draft Genome Sequence of Burkholderia sordidicola S170, a Potential Plant Growth Promoter Isolated from Coniferous Forest Soil in the Czech Republic. | Burkholderia species are key players in the accumulation of carbon from cellulose decomposition in coniferous forest ecosystems. We report here the draft genome of Burkholderia sordidicola strain S170, containing features associated with known genes involved in plant growth promotion, the biological control of plant diseases, and green remediation technologies. | 25,125,648 | [
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Draft Genome Sequence of Staphylococcus chromogenes Strain MU 970, Isolated from a Case of Chronic Bovine Mastitis. | Coagulase-negative staphylococcal species are a common cause of subclinical bovine mastitis, with Staphylococcus chromogenes being one of the most frequently identified species in these cases. The draft genome sequence of an S. chromogenes isolate (MU 970) recovered from the milk of a cow with a chronic intramammary infection is reported here. | 25,125,652 | [
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Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. | Eradicating malignant tumors by vaccine-elicited host immunity remains a major medical challenge. To date, correlates of immune protection remain unknown for malignant mesothelioma. In this study, we demonstrated that antigen-specific CD8(+) T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1-based DNA vaccine. Unlike the nonprotective tumor antigen WT1-based DNA vaccines, the model vaccine showed complete and long-lasting protection against lethal mesothelioma challenge in immunocompetent BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8(+) T cells conferred to the protective efficacy in a dose-dependent way. Also, these CD8(+) T cells functioned by releasing inflammatory IFNγ and TNFα in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live-vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1(+) and Tim-3(+) CD8(+) T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8(+) T cells inversely correlating with tumor mass. Our results provide new insights into quantitative and qualitative requirements of vaccine-elicited functional CD8(+) T cells in cancer prevention and immunotherapy. | 25,125,656 | [
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PAK1 tyrosine phosphorylation is required to induce epithelial-mesenchymal transition and radioresistance in lung cancer cells. | The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment. | 25,125,660 | [
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Translesion polymerase η is upregulated by cancer therapeutics and confers anticancer drug resistance. | DNA repair processes are a key determinant of the sensitivity of cancer cells to DNA-damaging chemotherapeutics, which may induce certain repair genes as a mechanism to promote resistance. Here, we report the results of a screen for repair genes induced in cancer cells treated with DNA crosslinking agents, which identified the translesion polymerase η (PolH) as a p53-regulated target acting as one defense against interstrand crosslink (ICL)-inducing agents. PolH was induced by fotemustine, mafosfamide, and lomustine in breast cancer, glioma, and melanoma cells in vitro and in vivo, with similar inductions observed in normal cells such as lymphocytes and diploid fibroblasts. PolH contributions to the protection against ICL-inducing agents were evaluated by its siRNA-mediated attenuation in cells, which elevated sensitivity to these drugs in all tumor cell models. Conversely, PolH overexpression protected cancer cells against these drugs. PolH attenuation reduced repair of ICL lesions as measured by host cell reactivation assays and enhanced persistence of γH2AX foci. Moreover, we observed a strong accumulation of PolH in the nucleus of drug-treated cells along with direct binding to damaged DNA. Taken together, our findings implicated PolH in ICL repair as a mechanism of cancer drug resistance and normal tissue protection. | 25,125,662 | [
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Reducing caregiver stress with internet-based interventions: a systematic review of open-label and randomized controlled trials. | The high level of stress associated with caring for others with medical conditions has been recognized for some time. Reducing caregiver stress can improve caregiver quality of life as well as improve the care they provide to loved ones. This systematic review assesses the effectiveness of internet-based interventions to decrease caregiver stress. A comprehensive literature search of Ovid MEDLINE (1946-2013), Embase (1988-2013), PsycINFO (1987-2013), and CINAHL was conducted using terms related to caregiver and internet-based interventions. Internet-based interventions involving informal caregivers in an open-label or randomized controlled trial setting were included. A pair of raters independently reviewed all published abstracts. Data regarding participants, interventions, and outcomes were extracted and, for randomized trials, methodology quality was also reviewed. Eight open-label trials met the review criteria: three showed positive benefit in reducing caregiver stress, four were partially positive (some outcomes positive, others negative), and one was a negative study. Sixteen randomized trials met the review criteria: six showed positive benefit, five were partially positive, and five were negative. There were no clear patterns as to the variables (such as study duration and complexity of intervention) associated with better outcomes, although earlier studies typically had more negative outcomes. Internet-based interventions were mostly effective in reducing aspects of caregiver stress and improving their well-being. Further studies to assess outcomes for caregivers and their recipients' health, different technology delivery methods, and the cost of such interventions are needed. | 25,125,686 | [
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Cross-sectional comparison of coronary artery calcium scores between Caucasian men in the United States and Japanese men in Japan: the multi-ethnic study of atherosclerosis and the Shiga epidemiological study of subclinical atherosclerosis. | The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or ≥3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of ≥10, ≥100, and ≥400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of ≥100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. | 25,125,689 | [
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Electrical interactions in the cell: Asymmetric screening in a watery antiverse. | The problem of electrostatics in biomolecular systems presents an excellent opportunity for cross-disciplinary science and a context in which fundamental physics is called for to answer complex questions. Due to the large density in biological cells of charged biomacromolecules such as protein factors and DNA, it is challenging to understand quantitatively the electric forces in these systems. Two questions are especially puzzling. First, how is it that such a dense system of charged molecules does not simply aggregate in random and non-functional ways? Second, since some mechanism apparently prevents such aggregation, how is it that binding of biomolecules still occurs so reliably? Recognizing the role of water as a universal solvent in living systems is key to understanding these questions. We present a simplified physical model in which water is regarded as a medium of high dielectric constant that nevertheless exhibits the key features essential for answering the two questions presented. The answer to the first question lies in the strong screening ability of water, which reduces the energy scale of the electrostatic interactions. Furthermore, our model reveals the existence of asymmetric screening, a pronounced asymmetry between the screening for a system with like charges and that for a system with opposite charges, and this provides an answer to the second question. | 25,125,701 | [
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Weighted Area Under the Receiver Operating Characteristic Curve and Its Application to Gene Selection. | Partial area under the ROC curve (PAUC) has been proposed for gene selection in Pepe et al. (2003) and thereafter applied in real data analysis. It was noticed from empirical studies that this measure has several key weaknesses, such as an inability to reflect nonuniform weighting of different decision thresholds, resulting in large numbers of ties. We propose the weighted area under the ROC curve (WAUC) in this paper to address the problems associated with PAUC. Our proposed measure enjoys a greater flexibility to describe the discrimination accuracy of genes. Nonparametric and parametric estimation methods are introduced, including PAUC as a special case, along with theoretical properties of the estimators. We also provide a simple variance formula, yielding a novel variance estimator for nonparametric estimation of PAUC, which has proven challenging in previous work. The proposed methods permit sensitivity analyses, whereby the impact of differing weight functions on gene rankings may be assessed and results may be synthesized across weights. Simulations and re-analysis of two well-known microarray datasets illustrate the practical utility of WAUC. | 25,125,706 | [
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"Reverse genomics" and human endogenous retroviruses. | Over millions of years, actively replicating retroviruses entered the human genome and through time became a stable and substantial part of the inherited genetic material. A remarkable 8% of the human genome is accounted for by endogenous retroviruses, whose biological importance has not yet been elucidated. In studying the RNA of these endogenous retroviruses in the blood of living human subjects with HIV infection, we have discovered a whole new family of these viruses that had been hidden in the centromeres of specific human chromosomes. These retroviruses have specific sequences that can elucidate their chromosome of origin. As centromeres represent the most substantial remaining frontier of human genomics, these viral sequences can provide a "bar-code" that can be used to study the role of centromeres in biology and in disease. This work also highlights the efficacy of using "reverse genomics" to understand and annotate the human genome. | 25,125,718 | [
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Curing genetic disease with gene therapy. | Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile. | 25,125,725 | [
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Impact of denervated myocardium on improving risk stratification for sudden cardiac death. | Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables. | 25,125,727 | [
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TGFBR1 and cancer susceptibility. | Transforming growth factor beta (TGF-β) is a potent inhibitor of cell growth. TGFBR1 6A is a polymorphism consisting of a 9-base pair in-frame deletion within exon 1 of the type I TGF-β receptor (TGFBR1), which results in a receptor with decreased TGF-β signaling capability. The discovery of an association between TGFBR1*6A and cancer susceptibility led to the hypothesis that hypomorphic variants of the TGF-β signaling pathway may predispose to the development of cancer. This hypothesis was tested in vivo with the development of a mouse model of Tgfbr1 haploinsufficiency. Tgfbr1 (+/-) mice developed twice as many intestinal tumors as Tgfbr1 (+/+). Tgfbr1 haploinsufficiency was also associated with early onset adenocarcinoma and increased tumor cell proliferation. A case control study identified two haplotypes associated with constitutively decreased TGFBR1 and substantially increased colorectal cancer risk indicating that TGFBR1 may act as a potent modifier of cancer risk. | 25,125,747 | [
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Perceptual and cognitive biases in individuals with body dysmorphic disorder symptoms. | Given the extreme focus on perceived physical defects in body dysmorphic disorder (BDD), we expected that perceptual and cognitive biases related to physical appearance would be associated with BDD symptomology. To examine these hypotheses, participants (<iN</i = 70) high and low in BDD symptoms completed tasks assessing visual perception and cognition. As expected, there were significant group differences in self-, but not other-, relevant cognitive biases. Perceptual bias results were mixed, with some evidence indicating that individuals high (versus low) in BDD symptoms literally see themselves in a less positive light. Further, individuals high in BDD symptoms failed to demonstrate a normative self-enhancement bias. Overall, this research points to the importance of assessing both cognitive and perceptual biases associated with BDD symptoms, and suggests that visual perception may be influenced by non-visual factors. | 25,125,771 | [
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Equilibrium Conformations of Concentric-tube Continuum Robots. | Robots consisting of several concentric, preshaped, elastic tubes can work dexterously in narrow, constrained, and/or winding spaces, as are commonly found in minimally invasive surgery. Previous models of these "active cannulas" assume piecewise constant precurvature of component tubes and neglect torsion in curved sections of the device. In this paper we develop a new coordinate-free energy formulation that accounts for general preshaping of an arbitrary number of component tubes, and which explicitly includes both bending and torsion throughout the device. We show that previously reported models are special cases of our formulation, and then explore in detail the implications of torsional flexibility for the special case of two tubes. Experiments demonstrate that this framework is more descriptive of physical prototype behavior than previous models; it reduces model prediction error by 82% over the calibrated bending-only model, and 17% over the calibrated transmissional torsion model in a set of experiments. | 25,125,773 | [
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The Development and Testing of a Checklist to Study Behaviour Change Techniques used in a Treatment Programme for Canadian Armed Forces Members with Chronic Non-specific Low Back Pain. | There are reports of increased use of a variety of behaviour change techniques (BCT) by physiotherapists and findings of beneficial effects of use. However, there is a lack of physiotherapy-specific definitions of these techniques, as well as a sense of how physiotherapists use them in practice. Through this study, the authors created and field tested a preliminary nomenclature and description for BCT in patients with chronic non-specific low back pain (CNSLBP). Items for the Physiotherapy Behaviour Change Technique (PT-BCT) checklist were derived from a nomenclature created for use in psychology and also from publications of studies using cognitive behaviour therapy-based approaches in physiotherapy. Content validity was tested via survey of clinical and research experts. Videotapes of a 6-week patient self-management rehabilitation programme were used for training, reliability testing, and field testing of the PT-BCT checklist. Checklist items were endorsed by the majority of experts surveyed; intra- and inter-rater reliability were moderate to high. In the field study, a broad range of BCT types (behavioural, cognitive, and motivational) were observed in both classroom and gym settings. The BCT nomenclature arising from this study and the PT-BCT checklist will be useful to further explore behaviour change in physiotherapy practice. The observation in this study that BCT were integrated into physiotherapists' practice illustrates how physiotherapists can play a role in changing behaviour, specifically in the presence of CNSLBP. | 25,125,787 | [
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What clinical instructors want: perspectives on a new assessment tool for students in the clinical environment. | Many Canadian physical therapy education programs use the 1997 version of the Physical Therapist Clinical Performance Instrument (PT-CPI) to evaluate students in their clinical placements. Recent evidence that clinical instructors (CIs) are unsatisfied with the PT-CPI, however, suggests a need to develop a new assessment tool. The purpose of this study was to gather Canadian CIs' perspectives on rating scales, preferred training methods, and format for future tool development. This qualitative descriptive study involved five focus groups from across Canada. English-speaking CIs who had supervised at least one Canadian student in clinical practice were eligible for the study. Participants identified concerns with the PT-CPI and indicated a preference for (1) more objective rating scales with clearly defined anchors, (2) both in-person and online training methods for CIs, and (3) a tool that could be completed and reviewed on paper or online. CIs affirmed the need to develop a new assessment tool. RESULTS of the study will be used to inform the development of a new assessment tool to better evaluate Canadian physical therapy students' performance in the clinical setting. | 25,125,788 | [
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Frustrated Freedom: The Effects of Agency and Wealth on Wellbeing in Rural Mozambique. | In Sen's capability view of poverty, wellbeing is threatened by both deficits of wealth and deficits of individual agency. Sen further predicts that "unfreedom," or low levels of agency will suppress the wellbeing effects of higher levels of wealth. The current paper extends Sen's view to include a condition, labeled "frustrated freedom," in which relatively higher levels of agency can heighten the poverty effects of relatively low levels of material wealth. Applying data from a large scale population study of female heads of household in rural Mozambique, the paper empirically tests Sen's view and the proposed extension. As predicted, agency is found to moderate the relationship between agency, wealth, and wellbeing, uncovering evidence of both unfreedom and frustrated freedom in the population. Further research into the complex dynamics of wellbeing and poverty are called for by the authors. | 25,125,791 | [
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Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an in vitro study. | Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2α , nitric oxide (nitrite), tumor necrosis factor-α (TNF); macrophage migration inhibitory factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in equine corpus luteum (CL) from early and mid-luteal stages. LEPR expression was decreased in late CL, while GHR/Ghr-R1A system was increased in the same stage. Regarding secretory activity, GHR decreased P4 in early CL, but increased PGF2α , nitrite and TNF in mid CL. Conversely, LEP increased P4, PGE2, angiogenic activity, MIF, TNF and nitrite during early CL, in a dose-dependent manner. The in vitro effect of LEP on secretory activity was reverted by GHR, when both factors acted together. The present results evidence the presence of LEP and GHR systems in the equine CL. Moreover, we suggest that LEP and GHR play opposing roles in equine CL regulation, with LEP supporting luteal establishment and GHR promoting luteal regression. Finally, a dose-dependent luteotrophic effect of LEP was demonstrated. | 25,125,800 | [
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... |
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