HIV transmission and HIV prevention associated with injecting drug use in the Russian Federation

Aims: We review recent evidence of trends in HIV infection, risk behaviour and HIV prevention associated with injecting drug use in the Russian Federation. Methods: Findings draw on a review of English and Russian language research, published international conference abstracts, international agency and assessment reports, and centrally registered HIV surveillance data. Findings: We note the continued major importance of injecting drug use in mediating HIV transmission within Russia, noting recent evidence of HIV outbreaks associated with drug injecting. We note that high levels of risk behaviour associated with drug injecting may persist, but that evidence associates syringe distribution and exchange with reductions in risk behaviour. We summarise the development of 75 syringe distribution and exchange schemes and outreach interventions in the Federation, providing crude estimates of IDU population coverage and syringe distribution coverage. Conclusions: In the context of continuing levels of risk behaviour sufficient to sustain HIV transmission alongside evidence associating syringe distribution and exchange with risk reduction among IDUs, we note the critical importance of policy interventions to maximise syringe distribution coverage among IDU populations. © 2003 Published by Elsevier B.V

Human Immunodeficiency Virus Type 1 in Illicit-Drug Solutions Used Intravenously Retains Infectivity

The stability of the human immunodeficiency virus type 1 (HIV-1) strain IIIB in drug solutions was studied. The data demonstrate that HIV-1 infectivity can be retained in drug solutions (e.g. , heroin, “Khanka,” and “Vint”) for long periods of time. This fact must be taken into account when designing health education programs for the prevention of HIV and AIDS in Eastern Europe

HCN2/SkM1 Gene Transfer Into Canine Left Bundle Branch Induces Stable, Autonomically Responsive Biological Pacing at Physiological Heart Rates

Objectives This study sought to test the hypothesis that hyperpolarization-activated cyclic nucleotide-gated (HCN)-based biological pacing might be improved significantly by hyperpolarizing the action potential (AP) threshold via coexpression of the skeletal muscle sodium channel 1 (SkM1). Background Gene-based biological pacemakers display effective in vivo pacemaker function. However, approaches used to date have failed to manifest optimal pacemaker properties, defined as basal beating rates of 60 to 90 beats/min, a brisk autonomic response achieving maximal rates of 130 to 160 beats/min, and low to absent electronic backup pacing. Methods We implanted adenoviral SkM1, HCN2, or HCN2/SkM1 constructs into left bundle branches (LBB) or left ventricular (LV) epicardium of atrioventricular-blocked dogs. Results During stable peak gene expression on days 5 to 7, HCN2/SkM1 LBB-injected dogs showed highly stable in vivo pacemaker activity superior to SkM1 or HCN2 alone and superior to LV-implanted dogs with regard to beating rates (resting approximately 80 beats/min; maximum approximately 130 beats/min), no dependence on electronic backup pacing, and enhanced modulation of pacemaker function during circadian rhythm or epinephrine infusion. In vitro isolated LV of dogs overexpressing SkM1 manifested a significantly more negative AP threshold. Conclusions LBB-injected HCN2/SkM1 potentially provides a more clinically suitable biological pacemaker strategy than other reported constructs. This superiority is attributable to the more negative AP threshold and injection into the LBB. (J Am Coll Cardiol 2013;61:1192-201) (C) 2013 by the American College of Cardiology Foundatio

Effect of Skeletal Muscle Na+ Channel Delivered Via a Cell Platform on Cardiac Conduction and Arrhythmia Induction

Background-In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel is largely inactivated, contributing to slow conduction and reentry. We have demonstrated that adenoviral delivery of the skeletal muscle Na+ channel (SkM1) to epicardial border zones normalizes conduction and reduces induction of ventricular tachycardia/ventricular fibrillation. We now studied the impact of canine mesenchymal stem cells (cMSCs) in delivering SkM1. Methods and Results-cMSCs were isolated and transfected with SkM1. Coculture experiments showed cMSC/SkM1 but not cMSC alone and maintained fast conduction at depolarized potentials. We studied 3 groups in the canine 7d infarct: sham, cMSC, and cMSC/SkM1. In vivo epicardial border zones electrograms were broad and fragmented in sham, narrower in cMSCs, and narrow and unfragmented in cMSC/SkM1 (P 0.05). Conclusion-cMSCs provide efficient delivery of SkM1 current. The interventions performed (cMSCs or cMSC/SkM1) were neither antiarrhythmic nor proarrhythmic. Comparing outcomes with cMSC/SkM1 and viral gene delivery highlights the criticality of the delivery platform to SkM1 antiarrhythmic efficacy. (Circ Arrhythm Electrophysiol. 2012;5:831-840.

The ctenophore genome and the evolutionary origins of neural systems

The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes, and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well recognized in ctenophores, many bilaterian neuron-specific genes and genes of 'classical' neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.This work was supported by NSF (NSF-0744649 and NSF CNS-0821622 to L.L.M.; NSF CHE-1111705 to J.V.S.), NIH (1R01GM097502, R01MH097062, R21RR025699 and 5R21DA030118 to L.L.M.; P30 DA018310 to J.V.S.; R01 AG029360 and 1S10RR027052 to E.I.R.), NASA/nNNX13AJ31G (to K.M.H., L.L.M. and K.M.K.), NSERC 458115 and 211598 (J.P.R.), University of Florida Opportunity Funds/McKnight Brain Research and Florida Biodiversity Institute (L.L.M.), Rostock Inc./A.V. Chikunov (E.I.R.), grant from Russian Federation Government 14.B25.31.0033 (Resolution No.220) (E.I.R.). F.A.K., I.S.P. and R.D.were supported by HHMI(55007424),EMBO and MINECO(BFU2012-31329 and Sev-2012-0208). Contributions of AU Marine Biology Program 117 and Molette laboratory 22