Arch Sex Behav

Thirty years after the beginning of the HIV epidemic, gay, bisexual, and other men who have sex with men (collectively called MSM) bear a disproportionate burden of HIV in the United States and continue to acquire a distressingly high number and proportion of new infections. Historically, HIV prevention for MSM has been focused on individual-level behavior change, rarely intervening with MSM as part of a couple. Yet, an estimated 33\u201367% of HIV infections among MSM are acquired from primary sexual partners, suggesting that work with MSM as couples could be an important contributor to prevention. Given the emergence of high impact combination HIV prevention, it is timely to consider how work with the broad variety of male couples can improve both personal and community health. Couples HIV testing and counseling for MSM is an important advance for identifying men who are unaware that they are HIV-positive, identifying HIV-discordant couples, and supporting men who want to learn their HIV status with their partner. Once men know their HIV status, new advances in biomedical prevention, which can dramatically reduce risk of HIV transmission or acquisition, allow men to make prevention decisions that can protect themselves and their partners. This paper highlights the present-day challenges and benefits of using a couples-based approach with MSM in the era of combination prevention to increase knowledge of HIV status, increase identification of HIV discordant couples to improve targeting prevention services,and support mutual disclosure of HIV status.CC999999/Intramural CDC HHS/United States2017-01-09T00:00:00Z24233328PMC5221480vault:2090

Nocturnal increase in cerebrospinal fluid secretion as a circadian regulator of intracranial pressure

Abstract Background It is crucial to maintain the intracranial pressure (ICP) within the physiological range to ensure proper brain function. The ICP may fluctuate during the light-dark phase cycle, complicating diagnosis and treatment choice in patients with pressure-related disorders. Such ICP fluctuations may originate in circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which in addition could support diurnal regulation of brain waste clearance. Methods ICP was monitored continuously in patients who underwent placement of an external ventricular drain (EVD) and by telemetric monitoring in experimental rats. CSF was collected via the EVD in patients and the rodent CSF secretion rate determined by in vivo experimentation. Rodent choroid plexus transporter transcripts were quantified with RNAseq and transport activity with ex vivo isotope transport assays. Results We demonstrated that ICP increases by 30% in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients (12%) and CSF production rate in rats (20%), the latter obtained with the ventriculo-cisternal perfusion assay. The dark-phase increase in CSF secretion in rats was, in part, assigned to increased transport activity of the choroid plexus Na+,K+,2Cl- cotransporter (NKCC1), which is implicated in CSF secretion by this tissue. Conclusion CSF secretion, and thus ICP, increases in the dark phase in humans and rats, irrespective of their diurnal/nocturnal activity preference, in part due to altered choroid plexus transport activity in the rat. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself

Immunolocalization of H⁺/K⁺-ATPases in Capan-1 cells grown on permeable membranes.

<p><b>A</b>: The gastric H^<b>+</b>/K^<b>+</b>-ATPase α subunit (HKα1) was labeled with Calbiochem 119101 (polyclonal, against HKα1C-terminal) and Alexa 488 (green). <b>B</b>: The gastric H^<b>+</b>/K^<b>+</b>-ATPase β subunit (HKβ) was detected with Sigma A-274 (2G11, anti HKβ, monoclonal) and Alexa 488 (green). <b>C</b>: The non-gastric H^<b>+</b>/K^<b>+</b>-ATPase α subunit (HKα2) was stained with non-gastric HKα2 antibody (C384-M79) and Alexa 488 (green) Three pairs of images are shown. <b>D</b>: Example of a control image without primary antibodies but with F-actin marker (phalloidin Texas red). DAPI was used to stain the nucleus (blue). All bars are 10 μm, and images from at least 10 independent experiments are presented as both x-y and x-z scans. In x-y scan the left images are taken mid-way through the monolayer, the right images are taken close to the apical membrane. Dotted lines in x-y scans indicate where the x-z scan was taken.</p

Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H⁺/K⁺-ATPases

<div><p>The mechanism by which pancreas secretes high HCO₃^- has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO₃^- from serosa to mucosa or by moving H⁺ in the opposite direction. The aim of the present study was to determine whether H⁺/K⁺-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (<i>ATP4A</i>; <i>ATP4B</i>) and non-gastric HKα2 subunits (<i>ATP12A</i>) of H⁺/K⁺-ATPases are expressed in human pancreatic cells. Pumps have similar localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO₃^-, pancreas also secretes K⁺. In conclusion, this study calls for a revision of the basic model for HCO₃^- secretion. We propose that proton transport is driving secretion, and that in addition it may provide a protective pH buffer zone and K⁺ recirculation. Furthermore, it seems relevant to re-evaluate whether PPIs should be used in treatment therapies where pancreatic functions are already compromised.</p></div

Expression of H⁺/K⁺-ATPases in human pancreatic duct cell lines Capan-1 (CA), CFPAC-1 (CF) and PANC-1 (PA).

<p><b>A:</b> RT-PCR analysis of gastric H^<b>+</b>/K^<b>+</b>-ATPase α (HKα1, 200 bp), non-gastric H^<b>+</b>/K^<b>+</b>-ATPase α (HKα2, 339 bp) and β (HKβ, 136 bp) subunits. Representative gels for at least three independent experiments. Real time PCR was used to evaluate the relative expression (2^{<b>-ΔΔCt</b>}). The house keeping genes 18S ribosomal RNA (18SrRNA), β-actin, β glucuronidase (GUSB) and glutaminyl-tRNA synthetase (QARS) were used and expression in Capan-1 cells was set to be 1. The graph shows data for three experiments (mean±SEM). Significance of expression was tested by one-way ANOVA using the value 2^<b>-ΔCt</b>. <b>B:</b> Western blot on cell lysates from duct cell lines, as well as control tissues—mouse stomach (S) and colon (C). Antibodies against gastric H^<b>+</b>/K^<b>+</b>-ATPase α subunits (HKα1, Abcam EPR12251), non-gastric H^<b>+</b>/K^<b>+</b>-ATPase α subunits (HKα2, Sigma, HPA039526) and gastric H^<b>+</b>/K^<b>+</b>-ATPase β subunits (HKβ, Sigma A274) were used. Loading control was β-actin detected at 43 kDa. All lanes were loaded with 60 μg of protein. Stomach and colon gels were run separately. Lower bargraphs show expression of the subunits normalized to actin: the bands at 115 kDa (HKα1); 100 kDa (HKα2) and 45 kDa (HKβ) were used. Data is from 3–4 independent experiments and * indicates <i>P</i><0.05 and ** <i>P</i><0.001 compared to Capan-1.</p