Search

Hypothalamic-Pituitary-Adrenal (HPA) axis activity is related to negative mental health outcomes, including depression. Most developmental research uses salivary cortisol to index HPA activity; however, hair cortisol concentrations (HCCs) reflect cortisol production over extended periods of time. While HCCs have been linked to adult depression, their relationship to the development of children's depressive symptoms is unclear. We assessed HCCs in 60 seven-year-old community-dwelling girls who were followed up one year later. In broader models, girls' age 7 HCCs were positively associated with age 8 depressive symptoms at a trend level, indicating that HCCs may be related to mental health early in development.

This is the second of the two White Papers from the fourth UC Davis Cardiovascular Symposium Systems Approach to Understanding Cardiac Excitation-Contraction Coupling and Arrhythmias (3-4 March 2016), a biennial event that brings together leading experts in different fields of cardiovascular research. The theme of the 2016 symposium was 'K+ channels and regulation', and the objectives of the conference were severalfold: (1) to identify current knowledge gaps; (2) to understand what may go wrong in the diseased heart and why; (3) to identify possible novel therapeutic targets; and (4) to further the development of systems biology approaches to decipher the molecular mechanisms and treatment of cardiac arrhythmias. The sessions of the Symposium focusing on the functional roles of the cardiac K+ channel in health and disease, as well as K+ channels as therapeutic targets, were contributed by Ye Chen-Izu, Gideon Koren, James Weiss, David Paterson, David Christini, Dobromir Dobrev, Jordi Heijman, Thomas O'Hara, Crystal Ripplinger, Zhilin Qu, Jamie Vandenberg, Colleen Clancy, Isabelle Deschenes, Leighton Izu, Tamas Banyasz, Andras Varro, Heike Wulff, Eleonora Grandi, Michael Sanguinetti, Donald Bers, Jeanne Nerbonne and Nipavan Chiamvimonvat as speakers and panel discussants. This article summarizes state-of-the-art knowledge and controversies on the functional roles of cardiac K+ channels in normal and diseased heart. We endeavour to integrate current knowledge at multiple scales, from the single cell to the whole organ levels, and from both experimental and computational studies.

BACKGROUND: Long QT syndrome type 1 (LQT1) is a congenital disease arising from a loss of function in the slowly activating delayed potassium current IKs, which causes early afterdepolarizations (EADs) and polymorphic ventricular tachycardia (pVT). OBJECTIVE: The purpose of this study was to investigate the mechanisms underlying pVT using a transgenic rabbit model of LQT1. METHODS: Hearts were perfused retrogradely, and action potentials were recorded using a voltage-sensitive dye and CMOS cameras. RESULTS: Bolus injection of isoproterenol (140 nM) induced pVT initiated by focal excitations from the right ventricle (RV; n = 16 of 18 pVTs). After the pVT was initiated, complex focal excitations occurred in both the RV and the left ventricle, which caused oscillations of the QRS complexes on ECG, consistent with the recent proposal of multiple shifting foci caused by EAD chaos. Moreover, the action potential upstroke in pVT showed a bimodal distribution, demonstrating the coexistence of 2 types of excitation that interacted to produce complex pVT: Na(+) current (INa)-mediated fast conduction and L-type Ca(2+) current (ICa)-mediated slow conduction coexist, manifesting as pVT. Addition of 2 μM tetrodotoxin to reduce INa converted pVT into monomorphic VT. Reducing late INa in computer simulation converted pVT into a single dominant reentry, agreeing with experimental results. CONCLUSION: Our study demonstrates that pVT in LQT1 rabbits is initiated by focal excitations from the RV and is maintained by multiple shifting foci in both ventricles. Moreover, wave conduction in pVT exhibits bi-excitability, that is, fast wavefronts driven by INa and slow wavefronts driven by ICa co-exist during pVT.

BackgroundRemodeling of cardiac repolarizing currents, such as the downregulation of slowly activating K+ channels (IKs), could underlie ventricular fibrillation (VF) in heart failure (HF). We evaluated the role of Iks remodeling in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long QT Type 1 (LQT1) syndrome.Methods and resultsLQT1 and littermate control (LMC) rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM). In vivo telemetry demonstrated steepening of the QT/RR slope in LQT1 with TICM (LQT1-TICM; pre: 0.26±0.04, post: 0.52±0.01, P

This study was designed to track the developmental trajectory, during the first 24 months of life, of 335 low-risk infants later diagnosed with Autism Spectrum Disorder and identify early deviations observed in routine Well Care checkups. We compared their achievements to typically developing children and to children later diagnosed with non-autistic developmental impairments. The results show that in the first 6 months, the children with autism showed normal acquisition of milestones, whereas by 9 months of age they began to fail the language/communication, as well as motor items when compared to typical and delayed non-autistic children. Regular check-up visits may be useful in detecting early failure in achieving milestones, leading to earlier referral for further evaluation and treatment.

BackgroundWe evaluated how computerized clinical decision support (CDS) affects the counseling women receive when primary care physicians (PCPs) prescribe potential teratogens and how this counseling affects women's behavior.MethodsBetween October 2008 and April 2010, all women aged 18-50 years visiting one of three community-based family practice clinics or an academic general internal medicine clinic were invited to complete a survey 5-30 days after their clinic visit. Women who received prescriptions were asked if they were counseled about teratogenic risks or contraception and if they used contraception at last intercourse.ResultsEight hundred one women completed surveys; 27% received a prescription for a potential teratogen. With or without CDS, women prescribed potential teratogens were more likely than women prescribed safer medications to report counseling about teratogenic risks. However, even with CDS 43% of women prescribed potential teratogens reported no counseling. In multivariable models, women were more likely to report counseling if they saw a female PCP (odds ratio: 1.97; 95% confidence interval: 1.26-3.09). Women were least likely to report counseling if they received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Women who were pregnant or trying to conceive were not more likely to report counseling. Nonetheless, women who received counseling about contraception or teratogenic risks were more likely to use contraception after being prescribed potential teratogens than women who received no counseling.ConclusionsPhysician counseling can reduce risk of medication-induced birth defects. However, efforts are needed to ensure that PCPs consistently inform women of teratogenic risks and provide access to highly effective contraception.