tbuckley/cabot-search huggingface dataset:
Lethal Autoimmune Myocarditis in Interferon-γ Receptor–Deficient Mice
Authors: U. Eriksson, M. O. Kurrer, R. Bingisser, H. P. Eugster, P. Saremaslani, F. Follath, S. Marsch, U. Widmer
Journal: Circulation (2001)

Background —Interferon-γ (IFN-γ) is an essential cytokine in the regulation of inflammatory responses in autoimmune diseases. Little is known about its role in inflammatory heart disease. Methods and Results —We showed that IFN-γ receptor–deficient mice (IFN-γR –/– ) on a BALB/c background immunized with a peptide derived from cardiac α-myosin heavy chain develop severe myocarditis with high mortality. Although myocarditis subsided in wild-type mice after 3 weeks, IFN-γR –/– mice showed persistent disease. The persistent inflammation was accompanied by vigorous in vitro CD4 T-cell responses and impaired inducible nitric oxide synthase expression, together with evidence of impaired nitric oxide production in IFN-γR –/– hearts. Treatment of wild-type mice with the nitric oxide synthetase inhibitor N -nitro-l-arginine-methyl-ester enhanced in vitro CD4 T-cell proliferation and prevented healing of myocarditis. Conclusions —Our data provide evidence that IFN-γ protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses.
Upregulation of Nox4 by Hypertrophic Stimuli Promotes Apoptosis and Mitochondrial Dysfunction in Cardiac Myocytes
Authors: Tetsuro Ago, Junya Kuroda, Jayashree Pain, Cexiong Fu, Hong Li, Junichi Sadoshima
Journal: Circulation Research (2010)

Rationale : NADPH oxidases are a major source of superoxide (O 2 − ) in the cardiovascular system. The function of Nox4, a member of the Nox family of NADPH oxidases, in the heart is poorly understood. Objective : The goal of this study was to elucidate the role of Nox4 in mediating oxidative stress and growth/death in the heart. Methods and Results : Expression of Nox4 in the heart was increased in response to hypertrophic stimuli and aging. Neither transgenic mice with cardiac specific overexpression of Nox4 (Tg-Nox4) nor those with catalytically inactive Nox4 (Tg-Nox4-P437H) showed an obvious baseline cardiac phenotype at young ages. Tg-Nox4 gradually displayed decreased left ventricular (LV) function with enhanced O 2 − production in the heart, which was accompanied by increased apoptosis and fibrosis at 13 to 14 months of age. On the other hand, the level of oxidative stress was attenuated in Tg-Nox4-P437H. Although the size of cardiac myocytes was significantly greater in Tg-Nox4 than in nontransgenic, the LV weight/tibial length was not significantly altered in Tg-Nox4 mice. Overexpression of Nox4 in cultured cardiac myocytes induced apoptotic cell death but not hypertrophy. Nox4 is primarily localized in mitochondria and upregulation of Nox4 enhanced both rotenone- and diphenyleneiodonium-sensitive O 2 − production in mitochondria. Cysteine residues in mitochondrial proteins, including aconitase and NADH dehydrogenases, were oxidized and their activities decreased in Tg-Nox4. Conclusions : Upregulation of Nox4 by hypertrophic stimuli and aging induces oxidative stress, apoptosis and LV dysfunction, in part because of mitochondrial insufficiency caused by increased O 2 − production and consequent cysteine oxidation in mitochondrial proteins.
Depletion of CLL-associated patrolling monocytes and macrophages controls disease development and repairs immune dysfunction in vivo
Authors: B S Hanna, F McClanahan, H Yazdanparast, N Zaborsky, V Kalter, P M Rößner, A Benner, C Dürr, A Egle, J G Gribben, P Lichter, M Seiffert
Journal: Leukemia (2015)
Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage
Authors: M Ahlmén, B Svensson, K Albertsson, K Forslind, I Hafström
Journal: Annals of the Rheumatic Diseases (2009)

Objective: To evaluate gender differences in score on 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional Impairment (SOFI) and to relate these scores to radiographic joint destruction. Methods: In all, 549 patients with early RA (62% women) from the BARFOT (for “Better Anti-Rheumatic FarmacOTherapy”) study were included. At baseline, 1, 2 and 5 years DAS28, HAQ and SOFI scoring, and radiographs of hands and feet were performed. The radiographs were scored using the van der Heijde–Sharp score. Results: In women the DAS28 was significantly higher than in men due to higher scores for general health and tender joints. Likewise, HAQ and VAS pain were rated significantly higher in women. The SOFI score was worse in men during the first 2 years, depending on higher upper limb scores. Total Sharp score (TotSharp), erosion score and joint space narrowing score did not differ between the sexes at any time point. The DAS28 area under the curve (AUC) correlated significantly with TotSharp at 5 years in both genders (r = 0.316, r = 0.313) mainly owing to swollen joints and erythrocyte sedimentation rate (ESR). The SOFI AUC correlated significantly with TotSharp in women (r = 0.135 to 0.220) but not in men. Conclusions: Despite a similar degree of radiographic joint destruction women had, compared with men, worse scores for DAS28 and HAQ, possibly due to higher pain perception and less muscular strength and perhaps because men overestimate their functional capacity.
STUDIES OF HEMOLYTIC STREPTOCOCCAL INFECTION I. FACTORS INFLUENCING THE OUTCOME OF ERYSIPELAS
Authors: Chester S. Keefer, Wesley W. Spink
Journal: Journal of Clinical Investigation (1936)

In order to gather more precise information regarding the factors influencing the course and outcome of certain hemolytic streptococcal infections, we have examined the hospital records of 1400 patients with erysipelas who were admitted to the Boston City Hospital during a period of CASES OF SCARLET ERYSI- FEVER *PELAS THOU-SAND 20 200 15 150 10 100 5 50of scarlet fever as it occurred in Massachusetts over an eleven-year period was found to be iden- tical with that of erysipelas as observed at the Boston City Hospital (Figure 1).If one is permitted to use scarlet fever as an index of such infections, it is evident, then, that erysipelas has 9 10 It 12 -FIG.1. THE
Beyond rationality: Counterfactual thinking and behavior regulation
Authors: Kai Epstude, Neal J. Roese
Journal: Behavioral and Brain Sciences (2007)

Abstract Counterfactual thinking may be described as disciplined, realistic, and rational, but we move a step further to describe a theoretical perspective centering on behavior regulation. According to this perspective, counterfactual thinking primarily centers on coordination of ongoing behavior. In short, most “if only” thoughts in daily life center on the acquisition of goals; hence, counterfactual thinking may be illuminated by considering the large literature on goal cognition.
GFR Normalized to Total Body Water Allows Comparisons across Genders and Body Sizes
Authors: Bjørn O. Eriksen, Toralf Melsom, Ulla D. Mathisen, Trond G. Jenssen, Marit D. Solbu, Ingrid Toft
Journal: Journal of the American Society of Nephrology (2011)

The normalization of GFR to a standardized body-surface area of 1.73 m(2) impedes comparison of GFR across individuals of different genders, heights, or weights. Ideally, GFR should be normalized to a parameter that best explains variation in GFR. Here, we measured true GFR by iohexol clearance in a representative sample of 1627 individuals from the general population who did not have diabetes, cardiovascular disease, or kidney disease. We also estimated total body water (TBW), extracellular fluid volume, lean body mass, liver volume, metabolic rate, and body-surface area. We compared two methods of normalizing GFR to these physiologic variables: (1) the conventional method of scaling GFR to each physiologic variable by simple division and (2) a method based on regression of the GFR on each variable. TBW explained a higher proportion of the variation in GFR than the other physiologic variables. GFR adjusted for TBW by the regression method exhibited less dependence on gender, height, and weight compared with the other physiologic variables. Thus, adjusting GFR for TBW by the regression method allows direct comparisons between individuals of different genders, weights, and heights. We propose that regression-based normalization of GFR to a standardized TBW of 40 L should replace the current practice of normalizing GFR to 1.73 m(2) of body-surface area.
Functional Diversity of DNA Methyltransferase Inhibitors in Human Cancer Cell Lines
Authors: Carlo Stresemann, Bodo Brueckner, Tanja Musch, Helga Stopper, Frank Lyko
Journal: Cancer Research (2006)

Abstract DNA methyltransferase inhibitors represent promising new drugs for cancer therapies. The first of these compounds (5-azacytidine, Vidaza) has recently been approved as an antitumor agent, and others are presently in various stages of their preclinical or clinical development. Most of the archetypal inhibitors have been established and characterized in different experimental systems, which has thus far precluded their direct comparison. We have now established defined experimental conditions that allowed a comparative analysis of the six most widely known DNA methyltransferase inhibitors: 5-azacytidine (5-aza-CR), 5-aza-2′-deoxycytidine (5-aza-CdR), zebularine, procaine, (−)-epigallocatechin-3-gallate (EGCG), and RG108. Of these, 5-aza-CR, 5-aza-CdR, zebularine, and EGCG were found to exhibit significant cytotoxicity in human cancer cell lines. 5-aza-CdR and EGCG were also found to be genotoxic, as evidenced by the induction of micronuclei. In addition, 5-aza-CR, 5-aza-CdR, zebularine, and RG108 caused concentration-dependent demethylation of genomic DNA, whereas procaine and EGCG failed to induce significant effects. Finally, the experiments in cancer cell lines were complemented by a cell-free in vitro assay with purified recombinant DNA methyltransferase, which indicated that RG108 is the only drug capable of direct enzyme inhibition. These results show a substantial diversity in the molecular activities of DNA methyltransferase inhibitors and provide valuable insights into the developmental potential of individual drugs. (Cancer Res 2006; 66(5): 2794-800)
The “chicken-and-egg” problem in political neuroscience
Authors: John T. Jost, Sharareh Noorbaloochi, Jay J. Van Bavel
Journal: Behavioral and Brain Sciences (2014)

Abstract A comprehensive review by Hibbing et al. establishes close links between physiological and psychological responses and ideological preferences. However, existing research cannot resolve the “chicken-and-egg problem” in political neuroscience: Which is cause and which is effect? We consider the possibility, which they reject, that general ideological postures, if consistently adopted, could shape psychological and physiological functioning.
A rare cause of abdominal pain
Authors: W H Chan
Journal: Gut (2004)

Background: The aim of this study was to evaluate whether patients with increased or decreased gastric motility can be differentiated from healthy volunteers by means of real time magnetic resonance imaging (MRI).Patients and methods: Ten healthy volunteers, 10 patients with gastroparesis, and 10 patients with functional pylorospasm/peptic pyloric stenosis underwent real time MRI.All patients were examined on two separate days; once prior to therapy and once after adequate therapy.Antral motility was quantified by calculating the gastric motility index.Results: Patients with gastroparesis showed a lower motility index compared with the reference volunteer group while the mean motility index of the patient group with pylorospasm was more than three times higher than that of the reference value of the volunteer group.However, the gastric motility index in the patient group with gastroparesis increased, and in the group with functional pylorospasm/peptic pyloric stenosis it decreased significantly after therapy.Conclusion: Real time MRI is a reliable tool for assessment of gastric motion.Furthermore, differences in gastric motility index in patients with increased or decreased gastric motility could be evaluated and quantified.Due to the non-invasive character of MRI, this imaging modality may be an attractive alternative to conventional invasive diagnostic tools for gastric motility disorders and therapeutic monitoring.
Risk and Recurrence of Serious Adverse Outcomes in the First and Second Pregnancies of Women With Preexisting Diabetes
Authors: Peter W.G. Tennant, Rudy W. Bilous, Shamini Prathapan, Ruth Bell
Journal: Diabetes Care (2015)

OBJECTIVE Women with preexisting (type 1 or type 2) diabetes experience an increased risk of serious adverse pregnancy outcomes. It is not known, however, how these risks change between the first and second pregnancy and whether there is an increased risk of recurrence. This study describes the absolute risks and recurrence of serious adverse pregnancy outcomes in 220 women with preexisting diabetes. RESEARCH DESIGN AND METHODS A total of 440 pregnancies occurring in 220 women with preexisting diabetes who delivered successive singleton pregnancies in the North of England during 1996–2008 were identified from the Northern Diabetes in Pregnancy Survey (NorDIP). Predictors of serious adverse outcome were estimated by competing-risks regression. RESULTS Sixty-seven first pregnancies (30.5%) ended in serious adverse outcome, including 14 (6.4%) with congenital anomalies and 53 (24.1%) additional fetal or infant deaths. Thirty-seven second pregnancies (16.8%) ended in serious adverse outcome—half the rate among first pregnancies (P = 0.0004)—including 21 (9.5%) with congenital anomalies and 16 (7.3%) additional fetal or infant deaths. Serious adverse outcomes in the second pregnancy occurred twice as frequently in women who experienced a previous adverse outcome than in those who did not (26.9% vs. 12.4%, P = 0.004), but previous adverse outcome was not associated with preparation for the following pregnancy. CONCLUSIONS Serious adverse outcomes are less common in the second pregnancies of women with preexisting diabetes, although the risk is comparable in those whose first pregnancy ends in adverse outcome. Reducing the risk of recurrence may require more support in the immediate period after an adverse pregnancy outcome.
The importance of social learning in the evolution of cooperation and communication
Authors: Willem Zuidema
Journal: Behavioral and Brain Sciences (2002)

The new emphasis that Rachlin gives to social learning is welcome, because its role in the emergence of altruism and communication is often underestimated. However, Rachlin's account is underspecified and therefore not satisfactory. I argue that recent computational models of the evolution of language show an alternative approach and present an appealing perspective on the evolution and acquisition of a complex, altruistic behavior like syntactic language.
Diabetes Care in an Australian Population
Authors: Robyn J. Tapp, Paul Z. Zimmet, C. Alex Harper, Maximilian P. de Courten, Beverley Balkau, Daniel J. McCarty, Hugh R. Taylor, Timothy A. Welborn, Jonathan E. Shaw
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this work was to study the frequency of examining for diabetic eye and foot complications in an Australian population and to study factors associated with regular screening. RESEARCH DESIGN AND METHODS—The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based study of 11,247 people from randomly selected areas of Australia. Participants identified as having previously diagnosed diabetes (n = 475) were invited to participate in the complications study. Measures included foot examination, retinopathy photography, and self-report use of health care services. RESULTS—Seventy-seven percent of participants reported having an eye examination within the previous 2 years, and 50% reported having their feet examined by a health professional in the previous year. Type of diabetes treatment (odds ratio 1.46, 95% CI 0.85–2.50 for tablets versus diet alone and 4.17, 1.71–10.17 for insulin or insulin and tablets versus diet alone) and visiting a diabetes nurse educator in the previous 12 months (2.14, 1.18–3.87) were independent predictors of having had an eye examination. Duration of diabetes (1.33, 1.06–1.67 per year) and visiting a diabetes nurse educator in the previous 12 months (1.89, 1.20–2.95) were independent predictors of a foot examination. CONCLUSIONS—This study has shown that retinopathy screening is performed more frequently than foot screening in Australia. This may be due to the implementation of eye screening programs and awareness campaigns. Foot screening appears to be poor, with less than one-half of the population reporting a regular examination for foot complications. In Australia, diabetes nurse educators play a key role in promoting screening for diabetes complications.
Randomized Trial of Behavioral Family Systems Therapy for Diabetes
Authors: Tim Wysocki, Michael A. Harris, Lisa M. Buckloh, Debbie Mertlich, Amanda S. Lochrie, Nelly Mauras, Neil H. White
Journal: Diabetes Care (2007)

OBJECTIVE—Studies showing that family communication and conflict resolution are critical to effective management of type 1 diabetes in adolescents have stimulated interest in evaluating psychological treatments targeting these processes. Previous trials have shown that Behavioral Family Systems Therapy (BFST) improved parent-adolescent relationships but not treatment adherence or glycemic control. This study evaluates a revised intervention, BFST for Diabetes (BFST-D), modified to achieve greater impact on diabetes-related family conflict, treatment adherence, and metabolic control. RESEARCH DESIGN AND METHODS—A sample of 104 families of adolescents with inadequate control of type 1 diabetes was randomized to either remain in standard care (SC) or to augmentation of that regimen by 12 sessions of either a multifamily educational support (ES) group or 12 sessions of BFST-D over 6 months. Pertinent measures were collected at baseline and at follow-up evaluations at 6, 12, and 18 months. RESULTS—BFST-D was significantly superior to both SC and ES in effects on A1C, while effects on treatment adherence and family conflict were equivocal. Improvement in A1C appeared to be mediated by improvement in treatment adherence. A significantly higher percentage of BFST-D youth achieved moderate or greater improvement (&amp;gt;0.5 SD) in treatment adherence compared with the SC group at each follow-up and the ES group at 6 and 18 months. Change in treatment adherence correlated significantly with change in A1C at each follow-up. CONCLUSIONS—These results support the efficacy of BFST-D in improving A1C, but further research is needed to identify the mechanisms of this effect and to achieve cost-effective dissemination of the intervention.
Medical results of preparticipation examination in adolescent athletes
Authors: Frank Mayer, Klaus Bonaventura, Michael Cassel, Steffen Mueller, Josefine Weber, Friederike Scharhag-Rosenberger, Anja Carlsohn, Heiner Baur, Juergen Scharhag
Journal: British Journal of Sports Medicine (2012)

Background Preparticipation examinations (PPE) are frequently used to evaluate eligibility for competitive sports in adolescent athletes. Nevertheless, the effectiveness of these examinations is under debate since costs are high and its validity is discussed controversial. Purpose To analyse medical findings and consequences in adolescent athletes prior to admission to a sports school. Methods In 733 adolescent athletes (318 girls, 415 boys, age 12.3±0.4, 16 sports disciplines), history and clinical examination (musculoskeletal, cardiovascular, general medicine) was performed to evaluate eligibility. PPE was completed by determination of blood parameters, ECG at rest and during ergometry, echocardiography and x-rays and ultrasonography if indicated. Eligibility was either approved or rated with restriction. Recommendations for therapy and/or prevention were given to the athletes and their parents. Results Historical (h) and clinical (c) findings (eg, pain, verified pathologies) were more frequent regarding the musculoskeletal system (h:120, 16.4%; c:247, 33.7%) compared to cardiovascular (h:9, 1.2%; c:23, 3.1%) or general medicine findings (h:116, 15.8%; c:71, 9.7%). ECG at rest was moderately abnormal in 46 (6.3%) and severely abnormal in 25 athletes (3.4%). Exercise ECG was suspicious in 25 athletes (3.4%). Relevant echocardiographic abnormalities were found in 17 athletes (2.3%). In 52 of 358 cases (14.5%), x-rays led to diagnosis (eg, Spondylolisthesis). Eligibility was temporarily restricted in 41 athletes (5.6%). Three athletes (0.4%) had to be excluded from competitive sports. Therapy (eg, physiotherapy, medication) and/or prevention (sensorimotor training, vaccination) recommendations were deduced due to musculoskeletal (t:n=76,10.3%;p: n=71,9.8%) and general medicine findings (t:n=80, 10.9%; p:n=104, 14.1%). Conclusion Eligibility for competitive sports is restricted in only 5.5% of adolescent athletes at age 12. Eligibility refusals are rare. However, recommendations for therapy and prevention are frequent, mainly regarding the musculoskeletal system. In spite of time and cost consumption, adolescent preparticipation before entering a career in high-performance sports is supported.
A Single Na <sup>+</sup> Channel Mutation Causing Both Long-QT and Brugada Syndromes
Authors: Connie Bezzina, Marieke W. Veldkamp, Maarten P. van den Berg, Alex V. Postma, Martin B. Rook, Jan-Willem Viersma, Irene M. van Langen, Ghita Tan-Sindhunata, Margreet Th. E. Bink-Boelkens, Annemarie H. van der Hout, Marcel M. A. M. Mannens, Arthur A. M. Wilde
Journal: Circulation Research (1999)

Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT(3)) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members. ECGs were obtained from 79 adults with a defined genetic status (carriers, n=43; noncarriers, n=36). In affected individuals, PR and QRS durations and QT intervals are prolonged (P<0.0001 for all parameters). ST segment elevation in the right precordial leads is present as well (P<0.0001). Twenty-five family members died suddenly, 16 of them during the night. Expression of wild-type and mutant Na(+) channels in Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV negative shift of the steady-state inactivation curve and an 8.1-mV positive shift of the steady-state activation curve. The functional consequence of both shifts is likely to be a reduced Na(+) current during the upstroke of the action potential. LQT(3) and Brugada syndrome are allelic disorders but may also share a common genotype.
A randomized, multicenter study of subcutaneous and intravenous darbepoetin alfa for the treatment of chemotherapy-induced anemia
Authors: G. Justice, J.F. Kessler, J. Jadeja, L. Campos, J. Weick, C.-F. Chen, A.C. Heatherington, R.G. Amado
Journal: Annals of Oncology (2005)