Investigating regulatory patterns of NLRP3 Inflammasome features and association with immune microenvironment in Crohn's disease.

Introduction: Crohn's disease is characterized of dysregulated inflammatory and immune reactions. The role of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in Crohn's disease remains largely unknown. Methods: The microarray-based transcriptomic data and corresponding clinical information of GSE100833 and GSE16879 were obtained from the Gene Expression Omnibus (GEO) database. Identification of in the NLRP3 inflammasome-related genes and construction of LASSO regression model. Immune landscape analysis was evaluated with ssGSEA. Classification of Crohn's-disease samples based on NLRP3 inflammasome-related genes with ConsensusClusterPlus. Functional enrichment analysis, gene set variation analysis (GSVA) and drug-gene interaction network. Results: The expressions of NLRP3 inflammasome-related genes were increased in diseased tissues, and higher expressions of NLRP3 inflammasome-related genes were correlated with generally enhanced immune cell infiltration, immune-related pathways and human leukocyte antigen (HLA)-gene expressions. The gene-based signature showed well performance in the diagnosis of Crohn's disease. Moreover, consensus clustering identified two Crohn's disease clusters based on NLRP3 inflammasome-related genes, and cluster 2 was with higher expressions of the genes. Cluster 2 demonstrated upregulated activities of immune environment in Crohn's disease. Furthermore, four key hub genes were identified and potential drugs were explored for the treatment of Crohn's disease. Conclusions: Our findings indicate that NLRP3 inflammasome and its related genes could regulate immune cells and responses, as well as involve in the pathogenesis of Crohn's disease from transcriptomic aspects. These findings provide in silico insights into the diagnosis and treatment of Crohn's disease and might assist in the clinical decision-making process.

Systematic Review Estimating the Burden of Dementia in the Latin America and Caribbean Region: A Bayesian Approach.

Background: The global burden of dementia has increasingly shifted to low- and middle-income regions that lack essential data for monitoring epidemiological progression, and policy and planning support. Drawing upon data that have emerged since the last known estimates published in 2015, this study aims to update dementia estimates in the Latin America and Caribbean (LAC) region for the years 2020, 2030, and 2050 through the application of a recently validated Bayesian approach for disease estimates useful when data sources are scarce. Methods: A comprehensive parallel systematic review of PubMed, EMBASE, PsycINFO, Global Health, and LILACS was conducted to identify prospective population-based epidemiological studies on dementia published in English from 2013 to 2018 in LAC. English and non-English data cited by a recent review on dementia estimates in LAC were also examined for additional data. A Bayesian normal-normal hierarchical model (NNHM) was developed to estimate age-specific and age-adjusted dementia prevalence in people aged 60+. Using age-specific population projections from the UN, the total number of people affected by dementia for the years 2020, 2030, and 2050 were estimated. Results: 1,414 studies were identified, of which only 7 met the inclusion criteria. The studies had 7,684 participants and 1,191 dementia cases. The age-standardized prevalence of all forms of dementia in LAC was 8% (95% CI: 5-11.5%) in people aged 60+. The estimated prevalence varied with age, increasing from 2.5% (95% CI: 0.08-4.0%) in the 60-69 age group, to 9.4% (95% CI: 5.4-13.2%) in the 70-79 age group and 28.9% (95% CI: 20.3-37.2%) in the ≥80 age group. The number of people age 60 and older living with dementia in LAC in 2020 was estimated at 6.86 (95% CI: 4.3-9.8) million, 9.94 (95% CI: 6.16-14.15) million in 2030, and 19.33 (95% CI: 12.3-13.6) million in 2050. Conclusion: We project an upward disease trajectory for dementia in LAC countries. The projection is likely an underestimation of the true dementia burden given the underrepresentation of rural and socio-economically deprived populations. More research is urgently needed to improve the accuracy of disease estimates, guide clinicians to improve evaluations for earlier recognition of dementia, and support the development of effective policies for improving dementia prevention, diagnosis and clinical management in LAC's diverse and aging communities.

Systematic review estimating the burden of dementia in the WHO Southeast Asia Region using Bayesian and frequentist approaches.

BACKGROUND: Rapid increase in life expectancy in low- and middle-income countries including the World Health Organization's Southeast Asia Region (SEAR) has resulted in an increase in the global burden of dementia, which is expected to become a leading cause of morbidity. Accurate burden estimates are key for informing policy and planning. Given the paucity of data, estimates were developed using both a Bayesian methodology and as well as a traditional frequentist approach to gain better insights into methodological approaches for disease burden estimates. METHODS: Seven databases were searched for studies published between 2010-2018 regarding dementia prevalence in SEAR, generating 8 relevant articles. A random-effects model (REM) and a Bayesian normal-normal hierarchical model (NNHM) were used to obtain the pooled prevalence estimate of dementia for people aged 60 and above in SEAR. The latter model was also developed to estimate age-specific dementia prevalence. Using UN population estimates for SEAR, total and age-specific projections of the burden of dementia in 2015, 2020 and 2030 were calculated. RESULTS: The prevalence of dementia in SEAR was found to be 3% (95% confidence interval (CI) = 2-6%) in those above age 60 based on REM, and 3.1% (95% credible interval = 1.5-5.0%) based on the NNHM. The estimated prevalence varies with age, increasing from 1.6% (95% credible interval = 0.8-2.5%) in people aged 60-69 to 12.4% (95% credible interval = 5.6-20%) in people above the age of 80. The risk of developing dementia increased exponentially with age. The number of people living with dementia in SEAR in 2015 was estimated at 5.51 million (95% credible interval = 2.66-8.82), with projections of 6.66 million (95% credible interval = 3.21-10.7) in 2020 and 9.6 million (95% credible interval = 4.62-15.36) in 2030. CONCLUSION: The burden of dementia in SEAR is substantial and will continue to increase rapidly by 2030. The lack of research focusing on dementia in SEAR points to a significant under-recognition of this disease. The projected rise in dementia cases in the future should prompt urgent governmental response to address this growing public health issue. We also argue that given the overall paucity of data for the region, the Bayesian approach offers a promising methodology for improved estimates of disease prevalence and burden and should continue to be explored.