Putnamhelms3267

Equilibrative nucleoside transporter 4 (ENT4), encoded by SLC29A4, mediates the flux of both 5-hydroxytryptamine (5-HT) and adenosine across cell membranes. We hypothesized that loss of ENT4 function in mice would modify the effects of these established regulators of vascular function. Male and female wild-type (WT) and slc29a4-null (ENT4-KO) mice were compared with respect to their hemodynamics and mesenteric vascular function. Male ENT4-KO mice had a complete loss of myogenic tone in their mesenteric resistance arteries. This was accompanied by a decrease in blood flow in the superior mesenteric artery in the male ENT4-KO mice, and a reduced responsiveness to 5-HT. In contrast, endothelium-dependent relaxations of mesenteric arteries from female ENT4-KO mice were more sensitive to Ca2+ -activated K+ (KCa ) channel blockade than WT mice. Female ENT4-KO mice also demonstrated an enhanced vasodilatory response to adenosine in vivo that was not seen in males. Ketanserin (5-HT2A inhibitor) and GR55562 (5-HT1B/1D inhibitor) decreased 5-HT-induced tone, but only ketanserin inhibited the relaxant effect of 5-HT in mesenteric arteries. 5-HT-evoked increases in tone were elevated in arteries from ENT4-KO mice upon block of endothelial relaxant pathways, with arteries from female ENT4-KO mice showing the greatest increase. Adenosine A2b receptor expression was decreased, while other adenosine transporter subtypes, as well as adenosine deaminase and adenosine kinase were increased in mesenteric arteries from male, but not female, ENT4-KO mice. These findings indicate that deletion of slc29a4 leads to sex-specific changes in vascular function with significant consequences for regulation of blood flow and pressure by adenosine and 5-HT. © 2020 The Authors. Wortmannin mw Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.RATIONALE Cytomegalovirus (CMV)-seronegative recipients receiving a seropositive allograft (D+/R-) are at a high risk of developing CMV disease. Our program increased the duration of CMV prophylaxis from 6 to 9 months in May 2013. Here, we present the impact on the incidence of CMV infection, disease, side effects, rejection, and other factors. METHODS Retrospective cohort of 241 CMV (D+/R-) patients transplanted between January 1, 2008, and December 31, 2017. Blood CMV testing was done according to protocol. All patients received ganciclovir/valganciclovir as prophylaxis. We compared the incidence and timing of CMV infection and disease up to 6 months after cessation of prophylaxis between patients who received 9 months (May 2013 onwards) and a historical control group who received 6 months of prophylaxis (prior to May 2013). CMV infection was defined as detectable CMV viremia in the absence of symptoms. CMV disease was defined as CMV syndrome or tissue-invasive disease. Side effects of prophylaxis and CMV rsk reduction achieved by extended CMV prophylaxis was 8%. The incidence of CMV infection, and ganciclovir resistance and side effects were similar between the two groups. Our results suggest that extending CMV prophylaxis in the highest risk CMV D+/R- group is effective in reducing CMV disease. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.OBJECTIVE Minimal prior research has examined the impact of inflammatory arthritis (IA) on men's perspectives on parenting. We aim to describe fathering roles and experiences, the effect of IA on parenting activities, and strategies used by fathers with IA to fulfill this role. METHOD A grounded theory approach guided data gathering and analysis. Nine men with IA, parenting at least one child under 19 years, were recruited through rheumatology practices, therapy clinics, and social media. Each engaged in one in-depth personal interview. Transcripts were analyzed using inductive and iterative steps to identify key themes and a preliminary explanatory framework of fathering experiences of men with IA. RESULTS All men were married, ages 31-62, with one to five children aged 6 months to 28 years. "Being an involved father" describes participants' perspectives on fulfilling their role as hands-on parents, role models, and financial providers. "Taking ownership" explains how participants managed daily life, comprised of two sub-themes, "taking care of yourself" using strategies like exercise and communicating with loved ones, and "redefining yourself," a process of adapting to reframed identity and lifestyle adjustments. "Accessing support" indicates men felt well-supported by social networks (most critically their wives), health care providers, and informational and educational resources. CONCLUSION This small, grounded theory study offers an enriched understanding of fatherhood experiences of men with IA. When social, practical, and educational supports are in place, these men found parenting joyful and rewarding. Despite task limitations, their perspectives on being involved fathers was unrestricted by arthritis. This article is protected by copyright. All rights reserved.BACKGROUND although interhemispheric disconnection significantly contributes to disability in multiple sclerosis (MS), the topography, timeline and relationship of callosal damage accrual with hemispheric damage are still unclear. METHODS streamline density and presence of focal lesions in 5 callosal subregions were computed in 55 people with MS (pwMS) (13 relapsing remitting-RR, 20 secondary progressive-SP, 22 primary progressive-PP) and 24 healthy controls. RESULTS streamline density decrease was identified in SPMS in all CC subregions, in PPMS in posterior CC and mid-posterior CC and in RRMS in posterior CC. CC density was independently predicted by CC lesion volume (LV) and hemispheric LV and independently predicted visuospatial memory, EDSS, manual dexterity and ambulation. CONCLUSIONS the reduction in CC density across phenotypes suggests an earlier involvement of the posterior regions, followed only at a later stage by involvement of the anterior portions of the CC. Such interhemispheric disconnection seems to develop as a consequence of white matter macroscopic damage and exerts a relevant impact on motor and, to a lesser extent, cognitive disability. This article is protected by copyright. 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