Mortality risk and burden of aortic aneurysm and dissection attributable to low temperatures: A nationwide case-crossover analysis in Brazil, a predominantly tropical country.

BACKGROUND: Low temperatures are adverse contributors to cardiovascular diseases, but the associations between short-term exposure to cold and the risk of death from aortic dissection and aneurysm remain unclear, particularly in tropical regions. OBJECTIVE: This study was conducted based on 123,951 records of deaths caused by aortic dissection and aneurysms extracted from the national Mortality Information System in Brazil between 2000 and 2019. METHODS: Relative risks and 95 % confidence intervals (CI) for the aortic-related deaths associated with low ambient temperatures were estimated using the conditional logistic model combined with the distributed lag nonlinear model. Subgroup analyses were performed by age group, sex, race, education level, and residential region. Furthermore, this study calculated the number and fraction of aortic-related deaths attributed to temperatures below the temperature threshold to quantify the cold-related mortality burden of aortic diseases. RESULTS: During the study period, aortic-related deaths and mortality rates in Brazil exhibited a steady increase, rising from 4419 (2.66/100,000) in 2000 to 8152 (3.88/100,000) in 2019. Under the identified temperature threshold (26 °C), per 1 °C decrease in daily mean temperature was associated with a 4.77 % (95 % CI: 4.35, 5.19) increase in mortality risk of aortic-related diseases over lag 0-3 days. Females, individuals aged 50 years or older, Asian and Black race, and northern residents were more susceptible to low temperatures. Low temperatures were responsible for 19.10 % (95 % CI: 17.71, 20.45) of aortic-related deaths in Brazil. CONCLUSION: This study highlights that low temperatures were associated with an increased risk of aortic-related deaths, with a remarkable burden even in this predominantly tropical country.

SIRT1 is transcriptionally repressed by YY1 and suppresses ferroptosis in rheumatoid arthritis

Abstract Background Sirtuin 1 (SIRT1) is reported downregulated in rheumatoid arthritis (RA), and the protective effects of SIRT1 on tissue damage and organ failure may be related to cellular ferroptosis. However, the exact mechanism by which SIRT1 regulates RA remains unclear. Methods Quantitative real-time PCR (qPCR) and western blot assays were performed to explore the expressions of SIRT1 and Yin Yang 1 (YY1). CCK-8 assay was used for cytoactive detection. The interaction between SIRT1 and YY1 was validated by dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). DCFH-DA assay and iron assay were applied to detect the reactive oxygen species (ROS) and iron ion levels. Results In the serum of RA patients, SIRT1 was downregulated, but YY1 was upregulated. In LPS-induced synoviocytes, SIRT1 could increase cell viability and decrease ROS and iron levels. Mechanistically, YY1 downregulated the expression of SIRT1 by inhibiting its transcription. YY1 overexpression partly revised the effects of SIRT1 on ferroptosis in synoviocytes. Conclusion SIRT1 is transcriptionally repressed by YY1 and inhibits the ferroptosis of synoviocytes induced by LPS, so as to relieve the pathological process of RA. Therefore, SIRT1 might be a new diagnosis and therapeutic target of RA. Highlights Combining SIRT1 with synoviocytes ferroptosis in rheumatoid arthritis for the first time. The transcription factor YY1 combined to the SIRT1 promoter in synovial cells and inhibited its expression and functional roles. The inhibition of SIRT1 with YY1 decreased the ferroptosis in synoviocytes.

Analysis of the role of the interleukins in colon cancer.

BACKGROUND: The role of interleukin family in colon cancer remained controversial. The purpose of this study was to investigate the association between interleukin family and colon cancer progression through bioinformatics methods and to validate such association in clinical patients. METHODS: A total of 15 differentially expressed interleukins between the colon cancer tissue and normal colon tissue were evaluated from the Cancer Genome Atlas (TCGA) database with R software and only interleukin-7 (IL-7) was significantly associated with survival. The signaling pathway associated with IL-7 was then investigated using gene enrichment analysis. In addition, subsets of TNM were analyzed in detail and univariate and multivariate COX regression analysis were conducted. Finally, we performed western blotting, immunohistochemistry, cell proliferation and cell apoptosis analysis to examine the expression of IL-7 in patients with intestinal cancer. RESULTS: The study demonstrated that IL-7 could inhibit the progression of colon cancer. In addition, IL-7 was found to be associated with overall survival (OS) and pathological stage. Further analysis of IL-7 expression with clinical data indicated that IL-7 was a key factor in inhibiting colon cancer progression. CONCLUSION: IL-7 was a key factor in inhibiting the progression of colon cancer and was closely related to overall survival.

Analysis of the role of the interleukins in colon cancer

BACKGROUND: The role of interleukin family in colon cancer remained controversial. The purpose of this study was to investigate the association between interleukin family and colon cancer progression through bioinformatics methods and to validate such association in clinical patients. METHODS: A total of 15 differentially expressed interleukins between the colon cancer tissue and normal colon tissue were evaluated from the Cancer Genome Atlas (TCGA) database with R software and only interleukin-7 (IL-7) was significantly associated with survival. The signaling pathway associated with IL-7 was then investigated using gene enrichment analysis. In addition, subsets of TNM were analyzed in detail and univariate and multivariate COX regression analysis were conducted. Finally, we performed western blotting, immunohistochemistry, cell proliferation and cell apoptosis analysis to examine the expression of IL-7 in patients with intestinal cancer. RESULTS: The study demonstrated that IL-7 could inhibit the progression of colon cancer. In addition, IL-7 was found to be associated with overall survival (OS) and pathological stage. Further analysis of IL-7 expression with clinical data indicated that IL-7 was a key factor in inhibiting colon cancer progression. CONCLUSION: IL-7 was a key factor in inhibiting the progression of colon cancer and was closely related to overall survival.

The Economic Model of Retinopathy of Prematurity (EcROP) Screening and Treatment: Mexico and the United States.

PURPOSE: To describe an economic (Ec) model for estimating the impact of screening and treatment for retinopathy of prematurity (ROP). DESIGN: EcROP is a cost-effectiveness, cost-utility, and cost-benefit analysis. METHODS: We surveyed caregivers of 52 children at schools for the blind or pediatric eye clinics in Atlanta, Georgia and 43 in Mexico City. A decision analytic model with sensitivity analysis determined the incremental cost-effectiveness (primary outcome) and incremental monetary benefit (secondary outcome) of an ideal (100% screening) national ROP program as compared to estimates of current practice. Direct costs included screening and treatment expenditures. Indirect costs estimated lost productivity of caretaker(s) and blind individuals as determined by face-to-face surveys. Utility and effectiveness were measured in quality-adjusted life years and benefit in US dollars. EcROP includes a sensitivity analysis to assesses the incremental cost-effectiveness and societal impact of ROP screening and treatment within a country or economic region. Estimates are based on evidence-based clinical data and region-specific economic data acquired from direct field survey. RESULTS: In both Mexico and the United States, an ideal national ROP screening and treatment program was highly cost-saving. The incremental net benefit of an ideal ROP program over current practice is $5556 per child ($206 574 333 annually) and $3628 per child ($205 906 959 annually) in Mexico and the United States, respectively. CONCLUSION: EcROP demonstrates that ROP screening and treatment is highly beneficial for quality of life, cost saving, and cost-effectiveness in the United States and Mexico. EcROP can be applied to any country or region to provide data for informed allocation of limited health care resources.

The societal burden of blindness secondary to retinopathy of prematurity in Lima, Peru.

PURPOSE: To determine the cost-effectiveness of laser treatment for retinopathy of prematurity (ROP) in Lima, Peru. DESIGN: A cost-of-illness study (in US dollars) to determine the direct cost of treatment, the indirect lifetime cost of blindness, and the quality-adjusted life years. METHODS: The direct cost of ROP-related treatment was determined by reviewing data retrospectively from a social security sector hospital. The indirect cost was determined using national economic data of Peru published by the Central Information Agency (CIA), including the per capita gross domestic product, the sex-adjusted income distribution, and years spent in the work force. Indirect costs per child that were avoided by treatment were calculated using the known natural history of ROP vs evidence-based treatment. RESULTS: For ROP-related neonatal blindness in Peru, we estimate the total indirect cost saving at $197,753 per child and the direct cost of laser treatment at $2496 per child. The societal lifetime cost saving per child is estimated at $195,257. The mean annual income per educated adult in Peru is $8000 and treating 1 child is equivalent to employing 24 educated Peruvians per year. The generational cost savings for society is approximately $516 million, or the equivalent of 64,500 educated Peruvian work years. CONCLUSIONS: The societal burden of blindness far exceeds the costs of treatment per child. Proper screening and treatment of ROP prevents blindness and leads to substantial cost savings for society. Public health policy in Peru and other middle-income countries should consider financial impact when allocating healthcare resources.