• Bryan Newman opublikował 1 rok, 3 miesiące temu

    In order to analyze the quantitative data we will use descriptive statistics and explore associations in uni- and multi-variable analyses. Qualitative data will be subjected to thematic analysis. DISCUSSION This is an exploratory study to identify characteristics and coping strategies that appear to help people to overcome experiences of violence in deprived areas without developing mental distress. The findings could inform policies to reduce mental distress and improve the quality of life of people living in urban areas affected by violence.BACKGROUND Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC). METHODS Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo. RESULTS We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy. CONCLUSION MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.BACKGROUND Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients. METHODS Expression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice. RESULTS We found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-β-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM. CONCLUSIONS These findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.BACKGROUND Spread of malaria and antimalarial resistance through human movement present major threats to current goals to eliminate the disease. Bordering the Greater Mekong Subregion, southeast Bangladesh is a potentially important route of spread to India and beyond, but information on travel patterns in this area are lacking. METHODS Using a standardised short survey tool, 2090 patients with malaria were interviewed at 57 study sites in 2015-2016 about their demographics and travel patterns in the preceding 2 months. RESULTS Most travel was in the south of the study region between Cox’s Bazar district (coastal region) to forested areas in Bandarban (31% by days and 45% by nights), forming a source-sink route. Less than 1% of travel reported was between the north and south forested areas of the study area. Farmers (21%) and students (19%) were the top two occupations recorded, with 67 and 47% reporting travel to the forest respectively. Males aged 25-49 years accounted for 43% of cases visiting forests but only 24% of the study population. Children did not travel. Women, forest dwellers and farmers did not travel beyond union boundaries. Military personnel travelled the furthest especially to remote forested areas. CONCLUSIONS The approach demonstrated here provides a framework for identifying key traveller groups and their origins and destinations of travel in combination with knowledge of local epidemiology to inform malaria control and elimination efforts. Working with the NMEP, the findings were used to derive a set of policy recommendations to guide targeting of interventions for elimination.BACKGROUND Timor Leste has made remarkable progress from malaria control to malaria elimination in a span of 10 years during which organized malaria control efforts were instituted. The good practices and possible factors that have contributed to the remarkable transition from malaria control to elimination in a newly independent country devastated by civil unrest which left the entire administrative structure including the health sector in a disrupted non-functional state are highlighted. METHODS Data from the National Malaria Control Programme were reviewed. A literature search was carried out using the key words „malaria”, „Timor Leste”, „East Timor”, and „malaria control” and „malaria elimination”. All relevant manuscripts and reports that were identified in the search were reviewed. Key personnel of the NMCP, WHO and the GFATM involved in the project were interviewed. RESULTS With the setting up of the National Malaria Control Programme just after independence in 2003 with two officers, the programme expmme within an evolving health system helped the transition from malaria control to malaria elimination. CONCLUSION Universal access to quality assured malaria diagnosis and treatment and focussed vector control, implemented throughout the country in an organized manner with adequate funding and political commitment were key to the successful interruption of malaria transmission in the country. All the practices or factors listed did not work in isolation but rather synergistically in an integrated manner. Malaria elimination is possible even in tropical areas of South and Southeast Asia.BACKGROUND Dyslipidemia often concurs with hyperuricemia. Our study was to discover different lipid levels of gout and asymptomatic hyperuricemia and the predictors of sUA (serum uric acid) levels. METHODS A cross-sectional study was performed to collect demographic, clinical variables, comorbidities and laboratory testing in patients with gout and asymptomatic hyperuricemia. Group comparison was performed with Student’s t-test or Mann Whitney U test for continuous variables and chi-squared tests for categorical variables (Fisher’s exact test where appropriate) and to screen potential risk factors. Correlation of sUA levels with demographic and biochemical variables were performed by using correlation analysis. The variable with s p-value less than 0.20 during the group comparison or clinical relevance was introduced into the stepwise multiple regression model. RESULTS Six hundred fifty-three patients with gout and 63 patients with asymptomatic hyperuricemia (> 420 μmol/L in male and > 360 μmol/L in female) w= 0.534, p  less then  0.001) were predictors of sUA levels in gout patients (adjusted R2 = 28.7%). CONCLUSIONS Dyslipidemia is more commonly seen in patients with gout, compared to asymptomatic hyperuricemia. HDL-C is a protective predictor of sUA levels in gout.BACKGROUND Evidence of causal relationship between mortality of older adults and low- concentration PM2.5 remains limited. OBJECTIVES This study investigates the effects of low-concentration PM2.5 on the mortality of adults older than 65 using the closure of coal-fired power plants in the Eastern United States as a natural experiment. METHODS We investigated power plants in the Eastern United States (US) that had production changes through unit shutdown or plant retirement between 1999 and 2013. We included only non-clustered power plants without scrubbers and with capacities greater than 50 MW. We used instrumental variable (IV) and difference-in-differences (DID) approaches to estimate the causal impact of PM2.5 concentrations on mortality among Medicare beneficiaries. We compared changes in monthly age-adjusted mortality before and after the retirement of coal-fired plants between the treated and control counties; we accounted for annual wind direction in our selection of treated and control counties. In t0 (or 3.6%) in treated counties relative to control counties. The mortality effects were higher among males than females and its impact was the greatest among people older than 75 years. CONCLUSION These findings provide evidence of the effectiveness of local, plant-level control measures in reducing near-plant PM2.5 and mortality among U.S. Medicare beneficiaries.BACKGROUND Transplant recipients are chronically ill patients, who require lifelong follow-up to manage co-morbidities and prevent graft loss. This necessitates a system of care that is congruent with the Chronic Care Model. The eleven-item self-report Patient Assessment of Chronic Illness Care (PACIC) scale assesses whether chronic care is congruent with the Chronic Care Model, yet its validity for heart transplant patients has not been tested. METHODS We tested the validity of the English version of the PACIC, and compared the similarity of the internal structure of the PACIC across English-speaking countries (USA, Canada, Australia and United Kingdom) and across six languages (French, German, Dutch, Spanish, Italian and Portuguese). This was done using data from the cross-sectional international BRIGHT study that included 1378 heart transplant patients from eleven countries across 4 continents. To test the validity of the instrument, confirmatory factor analyses to check the expected unidimensional internal structure, and relations to other variables, were performed. RESULTS Main analyses confirmed the validity of the English PACIC version for heart transplant patients. Exploratory analyses across English-speaking countries and languages also confirmed the single factorial dimension, except in Italian and Spanish. CONCLUSION This scale could help healthcare providers monitor level of chronic illness management and improve transplantation care. TRIAL REGISTRATION Clinicaltrials.gov ID NCT01608477, first patient enrolled in March 2012, registered retrospectively May 30, 2012.

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