Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). I3S is financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). I3S is financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A review of the influence of periodontal treatment in systemic diseases

The effects and consequences of periodontal diseases might not be confined to the oral cavity. A great body of evidence has arisen supporting the claim demonstrating an association with several systemic conditions and diseases. With different levels of evidence, an association between periodontal disease and cardiovascular disease, diabetes, psoriasis, rheumatoid arthritis, pregnancy outcomes and respiratory diseases has been established. However, the true nature of this association, if it is causal, still remains elusive. For a better understanding of the complex relationships linking different conditions, interventional studies now begin to focus on the possible outcomes of periodontal treatment in relation to the events, symptoms and biomarkers of several systemic disorders, assessing if periodontal treatment has any impact on them, hopefully reducing their severity or prevalence. Therefore, we proceeded to review the recent literature on the subject, attempting to present a brief explanation of the systemic condition or disease, what proposed mechanisms might give biological plausibility to its association with periodontal disease, and finally and more importantly, what data are currently available pertaining to the effects periodontal treatment may have. Raising awareness and discussing the possible benefits of periodontal treatment on overall systemic health is important, in order to change the perception that periodontal diseases are only limited to the oral cavity, and ultimately providing better and comprehensive care to patients