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Lisa Blom, Lucie Laflamme, Helle Mölsted Alvesson
BACKGROUND: Image-based teleconsultation between medical experts and healthcare staff at remote emergency centres can improve the diagnosis of conditions which are challenging to assess. One such condition is burns. Knowledge is scarce regarding how medical experts perceive the influence of such teleconsultation on their roles and relations to colleagues at point of care. METHODS: In this qualitative study, semi-structured interviews were conducted with 15 medical experts to explore their expectations of a newly developed App for burns diagnostics and care prior to its implementation...
2018: PloS One
Apostolos Kiaos, Ioannis Tziatzios, Stavros Hadjimiltiades, Charalambos Karvounis, Theodoros D Karamitsos
Stress perfusion cardiac magnetic resonance (CMR) has been proposed as an important gatekeeper for invasive coronary angiography (ICA) and percutaneous coronary interventions (PCI) in patients evaluated for possible coronary artery disease (CAD) (Fihn et al., 2012; Montalescot et al., 2013) [1], [2]. Several meta-analyses have evaluated the accuracy of stress perfusion CMR to diagnose CAD at the vessel level (Danad et al., 2017; Dai et al., 2016; Jiang et al., 2016; Takx et al., 2015; Li et al., 2015; Desai and Jha, 2013; Jaarsma et al...
February 2018: Data in Brief
Seung Joong Kim, Javier Fernandez-Martinez, Ilona Nudelman, Yi Shi, Wenzhu Zhang, Barak Raveh, Thurston Herricks, Brian D Slaughter, Joanna A Hogan, Paula Upla, Ilan E Chemmama, Riccardo Pellarin, Ignacia Echeverria, Manjunatha Shivaraju, Azraa S Chaudhury, Junjie Wang, Rosemary Williams, Jay R Unruh, Charles H Greenberg, Erica Y Jacobs, Zhiheng Yu, M Jason de la Cruz, Roxana Mironska, David L Stokes, John D Aitchison, Martin F Jarrold, Jennifer L Gerton, Steven J Ludtke, Christopher W Akey, Brian T Chait, Andrej Sali, Michael P Rout
Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility...
March 14, 2018: Nature
Anne-Marie Reid, Jeremy M Brown, Julie M Smith, Alexandra C Cope, Susan Jamieson
CONTEXT: For medical education researchers, a key concern may be the practicalities of gaining ethical approval where this is a national or local requirement. However, in qualitative studies, where the dynamics of human interaction pervade, ethical considerations are an ongoing process which continues long after approval has been granted. Responding to ethical dilemmas arising 'in the moment' requires a reflexive approach whereby the researcher questions his/her own motivations, assumptions and interests...
March 13, 2018: Perspectives on Medical Education
Kenyi Saito-Diaz, Hassina Benchabane, Ajit Tiwari, Ai Tian, Bin Li, Joshua J Thompson, Annastasia S Hyde, Leah M Sawyer, Jeanne N Jodoin, Eduardo Santos, Laura A Lee, Robert J Coffey, R Daniel Beauchamp, Christopher S Williams, Anne K Kenworthy, David J Robbins, Yashi Ahmed, Ethan Lee
Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation...
March 12, 2018: Developmental Cell
Jane S Richardson, Christopher J Williams, Bradley J Hintze, Vincent B Chen, Michael G Prisant, Lizbeth L Videau, David C Richardson
Traditionally, validation was considered to be a final gatekeeping function, but refinement is smoother and results are better if model validation actively guides corrections throughout structure solution. This shifts emphasis from global to local measures: primarily geometry, conformations and sterics. A fit into the wrong local minimum conformation usually produces outliers in multiple measures. Moving to the right local minimum should be prioritized, rather than small shifts across arbitrary borderlines...
February 1, 2018: Acta Crystallographica. Section D, Structural Biology
Bo Abrahamsen
Clinicians are trained in interpreting risk in our daily practice. While we understand the concept of absolute benefit and absolute harm rates, communicating such figures in a clear and intuitive way to patients is no easy task. And we do not of course work in a vacuum. Patient decisions are influenced by other healthcare providers and in some circumstances those providers will be the actual prescribers and the gatekeepers for testing and treatment.
March 12, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Drew A Vander Wood, Adrian T Keatinge-Clay
Here, the term "module" is redefined for trans-acyltransferase (trans-AT) assembly lines to agree with how its domains cooperate and evolutionarily co-migrate. The key domain in both the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) modules of assembly lines is the acyl carrier protein (ACP). ACPs not only relay growing acyl chains through the assembly line but also collaborate with enzymes in modules, both in cis and in trans, to add a specific chemical moiety. A ketosynthase (KS) downstream of ACP often plays the role of gatekeeper, ensuring that only a single intermediate generated by the enzymes of a module is passed downstream...
March 10, 2018: Proteins
Rao Mukkavilli, Gajanan Jadhav, Subrahmanyam Vangala
BACKGROUND: Drug transporters function as gatekeepers and modulate drug access into the body and various tissues. Thus a thorough and precise understanding of transporter liability for compound uptake and efflux is critical during drug development. METHODS: In the present study, we assessed the apparent permeability (Papp) and compared the efflux ratio of various compounds in stably transfected Madin-Darby Canine Kidney (MDCKII) cells overexpressing human P-gp (MDCKII-P-gp), human BCRP (MDCKII-BCRP), wild type (MDCKII-WT), and Caco-2 cell monolayers...
March 7, 2018: Current Pharmaceutical Biotechnology
Christine C Lee, Bing Li, Hongtao Yu, Michael J Matunis
The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core...
March 8, 2018: ELife
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
INTRODUCTION: A number of studies indicate that endothelin-1 (ET-1) may act as an inflammatory cell "gatekeeper," by regulating the influx of neutrophils following pulmonary injury. To further examine the role of ET-1 in modulating lung inflammation, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of amiodarone (AM) or 24 h afterwards. METHODS: In both cases, the extent of lung injury and repair was determined by (1) histopathological changes; (2) neutrophil content in bronchoalveolar lavage fluid (BALF); (3) lung collagen content; (4) tumor necrosis factor receptor 1 expression by BALF macrophages; (5) BALF levels of (a) transforming growth factor beta-1, (b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and (c) platelet-derived growth factor BB; (6) alveolar septal cell apoptosis...
March 7, 2018: Lung
Wenfang Dai, Weina Yu, Lixia Xuan, Zhen Tao, Jinbo Xiong
It is now recognized that some gut diseases attribute to polymicrobial pathogens infections. Thus, traditional isolation of single pathogen from disease subjects could bias the identification of causal agents. To fill this gap, using Illumina sequencing of the bacterial 16S rRNA gene, we explored the dynamics of gut bacterial communities over a shrimp disease progression. The results showed significant differences in the gut bacterial communities between healthy and diseased shrimp. Potential pathogens were inferred by a local pathogens database, of which two OTUs (affiliated with Vibrio tubiashii and Vibrio harveyi) exhibited significantly higher abundances in diseased shrimp as compared to healthy subjects...
March 7, 2018: Applied Microbiology and Biotechnology
Sophie Excoffier, Lilli Herzig, Alexandra A N'Goran, Anouk Déruaz-Luyet, Dagmar M Haller
OBJECTIVES: To estimate the prevalence of multimorbidity using a list of 75 chronic conditions derived from the International Classification for Primary Care, Second edition and developed specifically to assess multimorbidity in primary care. Our aim was also to provide prevalence data for multimorbidity in primary care in a country in which general practitioners (GPs) do not play a gatekeeping role in the health system. SETTING: A representative sample of GPs within the Swiss Sentinel Surveillance Network...
March 6, 2018: BMJ Open
F U Jung, C Luck-Sikorski, C Stroh, S G Riedel-Heller
The prevalence of obesity and overweight is constantly rising. Thus, obesity is increasingly considered as one of the most important healthcare problems in Germany. Surgical interventions have been proven to be the only treatment option to achieve sustained weight loss along with a reduction of obesity-related comorbidities in the vast majority of morbidly obese patients. With respect to the small numbers of weight loss surgeries conducted in Germany, several reasons are currently discussed. General practitioners play a very important role in gatekeeping when it comes to decisions about treatment...
March 2, 2018: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
Philip Ketterer, Adithya N Ananth, Diederik S Laman Trip, Ankur Mishra, Eva Bertosin, Mahipal Ganji, Jaco van der Torre, Patrick Onck, Hendrik Dietz, Cees Dekker
The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize artificial NPC mimics that allows controlling the type and copy number of FG-Nups. We constructed 34 nm-wide 3D DNA origami rings and attached different numbers of NSP1, a model yeast FG-Nup, or NSP1-S, a hydrophilic mutant...
March 2, 2018: Nature Communications
Hélène Strick-Marchand, David Durantel
Recently in Cell, Wu et al. (2018) demonstrated that intrinsic expression of a subset of interferon stimulated genes confers resistance to viral infections in stem cells both in vitro and in vivo, while differentiated cells lose this intrinsic gatekeeper expression pattern in favor of inducible interferon responses.
March 1, 2018: Cell Stem Cell
Abdul Hakeem, Fouzia Zahid, Guiting Zhan, Ping Yi, Hai Yang, Lu Gan, Xiangliang Yang
Background: Nanotechnology-based drug delivery systems exhibit promising therapeutic efficacy in cancer chemotherapy. However, ideal nano drug carriers are supposed to be sufficiently internalized into cancer cells and then release therapeutic cargoes in response to certain intracellular stimuli, which has never been an easy task to achieve. Objective: This study is to design mesoporous silica nanoparticles (MSNs)-based pH-responsive nano drug delivery system that is effectively internalized into cancer cells and then release drug in response to lysosomal/endosomal acidified environment...
2018: International Journal of Nanomedicine
Stephanie Zur Nedden, Rafaela Eith, Christoph Schwarzer, Lucia Zanetti, Hartwig Seitter, Friedrich Fresser, Alexandra Koschak, Angus Jm Cameron, Peter J Parker, Gottfried Baier, Gabriele Baier-Bitterlich
Increasing evidence suggests that synapse dysfunctions are a major determinant of several neurodevelopmental and neurodegenerative diseases. Here we identify protein kinase N1 (PKN1) as a novel key player in fine-tuning the balance between axonal outgrowth and presynaptic differentiation in the parallel fiber (PF)-forming cerebellar granule cells (Cgc). Postnatal Pkn1-/- animals showed a defective PF-Purkinje cell (PC) synapse formation. In vitro, Pkn1-/- Cgc exhibited deregulated axonal outgrowth, elevated AKT phosphorylation and higher levels of neuronal differentiation-2 (NeuroD2), a transcription factor preventing presynaptic maturation...
March 1, 2018: Journal of Clinical Investigation
Jennifer Danielson, Courtney Kraus, Curtis G Jefferson, Anita J Cleven, Luke E Rice, Teresa A O'Sullivan
Health system human resource departments are putting new requirements, paperwork, and processes in place to meet new Joint Commission standards for treating students like employees who onboard at the beginning of employment. These processes have significantly increased the workload of experiential education offices and present an additional burden to students. In an attempt to streamline these processes, health systems are contracting with third-party tracking and placement organizations. Converting this process to an electronic one (such as what third-party organizations offer) could present advantages; however, there are many concerns about going through a third-party organization that could control placement decisions...
February 2018: American Journal of Pharmaceutical Education
Aishwarya Pawar, Paradesi Naidu Gollavilli, Shaomeng Wang, Irfan A Asangani
BRD4 plays a major role in the transcription networks orchestrated by androgen receptor (AR) in castration-resistant prostate cancer (CRPC). Several BET inhibitors (BETi) that displace BRD4 from chromatin are being evaluated in clinical trials for CRPC. Here, we describe mechanisms of acquired resistance to BETi that are amenable to targeted therapies in CRPC. BETi-resistant CRPC cells displayed cross-resistance to a variety of BETi in the absence of gatekeeper mutations, exhibited reduced chromatin-bound BRD4, and were less sensitive to BRD4 degraders/knockdown, suggesting a BRD4-independent transcription program...
February 27, 2018: Cell Reports
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