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J Norton, M David, C Gandubert, C Bouvier, L-A Gutierrez, A Frangeuil, A Macgregor, A Oude Engberink, A Mann, D Capdevielle
OBJECTIVES: The general practitioner (GP) is the most frequently consulted health professional by patients with common mental disorders (CMD). Yet approximately half of cases are not detected by the GP. Many factors linked to the patient, the doctor and the health care system influence detection. For example, detection rates are higher when patients are better known to their GP. On the other hand, patients visiting a different GP for reasons of dissatisfaction with previous care are more likely to be detected on the survey-day...
October 14, 2016: L'Encéphale
Sang Joon Won, Dahvid Davda, Kristin J Labby, Sin Ye Hwang, Rachel E Pricer, Jaimeen D Majmudar, Kira A Armacost, Laura A Rodriguez, Christina L Rodriguez, Fei San Chong, Kristopher A Torossian, Jasmine Palakurthi, Edward S Hur, Jennifer L Meagher, Charles L Brooks, Jeanne A Stuckey, Brent R Martin
Post-translational S-palmitoylation directs the trafficking and membrane localization of hundreds of cellular proteins, often involving a coordinated palmitoylation cycle that requires both protein acyl transferases (PATs) and acyl protein thioesterases (APTs) to actively re-distribute S-palmitoylated proteins towards different cellular membrane compartments. This process is necessary for the trafficking and oncogenic signaling of S-palmitoylated Ras isoforms, and potentially other peripheral membrane proteins...
October 17, 2016: ACS Chemical Biology
Annelies Colliers, Roy Remmen, Marie-Luise Streffer, Barbara Michiels, Stefaan Bartholomeeusen, Koenraad G Monsieurs, Jef Goris, Samuel Coenen, Veronique Verhoeven, Hilde Philips
BACKGROUND: The implementation of general practitioner cooperatives (GPC) for out-of-hours (OOH) primary care, raises the question if the location of a GPC adjacent to a hospital reduces the OOH caseload of the emergency department (ED). METHODS: Two natural experiments were used in this before-after study, the effect of the implementation of two GPCs in two different regions on the out-of-hours caseload of the local EDs was compared. One GPC was located adjacent to the ED of a general hospital, the other was not...
October 17, 2016: Acta Clinica Belgica
Astra S Bryant, Anna K Greenwood, Scott A Juntti, Allie E Byrne, Russell D Fernald
Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish...
October 14, 2016: Journal of Experimental Biology
M Wassef, R Margueron
Genome sequencing of large cohorts of tumors has revealed that mutations in genes encoding chromatin regulators are frequent in cancer. However, the precise contribution of these mutations to tumor development often remains elusive. Here, we review the current knowledge concerning alterations of the Polycomb machinery in cancer, with a particular focus on the Polycomb Repressive Complex 2 (PRC2), a key chromatin modifier involved in the maintenance of transcriptional silencing. A broad variety of alterations can impair PRC2 activity yet, overall, only one type of alteration is found in a given class of tumor...
October 11, 2016: Journal of Molecular Biology
Alexandra Flynn, Rosalee Zackula, Nicole M Klaus, Liz McGinness, Susan Carr, Matthew Macaluso
OBJECTIVE: Yellow Ribbon is a gatekeeper-type suicide prevention program that is widely used in public schools. However, data on its effectiveness are limited. The purpose of our study was to evaluate self-reported changes in knowledge and comfort level communicating about suicide following Yellow Ribbon training for a large, representative sample of students from a public school system in the midwestern United States. METHODS: The program was administered to students within the same school district during 2006 through 2009...
2016: Primary Care Companion to CNS Disorders
Kayode K Ojo, Sriveny Dangoudoubiyam, Shiv K Verma, Suzanne Scheele, Amy E DeRocher, Michelle Yeargan, Ryan Choi, Tess R Smith, Kasey L Rivas, Matthew A Hulverson, Lynn K Barrett, Erkang Fan, Dustin J Maly, Marilyn Parsons, Jitender P Dubey, Daniel K Howe, Wesley C Van Voorhis
Sarcocystis neurona is the most frequent cause of equine protozoal myeloencephalitis, a debilitating neurological disease of horses that can be difficult to treat. We identified SnCDPK1, the S. neurona homologue of calcium-dependent protein kinase 1 (CDPK1), a validated drug target in Toxoplasma gondii. SnCDPK1 shares the glycine "gatekeeper" residue of the well-characterized T. gondii enzyme, which allows the latter to be targeted by bumped kinase inhibitors. This study presents detailed molecular and phenotypic evidence that SnCDPK1 can be targeted for rational drug development...
October 8, 2016: International Journal for Parasitology
Dong Xiao, Jing-Jing Hu, Jing-Yi Zhu, Shi-Bo Wang, Ren-Xi Zhuo, Xian-Zheng Zhang
In this study, we report a novel redox-responsive mesoporous silica nanoparticle (MSN)-based nanocarrier, capping with a therapeutic peptide ((RGDWWW)2KC) containing a RGD target motif, for tumor targeting synergistic therapy, which is designated as TTSTMSN. The MSN was decorated with a tumor-targeting therapeutic peptide as a potential gatekeeper. The two branched peptides containing rich tryptophans allowed the pores to be blocked via π-π stacking and hydrophobic interactions. Once the drug loaded nanoparticles were taken up by the cancer cells through integrin-mediated endocytosis, the therapeutic peptide capping shells on the surface of MSNs were released, inducing the loaded drug to diffuse into the cytoplasm after breaking of the disulfide bonds, triggered by the high concentration of glutathione (GSH) in cancer cells...
September 22, 2016: Nanoscale
Rasmus Borup, Susanne Kaae, Timo Minssen, Janine Traulsen
BACKGROUND: Many areas of pharmaceutical legislation in the European Union (EU) are harmonised in order to promote the internal market and protect public health. Ideally, harmonisation leads to less fragmented regulation and cross-border complexities. This study, however, focuses on an increasingly harmonised legislative area that is subject to increases in requirements and complexities: the distribution of medicines. This study compared Danish legislation governing the distribution of medicines before and after Denmark joined the EU in order to assess the impact of EU harmonisation, as well as to evaluate whether the drastic increases in requirements mandated by the Falsified Medicines Directive of 2011 correspond to a new approach to governing the pharmaceutical supply chain...
2016: Journal of Pharmaceutical Policy and Practice
Valeria Markova, Gro M Sandal
Objective: Refugees are at high risk of experiencing mental health problems due to trauma in their pasts and to acculturation stress as they settle in a new country. To develop efficient health services that meet the needs of refugees from different regions, an understanding is required of how they make sense of and prefer to cope with mental health problems. This study aims to investigate lay explanatory models of depression and preferred coping strategies among Somali refugees in Norway. Methods: The study used a mixed-method design with a vignette describing a moderately depressed person based on ICD-10 criteria...
2016: Frontiers in Psychology
Nevena Cvetesic, Ita Gruic-Sovulj
The covalent coupling of cognate amino acid-tRNA pairs by corresponding aminoacyl-tRNA synthetases (aaRS) defines the genetic code and provides aminoacylated tRNAs for ribosomal protein synthesis. Besides the cognate substrate, some non-cognate amino acids may also compete for tRNA aminoacylation. However, their participation in protein synthesis is generally prevented by an aaRS proofreading activity located in the synthetic site and in a separate editing domain. These mechanisms, coupled with the ability of certain aaRSs to discriminate well against non-cognate amino acids in the synthetic reaction alone, define the accuracy of the aminoacylation reaction...
October 3, 2016: Methods: a Companion to Methods in Enzymology
Shu Meng, Hongyan Wu, Jing Wang, Qiyuan Qiu
The proto-oncogene protein RET is a receptor tyrosine kinase that plays an important role in the development and progress of various human cancers. Currently, targeting RET with small-molecule tyrosine kinase inhibitors (TKIs) has been established as promising therapeutic strategy for thyroid carcinoma (TC). However, two gatekeeper mutations V804M and V804L in RET kinase domain have been frequently observed to cause drug resistance during the targeted therapy, largely limiting the application of reversible TKIs in TC...
October 2016: Molecular Informatics
Shih-Chi Su, Ming-Ju Hsieh, Wei-En Yang, Wen-Hung Chung, Russel J Reiter, Shun-Fa Yang
Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site...
October 5, 2016: Journal of Pineal Research
Katherine Lippel, Joan M Eakin, D Linn Holness, Dana Howse
BACKGROUND: This study sought to identify impacts of compensation system characteristics on doctors in Québec and Ontario. METHODS: (i) Legal analysis; (ii) Qualitative methods applied to documentation and individual and group interviews with doctors (34) and other system participants (31); and (iii) Inter-jurisdictional transdisciplinary analysis involving cross-disciplinary comparative and integrative analysis of policy contexts, qualitative data, and the relationship between the two...
October 4, 2016: American Journal of Industrial Medicine
Uta Duppel, Matthias Woenckhaus, Christian Schulz, Johannes Merk, Wolfgang Dietmaier
Aberrant promoter methylation of tumor relevant genes frequently occurs in early steps of carcinogenesis and during tumor progression. Epigenetic alterations could be used as potential biomarkers for early detection and for prediction of prognosis and therapy response in lung cancer. The present study quantitatively analyzed the methylation status of known and potential gatekeeper and tumor suppressor genes [O-6-methylguanine-DNA methyltransferase (MGMT), Ras association domain family member 1A (RASSF1A), Ras protein activator like 1 (RASAL1), programmed cell death 4 (PDCD4), metastasis suppressor 1 (MTSS1) and tumor suppressor candidate 3 (TUSC3)] in 42 lung cancers and in corresponding non-malignant bronchus and lung tissue using bisulfite-conversion independent methylation-quantification of endonuclease-resistant DNA (MethyQESD)...
October 2016: Oncology Letters
Eline Skirnisdottir Vik, Gunn Terese Haukeland, Bente Dahl
OBJECTIVE: To explore women's experiences with giving birth before arrival. DESIGN: A qualitative interview study. SETTING: Individual semi structured interviews with women from Western Norway conducted in their homes in 2015. PARTICIPANTS: 10 women who experienced BBA-births in 2014, or the beginning of 2015. Two primiparous and eight multiparous women participated in the study. KEY FINDINGS: Three themes were generated from the analysis...
September 22, 2016: Midwifery
Yawei Wang, Haiyan Zhang, Jisheng Li, Xiuwen Wang
An acquired T798M gatekeeper mutation in human epidermal growth factor receptor 2 (HER2) kinase can cause drug resistance to anti-HER2 chemotherapy drugs in lung cancer. Previously, the reversible pan-kinase inhibitor Staurosporine has been found to selectively inhibit the HER2 T798M mutant over wild-type kinase, suggesting that the Staurosporine scaffold is potentially to develop mutant-selective inhibitors. Here, we systematically evaluated the chemical space of Staurosporine scaffold-based compounds in response to HER2 T798M mutation at structural, energetic and molecular levels by using an integrated analysis strategy...
October 1, 2016: Chemistry & Biodiversity
Adam Fusheini
BACKGROUND: National/social health insurance schemes have increasingly been seen in many low- and middle-income countries (LMICs) as a vehicle to universal health coverage (UHC) and a viable alternative funding mechanism for the health sector. Several countries, including Ghana, have thus introduced and implemented mandatory national health insurance schemes (NHIS) as part of reform efforts towards increasing access to health services. Ghana passed mandatory national health insurance (NHI) legislation (ACT 650) in 2003 and commenced nationwide implementation in 2004...
April 27, 2016: International Journal of Health Policy and Management
Melissa Burton, Mike Reid, Anthony Worsley, Felix Mavondo
INTRODUCTION: Household food gatekeepers have the potential to influence the food attitudes and behaviours of family members, as they are mainly responsible for food-related tasks in the home. The aim of this study was to determine the role of gatekeepers' confidence in food-related skills and nutrition knowledge on food practices in the home. METHODS: An online survey was completed by 1059 Australian dietary gatekeepers selected from the Global Market Insite (GMI) research database...
September 28, 2016: Appetite
Gregory Segala, Marcela A Bennesch, Deo Prakash Pandey, Nicolas Hulo, Didier Picard
Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers...
September 15, 2016: Molecular Cell
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