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https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#1
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28735302/autopsy-interrogation-of-emergency-medicine-dispute-cases-how-often-are-clinical-diagnoses-incorrect
#2
Danyang Liu, Rongchang Gan, Weidi Zhang, Wei Wang, Hexige Saiyin, Wenjiao Zeng, Guoyuan Liu
AIMS: Emergency medicine is a 'high risk' specialty. Some diseases develop suddenly and progress rapidly, and sudden unexpected deaths in the emergency department (ED) may cause medical disputes. We aimed to assess discrepancies between antemortem clinical diagnoses and postmortem autopsy findings concerning emergency medicine dispute cases and to figure out the most common major missed diagnoses. METHODS: Clinical files and autopsy reports were retrospectively analysed and interpreted...
July 22, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28735291/subclinical-atherosclerosis-cardiac-and-kidney-function-heart-failure-and-dementia-in-the-very-elderly
#3
Lewis H Kuller, Oscar L Lopez, John S Gottdiener, Dalane W Kitzman, James T Becker, Yuefang Chang, Anne B Newman
BACKGROUND: Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury)...
July 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28735170/effects-of-different-solvents-on-the-conformations-of-apoptotic-cytochrome-c-structural-insights-from-molecular-dynamics-simulation
#4
Gurusamy Muneeswaran, Subramanian Kartheeswaran, Kaliappan Muthukumar, Christopher D Dharmaraj, Chandran Karunakaran
Cytochrome c (cyt-c) upon binding with cardiolipin acquires peroxidase activity and is strictly connected to the pathogenesis of many human diseases including neurodegenerative and cardiovascular diseases. Interaction of cyt-c with cardiolipin mimics partial unfolding/conformational changes of cyt-c in different solvent environments. Dynamic pictures of these conformational changes of cyt-c are crucial in understanding their physiological roles in mitochondrial functions. Therefore, atomistic molecular dynamics (MD) simulations have been carried out to investigate the effect of different solvents (water, urea/water, MeOH and DMSO) on the structure and conformations of apoptotic cyt-c (Fe(3+))...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28735153/self-monitoring-systems-for-personalised-health-care-and-lifestyle-surveillance
#5
EDITORIAL
Giuseppe Coppini, Sara Colantonio
The quality of life and individual well-being are universally recognised as key factors in disease prevention. In particular, lifestyle interventions are effective tools for reducing the risk and incidence of major illnesses, such as cardiovascular diseases and metabolic disorders. On the other hand, patient role is progressively shifting from being a passive recipient of care towards being a co-producer of her/his health. In this frame, novel devices and systems able to help individuals in self-evaluation are expected to play a crucial role...
July 19, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28735152/a-systematic-review-of-cardiovascular-emergency-department-visits-hospital-admissions-and-mortality-associated-with-ambient-black-carbon
#6
REVIEW
Thomas J Luben, Jennifer L Nichols, Steven J Dutton, Ellen Kirrane, Elizabeth O Owens, Laura Datko-Williams, Meagan Madden, Jason D Sacks
BACKGROUND: Black carbon (BC) is a ubiquitous component of particulate matter (PM) emitted from combustion-related sources and is associated with a number of health outcomes. OBJECTIVES: We conducted a systematic review to evaluate the potential for cardiovascular morbidity and mortality following exposure to ambient BC, or the related component elemental carbon (EC), in the context of what is already known about the associations between exposure to fine particulate matter (PM2...
July 20, 2017: Environment International
https://www.readbyqxmd.com/read/28735151/do-air-pollution-and-neighborhood-greenness-exposures-improve-the-predicted-cardiovascular-risk
#7
Maayan Yitshak-Sade, Itai Kloog, Victor Novack
BACKGROUND: Numerous studies show associations between exposure to Particulate Matter and Cardiovascular disease (CVD). Current cardiovascular equations incorporate the major risk factors for CVD. The patients' environment, however, is not incorporated in these equations. METHODS: In a retrospective analysis, we assessed the contribution of neighborhood greenness and particulate matter (coarse-PM and PM<2.5μm-PM2.5) to the development of CVD by analyzing the change in prediction abilities...
July 20, 2017: Environment International
https://www.readbyqxmd.com/read/28735097/protecting-the-heart-through-mk2-modulation-toward-a-role-in-diabetic-cardiomyopathy-and-lipid-metabolism
#8
REVIEW
Matthieu Ruiz, Lise Coderre, Bruce Gordon Allen, Christine Des Rosiers
Various signaling pathways have been identified in the heart as important players during development, physiological adaptation or pathological processes. This includes the MAPK families, particularly p38MAPK, which is involved in several key cellular processes, including differentiation, proliferation, apoptosis, inflammation, metabolism and survival. Disrupted p38MAPK signaling has been associated with several diseases, including cardiovascular diseases (CVD) as well as diabetes and its related complications...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735064/associations-of-fibroblast-growth-factor-21-with-cardiovascular-risk-and-%C3%AE-cell-function-in-patients-who-had-no-history-of-diabetes
#9
Jun-Sing Wang, Wayne Huey-Herng Sheu, Wen-Jane Lee, I-Te Lee, Shih-Yi Lin, Wen-Lieng Lee, Kae-Woei Liang, Shing-Jong Lin
BACKGROUND: We investigated the associations of fibroblast growth factor 21 (FGF-21) with cardiovascular risk and β-cell function in patients who had no history of diabetes. METHODS: We enrolled 269 outpatients who had been referred for an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and FGF-21 were measured before and at 2h after the OGTT. β-cell function was assessed using the insulinogenic index, corrected for insulin resistance. Patients' 10-year coronary heart disease (CHD) risk was assessed using the Chinese Multi-provincial Cohort Study functions...
July 19, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28734928/lv-mass-independently-predicts-mortality-and-need-for-future-revascularization-in%C3%A2-patients-undergoing-diagnostic-coronary-angiography
#10
Ahmed Abdi-Ali, Robert J H Miller, Danielle Southern, Mei Zhang, Yoko Mikami, Merril Knudtson, Bobak Heydari, Andrew G Howarth, Carmen P Lydell, Mathew T James, Stephen B Wilton, James A White
OBJECTIVES: The goal of this study was to assess associations between left ventricular (LV) mass, all-cause mortality, and need for revascularization in patients undergoing coronary angiography. BACKGROUND: LV hypertrophy is associated with adverse cardiovascular outcomes in healthy subjects. However, its influence in those with known or suspected coronary artery disease is poorly understood. METHODS: A total of 3,754 patients (mean age 59...
July 13, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28734922/warfarin-use-is-associated-with-progressive-coronary-arterial-calcification-insights-from-serial-intravascular-ultrasound
#11
Jordan Andrews, Peter J Psaltis, Ozgur Bayturan, Mingyuan Shao, Brian Stegman, Mohamed Elshazly, Samir R Kapadia, E Murat Tuzcu, Steven E Nissen, Stephen J Nicholls, Rishi Puri
OBJECTIVES: This study compared serial changes in coronary percent atheroma volume (PAV) and calcium index (CaI) in patients with coronary artery disease who were treated with and without warfarin. BACKGROUND: Warfarin blocks the synthesis and activity of matrix Gla protein, a vitamin K-dependent inhibitor of arterial calcification. The longitudinal impact of warfarin on serial coronary artery calcification in vivo in humans is unknown. METHODS: In a post hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound examinations, this study compared changes in PAV and CaI in matched arterial segments in patients with coronary artery disease who were treated with (n = 171) and without (n = 4,129) warfarin during an 18- to 24-month period...
July 13, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28734900/molecular-imaging-in-stem-cell-based-therapies-of-cardiac-diseases
#12
REVIEW
Xiang Li, Marcus Hacker
In the past 15years, despite regenerative medicine has shown great potential for cardiovascular diseases, the outcome and safety of stem cell transplantation has shown controversial results in the published literature. Medical imaging might be useful for monitoring and quantification transplanted cells within the heart and to serially characterize the effects of stem cell therapy of the myocardium. From the multiple available noninvasive imaging techniques, magnetic resonance imaging and nuclear imaging by positron (PET) or single photon emission computer tomography (SPECT) are the most used clinical approaches to follow the fate of transplanted stem cells in vivo...
July 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28734857/comorbidities-in-difficult-to-control-asthma
#13
Pieter-Paul W Hekking, Marijke Amelink, Reinier R Wener, Marcel L Bouvy, Elisabeth H Bel
BACKGROUND: Difficult-to-control asthma is associated with significant medical and financial burden. Comorbidities are known to contribute to uncontrolled asthma. Better insight into the prevalence, nature, and risk factors of comorbidities may optimize treatment strategies in patients with difficult-to-control asthma and decrease disease burden. OBJECTIVES: The objectives of this study were to assess the prevalence, number, and type of comorbidities in difficult-to-control asthma compared with not-difficult-to-control asthma, and to investigate whether specific patient characteristics are associated with particular comorbidities...
July 19, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28734575/outcomes-associated-to-serum-phosphate-levels-in-patients-with-suspected-acute-coronary-syndrome
#14
Hong Xu, Marie Evans, Alessandro Gasparini, Karolina Szummer, Jonas Spaak, Johan Ärnlöv, Bengt Lindholm, Tomas Jernberg, Juan Jesús Carrero
BACKGROUND: We investigated the association between phosphate and the risk of adverse clinical outcomes in patients with manifest cardiovascular disease (CVD). METHODS: Observational study of patients hospitalized during 2006-2011 in Stockholm, Sweden, because of suspected acute coronary syndrome (ACS). The exposure was serum phosphate during the hospitalization. We modeled the association between phosphate and in-hospital death or in-hospital events (composite of myocardial infarction, cardiogenic shock, resuscitated cardiac arrest, atrial fibrillation, or atrioventricular block) as well as the one-year post-discharge risk of death or cardiovascular event (composite of myocardial re-infarction, heart failure and stroke)...
July 17, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28734528/exploring-risk-patterns-for-incident-ischemic-stroke-during-more-than-a-decade-of-follow-up-a-survival-tree-analysis
#15
Donna Parizadeh, Azra Ramezankhani, Amir Abbas Momenan, Fereidoun Azizi, Farzad Hadaegh
BACKGROUND AND PURPOSE: The burden of stroke is increasing in low to middle income countries. Identifying risk patterns for ischemic stroke (IS) can help develop individualized preventive measures for at risk populations. METHODS: The study population included 3088 Iranian subjects (1426 men) aged ≥50 years, free of cardiovascular diseases at baseline. The risk factors for ischemic stroke were identified by multivariate Cox analysis. A survival tree model was used to explore interactions between risk factors...
August 2017: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/28734461/risk-factors-for-mortality-among-individuals-with-peripheral-arterial-disease
#16
Stephen M Amrock, Cherrie Z Abraham, Enjae Jung, Pamela B Morris, Michael D Shapiro
Morbidity and mortality from peripheral arterial disease (PAD) continues to increase. Traditional cardiovascular risk factors are implicated in the development of PAD, yet the extent to which those risk factors correlate with mortality in such patients remains insufficiently assessed. Using data from the 1999 to 2004 National Health and Nutrition Examination Survey, Cox proportional hazards models were used to examine the association of cardiovascular risk factors and all-cause and cardiovascular mortality...
June 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28734244/renal-denervation-attenuates-hypertension-and-renal-dysfunction-in-a-model-of-cardiovascular-and-renal-disease-which-is-associated-with-reduced-nadph-and-xanthine-oxidase-activity
#17
Maria Peleli, Peter Flacker, Zhengbing Zhuge, Cristina Gomez, Craig E Wheelock, A Erik G Persson, Mattias Carlstrom
Oxidative stress is considered a central pathophysiological event in cardiovascular disease, including hypertension. Early age reduction in renal mass is associated with hypertension and oxidative stress in later life, which is aggravated by increased salt intake. The aim of the present study was to examine if renal sympathetic denervation can exert blood pressure lowering effects in uninephrectomized (UNX) rats (3-week old) fed with high salt (HS, 4%; w/w) diet for 4 weeks. Moreover, we investigated if renal denervation is associated with changes in NADPH and xanthine oxidase-derived reactive oxygen species...
July 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28734077/integrative-studies-implicate-matrix-metalloproteinase-12-as-a-culprit-gene-for-large-artery-atherosclerotic-stroke
#18
Hovsep Mahdessian, Ljubica Perisic Matic, Mariette Lengquist, Karl Gertow, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino, Elena Tremoli, Anders Hamsten, Per Eriksson, Ulf Hedin, Anders Mälarstig
BACKGROUND: Ischemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischemic stroke. Here we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies...
July 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28733923/cardiovascular-mechanics-in-the-early-stages-of-pulmonary-hypertension-a-computational-study
#19
Sebastián Acosta, Charles Puelz, Béatrice Rivière, Daniel J Penny, Ken M Brady, Craig G Rusin
We formulate and study a new mathematical model of pulmonary hypertension. Based on principles of fluid and elastic dynamics, we introduce a model that quantifies the stiffening of pulmonary vasculature (arteries and arterioles) to reproduce the hemodynamics of the pulmonary system, including physiologically consistent dependence between compliance and resistance. This pulmonary model is embedded in a closed-loop network of the major vessels in the body, approximated as one-dimensional elastic tubes, and zero-dimensional models for the heart and other organs...
July 21, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28733905/glp-1-glucagon-receptor-co-agonism-for-treatment-of-obesity
#20
REVIEW
Miguel A Sánchez-Garrido, Sara J Brandt, Christoffer Clemmensen, Timo D Müller, Richard D DiMarchi, Matthias H Tschöp
Over a relatively short period, obesity and type 2 diabetes have come to represent a large medical and economic burden to global societies. The epidemic rise in the prevalence of obesity has metabolic consequences and is paralleled by an increased occurrence of other diseases, such as diabetes, cancer and cardiovascular complications. Together, obesity and type 2 diabetes constitute one of the more preventable causes of premature death and the identification of novel, safe and effective anti-obesity drugs is of utmost importance...
July 21, 2017: Diabetologia
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