tbuckley/cabot-search huggingface dataset:
Hip passive range of motion and frequency of radiographic hip osteoarthritis in former elite handball players
Authors: M L’Hermette, G Polle, C Tourny-Chollet, F Dujardin
Journal: British Journal of Sports Medicine (2005)

Objective: To establish the relation between handball playing, passive hip range of motion (ROM), and the development of radiological hip osteoarthritis (OA) in former elite handball players. Two related issues are addressed: ( a ) the relation between long term elite handball playing and the incidence of hip OA; ( b ) the relations between hip ROM, OA, and pain. Methods: Data on 20 former elite handball players and 39 control subjects were collected. A questionnaire yielded personal details, loading patterns during physical activity, and previous lower limb joint injury. Bilateral radiographs were analysed to diagnose and classify hip OA. Passive hip ROM was measured bilaterally with a goniometer. Results: A close relation was found between long term elite handball practice and the incidence of hip OA: 60% of the handball players were diagnosed with OA in at least one of the hip joints compared with 13% of the control subjects. Passive ROM measured in the handball players was significantly lower for hip flexion and medial rotation and higher for abduction, extension, and lateral rotation than the control values. The handball players with OA reported less pain in the hip joints during daily activities than the control subjects with OA. Conclusion: The risk of developing premature hip OA seems high for retired handball players and significantly greater than for the general population. Pain and discomfort represent two difficult diagnostic challenges to the sports physician, as the repetitive nature of movements that are specific to handball can lead to alterations that are rarely seen in the general population.
Synthetic Oleanane Triterpenoids: Multifunctional Drugs with a Broad Range of Applications for Prevention and Treatment of Chronic Disease
Authors: Karen T. Liby, Michael B. Sporn
Journal: Pharmacological Reviews (2012)

We review the rationale for the use of synthetic oleanane triterpenoids (SOs) for prevention and treatment of disease, as well as extensive biological data on this topic resulting from both cell culture and in vivo studies. Emphasis is placed on understanding mechanisms of action. SOs are noncytotoxic drugs with an excellent safety profile. Several hundred SOs have now been synthesized and in vitro have been shown to: 1) suppress inflammation and oxidative stress and therefore be cytoprotective, especially at low nanomolar doses, 2) induce differentiation, and 3) block cell proliferation and induce apoptosis at higher micromolar doses. Animal data on the use of SOs in neurodegenerative diseases and in diseases of the eye, lung, cardiovascular system, liver, gastrointestinal tract, and kidney, as well as in cancer and in metabolic and inflammatory/autoimmune disorders, are reviewed. The importance of the cytoprotective Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1/nuclear factor (erythroid-derived 2)-like 2/antioxidant response element (Keap1/Nrf2/ARE) pathway as a mechanism of action is explained, but interactions with peroxisome proliferator-activated receptor γ (PARPγ), inhibitor of nuclear factor-κB kinase complex (IKK), janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT), human epidermal growth factor receptor 2 (HER2)/ErbB2/neu, phosphatase and tensin homolog (PTEN), the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, mammalian target of rapamycin (mTOR), and the thiol proteome are also described. In these interactions, Michael addition of SOs to reactive cysteine residues in specific molecular targets triggers biological activity. Ultimately, SOs are multifunctional drugs that regulate the activity of entire networks. Recent progress in the earliest clinical trials with 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) methyl ester (bardoxolone methyl) is also summarized.
Liver-directed lentiviral gene therapy in a dog model of hemophilia B
Authors: Alessio Cantore, Marco Ranzani, Cynthia C. Bartholomae, Monica Volpin, Patrizia Della Valle, Francesca Sanvito, Lucia Sergi Sergi, Pierangela Gallina, Fabrizio Benedicenti, Dwight Bellinger, Robin Raymer, Elizabeth Merricks, Francesca Bellintani, Samia Martin, Claudio Doglioni, Armando D’Angelo, Thierry VandenDriessche, Marinee K. Chuah, Manfred Schmidt, Timothy Nichols, Eugenio Montini, Luigi Naldini
Journal: Science Translational Medicine (2015)

Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs with hemophilia B and does not show genotoxicity in tumor-prone mice.
Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes
Authors: Guillermo E. Umpierrez, Roma Gianchandani, Dawn Smiley, Sol Jacobs, David H. Wesorick, Christopher Newton, Farnoosh Farrokhi, Limin Peng, David Reyes, Sangeeta Lathkar-Pradhan, Francisco Pasquel
Journal: Diabetes Care (2013)

This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups.Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86).Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.
Effect of Nicotine on Cholesterol-Induced Atherosclerosis in the Rabbit
Authors: DUANE G. WENZEL, JAMES A. TURNER, DONALD KISSIL
Journal: Circulation Research (1959)

Nicotine was administered orally in three dosage levels to female rabbits fed a 1 per cent cholesterol, 5 per cent oil diet for 24 weeks. Serum cholesterol and phospholipid values and electrocardiograms, both with and without ergonovine stress, were obtained at eight week intervals. Gross and microaortic pathology and cardiac micropathology were determined at the end of the experiment. Serum cholesterol and phospholipid values and aortic atherosclerosis were not affected by the addition of nicotine. Mortality, the incidence of positive ergonovine stress tests, myocardial necrosis and fatty metamorphosis, and peripheral vascular changes were increased. A dose-response relationship could not be established for nicotine.
Contrasting Patterns of Molecular Evolution of the Genes on the New and Old Sex Chromosomes of Drosophila miranda
Authors: Soojin Yi, Brian Charlesworth
Journal: Molecular Biology and Evolution (2000)

In organisms with chromosomal sex determination, sex is determined by a set of dimorphic sex chromosomes that are thought to have evolved from a set of originally homologous chromosomes. The chromosome inherited only through the heterogametic sex (the Y chromosome in the case of male heterogamety) often exhibits loss of genetic activity for most of the genes carried on its homolog and is hence referred to as degenerate. The process by which the proto-Y chromosome loses its genetic activity has long been the subject of much speculation. We present a DNA sequence variation analysis of marker genes on the evolving sex chromosomes (neo-sex chromosomes) of Drosophila miranda. Due to its relatively recent origin, the neo-Y chromosome of this species is presumed to be still experiencing the forces responsible for the loss of its genetic activity. Indeed, several previous studies have confirmed the presence of some active loci on this chromosome. The genes on the neo-Y chromosome surveyed in the current study show generally lower levels of variation compared with their counterparts on the neo-X chromosome or an X-linked gene. This is in accord with a reduced effective population size of the neo-Y chromosome. Interestingly, the rate of replacement nucleotide substitutions for the neo-Y linked genes is significantly higher than that for the neo-X linked genes. This is not expected under a model where the faster evolution of the X chromosome is postulated to be the main force driving the degeneration of the Y chromosome.
Global Lung Function Initiative equations improve interpretation of FEV<sub>1</sub> decline among patients with cystic fibrosis
Authors: Sanja Stanojevic, Diana Bilton, Alexandra McDonald, Janet Stocks, Paul Aurora, Ammani Prasad, Tim J. Cole, Gwyneth Davies
Journal: European Respiratory Journal (2015)

The prognosis for individuals with cystic fibrosis has improved markedly over the last 50 years, with most countries now reporting that 50% of the population reach at least 35 years of age [1–3]. Despite this improvement, the average age at death is still in the late 20s and varies enormously between cystic fibrosis centres and countries [4]. To further improve the trajectory of lung disease, it is critical to identify patients that would benefit most from early intervention. Adolescent FEV 1 decline in cystic fibrosis may be an artefact of the spirometry reference equations used <http://ow.ly/J0com>
Screening for Primary Hypertension in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement*
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Update of the 2003 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for high blood pressure in children and adolescents.The USPSTF reviewed the evidence on screening and diagnostic accuracy of screening tests for blood pressure in children and adolescents, the effectiveness and harms of treatment of screen-detected primary childhood hypertension, and the association of hypertension with markers of cardiovascular disease in childhood and adulthood.This recommendation applies to children and adolescents who do not have symptoms of hypertension.The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood.
441 THE ITPA GENOTYPE CORRELATES WITH HEMOLYTIC ANEMIA AND OUTCOME AFTER TREATMENT WITH PEGYLATED-INTERFERON AND RIBAVIRIN IN GENOTYPE IB CHRONIC HEPATITIS C
Authors: M. Kurosaki, K. Tanaka, Y. Suzuki, Y. Hoshioka, N. Tamaki, T. Kato, Y. Yasui, T. Hosokawa, K. Ueda, K. Tsuchiya, T. Kuzuya, H. Nakanishi, J. Itakura, Y. Takahashi, Y. Asahina, M. Mizokami, Y. Tanaka, N. Sakamoto, N. Enomoto, N. Izumi
Journal: Journal of Hepatology (2011)
High Baseline Insulin Levels Associated With 6-Year Incident Observed Sleep Apnea
Authors: Beverley Balkau, Sylviane Vol, Sandrine Loko, Tiana Andriamboavonjy, Olivier Lantieri, Gaelle Gusto, Nicole Meslier, Jean-Louis Racineux, Jean Tichet
Journal: Diabetes Care (2010)

OBJECTIVE Obstructive sleep apnea is common in patients with type 2 diabetes, and its association with insulin and insulin resistance has been examined in cross-sectional studies. We evaluate risk factors for incident observed sleep apnea in a general population not selected for sleep disturbances. RESEARCH DESIGN AND METHODS A total of 1,780 men and 1,785 women, aged 33 to 68 years, from the cohort Data from an Epidemiologic Study on the Insulin Resistance Syndrome (D.E.S.I.R.) responded to the question, “Has someone said to you that you stop breathing during your sleep?” at baseline and 6 years. Anthropometric, clinical, and biological factors were recorded at both time points. RESULTS At baseline, 14% of men and 7% of women reported having observed sleep apnea (positive response to question); 6-year incidences were 14 and 6%, respectively. Age, anthropometric parameters, blood pressure, and sleep characteristics were all associated with prevalent, observed apnea episodes, in both sexes. Baseline waist circumference was the strongest predictor of incident apnea: standardized odds ratio (OR), adjusted for age and sex, 1.34 (95% CI 1.19–1.52). After adjustment for age, sex, and waist circumference, the standardized ORs for incident observed apnea were identical for fasting insulin and the homeostasis model assessment of insulin resistance: 1.31 (1.13–1.51) and 1.24 (1.09–1.41) for triglycerides and 1.52 (1.12–2.05) for smoking. Observed apnea at baseline was not associated with changes in anthropometric or biological parameters over the 6-year follow-up. CONCLUSIONS The most important baseline risk factor for incident apnea was adiposity. After accounting for adiposity, other risk factors were high insulin, insulin resistance, high triglycerides, and smoking, factors amenable to lifestyle intervention.
A model for dropout assessment of candidates with or without hepatocellular carcinoma on a common liver transplant waiting list
Authors: Christian Toso, Elise Dupuis-Lozeron, Pietro Majno, Thierry Berney, Norman M. Kneteman, Thomas Perneger, Philippe Morel, Gilles Mentha, Christophe Combescure
Journal: Hepatology (2012)

In many countries, the allocation of liver grafts is based on the Model of End-stage Liver Disease (MELD) score and the use of exception points for patients with hepatocellular carcinoma (HCC). With this strategy, HCC patients have easier access to transplantation than non-HCC ones. In addition, this system does not allow for a dynamic assessment, which would be required to picture the current use of local tumor treatment. This study was based on the Scientific Registry of Transplant Recipients and included 5,498 adult candidates of a liver transplantation for HCC and 43,528 for non-HCC diagnoses. A proportional hazard competitive risk model was used. The risk of dropout of HCC patients was independently predicted by MELD score, HCC size, HCC number, and alpha-fetoprotein. When combined in a model with age and diagnosis, these factors allowed for the extrapolation of the risk of dropout. Because this model and MELD did not share compatible scales, a correlation between both models was computed according to the predicted risk of dropout, and drop-out equivalent MELD (deMELD) points were calculated.The proposed model, with the allocation of deMELD, has the potential to allow for a dynamic and combined comparison of opportunities to receive a graft for HCC and non-HCC patients on a common waiting list.
Fish Oil Supplementation and Risk of Ventricular Tachycardia and Ventricular Fibrillation in Patients With Implantable Defibrillators
Authors: Merritt H. Raitt, William E. Connor, Cynthia Morris, Jack Kron, Blair Halperin, Sumeet S. Chugh, James McClelland, James Cook, Karen MacMurdy, Robert Swenson, Sonja L. Connor, Glenn Gerhard, Dale F. Kraemer, Daniel Oseran, Christy Marchant, David Calhoun, Reed Shnider, John McAnulty
Journal: JAMA (2005)

ContextClinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects.ObjectiveTo determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).Design and SettingRandomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003.PatientsTwo hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF.InterventionPatients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days).Main Outcome MeasuresTime to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses.ResultsPatients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001).ConclusionAmong patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.
Potential Vascular Mechanisms of Ramipril Induced Increases in Walking Ability in Patients With Intermittent Claudication
Authors: Anna A. Ahimastos, Celine Latouche, Alaina K. Natoli, Medini Reddy-luthmoodoo, Jonathan Golledge, Bronwyn A. Kingwell
Journal: Circulation Research (2014)

Rationale: We recently reported that ramipril more than doubled maximum walking times in patients with peripheral artery disease with intermittent claudication. Objective: Our aim was to conduct exploratory analyses of the effects of ramipril therapy on circulating biomarkers of angiogenesis/arteriogenesis, thrombosis, inflammation, and leukocyte adhesion in patients with intermittent claudication. Methods and Results: One hundred sixty-five patients with intermittent claudication (mean, 65.3 [SD, 6.7] years) were administered ramipril 10 mg per day (n=82) or matching placebo (n=83) for 24 weeks in a randomized, double-blind study. Plasma biomarkers of angiogenesis/arteriogenesis (vascular endothelial growth factor-A, fibroblast growth factor-2), thrombosis (D-dimer, von Willebrand factor, thrombin-antithrombin III), inflammation (high-sensitivity C-reactive protein, osteopontin), and leukocyte adhesion (soluble vascular cell adhesion molecule-1, soluble intracellular adhesion molecule-1) were measured at baseline and 24 weeks. Relative to placebo, ramipril was associated with increases in vascular endothelial growth factor-A by 38% (95% confidence interval [CI], 34%–42%) and fibroblast growth factor-2 by 64% (95% CI, 44–85%; P &lt;0.001 for both), and reductions in D-dimer by 24% (95% CI, −30% to −18%), von Willebrand factor by 22% (95% CI, −35% to −9%), thrombin-antithrombin III by 16% (95% CI, −19% to −13%), high-sensitivity C-reactive protein by 13% (95% CI, −14% to −9%), osteopontin by 12% (95% CI, −14% to −10%), soluble vascular cell adhesion molecule-1 by 14% (95% CI, −18% to −10%), and soluble intracellular adhesion molecule-1 by 15% (95% CI, −17% to −13%; all P &lt;0.001). With the exception of von Willebrand factor, all the above changes correlated significantly with the change in maximum walking time ( P =0.02−0.001) in the group treated with ramipril. Conclusions: Ramipril is associated with an increase in the biomarkers of angiogenesis/arteriogenesis and reduction in the markers of thrombosis, inflammation, and leukocyte adhesion. This study informs strategies to improve mobility in patients with intermittent claudication. Clinical Trial Registration Information: URL: http://clinicaltrials.gov . Unique identifier: NCT00681226.
Local resource depletion hypothesis as a mechanism for action selection in the brain
Authors: Aneta Brzezicka, Jan Kamiński, Andrzej Wróbel
Journal: Behavioral and Brain Sciences (2013)

Abstract As a comment on Kurzban et al.'s opportunity cost model, we propose an alternative view of mental effort and the action selection mechanism in the brain. Our hypothesis utilizes local resource depletion within neuronal networks, which justifies from a neurophysiological perspective why mental fatigue diminishes after switching to a novel task and explains action selection by means of neural competition theory.
Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: Identification of genetic indicators to predict patient outcome
Authors: Hiroto Katoh, Tatsuhiro Shibata, Akiko Kokubu, Hidenori Ojima, Panayiotis Loukopoulos, Yae Kanai, Tomoo Kosuge, Masashi Fukayama, Tadashi Kondo, Michiie Sakamoto, Fumie Hosoda, Misao Ohki, Issei Imoto, Johji Inazawa, Setsuo Hirohashi
Journal: Journal of Hepatology (2005)
Risk factors for morphoea disease severity: a retrospective review of 114 paediatric patients
Authors: M.S. Pequet, K.E. Holland, S. Zhao, B.A. Drolet, S.S. Galbraith, D.H. Siegel, Y.E. Chiu
Journal: British Journal of Dermatology (2013)

Morphoea is a rare fibrosing disease of the skin and subcutaneous tissue with an unpredictable disease course, running the spectrum from mild skin involvement to severe disfigurement or extracutaneous complications.Our objective was to describe the natural history of paediatric morphoea and determine patient variables that were associated with severe disease.We conducted a retrospective chart review of patients with morphoea seen in one paediatric hospital system. Information about demographics, clinical characteristics, disease course and treatment were collected. Statistical analysis was performed using appropriate univariate tests and a multivariable model.One hundred and fourteen patients met study inclusion criteria. The female : male ratio was 2·6 : 1, and the median age of onset was 7 years old. There were 55 patients (48%) with linear morphoea, 38 patients (33%) with circumscribed morphoea, 12 patients (11%) with generalized morphoea, and nine patients (8%) with mixed morphoea. Neurological symptoms and joint involvement were present in 27 subjects (24%). Extracutaneous manifestations occurred in 38% of subjects with linear morphoea, compared with 15% with generalized morphoea and 3% with circumscribed morphoea (P = 0·0001). Thirty-six per cent of children with disease onset prior to 10 years of age and 5% of children with disease onset after 10 years of age had extracutaneous manifestations (P = 0·0002). Both linear morphoea and early-onset disease were significantly associated with extracutaneous involvement in a multivariable model.Children with linear morphoea and disease onset before 10 years of age should be monitored closely for extracutaneous manifestations and need early treatment with systemic medications to prevent disease complications.