Gap junction channels are required for normal cardiac impulse propagation, and gap junction remodeling is associated with enhanced arrhythmic risk. Oculodentodigital dysplasia (ODDD) is a multisystem syndrome due to mutations in the connexin43 (Cx43) gap junction channel gene. To determine the effects of a human connexin channelopathy on cardiac electrophysiology and arrhythmogenesis, we generated a murine model of ODDD by introducing the disease-causing I130T mutant allele into the mouse genome. Cx43 abundance was markedly reduced in mutant hearts with preferential loss of phosphorylated forms that interfered with trafficking and assembly of gap junctions in the junctional membrane. Dual whole-cell patch-clamp studies showed significantly lower junctional conductance between neonatal cell pairs from mutant hearts, and optical mapping of isolated-perfused hearts with voltage-sensitive dyes demonstrated significant slowing of conduction velocity. Programmed electrical stimulation revealed a markedly increased susceptibility to spontaneous and inducible ventricular tachyarrhythmias. In summary, our data demonstrate that the I130T mutation interferes with Cx43 posttranslational processing, resulting in diminished cell-cell coupling, slowing of impulse propagation, and a proarrhythmic substrate.arrhythmia ͉ connexin43 ͉ transgenic ͉ channel ͉ mouse

Abstract-Pressure overload is a common pathological insult to the heart and the resulting hypertrophy is an independent risk factor for sudden cardiac death. Gap junction remodeling (GJR) has been described in hypertrophied hearts; however, a detailed understanding of the remodeling process and its effects on impulse propagation is lacking. Moreover, there has been little progress developing therapeutic strategies to diminish GJR. Accordingly, transverse aortic banding (TAC) was performed in mice to determine the effects of progressive pathological hypertrophy on connexin (Cx)43 expression, posttranslational phosphorylation, gap junction assembly, and impulse propagation. Within 2 weeks after TAC, total and phospho-Cx43 abundance was reduced and incorporation of Cx43 into gap junctional plaques was markedly diminished. These molecular changes were associated with progressive slowing of impulse propagation, as determined by optical mapping with voltage-sensitive dyes. Treatment with the aldosterone receptor antagonist spironolactone, which has been shown to diminish sudden arrhythmic death in clinical trials, was examined for its effects on GJR. We found that spironolactone blunted the development of GJR and also potently reversed established GJR, both at the molecular and functional levels, without diminishing the extent of hypertrophy. These data suggest a potential mechanism for some of the salutary electrophysiological and clinical effects of mineralocorticoid antagonists in myopathic hearts.

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When rate responsive pacing using a CRT device is achieved in patients with advanced CHF and severe CI, parameters of aerobic exercise performance improve acutely. Routine exercise testing to ensure successful restoration of heart rate response may be beneficial to optimize CRT settings in this patient population.

Black men who have sex with men (MSM) contract HIV at disproportionately high rates, and National HIV/AIDS Strategy goals to reduce HIV incidence cannot be successful without improved HIV prevention among racial minority MSM. 210 Black MSM from three cities (Cleveland, Miami, and Milwaukee) completed measures assessing their sexual behavior and demographic characteristics, as well as AIDS-specific psychosocial scales, broader contextual domains, and substance use. Nearly 50% of men reported recent unprotected anal intercourse (UAI), often with non-main partners, with partners not known to be HIV seroconcordant, or with multiple partners. 37% of men reported being HIV-positive. In multiple regression analyses, higher levels of unprotected behavior were predicted by weaker perceived peer norms for condom use, weaker risk reduction behavioral intentions, being HIV-negative, and recent use of marijuana, cocaine/crack, and poppers. Greater number of UAI partners was associated with weaker perceived peer condom use norms, lower risk reduction intentions, illicit use of prescribed opiates, and fewer AIDS conspiracy beliefs. These findings suggest important factors that should be targeted in HIV prevention programs for Black MSM.

Individuals who disclose their sexual orientation are more likely to also disclose their HIV status. Disclosure of HIV-serostatus is associated with better health outcomes. The goal of this study was to build and test comprehensive models of sexual orientation that included 8 theory-informed predictors of disclosure to mothers, fathers, and closest friends in a sample of HIV-positive Latino gay and bisexual men. US acculturation, gender non-conformity to hegemonic masculinity in self-presentation, comfort with sexual orientation, gay community involvement, satisfaction with social support, sexual orientation and gender of the closest friend emerged as significant predictors of disclosure of sexual orientation.

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It is known that hormones influence significantly the prostate tissue. However, we reported that mating induces an increase in androgen receptors, revealing a neural influence on the gland. These data suggested that somatic afferents (scrotal and genitofemoral nerves) and autonomic efferents (pelvic and hypogastric nerves) could regulate the structure of the prostate. Here we assessed the role of these nerves in maintaining the histology of the gland. Hence, afferent or efferent nerves of male rats were transected. Then, the ventral and dorsolateral regions of the prostate were processed for histology. Results showed that afferent transection affects prostate histology. The alveoli area decreased and increased in the ventral and dorsolateral prostate, respectively. The epithelial cell height increased in both regions. Efferent denervation produced dramatic changes in the prostate gland. The tissue lost its configuration, and the epithelium became scattered and almost vanished. Thus, afferent nerves are responsible for spinal processes pertaining to the trophic control of the prostate, activating its autonomic innervation. Hence, our data imply that innervation seems to be synergic with hormones for the healthy maintenance of the prostate. Thus, it is suggested that some prostate pathologies could be due to the failure of the autonomic neural pathways regulating the gland.