Hagan Davis (nephewsubway15)
Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract disease in infants and young children worldwide and a high priority for vaccine development. Despite over 50 years of research, however, no vaccine is yet available. One block to vaccine development is an incomplete understanding of the aberrant memory response to the formalin-inactivated RSV vaccine (FI-RSV) given to children in the 1960s. This vaccine caused enhanced respiratory disease (ERD) with later natural RSV infection. Concern that any non-live virus vaccine may also cause ERD has blocked development of subunit vaccines for young children. A number of animal FI-RSV studies suggest various immune mechanisms behind ERD. However, other than limited data from the original FI-RSV trial, there is no information on the human ERD-associated responses. An in vitro model with human blood specimens may shed light on the immune memory responses likely responsible for ERD. Memory T cell responses to an antigen are guided by the innate responses, particularly dendritic cells that present an antigen in conjunction with co-stimulatory molecules and cytokine signaling. Our in vitro model involves human monocyte derived dendritic cells (moDC) and allogenic T cell cultures to assess innate responses that direct T cell responses. Using this model, we evaluated human responses to live RSV, FI-RSV, and subunit RSV G vaccines (G-containing virus-like particles, G-VLP). Similar to findings in animal studies, FI-RSV induced prominent Th2/Th17-biased responses with deficient type-1 responses compared to live virus. Responses to G-VLPs were similar to live virus, i.e. biased towards a Th1 and not a Th2/Th17. Also mutating CX3C motif in G gave a more pronounced moDC responses associated with type-1 T cell responses. This in vitro model identifies human immune responses likely associated with ERD and provides another pre-clinical tool to assess the safety of RSV vaccines.OBJECTIVES Literature shows a high prevalence of MetS among Malaysians, varying across the major ethnicities. Since sociodemographic characteristics, lifestyle factors and diet habits of such communities have been reported to be diverse, the objective of this study was to investigate the association of various sociodemographic characteristics, lifestyle factors and diet habits with MetS overall, as well as with the three major ethnic communities in Malaysia, specifically. MATERIALS AND METHODS We conducted a cross-sectional study among 481 Malaysians of ages 18 years and above living in the state of Johor, Malaysia. Information on demographics, lifestyle and diet habits were collected using a structured questionnaire. Harmonized criteria were used to assess the status of MetS. Multiple logistic regression was employed to determine any associations between sociodemographic and lifestyle factors and dietary behaviours with MetS. RESULTS MetS was found among 32.2% of the respondents and was more prevalent among the Indians (51.9%), followed by the Malays (36.7%) and the Chinese (20.2%). Overall, increasing age (AOR = 2.44[95%CI = 1.27-4.70] at 40-49 years vs. AOR = 4.14[95%CI = 1.97-8.69] at 60 years and above) and Indian ethnicity (AOR = 1.95[95%CI = 1.12-3.38)] increased the odds of MetS, while higher education (AOR = 0.44[95%CI = 0.20-0.94] decreased the odds of MetS in this population. Quick finishing of meals (AOR = 2.17[95%CI = 1.02-4.60]) and low physical activity (AOR = 4.76[95%CI = 1.49-15.26]) were associated with increased odds of MetS among the Malays and the Chinese, respectively. CONCLUSION The population of Johor depicts a diverse lifestyle and diet behaviour, and some of these factors are associated with MetS in certain ethnic groups. In the light of such differences, ethnic specific measures would be needed to reduce the prevalence of MetS among those in this population.Obesity can initiate and accelerate the progression of kidney diseases. However, it remains u