Evidence of a Syndemic Among Young Canadian Gay and Bisexual Men: Uncovering the Associations Between Anti-gay Experiences,Psychosocial Issues,and HIV Risk

Syndemic has become an important theoretical model toward understanding how psychosocial issues may interact to increase HIV acquisition among gay and bisexual men. We measured the extent to which anti-gay experiences are associated with psychosocial issues, which in turn were hypothesized to have an additive effect on HIV risk, in a sample of Canadian young gay and bisexual men. Sixty-eight percent of men reported at least one form of anti-gay experience. For each additional form of anti-gay experience, our data demonstrated increased likelihood of psychosocial issues. Psychosocial issues had an additive effect, increasing the risk of unprotected intercourse in the last 12 months (doubling the risk for those with 3+ issues OR 1.95 [1.39–2.75]). Overall, our findings suggest that a syndemic is occurring among young Canadian gay and bisexual men, highlighting the need to expand HIV prevention efforts beyond sexual risk, to address stigma and gay men’s broader health concerns.     

Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

Optimal Seasonal Timing of Oral Azithromycin for Malaria

Mass administration of azithromycin for trachoma has been shown to reduce malarial parasitemia. However, the optimal seasonal timing of such distributions for antimalarial benefit has not been established. We performed numerical analyses on a seasonally forced epidemic model (of Ross-Macdonald type) with periodic impulsive annual mass treatment to address this question. We conclude that when azithromycin-based trachoma elimination programs occur in regions of seasonal malaria transmission, such as Niger, the optimal seasonal timing of mass drug administration (MDA) may not occur during the season of maximum transmission.     

Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT)

Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.Light perception begins with the absorption of a photon by an opsin pigment in the membranous outer segment (OS) of a rod or cone photoreceptor cell. The light-absorbing chromophore in most vertebrate opsins is 11-cis-retinaldehyde (11-cis-RAL). Photon capture isomerizes the 11-cis-RAL to all-trans-retinaldehyde (all-trans-RAL), inducing conformational changes in the protein that lead to its active meta-II state. After a brief period of signaling through the transduction cascade, meta II decays to yield apo-opsin and free all-trans-RAL. Light sensitivity is restored to the apo-opsin when it combines with 11-cis-RAL to regenerate the pigment. Conversion of all-trans-RAL to 11-cis-RAL is carried out by a multistep enzyme pathway called the visual cycle, located in cells of the retinal pigment epithelium (RPE) (1, 2). The retinoid isomerase in this pathway is Rpe65, which converts an all-trans-retinyl ester (all-trans-RE), such as all-trans-retinyl palmitate (all-trans-RP), to 11-cis-retinol (11-cis-ROL) and a free fatty acid (3–5). Retinyl esters are synthesized in RPE cells by lecithin:retinol acyl transferase (LRAT), which transfers a fatty acid from phosphatidylcholine to retinol (6, 7). LRAT converts both all-trans-ROL and 11-cis-ROL to their cognate esters with similar catalytic efficiency (8).A second visual cycle is present in Müller cells of the retina, providing 11-cis-ROL to cones (9–11). Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10, 12, 13). The isomerase in the noncanonical pathway is dihydroceramide desaturase (DES1) (11). DES1 catalyzes rapid equilibrium isomerization of retinol (11). At equilibrium, 11-cis-ROL is much less abundant than all-trans-ROL, due to the 4.1 kcal/mole difference in free energy between these isomers (14). Accordingly, a secondary source of energy is required to drive the conversion of all-trans-ROL to 11-cis-ROL by DES1. Retinas from cone-dominant species contain 11-cis-retinyl esters (11-cis-REs), whereas retinyl esters are much less abundant in retinas from rod-dominant species (11, 13, 15). Homogenates from cone-dominant chicken and ground-squirrel retinas convert all-trans-ROL predominantly to 11-cis-REs in the presence of palmitoyl CoA (palm CoA) (13, 16, 17). These observations suggest that selective esterification of 11-cis-ROL may be the driving force for 11-cis-retinoid formation. In the current work, we sought to identify the protein responsible for the 11-cis-RE-synthase activity in Müller cells. We evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this synthase. MFAT, also called acyl-CoA wax-alcohol acyltransferase-2 (AWAT2), catalyzes palm CoA-dependent synthesis of triglycerides, wax monoesters, and retinyl esters (18). It is present in the endoplasmic reticulum and predominantly expressed in skin (18). The retinol-isomer specificity of MFAT, and its expression in ocular tissues, has not been studied.     

Changing Selves in Changing Worlds: Youth Suicide on the Fault-Lines of Colliding Cultures

Abstract

A time series study of the Japanese suicide rate from 1970 to 1989 indicated that the establishment of suicide prevention centers may have been associated with a reduced suicide rate above and beyond the impact of social and economic factors. The effect was small and significant at only the 0.07 level, but sufficiently stable as to encourage further research to evaluate the effectiveness of suicide prevention centers.