Perceived Versus Calculated HIV Risk: Implications for Pre-exposure Prophylaxis Uptake in a Randomized Trial of Men Who Have Sex With Men.

BackgroundInaccurate HIV risk perception by men who have sex with men is a barrier to HIV prevention. Providing information about objective HIV risk could improve pre-exposure prophylaxis (PrEP) uptake.MethodsPrEP Accessibility Research & Evaluation 2 (PrEPARE2) was a randomized controlled trial of men who have sex with men to determine whether an objective risk score affects future PrEP uptake. Participants completed a baseline survey to assess demographics, risk behaviors, and HIV self-perceived risk (SPR). The survey generated a calculated HIV risk (CalcR) score, estimating HIV risk based on reported condomless anal intercourse and sexually transmitted infections, and was provided to individuals in the intervention arm. Participants were contacted 8 weeks later to determine whether they initiated PrEP.ResultsOf 171 participants (median age 32 years; 37% Hispanic or non-Hispanic Black; median 5 sexual partners in the past 6 months), 81% had heard of PrEP, and 57% believed they were good PrEP candidates. SPR had poor agreement with CalcR (kappa = 0.176) with 38% underestimating their HIV risk. At week 8, only 14 of 135 participants had initiated PrEP with no difference between arms (CalcR 11%, control 10%, P > 0.99). The most common reason for not starting PrEP was low HIV risk perception. There was a relative decrease in SPR over time (P = 0.06) but no difference between arms (P = 0.29).ConclusionProviding an objective HIV risk score alone did not increase PrEP uptake. HIV testing performed at testing sites may be a crucial time to correct misperceptions about risk and initiate same-day PrEP, given enthusiasm for PrEP on the testing day to facilitate greater uptake

Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase

Abstract Background Postprandial hyperglycemia is an early defect of type 2 diabetes and one of primary anti-diabetic targets. Treatment of postprandial hyperglycemia can be achieved by inhibiting intestinal α-glucosidase, the key enzyme for oligosaccharide digestion and further glucose absorption. Grape pomace is winemaking byproduct rich in bioactive food compounds such as phenolic antioxidants. This study evaluated the anti-diabetic potential of two specific grape pomace extracts by determining their antioxidant and anti-postprandial hyperglycemic activities in vitro and in vivo. Methods The extracts of red wine grape pomace (Cabernet Franc) and white wine grape pomace (Chardonnay) were prepared in 80% ethanol. An extract of red apple pomace was included as a comparison. The radical scavenging activities and phenolic profiles of the pomace extracts were determined through the measurement of oxygen radical absorbance capacity, DPPH radical scavenging activity, total phenolic content and flavonoids. The inhibitory effects of the pomace extracts on yeast and rat intestinal α-glucosidases were determined. Male 6-week old C57BLKS/6NCr mice were treated with streptozocin to induce diabetes. The diabetic mice were then treated with vehicle or the grape pomace extract to determine whether the oral intake of the extract can suppress postprandial hyperglycemia through the inhibition of intestinal α-glucosidases. Results The red grape pomace extract contained significantly higher amounts of flavonoids and phenolic compounds and exerted stronger oxygen radical absorbance capacity than the red apple pomace extract. Both the grape pomace extracts but not the apple pomace extract exerted significant inhibition on intestinal α-glucosidases and the inhibition appears to be specific. In the animal study, the oral intake of the grape pomace extract (400 mg/kg body weight) significantly suppressed the postprandial hyperglycemia by 35% in streptozocin-induced diabetic mice following starch challenge. Conclusion This is the first report that the grape pomace extracts selectively and significantly inhibits intestinal α-glucosidase and suppresses postprandial hyperglycemia in diabetic mice. The antioxidant and anti-postprandial hyperglycemic activities demonstrated on the tested grape pomace extract therefore suggest a potential for utilizing grape pomace-derived bioactive compounds in management of diabetes

Introduction of a Waterless Alcohol-based Hand Rub in a Long-term Care Facility

OBJECTIVE: To examine the impact of introduction of an alcohol-based hand rub on hand hygiene knowledge and compliance and hand colonization of healthcare workers (HCWs) in a long-term-care facility (LTCF). METHODS: Two floors of an LTCF participated. Ward A used the hand rub as an adjunct to soap and water; ward B was the control. HCWs\u27 hands were cultured using the bag-broth technique for Staphylococcus aureus, gram-negative bacilli (GNB), Candida, and vancomycin-resistant enterococci (VRE). HCWs completed a questionnaire at baseline and after an educational intervention and introduction of rub. RESULTS: Hand hygiene practices, knowledge, and opinions did not change after the educational or rub intervention. Ward A HCWs thought that the rub was faster (P = .002) and less drying (P = .04) than soap. Hand hygiene frequency did not differ at baseline between the two floors, but increased on ward A by the end of the study (P = .04). HCWs were colonized frequently with GNB (66%), Candida (41%), S. aureus (20%), and VRE (9%). Although colonization did not change from baseline on either ward, the rub was more effective in clearing GNB P =.03) and S. aureus (P = .003). Nosocomial infection rates did not change. CONCLUSION: The alcohol-based hand rub was a faster, more convenient, less drying method of hand hygiene for HCWs in an LTCF, and it improved compliance. Although microbial colonization did not change, the rub was more efficacious in removing pathogens already present on the hands of HCWs

Biomechanical microenvironment regulates fusogenicity of breast cancer cells

Fusion of cancer cells is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have demonstrated that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive area of the patterned substrates, reducing cytoskeletal tensions pharmacologically, altering matrix stiffness, and modulating pattern curvature all supported the spontaneous fusion and stability of these multinucleated giant cells. These observations highlight that the biomechanical microenvironment of cancer cells, including the matrix rigidity and interfacial curvature, can directly modulate their fusogenicity, an unexplored mechanism through which biophysical cues regulate tumor progression

The short-term association of selected components of fine particulate matter and mortality in the Denver Aerosol Sources and Health (DASH) study

Background: Associations of short-term exposure to fine particulate matter (PM2.5) with daily mortality may be due to specific PM2.5&nbsp;chemical components. Daily concentrations of PM2.5&nbsp;components were measured over five years in Denver to investigate whether specific PM2.5&nbsp;components are associated with daily mortality. Methods: Daily counts of total and cause-specific deaths were obtained for the 5-county Denver metropolitan region from 2003 through 2007. Daily 24-hour concentrations of PM2.5, elemental carbon (EC), organic carbon (OC), sulfate and nitrate were measured at a central residential monitoring site. Using generalized additive models, we estimated relative risks (RRs) of daily death counts for daily PM2.5&nbsp;and four PM2.5&nbsp;component concentrations at single and distributed lags between the current and three previous days, while controlling for longer-term time trend and meteorology. Results: RR of total non-accidental mortality for an inter-quartile increase of 4.55 &mu;g/m3&nbsp;in PM2.5&nbsp;distributed over 4 days was 1.012 (95 % confidence interval: 0.999, 1.025); RRs for EC and OC were larger (1.024 [1.005, 1.043] and 1.020 [1.000, 1.040] for 0.33 and 1.67 &mu;g/m3 increases, respectively) than those for sulfate and nitrate. We generally did not observe associations with cardiovascular and respiratory mortality except for associations with ischemic heart disease mortality at lags 3 and 0&ndash;3 depending on the component. In addition, there were associations with cancer mortality, particularly for EC and OC, possibly reflecting advanced deaths of a frail population. Conclusions: PM2.5 components possibly from combustion-related sources are more strongly associated with daily mortality than are secondary inorganic aerosols.</p

Clinical predictors of 3- and 6-month outcome for mild traumatic brain injury patients with a negative head CT scan in the emergency department: A TRACK-TBI pilot study

Aconsiderable subset of mild traumatic brain injury (mTBI) patients fail to return to baseline functional status at or beyond 3 months postinjury. Identifying at-risk patients for poor outcome in the emergency department (ED) may improve surveillance strategies and referral to care. Subjects with mTBI (Glasgow Coma Scale 13–15) and negative ED initial head CT < 24 h of injury, completing 3- or 6-month functional outcome (Glasgow Outcome Scale-Extended; GOSE), were extracted from the prospective, multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study. Outcomes were dichotomized to full recovery (GOSE = 8) vs functional deficits (GOSE < 8). Univariate predictors with p < 0.10 were considered for multivariable regression. Adjusted odds ratios (AOR) were reported for outcome predictors. Significance was assessed at p < 0.05. Subjects who completed GOSE at 3- and 6-month were 211 (GOSE < 8: 60%) and 185 (GOSE < 8: 65%). Risk factors for 6-month GOSE < 8 included less education (AOR = 0.85 per-year increase, 95% CI: (0.74–0.98)), prior psychiatric history (AOR = 3.75 (1.73–8.12)), Asian/minority race (American Indian/Alaskan/Hawaiian/Pacific Islander) (AOR = 23.99 (2.93–196.84)), and Hispanic ethnicity (AOR = 3.48 (1.29–9.37)). Risk factors for 3-month GOSE < 8 were similar with the addition of injury by assault predicting poorer outcome (AOR = 3.53 (1.17–10.63)). In mTBI patients seen in urban trauma center EDs with negative CT, education, injury by assault, Asian/minority race, and prior psychiatric history emerged as risk factors for prolonged disability

Programmed Autophagy in the Fat Body of Aedes aegypti Is Required to Maintain Egg Maturation Cycles

Autophagy plays a pivotal role by allowing cells to recycle cellular components under conditions of stress, starvation, development and cancer. In this work, we have demonstrated that programmed autophagy in the mosquito fat body plays a critical role in maintaining of developmental switches required for normal progression of gonadotrophic cycles. Mosquitoes must feed on vertebrate blood for their egg development, with each gonadotrophic cycle being tightly coupled to a separate blood meal. As a consequence, some mosquito species are vectors of pathogens that cause devastating diseases in humans and domestic animals, most importantly malaria and Dengue fever. Hence, deciphering mechanisms to control egg developmental cycles is of paramount importance for devising novel approaches for mosquito control. Central to egg development is vitellogenesis, the production of yolk protein precursors in the fat body, the tissue analogous to a vertebrate liver, and their subsequent specific accumulation in developing oocytes. During each egg developmental cycle, the fat body undergoes a developmental program that includes previtellogenic build-up of biosynthetic machinery, intense production of yolk protein precursors, and termination of vitellogenesis. The importance of autophagy for termination of vitellogenesis was confirmed by RNA interference (RNAi) depletions of several autophagic genes (ATGs), which inhibited autophagy and resulted in untimely hyper activation of TOR and prolonged production of the major yolk protein precursor, vitellogenin (Vg). RNAi depletion of the ecdysone receptor (EcR) demonstrated its activating role of autophagy. Depletion of the autophagic genes and of EcR led to inhibition of the competence factor, betaFTZ-F1, which is required for ecdysone-mediated developmental transitions. Moreover, autophagy-incompetent female mosquitoes were unable to complete the second reproductive cycle and exhibited retardation and abnormalities in egg maturation. Thus, our study has revealed a novel function of programmed autophagy in maintaining egg maturation cycles in mosquitoes

Dcc Regulates Asymmetric Outgrowth of Forebrain Neurons in Zebrafish

The guidance receptor DCC (deleted in colorectal cancer) ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt) neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates

S-nitrosation and neuronal plasticity

Nitric oxide (NO) has long been recognized as a multifaceted participant in brain physiology. Despite the knowledge that was gathered over many years regarding the contribution of NO to neuronal plasticity, for example the ability of the brain to change in response to new stimuli, only in recent years have we begun to understand how NO acts on the molecular and cellular level to orchestrate such important phenomena as synaptic plasticity (modification of the strength of existing synapses) or the formation of new synapses (synaptogenesis) and new neurons (neurogenesis). Post-translational modification of proteins by NO derivatives or reactive nitrogen species is a non-classical mechanism for signalling by NO. S-nitrosation is a reversible post-translational modification of thiol groups (mainly on cysteines) that may result in a change of function of the modified protein. S-nitrosation of key target proteins has emerged as a main regulatory mechanism by which NO can influence several levels of brain plasticity, which are reviewed in this work. Understanding how S-nitrosation contributes to neural plasticity can help us to better understand the physiology of these processes, and to better address pathological changes in plasticity that are involved in the pathophysiology of several neurological diseases. Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visitFEDER funds via Programa Operacional Factores de Competitividade (COMPETE); COST action [BM1005]; Foundation for Science and Technology (FCT, Portugal) [PTDC/SAU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; Spanish-Portuguese Integrated Action grant [PRI-AIBPT-2011-1015/E-10/12]; FCT [SFRH/BD/77903/2011]; I3SNS programme (ISCIII, Spanish Government