Mahidol University

About: Mahidol University is a education organization based out in Bangkok, Nakhon Pathom, Thailand. It is known for research contribution in the topics: Population & Malaria. The organization has 23758 authors who have published 39761 publications receiving 878781 citations.

Role of Dendritic Cells in Antibody-Dependent Enhancement of Dengue Virus Infection

Abstract: Dengue viruses (DV), composed of four distinct serotypes (DV1 to DV4), cause 50 to 100 million infections annually. Durable homotypic immunity follows infection but may predispose to severe subsequent heterotypic infections, a risk conferred in part by the immune response itself. Antibody-dependent enhancement (ADE), a process best described in vitro, is epidemiologically linked to complicated DV infections, especially in Southeast Asia. Here we report for the first time the ADE phenomenon in primary human dendritic cells (DC), early targets of DV infection, and human cell lines bearing Fc receptors. We show that ADE is inversely correlated with surface expression of DC-SIGN (DC-specific intercellular adhesion molecule-3-grabbing nonintegrin) and requires Fc gamma receptor IIa (FcγRIIa). Mature DC exhibited ADE, whereas immature DC, expressing higher levels of DC-SIGN and similar FcγRIIa levels, did not undergo ADE. ADE results in increased intracellular de novo DV protein synthesis, increased viral RNA production and release, and increased infectivity of the supernatants in mature DC. Interestingly, tumor necrosis factor alpha and interleukin-6 (IL-6), but not IL-10 and gamma interferon, were released in the presence of dengue patient sera but generally only at enhancement titers, suggesting a signaling component of ADE. FcγRIIa inhibition with monoclonal antibodies abrogated ADE and associated downstream consequences. DV versatility in entry routes (FcγRIIa or DC-SIGN) in mature DC broadens target options and suggests additional ways for DC to contribute to the pathogenesis of severe DV infection. Studying the cellular targets of DV infection and their susceptibility to ADE will aid our understanding of complex disease and contribute to the field of vaccine development.

Prevalence, risk factors and disability associated with fall-related injury in older adults in low- and middle-incomecountries: results from the WHO Study on global AGEing and adult health (SAGE)

Abstract: Background: In 2010 falls were responsible for approximately 80 % of disability stemming from unintentional injuries excluding traffic accidents in adults 50 years and over Falls are becoming a major public health problem in low- and middle-income countries (LMICs) where populations are ageing rapidly Methods: Nationally representative standardized data collected from adults aged 50 years and over participating in the World Health Organization (WHO) Study on global AGEing and adult health (SAGE) Wave 1 in China, Ghana, India, Mexico, the Russian Federation and South Africa are analysed The aims are to identify the prevalence of, and risk factors for, past-year fall-related injury and to assess associations between fall-related injury and disability Regression methods are used to identify risk factors and association between fall-related injury and disability Disability was measured using the WHO Disability Assessment Schedule Version 20 (WHODAS 20) Results: The prevalence of past-year fall-related injuries ranged from 66 % in India to 10 % in South Africa and was 40 % across the pooled countries The proportion of all past-year injuries that were fall-related ranged from 733 % in the Russian Federation to 444 % in Ghana Across the six countries this was 657 % In the multivariable logistic regression, the odds of past-year fall-related injury were significantly higher for: women (OR: 127; 95 % CI: 099,162); respondents who lived in rural areas (OR: 136; 95 % CI: 106,175); those with depression (OR: 143; 95 % CI: 101,202); respondents who reported severe or extreme problems sleeping (OR: 154; 95 % CI: 115,208); and those who reported two or more (compared with no) chronic conditions (OR: 215; 95 % CI: 145,319) Poor cognition was also a significant risk factor for fall-related injury The association between fall-related injury and the WHODAS measure of disability was highly significant (P<00001) with some attenuation after adjusting for confounders Reporting two or more chronic conditions (compared with none) was significantly associated with disability (P<00001) Conclusions: The findings provide a platform for improving understanding of risk factors for falls in older adults in this group of LMICs Clinicians and public health professionals in these countries must be made aware of the extent of this problem and the need to implement policies to reduce the risk of falls in older adults

Global implementation of genomic medicine: We are not alone

Abstract: Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Efforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in efforts to improve clinical care worldwide.