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https://www.readbyqxmd.com/read/27903281/improving-the-clinical-management-of-traumatic-brain-injury-through-the-pharmacokinetic-modeling-of-peripheral-blood-biomarkers
#1
Aaron Dadas, Jolewis Washington, Nicola Marchi, Damir Janigro
BACKGROUND: Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence on variables other than the disease condition itself. These include half-life in blood, molecular weight, and marker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To study these factors, and to provide a method for markers' analyses, we developed a kinetic model that allows the integrated interpretation of these properties...
November 30, 2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27902866/bacterial-community-collapse-a-meta-analysis-of-the-sinonasal-microbiota-in-chronic-rhinosinusitis
#2
Brett Wagner Mackenzie, David W Waite, Michael Hoggard, Richard G Douglas, Michael W Taylor, Kristi Biswas
Chronic rhinosinusitis (CRS) is a common, debilitating condition characterized by long-term inflammation of the nasal cavity and paranasal sinuses. The role of the sinonasal bacteria in CRS is unclear. We conducted a meta-analysis combining and reanalyzing published bacterial 16S rRNA sequence data to explore differences in sinonasal bacterial community composition and predicted function between healthy and CRS affected subjects. The results identify the most abundant bacteria across all subjects as Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus, and an unclassified lineage of Actinobacteria...
November 30, 2016: Environmental Microbiology
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#3
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27891677/staurosporine-scaffold-based-rational-discovery-of-the-wild-type-sparing-reversible-inhibitors-of-egfr-t790m-gatekeeper-mutant-in-lung-cancer-with-analog-sensitive-kinase-technology
#4
Xiaoyun Song, Xingcai Liu, Xi Ding
The human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first-line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small-molecule kinase inhibitors in EGFR-targeted chemotherapy. Previously, the reversible pan-kinase inhibitor staurosporine and its several analogs such as Gö6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFR(T790M) ) over wild-type kinase (EGFR(WT) ), suggesting that the staurosporine scaffold is potentially to develop the wild-type sparing reversible inhibitors of EGFR(T790M) ...
November 28, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27891077/presynaptic-g-protein-coupled-receptors-gatekeepers-of-addiction
#5
REVIEW
Kari A Johnson, David M Lovinger
Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses and G protein-coupled receptors (GPCRs) that have slower neuromodulatory actions...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27890732/programmed-near-infrared-light-responsive-drug-delivery-system-for-combined-magnetic-tumor-targeting-magnetic-resonance-imaging-and-chemo-phototherapy
#6
Qianhua Feng, Yuanyuan Zhang, Wanxia Zhang, Yongwei Hao, Yongchao Wang, Hongling Zhang, Lin Hou, Zhenzhong Zhang
: In this study, an intelligent drug delivery system was developed by capping doxorubicin (DOX)-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with superparamagnetic iron oxide nanoparticles (IONPs). Under near infrared (NIR) light irradiation, the versatile HMCuS NPs could exploit the merits of both photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Herein, the multifunctional IONPs as gatekeeper with the enhanced capping efficiency were supposed to realize "zero premature release" and minimize the adverse side effects during the drug delivery in vivo...
November 24, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27888070/phosphoramide-mustard-induces-autophagy-markers-and-mtor-inhibition-prevents-follicle-loss-due-to-phosphoramide-mustard-exposure
#7
Jill A Madden, Porsha Q Thomas, Aileen F Keating
Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide. Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO) or PM (60μM) ± LY294002 or rapamycin for 2 or 4 d. Transmission election microscopy revealed abnormally large golgi apparatus and electron dense mitochondria in PM-exposed ovaries prior to and at the time of follicle depletion. PM exposure increased (P<0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr, Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P<0...
November 22, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27885005/immunity-around-the-clock
#8
REVIEW
Kevin Man, Andrew Loudon, Ajay Chawla
Immunity is a high-cost, high-benefit trait that defends against pathogens and noxious stimuli but whose overactivation can result in immunopathologies and sometimes even death. Because many immune parameters oscillate rhythmically with the time of day, the circadian clock has emerged as an important gatekeeper for reducing immunity-associated costs, which, in turn, enhances organismal fitness. This is mediated by interactions between extrinsic environmental cues and the intrinsic oscillators of immune cells, which together optimize immune responses throughout the circadian cycle...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27883305/understanding-transgender-and-medically-assisted-gender-transition-feminism-as-a-critical-resource
#9
Jamie Lindemann Nelson
Feminism has fought the trivialization of women's experiences, championed women's security, and insisted on respect for women's choices. In so doing, feminism has developed important perspectives on the complicated connections between what gender means as it plays itself in people's lives, and the inequalities of power and authority that structure much of human experience. Here, I put a few of these perspectives into contact with an issue where the interactions of gender and power are squarely in play: medicine's role in assisting gender transitioning generally and, specifically, the enduring controversy between medicine and many transgender people about the pathologization of transgender and the role of clinicians as gatekeepers to gender-transition interventions...
November 1, 2016: AMA Journal of Ethics
https://www.readbyqxmd.com/read/27881216/interacting-network-of-hippo-wnt-%C3%AE-catenin-and-notch-signaling-represses-liver-tumor-formation
#10
Wantae Kim, Sanjoy Kumar Khan, Yingzi Yang
Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to very rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper in hepatocytes that restrains abnormal growth. By rigorous genetic approaches, we have identified an interacting network of the Hippo, Wnt/β-catenin and Notch signaling pathways that controls organ size and HCC development...
November 24, 2016: BMB Reports
https://www.readbyqxmd.com/read/27878688/outpatient-visits-after-retirement-in-europe-and-the-us
#11
Anikó Bíró
I conduct an empirical analysis of the relation between retirement and outpatient care use in Europe and the US, and investigate the potential driving factors of that. I link the empirical analysis to a theoretical model of medical care demand. I document that pensioners tend to visit a doctor with higher probability and more often than the rest of the 50+ population. Ceteris paribus, being retired implies 3-10 % more outpatient visits in Europe. The estimates are of similar magnitude in the US. The paper contributes to the understanding of how population ageing plays a part in the rising health care expenditures...
December 2016: Int J Health Econ Manag
https://www.readbyqxmd.com/read/27878675/supplementing-gatekeeping-with-a-revenue-scheme-for-secondary-care-providers
#12
Tor Iversen, Anastasia Mokienko
We study implications of a change in the payment scheme for radiology providers in Norway that was implemented in 2008. The change implies reduced fee-for-service and increased fixed budget for a contracted volume of services. A consequence of the change is that private providers have less incentive to conduct examinations beyond the contracted volume. Different from the situation observed before the change in 2008, the volume is no longer determined by the demand side, and a rationing of the supply occurs...
September 2016: Int J Health Econ Manag
https://www.readbyqxmd.com/read/27875018/the-process-and-challenges-of-obtaining-and-sustaining-clinical-placements-for-nursing-and-allied-health-students
#13
Christine Taylor, Liz Angel, Lucy Nyanga, Cathy Dickson
AIMS AND OBJECTIVES: This paper describes the process and challenges from a project that aimed to develop processes, source new placements, and place students primarily in the discipline of Nursing, but also Occupational Therapy, Physiotherapy, Podiatry, Social Work, and Speech Therapy. BACKGROUND: Clinical experience in health facilities is an essential element of health professional education, yet globally there is a lack of clinical placements to meet demands...
November 22, 2016: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/27874013/crystal-structure-of-fabz-acp-complex-reveals-a-dynamic-seesaw-like-catalytic-mechanism-of-dehydratase-in-fatty-acid-biosynthesis
#14
Lin Zhang, Jianfeng Xiao, Jianrong Xu, Tianran Fu, Zhiwei Cao, Liang Zhu, Hong-Zhuan Chen, Xu Shen, Hualiang Jiang, Liang Zhang
Fatty acid biosynthesis (FAS) is a vital process in cells. Fatty acids are essential for cell assembly and cellular metabolism. Abnormal FAS directly correlates with cell growth delay and human diseases, such as metabolic syndromes and various cancers. The FAS system utilizes an acyl carrier protein (ACP) as a transporter to stabilize and shuttle the growing fatty acid chain throughout enzymatic modules for stepwise catalysis. Studying the interactions between enzymatic modules and ACP is, therefore, critical for understanding the biological function of the FAS system...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27871239/lesbian-womens-access-to-healthcare-experiences-with-and-expectations-towards-gps-in-german-primary-care
#15
Oliver Hirsch, Karina Löltgen, Annette Becker
BACKGROUND: Lesbian women have higher rates of physical and psychiatric disorders associated with experiences of discrimination, homophobia and difficulties with coming out. Therefore, easy access to specialized healthcare in an open atmosphere is needed. We aimed to describe women's access to and experiences with healthcare in Germany, and to assess the responsibility of the general practitioner (GP) compared to other specialities providing primary health care. METHODS: A questionnaire study was conducted via internet and paper-based sampling...
November 21, 2016: BMC Family Practice
https://www.readbyqxmd.com/read/27868108/inflammatory-monocytes-hinder-antiviral-b-cell-responses
#16
Stefano Sammicheli, Mirela Kuka, Pietro Di Lucia, Nereida Jimenez de Oya, Marco De Giovanni, Jessica Fioravanti, Claudia Cristofani, Carmela G Maganuco, Benedict Fallet, Lucia Ganzer, Laura Sironi, Marta Mainetti, Renato Ostuni, Kevin Larimore, Philip D Greenberg, Juan Carlos de la Torre, Luca G Guidotti, Matteo Iannacone
Antibodies are critical for protection against viral infections. However, several viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction of early protective antibody responses by poorly understood mechanisms. Here we analyzed the spatiotemporal dynamics of B cell activation to show that, upon subcutaneous infection, LCMV-specific B cells readily relocate to the interfollicular and T cell areas of the draining lymph node where they extensively interact with CD11b(+)Ly6C(hi) inflammatory monocytes...
October 21, 2016: Science Immunology
https://www.readbyqxmd.com/read/27864349/substantial-equivalence-standards-in-tobacco-governance-statutory-clarity-and-regulatory-precedent-for-the-fsptca
#17
Daniel Carpenter, Gregory N Connolly, Lauren Kass Lempert
The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 creates the first national system of pre-market regulation of tobacco products in American history. The FDA must now review and give marketing authorization to all new tobacco products, based upon a public health standard, before they can be legally marketed. Yet the law also contains an alternative pathway for market entry-the substantial equivalence (SE) clause-by which novel and altered tobacco products can be marketed by demonstrating their substantial equivalence to existing products...
November 18, 2016: Journal of Health Politics, Policy and Law
https://www.readbyqxmd.com/read/27859876/power-and-resistance-within-the-hospital-s-hierarchical-system-the-experiences-of-chronically-ill-patients
#18
Odette Griscti, Megan Aston, Grace Warner, Ruth Martin-Misener, Deborah McLeod
AIMS AND OBJECTIVES: To explore experiences of chronically ill patients and registered nurses when they negotiate patient care in hospital settings. Specifically, we explored how social and institutional discourses shape power relations during the negotiation process. BACKGROUND: The hospital system is embedded in a hierarchical structure where the voice of the healthcare provider as expert is often given more importance than the patient. This system has been criticised as being oppressive to patients who are perceived to be lower in the hierarchy...
May 18, 2016: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/27856705/the-plant-energy-sensor-evolutionary-conservation-and-divergence-of-snrk1-structure-regulation-and-function
#19
REVIEW
Tom Broeckx, Sander Hulsmans, Filip Rolland
The SnRK1 (SNF1-related kinase 1) kinases are the plant cellular fuel gauges, activated in response to energy-depleting stress conditions to maintain energy homeostasis while also gatekeeping important developmental transitions for optimal growth and survival. Similar to their opisthokont counterparts (animal AMP-activated kinase, AMPK, and yeast Sucrose Non-Fermenting 1, SNF), they function as heterotrimeric complexes with a catalytic (kinase) α subunit and regulatory β and γ subunits. Although the overall configuration of the kinase complexes is well conserved, plant-specific structural modifications (including a unique hybrid βγ subunit) and associated differences in regulation reflect evolutionary divergence in response to fundamentally different lifestyles...
December 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27855579/engaging-offenders-on-probation-in-health-research-lessons-from-the-field
#20
Coral Sirdifield, Sara Owen, Charlie Brooker
Background Offenders on probation are considered to be 'hard to reach' by researchers because probation is a 'closed setting' and engaging offenders in research can be problematic due to issues such as return to custody and chaotic lifestyles. Aim To share learning about the challenges encountered when undertaking research with offenders on probation in the UK, strategies for overcoming them and the implications for research design and outcomes. Discussion The authors identify challenges in gaining and maintaining access; recruitment; ethics; data collection and analysis; and dissemination of findings...
November 18, 2016: Nurse Researcher
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