METHODS: Diabetes data were derived from the Malaysian National Health and Morbidity Surveys conducted in 2006, 2011 and 2015. The air pollution data (NOx, NO2, SO2, O3 and PM10) were obtained from the Department of Environment Malaysia. Using multiple logistic and linear regression models, the association between long-term exposure to these pollutants and prevalence of diabetes among Malaysian adults was evaluated.
RESULTS: The PM10 concentration decreased from 2006 to 2014, followed by an increase in 2015. Levels of NOx decreased while O3 increased annually. The air pollutant levels based on individual modelled air pollution exposure as measured by the nearest monitoring station were higher than the annual averages of the five pollutants present in the ambient air. The prevalence of overall diabetes increased from 11.4% in 2006 to 21.2% in 2015. The prevalence of known diabetes, underdiagnosed diabetes, overweight and obesity also increased over these years. There were significant positive effect estimates of known diabetes at 1.125 (95% CI, 1.042, 1.213) for PM10, 1.553 (95% CI, 1.328, 1.816) for O3, 1.271 (95% CI, 1.088, 1.486) for SO2, 1.124 (95% CI, 1.048, 1.207) for NO2, and 1.087 (95% CI, 1.024, 1.153) for NOx for NHMS 2006. The adjusted annual average levels of PM10 [1.187 (95% CI, 1.088, 1.294)], O3 [1.701 (95% CI, 1.387, 2.086)], NO2 [1.120 (95% CI, 1.026, 1.222)] and NOx [1.110 (95% CI, 1.028, 1.199)] increased significantly from NHMS 2006 to NHMS 2011 for overall diabetes. This was followed by a significant decreasing trend from NHMS 2011 to 2015 [0.911 for NO2, and 0.910 for NOx].
CONCLUSION: The findings of this study suggest that long-term exposure to O3 is an important associated factor of underdiagnosed DM risk in Malaysia. PM10, NO2 and NOx may have mixed effect estimates towards the risk of DM, and their roles should be further investigated with other interaction models. Policy and intervention measures should be taken to reduce air pollution in Malaysia.
MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.
CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.
METHODS: This is a meta-analysis of observational studies reporting effect estimates on how HIV is associated with extrapulmonary tuberculosis. We searched for the eligible studies in the electronic databases using search terms related to HIV and extrapulmonary tuberculosis. Where possible, we estimated the summary odds ratios using random effects meta-analysis. We stratified analysis by the type of study design. We assessed heterogeneity of effect estimates within each group of studies was assessed using I (2) test.
RESULTS: Nineteen studies (7 case control studies and 12 cohort studies) were identified for the present study. The pooled analysis shows a significant association between HIV and extrapulmonary tuberculosis (summary odds ratio: 1.3; 95 % confidence interval (CI) 1.05-1.6; I (2): 0 %). In a subgroup analysis with two studies, a significant association was found between CD4+ count less than 100 and the incidence of extrapulmonary tuberculosis (summary OR: 1.31; 95 % CI 1.02-1.68; I (2): 0 %).
CONCLUSIONS: Findings show evidence on the association between extrapulmonary tuberculosis and HIV, based on case control studies. Further studies to understand the mechanisms of interaction of the two pathogens are recommended.
METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas.
RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy.
CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.