tbuckley/cabot-search huggingface dataset:
NHS must prioritise health of children and young people
Authors: Russell M Viner
Journal: BMJ (2018)

RE: NHS must prioritise health of children and young peopleViner [1] provides a compelling and timely insight into the health of our children and the importance of enhancing the current status quo, for few could argue the moral and economic rationale for looking after the children, our future.One key part of children's lives is education.It is pertinent to bring in a hotly debated topic, Physical Education and School Sport (PESS).The growing political interest in sport, echoed in education, highlighted the potential of PESS to contribute to broader political policy objectives.Consequently, back in 2002, the New Labour government decided to make PESS one of its policy priorities.The launch of the national PESS and Club Links (PESSCL) strategy in 2002 represented a major political and financial commitment by the Labour government to the creation of aground-breaking infrastructure for PESS.The rationale was that all children, whatever their circumstances or abilities, should be able to participate in and enjoy PESS [2].
Planetary health in the tropics: how community health-care doubles as a conservation tool
Authors: Kinari Webb
Journal: The Lancet Global Health (2018)

BackgroundThe Indonesian non-profit organisation Alam Sehat Lestari (ASRI), with support from the US non-profit organisation Health In Harmony, was created in 2007 to protect biodiverse rainforest in Gunung Palung National Park (GPNP) in Borneo, Indonesia, and to improve the lives of the communities surrounding the park. ASRI used a process of radical listening to identify the drivers of deforestation within the park and to help the community design and execute solutions.MethodsBased on community design, multiple strategies relating to health service provision and alternative livelihoods training were implemented. To understand the health and conservation changes in the project communities, we did three quantitative surveys of 25 villages surrounding GPNP: one in 2007 (baseline), one in 2012 (5 years), and one in 2017 (10 years). Pairs of trained nurses systematically interviewed 1300 households out of 60 000 in the region. Additionally, to assess how the project was working, a qualitative study using realist methodology was selected to help determine whether there were aspects of ASRI's multipronged approach that the communities saw as effective in motivating conservation behaviour, and under what circumstances the model might be replicable in other areas of high-conservation value under threat by local communities. 70 interviews were conducted among loggers, patients, government officials, and random community members.FindingsThe quantitative results demonstrated that positive changes were being achieved, with a 68% drop by 2012 and a 89% drop by 2017 in households practising illegal logging (a decrease from an estimated 1350 logging households to 150 logging households currently) and a concomitant stabilisation of primary forest loss. By 2012, infant mortality decreased from 3·2 per 100 households to 1·1 per 100 households (70% decrease). The qualitative survey indicated that social capital and female empowerment played an important part in the positive community responses to the project's conservation messaging.InterpretationHealth In Harmony and the ASRI clinic have improved the health of the people and of the forest in the GPNP region in Borneo. This comprehensive approach to conservation and health care provides innovative solutions to conserving the environment while empowering individuals to improve the health of their communities.FundingNone.
Half of junior doctors have concerns about quality of care, survey finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Half of junior doctors have concerns about the quality of care in their workplace, a survey has found.

An online survey conducted by the Medical Protection Society received 1052 responses from its foundation doctor members, representing 7% of all 14 975 foundation doctors.1

The survey, which included foundation year 1 (F1) and foundation year 2 (F2) doctors, found that over half (51%) …
Ultrasound molecular imaging of acute cardiac transplantation rejection using nanobubbles targeted to T lymphocytes
Authors: Jinfeng Liu, Yihan Chen, Guohua Wang, Qing Lv, Yali Yang, Jing Wang, Pingyu Zhang, Jie Liu, Yu Xie, Li Zhang, Mingxing Xie
Journal: Biomaterials (2018)

Clinical surveillance of acute heart transplantation rejection requires repeated invasive endomyocardial biopsies and noninvasive diagnostic techniques are desperately needed. It is acknowledged that T lymphocyte infiltration is the central process of acute rejection. We hypothesized that ultrasound molecular imaging with T lymphocyte-targeted nanobubbles could be used to detect acute rejection in heart transplantation. In this study, nanobubbles bearing anti-CD3 antibody (NBCD3) or isotype antibody (NBcon) were prepared and characterized. There was significant adhesion of NBCD3 to T lymphocytes compared with NBcon in vitro. The signal intensity of the adherent NBCD3 was significantly higher than that of the NBcon in allograft rats, but not significantly different in isograft rats. Furthermore, the signal intensity of NBCD3 in allograft rats was significantly higher than that in isograft rats, indicating more T lymphocyte infiltration in allograft rats compared with isograft rats. These results were further confirmed by immunohistochemistry examination, and the signal intensity of NBCD3 was positively correlated with the number of T lymphocytes in allograft rats. In summary, ultrasound molecular imaging with T lymphocyte-targeted nanobubbles can detect T lymphocyte infiltration in acute rejection and could be used as a noninvasive method in acute rejection detection after cardiac transplantation.
Cyclic cRGDfk peptide and Chlorin e6 functionalized silk fibroin nanoparticles for targeted drug delivery and photodynamic therapy
Authors: Baiping Mao, Caixia Liu, Wenwen Zheng, Xiaoheng Li, Renshan Ge, Haifa Shen, Xiaoling Guo, Qingquan Lian, Xian Shen, Chao Li
Journal: Biomaterials (2018)
Drinking very hot tea linked to oesophageal cancer
Authors: Jacqui Wise
Journal: BMJ (2018)

Regularly drinking very hot tea, when combined with tobacco or alcohol use, is associated with an increased risk for oesophageal cancer, according to a Chinese study with more than 450 000 participants.1

However, the study, published in Annals of Internal Medicine, found no increased risk of oesophageal cancer in those who drank hot tea but did not smoke or regularly drink alcohol.

Alcohol consumption and tobacco smoking are already well established causes of oesophageal squamous cell cancer. China is among the countries with the highest incidence of oesophageal cancer. Tea drinkers, especially Chinese men, are more likely to smoke …
GMC expresses doubt over EC plans to free movement of doctors across Europe
Authors: Adrian O’Dowd
Journal: BMJ (2011)

Plans by the European Commission to simplify legislation that allows doctors to work anywhere in the European Union do not provide sufficient assurance of migrant doctors’ education, competency, or language skills, the General Medical Council has said.

The United Kingdom’s medical regulator gave a stark warning about the commission’s proposals when giving evidence on 30 June to the House of Lords EU social policies and consumer protection subcommittee, as part of its inquiry into the mobility of healthcare professionals ( BMJ Careers 14 May, http://careers.bmj.com/careers/advice/view-article.html?id=20002963).

Peers on the committee are holding the inquiry in response to the ongoing European Commission review of its directive on the mutual recognition of professional qualifications, which aims to have all member states recognise each other’s healthcare qualifications and simplify the movement of clinicians across countries.

Giving evidence to the Lords select committee, Peter Rubin, the GMC’s chairman, said, “We support the principle of free movement of doctors in the EU, and we …
Unique clinical and serological features of bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors
Authors: H. Horikawa, Y. Kurihara, T. Funakoshi, N. Umegaki-Arao, H. Takahashi, A. Kubo, A. Tanikawa, N. Kodani, Y. Minami, S. Meguro, H. Itoh, K. Izumi, W. Nishie, H. Shimizu, M. Amagai, J. Yamagami
Journal: British Journal of Dermatology (2018)
THE RELATIONSHIP BETWEEN EMOTIONAL STATUS, DEPRESSION AND CAROTID ATHEROMATIC BURDEN: THE CORINTHIA STUDY
Authors: Evangelos Oikonomou, George Lazaros, Evangelia Christoforatou, Christos Chasikidis, Sotirios Tsalamandris, George-Angelo Papamikroulis, Georgia Vogiatzi, Margenti Papakonstantinou, Athina Goliopoulou, Maria Anastasiou, Maria Tousouli, Efthimia Stofa, Georgios Georgiopoulos, Panagiotis Theofilis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
I would like to get experience in the field of blood transfusion and blood cross matching. Are there any courses that may help me?
Authors: Adrian Newland
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 (www.bmjcareers.com/advicezone) 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.
Statins Synergize with Hedgehog Pathway Inhibitors for Treatment of Medulloblastoma
Authors: Renata E. Gordon, Li Zhang, Suraj Peri, Yin-Ming Kuo, Fang Du, Brian L. Egleston, Jessica M. Y. Ng, Andrew J. Andrews, Igor Astsaturov, Tom Curran, Zeng-Jie Yang
Journal: Clinical Cancer Research (2018)

Purpose: The role of cholesterol biosynthesis in hedgehog pathway activity and progression of hedgehog pathway medulloblastoma (Hh-MB) were examined in vivo Statins, commonly used cholesterol-lowering agents, were utilized to validate cholesterol biosynthesis as a therapeutic target for Hh-MB.Experimental Design: Bioinformatic analysis was performed to evaluate the association between cholesterol biosynthesis with hedgehog group medulloblastoma in human biospecimens. Alterations in hedgehog signaling were evaluated in medulloblastoma cells after inhibition of cholesterol biosynthesis. The progression of endogenous medulloblastoma in mice was examined after genetic blockage of cholesterol biosynthesis in tumor cells. Statins alone, or in combination with vismodegib (an FDA-approved Smoothened antagonist), were utilized to inhibit medulloblastoma growth in vivoResults: Cholesterol biosynthesis was markedly enhanced in Hh-MB from both humans and mice. Inhibition of cholesterol biosynthesis dramatically decreased Hh pathway activity and reduced proliferation of medulloblastoma cells. Statins effectively inhibited medulloblastoma growth in vivo and functioned synergistically in combination with vismodegib.Conclusions: Cholesterol biosynthesis is required for Smoothened activity in the hedgehog pathway, and it is indispensable for the growth of Hh-MB. Targeting cholesterol biosynthesis represents a promising strategy for treatment of Hh-MB. Clin Cancer Res; 24(6); 1375-88. ©2018 AACR.
Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset
Authors: Jan Hülsdünker, Katja J. Ottmüller, Hannes P. Neeff, Motoko Koyama, Zhan Gao, Oliver S. Thomas, Marie Follo, Ali Al-Ahmad, Gabriele Prinz, Sandra Duquesne, Heide Dierbach, Susanne Kirschnek, Tim Lämmermann, Martin J. Blaser, Brian T. Fife, Bruce R. Blazar, Andreas Beilhack, Geoffrey R. Hill, Georg Häcker, Robert Zeiser
Journal: Blood (2018)
Cyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates hepatic steatosis
Authors: Xiaolei Wang, Heng Du, Shanshan Shao, Tao Bo, Chunxiao Yu, Wenbin Chen, Lifang Zhao, Qiu Li, Li Wang, Xiaojing Liu, Xiaohui Su, Mingqi Sun, Yongfeng Song, Ling Gao, Jiajun Zhao
Journal: Hepatology (2018)

Physiological opening of the mitochondrial permeability transition pore (mPTP) is indispensable for maintaining mitochondrial function and cell homeostasis, but the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated by an increase of CypD expression induced hepatic mitochondrial dysfunction. Notably, such mitochondrial perturbation occurred before detectable triglyceride accumulation in the liver of high‐fat diet–fed mice. Moreover, either genetic knockout or pharmacological inhibition of CypD could ameliorate mitochondrial dysfunction, including excess mPTP opening and stress, and down‐regulate the transcription of sterol regulatory element–binding protein‐1c, a key factor of lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of CypD–infected mice was aggravated relative to the control group. Blocking p38 mitogen‐activated protein kinase or liver‐specific Ire1α knockout could resist CypD‐induced sterol regulatory element–binding protein‐1c expression and steatosis. Importantly, CypD inhibitor applied prior to or after the onset of triglyceride deposition substantially prevented or ameliorated fatty liver. Conclusion: CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen‐activated protein kinase activation, and results in enhanced sterol regulatory element–binding protein‐1c transcription and hepatic steatosis. (Hepatology 2018;68:62‐77).
Mindfulness-based cognitive therapy in COPD: a cluster randomised controlled trial
Authors: Ingeborg Farver-Vestergaard, Mia S. O'Toole, Maja O'Connor, Anders Løkke, Elisabeth Bendstrup, Sharee A. Basdeo, Donal J. Cox, Pádraic J. Dunne, Kai Ruggeri, Frances Early, Robert Zachariae
Journal: European Respiratory Journal (2018)

A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) entering pulmonary rehabilitation (PR) report psychological distress, which is often accompanied by poor physical health status. Mindfulness-based cognitive therapy (MBCT) has been shown to improve psychological and physical outcomes in other chronic diseases. We therefore evaluated the efficacy of MBCT as an add-on to a standard PR programme in COPD. COPD patients eligible for PR were cluster randomised to receive either an 8-week, group-based MBCT programme as an add-on to an 8-week PR programme (n=39), or PR alone (n=45). The primary outcomes of psychological distress and physical health status impairment were measured with the Hospital Anxiety and Depression Scale (HADS) and the COPD Assessment Test (CAT) before randomisation (T1), mid- (T2) and post-intervention (T3), and at 3 (T4) and 6 (T5) months’ follow-up . A statistically significant time×arm effect was found for the HADS (Cohen's d =0.62, 95% CIs ( d )=0.18–1.06, p=0.010). The treatment effect on the CAT failed to reach statistical significance ( d =0.42, 95% CIs ( d )=−0.06–0.90, p=0.061). MBCT showed a statistically significant and durable effect on psychological distress, indicating that MBCT may be an efficacious add-on to standard PR programmes in COPD.
COST EFFECTIVENESS OF ORAL ANTICOAGULATION THERAPY FOR NON-VALVULAR ATRIAL FIBRILLATION PATIENTS: WARFARIN VERSUS THE NEW ORAL ANTICOAGULANTS RIVAROXABAN, DABIGATRAN AND APIXABAN
Authors: Ismael Ortiz-Cartagena, Antonio Orraca Gotay, Jose Acevedo
Journal: Journal of the American College of Cardiology (2018)
TRENDS AND PREDICTORS OF PALLIATIVE CARE REFERRALS IN ACUTE HEART FAILURE PATIENTS: INSIGHT FROM NATIONAL INPATIENT SAMPLE DATABASE
Authors: Brijesh Patel, Paul Secheresiu, Lekha Racharla, Mahek Shah, Lohit Garg, Daniel Ray, Ronald Freudenberger
Journal: Journal of the American College of Cardiology (2018)
Deposition characteristics and resulting DNA damage patterns of liposomal irinotecan (nal-IRI) in pancreatic cancer xenografts.
Authors: Shannon C. Leonard, Nancy Paz, Stephan G Klinz, Daniel Gaddy, Helen Lee, Bart S Hendriks, Jonathan B Fitzgerald
Journal: Journal of Clinical Oncology (2018)

335 Background: Liposomal irinotecan (nal-IRI, ONIVYDE) is approved in the US, EU and other countries in combination with 5-fluorouracil/leucovorin for treatment of patients with metastatic pancreatic cancer after disease progression following gemcitabine-based therapy. We report pharmacokinetic and extended pharmacodynamic effects of nal-IRI in pancreatic tumor models compared to non-liposomal irinotecan HCl. Methods: AsPC-1, BxPC-3 and CFPAC-1 tumors were grown in NOD-SCID mice. For efficacy animals were dosed q7d with 25-50 mg/kg irinotecan HCl or at 5x lower doses of nal-IRI. For PK-PD studies doses of 10-50 mg/kg of fluorescently-labeled nal-IRI were used; samples were collected up to 72 hr for irinotecan HCl and up to 168 hr for nal-IRI. Tumor samples were evaluated for liposome localization, macrophage and tumor markers, vessels, DNA damage and apoptosis. Results: nal-IRI yields sustained circulation and delivery of its payload to tumors compared to irinotecan HCl. This results in improved control of growth rates across a range of pancreatic tumor models even at 5x lower doses. DNA damage in BxPC-3 tumors has a comparable extent with both formulations, but is maximal at 6 hr after irinotecan HCl (50 mg/kg) and at 72 hr after nal-IRI (10 mg/kg). Liposomes deposit in tumors heterogeneously around functional vessels. Accumulation peaks at 6 - 24 hr with similar deposition patterns in cell- or patient-derived xenografts. Liposomes are predominantly taken up by macrophages and to a lesser extent by tumor or other stromal cells. DNA damage is mostly confined to tumor cells, a majority of which have not internalized liposomes. DNA damage and apoptosis are seen only minimally in non-tumor cells even when displaying high liposome uptake. Conclusions: nal-IRI improves tumoral deposition of its payload in pancreatic tumor models. Deposition is heterogeneous and restricted to perivascular areas. DNA damage predominantly in tumor cells outside of the liposomal deposition area suggests sufficient intratumoral levels of the SN-38 active metabolite, possibly after payload release by stromal macrophages and concomitant conversion. Effects of repeated dosing cycles should be explored.
Opening the Book on Maintenance of Certification
Authors: Philip L. Schiffman
Journal: Annals of Internal Medicine (2018)

Letters20 March 2018Opening the Book on Maintenance of CertificationPhilip L. Schiffman, MDPhilip L. Schiffman, MDRutgers Robert Wood Johnson Medical School, East Brunswick, New Jersey (P.L.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0642 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Weinberger's commentary (1) with great interest. Physicians should be up to date in their practice of medicine, and their patients have every right to expect that. Board certification should signify that physicians are prepared for what they will encounter on a day-to-day basis. We were trained not to look for zebras when we hear hoofbeats. However, test writers on board and certification examinations so often seem more concerned with zebras than the bread-and-butter practice of medicine. I used to joke that I had seen 3 cases of tularemia over my many years in practice: on ...Reference1. Weinberger SE. Opening the book on maintenance of certification [Editorial]. Ann Intern Med. 2017;167:353-4. [PMID: 28806790]. doi:10.7326/M17-1853 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Rutgers Robert Wood Johnson Medical School, East Brunswick, New Jersey (P.L.S.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0642. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOpening the Book on Maintenance of Certification Steven E. Weinberger Opening the Book on Maintenance of Certification Steven E. Weinberger Metrics 20 March 2018Volume 168, Issue 6Page: 460KeywordsConflicts of interestCritical careDisclosurePatient advocacyTularemia ePublished: 20 March 2018 Issue Published: 20 March 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PREVALENCE OF FAMILIAL HYPERCHOLESTEROLEMIA AND LDL CHOLESTEROL REDUCTION AMONG YOUNG ADULTS WITH MYOCARDIAL INFARCTION
Authors: Avinainder Singh, Bradley Collins, Ankur Gupta, Amber Fatima, Arman Qamar, David Biery, Sekar Kathiresan, Marcelo Di Carli, Khurram Nasir, Deepak Bhatt, Ron Blankstein
Journal: Journal of the American College of Cardiology (2018)
ASSOCIATION OF IMPAIRED LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN WITH MALADAPTIVE LEFT VENTRICULAR REMODELLING AND PROGNOSIS IN SEVERE AORTIC STENOSIS AFTER AORTIC VALVE REPLACEMENT
Authors: Elise Mara Vollema, Arnold Ng, Nina Marsan, Jeroen J. Bax, Victoria Delgado
Journal: Journal of the American College of Cardiology (2018)
Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline Cardiotoxicity and Reduces Tumor Growth
Authors: Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G. Tocchetti, Braulio H.F. Lima, Mauro M. Teixeira, Paolo E. Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P. Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Journal: Circulation (2018)

Background: Anthracyclines, such as doxorubicin (DOX), are potent anticancer agents for the treatment of solid tumors and hematologic malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of phosphoinositide 3-kinase γ (PI3Kγ) in DOX-induced cardiotoxicity and the potential cardioprotective and anticancer effects of PI3Kγ inhibition. Methods: Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ-selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography, and DOX-mediated signaling was assessed in whole hearts or isolated cardiomyocytes. The dual cardioprotective and antitumor action of PI3Kγ inhibition was assessed in mouse mammary tumor models. Results: PI3Kγ kinase-dead mice showed preserved cardiac function after chronic low-dose DOX treatment and were protected against DOX-induced cardiotoxicity. The beneficial effects of PI3Kγ inhibition were causally linked to enhanced autophagic disposal of DOX-damaged mitochondria. Consistently, either pharmacological or genetic blockade of autophagy in vivo abrogated the resistance of PI3Kγ kinase-dead mice to DOX cardiotoxicity. Mechanistically, PI3Kγ was triggered in DOX-treated hearts, downstream of Toll-like receptor 9, by the mitochondrial DNA released by injured organelles and contained in autolysosomes. This autolysosomal PI3Kγ/Akt/mTOR/Ulk1 signaling provided maladaptive feedback inhibition of autophagy. PI3Kγ blockade in models of mammary gland tumors prevented DOX-induced cardiac dysfunction and concomitantly synergized with the antitumor action of DOX by unleashing anticancer immunity. Conclusions: Blockade of PI3Kγ may provide a dual therapeutic advantage in cancer therapy by simultaneously preventing anthracyclines cardiotoxicity and reducing tumor growth.