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https://www.readbyqxmd.com/read/28449207/targeting-anti-apoptotic-bcl2-family-proteins-in-haematological-malignancies-from-pathogenesis-to-treatment
#1
REVIEW
Meike Vogler, Harriet S Walter, Martin J S Dyer
The B-cell lymphoma 2 (BCL2) family of proteins comprise key regulators of apoptosis and are implicated in the pathogenesis of many malignancies, including lymphomas and leukaemias. Targeting of BCL2 proteins can be directly toxic to tumour cells or render them more sensitive to chemotherapy. Inhibition of the anti-apoptotic functions of BCL2 proteins using structure-based design to produce specific inhibitors of protein-protein interactions has been achieved for BCL2, MCL1 and BCL-XL (also termed BCL2L1), providing an armamentarium of new targeted therapies called BH3-mimetics...
April 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28448209/solution-focused-brief-therapy-for-chilean-primary-care-patients-exploring-a-linguistic-adaptation
#2
Karla González Suitt, Cynthia Franklin, Rayen Cornejo, Yessenia Castro, Sara Smock Jordan
Solution-focused brief therapy (SFBT) is a resource-based, future-oriented therapeutic approach that focuses on finding exceptions to problems and identifying coping strategies to build solutions. SFBT has been efficacious with individuals with alcohol use disorders. Chile experiences high levels of alcohol consumption and alcohol-related health consequences. Despite the international dissemination of SFBT, this is the first study to attempt a linguistic adaptation of SFBT in a Latin American country. We conducted 9 cognitive interviews to examine 13 translated main SFBT tools and 3 focus groups to gather information on cultural aspects of alcohol use in primary care...
April 27, 2017: Journal of Ethnicity in Substance Abuse
https://www.readbyqxmd.com/read/28446522/improving-opioid-safety-practices-in-primary-care-protocol-for-the-development-and-evaluation-of-a-multifaceted-theory-informed-pilot-intervention-for-healthcare-providers
#3
Pamela Leece, Daniel Z Buchman, Michael Hamilton, Caitlyn Timmings, Yalnee Shantharam, Julia Moore, Andrea D Furlan
INTRODUCTION: In North America, drug overdose deaths are reaching unprecedented levels, largely driven by increasing prescription opioid-related deaths. Despite the development of several opioid guidelines, prescribing behaviours still contribute to poor patient outcomes and societal harm. Factors at the provider and system level may hinder or facilitate the application of evidence-based guidelines; interventions designed to address such factors are needed. METHODS AND ANALYSIS: Using implementation science and behaviour change theory, we have planned the development and evaluation of a comprehensive Opioid Self-Assessment Package, designed to increase adherence to the Canadian Opioid Guideline among family physicians...
April 26, 2017: BMJ Open
https://www.readbyqxmd.com/read/28446516/access-to-non-statin-lipid-lowering-therapies-in-patients-at-high-risk-of-atherosclerotic-cardiovascular-disease
#4
Joshua W Knowles, William B Howard, Lala Karayan, Seth J Baum, Katherine A Wilemon, Christie M Ballantyne, Kelly D Myers
High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins(1, 2) In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level <100.(3) Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28446118/motor-neurone-disease-progress-and-challenges
#5
Thanuja Dharmadasa, Robert D Henderson, Paul S Talman, Richard Al Macdonell, Susan Mathers, David W Schultz, Merrillee Needham, Margaret Zoing, Steve Vucic, Matthew C Kiernan
Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals...
May 1, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#6
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28444652/-establishment-of-specialized-pediatric-palliative-home-care-in-the-medical-valley-of-the-european-metropolitan-area-nuremberg
#7
Steven Hébert, Chara Gravou-Apostolatou, Wolfgang Rascher
Background As part of the 2007 health reform in Germany the structure of outpatient palliative care for children and adolescents was adopted for the first time and then implemented in Erlangen-Nuremberg in 2009. Methods The introduction of Pediatric Palliative Home Care (PPHC) at the Hospital for Children and Adolescents at the University of Erlangen-Nuremberg was retrospectively analyzed between the years 2009 to 2014. Referring medical records (paper-based and electronic) were evaluated systematically. Results Considering 69 patients within this study, 44 (63...
March 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28443133/analysis-of-purified-pancreatic-islet-beta-and-alpha-cell-transcriptomes-reveals-11%C3%AE-hydroxysteroid-dehydrogenase-hsd11b1-as-a-novel-disallowed-gene
#8
Timothy J Pullen, Mark O Huising, Guy A Rutter
We and others have previously identified a group of genes, dubbed "disallowed," whose expression is markedly lower in pancreatic islets than in other mammalian cell types. Forced mis-expression of several members of this family leads to defective insulin secretion, demonstrating the likely importance of disallowance for normal beta cell function. Up to now, transcriptomic comparisons have been based solely on data from whole islets. This raises the possibilities that (a) there may be important differences in the degree of disallowance of family members between beta and other either neuroendocrine cells; (b) beta (or alpha) cell disallowed genes may have gone undetected...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28441986/medical-therapy-versus-dietary-avoidance-in-eosinophilic-esophagitis-which-approach-is-better
#9
Mirna Chehade, Ellen Sher
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is induced by food triggers and by environmental allergens in some patients. No U.S. Food and Drug Administration approved therapies exist for patients with EoE. Common therapies include topical corticosteroids (TCS) and dietary restriction. METHODS: This article reviewed the pros and cons of a medical versus dietary approach in treating EoE in children and adults...
May 1, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28440681/discovery-and-preclinical-development-of-dasabuvir-for-the-treatment-of-hepatitis-c-infection
#10
Mohamed El Kassas, Tamer Elbaz, Enas Hafez, Mohamed Naguib Wifi, Gamal Esmat
Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families...
April 25, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28439953/feasibility-trial-for-primary-stroke-prevention-in-children-with-sickle-cell-anemia-in-nigeria-spin-trial
#11
Najibah Galadanci, Shehu Umar Abdullahi, Leah D Vance, Abdulkadir Musa Tabari, Shehi Ali, Raymond Belonwu, Auwal Salihu, Aisha Amal Galadanci, Binta Wudil Jibir, Halima Bello-Manga, Kathleen Neville, Fenella J Kirkham, Yu Shyr, Sharon Phillips, Brittany V Covert, Adetola A Kassim, Lori C Jordan, Muktar H Aliyu, Michael R DeBaun
The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥ 200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements < 200 cm/s was followed prospectively...
April 25, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28438729/gathering-opinions-on-depression-information-needs-and-preferences-samples-and-opinions-in-clinic-versus-web-based-surveys
#12
Matthew T Bernstein, John R Walker, Kathryn A Sexton, Alan Katz, Brooke E Beatie
BACKGROUND: There has been limited research on the information needs and preferences of the public concerning treatment for depression. Very little research is available comparing samples and opinions when recruitment for surveys is done over the Web as opposed to a personal invitation to complete a paper survey. OBJECTIVE: This study aimed to (1) to explore information needs and preferences among members of the public and (2) compare Clinic and Web samples on sample characteristics and survey findings...
April 24, 2017: JMIR Mental Health
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#13
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28434913/development-of-school-based-asthma-management-programs-in-rochester-ny
#14
REVIEW
Jill S Halterman, Reynaldo Tajon, Paul Tremblay, Maria Fagnano, Arlene Butz, Tamara Perry, Ken McConnochie
In the spirit of Dr. Haggerty's teachings, we present an overview of our work to improve care for children with asthma in the context of 3 lessons learned:(1) 1) The importance of providing integrated services across disciplinary boundaries for children with chronic illness, 2) The need to move from a care model focused only on the individual child to a model focused on the child, family, and community, and 3) The need to expand beyond the local community and take a broad perspective on improving health on a national level...
April 18, 2017: Academic Pediatrics
https://www.readbyqxmd.com/read/28434482/how-to-implement-clinical-guidelines-to-optimise-familial-hypercholesterolaemia-diagnosis-and-treatment
#15
Michel Farnier, Fernando Civeira, Olivier Descamps
BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is a genetic disorder associated with significantly elevated plasma low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease (CHD). Optimal management of FH relies on early identification and treatment with statins alone or in combination with other lipid-lowering therapies. A lack of awareness of FH and its manifestations among primary care physicians and specialists has led to many individuals being misdiagnosed in the early stages of the disease, further increasing the risk of CHD and requiring much more intensive lipid-lowering strategies...
April 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/28434268/ubiquitin-c-terminal-hydrolase-l1-uch-l1-as-a-therapeutic-and-diagnostic-target-in-neurodegeneration-neurotrauma-and-neuro-injuries
#16
Kevin K Wang, Zhihui Yang, George Sarkis, Isabel Torres, Vijaya Raghavan
Since its discovery as a major CNS-abundant protein 25 years ago, Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has emerged as an important enzyme in regulating brain protein metabolism, by coupling to the proteasome pathway of protein degradation. Areas covered: UCH-L1 is implicated in both familial and sporadic Parkinson disease and other chronic neurodegenerative diseases. Also, UCH-L1 has been recently emerging as a biofluid-based biomarker for various forms of acute neurotrauma and CNS injury. Expert opinion: The loss of UCH-L1 activity coupled with the gain of proteinopathy function are linked to neurodegeneration such as Parkinsonism and Alzheimer's disease...
April 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28432148/systolic-blood-pressure-trajectory-frailty-and-all-cause-mortality-over-80-years-of-age-cohort-study-using-electronic-health-records
#17
Rathi Ravindrarajah, Nisha C Hazra, Shota Hamada, Judith Charlton, Stephen H D Jackson, Alex Dregan, Martin C Gulliford
Background -Clinical trials show benefit from lowering systolic blood pressure in people aged ≥80 years but non-randomised epidemiological studies suggest lower systolic blood pressure may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category over 80 years of age and to evaluate SBP trajectories before death. Methods -A population-based cohort study was conducted using electronic health records of 144,403 participants aged 80 and older registered with family practices in the United Kingdom from 2001 to 2014...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#18
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28429794/bone-in-culture-array-as-a-platform-to-model-early-stage-bone-metastases-and-discover-anti-metastasis-therapies
#19
Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin-Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T C Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A Mancini, Xiang H-F Zhang
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28427526/potential-application-and-prevalence-of-the-cd30-ki-1-antigen-among-solid-tumors-a-focus-review-of-the-literature
#20
REVIEW
Garrett K Berger, Kevin Gee, Cassandra Votruba, Ali McBride, Faiz Anwer
BACKGROUND: CD30 (Ki-1) is a cell membrane protein derived from the tumor necrosis factor (TNF) receptor family. The CD30 antigen has been associated primarily with Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Brentuximab vedotin (BV) is an antibody-drug conjugate targeting the CD30 antigen. FDA approval for BV includes relapsed and refractory HL and sALCL. The CD30 antigen also has been identified in many solid tumors, predominantly of germ cell origins and early clinical data is promising...
May 2017: Critical Reviews in Oncology/hematology
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