Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

Macrophage immunomodulation through new polymers that recapitulate functional effects of itaconate as a power house of innate immunity.

Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. We developed a library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers resulted in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibited bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrated a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA.

All-Order Full-Coulomb Quantum Spectral Line-Shape Calculations.

Understanding how atoms interact with hot dense matter is essential for astrophysical and laboratory plasmas. Interactions in high-density plasmas broaden spectral lines, providing a rare window into interactions that govern, for example, radiation transport in stars. However, up to now, spectral line-shape theories employed at least one of three common approximations: second-order Taylor treatment of broadening operator, dipole-only interactions between atom and plasma, and classical treatment of perturbing electrons. In this Letter, we remove all three approximations simultaneously for the first time and test the importance for two applications: neutral hydrogen and highly ionized magnesium and oxygen. We found 15%-50% change in the spectral line widths, which are sufficient to impact applications including white-dwarf mass determination, stellar-opacity research, and laboratory plasma diagnostics.

Water quality risks of 'improved' water sources: evidence from Cambodia.

OBJECTIVES: The objective of this study was to investigate the quality of on-plot piped water and rainwater at the point of consumption in an area with rapidly expanding coverage of 'improved' water sources. METHODS: Cross-sectional study of 914 peri-urban households in Kandal Province, Cambodia, between July-August 2011. We collected data from all households on water management, drinking water quality and factors potentially related to post-collection water contamination. Drinking water samples were taken directly from a subsample of household taps (n = 143), stored tap water (n = 124), other stored water (n = 92) and treated stored water (n = 79) for basic water quality analysis for Escherichia coli and other parameters. RESULTS: Household drinking water management was complex, with different sources used at any given time and across seasons. Rainwater was the most commonly used drinking water source. Households mixed different water sources in storage containers, including 'improved' with 'unimproved' sources. Piped water from taps deteriorated during storage (P < 0.0005), from 520 cfu/100 ml (coefficient of variation, CV: 5.7) E. coli to 1100 cfu/100 ml (CV: 3.4). Stored non-piped water (primarily rainwater) had a mean E. coli count of 1500 cfu/100 ml (CV: 4.1), not significantly different from stored piped water (P = 0.20). Microbial contamination of stored water was significantly associated with observed storage and handling practices, including dipping hands or receptacles in water (P < 0.005), and having an uncovered storage container (P = 0.052). CONCLUSIONS: The microbial quality of 'improved' water sources in our study area was not maintained at the point of consumption, possibly due to a combination of mixing water sources at the household level, unsafe storage and handling practices, and inadequately treated piped-to-plot water. These results have implications for refining international targets for safe drinking water access as well as the assumptions underlying global burden of disease estimates, which posit that 'improved' sources pose minimal risks of diarrhoeal diseases.

Management of children in the deployed intensive care unit at Camp Bastion, Afghanistan.

BACKGROUND: The deployed Intensive Therapy Unit (ITU) in the British military field hospital in Camp Bastion, Afghanistan, admits both adults and children. The purpose of this paper is to review the paediatric workload in the deployed ITU and to describe how the unit copes with the challenge of looking after critically injured and ill children. METHODS: Retrospective review of patients <16 years of age admitted to the ITU in the British military field hospital in Camp Bastion, Afghanistan, over a 1-year period from April 2011 to April 2012. RESULTS: 112/811 (14%) admissions to the ITU were paediatric (median age 8 years, IQR 6-12, range 1-16). 80/112 were trauma admissions, 13 were burns, four were non-trauma admissions and 15 were readmissions. Mechanism of injury in trauma was blunt in 12, blast (improvised explosive device) in 45, blast (indirect fire) in seven and gunshot wound in 16. Median length of stay was 0.92 days (IQR 0.45-2.65). 82/112 admissions (73%) were mechanically ventilated, 16/112 (14%) required inotropic support. 12/112 (11%) died before unit discharge. Trauma scoring was available in 65 of the 80 trauma admissions. Eight had Injury Severity Score or New Injury Severity Score >60, none of whom survived. However, of the 16 patients with predicted mortality >50% by Trauma Injury Severity Score, seven survived. Seven cases required specialist advice and were discussed with the Birmingham Children's Hospital paediatric intensive care retrieval service. The mechanisms by which the Defence Medical Services support children admitted to the deployed adult ITU are described, including staff training in clinical, ethical and child protection issues, equipment, guidelines and clinical governance and rapid access to specialist advice in the UK. CONCLUSIONS: With appropriate support, it is possible to provide intensive care to children in a deployed military ITU.

Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding.

AIMS/HYPOTHESIS: Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated strain-dependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). METHODS: Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to measure markers of mitochondrial metabolism, inflammation, oxidative stress and lipid accumulation. RESULTS: BL6, 129X1, DBA/2 and FVB/N mice were all susceptible to varying degrees to HFD-induced obesity, glucose intolerance and insulin resistance, but BALB/c mice exhibited some protection from these detrimental effects. This protection could not be explained by differences in mitochondrial metabolism or oxidative stress in liver or muscle, or inflammation in adipose tissue. Interestingly, in contrast with the other strains, BALB/c mice did not accumulate excess lipid (triacylglycerols and diacylglycerols) in the liver; this is potentially related to lower fatty acid uptake rather than differences in lipogenesis or lipid oxidation. CONCLUSIONS/INTERPRETATION: Collectively, our findings indicate that most mouse strains develop metabolic defects on an HFD. However, there are inherent differences between strains, and thus the genetic background needs to be considered carefully in metabolic studies.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

OBJECTIVE: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear. The aim of this study was to investigate the role of BAT thermogenesis in the efficacy of VSG in a rodent model. METHODS: Diet-induced obese male Sprague-Dawley rats were either sham-operated, underwent VSG surgery or were pair-fed to the food consumed by the VSG group. Rats were also implanted with biotelemetry devices between the interscapular lobes of BAT to assess local changes in BAT temperature as a surrogate measure of thermogenic activity. Metabolic parameters including food intake, body weight and changes in body composition were assessed. To further elucidate the contribution of energy expenditure via BAT thermogenesis to VSG-induced weight loss, a separate cohort of chow-fed rats underwent complete excision of the interscapular BAT (iBAT lipectomy) or chemical denervation using 6-hydroxydopamine (6-OHDA). To localize glucose uptake in specific tissues, an oral glucose tolerance test was combined with an intraperitoneal injection of 14C-2-deoxy-d-glucose (14C-2DG). Transneuronal viral tracing was used to identify 1) sensory neurons directed to the stomach or small intestine (H129-RFP) or 2) chains of polysynaptically linked neurons directed to BAT (PRV-GFP) in the same animals. RESULTS: Following VSG, there was a rapid reduction in body weight that was associated with reduced food intake, elevated BAT temperature and improved glucose regulation. Rats that underwent VSG had elevated glucose uptake into BAT compared to sham operated animals as well as elevated gene markers related to increased BAT activity (Ucp1, Dio2, Cpt1b, Cox8b, Ppargc) and markers of increased browning of white fat (Ucp1, Dio2, Cited1, Tbx1, Tnfrs9). Both iBAT lipectomy and 6-OHDA treatment significantly attenuated the impact of VSG on changes in body weight and adiposity in chow-fed animals. In addition, surgical excision of iBAT following VSG significantly reversed VSG-mediated improvements in glucose tolerance, an effect that was independent of circulating insulin levels. Viral tracing studies highlighted a patent neural link between the gut and BAT that included groups of premotor BAT-directed neurons in the dorsal raphe and raphe pallidus. CONCLUSIONS: Collectively, these data support a role for BAT in mediating the metabolic sequelae following VSG surgery, particularly the improvement in glucose regulation, and highlight the need to better understand the contribution from this tissue in human patients.

Density measurements for the National Ignition Facility (NIF) opacity platform.

The Opacity Platform on the National Ignition Facility (NIF) has been developed to measure opacities at varying densities and temperatures relevant to the solar interior and thermal cooling rates in white dwarf stars. The typical temperatures reached at NIF range between 150 and 210 eV, which allow these measurements to be performed experimentally. The captured opacities are crucial to validating radiation-hydrodynamic models that are used in astrophysics. The NIF opacity platform has a unique new capability that allows in situ measurement of the sample expansion. The sample expansion data are used to better understand the plasma conditions in our experiments by inferring the sample density throughout the duration of the laser drive. We present the details of the density measurement technique, data analysis, and recent results for Fe and MgO.

Quadratic Zeeman effect in hydrogen at 2-3 MG magnetic fields.

The Zeeman effect is used for measurement of magnetic fields in astrophysical and laboratory plasmas. Magnetic fields in atmospheres of magnetic white dwarf stars are in the range 40 kG-1 GG. The quadratic Zeeman effect results in the additional split and shift of lines for magnetic fields >2 MG. Hydrogen Balmer lines were studied in magnetic fields delivered by a 1 MA pulse power generator. The magnetic field was generated by rod loads 0.8-1 mm in diameter. A droplet of CH oil on the load center was the source of hydrogen. A low ionized oil layer was backlit by blackbody emission from the rod with a temperature of 0.5-0.6 eV. Zeeman splitting of H-alpha and H-beta absorption lines were with a grating spectrometer. A spectral shift of the central component of the triplet indicated the quadratic Zeeman effect in hydrogen lines.

Some sex hormone profiles are consistent over time in normal menstruating women: implications for sports injury epidemiology.

PURPOSE: It is unclear whether sex hormone profiles obtained in two consecutive months are consistent within women. Month-to-month consistency in daily, nadir, peak and mean hormone concentrations during the early follicular and luteal phases in recreationally active, young eumenorrheic women was prospectively examined. METHODS: 60 healthy, non-smoking women who reported normal and consistent menstrual cycles lasting 26-32 days for the past 6 months were followed prospectively to obtain serum samples for the first 6 days of menses and for 8 days after a positive ovulation test over two consecutive months. Month-to-month consistency of daily concentrations of oestradiol (pg/ml), progesterone (ng/ml), testosterone (ng/dl), sex hormone-binding globulin (nmol/l) and free androgen index were determined using linear mixed models. Month-to-month consistency in nadir, peak and mean concentrations were then assessed using intraclass correlation coefficients and SEM to more precisely examine intraindividual consistency. RESULTS: Linear mixed models revealed stable hormone concentrations across cycles and cycles by day. Reliability estimates for nadir, peak, mean menses and mean postovulatory concentrations range from 0.56 to 0.86 for oestradiol, 0.44 to 0.91 for progesterone, 0.60 to 0.86 for testosterone, 0.88 to 0.97 for sex hormone-binding globulin and 0.78 to 0.91 for free androgen index. CONCLUSIONS: Hormone profiles were reproducible over two consecutive months. To reduce month-to-month intraindividual variations and improve measurement consistency, it is recommended that multiple samples be taken over consecutive days as opposed to a single sample.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

Autologous attenuated T-cell vaccine (Tovaxin) dose escalation in multiple sclerosis relapsing-remitting and secondary progressive patients nonresponsive to approved immunomodulatory therapies.

An open-label dose escalation study of T-cell vaccination in multiple sclerosis patients was conducted using attenuated myelin reactive T-cells (MRTC) selected with six myelin peptides, two each from MBP, PLP and MOG. The dose range of subcutaneous injections given at weeks 0, 4, 12 and 20 was 6-9E6, 30-45E6 and 60-90E6 irradiated MRTC. Assessments were over 52 weeks for MRTC levels, EDSS, MSIS-29, brain MRI and relapses. The 30-45E6 dose was the most effective with reductions in MRTC ranging from 92.4% at week 5 to 64.8% at week 52. The reduction in relapses compared to baseline for the M-ITT and evaluable per-protocol analyses were 63.5%, and 85.0% at week 52. The MRI lesions were stable while there was an improvement trend in the EDSS and MSIS-29 physical subscore following the second injection. Adverse events were mild to moderate in intensity with mild injection site reactions occurring with increasing dosage. The mid-dose was selected for further clinical development studies because of the rapid depletion of peripheral blood MRTC and a trend for improvements in clinical outcomes following immunization.

Ant-aphid association: role of aphid alarm pheromone.

When attacked by predators, aphids secrete alarm pheromones that cause nearby aphids to disperse. Ant-associated (myrmecophilous) aphid species disperse less readily than nonmyrmecophilous species. The ant Formica subsericea responds to aphid alarm pheromone in a way that is beneficial to the aphid. These findings support our hypothesis that myrmecophilous aphids depend more on ants for protection from predators than on their own dispersive powers.

Sesquiterpene progenitor, germacrene A: an alarm pheromone in aphids.

Germacrene A, the elusive biogenetic "parent" of many sesquiterpenes, has been isolated from the spotted alfalfa aphid and identified as a new intrageneric aphid alarm pheromone.

Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993-2003.

Exposure to certain environmental toxicants may be associated with increased risk of developing diabetes. The authors' aim was to investigate the relation between lifetime exposure to specific agricultural pesticides and diabetes incidence among pesticide applicators. The study included 33,457 licensed applicators, predominantly non-Hispanic White males, enrolled in the Agricultural Health Study. Incident diabetes was self-reported in a 5-year follow-up interview (1999-2003), giving 1,176 diabetics and 30,611 nondiabetics for analysis. Lifetime exposure to pesticides and covariate information were reported by participants at enrollment (1993-1997). Using logistic regression, the authors considered two primary measures of pesticide exposure: ever use and cumulative lifetime days of use. They found seven specific pesticides (aldrin, chlordane, heptachlor, dichlorvos, trichlorfon, alachlor, and cyanazine) for which the odds of diabetes incidence increased with both ever use and cumulative days of use. Applicators who had used the organochlorine insecticides aldrin, chlordane, and heptachlor more than 100 lifetime days had 51%, 63%, and 94% increased odds of diabetes, respectively. The observed association of organochlorine and organophosphate insecticides with diabetes is consistent with results from previous human and animal studies. Long-term exposure from handling certain pesticides, in particular, organochlorine and organophosphate insecticides, may be associated with increased risk of diabetes.

Ambulance and aeromedical accident rates during emergency retrieval in Great Britain.

The retrieval of critically ill patients is frequently done in difficult circumstances and often under considerable time pressures. These adverse conditions have a finite risk of serious injury or death. The level of risk is poorly described in the literature and reliable data on accident rates are hard to find. Most of the information comes from North America. There are no clear published statistics for the UK. We report for the first time data on accidents and casualties involving vehicles classified as having an ambulance body type and air ambulances within Great Britain between 1999 and 2004.

Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells.

Oxidative damage to the vascular endothelium may play an important role in the pathogenesis of atherosclerosis and aging, and may account in part for reduced vascular prostacyclin (PGI2) synthesis associated with both conditions. Using H2O2 to induce injury, we investigated the effects of oxidative damage on PGI2 synthesis in cultured endothelial cells (EC). Preincubation of EC with H2O2 produced a dose-dependent inhibition (inhibitory concentration [IC50] = 35 microM) of PGI2 formation from arachidonate. The maximum dose-related effect occurred within 1 min after exposure although appreciable H2O2 remained after 30 min (30% of original). In addition, H2O2 produced both a time- and dose-dependent injury leading to cell disruption, lactate dehydrogenase release, and 51Cr release from prelabeled cells. However, in dramatic contrast to H2O2 effects on PGI2 synthesis, loss of cellular integrity required doses in excess of 0.5 mM and incubation times in excess of 1 h. The superoxide-generating system, xanthine plus xanthine oxidase, produced a similar inhibition of PGI2 formation. Such inhibition was dependent on the generation of H2O2 but not superoxide in that catalase was completely protective whereas superoxide dismutase was not. H2O2 (50 microM) also effectively inhibited basal and ionophore A23187 (0.5 microM)-stimulated PGI2 formation. However, H2O2 had no effect on phospholipase A2 activity, because ionophore A23187-induced arachidonate release was unimpaired. To determine the effects on cyclooxygenase and PGI2 synthase, prostaglandin products from cells prelabeled with [3H]arachidonate and stimulated with ionophore A23187, or products formed from exogenous arachidonate were examined. Inhibition of cyclooxygenase but not PGI2 synthase was observed. Incubation of H2O2-treated cells with prostaglandin cyclic endoperoxide indicated no inhibition of PGI2 synthase. Thus, in EC low doses of H2O2 potently inhibit cyclooxygenase after brief exposure whereas larger doses and prolonged exposure are required for classical cytolytic effects. Surprisingly, PGI2 synthase, which is known to be extremely sensitive to a variety of lipid peroxides, is not inhibited by H2O2. Lipid solubility, enzyme location within the EC membrane, or the local availability of reducing factors may explain these results, and may be important determinants of the response of EC to oxidative stress.