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https://www.readbyqxmd.com/read/29149179/postmenopausal-hormone-therapy-and-risk-of-stroke-a-pooled-analysis-of-data-from-population-based-cohort-studies
#1
Germán D Carrasquilla, Paolo Frumento, Anita Berglund, Christer Borgfeldt, Matteo Bottai, Chiara Chiavenna, Mats Eliasson, Gunnar Engström, Göran Hallmans, Jan-Håkan Jansson, Patrik K Magnusson, Peter M Nilsson, Nancy L Pedersen, Alicja Wolk, Karin Leander
BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29148565/tobacco-cessation-interventions-for-young-people
#2
REVIEW
Thomas R Fanshawe, William Halliwell, Nicola Lindson, Paul Aveyard, Jonathan Livingstone-Banks, Jamie Hartmann-Boyce
BACKGROUND: Most tobacco control programmes for adolescents are based around prevention of uptake, but teenage smoking is still common. It is unclear if interventions that are effective for adults can also help adolescents to quit. This is the update of a Cochrane Review first published in 2006. OBJECTIVES: To evaluate the effectiveness of strategies that help young people to stop smoking tobacco. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register in June 2017...
November 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29147630/sulforaphane-from-broccoli-reduces-symptoms-of-autism-a-follow-up-case-series-from-a-randomized-double-blind-study
#3
Rhoda Lynch, Eileen L Diggins, Susan L Connors, Andrew W Zimmerman, Kanwaljit Singh, Hua Liu, Paul Talalay, Jed W Fahey
Introduction: Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD...
2017: Global Advances in Health and Medicine: Improving Healthcare Outcomes Worldwide
https://www.readbyqxmd.com/read/29146569/found-in-translation-how-preclinical-research-is-guiding-the-clinical-development-of-the-bcl2-selective-inhibitor-venetoclax
#4
REVIEW
Joel D Leverson, Deepak Sampath, Andrew J Souers, Saul H Rosenberg, Wayne J Fairbrother, Martine Amiot, Marina Konopleva, Anthony Letai
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax...
November 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29142981/commercial-kidney-transplantation-attitude-knowledge-perception-and-experience-of-recipients
#5
Fatma Al Rahbi, Issa Al Salmi
Introduction: Kidney transplantation is the gold standard for patients with end-stage kidney disease. In view of shortages of available organs, long wait times for possible transplantation, and strict regulation, many patients opt for commercial transplantation. This study elicits the reasons and motivations for patients with end-stage kidney disease to elect for commercial transplant. Methods: A questionnaire-based evaluation was conducted during the period from July 2015 until late December 2015...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29137385/improved-outcome-of-haploidentical-transplantation-in-severe-aplastic-anemia-using-reduced-intensity-fludarabine-based-conditioning
#6
Wu Yamei, Luo Rongmu, Cao Yongbin, Si Yingjian, Li Xiaohong, Zhang Xiaomei, Yan Pei, Du Zhenlan, Wang Haitao, Wang Jing, Wang Bojing, Wu Xiaoxiong, Da Wanming
Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137309/anti-proliferative-and-pro-apoptotic-effects-induced-by-simultaneous-inactivation-of-her1-and-her2-through-endogenous-polyclonal-antibodies
#7
Narjara González Suárez, Gretchen Bergado Báez, Mabel Cruz Rodríguez, Amelia Gutiérrez Pérez, Lisset Chao García, Diana Rosa Hernández Fernández, Judith Raymond Pous, Belinda Sánchez Ramírez
The human epidermal growth factor receptor (HER1) and its partner HER2 are extensively described oncogenes and validated targets for cancer therapy. However, the effectiveness of monospecific therapies targeting these receptors is hampered by resistance emergence, which is frequently associated with the upregulation of other members of HER family. Combined therapies using monoclonal antibodies or tyrosine kinase inhibitors have been suggested as a promising strategy to circumvent this resistance mechanism. We propose an alternative approach based on simultaneous inactivation of HER1 and HER2 by multi-epitope blockade with specific polyclonal antibodies induced by vaccination...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133936/the-rho-gtpase-signalling-pathway-in-urothelial-carcinoma
#8
REVIEW
Solomon L Woldu, Ryan C Hutchinson, Laura-Maria Krabbe, Oner Sanli, Vitaly Margulis
Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29133366/lifestyle-and-reproductive-factors-and-ovarian-cancer-risk-by-p53-and-mapk-expression
#9
Holly R Harris, Megan S Rice, Amy L Shafrir, Elizabeth M Poole, Mamta Gupta, Jonathan L Hecht, Kathryn L Terry, Shelley S Tworoger
BACKGROUND: One model of ovarian cancer development model divides tumors into two types. Type I tumors are characterized by KRAS and BRAF mutations, which can activate mitogen-activated protein kinase (MAPK). Type II tumors are characterized by tubal precursor lesions with p53 mutations. We evaluated the association between lifestyle and reproductive factors and risk of ovarian cancer defined by p53 and MAPK expression. METHODS: Epithelial ovarian cancer cases (n=274) and controls (n=1907) were identified from the Nurses' Health Study (NHS) and NHSII prospective cohorts, and the population-based New England Case-Control study...
November 13, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29132018/the-provision-of-accredited-higher-education-on-dementia-in-six-european-countries-an-exploratory-study
#10
Simona Hvalič-Touzery, Brigita Skela-Savič, Rhoda Macrae, Anna Jack-Waugh, Debbie Tolson, Amanda Hellström, Wilson de Abreu, Katja Pesjak
BACKGROUND: The World Health Organization has identified developing the knowledge and skills of healthcare professionals who are involved in dementia care as a priority. Most healthcare professionals lack the necessary knowledge, skills and understanding to provide high quality dementia care. While dementia education amongst most UK university health and social care programmes is inconsistent, we know little about the provision of dementia education in European universities. OBJECTIVES: To examine the provision of accredited higher education on dementia in European countries, to illustrate that it is highly variable despite universities being the major provider of education for healthcare professionals internationally...
November 6, 2017: Nurse Education Today
https://www.readbyqxmd.com/read/29130289/development-and-pilot-testing-of-a-parent-reported-health-related-quality-of-life-measure-for-children-on-the-ketogenic-diet-the-ketoqol
#11
Katie Barwick, Tamara Parker, Nicole Murphy, Alwyn Todd, Michael Leveritt, Shelley A Wilkinson
AIM: The aim of the present study was to develop a parent-reported tool that will measure health-related quality of life (HRQoL) in children following ketogenic diet (KD) therapies for refractory epilepsy once it has been pilot tested and analysed. METHODS: Parents of children following KD therapies for epilepsy were recruited through a public hospital in Queensland, Australia, in 2012 and 2014. Qualitative semistructured interviews were conducted in 2012 with 13 parents who described changes seen in their child's HRQoL while on the KD...
November 2017: Nutrition & Dietetics: the Journal of the Dietitians Association of Australia
https://www.readbyqxmd.com/read/29130076/crispr-correction-of-a-homozygous-low-density-lipoprotein-receptor-mutation-in-familial-hypercholesterolemia-induced-pluripotent-stem-cells
#12
Linda Omer, Elizabeth A Hudson, Shirong Zheng, James B Hoying, Yuan Shan, Nolan L Boyd
Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans...
November 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29129184/identifying-attributes-of-care-that-may-improve-cost-effectiveness-in-the-youth-mental-health-service-system
#13
Matthew P Hamilton, Sarah E Hetrick, Cathrine Mihalopoulos, David Baker, Vivienne Browne, Andrew M Chanen, Kerryn Pennell, Rosemary Purcell, Heather Stavely, Patrick D McGorry
OBJECTIVE: To identify attributes of youth mental health care for which there is evidence of potential cost-effectiveness. STUDY DESIGN: We performed a literature review of economic evaluations that examined both costs and outcomes for attributes of youth mental health care other than pharmacological or individual psychological therapies for full-threshold disorders. DATA SOURCES: We searched the United Kingdom National Health Service Economic Evaluations Database for evaluations published to the end of 2014; and MEDLINE, Google Scholar and the citation lists of relevant publications for peer-reviewed studies published in English since 1997...
November 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/29128371/assessments-of-neurocognitive-and-behavioral-function-in-the-mucopolysaccharidoses
#14
REVIEW
Elsa G Shapiro, Maria L Escolar, Kathleen A Delaney, John J Mitchell
The mucopolysaccharidoses (MPS) are a group of rare, inherited lysosomal storage disorders in which accumulation of glycosaminoglycans (GAGs) leads to progressive tissue and organ dysfunction. In addition to a variety of somatic signs and symptoms, patients with rapidly progressing MPS I (Hurler), II, III, and VII can present with significant neurological manifestations, including impaired cognitive abilities, difficulties in language and speech, behavioral abnormalities, sleep problems, and/or seizures. Neurological symptoms have a substantial impact on the quality of life of MPS patients and their families...
September 15, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29127708/calcimimetic-and-calcilytic-therapies-for-inherited-disorders-of-the-calcium-sensing-receptor-signalling-pathway
#15
REVIEW
Fadil M Hannan, Mie K Olesen, Rajesh V Thakker
THE CALCIUM-SENSING RECEPTOR (CAS RECEPTOR) PLAYS A PIVOTAL ROLE IN EXTRACELLULAR CALCIUM HOMEOSTASIS AND GERMLINE LOSS- AND GAIN-OF-FUNCTION MUTATIONS CAUSE FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) AND AUTOSOMAL DOMINANT HYPOCALCAEMIA (ADH), RESPECTIVELY. CAS RECEPTOR SIGNAL TRANSDUCTION IN THE PARATHYROID GLANDS IS LIKELY REGULATED BY G-PROTEIN SUBUNIT Α11 (GΑ11) AND ADAPTOR-RELATED PROTEIN COMPLEX-2 SIGMA SUBUNIT (AP2Σ), AND RECENT STUDIES HAVE IDENTIFIED GERMLINE MUTATIONS OF THESE PROTEINS AS A CAUSE OF FHH AND/OR ADH...
November 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29127433/targeting-and-suppression-of-her3-positive-breast-cancer-by-t-lymphocytes-expressing-a-heregulin-chimeric-antigen-receptor
#16
Bai-Le Zuo, Bo Yan, Guo-Xu Zheng, Wen-Jin Xi, Xiao Zhang, An-Gang Yang, Lin-Tao Jia
Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. In this study, we engineered T cells with a CAR consisting of the extracellular domain of heregulin-1β (HRG1β) that is a natural ligand for HER3/HER4, and evaluated the specific cytotoxicity of these CAR-T cells in cultured HER3 positive breast cancer cells and xenograft tumors...
November 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123418/evaluating-the-cost-effectiveness-of-afatinib-after-platinum-based-therapy-for-the-treatment-of-squamous-non-small-cell-lung-cancer-in-france
#17
Maud Pignata, Christos Chouaid, Katell Le Lay, Laura Luciani, Ceilidh McConnachie, James Gordon, Stéphane Roze
Background and aims: Lung cancer has the highest mortality rate of all cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and has an extremely poor prognosis. Afatinib is an irreversible ErbB family blocker designed to suppress cellular signaling and inhibit cellular growth and is approved in Europe after platinum-based therapy for squamous NSCLC. The objective of the present analysis was to evaluate the cost-effectiveness of afatinib after platinum-based therapy for squamous NSCLC in France...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29121992/a-mouse-anti-myostatin-antibody-increases-muscle-mass-and-improves-muscle-strength-and-contractility-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-and-its-humanized-equivalent-domagrozumab-pf-06252616-increases-muscle-volume-in-cynomolgus-monkeys
#18
Michael St Andre, Mark Johnson, Prashant N Bansal, Jeremy Wellen, Andrew Robertson, Alan Opsahl, Peter M Burch, Peter Bialek, Carl Morris, Jane Owens
BACKGROUND: The treatments currently approved for Duchenne muscular dystrophy (DMD), a progressive skeletal muscle wasting disease, address the needs of only a small proportion of patients resulting in an urgent need for therapies that benefit all patients regardless of the underlying mutation. Myostatin is a member of the transforming growth factor-β (TGF-β) family of ligands and is a negative regulator of skeletal muscle mass. Loss of myostatin has been shown to increase muscle mass and improve muscle function in both normal and dystrophic mice...
November 9, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/29118225/activity-of-entrectinib-in-a-patient-with-the-first-reported-ntrk-fusion-in-neuroendocrine-cancer
#19
Darren Sigal, Marie Tartar, Marin Xavier, Fei Bao, Patrick Foley, David Luo, Jason Christiansen, Zachary Hornby, Edna Chow Maneval, Pratik Multani
Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether NTRK alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29115211/measurement-of-gastrointestinal-hormones
#20
Nicolai J Wewer Albrechtsen
Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels...
November 2017: Danish Medical Journal
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