tbuckley/cabot-search huggingface dataset:
Depot Medroxyprogesterone Acetate Use and Blood Lead Levels in a Cohort of Young Women
Authors: Kristen Upson, Quaker E. Harmon, Renee Heffron, Janet E. Hall, Lauren A. Wise, Ganesa Wegienka, Erik J. Tokar, Donna D. Baird
Journal: Environmental Health Perspectives (2020)

Background: Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead. Objective: The objective of our study was to investigate the association between current DMPA use and blood lead concentrations. Methods: We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23–35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression. Results: Geometric mean blood lead concentration was 0.69μg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss. Discussion: Our results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017
Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases
Authors: Francesca Tucci, Samantha Scaramuzza, Alessandro Aiuti, Alessandra Mortellaro
Journal: Molecular Therapy (2020)

Gene transfer into autologous hematopoietic stem progenitor cells (HSPCs) has the potential to cure monogenic inherited disorders caused by an altered development and/or function of the blood system, such as immune deficiencies and red blood cell and platelet disorders. Gene-corrected HSPCs and their progeny can also be exploited as cell vehicles to deliver molecules into the circulation and tissues, including the central nervous system. In this review, we focus on the progress of clinical development of medicinal products based on HSPCs engineered and modified by integrating viral vectors for the treatment of monogenic blood disorders and metabolic diseases. Two products have reached the stage of market approval in the EU, and more are foreseen to be approved in the near future. Despite these achievements, several challenges remain for HSPC gene therapy (HSPC-GT) precluding a wider application of this type of gene therapy to a wider set of diseases while gene-editing approaches are entering the clinical arena.
Abstract 13503: Relative Efficacy of Alirocumab, Bempedoic Acid, Evolocumab, Ezetimibe and Inclisiran Added to Statins for Reduction of Low Density Lipoprotein Cholesterol - A Network Meta-Analysis of Randomized Clinical Trials
Authors: Peter P Toth, Sarah Bray, Gavin Worth
Journal: Circulation (2020)

Background: Many patients with hypercholesterolemia and/or cardiovascular disease are unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) reduction with statins alone (or are statin intolerant). This is increasingly the case with clinical guidelines recommending that lower LDL-C levels are beneficial for patients. This network meta-analysis (NMA) assessed the relative efficacy of lipid lowering therapies (LLTs) added to statins for reducing LDL-C. Methods: A systematic review of randomized controlled clinical trials to May 2020 identified 48 studies for inclusion in the primary NMA. The primary NMA included studies ≥12 weeks duration in which alirocumab, bempedoic acid, evolocumab, ezetimibe, or inclisiran were added to moderate-high intensity statins (or lower intensity / no statin in statin intolerant patients). Random effects NMA was used to analyse % change in LDL-C to compare the treatment effects indirectly. Results: Over 12 weeks, all non-statin LLTs significantly reduced LDL-C from baseline versus placebo. Evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were associated with largest LDL-C reductions, which were greater than those achieved with lower/alternative doses of alirocumab, bempedoic acid (± ezetimibe), ezetimibe and inclisiran (Table). Consistent results were observed in sensitivity analyses to address heterogeneity (excluding familial hypercholesterolemia and east Asian studies), in the subgroup NMA of studies in predominantly atherosclerotic cardiovascular disease patients, and in the statin intolerant subgroup NMA. Conclusions: All agents reduced LDL-C, however, the PCSK9 inhibitors evolocumab 140 mg Q2W / 420 mg QM and alirocumab 150 mg Q2W were the most effective LLT regimens for reducing LDL-C when added to statins.
Immunopathobiology and therapeutic targets related to cytokines in liver diseases
Authors: Yong He, Seonghwan Hwang, Yeni Ait Ahmed, Dechun Feng, Na Li, Marcelle Ribeiro, Fouad Lafdil, Tatiana Kisseleva, Gyongyi Szabo, Bin Gao
Journal: Cellular and Molecular Immunology (2020)

Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma. The progression of liver disease is controlled by a variety of factors, including liver injury, inflammatory cells, inflammatory mediators, cytokines, and the gut microbiome. In the current review, we discuss recent data on a large number of cytokines that play important roles in regulating liver injury, inflammation, fibrosis, and regeneration, with a focus on interferons and T helper (Th) 1, Th2, Th9, Th17, interleukin (IL)-1 family, IL-6 family, and IL-20 family cytokines. Hepatocytes can also produce certain cytokines (such as IL-7, IL-11, and IL-33), and the functions of these cytokines in the liver are briefly summarized. Several cytokines have great therapeutic potential, and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases, which are also described.
Abstract 14928: The Factors Impacting on Resting Energy Expenditure in Refractory Heart Failure Patients and the Probability of Urine Amino Acids Analysis as an Indicator for Calorie Intake Insufficiency
Authors: Yoko Kudo-sakamoto, Tomohito Ohtani, kei nakamoto, Fusako Sera, Shungo Hikoso, Yasushi Sakata
Journal: Circulation (2020)

Introduction: Cachexia is a critical issue in patients with refractory heart failure (HF). Although the elevation of resting energy expenditure (REE) can progress cachexia through relatively insufficient calorie intake, the detail of REE in HF patients remains uncertain and no useful marker for predicting insufficient calorie intake has been established. This study aimed to assess the REE of HF patients and to evaluate the detectability of serum and urine laboratory markers for insufficient calorie intake. Methods: We measured REE using indirect calorimetry in 69 HF patients (NYHA class II-IV) in our hospital. In 25 out of 69 patients, serum albumin, amino acids, and 24-hour urine amino acids were measured. The calorie intake insufficiency was determined based on measured REE multiplied by activity index Results: As compared to the predicted values by Harris-Benedict equation, 43 patients (63%) had an elevated REE and the mean REE was approximately 4% elevated. There was no significant correlation between the REE and parameters indicating HF severity, including cardiac index on right heart catheterization and BNP level. Only body mass index (BMI) negatively correlated with the REE (r=-0,66, p&lt;0.01). Of 25 patients, 16 (64%) had calorie intake insufficiency. The excreted amount of urine essential amino acids was lower and mostly under normal range, especially significantly decreased in Histidine and Phenylalanine levels in the patients with calorie intake insufficiency compared to those without calorie intake insufficiency, whereas serum levels of albumin and essential amino acids were kept within a normal range in the both. Conclusions: Our findings suggest that the patients with refractory HF, especially having low BMI, are likely to be under inadequate calorie intake due to elevated REE. The calorie intake insufficiency could not be identified with serum levels of albumin nor essential amino acids. Instead, urine essential amino acids would decrease first prior to plasma levels, indicating this measurement would be a useful marker to detect calorie intake insufficiency.
Abstract 342: Initial Serum Uric Acid and Post Cardiac Arrest Patient Outcomes with Respect to Cardiogenic Causes of Arrest
Authors: Eun Bee Yoon, Minjung K Chae, Sung Eun Lee, Eun Jung Park, Sumin Cho
Journal: Circulation (2020)

Objective: Post cardiac arrest patients experience neurologic and systemic ischemic-reperfusion injury. Uric acid (UA) can be a marker of oxidative stress and severity of various cardiogenic diseases, but also has antioxidant capacity with neuroprotective effects. We aimed to evaluate the association between initial UA and neurologic outcomes of survivors of non-cardiogenic and cardiogenic causes of cardiac arrest. Methods: This was a retrospective observational study of out of hospital post cardiac arrest patients who had initial UA at admission. Association between UA and cardiogenic cause of arrest was analyzed by linear regression. Then neurologic outcome and UA was assessed with multivariate logistic regression analysis by cardiogenic and non-cardiogenic cause of arrest. Results: A total of 126 patients were analyzed. UA was significantly lower in the poor neurologic outcome group than in the good neurologic outcome group [7.9 (1.6) vs. 7.0 (1.8), P&lt;0.01]. Cardiogenic cause of arrest was significantly associated with UA levels [β coefficient 0.87 (0.26-1.49), P=0.01]. In the logistic regression of neurologic outcome and UA by cardiogenic cause of arrest, poor neurologic outcome was not associated with UA in cardiogenic causes of arrest [OR 0.91 (0.62-1.33) P=0.62], but was associated with UA in non-cardiogenic causes of arrest [OR 0.47 (0.23-0.97), P=0.04]. Conclusion: With respect to neurologic outcome by cardiogenic cause of arrest, lower uric acid was associated with poor neurologic outcomes in non-cardiogenic causes of arrest.
Abstract 13205: Underrepresentation of Women as Clinical Trialists in Heart Failure: A Systematic Review of Randomized Controlled Trials Published in High-impact Medical Journals
Authors: Sera Whitelaw, Kristen Sullivan, Harriette G Van Spall
Journal: Circulation (2020)

Introduction: Clinical trials change practice in cardiology but leading them typically requires advanced research training, mentorship, sponsorship, and networking. Women are underrepresented in cardiology and report challenges in obtaining mentorship and networking opportunities. Objective: To evaluate the gender distribution of first and senior authors in practice-changing clinical trials in heart failure (HF), and explore clinical trial characteristics associated with women as first authors. Methods: We searched MEDLINE, EMBASE and CINAHL databases for randomized controlled trials (RCTs) published January 2000 - May 2019. We included RCTs that recruited adults with HF with reduced ejection fraction that were published in medical journals with an impact factor of &gt; 10. Two reviewers screened and extracted data independently. We determined the gender distribution of the authors, assessed temporal trends in authorship, and used logistic regression to identify characteristics associated with women in first authorship positions. Results: The search identified 10,596 unique studies, of which 317 met eligibility criteria. We found that 15.8%, 11.7%, and 10.7% of first, senior, and corresponding authors, respectively, were women. Multivariable analysis revealed that the first author was more likely to be a woman if the senior author of a clinical trial was a woman (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.04-4.66, p=0.039), and if the trial was conducted at a single rather than multiple centers (OR 1.40, 95% CI 1.09-6.48, p=0.035). Source of funding (public or industry), type of intervention (health service, drug, device, or surgery), and region of trial coordination (Europe, North America, Central and South America, Asia, and Australia) were not associated with gender of first authors. The proportion of trials that included women as authors has decreased from 2000 to present. Conclusion: Women are under-represented as clinical trialists in HF. Adjusting for other trial characteristics, the first author of a clinical trial was more likely to be a woman if the senior author was a woman. Mentoring women as clinical trialists in the present era may be a strategic way to increase the gender diversity of clinical trialists in years to come.
Abstract 14724: Sex Differences in the Associations of Visceral Adipose Tissue and Cardiometabolic and Cardiovascular Disease Risk: The Framingham Heart Study
Authors: Andreas Kammerlander, Asya Lyass, Taylor Mahoney, Joseph Massaro, Michelle T Long, Vasan S Ramachandran, Udo Hoffmann
Journal: Circulation (2020)

Background: The current clinical practice of defining obesity based on body mass index (BMI) does not capture differences in fat distribution between men and women. Visceral adipose tissue (VAT) as measured by computed tomography (CT), is an advanced measure of obesity that closely correlates with cardiometabolic risk independent of BMI. However, it remains unknown whether VAT adds additional prognostic significance over BMI in men or women. Methods: In participants of the Framingham Heart Study, we tested the associations of BMI and VAT with incident cardiometabolic events (diabetes, hypertension, low HDL, hypertriglyceridemia), and incident cardiovascular events and death. Mean follow-up was 12.7±2.1 years. Logistic and Cox-regression models were adjusted for age and smoking and adjusted odds and hazard ratios (adj. OR, adj. HR), are presented per 1-SD increase of each measure of body fat. Results: The study cohort comprised 3,482 participants (48.1% women, 50.8±10.3 years old). In men, VAT, as compared to BMI, had a similar strength of association with all cardiometabolic outcomes and incident cardiovascular disease (Figure). In women, however, VAT conferred a markedly greater association with incident cardiometabolic and cardiovascular disease compared to BMI (Figure). Conclusion and Relevance: BMI adequately captures VAT-associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal CT-based VAT measures permit more precise assessment of obesity-associated cardiometabolic and cardiovascular risk.
Document, create and translate knowledge: the mission of ReFORM, the Francophone IOC Research Centre for Prevention of Injury and Protection of Athlete Health
Authors: Géraldine Martens, Pascal Edouard, Philippe Tscholl, François Bieuzen, Laurent Winkler, Jan Cabri, Axel Urhausen, Gaël Guilhem, Jean-Louis Croisier, Patricia Thoreux, Suzanne Leclerc, Didier Hannouche, Jean-François Kaux, Sébastien Le Garrec, Romain Seil
Journal: British Journal of Sports Medicine (2020)

The International Olympic Committee (IOC) has supported athletes' health protection 1 by funding research centres dedicated to prevention and treatment of sports-related injuries and illnesses. 2After establishing four centres in 2009, 2 the IOC research centres network expanded to 9 institutions in 2014 3 and the 2019 round recognised 11 centres. 4 Here we introduce ReFORM-an international Frenchspeaking network of five institutions. 5Who is REfoRm?
Presence of streptococci and frequent tonsillitis among adolescents with psoriasis
Authors: J. Groot, C. Blegvad, A.‐M. Nybo Andersen, C. Zachariae, J.O. Jarløv, L. Skov
Journal: British Journal of Dermatology (2020)

Many dermatologists may appreciate the role that tonsillar infections with Streptococcus pyogenes play in exacerbating or triggering their patients' psoriasis. Especially relevant is the role of tonsillar streptococcal colonization in guttate psoriasis and in some cases in plaque psoriasis.1, 2 Perianal streptococcal infection has been observed in guttate psoriasis.
Abstract 15011: Association of Pulmonary Hemodynamics and Right Ventricular Function With Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Romil R Parikh, Faye L Norby, Wendy Wang, Thenappan Thenappan, Kurt W Prins, Pamela L Lutsey, Scott Solomon, Amil M Shah, Lin Y Chen
Journal: Circulation (2020)

Introduction: Higher pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction are associated with higher risk of heart failure (HF) and mortality. Whether higher PASP and lower RV function are associated with risk of atrial fibrillation (AF) is unclear. Hypothesis: Higher PASP, higher pulmonary vascular resistance (PVR), and lower RV function are associated with incident AF after accounting for left atrial (LA) size and function, and left ventricular (LV) systolic and diastolic function. Methods: ARIC participants free of prevalent coronary heart disease (CHD), HF, AF, and with LA volume index (LAVi) &lt;34ml/m 2 and average E/e’ ratio &lt;14 in 2011-13 were included. We measured PASP, PVR, RV fractional area change (RVFAC), and RV-PA coupling (defined as RVFAC/PASP ratio) from 2D-echocardiograms. Incident AF (through 2018) was ascertained from hospital discharge codes and death certificates. We used Cox proportional hazards regression in our analysis. Results: We included 1915 participants (mean age 75 years, 69% female, 24% black) of whom 176 developed AF over a median follow-up of 6.3 years. PASP, PVR, and RV-PA coupling were significantly associated with incident AF after adjusting for measures of LA and LV structural and functional remodeling. RVFAC was not significantly associated with incident AF. Conclusions: In persons without CHD, HF, and LA enlargement, higher PASP and lower RV-PA coupling are associated with higher risk of AF after accounting for LA and LV structural and functional remodeling. This finding, which suggests a possible etiological role of RV remodeling for AF, needs further confirmation.
FRI0151 Bcl-2 levels of peripheral mononuclear cells in patients with behcet’s disease
Authors: HT Ozer, E Erken, R Gunesacar
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Apoptosis is strictly programmed cell death of aged, disrupted or unnecessary cells. It has substantial role in the development and control of immune system. Its dysregulation may play a part in the pathogenesis of autoimmune disorders. Bcl-2 is an protooncogen of controlling apoptosis in immunocompetent cells. <h3>Objectives</h3> Bcl-2 levels of peripheral mononuclear cells in patients with Behcet’s disease were investigated in order to have information about the apoptotic processes of this vasculitis which pathogenesis is unknown. <h3>Methods</h3> Twenty-eight Behcet’s (mean age ± SD, 41.9 ± 7.8; 15 male,13 female), 21 familial Mediterranean fever (FMF), (mean age 34.5 ± 12.4; 9 male,12 female), 11 rheumatoid arthritis (RA) patients (mean age 44.9 ± 18.5; 1 male, 10 female) and 22 controls (mean age 37.7 ± 6.9; 11 male, 11 female) were taken into the study. Peripheral mononuclear cells of the subjects were isolated by phicol gradient method; after cell counts were standardised according to the kit instructions, the cells were lysed and Bcl-2 levels were studied by ELISA method. <h3>Results</h3> Mean Bcl-2 levels of the Behcet’s patients (mean ± SEM, 78.58 ± 16.38 U/ml) were found significantly lower than that of the controls (161.70 ± 23.97 U/ml), (p = 0.006). No difference was found between the mean Bcl-2 levels of the active and inactive Behcet’s patients. The mean Bcl-2 level of Behcet group was not significantly different than those of the FMF (112.97 ± 29.97 U/ml) and the RA (82.63 ± 31.87 U/ml) groups. Mean Bcl-2 levels of the FMF (p = 0.061) and the RA (p = 0.076) groups were also not different than that of the controls. <h3>Conclusion</h3> Low levels of Bcl-2 in peripheral mononuclear cells of Behcet’s patients might be a clue to the dysregulation of programmed cell death in mononuclear cells of this vasculitis.
Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice
Authors: Lawrence S. Hsieh, John H. Wen, Lena H. Nguyen, Longbo Zhang, Stephanie A. Getz, Juan Torres-Reveron, Ying Wang, Dennis D. Spencer, Angélique Bordey
Journal: Science Translational Medicine (2020)

The causative link between focal cortical malformations (FCMs) and epilepsy is well accepted, especially among patients with focal cortical dysplasia type II (FCDII) and tuberous sclerosis complex (TSC). However, the mechanisms underlying seizures remain unclear. Using a mouse model of TSC- and FCDII-associated FCM, we showed that FCM neurons were responsible for seizure activity via their unexpected abnormal expression of the hyperpolarization-activated cyclic nucleotide-gated potassium channel isoform 4 (HCN4), which is normally not present in cortical pyramidal neurons after birth. Increasing intracellular cAMP concentrations, which preferentially affects HCN4 gating relative to the other isoforms, drove repetitive firing of FCM neurons but not control pyramidal neurons. Ectopic HCN4 expression was dependent on the mechanistic target of rapamycin (mTOR), preceded the onset of seizures, and was also found in diseased neurons in tissue resected from patients with TSC and FCDII. Last, blocking HCN4 channel activity in FCM neurons prevented epilepsy in the mouse model. These findings suggest that HCN4 play a main role in seizure and identify a cAMP-dependent seizure mechanism in TSC and FCDII. Furthermore, the unique expression of HCN4 exclusively in FCM neurons suggests that gene therapy targeting HCN4 might be effective in reducing seizures in FCDII or TSC.
Focal Liver 18F-FDG Uptake in a Patient Who Underwent Thrombolysis for Brachiocephalic and Subclavian Thrombosis
Authors: Alexis Huot Daneault, Richard Le Blanc, Nathalie Voyer, Éric Turcotte, Etienne Rousseau
Journal: Clinical Nuclear Medicine (2020)

A 19-year-old woman presented with a primary mediastinal B-cell lymphoma invading the superior vena cava with associated thrombosis of the left brachiocephalic and subclavian vein. She underwent thrombolysis followed by chemotherapy. The midtreatment 18F-FDG PET/CT demonstrated important regression of the primary mediastinal B-cell lymphoma, but showed intense focal hepatic uptake in segment IV, without a corresponding lesion on ultrasonography, non-contrast-enhanced low-dose CT, and MRI. This focal uptake disappeared on a subsequent 18F-FDG PET/CT study when the radiotracer was injected in the foot, suggesting an anomalous venous return pathway that persisted despite thrombolysis.
<i>In Vivo</i> Characterization of the Toxicological Properties of DPhP, One of the Main Degradation Products of Aryl Phosphate Esters
Authors: Samia Selmi-Ruby, Jesús Marín-Sáez, Aurélie Fildier, Audrey Buleté, Myriam Abdallah, Jessica Garcia, Julie Deverchère, Loïc Spinner, Barbara Giroud, Sébastien Ibanez, Thierry Granjon, Claire Bardel, Alain Puisieux, Béatrice Fervers, Emmanuelle Vulliet, Léa Payen, Arnaud M. Vigneron
Journal: Environmental Health Perspectives (2020)

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