tbuckley/cabot-search huggingface dataset:
Comparison of two techniques assessing thoracoabdominal asynchrony in COPD patients
Authors: Desiderio Cano Porras, Denise de Moraes Paisani, Adriana Claudia Lunardi, Henrique Takachi Moriya, Celso R.F. Carvalho
Journal: European Respiratory Journal (2014)

COPD patients usually present thoracoabdominal asynchrony (TAA) that is considered as clinically relevant. Although there are several TAA estimation techniques, there is no consensus about which is the most appropriate to measure it. AIM: to compare two TAA quantification techniques in COPD patients at rest and during exercise. METHODS : 22 severe and very severe COPD patients (FEV1 40.2±10.5%pred) were assessed by optoelectronic plethysmography at rest and at mild (unload) and moderate (70% maximum workload) exercise in a cycle ergometer. TAA was estimated by the phase angle (PA) through Lissajous approach and by the percentage of time of paradoxical motion (PM). Also, TAA was calculated among all 3 compartments: upper (URC) and lower ribcage (LRC) and abdomen (AB). PM percentage values were expressed in a scale ranging from 0 to 180° to permit comparison with PA. Positive TAA values represent that the superior compartment is leading relative to the inferior. Two-way repeated measure ANOVA and the Holm-Sidak method were used. RESULTS : PM and PA techniques estimated differently TAA during mild exercise between URC-AB (respectively, -15.5±34.2° vs. -7.57±15.2°; p<0.05) and LRC-AB (-59.8±36.1° vs. -37.7±37.9°; p<0.05) and moderate exercise between URC-AB (-14.6±29.9° vs. -4.56±13.1°; p<0.05). Also, it was observed that using PM technique, TAA increased during mild exercise between LRC-AB (-59.8±36.1°; p<0.05) and moderate exercise between URC-LRC (54.1±43.7°; p<0.05) and LRC-AB (-54.5±37.1°; p<0.05) when compared to rest. CONCLUSION : PA and PM differently quantify thoracoabdominal asynchrony in COPD patients. It is important to consider the technique during respiratory evaluation in this population.
A Korean Patient With Fulminant Autoantibody-Negative Type 1 Diabetes
Authors: Tae S. Jung, Soon I. Chung, Me A. Kim, Sun J. Kim, Myoung H. Park, Deok R. Kim, Mi Y. Kang, Jong R. Hahm
Journal: Diabetes Care (2004)

Since 11 novel cases of fulminant autoantibody-negative type 1 diabetes were introduced by Imagawa and colleagues (1,2), about 150 additional cases have been reported. The development of typical fulminant autoantibody-negative type 1 diabetes is strictly confined to Japan. Although the pathogenetic mechanism still remains unclear, there is some evidence supporting the immunogenetic predisposition mechanism in the development of this subtype. A fulminant autoantibody-negative type 1 diabetic patient with insulitis and exocrine pancreatitis showed infiltration of a large number of CD8+ T-cell and peripheral GAD-reactive interferon-γ-producing CD4+ T-cell (3). According to previous reports, some HLA haplotypes, DRB1\*0405-DQB1\*0401, DQA1\*0303-DQB1\*0401, DQA1\*0302-DQB1\*0303, and DRB*0901 are closely associated with fulminant autoantibody-negative …
Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes
Authors: Ying-Gang Sun, Yin-Xiang Cao, Wen-Wei Wang, Shan-Feng Ma, Tai Yao, Yi-Chun Zhu
Journal: Cardiovascular Research (2008)

Hydrogen sulphide (H2S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H2S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H2S is a novel inhibitor of the L-type calcium channel current (ICa,L). Electrophysiological measurements were performed in cardiomyocytes isolated from Wistar-Kyoto and spontaneously hypertensive rats. Bath application of 100 µM NaHS (a H2S donor) significantly reduced the time required for the repolarization of the action potential. Inhibition of the peak ICa,L by NaHS was determined to be concentration-dependent (25, 50, 100, 200, and 400 µM). NaHS inhibited the recovery from depolarization-induced inactivation. Electric field-induced [Ca2+]i transients and contraction of single cardiomyocytes and isolated papillary muscles were reduced by NaHS treatment. In contrast, caffeine induced an increase in [Ca2+]i that was not altered by NaHS. NaHS had no effect on the KATP current or on the levels of cAMP and cGMP in the current study. H2S is a novel inhibitor of L-type calcium channels in cardiomyocytes. Moreover, H2S-induced inhibition of [Ca2+]i appears to be a secondary effect owing to its initial action towards ICa,L. The inhibitory effect of H2S on ICa,L requires further investigation, particularly in the exploration of new pathways involved in cardiac calcium homeostasis and disease pathology.
Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance
Authors: K. Kamiya, Y. Aoyama, Y. Shirafuji, T. Hamada, S. Morizane, K. Fujii, K. Hisata, K. Iwatsuki
Journal: British Journal of Dermatology (2012)

Antidesmoglein (anti-Dsg) 3 serum antibody titres are usually correlated with the disease activity of pemphigus vulgaris (PV), but some patients retain high titres even in remission.The aim of our study was to determine whether anti-Dsg3 antibodies in PV sera recognized calcium (Ca(2+) )-dependent or non-Ca(2+) -dependent epitopes, and to evaluate their pathogenicity.Dsg3 baculoprotein-coated enzyme-linked immunosorbent assay (ELISA) plates were treated with 0.5 mmol L(-1) ethylenediaminetetraacetic acid (EDTA). The binding ability of anti-Dsg3 monoclonal antibodies (mAbs) was analysed. Eight of the 83 patients with PV who were screened had elevated Dsg3 ELISA index values > 00 in remission. The binding ability of these PV sera was analysed. We evaluated the pathogenicity of anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes using a dissociation assay.The reactivity of pathogenic anti-Dsg3 mAbs against the Ca(2+) -dependent epitopes diminished markedly in the EDTA-treated ELISA, whereas no such reduction was observed in mAbs against the non-Ca(2+) -dependent epitopes. The sera of all the patients contained antibodies against both Ca(2+) -dependent and non-Ca(2+) -dependent epitopes. In six out of the eight patients, the ratio of antibodies against Ca(2+) -dependent to non-Ca(2+) -dependent epitopes decreased in remission. EDTA-treated Dsg3 baculoproteins adsorbed anti-Dsg3 serum antibodies against the non-Ca(2+) -dependent epitopes, but the remnant PV antibodies retained the ability to induce acantholysis in the dissociation assay.We have established an assay to measure indirectly the titres of anti-Dsg3 serum antibodies against the Ca(2+) -dependent epitopes, based on the differences between EDTA-untreated and EDTA-treated ELISA index values, as a routine laboratory test to reflect the pathogenic anti-Dsg3 serum antibody titres more accurately.
The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network
Authors: E. Terpos, O. Sezer, P.I. Croucher, R. García-Sanz, M. Boccadoro, J. San Miguel, J. Ashcroft, J. Bladé, M. Cavo, M. Delforge, M.-A. Dimopoulos, T. Facon, M. Macro, A. Waage, P. Sonneveld
Journal: Annals of Oncology (2009)
Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease in Men and Women
Authors: Tien Yin Wong, Ronald Klein, A. Richey Sharrett, Bruce B. Duncan, David J. Couper, James M. Tielsch, Barbara E. K. Klein, Larry D. Hubbard
Journal: JAMA (2002)

OF microvascular and macrovascular processes to the risk of coronary heart disease (CHD) is unknown, but its elucidation is important from etiological, preventive, and therapeutic perspectives. 1,2Coronary microvascular disease may explain the occurrence of myocardial ischemia without overt coronary artery blockage, [3][4][5][6][7] as well as risk of heart failure 8,9 and mortality 9 after myocardial infarction (MI).Because women with chest pain are more likely to have normal coronary arteries, 1-4,7 have higher mortality rates after an MI, 10,11 and have poorer outcomes after coronary artery bypass graft surgery, 12 it has been hypothesized that microvascular disease may play a more prominent role in the development of myocardial ischemia and definite CHD in women. 13,14However, most studies of microvascular dysfunction have been conducted in small numbers of highly selected symptomatic patients, [3][4][5][6][7]9 few have been prospective, 9 and none have been population based.][2][3][4][5][6][7] The retinal arterioles offer an opportunity to noninvasively explore the relation of systemic microvascular disease to CHD. 15 These arterioles narrow, and their media thicken and show sclerotic changes, in response to hypertension and other processes.16 In the population-based Atherosclerosis Risk in Communities (ARIC) study, we developed a computer-assisted, digital
Understanding the clinical dilemmas that shape medical students' ethical development: questionnaire survey and focus group study
Authors: L. K Hicks
Journal: BMJ (2001)

<h3>Background</h3> A patient decision aid (PDA) is a tool for shared decision making (SDM), which emphasises patient empowerment. It is useful in chronic diseases and when there are multiple, no best single treatment option. Although SDM is prevalent in Western countries, its use is limited in Chinese societies, where the adoption of a paternalistic approach is strong. Here, we report the development, acceptance and pilot test results of a PDA targeted at Chinese patients with primary open-angle glaucoma (POAG). <h3>Methods</h3> We developed a PDA designed for use in Chinese patients with POAG. Recruited subjects were given our PDA. Baseline evaluation included decision conflict scale (DCS), validated glaucoma adherence questionnaires and glaucoma knowledge questionnaire. Subjects were briefed through the PDA and instructed to read it that day. Three to four weeks later, follow-up questionnaire as described above were conducted with the addition of acceptance questionnaires. <h3>Results</h3> Data from 65 subjects were available. The PDA was well received among subjects. DCS improved from 48.9±20.4 at baseline to 34.3±20.3 during follow-up, with P&lt;0.01. Validated medication adherence questionnaires and knowledge showed improvement from baseline, which was statistically significant. <h3>Conclusions</h3> The use of PDA among Chinese subjects with POAG demonstrated positive reception and acceptance. Evaluation of its initial effects shows improvement in DCS, medication adherence and glaucoma knowledge. The implementation of SDM and PDA among Chinese subjects with POAG is encouraged. Future studies with randomised design and later evaluation time points can further reveal the impacts of PDA among Chinese subjects with POAG.
Reliability of the Snellen chart
Authors: P. McGraw, B. Winn, D. Whitaker
Journal: BMJ (1995)

robust scientific and informational infrastructure to support basic research.As a result they often cannot provide the academic and economic incentives to produce the associated research literature.Their journals generally have linguistic, financial, and production difficulties undreamt of by their Western counterparts, leading to irregular publication, indifferent aesthetic qualities, and poor editing and proof reading.Despite all these factors, and even though many of the journals are not subject to stringent peer review, they are nevertheless well worth exploring.Another reason for the lack of Third World literature in global databases is the simple fact that it is very difficult to find.International services such as Medline or the Science Citation Index typically index some 3000 journals-98% from the First World and only 2% from the Third World.This is a starting point for the vicious cycle affecting Third World literature: joumals that are not indexed are rarely stocked by librarians, hence rarely cited by authors, and hence rarely indexed. Extreme complacencyThe lack of interest in Third World literature is also a symptom of extreme complacency.Despite the acknowledged weaknesses of the Third World's abilities to collect and disseminate information can we believe that all knowledge lies in the West and, more particularly-since over 80% of all scientific research published in indexed journals is in English -in the English speaking part of the West?' Are we right in suggesting that the rest of the world adds nothing to the body of knowledge?Even if we should presume that most of the world's valid, important biomedical information originates in the West-and there is evidence (see, for example, Gaillard2) to suggest that this is wilful self delusion-what about at least a minority contribution from the rest?The 2% participation in international scientific discourse allowed by Western indexing services is simply too little to account for the scientific output of 80% of the world.
Author's response: co-trimoxazole treatment in idiopathic pulmonary fibrosis
Authors: Ludmila Shulgina, Anthony P Cahn, Edwin R Chilvers, Helen Parfrey, Allan B Clark, Edward C F Wilson, Orion P Twentyman, Anthony G Davison, John J Curtin, Michael B Crawford, Andrew M Wilson
Journal: Thorax (2013)

We thank Neto et al 1 for their comments on our paper2 and for reiterating the points contained within it. ‘The survival benefit conferred by co-trimoxazole, if real, could be due to its antimicrobial activity as there was a significant reduction in the number of infections in the group receiving active treatment’, and this is likely to occur more frequently in patients receiving immunosuppressive treatment. The proportion of deaths in the intention-to-treat group on immunosuppression was 29 of 37. As stated, ‘this study was not designed to collect microbiological information’ however, the results were adjusted for baseline azathioprine or mycophenylate …
Biased mutations and microsatellite variation
Authors: L. A. Zhivotovsky, M. W. Feldman, S. A. Grishechkin
Journal: Molecular Biology and Evolution (1997)

Mutation bias is one of the forces that may constrain the variation at microsatellite loci. Here, we study the dynamics of population statistics and the genetic distance between two populations under multiple stepwise mutations with linear bias and random drift. Expressions are derived for these statistics as functions of time, as well as at mutation-drift equilibrium. Applying these expressions to published data on humans and chimpanzees, the regression coefficient of mutation bias on allele size was estimated to be at least between -0.0064 and -0.013. The assumption of mutational bias produces larger estimates of divergence times than are obtained in its absence; in particular, the time of split between African and non-African human populations is estimated to be between 183,000 and 222,000 years, assuming one-step mutations and no selection. With multistep mutations, the divergence time is estimated to be lower.
Differing Causes of Pregnancy Loss in Type 1 and Type 2 Diabetes
Authors: Tim Cundy, Greg Gamble, Leonie Neale, Rose Elder, Paul McPherson, Patrick Henley, Janet Rowan
Journal: Diabetes Care (2007)

Women with type 2 and type 1 diabetes have differing risk factors for pregnancy loss. We compared the rates and causes of pregnancy loss in women with type 1 and type 2 diabetes.We utilized prospectively collected data on all pregnancies in a 20-year period (1986-2005) from a single center with a high prevalence of type 2 diabetes. Pregnancy losses included terminations for medical reasons and deaths up to 1 month postpartum but not spontaneous pregnancy losses <20 weeks' gestation.There were 870 pregnancies in women with known diabetes (330 with type 1 and 540 with type 2 diabetes) and 325 in women with diabetes diagnosed in pregnancy but persisting postpartum (97% type 2 diabetes). The rate of pregnancy loss was similar in type 1 and type 2 diabetes (2.6 vs. 3.7%, P = 0.39), but the causes of pregnancy loss differed. In type 1 diabetes >75% were attributable to major congenital anomalies or prematurity; in type 2 diabetes >75% were attributable to stillbirth or chorioamnionitis (P = 0.017). Women with type 2 and type 1 diabetes had similar A1C at presentation and near term, but the former were older (P < 0.001) and more obese (P < 0.0001).There are significant differences in the main causes of pregnancy loss in women with type 1 and type 2 diabetes. The higher rates of stillbirth in women with type 2 diabetes, suggest that other features, such as obesity, contribute significantly to pregnancy losses.
Pathological Role of Serum- and Glucocorticoid-Regulated Kinase 1 in Adverse Ventricular Remodeling
Authors: Saumya Das, Takeshi Aiba, Michael Rosenberg, Katherine Hessler, Chunyang Xiao, Pablo A. Quintero, Filomena G. Ottaviano, Ashley C. Knight, Evan L. Graham, Pontus Boström, Michael R. Morissette, Federica del Monte, Michael J. Begley, Lewis C. Cantley, Patrick T. Ellinor, Gordon F. Tomaselli, Anthony Rosenzweig
Journal: Circulation (2012)

Background— Heart failure is a growing cause of morbidity and mortality. Cardiac phosphatidylinositol 3-kinase signaling promotes cardiomyocyte survival and function, but it is paradoxically activated in heart failure, suggesting that chronic activation of this pathway may become maladaptive. Here, we investigated the downstream phosphatidylinositol 3-kinase effector, serum- and glucocorticoid-regulated kinase-1 (SGK1), in heart failure and its complications. Methods and Results— We found that cardiac SGK1 is activated in human and murine heart failure. We investigated the role of SGK1 in the heart by using cardiac-specific expression of constitutively active or dominant-negative SGK1. Cardiac-specific activation of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular arrhythmias. The proarrhythmic effects of SGK1 were linked to biochemical and functional changes in the cardiac sodium channel and could be reversed by treatment with ranolazine, a blocker of the late sodium current. Conversely, cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress from fibrosis, heart failure, and sodium channel alterations. Conclusions— SGK1 appears both necessary and sufficient for key features of adverse ventricular remodeling and may provide a novel therapeutic target in cardiac disease.
Health effects of passive smoking 10: Summary of effects of parental smoking on the respiratory health of children and implications for research
Authors: D. G Cook, D. P Strachan
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Two recent reviews have assessed the effect of parental smoking on respiratory disease in children. <h3>METHODS</h3> The results of the systematic quantitative review published as a series in<i>Thorax</i> are summarised and brought up to date by considering papers appearing on Embase or Medline up to June 1998. The findings are compared with those of the review published recently by the Californian Environmental Protection Agency (EPA). Areas requiring further research are identified. <h3>RESULTS</h3> Overall there is a very consistent picture with odds ratios for respiratory illnesses and symptoms and middle ear disease of between 1.2 and 1.6 for either parent smoking, the odds usually being higher in pre-school than in school aged children. For sudden infant death syndrome the odds ratio for maternal smoking is about 2. Significant effects from paternal smoking suggest a role for postnatal exposure to environmental tobacco smoke. Recent publications do not lead us to alter the conclusions of our earlier reviews. While essentially narrative rather than systematic and quantitative, the findings of the Californian EPA review are broadly similar. In addition they have reviewed studies of the effects of environmental tobacco smoke on children with cystic fibrosis and conclude from the limited evidence that there is a strong case for a relationship between parental smoking and admissions to hospital. They also review data from adults of the effects of acute exposure to environmental tobacco smoke under laboratory conditions which suggest acute effects on spirometric parameters rather than on bronchial hyperresponsiveness. It seems likely that such effects are also present in children. <h3>CONCLUSIONS</h3> Substantial benefits to children would arise if parents stopped smoking after birth, even if the mother smoked during pregnancy. Policies need to be developed which reduce smoking amongst parents and protect infants and young children from exposure to environmental tobacco smoke. The weight of evidence is such that new prevalence studies are no longer justified. What are needed are studies which allow comparison of the effects of critical periods of exposure to cigarette smoke, particularly in utero, early infancy, and later childhood. Where longitudinal studies are carried out they should be analysed to look at the way in which changes in exposure are related to changes in outcome. Better still would be studies demonstrating reversibility of adverse effects, especially in asthmatic subjects or children with cystic fibrosis.
Dynamin 2–dependent endocytosis is required for sustained S1PR1 signaling
Authors: Tim Willinger, Shawn M. Ferguson, João P. Pereira, Pietro De Camilli, Richard A. Flavell
Journal: The Journal of Experimental Medicine (2014)

Sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) is critical for lymphocyte egress from lymphoid organs. Lymphocytes encounter low S1P concentrations near exit sites before transmigration, yet S1PR1 signaling is rapidly terminated after exposure to S1P. How lymphocytes maintain S1PR1 signaling in a low S1P environment near egress sites is unknown. Here we identify dynamin 2, an essential component of endocytosis, as a novel regulator of T cell egress. Mice with T cell–specific dynamin 2 deficiency had profound lymphopenia and impaired egress from lymphoid organs. Dynamin 2 deficiency caused impaired egress through regulation of S1PR1 signaling, and transgenic S1PR1 overexpression rescued egress in dynamin 2 knockout mice. In low S1P concentrations, dynamin 2 was essential for S1PR1 internalization, which enabled continuous S1PR1 signaling and promoted egress from both thymus and lymph nodes. In contrast, dynamin 2–deficient cells were only capable of a pulse of S1PR1 signaling, which was insufficient for egress. Our results suggest a possible mechanism by which T lymphocytes positioned at exit portals sense low S1P concentrations, promoting their egress into circulatory fluids.