A nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer's disease.

A disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aß deposition, neuroinflammation and neurodegeneration in Alzheimer's disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. The p65 binding domain of GILZ adopts a polyproline type II helical conformation, a motif that acts as an adaptable glove in the interface with the binding partner and constitutes an excellent template for drug design. Previously, peptide analogs of the p65 binding domain of GILZ, referred to as GA have been shown to suppress pathology in the lipopolysaccharide induced model of neuroinflammation. In this study, we investigated the CNS delivery of labeled GA administered intraperitoneally in adult mice for a period of upto 24 h. Further, we evaluated the suppressive potential of GA in 5xFAD mice, an aggressive model with five genetic mutations closely associated with human AD. Groups of 5xFAD mice administered GA or control peptide intraperitoneally on alternate days for six weeks were evaluated for Aß deposition, microglia, inflammation and innate immune responses by immunohistochemistry and real time polymerase reaction. GA was observed in proximity with NeuN positive neurons suggesting that the compound crossed the blood brain barrier to reach the brain parenchyma. Further, GA treatment decreased Aß load, reduced Iba1 + microglia and glial fibrillary acidic protein (GFAP)+ astrocytes, inhibited inflammatory cytokines and suppressed toll like receptor (TLR-2, TLR-4) expressions in 5xFAD mice.

Gender norms and sexual behaviours among men in western Jamaica.

UNLABELLED: Objectives Gender norms, especially among men, can reduce the effectiveness of HIV prevention programs. We sought to assess the association between attitudes towards gender norms and risky sexual behaviours, and identify sociodemographic factors that predict gender-inequitable and masculinity norms among men in western Jamaica. METHODS: A cross-sectional, survey of 549 men aged 19-54 years was conducted. Attitudes towards gender norms were measured using the Gender Equitable Men and Macho scales. Logistic regression and general linear models were used to assess associations between gender norms and multiple sexual partners, and to identify the associated sociodemographic factors. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) are presented. RESULTS: Fifty-four percent of the participants (mean age=32.4 years) reported multiple sex partners and 22% reported unprotected sex with non-regular partner in the past 12 months. Men with moderate (AOR=2.2; 95% CI=1.4-3.3) and high (AOR=4.2; 95% CI=2.0-8.5) support for inequitable gender norms, and moderate (AOR=1.7; 95% CI=1.1-2.7) and high (AOR=2.5; 95% CI=1.5-4.3) support for masculinity norms were more likely to report multiple sex partners. Similarly, men with moderate (AOR=2.4; 95% CI=1.3-4.3) and high (AOR=2.5; 95% CI=1.2-5.2) support for inequitable gender norms were more likely to report unprotected sex with a nonregular partner. CONCLUSION: A high proportion of Jamaican men engage in risky sexual behaviours. These results highlight the need for behaviour change interventions addressing gender norms targeting Jamaican men.

Factors associated with the acceptability of male circumcision among men in Jamaica.

OBJECTIVES: To determine the prevalence of male circumcision (MC) among men in the western region of Jamaica, and to identify factors associated with acceptability of MC for self, infants (<1 year) and older sons (1-17 years). METHODS: A cross-sectional, interviewer-administered questionnaire survey of 549 men aged 19-54 years was conducted in the western region of Jamaica. The survey included questions about the acceptance of MC for self, infants, and sons before and after an information session about the benefits of MC in preventing HIV/STI transmission. Logistic regression models were used to identify factors that were associated with acceptability of MC. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated from the models. RESULTS: Fourteen percent of the men reported that they were circumcised. In the multivariable model, which adjusted for age, education, religion and income, there were increased odds of accepting MC for infants/sons among uncircumcised men who accepted MC for self (AOR=8.1; 95% CI = 4.1-15.9), believed they would experience more pleasure during sex if circumcised (AOR=4.0; 95% CI = 2.0-8.2), and reported having no concerns regarding MC (AOR=3.0; 95% CI = 1.8-4.8). Similarly, uncircumcised men who reported no concerns about MC or who believed that they would experience more pleasure during sex if circumcised were more likely to accept MC for self. CONCLUSION: Providing men with information about MC increased acceptance of MC for self, infants (<17 years) and sons (1-17 years). Since targeted education on the benefits of male circumcision for prevention of HIV/STI can be effective in increasing acceptability of MC, health professionals should be trained, and willing to discuss MC with men in healthcare facilities and in the community.