tbuckley/cabot-search huggingface dataset:
Abstract P6-05-02: Targeting vesicular trafficking machinery for breast cancer therapeutics
Authors: S Mitra, J Vykoukal, K Jeong, G Mills
Journal: Cancer Research (2018)

Abstract The Rab GTPase family is a key regulator of vesicular import, transport and export. Deregulation of vesicular trafficking promotes undesirable intercellular cross talk via exosomes that contribute to cancer pathophysiology. Preclinical and clinical studies underscore a role for exosomes and their cargo in breast cancer development, progression, metastasis, and resistance to therapy. While many studies have approached the role of exosomes in cancer pathophysiology, the 'rules' governing their production and cargo sorting represents a major unexplored gap in knowledge. Exosomes arise from internal budding of specific endosomal compartments. Rab11 GTPase family members comprised of Rab11a, Rab11b and Rab25 are critical regulators of endocytic cargo trafficking specifically of apical and recycling endosomes. Previously, our lab has shown that Rab25 is amplified and contributes to oncogenesis in both ovarian and Luminal B breast cancers. However, Rab25 is lost and when re-expressed ectopically, it inhibits invasion and migration in Claudin Low tumors suggesting a cell-lineage and context dependent function. Importantly, while in Luminal B cancer, Rab25 and its downstream effector RCP (Rab coupling protein), collaborate in driving oncogenesis, in Her2+ cancers, RCP expression is protective. Further our group recently uncovered the presence of a stroma enriched “reactive protein signature” in ER+/Her- group that is indicative of good outcome for patients. Indeed, many of the “reactive signature” proteins are reported in exosomal cargo by others. Taking together, our ongoing study utilizes a panel of breast cancer cell lines representing ER+ve/Her2+; ER+/Her-, ER-/Her2+, and ER-/Her- to evaluate the role of Rab11 family in modulating vesicular trafficking that alters the exosome biology and how that may contribute to tumor- stroma communications. Our preliminary results show that indeed over expression of Rab25 differentially alters size and number of extracellular vesicles in Luminal B cancers when compared to the Claudin Low subtype. Using a novel class of peptides that interrupt the cellular functions 25, we are investigating if Rab25 expression can be associated with an exosomal cargo profile in each subtype of breast cancer, which could then serve as a biomarker for tumor-stroma interaction. Citation Format: Mitra S, Vykoukal J, Jeong K, Mills G. Targeting vesicular trafficking machinery for breast cancer therapeutics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-02.
Urinary Metabolites Associated with Blood Pressure on a Low- or High-Sodium Diet
Authors: Yuan Cheng, Haiying Song, Xiaoqing Pan, Hong Xue, Yifei Wan, Tao Wang, Zhongmin Tian, Entai Hou, Ian R. Lanza, Pengyuan Liu, Yong Liu, Purushottam W. Laud, Kristie Usa, Yongcheng He, Mingyu Liang
Journal: Theranostics (2018)

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension.Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically.Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day).Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle.The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats.Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex.Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure.The differences in homocysteine levels between low-and high-sodium intakes were significantly associated with the differences in diastolic blood pressure.These associations were significant with or without considering demographic factors.Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats.Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension.
Cost-effectiveness of safer reproduction strategies to prevent HIV in Zimbabwe
Authors: Carolyn Smith Hughes, Caroline Murombedzi, Thandiwe Chirenda, Gift Chareka, Felix Mhlanga, Bismark Mateveke, Serah Gitome, Tinei Makurumure, Allen Matubu, Nyaradzo Mgodi, Zvavahera Chirenje, James G Kahn, Joelle Brown
Journal: The Lancet Global Health (2018)

BackgroundHIV discordance in stable couples is a major driver of new infections, and discordant couples trying to conceive may be particularly at risk. Strategies that can reduce the risk of HIV transmission in these couples include antiretroviral therapy with adequate viral load suppression (ART/VL), oral pre-exposure prophylaxis (PrEP), artificial vaginal insemination (AVI), and semen washing (SW). Understanding the cost-effectiveness of these strategies is important, particularly in HIV endemic settings. Leveraging the ongoing SAFER study in Zimbabwe, we examined the cost-effectiveness of offering these strategies compared to current practice.MethodsThe SAFER study is an observational cohort of discordant couples who are trying to conceive. SAFER participants are given a package of safer reproduction services, including counselling and a choice of one or more HIV prevention strategies: ART/VL, PrEP, AVI, or SW. We developed decision models to simulate the use of these strategies and to estimate their cost-effectiveness individually and in combination. Patient uptake of strategies was based on SAFER data. Total net costs and outcomes were assessed over a 30-year horizon from a health system perspective. Costs were derived from SAFER activities using micro-costing, including time and motion observations, and from published literature. Health outcomes were estimated using published literature and were measured in terms of disability-adjusted life-years (DALYs) associated with HIV infection. Incremental cost-effectiveness ratios (ICERs) were calculated using discounted total net health-care costs associated with each safer strategy versus current practice, and discounted DALYs for the seronegative partner and infant.FindingsProviding safer reproduction counselling and a choice of strategies is cost-effective compared with current practice, per the WHO standard of annual gross domestic product (GDP) per capita (US$1008 in Zimbabwe), and remains cost-effective up to 97% ART coverage in the general population. Each individual strategy is more cost-effective than current practice, and each has an ICER less than $875 per DALY averted. Both AVI and ART/VL are cost-saving for couples with an HIV-positive woman, and ART/VL and SW were the most cost-effective strategies for couples with an HIV-positive man.InterpretationModelling suggests that offering safer reproduction counselling and services to HIV-discordant couples trying to conceive is likely to be highly cost-effective for HIV prevention. Our findings may inform implementation of these strategies in Zimbabwe, and sub-Saharan Africa.FundingNone.
I'm considering changing to a career in ophthalmology. I am currently an anaesthetic SHO and have MRCS part 1 and a BSc in neuroscience. What are the options and chances?
Authors: Amar Alwitry
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
EFFICACY OF EXTRACORPOREAL SHOCKWAVE MYOCARDIAL REVASCULARIZATION THERAPY IN PATIENTS WITH STABLE ANGINA PECTORIS: MULTICENTRE RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED STUDY
Authors: Evgeny Shkolnik, Greta Burneikaite, Jelena Celutkiene, Mikhail Scherbak, Gitana Zuoziene, Birute Petrauskiene, Irena Butkuviene, Ekaterina Trush, Aleksandras Laucevicius, Yury Vasyuk
Journal: Journal of the American College of Cardiology (2018)
The Role of Regulatory T Lymphocytes in Amyotrophic Lateral Sclerosis
Authors: David R. Beers, Weihua Zhao, Stanley H. Appel
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
The Foundation Programme for Doctors: Getting in, Getting on and Getting out
Authors: Emily Spry
Journal: BMJ (2007)

The Foundation Programme for Doctors: Getting in, Getting on and Getting out 

Ferras Alwan, Rohin Francis, and Emma-Jane Smith

Radcliffe, 2007

£16.95, 136 pages

ISBN: 1 84619 116 5

Rating:⋆⋆⋆⋆/5



This book aims to provide practical advice on the foundation programme to all those whose first experience of practising medicine will be as a foundation doctor. It does so in an upbeat, engaging style, with useful summaries at the end of each chapter. The gags, though un-PC at times, bring welcome relief. For quick reference, the FAQs at the end …
Campaign launches to introduce schoolchildren to health careers
Authors: Caroline White
Journal: BMJ (2015)

Medical students, doctors, and other healthcare professionals are being asked to volunteer to talk to primary school children across the country about their jobs as part of a national campaign to boost career aspirations and widen participation from an early age.

The Who’s in Health? campaign, which formally launched this month, is a joint initiative between the Medical Schools Council (MSC), the National Association of Head Teachers, and the charity Education and Employers. The scheme aims to provide a bank of volunteers for all 23 000 primary schools in England to help 7-11 year …
Health-Risk Behaviors and Chronic Conditions Among Adults with Inflammatory Bowel Disease — United States, 2015 and 2016
Authors: Fang Xu, James M. Dahlhamer, Emily P. Zammitti, Anne G. Wheaton, Janet B. Croft
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. In 2015, an estimated 3.1 million adults in the United States had ever received a diagnosis of IBD (1). Nationally representative samples of adults with IBD have been unavailable or too small to assess relationships between IBD and other chronic conditions and health-risk behaviors (2). To assess the prevalence of health-risk behaviors and chronic conditions among adults with and without IBD, CDC aggregated survey data from the 2015 and 2016 National Health Interview Survey (NHIS). An estimated 3.1 million (unadjusted lifetime prevalence = 1.3%) U.S. adults had ever received a diagnosis of IBD. Adults with IBD had a significantly lower prevalence of having never smoked cigarettes than did adults without the disease (55.9% versus 63.5%). Adults with IBD had significantly higher prevalences than did those without the disease in the following categories: having smoked and quit (26.0% versus 21.0%; having met neither aerobic nor muscle-strengthening activity guidelines (50.4% versus 45.2%); reporting <7 hours of sleep, on average, during a 24-hour period (38.2% versus 32.2%); and having serious psychological distress (7.4% versus 3.4%). In addition, nearly all of the chronic conditions evaluated were more common among adults with IBD than among adults without IBD. Understanding the health-risk behaviors and prevalence of certain chronic conditions among adults with IBD could inform clinical practice and lead to better disease management.
Survival stratification using a baseline inflammatory physiology based scoring system in advanced non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (anti-PD-1) therapy.
Authors: Abdul Rafeh Naqash, Chipman Robert Geoffrey Stroud, Mahvish Muzaffar, Li V. Yang, Paul R. Walker
Journal: Journal of Clinical Oncology (2018)

152 Background: Immune checkpoint blockade (ICB) has shown promise in NSCLC with improved survival and durability in disease control. Despite these advances, the response to ICB remains variable. Thus identifying easily available biomarkers that can assist in the optimal selection of patients for ICB holds paramount importance. Methods: Retrospectively we identified 87 stage III/IV NSCLC patients initiated on anti-PD-1 therapy from April 2015 to March 2017 after progressing on a platinum doublet. These patients were part of an ongoing prospective biomarker-based study at our institution. Follow up cutoff for survival analysis was set at October 1, 2017. Enrolled participants had inflammatory markers (C-reactive protein, absolute neutrophil count, absolute lymphocyte count, serum albumin) measured on the day of first dose of anti-PD-1 administration as well as subsequent doses. Using multivariate Cox analysis, factors demonstrating an association with overall survival after immunotherapy (OSI) were used to develop a composite score to stratify patient survival. Results: The median age was 64 years with predominant histology being adenocarcinoma in 46.0 % followed by squamous cell carcinoma (43.7 %). Stage IV disease was present in 70.1%, with skeletal involvement (54.1 %) and liver (27.9 %) being the most common metastatic sites. In the multivariate Cox regression with backward elimination, factors independently associated with OSI were noted to be: CRP, neutrophil-lymphocyte ratio, and prognostic nutritional index. A composite inflammatory biomarker score was developed using the B-coefficients from the Cox multivariate regression. A score &gt; 1 demonstrated inferior OSI compared to a score of ≤ 1 [1.7 vs. 9.3 months; P &lt; 0.001, HR 4.00, 95% CI (2.21-7.25)]. Conclusions: This study provides preliminary evidence in favor of a composite inflammation based score that can aid in survival stratification of these patients. Validation of this score in prospective NSCLC trials to elucidate its potential utility as a predictive or prognostic tool in facilitating optimal patient selection for ICB is required.
Diploma in geriatric medicine (DGM)
Authors: Andrea Nies
Journal: BMJ (2005)

SH: This diploma is designed for any doctor working in care of the elderly. It's primarily for general practitioners (GPs), staff grades, or associate specialists in medicine for the elderly, but is increasingly popular with old age psychiatrists. Doctors must either have held or currently hold a post approved for professional training in a department specialising in the care of the elderly, or have experience over a period of two years since qualification in which care of the elderly formed an appreciable part.

SH: I took the exam in winter 2004. I am currently a specialist registrar in old age psychiatry.

JC: In 2004, during my six month placement in geriatric medicine as part of the general practice vocational training scheme.

AN: I did it in spring 2004, when I was applying and preparing for my general practice vocational training scheme rotation.

SH: I felt it important to be aware of current medical thinking, for example, on stroke—its prevention and treatment—as I …
Most NHS commissioning support services pass second quality test
Authors: Helen Jaques
Journal: BMJ (2012)

Most of the commissioning support services being set up by primary care trust staff to assist clinical commissioning groups have passed the second stage of the NHS Commissioning Board’s business review process, although some quite narrowly.

A total of 25 regional NHS commissioning support services and the nationwide NHS Communications and Engagement Service submitted outline business plans and detailed financial information for “checkpoint 2” of the assurance process.

Fourteen of these organisations passed the …
Early Intervention in Bipolar Disorder
Authors: Eduard Vieta, Estela Salagre, Iria Grande, André F. Carvalho, Brisa S. Fernandes, Michael Berk, Boris Birmaher, Mauricio Tohen, Trisha Suppes
Journal: American Journal of Psychiatry (2018)

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and "tantalizing beyond reach." (Am J Psychiatry 1925: 81: 643-662 ).
Consultants back vote of no confidence in DDRB
Authors: Caroline White
Journal: BMJ (2013)

Consultants have stated that they have no confidence in the authority of the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) or in its credibility to make recommendations on their terms and conditions.

In December 2012 the DDRB published its long delayed report on compensation levels and award schemes for consultants working in UK health services. The report proposed a new tier of “principal consultant,” intended for high performers, and curbs on the top tier of earnings.1

Delegates to the BMA’s annual consultants’ conference in London on 6 March voted to jettison the report’s findings ahead of formal contractual negotiations. They stopped short of voting in favour of a ballot on industrial action in …
Pulmonary arterial hypertension: pathogenesis and clinical management
Authors: Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Journal: BMJ (2018)

<h3>ABSTRACT</h3> Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells. Progress has been made in identifying the causes of PAH and approving new drug therapies. A cancer-like increase in cell proliferation and resistance to apoptosis reflects acquired abnormalities of mitochondrial metabolism and dynamics. Mutations in the type II bone morphogenetic protein receptor (<i>BMPR2)</i> gene dramatically increase the risk of developing heritable PAH. Epigenetic dysregulation of DNA methylation, histone acetylation, and microRNAs also contributes to disease pathogenesis. Aberrant bone morphogenetic protein signaling and epigenetic dysregulation in PAH promote cell proliferation in part through induction of a Warburg mitochondrial-metabolic state of uncoupled glycolysis. Complex changes in cytokines (interleukins and tumor necrosis factor), cellular immunity (T lymphocytes, natural killer cells, macrophages), and autoantibodies suggest that PAH is, in part, an autoimmune, inflammatory disease. Obstructive pulmonary vascular remodeling in PAH increases right ventricular afterload causing right ventricular hypertrophy. In some patients, maladaptive changes in the right ventricle, including ischemia and fibrosis, reduce right ventricular function and cause right ventricular failure. Patients with PAH have dyspnea, reduced exercise capacity, exertional syncope, and premature death from right ventricular failure. PAH targeted therapies (prostaglandins, phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and soluble guanylate cyclase stimulators), used alone or in combination, improve functional capacity and hemodynamics and reduce hospital admissions. However, these vasodilators do not target key features of PAH pathogenesis and have not been shown to reduce mortality, which remains about 50% at five years. This review summarizes the epidemiology, pathogenesis, diagnosis, and treatment of PAH.
NHS Employers seeks to freeze doctors’ pay for another year
Authors: Matthew Limb
Journal: BMJ (2013)

NHS Employers is seeking to freeze the pay of doctors and dentists for another year, saying an increase for 2014-15 would be “unaffordable” for trusts.

The organisation will formally submit its evidence and detailed reasons for the recommendation to the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) on Friday 27 September. It will say that NHS pay remains attractive and competitive and will warn that the NHS is under such pressure that any increase …