BACKGROUND Few evidence-based treatments and guidelines reflect greater uncertainty regarding consensus treatment algorithms than those for unipolar disorder. This meta-analysis aimed to evaluate the efficacy and side effects of lurasidone by comparing with placebo in bipolar I depression. METHODS Electronic databases, such as PubMed, the Cochrane Library, Web of Science, and Embase, were searched until May 30, 2018, for randomized controlled trials on comparison lurasidone therapy with placebo. The primary efficacy assessment included MADRS total score and CGI-BP-S total score, the secondary efficacy assessment included the response and the remission rates and the safety and tolerability were also evaluated applying the Simpson-Angus Scale. RESULTS The meta-analysis compromised 7 studies. Efficacy analysis suggested that lurasidone was more effective than placebo MADRS total score (MD-4.31, 95%CI (-6.93,-1.7), P = 0.001) and the CGI-BP-S total score (MD-0.37, 95%CI (-0.59,-0.15), P = 0.0008) were obtained for both lurasidone-treated and placebo groups. Response rates (RR 1.73, 95%CI (1.46, 2.05), P  less then  0.00001) and Remission rates (RR 1.57, 95%CI (1.38, 1.79), P  less then  0.00001). The safety analysis between lurasidone and placebo showed no difference at least one event (RR 1.12, 95% CI (1.00, 1.26), p = 0.05 and the influence on glucose (MD 0.35, 95% CI (-1.09, 1.79), p = 0.63. LIMITATION The present conclusion is limited by the limited included studies. The different dose of lurasidone should be considered in the future. CONCLUSION Compared with placebo, adjunctive lurasidone significantly improved depressive symptoms and is very well tolerated with minimal side effects on the endocrine and cardiovascular systems in clinical patients with bipolar I depression. Key words Bipolar I depression; Lurasidone; Meta-analysis; Remission rates; Adverse effect. V.BACKGROUND An atypical immune response to Epstein-Barr virus (EBV) infection has been associated with several complex diseases including schizophrenia. The etiology of MDD is unclear; host immune response to EBV infection could play a role. METHODS We utilized solid phase immunoassays and western blots to measure antibodies to EBV virions, specific viral proteins, and 5 other herpesviruses in 87 individuals with MDD and 312 control individuals. RESULTS Individuals with MDD had significantly reduced levels of reactivity to EBV Nuclear Antigen-1. Quantitative levels of antibodies to EBV virions and Viral Capsid Antigen did not differ between groups. Individuals with decreased levels of anti-Nuclear Antigen-1, or elevated levels of anti-virion had increased odds of being in the MDD group. The odds of MDD were elevated in individuals who had the combination of high levels of anti-virion and low levels of anti-Nuclear Antigen-1 (OR =13.6). Western blot analysis corroborated decreased reactivity to Nuclear Antigen-1 in the MDD group and revealed altered levels of antibodies to other EBV proteins. https://www.selleckchem.com/products/brd3308.html There was a trend towards decreased levels of antibodies to varicella virus in the group of individuals with MDD. LIMITATIONS The MDD sample size was relatively small. There could be unmeasured factors that account for the association between MDD and the immune response to EBV. CONCLUSIONS Individuals with MDD have altered levels and patterns of antibodies to EBV antigens. This atypical response could contribute to the immunopathology of MDD. Therapeutic interventions available for treatment of EBV infection could potentially be of benefit in MDD. V.BACKGROUND Magnetic Seizure therapy (MST) is an emerging treatment for major depressive disorder (MDD) that is associated with fewer cognitive side effects compared to electroconvulsive therapy. The present pilot study sought to investigate whether daily MST treatments were associated to antidepressant effect and assess cognitive side effects associated with an accelerated MST (aMST) treatment schedule. METHODS Fifteen MDD patients underwent a six-day course of MST treatment to the vertex following assessment of symptom severity and neuropsychological testing. The primary outcome was severity on the Hamilton Rating Scale for Depression 17-item (HRSD-17). Patient also underwent neuropsychological assessment with the RBANS and Stroop Colour-Word test. RESULTS There were no instances of delirium or disturbance of consciousness following aMST sessions. Patients showed significant decreases on indices of depression and anxiety symptoms, with 9 (60%) patients showing a clinical response and 7 (47%) patients experiencing remission. Significant improvements were reported in RBANS total score, as well as indices of immediate memory and delayed memory. No changes at follow-up were reported for visuospatial/constructional, language, and attention RBANS indices, nor for Stroop Colour/Word performance. LIMITATIONS The results should be interpreted with caution as they are part of a non-randomized, open-label pilot study. Further, the short duration of the study does not provide longitudinal follow-up to determine whether treatment response lasts a meaningful duration of time. CONCLUSIONS aMST well tolerated without significant evidence of cognitive side effects and rapid improvement in symptoms. Further research is required to fully characterize these changes and replicate them in independent samples. V.INTRODUCTION Obsessive compulsive disorder (OCD) is a chronic psychiatric disorder where most patients do not reach full symptomatic remission. Identifying predictors of course can improve patients' care by informing clinicians on prognosis and enhancing treatment strategies. Several predictors associated with improved outcome of OCD were identified. However, research focused mainly on clinical, illness-related predictors of the course of OCD. This study examined the contribution of environmental and interpersonal predictors on the long-term outcome of OCD, in addition to the previously identified clinical indicators. METHODS We used the baseline, two and four-year data of 382 adult OCD patients participating in the naturalistic cohort study of the Netherlands Obsessive Compulsive Disorder Association (NOCDA). Remission was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Predictors of outcome were assessed at baseline, via clinician-rated and self-report instruments. RESULTS Remission at two and at four-year follow-up ranged from 11% to 26%.

OBJECTIVE This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement. METHODS MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019. RESULTS A total of five documents were analysed three CPGs, one medical consensus and one position paper. All publications were consistent in recommending DAA treatment for adolescents (12-17 years-old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies. CONCLUSIONS There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. https://www.selleckchem.com/products/agk2.html Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.OBJECTIVE Percutaneous endoscopic gastrostomy (PEG) provides a long-term solution for tube dependency. Pediatric guidelines recommend prophylactic antibiotic treatment (ABT) based on adult studies. AIM To compare wound infection and other complications in children receiving a PEG with and without prophylactic ABT. METHODS Retrospective study including children 0-18 years undergoing PEG placement. Patients with (2010-2013) and without (2000-2010) ABT were compared with respect to the occurrence of wound infection and other complications. RESULTS In total, 297 patients were included (median age 2.9 years, 53% male). Patients receiving ABT per PEG protocol (n = 78) had a similar wound infection rate (17.9 vs. 21%, p 0.625), significantly less fever (3.8 vs. 14.6%, p 0.013), leakage (0 vs. 9.1%, p 0.003) and shorter hospital admission (2 vs. 4 days, p 0.000), but more overgranulation (28.2 vs. 8.7%, p 0.000) compared to those without (n = 219).Patients receiving any ABT, per PEG protocol or clinical indication (n = 115), had similar occurrence of wound infection (19.1 vs. 20.9%, p 0.768), fever (7.8 vs. 14.3%, p 0.100) and leakage (3.5 vs. 8.8%, p 0.096), a significantly shorter hospital admission (3 vs. 4 days, p 0.000), but more overgranulation (21.7 vs. 8.8%, p 0.003) compared to those without (n = 182). CONCLUSIONS Prophylactic ABT does not seem to reduce the occurrence of wound infection but it might be beneficial with respect to fever, leakage and duration of hospital admission, but not overgranulation. A randomized controlled trial is needed to confirm our results.Global childhood obesity increased more than 8fold over 40 years, inducing a very large personal, societal and economic burden. Effects of available treatments are less than satisfactory, therefore effective prevention is of high priority. In this narrative review, we explore preventive opportunities. The available evidence indicates large benefits of improving nutrition and lifestyle during early life, such as promoting breastfeeding and improving the quality of infant and early childhood feeding. Promoting healthy eating patterns and limiting sugar containing beverage consumption from early childhood onwards are of great benefit. Regular physical activity and limited sedentary lifestyle and screen time alone have limited effects but are valuable elements in effective multicomponent strategies. The home environment is important, particularly for young children, and can be improved by educating and empowering families. School and community based interventions can be effective, such as installing water fountains, improving cafeteria menus and facilitating regular physical activity. Reducing obesogenic risk factors through societal standards is essential for effective prevention and limiting socioeconomic disparity; these may comprise food, drink and physical activity standards for daycares and schools, general food quality standards, front of pack food labelling, taxation of unhealthy foods, restriction of food advertisements to children, and others. Effective prevention of childhood obesity is not achieved by single interventions but by integrated multicomponent approaches involving multiple stakeholders that address children, families and societal standards. Paediatricians and their organisations should be proactive in supporting and empowering families to support their children's health, and in promoting societal measures that protect children.OBJECTIVE The aim of the study was to evaluate the effect of lipotransfer in women presenting with fibrosis and scarring due to lichen sclerosus. MATERIALS AND METHODS This prospective cohort study included 33 women attending the vulvar clinic of a public hospital. Patients received one lipotransfer treatment. Validated measures were used prospectively to assess the sexual function (Female Sexual Function Index, Female Sexual Distress Scale); symptoms (visual analog scale for itching, burning, soreness), pain (Pain Anxiety Symptoms Scale 20); psychological status and quality of life (Hospital Anxiety and Depression Scale, Relationship Assessment Scale, Wound Management Questionnaire Revised); physician-based disease signs (Vulvar Architecture Severity Scale). Data were analyzed using paired t test with nonparametric Wilcoxon matched-pairs signed rank test and unpaired t test with nonparametric Mann-Whitney test (Prism6 Software). RESULTS The mean (SD) follow-up was 12.9 (3.5) months. Sexual function improved after treatment (p less then .

The most stable reference gene was 18S. Reliable extraction method of high quality RNA yield could be a step forward for understanding mechanisms of spermatogenesis for improving male fertility. © 2020 Blackwell Verlag GmbH.This study develops a two-part hidden Markov model (HMM) for analyzing semicontinuous longitudinal data in the presence of missing covariates. The proposed model manages a semicontinuous variable by splitting it into two random variables a binary indicator for determining the occurrence of excess zeros at all occasions and a continuous random variable for examining its actual level. For the continuous longitudinal response, an HMM is proposed to describe the relationship between the observation and unobservable finite-state transition processes. The HMM consists of two major components. The first component is a transition model for investigating how potential covariates influence the probabilities of transitioning from one hidden state to another. The second component is a conditional regression model for examining the state-specific effects of covariates on the response. A shared random effect is introduced to each part of the model to accommodate possible unobservable heterogeneity among observation processes and the nonignorability of missing covariates. A Bayesian adaptive least absolute shrinkage and selection operator (lasso) procedure is developed to conduct simultaneous variable selection and estimation. The proposed methodology is applied to a study on the Alzheimer's Disease Neuroimaging Initiative dataset. New insights into the pathology of Alzheimer's disease and its potential risk factors are obtained. © 2020 John Wiley & Sons, Ltd.Fatty acids (FA) of two species of abyssal Echinodermata-the sea star (Asteroidea) Eremicaster vicinus and the sea urchin (Echinoidea) Kamptosoma abyssale-from the Kuril-Kamchatka Trench, collected at depths of 5210 and 6183 m, were analyzed. Lipids of these deposit-feeding animals showed similar FA compositions 20.05-16.08% saturated, 42.20-39.50% monoenoic, and 37.75-44.42% polyunsaturated FA, respectively. The contents of odd- and branched-chain FA were 17.35% and 8.80%, respectively. A significant part of FA was represented by uncommon FA such as 214(n-7), 224(n-8), 225(n-5), and 234(n-9), earlier discovered in deep-sea foraminifera. Also, the newly found acid, related to the ω2 family, Δ5,8,11,14,17,20-226(n-2), amounted 1.60% and 0.33% of total FA, respectively, for the two species. Such unusual FA composition of these abyssal species can be explained by the transfer and modification of FA from consumed foraminifera, which in turn, feed on bacteria. © 2020 AOCS.Empirical investigations of humans, pigeons, rats, and monkeys have indicated that these species will select free over forced choice, even when faced with identical outcomes. https://www.selleckchem.com/products/zcl278.html However, the same has yet to be quantitatively confirmed in nonhuman great apes. This experiment is the first systematic investigation of preference for free or forced choice in great apes using a paradigm in which extraneous variables are highly controlled. Three orangutans were given a choice of one of two virtual routes, one that provided a choice and one that did not via a touchscreen computer program. Choice of either route was rewarded with the same type and quantity of food. Initial results indicated a preference for free choice across all three participants. However, in two control conditions, orangutans' preferences varied, suggesting a weaker tendency to exercise choice than species previously tested. We suggest further investigation of preference for free and forced choice in orangutans and other great apes through alternative experimental paradigms that focus on increasing the fidelity of free and forced choice options. © 2020 Society for the Experimental Analysis of Behavior.Overexpression of bcl-2 and c-myc are defining features of double-expressor-lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c-myc and bcl-2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first-line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5-fold and 13-fold higher 5-year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN-IPI. DEL improved the discriminatory capability of the NCCN-IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN-IPI significantly improved the score's discriminatory potential both toward progression-free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple-to-use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN-IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy. © 2020 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.AIM OF STUDY We aimed to verify the value of computerised tomography angiography (CTA) on predicting the extent of anterior clinoidectomy that is optimal for particular carotid-ophthalmic aneurysms (COAs). CLINICAL RATIONALE FOR STUDY The anterior clinoid process (ACP) often impedes the complex microsurgery of COA. Complete removal of the ACP ensures safe clipping; however, it also may increase the risk of severe complications. The probability of performing a successful partial anterior clinoidectomy could be evaluated by preoperative CTA. MATERIALS AND METHODS 28 patients with either a ruptured (n=4) or unruptured COA were included in this prospective, single-centre, observational study. One aneurysm was giant, two were large, and the rest were smaller. Successful aneurysm clipping was the aim in all cases. The anterior clinoidectomy was preoperatively planned on multiplanar three-dimensional reconstructions of CTA images (3D-CTA) which resembled the typical view of a frontotemporal craniotomy. Finally, the predicted clinoidectomy was compared to the extent of the actual clinoidectomy.

With respect to the daily cleaning of the fistula, a special skin protection paste was applied on the skin around the fistula to create a waterproof film that entirely sealed the skin. Additionally, foam material was inserted between the retaining ring and the skin to absorb the leaking digesta. Monitoring of the pigs throughout the trial showed that modifications in cannula design proved to be useful as they facilitated exteriorization of the cannula through the ribs and stability of the cannula behind the ribs. Moreover, the use of the skin protection paste and foam material during postsurgical treatment of growing pigs effectively prevented skin irritation around the flank area. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood hematologic disorder characterized by lymphadenopathy, systemic inflammation, cytopenias, and life-threatening multi-organ dysfunction. Interleukin-6 (IL-6) inhibition effectively treats approximately one-third of patients. Limited options exist for non-responders, because the etiology, dysregulated cell types, and signaling pathways are unknown. We previously reported three anti-IL-6 non-responders with increased mTOR activation who responded to mTOR inhibition with sirolimus. We investigated mTOR signaling in tissue and serum proteomes from iMCD patients and controls. mTOR activation was increased in the interfollicular space of iMCD lymph nodes (N=26) compared to control lymph nodes by immunohistochemistry (IHC) for pS6, p4EBP1, and p70S6K, known effectors and read-outs of mTORC1 activation. IHC for pS6 also revealed increased mTOR activation in iMCD compared to Hodgkin lymphoma, systemic lupus erythematosus, and reactive lymph nodes, suggesting that the mTOR activation in iMCD is not just a product of lymphoproliferation/inflammatory lymphadenopathy. Further, the degree of mTOR activation in iMCD was comparable to autoimmune lymphoproliferative syndrome, a disease driven by mTOR hyperactivation that responds to sirolimus treatment. Geneset enrichment analysis of serum proteomic data from iMCD patients (n=88) and controls (n=42) showed significantly enriched mTORC1 signaling. Finally, functional studies revealed increased baseline mTOR pathway activation in peripheral monocytes and T-cells from iMCD remission samples compared to healthy controls. IL-6 stimulation augmented mTOR activation in iMCD patients, which was abrogated with JAK1/2 inhibition. https://www.selleckchem.com/products/aebsf-hcl.html These findings support mTOR activation as a novel therapeutic target for iMCD, which is being investigated through a trial of sirolimus (NCT03933904). Copyright © 2020 American Society of Hematology.OBJECTIVES The technique of simultaneously visualizing pulmonary nodules and the intersegmental plane using fluorescent images was developed to measure the distance between them intraoperatively. METHODS Patients who underwent pulmonary segmentectomy were consecutively included in this study between March 2016 and July 2019. Computed tomography or electromagnetic bronchoscopy-guided localization with indocyanine green-lipiodol emulsion was performed on the day of surgery. In the middle of the surgery, after dividing the segmental artery, vein and bronchus to a targeted segment, 0.3-0.5 mg/kg of indocyanine green was injected intravenously. RESULTS In total, 31 patients (17 men and 14 women with a mean age of 63.2 ± 9.8 years) were included in this study. The mean size and depth of the nodules were 1.2 ± 0.5 (range 0.3-2.5) cm and 16.4 ± 9.9 (range 1.0-42.0) mm, respectively. Pulmonary nodules and intersegmental plane of all the patients were visualized using a fluorescent thoracoscope. The resection margins were more than the size of the tumour or were 2 (mean 2.4 ± 1.2) cm in size in all patients except one. The resection margin of this patient looked sufficient on the intraoperative view. However, adenocarcinoma in situ at the resection margin was identified based on the pathological report. The mean duration of the operation was 168.7 ± 53.3 min, and the chest tube was removed on an average of 4.7 ± 1.8 days after surgery in all patients. CONCLUSIONS The dual visualization technique using indocyanine green could facilitate an easier measurement of the distance between pulmonary nodules and the intersegmental plane during pulmonary segmentectomy. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-β40 and amyloid-β42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ε4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during folasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.In human-to-mouse xenogeneic transplantation, polymorphisms of signal-regulatory protein α (SIRPA) that decide their binding affinity for human CD47 are critical for engraftment efficiency of human cells. In the present study, we generated a new C57BL/6.Rag2nullIl2rgnull (BRG) mouse line with Sirpahuman/human (BRGShuman), in which mouse Sirpa was replaced by human SIRPA encompassing all 8 exons. Macrophages in C57BL/6 with Sirpahuman/human had an affinity for human CD47 significantly stronger than those with SirpaNOD/NOD, and did not show detectable phagocytosis against human hematopoietic stem cells. In turn, Sirpahuman/human macrophages had a moderate affinity to mouse CD47, and BRGShuman mice did not show blood cytopenia that was seen in Sirpa-/- mice. In xenotransplantation, BRGShuman mice showed significantly efficient engraftment and maintenance of human hematopoiesis with a high level of myeloid reconstitution, and improved reconstitution in peripheral tissues, as compared to BRG with SirpaNOD/NOD (BRGSNOD) mice.

Pyriproxyfen is an insect growth regulator acting as larvicide against a large spectrum of public health insect pests, especially dipterans. It is also widely used in agriculture and horticulture for the control of many insect species. Disrupting the endocrine system by mimicking the activity of the juvenile hormone, pyriproxyfen interferes with metamorphosis in insects and prevents them from reaching maturity and reproducing. Because the aquatic ecosystems can be directly or indirectly contaminated by pyriproxyfen, the goal of this study was to establish the aquatic ecotoxicological profile of pyriproxyfen and to identify the gaps that need to be filled. Pyriproxyfen is photodegraded quickly in water. In the absence of organic matter, its persistence in aerobic water media is also limited especially with high temperature and sunlight. Analysis of the laboratory and in situ results for more than 60 aquatic algae, plants, invertebrates, and vertebrates shows that the toxicity of pyriproxyfen is highly variable including within a same taxonomical group. Abiotic and biotic factors can highly influence the toxicity of the molecule. Pyriproxyfen disrupts the development of numerous species and adversely impacts various physiological events. It can also disturb the behavior of the organisms such as their predatory and swimming performances. Although some experimental studies focus on the environmental fate of pyriproxyfen metabolites, those dealing with their aquatic ecotoxicity assessment are scarce. In the same way, the limited number of studies dealing with the search of pyriproxyfen residues in lake, river, and other natural aquatic media does not include the identification of the metabolites.In modern agriculture, farm produce accumulates a lot of nitrates that can reach toxic levels owing to the unfair use of nitrogen fertilizers, cultural methods, farming policies in multiple areas of the world, thereby increasing concerns about the availability of hygienic food supply and environmental hazards. Over the past few decades, global interest in achieving greater output through intensive fertilization has been a growing trend. The fertilizer based on urea or ammonium mainly yields ammonium, which is then transformed to nitrate through the oxidation process that is biologically mediated. Nitrate tends to accumulate differently in distinct crop plants and distinct components of agricultural commodities based on species, crop variety, genetic history, environmental circumstances, harvest phase, post-harvest storage conditions, agronomic variables, nature, and fertilizer application rate. The current article highlights various factors that could directly or indirectly contribute to the accumulation of nitrates in different parts of crop plants and discusses strategies to minimize the accumulation of nitrates in farm produce, thus ensuring healthy food supply and protecting the environment from the accumulation of nitrates.BACKGROUND Tumor-infiltrating lymphocytes are an important component of the tumor microenvironment (TME) in breast cancer. They have been linked with tumor pathogenesis in advanced stages. However, little is known about their contribution in early phases. In this study, we analyzed the infiltration of leukocytes and cancer stem cells (CSC) in tumors from patients with early breast cancer. METHODS Samples of blood and tumor tissue from 30 patients with breast cancer were collected, and the number of dendritic cells (DC), T cells, and CSC were analyzed by flow cytometry. RESULTS Tumor-infiltrating CD4 and CD8 T cells expressed higher levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) compared with peripheral T cells. Regulatory T cells (Treg) were enriched in tumors and overexpressed glucocorticoid-induced TNFR-related protein and CTLA-4. Tumor Treg had a positive correlation with the amount of myeloid DC (mDC) and disease progression. The CD8/Treg ratio was associated with lymph node metastasis and tumor stages. The main subset of DC in early breast tumors was mDC, while plasmacytoid DC were almost absent. CSC were present in most tumors with higher frequencies in patients with lymph node metastasis. CSC were also associated with the amount of tumor-infiltrating Treg. CONCLUSION Early breast cancer has an inflammatory milieu characterized by mDC, Treg, and CSC infiltration. The frequencies of Treg, CSC and CD8/Treg ratio were associated with disease progression. The composition of leukocytes and the presence of CSC in early breast tumors should be considered for the development of new therapeutic approaches.BACKGROUND Coronovirus disease 2019 (COVID-19) has spread rapidly across the globe. People of all ages are susceptible to COVID-19. However, literature reports on pediatric patients are limited. METHODS To improve the recognition of COVID-19 infection in children, we retrospectively reviewed two confirmed pediatric cases from two family clusters. Both clinical features and laboratory examination results of the children and their family members were described. RESULTS The two confirmed children only presented with mild respiratory or gastrointestinal symptoms. Both of them had normal chest CT images. After general and symptomatic treatments, both children recovered quickly. Both families had travel histories to Hubei Province. CONCLUSIONS Pediatric patients with COVID-19 are mostly owing to family cluster or with a close contact history. Infected children have relatively milder clinical symptoms than infected adults. We should attach importance to early recognition, early diagnosis, and early treatment of infected children.INTRODUCTION Cigarettes and other tobacco products may be extinguished by submersion in liquids in beverage cans or bottles. Cases of nicotine poisoning in children have been reported following ingestion of such liquids. The aim of this study is to analyze the variability of nicotine concentrations with respect to number of cigarettes immersed and the duration of immersion in a soda can METHODS One unsmoked cigarette was immersed in a cola containing soda can. Three separate samples of the mixture were obtained at different intervals of time post immersion up to 1 week. At the same time, a set of four cola cans were immersed with an increasing number of unsmoked cigarettes and samples obtained. All the samples were then analyzed for nicotine concentrations using liquid chromatography-mass spectrometry. https://www.selleckchem.com/products/sb239063.html RESULTS The mean concentration of nicotine measured over the course of 6 hours from one full cigarette in 55 ml of a cola beverage was 0.48 mg/ml. Nicotine concentrations steadily increased in the first 6 hours following submersion, after which, the levels plateaued (r = 0.

Background Targeting G protein-coupled receptors (GPCRs) in pancreatic cells is feasible to modulate glucose-induced insulin secretion. Because pancreatic islets consist of several cell types and GPCRs can couple to more than one G-protein family, results obtained in pancreatic cell lines do not always match the response in primary cells or intact islets. Therefore, we set out to establish a protocol to analyze second messenger activation in mouse pancreatic islets. Results Activation of Gq/11-coupled receptor expressed in primary β cells increased the second messenger IP1 in an accumulation assay. Applying a Gq/11 protein inhibitor completely abolished this signal. Activation of the V1 vasopressin and ghrelin receptors, predominantly expressed in the less abundant alpha and delta cells, was not sufficient to induce a significant IP1 increase in this assay. However, fura-2-based fluorescence imaging showed calcium signals upon application of arginine vasopressin or ghrelin within intact pancreatic islets. Using the here established protocol we were also able to determine changes in intracellular cAMP levels induced by receptors coupling to Gs and Gi/o proteins. Conclusions Detection of the second messengers IP1, cAMP, and calcium, can be used to reliably analyze GPCR activation in intact islets. © The Author(s). 2020.Background Therapeutic potential of low-intensity ultrasound (LIUS) has become evident in various musculoskeletal diseases. We have previously shown that LIUS has an inhibitory effect on local edema in various diseases including the arthritis and brain injury. In this study, we examined whether LIUS can attenuate paw edema formation vis-à-vis vascular permeability and inflammation in rats induced by carrageenan. LIUS with a frequency of 1 MHz and the intensities of 50, 100, or 200 mW/cm2 were exposed on rat paws for 10 min immediately after carrageenan injection. Results Carrageenan injection induced paw edema which was peaked at 6 h and gradually decreased nearly to the initial baseline value after 72 h. LIUS showed a significant reduction of paw edema formation at 2 and 6 h at all intensities tested. The highest reduction was observed at the intensity of 50 mW/cm2. Histological analyses confirmed that LIUS clearly decreased the carrageenan-induced swelling of interstitial space under the paw skin and infiltration of polymorphonuclear leukocytes. Moreover, Evans Blue extravasation analyses exhibited a significant decreases of vascular permeability by LIUS. Finally, immunohistochemical staining showed that expression of pro-inflammatory proteins, namely, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) induced by carrageenan injection was reduced back to the normal level after LIUS stimulation. Conclusions These results provide a new supporting evidence for LIUS as a therapeutic alternative for the treatment of edema in inflammatory diseases such as cellulitis. © The Author(s). 2020.The occurrence of neurodegenerative disease is increasingly raised. From physiopathological aspect, the emergence of auto-reactive antibodies against the nervous system antigens contributes to de-myelination in Multiple sclerosis (MS). These features cause the nervous system dysfunction. The follow-up of molecular alterations could give us a real-state vision about intracellular status during pathological circumstances. In this review, we focus on the autophagic response during MS progression and further understand the relationship between autophagy and MS and its modulatory effect on the MS evolution. The authors reviewed studies published on the autophagy status in neurodegenerative disease and on the autophagy modulation in MS prognosis, diagnosis, and possible therapies. The inevitable role of autophagy was shown in the early-stage progression of MS. Due to critical role of autophagy in different stage of cell activity in nervous system, the distinct role of autophagy should not be neglected in the development, pathogenesis, and treatment of MS. © The Author(s). 2020.Background The urgent problem in the treatment of breast cancer is the recurrence induced by breast cancer stem cells (CSCs). https://www.selleckchem.com/products/lji308.html Understanding the role and molecular mechanism of specific molecules in breast cancer stem cells can provide a theoretical basis for better treatment. TRIP6 is an adapter protein which belongs to the zyxin family of LIM proteins and is important in regulating the functions of CSCs. The present study aims to investigate the effects and mechanism of TRIP6 in breast cancer. Methods TRIP6 expression in breast cancer cells and tissues were detected by Real-Time PCR, western blot and immunohistochemistry (IHC). MTT assays, colony formation assays, Xenografted tumor model and mammosphere formation assays were performed to investigate the oncogenic functions of TRIP6 in the tumorigenic capability and the tumor-initiating cell-like phenotype of breast cancer cells in vitro and in vivo. Luciferase reporter, subcellular fractionation and immunofluorescence staining assays were performed to determof breast cancer. © The Author(s) 2020.Background Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear. Methods To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC. Results We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion.

IFN-β-luciferase report assay results showed that the relative expressions of luciferin were remarkably increased in MFF-1 cells. Site mutation of serine (S) on C-terminus of scSTING showed that both S388 and S396 were important for mediated signaling. Furthermore, scSTING overexpression inhibited ISKNV infection, and knockdown of scSTING promoted ISKNV infection, indicating that scSTING could suppress ISKNV infection in MFF-1 cells. These observations suggested that the scSTING played an important role in innate immune against ISKNV infection. Our work would help elucidate the roles of teleost fish STING in innate immunity. Eriocheir sinensis is an important aquaculture species in China, and its yield and quality are threatened by oxidative stress caused by deteriorating water conditions. Reduced glutathione (GSH) is an endogenous antioxidant, but whether dietary GSH can increase the resistance of E. sinensis to environmental stress remains unclear. Therefore, in this study, crabs were fed with dietary GSH (0, 300, 600, 900, and 1200 mg/kg diet weight) for up to 10 weeks to determine the effects of different dietary GSH concentrations on growth, antioxidant capacity, and immunity of E. https://www.selleckchem.com/products/acy-738.html sinensis. The results showed that the weight gain rate and survival rate increased significantly as dietary GSH levels increased from 0 to 900 mg/kg, but decreased at 1200 mg/kg. Compared with the control group, the diet supplemented with 900 mg/kg GSH not only increased the concentration of GSH in the haemolymph and hepatopancreas, but also enhanced the activity of glutathione peroxidase (GSH-Px) (p  less then  0.05). Diets supplemented with 600 or 900 mg/kg GSH significantly increased the enzymes activities of superoxide dismutase (SOD), lysozyme (LZM), alkaline phosphatase, and acid phosphatase, and significantly decreased the content of malondialdehyde. To understand the changes in the activity of these enzymes further, the expression of related genes was detected. Diets supplemented with 600 or 900 mg/kg GSH significantly upregulated the genes expressions of cytosolic manganese SOD, mitochondrial manganese SOD, copper, zinc-SOD, GSH-Px, LZM, and prophenoloxidase activating factor, and significantly down regulated the expression of Toll-like receptor 1, Toll-like receptor 2, Dorsal, and the myeloid differentiation factor 88. However, a diet supplemented with 1200 mg/kg GSH decreased those positive indicators. Overall, our results demonstrated that an appropriate diet supplemented with 600 or 900 mg/kg GSH enhances antioxidant capacity and immunity, which will enhance the general health of E. sinensis. Chemokines are small cytokines that are classified into four groups, one of which is called CC chemokines. In the present study, the full-length cDNA of a CCL25 chemokine was identified from black rockfish, Sebastes schlegelii (named as SsCCL25) by EST (expressed sequence tag) analysis. The cDNA of SsCCL25 consisted of a 5-terminal untranslated region (UTR) of 74 bp, a 3-UTR of 882 bp with a poly (A) tail, and an open reading frame (ORF) of 303 bp encoding a polypeptide of 100 amino acids with the putative molecular mass of 11.5 kDa. There was a SCY domain in the deduced amino acid sequence of SsCCL25. The phylogenetic relationships and syntenic analyses provided evidences for the identities of SsCCL25 with CCL25 group. The mRNA transcripts of SsCCL25 were expressed in all detected tissues and dominantly in liver, muscle and gill. Moreover, after Vibrio anguillarum stimulation, the mRNA expression levels of SsCCL25 were significantly up-regulated at 24 h (p  less then  0.05) in the liver and during 4-8 h (p  less then  0.05) in the spleen. Recombinant SsCCL25 protein induced chemotaxis of both control and LPS-stimulated peripheral blood leukocytes (PBL) and enhanced their resistance to bacterial infection in a dose-dependent manner. Furthermore, rSsCCL25 showed significant inhibitory effect on V. anguillarum and Edwardsiella tarda growth. All these results collectively indicated that SsCCL25 might contribute to the defense against microbe infection and function as a chemoattractant in black rockfish. Licorice is a widely used herbal medicine for the treatment of various diseases in southern Europe and parts of Asia. It has been reported that the isoliquiritin (ISL) from Glycyrrhiza root has the activity of promoting angiogenesis. The purpose of this study was to investigate the effect of ISL on the wound healing activity of zebrafish and its mechanism. 6-month-old zebrafish were injured in the skin (2 mm in diameter) and then treated with ISL. By measuring wound size and by histological examination, we found that ISL improved wound healing. In addition, 4-day-old zebrafish embryos of double transgenic line [Tg(fli-1EGFP)]/[Tg(mpegmCherry)] were suffered from tissue traumas and then treated with ISL. Through fluorescent microscopy, we found that ISL promoted macrophage recruitment and angiogenesis in the wound area. Through qPCR analysis, we found that ISL up-regulated the expression of genes related to inflammation and angiogenesis in zebrafish embryos. These results showed that ISL could promote inflammatory response and angiogenesis, which played key roles in promoting wound healing. Therefore, ISL can be used as a promising candidate to promote wound healing. Fermentation has been reported to improve the utilization of plant ingredients including soybean meal (SBM) by fish, but the detailed mechanism is still poorly understood. This study compared the effects of partial replacement of fish meal (FM) protein with SBM or Enterococcus faecium fermented SBM (EFSM) on the growth, antioxidant status, intestinal microbiota, morphology, and inflammatory responses in turbot (Scophthalmus maximus L.). The FM-based diet was used as the control (CONT). Two experimental diets were formulated in which 45% of the FM protein was replaced with SBM or EFSM. Each diet was fed to triplicate groups of fish (7.57 ± 0.01 g) twice daily for 79 d. Inferior growth performance was observed in SBM group, however, no significant depression was observed in EFSM group compared to the CONT group. The CONT group had the highest values of lysozyme, complement component 3, total antioxidant capacity, superoxide dismutase and catalase, followed by the EFSM group, and the lowest in SBM group. The malondialdehyde content was lowest in the CONT group, followed by the EFSM group, and was highest in the SBM group.

Regarding the evaluation of tobacco addiction, the most commonly used questionnaires are the Fagerström tests (FTCD, HSI...), which are well correlated with cotinine concentration. However, there is insufficient evidence of their usefulness in reducing tobacco consumption during pregnancy to recommend them in current practice.DSM-V diagnostic criteria for addiction should be known as they can also be used to characterize the intensity of this addiction. INTRODUCTION The consequences of smoking have been studied more during pregnancy than during breastfeeding. There is a passage of nicotine and other substances in breast milk and some modifications of milk composition. The objectives of this chapter are to study the benefits of breastfeeding in women who smoke, and the adaptation of smoking, medication and behavioral habits in case of incomplete withdrawal to better guide women. METHODS The MedLine database, the Cochrane Library and foreign guidelines from 1999 to 2019 have been consulted. RESULTS The conservation of the benefit of breastfeeding in smokers with regard to the prevention of respiratory infections, infantile colic, cognitive deficits, obesity, sudden infant death, is not known to date. It is therefore not recommended to include smoking status in the choice of feeding mode for the newborn (Professional Agreement). However, since breastfeeding is a factor associated with a reduction in smoking and / or withdrawal (NP2), it is recommended to promote breastfeeding in non-weaned women in order to limit smoking (grade B). The use of nicotine replacement therapy is possible during breastfeeding (Professional Agreement). In the absence of data, bupropion (Zyban®) and varenicline (Champix®) are not recommended for women who are breast-feeding (Professional Agreement). A free interval between smoking and breastfeeding reduces the concentration of nicotine in milk (NP4). For non-weaned women who are breastfeeding, it is therefore recommended not to smoke just before breast-feeding (Professional Agreement). CONCLUSION The results indicate that breastfeeding is possible in smokers, although less often initiated by them. If the conservation of its benefits for the child is not demonstrated to date, breastfeeding allows the mother to limit smoking. OBJECTIVE The objective of this chapter is to evaluate the risks of second-hand-smoke during pregnancy and to assess the benefits of antenatal care. https://www.selleckchem.com/products/h3b-120.html METHODS Bibliographical research in French and English using the Medline and Cochrane databases and the recommendations of international societies. RESULTS Exposure to second-hand smoke appears to be higher at home and in the car, with potential consequences for pregnancy, especially prematurity (NP3). Complete avoidance of smoking at home significantly reduces exposure to passive smoking compared to incomplete avoidance (NP4). The more numerous the sources, the higher the intoxication is (NP4). The major risk factor associated with passive smoking is the presence of a spouse who smokes. Other associated factors are the presence of a smoker at home or in the car, young population ( less then 25 years), low level of education, old smoking (NP4). Passive smoking is associated with an increased risk of fetal death in utero, fetal malformations, prematurity and birth weight under 2500g (NP 2). No specific management is recommended for all pregnant women. Nevertheless, in a specific population of pregnant women with vulnerabilities, a behavioral approach aimed at teaching them to negotiate with their entourage may be beneficial in order to reduce the effects of passive smoking on pregnancy (NP2). CONCLUSION It is recommended to advise women and their family (especially spouses) to create a smoke-free environment, especially at home and in the car (Professional consensus). It is recommended to provide a minimum amount of smoking cessation advice to pregnant women's entourage (Professional consensus). Other methods of cigarette consumption include a variety of electronic products, as well as heated tobacco, snus and shisha. The questions in this chapter are What other methods of consumption are used during pregnancy (either electronic or containing tobacco) and what is their prevalence? What is their benefit/risk balance? Can their use during pregnancy be proposed?.Although the fetus is not exposed to the combustible toxins of tobacco, e-cigarette products may contain nicotine, which maintains the exposure of the fetus. Further research is needed on the other components of the electronic cigarette, such as flavorings and propylene glycol and/or glycerol, in order to assess the benefit/risk balance. In addition, some solvents contain ethanol. In the current state of knowledge, the precautionary principle should be respected and not recommend the initiation or continuation of the electronic cigarette during pregnancy (professional agreement). For smoking cessation or electronic cigarette cessation, it is recommended to provide the same advice and to use methods that have already been evaluated (professional agreement). For the JUUL, there are currently no data on obstetrical outcome when used.The use of shisha during pregnancy is associated with decreased fetal growth. It is recommended not to use shisha during pregnancy (Grade C). There are currently no data on the use of heated tobacco and obstetrical outcome. World tobacco consumption during pregnancy is estimated to be 1.7% (95% CI 0.0 - 4.5%). Among the 50 European countries evaluated, France ranks 7th among the countries most affected by active smoking during pregnancy. In the 2016 National Perinatal Survey, 30.0% of women reported active smoking before they started their pregnancy and 16.6% still smoked in the 3rd trimester of pregnancy. There are also disparities in consumption between regions in France (24.0% of pregnant women with active smoking in the 3rd trimester of pregnancy in Bretagne against 9.4% in the Paris region and 5.2% in the French departments and overseas regions). A young age, a low level of education, a low socioeconomic level, primiparity, a geographical origin of mainland France, unemployment, a smoking partner, no partner or a depression are risk factors for smoking during pregnancy. Multiparity is a risk factor for failure of smoking cessation during pregnancy. For health professionals in contact with women of childbearing age, it is recommended to identify a tobacco consumption in women or their partners before pregnancy or as early as possible during pregnancy.

AIMS To analyze the efficacy and safety of sofosbuvir (SOF)-based regimens in Thai patients with chronic hepatitis C virus infection who had pre-existing significant liver fibrosis. PATIENTS AND METHODS This was a retrospective cohort study, conducted between 1 June 2018 and 31 May 2019 at Rajavithi Hospital, Bangkok, Thailand. All patients completed 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) 12 weeks after the end of therapy. RESULT A total of 185 patients were included, with 52, 63 and 70 taking SOF+Ledipasvir (SOF+LDV), SOF+LDV+ribavirin (RBV) and SOF+Pegylated interferon (Peg-IFN)+RBV (SOF+Peg-IFN+RBV) respectively. Genotype (GT) 1 was predominant at 40.0%, followed by GT3 at 37.8%, and GT6 at 22.2%. Overall 95.1% of patients in this study achieved SVR (n = 176/185), and the only factor associated with SVR was HCV genotype (p = 0.001). GT6 patients had lower SVR rates compared to GT1 and GT3 patients (82.9%, 98.6%, and 98.6% respectively) while there was no association between SVR and other factors (p >0.05) such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history. No serious adverse events were reported in the present study. CONCLUSION Sofosbuvir-based regimens in the treatment of patients with chronic HCV infection were highly efficacious with excellent safety and tolerability profiles in a real-world setting; however, further research is required to establish whether or not such a regimen is an adequate treatment for all genotype 6 patients.Studies on the thalamus have mostly focused on sensory relay nuclei, but the organization of pathways associated with emotions is not well understood. We addressed this issue by testing the hypothesis that the primate amygdala acts, in part, like a sensory structure for the affective import of stimuli and conveys this information to the mediodorsal thalamic nucleus, magnocellular part (MDmc). We found that primate sensory cortices innervate amygdalar sites that project to the MDmc, which projects to the orbitofrontal cortex. As in sensory thalamic systems, large amygdalar terminals innervated excitatory relay and inhibitory neurons in the MDmc that facilitate faithful transmission to the cortex. The amygdala, however, uniquely innervated a few MDmc neurons by surrounding and isolating large segments of their proximal dendrites, as revealed by three-dimensional high-resolution reconstruction. Physiologic studies have shown that large axon terminals are found in pathways issued from motor systems that innervate other brain centers to help distinguish self-initiated from other movements. By analogy, the amygdalar pathway to the MDmc may convey signals forwarded to the orbitofrontal cortex to monitor and update the status of the environment in processes deranged in schizophrenia, resulting in attribution of thoughts and actions to external sources.The purpose of this study was to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve (AUC) of 0.62 (p = 0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC.We report surface hardening or crust formation, like caking, during evaporation when a porous medium was heated from above using IR radiation. These crusts had higher strength than their closest counterparts such as sandcastles and mud-peels which essentially are clusters of a partially wet porous medium. Observed higher strength of the crusts was mostly due to surface tension between the solid particles, which are connected by liquid bridges (connate water). https://www.selleckchem.com/products/mrt68921.html Qualitative (FTIR) and quantitative (TGA) measurements confirmed the presence of trapped water within the crust. Based on the weight measurements, the amount of water trapped in the crusts was ~1.5%; trapped water was also seen as liquid bridges in the SEM images. Further, in the fixed particle sizes case, the crust thickness varied slightly (only 10-20 particle diameters for cases with external heating) while with the natural sand whole porous column was crusted; surprisingly, the crust was also found with the hydrophobic glass beads. Fluorescein dye visualization technique was used to determine the crust thickness. We give a power-law relation between the crust thickness and the incident heat flux for various particle sizes. The strength of the crust decreased drastically with increasing hydrophilic spheres diameter while it increased with higher surface temperature.In collaboration-based creative industries, such as film production, creators in the network core enjoy prestige and legitimacy that are key for creative success. However, core creators are challenged to maintain diverse access to new ideas or alternative views that often emerge from the network periphery. In this paper, we demonstrate that creators in the network core can increase the probability of their creative success by brokering peripheral collaborators to the core. The argument is tested on a dynamic collaboration network of movie creators constructed from a unique dataset of Hungarian feature films for the 1990-2009 period. We propose a new way to capture brokers' role in core/periphery networks and provide evidence that being in the core and at the same time bridging between the core and the periphery of the network significantly increases the likelihood of award winning.