Work volume and strength training responses to resistive exercise improve with periodic heat extraction from the palm

Body core cooling via the palm of a hand increases work volume during resistive exercise. We asked: (a) "Is there a correlation between elevated core temperatures and fatigue onset during resistive exercise?" and (b) "Does palm cooling between sets of resistive exercise affect strength and work volume training responses?" Core temperature was manipulated by 30-45 minutes of fixed load and duration treadmill exercise in the heat with or without palm cooling. Work volume was then assessed by 4 sets of fixed load bench press exercises. Core temperatures were reduced and work volumes increased after palm cooling (Control: Tes = 39.0 ± 0.1° C, 36 ± 7 reps vs. Cooling: Tes = 38.4 ± 0.2° C, 42 ± 7 reps, mean ± SD, n = 8, p < 0.001). In separate experiments, the impact of palm cooling on work volume and strength training responses were assessed. The participants completed biweekly bench press or pull-up exercises for multiple successive weeks. Palm cooling was applied for 3 minutes between sets of exercise. Over 3 weeks of bench press training, palm cooling increased work volume by 40% (vs. 13% with no treatment; n = 8, p < 0.05). Over 6 weeks of pull-up training, palm cooling increased work volume by 144% in pull-up experienced subjects (vs. 5% over 2 weeks with no treatment; n = 7, p < 0.001) and by 80% in pull-up na?ve subjects (vs. 20% with no treatment; n = 11, p < 0.01). Strength (1 repetition maximum) increased 22% over 10 weeks of pyramid bench press training (4 weeks with no treatment followed by 6 weeks with palm cooling; n = 10, p < 0.001). These results verify previous observations about the effects of palm cooling on work volume, demonstrate a link between core temperature and fatigue onset during resistive exercise, and suggest a novel means for improving strength and work volume training responses.     

PGE2 through the EP4 receptor controls smooth muscle gene expression patterns in the ductus arteriosus critical for remodeling at birth

The ductus arteriosus (DA) is a fetal shunt that directs right ventricular outflow away from pulmonary circulation and into the aorta. Critical roles for prostaglandin E(2) (PGE(2)) and the EP4 receptor (EP4) have been established in maintaining both the patency of the vessel in utero and in its closure at birth. Here we have generated mice in which loss of EP4 expression is limited to either the smooth muscle (SMC) or endothelial cells and demonstrated that SMC, but not endothelial cell expression of EP4 is required for DA closure. The genome wide expression analysis of full term wild type and EP4(-/-) DA indicates that PGE(2)/EP4 signaling modulates expression of a number of unique pathways, including those involved in SMC proliferation, cell migration, and vascular tone. Together this supports a mechanism by which maturation and increased contractility of the vessel is coupled to the potent smooth muscle dilatory actions of PGE(2).     

Performance of Thirteen Clinical Rules to Distinguish Bacterial and Presumed Viral Meningitis in Vietnamese Children

Background and Purpose

Successful outcomes from bacterial meningitis require rapid antibiotic treatment; however, unnecessary treatment of viral meningitis may lead to increased toxicities and expense. Thus, improved diagnostics are required to maximize treatment and minimize side effects and cost. Thirteen clinical decision rules have been reported to identify bacterial from viral meningitis. However, few rules have been tested and compared in a single study, while several rules are yet to be tested by independent researchers or in pediatric populations. Thus, simultaneous test and comparison of these rules are required to enable clinicians to select an optimal diagnostic rule for bacterial meningitis in settings and populations similar to ours.

Methods

A retrospective cross-sectional study was conducted at the Infectious Department of Pediatric Hospital Number 1, Ho Chi Minh City, Vietnam. The performance of the clinical rules was evaluated by area under a receiver operating characteristic curve (ROC-AUC) using the method of DeLong and McNemar test for specificity comparison.

Results

Our study included 129 patients, of whom 80 had bacterial meningitis and 49 had presumed viral meningitis. Spanos''s rule had the highest AUC at 0.938 but was not significantly greater than other rules. No rule provided 100% sensitivity with a specificity higher than 50%. Based on our calculation of theoretical sensitivity and specificity, we suggest that a perfect rule requires at least four independent variables that posses both sensitivity and specificity higher than 85–90%.

Conclusions

No clinical decision rules provided an acceptable specificity (>50%) with 100% sensitivity when applying our data set in children. More studies in Vietnam and developing countries are required to develop and/or validate clinical rules and more very good biomarkers are required to develop such a perfect rule.     

A Potent Class of GPR40 Full Agonists Engages the EnteroInsular Axis to Promote Glucose Control in Rodents

Type 2 diabetes is characterized by impaired glucose homeostasis due to defects in insulin secretion, insulin resistance and the incretin response. GPR40 (FFAR1 or FFA1) is a G-protein-coupled receptor (GPCR), primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine. Several GPR40 agonists, including AMG 837 and TAK-875, have been disclosed, but no GPR40 synthetic agonists have been reported that engage both the insulinogenic and incretinogenic axes. In this report we provide a molecular explanation and describe the discovery of a unique and potent class of GPR40 full agonists that engages the enteroinsular axis to promote dramatic improvement in glucose control in rodents. GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes. The improvement in hyperglycemia by AM-1638 was reduced in the presence of the GLP-1 receptor antagonist Ex(9–39)NH₂.     

Controlling HIV Epidemics among Injection Drug Users: Eight Years of Cross-Border HIV Prevention Interventions in Vietnam and China

Introduction

HIV in Vietnam and Southern China is driven by injection drug use. We have implemented HIV prevention interventions for IDUs since 2002–2003 in Lang Son and Ha Giang Provinces, Vietnam and Ning Ming County (Guangxi), China.

Methods

Interventions provide peer education and needle/syringe distribution. Evaluation employed serial cross-sectional surveys of IDUs 26 waves from 2002 to 2011, including interviews and HIV testing. Outcomes were HIV risk behaviors, HIV prevalence and incidence. HIV incidence estimation used two methods: 1) among new injectors from prevalence data; and 2) a capture enzyme immunoassay (BED testing) on all HIV+ samples.

Results

We found significant declines in drug-related risk behaviors and sharp reductions in HIV prevalence among IDUs (Lang Son from 46% to 23% [p<0.001], Ning Ming: from 17% to 11% [p = 0.003], and Ha Giang: from 51% to 18% [p<0.001]), reductions not experienced in other provinces without such interventions. There were significant declines in HIV incidence to low levels among new injectors through 36–48 months, then some rebound, particularly in Ning Ming, but BED-based estimates revealed significant reductions in incidence through 96 months.

Discussion

This is one of the longest studies of HIV prevention among IDUs in Asia. The rebound in incidence among new injectors may reflect sexual transmission. BED-based estimates may overstate incidence (because of false-recent results in patients with long-term infection or on ARV treatment) but adjustment for false-recent results and survey responses on duration of infection generally confirm BED-based incidence trends. Combined trends from the two estimation methods show sharp declines in incidence to low levels. The significant downward trends in all primary outcome measures indicate that the Cross-Border interventions played an important role in bringing HIV epidemics among IDUs under control. The Cross-Border project offers a model of HIV prevention for IDUs that should be considered for large-scale replication.     

Feasibility of intensity-modulated and image-guided radiotherapy for functional organ preservation in locally advanced laryngeal cancer

Purpose

The study aims to assess the feasibility of intensity-modulated and image-guided radiotherapy (IMRT, and IGRT, respectively) for functional preservation in locally advanced laryngeal cancer. A retrospective review of 27 patients undergoing concurrent chemoradiation for locally advanced laryngeal cancers (8 IMRT, 19 IGRT) was undertaken. In addition to regular clinical examinations, all patients had PET imaging at 4 months and 10 months after radiotherapy, then yearly. Loco-regional control, speech quality and feeding-tube dependency were assessed during follow-up visits.

Results

At a median follow-up of 20 months (range 6–57 months), four out of 27 patients (14.8%) developed local recurrence and underwent salvage total laryngectomy. One patient developed distant metastases following salvage surgery. Among the 23 patients who conserved their larynx with no sign of recurrence at last follow-up, 22 (95%) reported normal or near normal voice quality, allowing them to communicate adequately. Four patients (14.8%) had long-term tube feeding-dependency because of severe dysphagia (2 patients) and chronic aspiration (2 patients, with ensuing death from aspiration pneumonia in one patient).

Conclusions and Clinical Relevance

Functional laryngeal preservation is feasible with IMRT and IGRT for locally advanced laryngeal cancer. However, dysphagia and aspiration remain serious complications, due most likely to high radiation dose delivery to the pharyngeal musculatures.     

Adolescent expectations of early death predict adult risk behaviors

Only a handful of public health studies have investigated expectations of early death among adolescents. Associations have been found between these expectations and risk behaviors in adolescence. However, these beliefs may not only predict worse adolescent outcomes, but worse trajectories in health with ties to negative outcomes that endure into young adulthood. The objectives of this study were to investigate perceived chances of living to age 35 (Perceived Survival Expectations, PSE) as a predictor of suicidal ideation, suicide attempt and substance use in young adulthood. We examined the predictive capacity of PSE on future suicidal ideation/attempt after accounting for sociodemographics, depressive symptoms, and history of suicide among family and friends to more fully assess its unique contribution to suicide risk. We investigated the influence of PSE on legal and illegal substance use and varying levels of substance use. We utilized the National Longitudinal Study of Adolescent Health (Add Health) initiated in 1994-95 among 20,745 adolescents in grades 7-12 with follow-up interviews in 1996 (Wave II), 2001-02 (Wave III) and 2008 (Wave IV; ages 24-32). Compared to those who were almost certain of living to age 35, perceiving a 50-50 or less chance of living to age 35 at Waves I or III predicted suicide attempt and ideation as well as regular substance use (i.e., exceeding daily limits for moderate drinking; smoking ≥ a pack/day; and using illicit substances other than marijuana at least weekly) at Wave IV. Associations between PSE and detrimental adult outcomes were particularly strong for those reporting persistently low PSE at both Waves I and III. Low PSE at Wave I or Wave III was also related to a doubling and tripling, respectively, of death rates in young adulthood. Long-term and wide-ranging ties between PSE and detrimental outcomes suggest these expectations may contribute to identifying at-risk youth.