Using Bilateral and Unilateral Exercise to Better Understand the Blood Pressure Lowering Effects of Isometric Handgrip Training: Preliminary Findings

Isometric handgrip (IHG) training reduces resting blood pressure (BP) in normotensive individuals following 8-10 weeks of unilateral (4 x 2 minute sustained contractions at 30% maximal voluntary contraction (MVC) performed by the non-dominant limb, separated by 4 minutes rest) or bilateral IHG training (contractions alternating between dominant and non-dominant limb, separated by 1 minute rest), performed 3-5 times per week. Investigating the effects of a single bout of unilateral or bilateral IHG on vascular function (brachial artery flow-mediated dilation (FMD) and low-flow mediated constriction (L-FMC)) may provide insight into the underlying hypotensive mechanisms of IHG training. Eight young adult (25.3 ± 3.81 years), normotensive (99.65/61.25 ± 11.72/9.14 mmHg) women performed a single bout of bilateral (n=4) or unilateral (n=4) IHG exercise. FMD and L-FMC were assessed using ultrasound pre- and post-IHG bout. Following a single IHG bout, no significant changes were observed in FMD (unilateral: pre- = 13.56 ± 7.8%, post- =17.26 ± 21%, bilateral: pre- = 17.11 ± 1.1%, post- = 21.18 ± 8.9%) or L-FMC (unilateral: pre- = 3.36 ± 11%, post- =-2.26 ± 16%, bilateral: pre- = -2.86 ± 3.1%, post- = -1.94 ± 9.7%) in either group (all p > 0.05). Taken together these preliminary data suggest that in young healthy women, irrespective of isometric exercise on 1 or 2 limbs, the endothelium is not altered significantly. Further research with a larger sample is warranted to confirm that mechanisms other than improved vascular function play a role in IHG-training induced BP lowering

Conduit Dynamics in Transitional Rhyolitic Activity Recorded by Tuffisite Vein Textures from the 2008–2009 Chaitén Eruption

The mechanisms of hazardous silicic eruptions are controlled by complex, poorly-understood conduit processes. Observations of recent Chilean rhyolite eruptions have revealed the importance of hybrid activity, involving simultaneous explosive and effusive emissions from a common vent. Such behavior hinges upon the ability of gas to decouple from magma in the shallow conduit. Tuffisite veins are increasingly suspected to be a key facilitator of outgassing, as they repeatedly provide a transient permeable escape route for volcanic gases. Intersection of foam domains by tuffisite veins appears critical to efficient outgassing. However, knowledge is currently lacking into textural heterogeneities within shallow conduits, their relationship with tuffisite vein propagation, and the implications for fragmentation and degassing processes. Similarly, the magmatic vesiculation response to upper conduit pressure perturbations, such as those related to the slip of dense magma plugs, remains largely undefined. Here we provide a detailed characterization of an exceptionally large tuffisite vein within a rhyolitic obsidian bomb ejected during transitional explosive-effusive activity at Chaitén, Chile in May 2008. Vein textures and chemistry provide a time-integrated record of the invasion of a dense upper conduit plug by deeper fragmented magma. Quantitative textural analysis reveals diverse vesiculation histories of various juvenile clast types. Using vesicle size distributions, bubble number densities, zones of diffusive water depletion, and glass H2O concentrations, we propose a multi-step degassing/fragmentation history, spanning deep degassing to explosive bomb ejection. Rapid decompression events of ~3–4 MPa are associated with fragmentation of foam and dense magma at ~200–360 m depth in the conduit, permitting vertical gas and pyroclast mobility over hundreds of meters. Permeable pathway occlusion in the dense conduit plug by pyroclast accumulation and sintering preceded ultimate bomb ejection, which then triggered a final bubble nucleation event. Our results highlight how the vesiculation response of magma to decompression events is highly sensitive to the local melt volatile concentration, which is strongly spatially heterogeneous. Repeated opening of pervasive tuffisite vein networks promotes this heterogeneity, allowing juxtaposition of variably volatile-rich magma fragments that are derived from a wide range of depths in the conduit. This process enables efficient but explosive removal of gas from rhyolitic magma and creates a complex textural collage within dense rhyolitic lava, in which neighboring fused clasts may have experienced vastly different degassing histories

Isometric handgrip (IHG) training-induced reductions in resting blood pressure: Reactivity to a 2-minute handgrip task identifies responders and non-responders in young normotensive individuals

In people with hypertension, systolic blood pressure (SBP) reactivity to an isometric handgrip task (IHGT), but not a cold pressure task (CPT), is predictive of IHG training-induced reductions in resting SBP. To investigate whether these findings could be extended to include young normotensives, resting BP and BP reactivity to an IHGT (2-minute sustained contraction at 30% maximal voluntary contraction, MVC) and a CPT (2-minute hand immersion in a cold water bath) were measured prior to and following 10 weeks of IHG training (4, 2-minute IHG contractions at 30% MVC, using alternating hands, interspersed with 1-minute rest periods, 3X/week) in 7 normotensive individuals (3 females, 4 males; age=25 ± 5.7 years). BP reactivity was derived by calculating the difference between peak stress BP and mean baseline resting BP. Significant training-induced reductions in resting SBP (p<0.001) were strongly correlated with pre-training SBP reactivity to the IHGT (r=-0.8, p=0.03), but not the CPT (r= 0.2, p=0.6). These preliminary findings suggest that SBP reactivity to a short and simple handgrip task can be used as a predictive tool to identify who will respond best to IHG training. It might be possible to further explore how the IHG training stimulus could be optimized in non-responders, to ensure that they too, experience reductions in resting BP

Isometric exercise training for hypertension

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: We will aim to conduct a systematic review and meta-analysis quantifying the effects of IRT on systolic, diastolic, mean arterial and 24-hour ambulatory blood pressure. We will also quantify changes in heartrate and heartrate variability, and will attempt to determine which patient demographics and exercise program characteristics are associated with the largest blood pressure changes

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Isometric handgrip as an adjunct for blood pressure control: a primer for clinicians

Considered a global health crisis by the World Health Organization, hypertension (HTN) is the leading risk factor for death and disability. The majority of treated patients do not attain evidence-based clinical targets, which increases the risk of potentially fatal complications. HTN is the most common chronic condition seen in primary care; thus, implementing therapies that lower and maintain BP to within-target ranges is of tremendous public health importance. Isometric handgrip (IHG) training is a simple intervention endorsed by the American Heart Association as a potential adjuvant BP-lowering treatment. With larger reductions noted in HTN patients, IHG training may be especially beneficial for those who (a) have difficulties continuing or increasing drug-based treatment; (b) are unable to attain BP control despite optimal treatment; (c) have pre-HTN or low-risk stage I mild HTN; and (d) wish to avoid medications or have less pill burden. IHG training is not routinely prescribed in clinical practice. To shift this paradigm, we focus on (1) the challenges of current HTN management strategies; (2) the effect of IHG training; (3) IHG prescription; (4) characterizing the population for whom it works best; (5) clinical relevance; and (6) important next steps to foster broader implementation by clinical practitioners

Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis

Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants

ABSTRACT Clindamycin may be active against methicillin-resistant Staphylococcus aureus , a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials. Intravenous data were collected from 62 infants (135 plasma PK samples) with postnatal ages of 40 to 60 weeks PMA, 9 mg/kg) resulted in an unbound, steady-state concentration at half the dosing interval greater than a MIC for S. aureus of 0.12 μg/ml in >90% of infants. There were no adverse events related to clindamycin use. (This study has been registered at ClinicalTrials.gov under registration no. NCT01728363.

How common and frequent is heterosexual anal intercourse among South Africans? A systematic review and meta-analysis.

BACKGROUND: HIV is transmitted more effectively during anal intercourse (AI) than vaginal intercourse (VI). However, patterns of heterosexual AI practice and its contribution to South Africa's generalized epidemic remain unclear. We aimed to determine how common and frequent heterosexual AI is in South Africa. METHODS: We searched for studies reporting the proportion practising heterosexual AI (prevalence) and/or the number of AI and unprotected AI (UAI) acts (frequency) in South Africa from 1990 to 2015. Stratified random-effects meta-analysis by sub-groups was used to produce pooled estimates and assess the influence of participant and study characteristics on AI prevalence. We also estimated the fraction of all sex acts which were AI or UAI and compared condom use during VI and AI. RESULTS: Of 41 included studies, 31 reported on AI prevalence and 14 on frequency, over various recall periods. AI prevalence was high across different recall periods for sexually active general-risk populations (e.g. lifetime = 18.4% [95%CI:9.4-27.5%], three-month = 20.3% [6.1-34.7%]), but tended to be even higher in higher-risk populations such as STI patients and female sex workers (e.g. lifetime = 23.2% [0.0-47.4%], recall period not stated = 40.1% [36.2-44.0%]). Prevalence was higher in studies using more confidential interview methods. Among general and higher-risk populations, 1.2-40.0% and 0.7-21.0% of all unprotected sex acts were UAI, respectively. AI acts were as likely to be condom protected as vaginal acts. CONCLUSION: Reported heterosexual AI is common but variable among South Africans. Nationally and regionally representative sexual behaviour studies that use standardized recall periods and confidential interview methods, to aid comparison across studies and minimize reporting bias, are needed. Such data could be used to estimate the extent to which AI contributes to South Africa's HIV epidemic

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al