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https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#1
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27896312/the-memory-trace-supporting-lose-shift-responding-decays-rapidly-after-reward-omission-and-is-distinct-from-other-learning-mechanisms-in-rats
#2
Aaron J Gruber, Rajat Thapa
The propensity of animals to shift choices immediately after unexpectedly poor reinforcement outcomes is a pervasive strategy across species and tasks. We report here that the memory supporting such lose-shift responding in rats rapidly decays during the intertrial interval and persists throughout training and testing on a binary choice task, despite being a suboptimal strategy. Lose-shift responding is not positively correlated with the prevalence and temporal dependence of win-stay responding, and it is inconsistent with predictions of reinforcement learning on the task...
November 2016: ENeuro
https://www.readbyqxmd.com/read/27892514/gwas-study-using-dna-pooling-strategy-identifies-association-of-variant-rs4910623-in-or52b4-gene-with-anti-vegf-treatment-response-in-age-related-macular-degeneration
#3
Moeen Riaz, Laura Lorés-Motta, Andrea J Richardson, Yi Lu, Grant Montgomery, Amer Omar, Robert K Koenekoop, John Chen, Philipp Muether, Lebriz Altay, Tina Schick, Sascha Fauser, Dzenita Smailhodzic, Freekje van Asten, Eiko K de Jong, Carel B Hoyng, Kathryn P Burdon, Stuart MacGregor, Robyn H Guymer, Anneke I den Hollander, Paul N Baird
Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients who lost ≥5 ETDRS letters classified as non-responders and all remaining classified as responders)...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27884140/phase-ii-clinical-study-of-valproic-acid-plus-cisplatin-and-cetuximab-in-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-head-and-neck-v-chance-trial
#4
Francesco Caponigro, Elena Di Gennaro, Franco Ionna, Francesco Longo, Corrado Aversa, Ettore Pavone, Maria Grazia Maglione, Massimiliano Di Marzo, Paolo Muto, Ernesta Cavalcanti, Antonella Petrillo, Fabio Sandomenico, Piera Maiolino, Roberta D'Aniello, Gerardo Botti, Rossella De Cecio, Nunzia Simona Losito, Stefania Scala, Annamaria Trotta, Andrea Ilaria Zotti, Francesca Bruzzese, Antonio Daponte, Ester Calogero, Massimo Montano, Monica Pontone, Gianfranco De Feo, Francesco Perri, Alfredo Budillon
BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds...
November 25, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27851831/speeding-access-to-vaccines-and-medicines-in-low-and-middle-income-countries-a-case-for-change-and-a-framework-for-optimized-product-market-authorization
#5
Vincent Ahonkhai, Samuel F Martins, Alexandre Portet, Murray Lumpkin, Dan Hartman
BACKGROUND: The United Nations Millennium Development Goals galvanized global efforts to alleviate suffering of the world's poorest people through unprecedented public-private partnerships. Donor aid agencies have demonstrably saved millions of lives that might otherwise have been lost to disease through increased access to quality-assured vaccines and medicines. Yet, the introduction of these health interventions in low- and middle-income countries (LMICs) continues to face a time lag due to factors which remain poorly understood...
2016: PloS One
https://www.readbyqxmd.com/read/27846237/integrated-genomics-identifies-mir-32-mcl-1-pathway-as-a-critical-driver-of-melanomagenesis-implications-for-mir-replacement-and-combination-therapy
#6
Prasun J Mishra, Pravin J Mishra, Glenn Merlino
AIMS: Cutaneous malignant melanoma is among the deadliest human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous...
2016: PloS One
https://www.readbyqxmd.com/read/27793425/impact-of-tofacitinib-treatment-on-human-b-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#7
Marta Rizzi, Raquel Lorenzetti, Kathleen Fischer, Julian Staniek, Iga Janowska, Arianna Troilo, Valentina Strohmeier, Miriam Erlacher, Mirjam Kunze, Bettina Bannert, Diego Kyburz, Reinhard E Voll, Nils Venhoff, Jens Thiel
B-cells are pivotal to the pathogenesis of rheumatoid arthritis and tofacitinib, a JAK inhibitor, is effective and safe in its treatment. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain. Despite extensive data on T-lymphocytes, the impact of tofacitinib on B-lymphocytes is poorly understood. In this study we assessed the effect of tofacitinib on B-lymphocyte differentiation and function. Tofacitinib treatment strongly impaired in vitro plasmablast development, immunoglobulin secretion and induction of B-cell fate determining transcription factors, Blimp-1, Xbp-1, and IRF-4, in naïve B-cells...
October 26, 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27781005/an-independent-review-and-accountability-mechanism-for-the-sustainable-development-goals-the-possibilities-of-a-framework-convention-on-global-health
#8
Eric A Friedman
The Framework Convention on Global Health (FCGH), a proposed global treaty to be rooted in the right to health and aimed at health equity, could establish a nuanced, layered, and multi-faceted regime of compliance with, and accountability to, the right to health. In so doing, it would significantly strengthen accountability for the health-related Sustainable Development Goals (SDGs), which it would encompass. Legally binding, the FCGH could facilitate accountability through the courts and catalyze comprehensive domestic accountability regimes, requiring national strategies that include transparency, community and national mechanisms for accountability and participation and an enabling environment for social empowerment...
June 2016: Health and Human Rights
https://www.readbyqxmd.com/read/27761200/catch-me-if-you-can-leukemia-escape-after-cd19-directed-t-cell-immunotherapies
#9
Marco Ruella, Marcela V Maus
Immunotherapy is the revolution in cancer treatment of this last decade. Among multiple approaches able to harness the power of the immune system against cancer, T cell based immunotherapies represent one of the most successful examples. In particular, biotechnological engineering of protein structures, like the T cell receptor or the immunoglobulins, allowed the generation of synthetic peptides like chimeric antigen receptors and bispecific antibodies that are able to redirect non-tumor specific T cells to recognize and kill leukemic cells...
2016: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/27751673/differences-in-the-association-of-nocturia-and-functional-outcomes-of-sleep-by-age-and-gender-a-cross-sectional-population-based-study
#10
Camille P Vaughan, Constance H Fung, Alison J Huang, Theodore M Johnson, Alayne D Markland
PURPOSE: Nocturia is associated with poor sleep quality; however, little is known about the relationship between nocturia and sleep quality across different workforce-relevant age groups of adults. This has implications for developing new treatment strategies that are well tolerated across populations. METHODS: We conducted a cross-sectional study involving merged data from the 2005-2006 and 2007-2008 waves of the National Health and Nutrition Examination Survey...
November 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27737684/management-of-delayed-cerebral-ischemia-after-subarachnoid-hemorrhage
#11
Charles L Francoeur, Stephan A Mayer
For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization...
October 14, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27716339/improving-ghana-s-mental-healthcare-through-task-shifting-psychiatrists-and-health-policy-directors-perceptions-about-government-s-commitment-and-the-role-of-community-mental-health-workers
#12
Vincent Israel Opoku Agyapong, Conor Farren, Eilish McAuliffe
BACKGROUND: The scarcity of mental health professionals places specialist psychiatric care out of the reach of most people in low and middle income countries. There is growing interest in the effectiveness of task shifting as a strategy for targeting expanding health care demands in settings with shortages of qualified health personnel. Given this background, the aim of our study was to examine the perceptions of psychiatrists and health policy directors about the policy to expand mental health care delivery in Ghana through a system of task-shifting from psychiatrists to community mental health workers (CMHWs)...
October 1, 2016: Globalization and Health
https://www.readbyqxmd.com/read/27709236/pre-frailty-frailty-and-multimorbidity-prevalences-and-associated-characteristics-from-two-french-national-surveys
#13
C Le Cossec, A-L Perrine, N Beltzer, C Fuhrman, L Carcaillon-Bentata
OBJECTIVE: To estimate the prevalence of pre-frailty, frailty and multimorbidity in individuals without disability in France. To describe independent determinants of each indicators. DESIGN: Two nationally representative cross-sectional French surveys. SETTINGS: Wave 2012 of the Health, Health Care and Insurance Survey (Enquête Santé et Protection Sociale, ESPS) and data from the Disability Healthcare Household section Survey (Enquête Handicap Santé - Ménages, HSM) from 2008...
2016: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/27668691/health-literacy-mediates-the-relationship-between-educational-attainment-and-health-behavior-a-danish-population-based-study
#14
Karina Friis, Mathias Lasgaard, Gillian Rowlands, Richard H Osborne, Helle T Maindal
Individuals with a lower education level frequently have unhealthier behaviors than individuals with a higher education level, but the pathway is not fully understood. The aim of this study was to investigate whether health literacy mediates the association between educational attainment and health behavior (smoking, physical inactivity, poor diet) and obesity. The study included respondents ages 25 years or older drawn from a large population-based survey conducted in 2013 (N = 29,473). Two scales from the Health Literacy Questionnaire were used: (a) Understanding health information well enough to know what to do and (b) Ability to actively engage with health care providers...
2016: Journal of Health Communication
https://www.readbyqxmd.com/read/27663199/identifying-candidates-for-targeted-gait-rehabilitation-after-stroke-better-prediction-through-biomechanics-informed-characterization
#15
Louis N Awad, Darcy S Reisman, Ryan T Pohlig, Stuart A Binder-Macleod
BACKGROUND: Walking speed has been used to predict the efficacy of gait training; however, poststroke motor impairments are heterogeneous and different biomechanical strategies may underlie the same walking speed. Identifying which individuals will respond best to a particular gait rehabilitation program using walking speed alone may thus be limited. The objective of this study was to determine if, beyond walking speed, participants' baseline ability to generate propulsive force from their paretic limbs (paretic propulsion) influences the improvements in walking speed resulting from a paretic propulsion-targeting gait intervention...
September 23, 2016: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/27662653/high-grade-salivary-gland-involvement-assessed-by-histology-or-ultrasonography-is-associated-with-a-poor-response-to-a-single-rituximab-course-in-primary-sj%C3%A3-gren-s-syndrome-data-from-the-tears-randomized-trial
#16
Divi Cornec, Sandrine Jousse-Joulin, Sebastian Costa, Thierry Marhadour, Pascale Marcorelles, Jean-Marie Berthelot, Eric Hachulla, Pierre-Yves Hatron, Vincent Goeb, Olivier Vittecoq, Emmanuel Nowak, Jacques-Olivier Pers, Valérie Devauchelle-Pensec, Alain Saraux
PURPOSE: To determine whether the severity of salivary-gland involvement, assessed using salivary gland ultrasonography [SGUS], histological focus score, or the unstimulated whole salivary flow [UWSF], was associated with the response to rituximab in patients with primary Sjögren's syndrome [pSS]. MATERIALS AND METHODS: Among the 120 patients with pSS enrolled in the randomised TEARS trial of rituximab versus placebo, 35 underwent either centralised minor salivary-gland biopsy or SGUS at inclusion...
2016: PloS One
https://www.readbyqxmd.com/read/27641075/a-systematic-review-of-health-outcomes-among-disaster-and-humanitarian-responders
#17
Stephanie C Garbern, Laura G Ebbeling, Susan A Bartels
: Introduction Disaster and humanitarian responders are at-risk of experiencing a wide range of physical and psychological health conditions, from minor injuries to chronic mental health problems and fatalities. This article reviews the current literature on the major health outcomes of responders to various disasters and conflicts in order to better inform individuals of the risks and to inform deploying agencies of the health care needs of responders. METHODS: In March 2014, an EMBASE search was conducted using pre-defined search criteria...
December 2016: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/27639173/a-qualitative-analysis-of-low-income-smokers-responses-to-tobacco-excise-tax-increases
#18
Janet Hoek, Katie Smith
BACKGROUND: While increasing the excise tax applied to tobacco products reduces consumption and smoking prevalence, it may also cause hardship among smokers who do not quit. We explored how smokers living on a low income respond to increasing tobacco excise taxes. METHODS: Using a social justice perspective, we explored the increasing costs of tobacco with a sample of 27 adult smokers who live below the poverty line (i.e., with an income less than 60% of the median New Zealand income)...
September 14, 2016: International Journal on Drug Policy
https://www.readbyqxmd.com/read/27633317/a-mixed-methods-study-of-the-administration-of-flucloxacillin-oral-liquid-identifying-strategies-to-overcome-administration-issues-of-medicines-with-poor-palatability
#19
Claudia Rouse, Punam Mistry, Oli Rayner, Jess Nickless, Mandy Wan, Kevin W Southern, Hannah K Batchelor
BACKGROUND: The palatability of flucloxacillin oral liquid is poor. Parents/carers use strategies to aid the administration of poorly palatable medicines. AIM: To assess views on the palatability of flucloxacillin oral liquid and identify factors associated with successful administration. METHODS: A mixed methods study which included a structured review of online forums and a survey of parent/carers of children with cystic fibrosis (CF) to obtain parent/carer views on the administration of flucloxacillin oral liquid...
September 16, 2016: International Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/27631112/caregiver-activation-and-home-hospice-nurse-communication-in-advanced-cancer-care
#20
Catherine E Dingley, Margaret Clayton, Djin Lai, Katherine Doyon, Maija Reblin, Lee Ellington
BACKGROUND: Activated patients have the skills, knowledge, and confidence to manage their care, resulting in positive outcomes such as lower hospital readmission and fewer adverse consequences due to poor communication with providers. Despite extensive evidence on patient activation, little is known about activation in the home hospice setting, when family caregivers assume more responsibility in care management. OBJECTIVE: We examined caregiver and nurse communication behaviors associated with caregiver activation during home hospice visits of patients with advanced cancer using a prospective observational design...
September 14, 2016: Cancer Nursing
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