tbuckley/cabot-search huggingface dataset:
Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation
Authors: Farzad Moazed, Ellen L Burnham, R William Vandivier, Cecilia M O'Kane, Murali Shyamsundar, Umar Hamid, Jason Abbott, David R Thickett, Michael A Matthay, Daniel F McAuley, Carolyn S Calfee
Journal: Thorax (2016)

<h3>Rationale</h3> Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. <h3>Objective</h3> To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. <h3>Methods</h3> We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 μg LPS inhalation (n=30). <h3>Measurements and main results</h3> After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p&lt;0.0001) with increased soluble VEGF receptor-1 (p=0.0001). <h3>Conclusions</h3> Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products.
One in 10 practices in England faces financial collapse, survey shows
Authors: Anne Gulland
Journal: BMJ (2016)

Around a 10th of general practices that responded to a BMA survey face closure because of financial problems.

The survey of 2830 practices in England—around a third of the total—found that 900 GP surgeries were in a weak financial position, 294 of these saying that they were financially “unsustainable.” A further one in five practices (22%) is making plans to improve finances, and just one in 20 (5%) reported …
Abstract 18919: Race/Ethnic Differences in Mortality Among Patients Hospitalized with Intracerebral Hemorrhage
Authors: Ying Xian, Robert G Holloway, Eric E Smith, Lee H Schwamm, Mathew J Reeves, Margueritte Cox, DaiWai M Olson, Adrian F Hernandez, Barbara Lytle, Gregg C Fonarow, Eric D Peterson
Journal: Circulation (2012)

Background: Despite higher burden of stroke in minorities, limited data exists in comparing mortality for patients with intracerebral hemorrhage of different racial and ethnic background. Methods: Data from 123,736 patients (83,280 white, 22,165 black, 10,541 Hispanic, and 7,750 other race) with intracerebral hemorrhage admitted to 1,199 Get With The Guidelines-Stroke hospitals between 2003 and 2012. Multivariate logistic regressions with generalized estimating equations were performed to evaluate the association between race and in-hospital mortality. Results: Compared with white patients, black, other race, and Hispanic patients were younger (median 75, 59, 67, and 64), had less comorbidities except for diabetes mellitus and hypertension, and had more severe stroke (National Institutes of Health Stroke Scale [NIHSS], median 9, 10, 11, and 10; all p&lt;0.001). Black (23.0%, adjusted OR 0.91, 95% CI 0.87-0.95), Hispanic (22.8%, adjusted OR 0.85, 95% CI 0.79-0.91), and other racial/ethnic patients (25.3%, adjusted OR 0.87, 95% CI 0.81-0.93) were less likely to die in hospital than white patients (27.6%) after adjustment for patient and hospital characteristics. The mortality differences remained consistent after further adjustment for NIHSS in NIHSS complete records (N=47,436). To determine whether race/ethnic differences in mortality varied by age, we examined the interaction between race and age (p &lt;0.009). The survival advantage was observed in older age groups but was not evident in younger age groups (Table). In contrast to lower mortality, minorities had longer length of stay than white patients (median 6, 6, 6, and 5 days for black, Hispanic, other, and white respectively, p&lt;0.001). Conclusion: Among patients hospitalized with intracerebral hemorrhage, black, Hispanic, and other race/ethnic groups have lower risk of in-hospital mortality compared to white patients, though these race/ethnic differences were confined to patients age 60 and older.
Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera
Authors: Heinz Gisslinger, Oleh Zagrijtschuk, Veronika Buxhofer-Ausch, Josef Thaler, Ernst Schloegl, Guenther A. Gastl, Dominik Wolf, Robert Kralovics, Bettina Gisslinger, Karin Strecker, Alexander Egle, Thomas Melchardt, Sonja Burgstaller, Ella Willenbacher, Martin Schalling, Nicole C. Them, Pavla Kadlecova, Christoph Klade, Richard Greil
Journal: Blood (2015)
Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease
Authors: Michael J. Blaha, Miguel Cainzos-Achirica, Philip Greenland, John W. McEvoy, Ron Blankstein, Matthew J. Budoff, Zeina Dardari, Christopher T. Sibley, Gregory L. Burke, Richard A. Kronmal, Moyses Szklo, Roger S. Blumenthal, Khurram Nasir
Journal: Circulation (2016)

Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision making. We compared 13 negative risk markers using diagnostic likelihood ratios (DLRs), which model the change in risk for an individual after the result of an additional test. We examined 6814 participants from the Multi-Ethnic Study of Atherosclerosis. Coronary artery calcium score of 0, carotid intima-media thickness <25th percentile, absence of carotid plaque, brachial flow-mediated dilation >5% change, ankle-brachial index >0.9 and <1.3, high-sensitivity C-reactive protein <2 mg/L, homocysteine <10 µmol/L, N-terminal pro-brain natriuretic peptide <100 pg/mL, no microalbuminuria, no family history of coronary heart disease (any/premature), absence of metabolic syndrome, and healthy lifestyle were compared for all and hard coronary heart disease and all CVD events over the 10-year follow-up. Models were adjusted for traditional CVD risk factors. Among all negative risk markers, coronary artery calcium score of 0 was the strongest, with an adjusted mean DLR of 0.41 (SD, 0.12) for all coronary heart disease and 0.54 (SD, 0.12) for CVD, followed by carotid intima-media thickness <25th percentile (DLR, 0.65 [SD, 0.04] and 0.75 [SD, 0.04], respectively). High-sensitivity C-reactive protein <2 mg/L and normal ankle-brachial index had DLRs >0.80. Among clinical features, absence of any family history of coronary heart disease was the strongest (DLRs, 0.76 [SD, 0.07] and 0.81 [SD, 0.06], respectively). Net reclassification improvement analyses yielded similar findings, with coronary artery calcium score of 0 resulting in the largest, most accurate downward risk reclassification. Negative results of atherosclerosis-imaging tests, particularly coronary artery calcium score of 0, resulted in the greatest downward shift in estimated CVD risk. These results may help guide discussions on the identification of individuals less likely to receive net benefit from lifelong preventive pharmacotherapy.
Spiritual Care Providers and Goals-of-Care Discussions—Reply
Authors: Natalie C. Ernecoff, Farr A. Curlin, Douglas B. White
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice
Authors: Matthew E. Wikstrom, Peter Fleming, Rachel D. Kuns, Iona S. Schuster, Valentina Voigt, Gregory Miller, Andrew D. Clouston, Siok-Keen Tey, Christopher E. Andoniou, Geoffrey R. Hill, Mariapia A. Degli-Esposti
Journal: Blood (2015)
Genomic Approaches to Phenotype Prediction
Authors: Anna R. Docherty
Journal: JAMA Psychiatry (2016)

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 Psychiatry 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 Psychiatry journal
FRI0597 Near-Infrared Spectroscopic Hand Imaging: A New Tool to Assess Microcirculatory Impairment in Systemic Sclerosis
Authors: L. Gargani, T. Barskova, V. Hartwig, M. Marinelli, S. Guiducci, S. Bellando Randone, J. Blagojevic, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Patients affected by systemic sclerosis (SSc) develop functional and structural microcirculatory dysfunction, which leads to skin fibrosis initially affecting distal extremity. Recent studies have tested the possibility of evaluating the skin microcirculation of the entire hand and its spatial heterogeneity by means of optical Near-Infrared Spectroscopic (NIRS) of blood HbO2 saturation (stO<sub>2</sub>). The NIRS-sensitive camera is a non-invasive tissue oxygenation measurement system based on near infrared light. The camera reports and approximates value of stO<sub>2</sub> in superficial tissue. Processing software of the NIRS-camera generates 2D imaging maps automatically in real time. <h3>Objectives</h3> To test whether NIRS hand imaging may evaluate microcirculatory dysfunction in SSc <h3>Methods</h3> Forty-two SSc patients (90% women, mean age 55.1±15.6 years) and 18 sex and age-matched healthy controls (86% women, mean age 54.3±14.5 years, p=.89) underwent evaluation of the hand microcirculation by NIRS 2D imaging. A blood pressure cuff was applied to the forearm and 3-min ischemia was induced. Images were acquired at basal conditions at each 10 seconds during 3 minutes of ischemia and during reperfusion condition. Four regions of interest (ROI) were positioned on each fingertip, from the second to the fifth finger. <h3>Results</h3> A significant difference was found between controls and SSc in basal stO<sub>2</sub> (84.4±9.9 vs 75.9±12.5%, p&lt;.01), minimum stO<sub>2</sub> (65.6±10.2 vs 54.4±10.9%, p&lt;.001), maximum stO<sub>2</sub> (92.4±3.9 vs 86.8±6.6%, p&lt;.001), time to maximum stO<sub>2</sub> (247±42 vs 277±60 msec, p&lt;.05). Patients with anti-topoisomerase positivity had lower values of basal stO<sub>2</sub> compared to patients without (78.8±11.7 vs 69.3±12.7, p&lt;.05). No significant differences were found among different degrees of impairment at nailfold capillaroscopy (early, active, late). <h3>Conclusions</h3> Data show that NIRS hand imaging is a simple, automated promising tool to non-invasively assess the skin microcirculation of the entire hand, which can complement information deriving from nailfold capillaroscopy. <h3>Acknowledgements</h3> We thank Mr. Gennaro D9Angelo for his technical support. <h3>Disclosure of Interest</h3> None declared
B- and T-Cell Markers on Canine Lymphosarcoma Cells2
Authors: David Onions
Journal: JNCI Journal of the National Cancer Institute (1977)

Presumptive T- and B-cell populations were detected in normal canine lymphoid tissue and in 39 cases of spontaneous canine lymphosarcoma. Rosette-forming techniques with indicator erythrocytes were used to detect surface immunoglobulin, receptors for human erythrocytes (E), receptors for complement (EAC), and the Fc portion of immunoglobulin (EA). The sum of E + EAC rosette-forming cells could account for nearly all the lymphoid cells of the spleen (98%) but only 70% of lymph node cells. Only a small percentage of normal thymocytes formed E-rosettes. Phytohemagglutinin stimulation dramatically increased the number of E-rosette-forming thymocytes (RT-cells), though a major population remained nonrosetting (NRT-cells). Most multicentric cases and the single alimentary case of lymphosarcoma had B-cell properties. T-cell, possible null-cell, and double-labeled T + B-cell multicentric cases were also found. Tumors with mixtures of T- and B-cells consisted of both morphologically normal and neoplastic cells. Of the 4 cases of thymic lymphosarcoma described, 2 had RT-cell characteristics and 2 had NRT-cell characteristics. An association was found between skin infiltration and T-cell tumors. Two cases of acute lymphoblastic leukemia were also observed; the first was associated with a thymic mass, whereas the second case showed extensive bone marrow involvement. Both leukemias consisted of cells devoid of surface receptors.
Efficacy and safety of bovine activated factors IIa/VIIa/IXa/Xa in patients with active gastrointestinal bleeding: a proof of concept study
Authors: Arnulf Ferlitsch, Andreas Puspok, Simona Bota, Friedrich Wewalka, Rainer Schoefl, Eva Brownstone, Christian Madl, Henrike Lenzen, Tim Lankisch, Werner Dolak, Michael Trauner, Monika Ferlitsch
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Endoscopic treatment of active gastrointestinal bleeding often remains difficult, and considerable technical expertise is required. Our aim was to assess the efficacy and safety of endoscopic hemostasis with a liquid combination of bovine activated factors IIa/VIIa/IXa/Xa (SeraSeal). <b>Methods:</b> Patients with active gastrointestinal bleeding were prospectively included. In group A, 5 mL of bovine activated factors IIa/VIIa/IXa/Xa was topically applied via catheters to the bleeding site as initial hemostasis; group B received a similar application but as rescue therapy after failure of conventional endoscopic hemostasis. <b>Results:</b> In group A, bleeding was stopped by the agent in 15 /22 patients (68 %) and by conventional endoscopic hemostasis in 5 of the other 7, with coiling and surgery required for definitive hemostasis in 2. In group B, the addition of the agent definitively stopped bleeding in 13 /15 patients (87 %), with hemostasis in the remaining 2 achieved with fibrin glue. Rebleeding was observed in 1 patient. <b>Conclusions:</b> Our proof of concept study suggests that the use of bovine activated factors IIa/VIIa/IXa/Xa might be a safe and effective addition to current endoscopic hemostatic strategies, but further studies are necessary. ClinicalTrials.gov identifier: NCT02349490
Accounting for Missing Data in Clinical Research—Reply
Authors: Craig D. Newgard, Roger J. Lewis
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Improved Cardio-metabolic Risk Profile through Targeted Life Style Modification Program
Authors: Sankalp Das, Maribeth Rouseff, Thinh Tran, Khurram Nasir, Josette Bou-Khalil, Joseph Mora, Henry Guzman, Doris Brown, Joann Santiago-Charles, Teresa Ochoa, Cynthia Gilliam, Virginia Lehn, Beatriz Castillo, Ehimen Aneni, Lara Roberson, Emir Veledar, Ebenezer Oni, Janisse Post
Journal: Circulation (2014)
Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force
Authors: Cindy Strehl, Johannes W J Bijlsma, Maarten de Wit, Maarten Boers, Nele Caeyers, Maurizio Cutolo, Bhaskar Dasgupta, William G Dixon, Rinie Geenen, Tom W J Huizinga, Alison Kent, Annette Ladefoged de Thurah, Joachim Listing, Xavier Mariette, David W Ray, Hans U Scherer, Raphaèle Seror, Cornelia M Spies, Simon Tarp, Dieter Wiek, Kevin L Winthrop, Frank Buttgereit
Journal: Annals of the Rheumatic Diseases (2016)

There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term glucocorticoid therapy was often lacking since relevant study results were often either missing, contradictory or carried a high risk of bias. The group agreed that the risk of harm is low for the majority of patients at long-term dosages of ≤5 mg prednisone equivalent per day, whereas at dosages of &gt;10 mg/day the risk of harm is elevated. At dosages between &gt;5 and ≤10 mg/day, patient-specific characteristics (protective and risk factors) determine the risk of harm. The level of harm of glucocorticoids depends on both dose and patient-specific parameters. General and glucocorticoid-associated risk factors and protective factors such as a healthy lifestyle should be taken into account when evaluating the actual and future risk.
Mitochondrial Mechanisms of Neuronal Cell Death: Potential Therapeutics
Authors: Ted M. Dawson, Valina L. Dawson
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Mitochondria lie at the crossroads of neuronal survival and cell death. They play important roles in cellular bioenergetics, control intracellular Ca 2+ homeostasis, and participate in key metabolic pathways. Mutations in genes involved in mitochondrial quality control cause a myriad of neurodegenerative diseases. Mitochondria have evolved strategies to kill cells when they are not able to continue their vital functions. This review provides an overview of the role of mitochondria in neurologic disease and the cell death pathways that are mediated through mitochondria, including their role in accidental cell death, the regulated cell death pathways of apoptosis and parthanatos, and programmed cell death. It details the current state of parthanatic cell death and discusses potential therapeutic strategies targeting initiators and effectors of mitochondrial-mediated cell death in neurologic disorders.
Ataxia telangiectasia mutated in cardiac fibroblasts regulates doxorubicin-induced cardiotoxicity
Authors: Hong Zhan, Kenichi Aizawa, Junqing Sun, Shota Tomida, Kinya Otsu, Simon J. Conway, Peter J. Mckinnon, Ichiro Manabe, Issei Komuro, Kiyoshi Miyagawa, Ryozo Nagai, Toru Suzuki
Journal: Cardiovascular Research (2016)

Doxorubicin (Dox) is a potent anticancer agent that is widely used in the treatment of a variety of cancers, but its usage is limited by cumulative dose-dependent cardiotoxicity mainly due to oxidative damage. Ataxia telangiectasia mutated (ATM) kinase is thought to play a role in mediating the actions of oxidative stress. Here, we show that ATM in cardiac fibroblasts is essential for Dox-induced cardiotoxicity. ATM knockout mice showed attenuated Dox-induced cardiotoxic effects (e.g. cardiac dysfunction, apoptosis, and mortality). As ATM was expressed and activated predominantly in cardiac fibroblasts, fibroblast-specific Atm-deleted mice (Atmfl/fl;Postn-Cre) were generated to address cell type-specific effects, which showed that the fibroblast is the key lineage mediating Dox-induced cardiotoxicity through ATM. Mechanistically, ATM activated the Fas ligand, which subsequently regulated apoptosis in cardiomyocytes at later stages. Therapeutically, a potent and selective inhibitor of ATM, KU55933, when administered systemically was able to prevent Dox-induced cardiotoxicity. ATM-regulated effects within cardiac fibroblasts are pivotal in Dox-induced cardiotoxicity, and antagonism of ATM and its functions may have potential therapeutic implications.