Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense

Infectious diseases have been paramount among the threats to health and survival throughout human evolutionary history. Natural selection is therefore expected to act strongly on host defense genes, particularly on innate immunity genes whose products mediate the direct interaction between the host and the microbial environment. In insects and mammals, the Toll-like receptors (TLRs) appear to play a major role in initiating innate immune responses against microbes. In humans, however, it has been speculated that the set of TLRs could be redundant for protective immunity. We investigated how natural selection has acted upon human TLRs, as an approach to assess their level of biological redundancy. We sequenced the ten human TLRs in a panel of 158 individuals from various populations worldwide and found that the intracellular TLRs—activated by nucleic acids and particularly specialized in viral recognition—have evolved under strong purifying selection, indicating their essential non-redundant role in host survival. Conversely, the selective constraints on the TLRs expressed on the cell surface—activated by compounds other than nucleic acids—have been much more relaxed, with higher rates of damaging nonsynonymous and stop mutations tolerated, suggesting their higher redundancy. Finally, we tested whether TLRs have experienced spatially-varying selection in human populations and found that the region encompassing TLR10-TLR1-TLR6 has been the target of recent positive selection among non-Africans. Our findings indicate that the different TLRs differ in their immunological redundancy, reflecting their distinct contributions to host defense. The insights gained in this study foster new hypotheses to be tested in clinical and epidemiological genetics of infectious disease

Level of urbanization and noncommunicable disease risk factors in Tamil Nadu, India

Objective To investigate the poorly understood relationship between the process of urbanization and noncommunicable diseases (NCDs) through the application of a quantitative measure of urbanicity.Methods We constructed a measure of the urban environment for seven areas using a seven-item scale based on data from the Census of India 2001 to develop an &ldquo;urbanicity&rdquo; scale. The scale was used in conjunction with data collected from 3705 participants in the World Health Organization&rsquo;s 2003 STEPwise risk factor surveillance survey in Tamil Nadu, India, to analyse the relationship between the urban environment and major NCD risk factors. Linear and logistic regression models were constructed examining the relationship between urbanicity and chronic disease risk.Findings Among men, urbanicity was positively associated with smoking (odds ratio, OR: 3.54; 95% confidence interval, CI: 2.4&ndash;5.1), body mass index (OR: 7.32; 95% CI: 4.0&ndash;13.6), blood pressure (OR: 1.92; 95% CI: 1.4&ndash;2.7) and low physical activity (OR: 3.26; 95% CI: 2.5&ndash;4.3). Among women, urbanicity was positively associated with low physical activity (OR: 4.13; 95% CI: 3.0&ndash;5.7) and high body mass index (OR: 6.48; 95% CI: 4.6&ndash;9.2). In both sexes urbanicity was positively associated with the mean number of servings of fruit and vegetables consumed per day (P &lt; 0.05).Conclusion Urbanicity is associated with the prevalence of several NCD risk factors in Tamil Nadu, India.<br /

Maxillary Sinus Augmentation with Autologous and Heterologous Bone Graft: A Clinical and Radiographic Report of Immediate and Delayed Implant Placement

The aim of this study was to evaluate cumulative survival rate of implants placed on augmented maxillary sinus using a mixture of autologous bone harvested from the maxillary tuberosity and bovine-derived HA and to assess the height of the grafted material through radiographic evaluation