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Structure heart

Joanne Philp, Brian G Lawhorn, Alan P Graves, Lisa Shewchuk, Katrina L Rivera, Larry J Jolivette, Dennis A Holt, Gregory J Gatto, Lara S Kallander
Structure-guided progression of a purine-derived series of TNNI3K inhibitors directed design efforts that produced a novel series of 4,6-diaminopyrimidine inhibitors, an emerging kinase binding motif. Herein, we report a detailed understanding of the intrinsic conformational preferences of the scaffold, which impart high specificity for TNNI3K. Further manipulation of the template based on the conformational analysis and additional structure-activity relationship studies provided enhancements in kinase selectivity and pharmacokinetics that furnished an advanced series of potent inhibitors...
March 21, 2018: Journal of Medicinal Chemistry
Fang-Yu Liu, Te-Cheng Hsu, Patrick Choong, Min-Hsuan Lin, Yung-Jen Chuang, Bor-Sen Chen, Che Lin
BACKGROUND: Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike's Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina...
March 19, 2018: BMC Systems Biology
Houda Bahig, Jacques de Guise, Toni Vu, Danis Blais, Carl Chartrand-Lefebvre, Nhu Tram Nguyen, Sophie Lavertu, Jean-Pierre Guay, Stephane Bedwani, David Roberge
PURPOSE: To assess radiation dose variation to the left anterior descending artery (LAD), left main coronary artery (LMCA), left ventricle (LV), and whole heart (WH) during the cardiac cycle using dual source computed tomography (DSCT). METHODS AND MATERIALS: The present prospective study included patients with left-side breast cancer planned to undergo tangential radiation therapy. An electrocardiogram-synchronized contrast-injected DSCT scan was obtained with the patient in the treatment position, in deep-inspiration breath-hold, using retrospective sequential acquisition...
January 31, 2018: International Journal of Radiation Oncology, Biology, Physics
Miłosz Zajączkowski, Adam Kosiński, Marek Grzybiak, Rafał Kamiński, Agata Kaczyńska, Stanisław Zajączkowski, Ewa Nowicka
BACKGROUND: In cardiology, the paths of the arteries penetrating the septomarginal trabecula (SMT) are especially important. They provide blood supply to the apparatus of the right atrioventricular orifice and often form anastomoses with the system of the right coronary artery. Despite this, only a few publications discuss the morphological aspect of the septomarginal trabecula, and available histological analyses seldom deal with its blood supply. OBJECTIVES: The aim of this study was to analyze the vessel structure of the septomarginal trabecula in terms of the variability of the area of the cross-section of the lumen and the muscular layer of the artery...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Tim L Wigal, Jeffrey H Newcorn, Nelson Handal, Sharon B Wigal, Ioulietta Mulligan, Virginia Schmith, Eric Konofal
BACKGROUND: Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel controlled-release (CR) formulation of mazindol was developed to allow once-daily dosing. OBJECTIVE: The aim of this study was to evaluate the efficacy of mazindol CR in adults with ADHD. DESIGN: We conducted a randomized, double-blind, placebo-controlled 6-week trial. METHODS: Subjects diagnosed with ADHD using the Mini-International Neuropsychiatric Structured Interview (MINI) and with an ADHD Rating Scale, Diagnostic and Statistical Manual of Mental Disorders 5th Edition (ADHD-RS-DSM5) score ≥ 28 were randomized to receive placebo or 1-3 mg/day of mazindol for 6 weeks...
March 19, 2018: CNS Drugs
Jingtao Lu, Jianguo Li, Gabriel Helmlinger, Nidal Al-Huniti
Modeling the relationship between drug concentrations and heart rate corrected QT interval (QTc) change from baseline (C-∆QTc), based on Phase I single ascending dose (SAD) or multiple ascending dose (MAD) studies, has been proposed as an alternative to thorough QT studies (TQT), in assessing drug-induced QT prolongation risk. The present analysis used clinical SAD, MAD and TQT study data of an experimental compound, AZD5672, to evaluate the performance of: (i) three computational platforms (linear mixed-effects modeling implemented via PROC MIXED in SAS, as well as in R using LME4 package and linear quantile mixed models (LQMM) implemented via LQMM package; (ii) different model structures with and without treatment- or time-specific intercepts; and (iii) three methods for calculating the confidence interval (CI) of QTc prolongation (analytical and bootstrap methods with fixed or varied geometric mean concentrations)...
March 19, 2018: Journal of Pharmacokinetics and Pharmacodynamics
K Schneider
The radiographic technique of pediatric chest X‑rays is substantially different from that in adults. In nearly all cases ap/pa X‑rays are sufficient and lateral radiographs are rarely needed. In the first years of life the thymus may overshadow the heart, the great vessels and the lung hila. The most important anatomical structures essential for diagnosing pathological findings of the lungs and mediastinum are the trachea with the bifurcation and the main bronchi with the adjacent great vessels. For the assessment of distended lungs and intrathoracic consolidations, fundamental knowledge of the anatomy in childhood and malformations which can involve the airways, the lungs, the heart, as well as systemic and pulmonary vessels are indispensable...
March 19, 2018: Der Radiologe
Justin O Szot, Hartmut Cuny, Gillian M Blue, David T Humphreys, Eddie Ip, Katrina Harrison, Gary F Sholler, Eleni Giannoulatou, Paul Leo, Emma L Duncan, Duncan B Sparrow, Joshua W K Ho, Robert M Graham, Nicholas Pachter, Gavin Chapman, David S Winlaw, Sally L Dunwoodie
BACKGROUND: Congenital heart disease (CHD)-structural abnormalities of the heart that arise during embryonic development-is the most common inborn malformation, affecting ≤1% of the population. However, currently, only a minority of cases can be explained by genetic abnormalities. The goal of this study was to identify disease-causal genetic variants in 30 families affected by CHD. METHODS: Whole-exome sequencing was performed with the DNA of multiple family members...
March 2018: Circ Genom Precis Med
Shuyi Wang, Jun Ren
Alcoholism is accompanied with a high incidence of cardiac morbidity and mortality due to the development of alcoholic cardiomyopathy, manifested as dilation of one or both ventricles, reduced ventricular wall thickness, myofibrillary disarray, interstitial fibrosis, hypertrophy and contractile dysfunction. Several theories have been postulated for the etiology of alcoholic cardiomyopathy including ethanol/acetaldehyde toxicity, mitochondrial production of reactive oxygen species, oxidative injury, apoptosis, impaired myofilament Ca2+ sensitivity and protein synthesis, altered fatty acid extraction and deposition, as well as accelerated protein catabolism...
March 16, 2018: Biochimica et Biophysica Acta
Rui Zhang, Caihong Huo, Xingning Wang, Bo Dang, Yaning Mu, Yuying Wang
BACKGROUND/AIMS: Published studies indicated that the MTHFR gene polymorphisms C677T and A1298C are associated with congenital heart disease (CHD) risk in children, but obtained inconsistent results. Our study aims to reach a more accurate association between these two polymorphisms and CHD risk. METHODS: Eligible studies were obtained by screening the PubMed, Embase, China National Knowledge Infrastructure, Wan Fang and VIP databases based on designed searching strategy...
March 15, 2018: Cellular Physiology and Biochemistry
Hironori Sagawa, Shinsuke Hoshino, Kengo Yoshioka, Wei-Guang Ding, Mariko Omatsu-Kanbe, Masao Nakagawa, Yoshihiro Maruo, Hiroshi Matsuura
BACKGROUND: In the clinical setting, verapamil is contraindicated in neonates and infants because of the perceived risk of hypotension or bradyarrhythmia. However, it remains unclear whether there is an age-dependent difference in the sensitivity of cardiac L-type Ca2+ channel current (ICa,L ) to inhibition by verapamil. METHODS: Ventricular myocytes were enzymatically dissociated from the hearts of 6 different age groups (0, 7, 14, 21, 28 days and 10-15 weeks) of mice using a similar Langendorff-perfusion method...
March 19, 2018: Pediatric Research
Renee Wei-Yan Chow, Paola Lamperti, Emily Steed, Francesco Boselli, Julien Vermot
During embryogenesis, cells undergo dynamic changes in cell behavior, and deciphering the cellular logic behind these changes is a fundamental goal in the field of developmental biology. The discovery and development of photoconvertible proteins have greatly aided our understanding of these dynamic changes by providing a method to optically highlight cells and tissues. However, while photoconversion, time-lapse microscopy, and subsequent image analysis have proven to be very successful in uncovering cellular dynamics in organs such as the brain or the eye, this approach is generally not used in the developing heart due to challenges posed by the rapid movement of the heart during the cardiac cycle...
February 20, 2018: Journal of Visualized Experiments: JoVE
Abeer A Nasir, Razan Salah, Abla Sayyed Ahmad, Samah Abu Hijleh, Sa'eed Abu Kattab, Alia Al Kurd, Rawan Al Sharif, Raed Amro, Ahmad Khatib, Hana' Mousa, Walaa Shamasnah, Khammisa Shqerat, Rita Giacaman
BACKGROUND: Hamm is an Arabic word that is used to express suffering. Idioms of distress are communicated differently in different contexts and cultures. Understanding idioms of distress and symptoms can help in diagnosis and lead to socioculturally sensitive health care. METHODS: In this qualitative study, we did semi-structured interviews with men and women of all age groups. Questions focused on the definition, causes, and consequences of Hamm. Responses were analysed by reading and re-reading interview transcripts until themes and subthemes emerged...
February 21, 2018: Lancet
Ting-Bo Chen, Yi-Han Zuo, Geng-Ting Dong, Liang Liu, Hua Zhou
BACKGROUND: Guanxin Kangtai preparation (GXKT), consisting of Panax ginseng, Panax notoginseng and Ilex pubescens, is a new proprietary Chinese medicines under development for treating coronary heart disease. Like other Chinese medicines, the components of GXKT were complex and the bioactive compounds remained unclear. PURPOSE: To discover bioactive compounds as quality markers (Q-markers) for better quality control of GXKT. STUDY DESIGN: Chinese medicines was separated into fractions...
March 6, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Cory S Inman, Kelly R Bijanki, David I Bass, Robert E Gross, Stephan Hamann, Jon T Willie
The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation...
March 15, 2018: Neuropsychologia
David Hasler, Dominik Obrist
The flow field past a prosthetic aortic valve comprises many details that indicate whether the prosthesis is functioning well or not. It is, however, not yet fully understood how an optimal flow scenario would look, i.e. which subtleties of the fluid dynamics in place are essential regarding the durability and compatibility of a prosthetic valve. In this study, we measured and analyzed the 3D flow field in the vicinity of a bio-prosthetic heart valve in function of the aortic root size. The measurements were conducted within aortic root phantoms of different size, mounted in a custom-built hydraulic setup, which mimicked physiological flow conditions in the aorta...
2018: PloS One
Arthur Bob Karnuah, Gregory Dunga, Arthur Wennah, Walter T Wiles, Edmond Greaves, Roland Varkpeh, Richard Osei-Amponsah, Paul Boettcher
Phenotypic characterization of animal genetic resources (AnGR) involves identification of distinct breed populations, describing their external and production characteristics in a given environment and management, and taking into account the social and economic factors that affect them. A survey involving 346 livestock farmers was conducted in the 15 counties of Liberia to collect data on production practices and phenotypic characteristics of beef cattle. A pre-tested structured questionnaire, focus group discussions, and in-depth interviews were utilized in data collection...
March 15, 2018: Tropical Animal Health and Production
Natalia A Trayanova, Patrick M Boyle, Plamen P Nikolov
The goal of this article is to review advances in computational modeling of the heart, with a focus on recent non-invasive clinical imaging- and simulation-based strategies aimed at improving the diagnosis and treatment of patients with arrhythmias and structural heart disease. Following a brief overview of the field of computational cardiology, we present recent applications of the personalized virtual-heart approach in predicting the optimal targets for infarct-related ventricular tachycardia and atrial fibrillation ablation, and in determining risk of sudden cardiac death in myocardial infarction patients...
March 2018: Current Opinion in Biomedical Engineering
Luqing Wei, Hong Chen, Guo-Rong Wu
The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV...
2018: Frontiers in Human Neuroscience
Sini M Kinnunen, Marja Tölli, Mika J Välimäki, Erhe Gao, Zoltan Szabo, Jaana Rysä, Mónica P A Ferreira, Pauli Ohukainen, Raisa Serpi, Alexandra Correia, Ermei Mäkilä, Jarno Salonen, Jouni Hirvonen, Hélder A Santos, Heikki Ruskoaho
Transcription factors are fundamental regulators of gene transcription, and many diseases, such as heart diseases, are associated with deregulation of transcriptional networks. In the adult heart, zinc-finger transcription factor GATA4 is a critical regulator of cardiac repair and remodelling. Previous studies also suggest that NKX2-5 plays function role as a cofactor of GATA4. We have recently reported the identification of small molecules that either inhibit or enhance the GATA4-NKX2-5 transcriptional synergy...
March 15, 2018: Scientific Reports
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