tbuckley/cabot-search huggingface dataset:
Homocysteine Levels and the Risk of Osteoporotic Fracture
Authors: Joyce B.J. van Meurs, Rosalie A.M. Dhonukshe-Rutten, Saskia M.F. Pluijm, Marjolein van der Klift, Robert de Jonge, Jan Lindemans, Lisette C.P.G.M. de Groot, Albert Hofman, Jacqueline C.M. Witteman, Johannes P.T.M. van Leeuwen, Monique M.B. Breteler, Paul Lips, Huibert A.P. Pols, André G. Uitterlinden
Journal: New England Journal of Medicine (2004)

Very high plasma homocysteine levels are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures.We studied the association between circulating homocysteine levels and the risk of incident osteoporotic fracture in 2406 subjects, 55 years of age or older, who participated in two separate prospective, population-based studies. In the Rotterdam Study, there were two independent cohorts: 562 subjects in cohort 1, with a mean follow-up period of 8.1 years; and 553 subjects in cohort 2, with a mean follow-up period of 5.7 years. In the Longitudinal Aging Study Amsterdam, there was a single cohort of 1291 subjects, with a mean follow-up period of 2.7 years. Multivariate Cox proportional-hazards regression models were used for analysis of the risk of fracture, with adjustment for age, sex, body-mass index, and other characteristics that may be associated with the risk of fracture or with increased homocysteine levels.During 11,253 person-years of follow-up, osteoporotic fractures occurred in 191 subjects. The overall multivariable-adjusted relative risk of fracture was 1.4 (95 percent confidence interval, 1.2 to 1.6) for each increase of 1 SD in the natural-log-transformed homocysteine level. The risk was similar in all three cohorts studied, and it was also similar in men and women. A homocysteine level in the highest age-specific quartile was associated with an increase by a factor of 1.9 in the risk of fracture (95 percent confidence interval, 1.4 to 2.6). The associations between homocysteine levels and the risk of fracture appeared to be independent of bone mineral density and other potential risk factors for fracture.An increased homocysteine level appears to be a strong and independent risk factor for osteoporotic fractures in older men and women.
Atrium-Selective Sodium Channel Block as a Strategy for Suppression of Atrial Fibrillation
Authors: Alexander Burashnikov, José M. Di Diego, Andrew C. Zygmunt, Luiz Belardinelli, Charles Antzelevitch
Journal: Circulation (2007)

Background— The development of selective atrial antiarrhythmic agents is a current strategy for suppression of atrial fibrillation (AF). Methods and Results— Whole-cell patch clamp techniques were used to evaluate inactivation of peak sodium channel current ( I Na ) in myocytes isolated from canine atria and ventricles. The electrophysiological effects of therapeutic concentrations of ranolazine (1 to 10 μmol/L) and lidocaine (2.1 to 21 μmol/L) were evaluated in canine isolated coronary-perfused atrial and ventricular preparations. Half-inactivation voltage of I Na was ≈15 mV more negative in atrial versus ventricular cells under control conditions; this difference increased after exposure to ranolazine. Ranolazine produced a marked use-dependent depression of sodium channel parameters, including the maximum rate of rise of the action potential upstroke, conduction velocity, and diastolic threshold of excitation, and induced postrepolarization refractoriness in atria but not in ventricles. Lidocaine also preferentially suppressed these parameters in atria versus ventricles, but to a much lesser extent than ranolazine. Ranolazine produced a prolongation of action potential duration (APD 90 ) in atria, no effect on APD 90 in ventricular myocardium, and an abbreviation of APD 90 in Purkinje fibers. Lidocaine abbreviated both atrial and ventricular APD 90 . Ranolazine was more effective than lidocaine in terminating persistent AF and in preventing the induction of AF. Conclusions— Our study demonstrates important differences in the inactivation characteristics of atrial versus ventricular sodium channels and a striking atrial selectivity for the action of ranolazine to produce use-dependent block of sodium channels, leading to suppression of AF. Our results point to atrium-selective sodium channel block as a novel strategy for the management of AF.
Diaphragm Sarcolemmal Injury Is Induced by Sepsis and Alleviated by Nitric Oxide Synthase Inhibition
Authors: MENG-CHIH LIN, SATORU EBIHARA, QASIM EL DWAIRI, SABAH N. A. HUSSAIN, LIYING YANG, STEWART B. GOTTFRIED, ALAIN COMTOIS, BASIL J. PETROF
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Endotoxemia is associated with impaired diaphragm contractility, and increased nitric oxide (NO) production has recently been implicated in this phenomenon. However, the precise nature of sepsis-related alterations in diaphragm myofiber function remains unclear. We tested the hypothesis that enhanced NO synthesis during sepsis produces diaphragm sarcolemmal injury with attendant abnormalities of myofiber membrane electrophysiology. Two different rat sepsis models were employed: acute (4 h) intraarterial endotoxin (LPS; 20 mg/kg) and subacute (24 h) peritonitis induced by cecal ligation and perforation (CLP). Diaphragm damage occurred after both LPS and CLP, as indicated by hyperpermeability of myofibers to a low molecular weight tracer dye, which is normally unable to penetrate the sarcolemma. Sarcolemmal injury was significantly correlated with reductions in the resting membrane potential (E m) of single diaphragm myofibers. Western analysis revealed increased diaphragmatic expression of the inducible isoform of NO synthase (iNOS) after LPS and CLP. An inhibitor of NOS activity, lNMMA, significantly decreased morphologic as well as electrophysiologic signs of myofiber membrane injury and dysfunction. Therefore, we conclude that both acute endotoxemia and subacute peritonitis models of sepsis lead to significant sarcolemmal damage and altered E m in diaphragm myofibers. These changes appear to be mediated, at least in part, through the pathway of increased nitric oxide production.
Survival and Clonal Expansion of Mutating “Forbidden” (Immunoglobulin Receptor–Deficient) Epstein-Barr Virus–Infected B Cells in Angioimmunoblastic T Cell Lymphoma
Authors: Andreas Bräuninger, Tilmann Spieker, Klaus Willenbrock, Philippe Gaulard, Hans-Heinrich Wacker, Klaus Rajewsky, Martin-Leo Hansmann, Ralf Küppers
Journal: The Journal of Experimental Medicine (2001)

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a peculiar T cell lymphoma, as expanding B cell clones are often present besides the malignant T cell clones. In addition, large numbers of Epstein-Barr virus (EBV)-infected B cells are frequently observed. To analyze the differentiation status and clonal composition of EBV-harboring B cells in AILD, single EBV-infected cells were micromanipulated from lymph nodes of six patients with frequent EBV+ cells and their rearranged immunoglobulin (Ig) genes analyzed. Most EBV-infected B cells carried mutated Ig genes, indicating that in AILD, EBV preferentially resides in memory and/or germinal center B cells. EBV+ B cell clones observed in all six cases ranged from small polyclonal to large monoclonal expansions and often showed ongoing somatic hypermutation while EBV− B cells showed little tendency for clonal expansion. Surprisingly, many members of expanding B cell clones had acquired destructive mutations in originally functional V gene rearrangements and showed an unfavorable high load of replacement mutations in the framework regions, indicating that they accumulated mutations over repeated rounds of mutation and division while not being selected through their antigen receptor. This sustained selection-free accumulation of somatic mutations is unique to AILD. Moreover, the survival and clonal expansion of “forbidden” (i.e., Ig-deficient) B cells has not been observed before in vivo and thus represents a novel type of viral latency in the B cell compartment. It is likely the interplay between the microenvironment in AILD lymph nodes and the viral transformation that leads to the survival and clonal expansion of Ig-less B cells.
Extending the behavioral sciences framework: Clarification of methods, predictions, and concepts
Authors: Alex Mesoudi, Kevin N. Laland
Journal: Behavioral and Brain Sciences (2007)

We applaud Gintis's attempt to provide an evolutionary-based framework for the behavioral sciences, and note a number of similarities with our own recent cultural evolutionary structure for the social sciences. Gintis's proposal would be further strengthened by a greater emphasis on additional methods to evolutionary game theory, clearer empirical predictions, and a broader consideration of cultural transmission.
Absence of Deep Inspiration–induced Bronchoprotection against Inhaled Allergen
Authors: George Pyrgos, Trisevgeni Kapsali, Solbert Permutt, Alkis Togias
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Deep inspiration-induced bronchoprotection appears to be a major mechanism through which airway obstruction by spasmogens is avoided. Loss of bronchoprotection is associated with airway hyper-responsiveness. Individuals with allergic rhinitis and no airway hyperresponsiveness develop obstruction after allergen inhalation. To test the hypothesis that deep inspiration-induced bronchoprotection is not active against allergic reactions, we performed four single-dose bronchial challenges, two with methacholine and two with allergen, on 10 subjects with allergic rhinitis. Without deep inspirations, the methacholine-induced reduction in FEV1 from baseline was 36.9 +/- 3.6% (mean +/- SEM); this was attenuated to 15.0 +/- 2.0 when five deep inspirations preceded methacholine inhalation (p = 0.0001). When allergen was inhaled, the reduction in FEV1 was 24.7 +/- 2.9% and 28.8 +/- 6.4% without and with deep inspirations, respectively. We conclude that bronchoprotection by deep inspirations is absent against allergic reactions. Understanding the cause of this phenomenon may shed light into the pathogenesis of airway hyperresponsiveness in allergic asthma.
Subepithelial collagen in intestinal malabsorption.
Authors: R Bossart, K Henry, C C Booth, W F Doe
Journal: Gut (1975)

Intestinal biopsies from 146 patients with adult coeliac disease and 13 patients with intestinal villous atrophy of different aetiology were assessed for the presence of subepithelial collagen and compared with a group of 20 control subjects. Subepithelial collagen was a common and non-specific finding observed in intestinal biopsies from patients suffering from adult coeliac disease (36%) and tropical sprue. In adult coeliac disease the described subepithelial changes usually regress following treatment, though marked subepithelial collagen deposition may indicate a poor prognosis. The study showed that the presence of marked subepithelial collagen in a flat jejunal biopsy does not define a separate clinical entity.
Online registration of monthly sports participation after anterior cruciate ligament injury: a reliability and validity study
Authors: Hege Grindem, Ingrid Eitzen, Lynn Snyder-Mackler, May Arna Risberg
Journal: British Journal of Sports Medicine (2013)

Background The current methods measuring sports activity after anterior cruciate ligament (ACL) injury are commonly restricted to the most knee-demanding sports, and do not consider participation in multiple sports. We therefore developed an online activity survey to prospectively record the monthly participation in all major sports relevant to our patient-group. Objective To assess the reliability, content validity and concurrent validity of the survey and to evaluate if it provided more complete data on sports participation than a routine activity questionnaire. Methods 145 consecutively included ACL-injured patients were eligible for the reliability study. The retest of the online activity survey was performed 2 days after the test response had been recorded. A subsample of 88 ACL-reconstructed patients was included in the validity study. The ACL-reconstructed patients completed the online activity survey from the first to the 12th postoperative month, and a routine activity questionnaire 6 and 12 months postoperatively. Results The online activity survey was highly reliable (κ ranging from 0.81 to 1). It contained all the common sports reported on the routine activity questionnaire. There was a substantial agreement between the two methods on return to preinjury main sport (κ=0.71 and 0.74 at 6 and 12 months postoperatively). The online activity survey revealed that a significantly higher number of patients reported to participate in running, cycling and strength training, and patients reported to participate in a greater number of sports. Conclusions The online activity survey is a highly reliable way of recording detailed changes in sports participation after ACL injury. The findings of this study support the content and concurrent validity of the survey, and suggest that the online activity survey can provide more complete data on sports participation than a routine activity questionnaire.
Expression of Wnt-5a Is Correlated with Aggressiveness of Gastric Cancer by Stimulating Cell Migration and Invasion
Authors: Manabu Kurayoshi, Naohide Oue, Hideki Yamamoto, Michiko Kishida, Atsuko Inoue, Toshimasa Asahara, Wataru Yasui, Akira Kikuchi
Journal: Cancer Research (2006)

Abstract Wnt-5a is a representative ligand that activates a β-catenin-independent pathway in the Wnt signaling. Although abnormal activation of β-catenin-dependent pathway is often observed in human cancer, the relationship between β-catenin-independent pathway and tumorigenesis is not clear. We sought to clarify how Wnt-5a is involved in aggressiveness of gastric cancer. Abnormal expression of Wnt-5a was observed in 71 of 237 gastric cancer cases by means of immunohistochemistry. The positivity of Wnt-5a expression was correlated with advanced stages and poor prognosis of gastric cancer. Wnt-5a had the abilities to stimulate cell migration and invasion in gastric cancer cells. Wnt-5a activated focal adhesion kinase and small GTP-binding protein Rac, both of which are known to play a role in cell migration. Cell migration, membrane ruffling, and turnover of paxillin were suppressed in Wnt-5a knockdown cells. Furthermore, anti-Wnt-5a antibody suppressed gastric cancer cell migration. These results suggest that Wnt-5a stimulates cell migration by regulating focal adhesion complexes and that Wnt-5a is not only a prognostic factor but also a good therapeutic target for gastric cancer. (Cancer Res 2006; 66(21): 10439-48)
Health experts launch campaign to reverse NHS reforms
Authors: A. O'Dowd
Journal: BMJ (2014)

Leading health experts and academics have launched a campaign that aims to reverse some of the fundamental aspects of the NHS changes brought about by the Health and Social Care Act 2012.

The campaign seeks support for the so called NHS Reinstatement Bill 2015,1 which was launched on 4 October by Allyson Pollock, professor of public health research and policy at Queen Mary University of London, and …
Postoperative bile leakage: endoscopic management.
Authors: P H Davids, E A Rauws, G N Tytgat, K Huibregtse
Journal: Gut (1992)

Bile leakage is an infrequent but serious complication after biliary tract surgery. This non-randomised single centre study evaluated the endoscopic management of this problem in 55 consecutive cases. Treatment consisted of standard sphincterotomy and, if needed, subsequent stone extraction with or without endoprosthesis placement. The aim of all treatments was to facilitate bile flow into the duodenum. The biliary tract and the site of the leakage were visualised during endoscopic retrograde cholangiopancreatography (ERCP) in 98%. There was distal obstruction in 33--caused by retained gall stones in 15 patients and concomitant strictures in 18. Overall, 48 of 55 patients were treated endoscopically. An excellent outcome (clinical and radiological resolution of the bile leak) was achieved in 43 patients (90%). Five patients (10%) had continuing sepsis from which they died. Postoperative bile leakage can be diagnosed safely and effectively by ERCP and subsequent endoscopic management is successful in most cases.
Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure
Authors: Julio Núñez, Eduardo Núñez, Gema Miñana, Vicent Bodí, Gregg C. Fonarow, Vicente Bertomeu‐González, Patricia Palau, Pilar Merlos, Silvia Ventura, Francisco J. Chorro, Pau Llàcer, Juan Sanchis
Journal: European Journal of Heart Failure (2012)
Predicting poor functional outcome in community-dwelling older adults with knee pain: prognostic value of generic indicators
Authors: C. D Mallen, G. Peat, E. Thomas, R. Lacey, P. Croft
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> In longitudinal studies across a range of regional musculoskeletal pain syndromes, certain prognostic factors consistently emerge. They are "generic" in the sense that they appear to apply regardless of the particular anatomical site or underlying cause of the pain. <h3>Objective:</h3> To investigate the value of generic indicators of poor functional outcome for knee pain and osteoarthritis in the community. <h3>Methods:</h3> We conducted a population-based cohort study of adults aged ⩾50 years with knee pain as part of the Clinical Assessment Study (Knee) (CAS(K)). At baseline, participants completed a postal questionnaire and attended a research clinic where they completed a further questionnaire and underwent structured physical examination and <i>x</i> rays. The 18-month follow-up was via a self-completed questionnaire. Risk ratios were calculated using Cox regression with a fixed time period assigned to each participant. <h3>Results:</h3> In total, 60% of participants experienced a poor outcome at 18 months. Twelve univariate associations were associated with poor outcome, with four variables remaining in the multivariate model (older age, being overweight or obese, having possible or probable anxiety, and more severe pain).Using a simple unweighted additive risk score (1 point each for age ⩾60 years, body mass index ⩾25 kg/m<sup>2</sup>, possible or probable anxiety, Chronic Pain Grade II–IV), 90% of participants with all four generic indicators were correctly classified. <h3>Conclusions:</h3> This study has demonstrated that generic prognostic indicators can be used to determine the prognosis of older people in the community with knee pain.
Evidence Mounts That Nitrite Contributes to Hypoxic Vasodilation in the Human Circulation
Authors: Mark T. Gladwin
Journal: Circulation (2008)

ypoxic vasodilation is a conserved physiological re- sponse to hypoxia that matches blood flow and oxygen delivery to tissue metabolic demand.This fundamental physiological process has been characterized for Ͼ100 years since the initial description by Roy and Brown 1 in 1880.Hypoxic vasodilation requires a sensor mechanism that can detect a divergence in the normal relationship between delivered blood oxygen and tissue oxygen consumption. 2This hypoxic sensor mechanism must be coupled to the feedback generation of vasodilatory effectors that increase blood flow to maintain adequate tissue oxygenation.In short, hypoxic vasodilation requires hypoxia and/or pH sensing coupled to the release of a vasodilating signal.In mammalian species, the set point for hypoxic vasodilation occurs as the hemoglobin desaturates from 60% to 40%, around a partial pressure of oxygen ranging from 40 to 20 mm Hg. 3 Despite the fact that the hypoxic vasodilation response was discovered almost 150 years ago, the identities of the oxygen sensor mechanism and the specific feedback vasodilator effectors remain uncertain.Although a number of mediators have been considered, including adenosine, nitric oxide (NO), ATP-sensitive potassium (K ATP ) channels, endothelium-derived hyperpolarizing factor (candidates include CO, H 2 O 2 , or ONOO Ϫ ), and prostacyclin, 2,4 the specific blockade of many of these pathways fails to completely inhibit hypoxic vasodilation.
The Influence of Active and Passive Smoking on Habitual Snoring
Authors: Karl A. Franklin, Thórarinn Gíslason, Ernst Omenaas, Rain Jõgi, Erik Juel Jensen, Eva Lindberg, Maria Gunnbjörnsdóttir, Lennarth Nyström, Birger N. Laerum, Eythor Björnsson, Kjell Torén, Christer Janson
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The impact of active smoking, passive smoking, and obesity on habitual snoring in the population is mainly unknown. We aimed to study the relationship of habitual snoring with active and passive tobacco smoking in a population-based sample. A total of 15,555 of 21,802 (71%) randomly selected men and women aged 25–54 years from Iceland, Estonia, Denmark, Norway, and Sweden answered a postal questionnaire. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was more prevalent among current smokers (24.0%, p < 0.0001) and ex-smokers (20.3%, p < 0.0001) than in never-smokers (13.7%). Snoring was also more prevalent in never-smokers exposed to passive smoking at home on a daily basis than in never-smokers without this exposure (19.8% vs. 13.3%, p < 0.0001). The frequency of habitual snoring increased with the amount of tobacco smoked. Active smoking and passive smoking were related to snoring, independent of obesity, sex, center, and age. Ever smoking accounted for 17.1% of the attributable risk of habitual snoring, obesity (body mass index ⩾ 30 kg/m2) for 4.3%, and passive smoking for 2.2%. Smoking, both current and ex-smoking, is a major contributor to habitual snoring in the general population. Passive smoking is a previously unrecognized risk factor for snoring among adults.
Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors
Authors: Sheila Dias, Hamilton Silva, Ana Cumano, Paulo Vieira
Journal: The Journal of Experimental Medicine (2005)

Interleukin-7 (IL-7) promotes survival and expansion of lymphoid precursors. We show here that, in addition, IL-7 has a fundamental role, as early as the stage of the multipotent (B/T/NK) common lymphoid progenitor (CLP), in maintaining the B cell differentiation program open. CLPs generated in the absence of IL-7 have normal T/NK differentiation potential, but severely impaired B potential. Accordingly, CLPs from IL-7-deficient mice express lower amounts of early B cell factor (EBF) and Pax5 than wild-type CLPs, but similar amounts of GATA-3. Importantly, induced overexpression of EBF is sufficient to restore the B potential in these cells. These results indicate that IL-7 directs commitment of CLPs by modulating EBF expression. This is the first example of a cytokine influencing lymphoid lineage commitment in multipotent progenitors and highlights the relevance of the expression of a functional IL-7 receptor at the CLP stage.
Relationship of IgE to basophil phenotypes in peanut-sensitized adults
Authors: Emily C. McGowan, Jessica H. Savage, Jean-Paul Courneya, Patricia M. Sterba, Saitu Parihar, Jing Lin, Gustavo Gimenez, Hugh A. Sampson, John Schroeder, Donald MacGlashan, Robert A. Wood, Robert G. Hamilton, Sarbjit Saini
Journal: Journal of Allergy and Clinical Immunology (2014)