Cause Of Death In Individuals Research Articles

CDK12 orchestrates super-enhancer-associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer.

BackgroundHepatic metastasis is the primary and direct cause of death in individuals with colorectal cancer (CRC) attribute to lack of effective therapeutic targets. The present study aimed to identify potential druggable candidate targets for patients with liver metastatic CRC.MethodsThe transcriptional profiles of super‐enhancers (SEs) in primary and liver metastatic CRC were evaluated in publicly accessible CRC datasets. Immunohistochemistry of human CRC tissues was conducted to determine the expression level of CDK12. Cellular proliferation, survival and stemness were examined upon CDK12 inhibition by shCDK12 or a selective CDK12 inhibitor named SR‐4835 with multiple in vitro and in vivo assays. RNA sequencing and bioinformatics analyses were carried out to investigate the mechanisms of CDK12 inhibition in CRC cells.ResultsWe identified CDK12 as a driver gene for direct hepatic metastasis in CRC. Suppression of CDK12 led to robust inhibition of proliferation, survival and stemness. Mechanistically, CDK12 intervention preferentially repressed the transcription of SE‐associated genes. Integration of the SE landscape and RNA sequencing, BCL2L1 and CCDC137 were identified as SE‐associated oncogenic genes to strengthen the abilities of cellular survival, proliferation and stemness, eventually increasing liver metastasis of CRC.ConclusionsOur data highlight the potential of CDK12 and SE‐associated oncogenic transcripts as therapeutic targets for patients with liver metastatic CRC.

Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk. Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (∼76014 cases and ∼264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018). ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.

Effect of healthy lifestyle index and lifestyle patterns on the risk of mortality: A community-based cohort study

BackgroundLimited evidence was available on the association of the integrated effect of multidimensional lifestyle factors with mortality among Chinese populations. This cohort study was to examine the effect of combined lifestyle factors on the risk of mortality by highlighting the number of healthy lifestyles and their overall effects.MethodsA total of 11,395 participants from the Guangzhou Heart Study (GZHS) were followed up until 1 January 2020. Individual causes of death were obtained from the platform of the National Death Registry of China. The healthy lifestyle index (HLI) was established from seven dimensions of lifestyle, and lifestyle patterns were extracted from eight dimensions of lifestyle using principal component analysis (PCA). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard regression model.ResultsDuring 35,837 person-years of follow-up, 184 deaths (1.61%) were observed, including 64 from cardiovascular disease. After adjustment for confounders, HLI was associated with a 50% (HR: 0.50, 95% CI: 0.25–0.99) reduced risk of all-cause mortality when comparing the high (6–7 lifestyle factors) with low (0–2 lifestyle factors) categories. Three lifestyle patterns were defined and labeled as pattern I, II, and III. Lifestyle pattern II with higher factor loadings of non-smoking and low-level alcohol drinking was associated with a decreased risk of all-cause mortality (HR: 0.63, 95% CI: 0.43–0.92, P–trend = 0.023) when comparing the high with low tertiles of pattern score, after adjustment for confounders. Every 1-unit increment of pattern II score was associated with a decreased risk (HR: 0.97, 95% CI: 0.95–0.99) of all-cause mortality. The other two patterns were not associated with all-cause mortality, and the association of cardiovascular mortality risk was observed with neither HLI nor any lifestyle pattern.ConclusionThe results suggest that the more dimensions of the healthy lifestyle the lower the risk of death, and adherence to the lifestyle pattern characterized with heavier loading of non-smoking and low-level alcohol drinking reduces the risk of all-cause mortality. The findings highlight the need to consider multi-dimensional lifestyles rather than one when developing health promotion strategies.

Applications of cardiac biomarkers in chronic kidney disease.

Cardiovascular disease is the leading cause of death in individuals with chronic kidney disease (CKD). The mechanisms connecting CKD and cardiovascular disease are complex, and serum biomarkers can help improve our understanding. Nt-proBNP and troponin have documented success as biomarkers to diagnose and provide mechanistic insights in non-CKD populations. The purpose of this review is to summarize evidence suggesting efficacy and potential for clinical application of Nt-proBNP and troponin in individuals with CKD. Our understanding of how Nt-proBNP and Troponin should be interpreted in those with CKD is evolving. Although both biomarkers are in part cleared by the kidney, elevated levels predominantly reflect cardiovascular disease. Both Nt-proBNP and troponin are associated with risk for future cardiovascular events in CKD. Determining CKD-specific cutoffs and using biomarkers to guide therapy remains under active investigation. Of the many serum biomarkers under investigation, Nt-proBNP and troponin best meet the criteria for effective biomarkers in CKD. Assays are widely available and proven to be accurate in CKD populations. Nt-proBNP and troponin deserve special focus in ongoing research of cardiovascular risk reduction in CKD, especially to identify patients at the highest risk, suggest targetable mechanisms and assess treatment efficacy.

The role of activator protein-1 (AP-1) transcription factors in diabetes associated atherosclerosis

Background and Aims : Atherosclerotic cardiovascular disease is the leading cause of death in individuals with diabetes. Endothelial activation and foam cell formation are crucial steps in the plaque development. Diabetes and blood flow-mediated shear stress are independent risk factors. Regions of turbulent blood flow where the blood flow represents low shear stress such as arterial bends are known to develop atherosclerosis. However, the mechanisms linking diabetes and shear stress to the atherosclerosis are not known.

What was Killing Babies in Ipswich Between 1872 and 1909?

This paper examines the causes of infant mortality for the port town of Ipswich between 1872 and 1909. Ipswich is the only town in England for which a complete run of computer-readable, individual-level causes of death are available in the late 19th and early 20th century. Our work makes use of the ICD10h coding system being developed to contribute to two projects: Digitising Scotland (University of Edinburgh) and SHiP — Studying the history of Health in Port Cities (Radboud University, Nijmegen). We consider annual and quinquennial mortality rates amongst Ipswich's youngest residents by age, sex, seasonality and cause. The individual causes of death not only offer insight into conditions in the town, but also highlight questions concerning how best to interpret the information provided when both medical terminology and registration practices were changing over the decades of the study. Ipswich infant mortality rates very closely mirrored those of England as a whole, rather than the most unhealthy large cities, such as Liverpool or Manchester. It becomes clear that birth itself was a major cause of neonatal, even some post-neonatal, deaths. While water-food borne diseases killed large numbers in the summer months, it was the ever-present airborne diseases which carried off a greater number of small victims. Although the records offer a rich vein of data to explore, some causes of death, such as convulsions and teething, remain enigmatic and require further research.

Association of Habitual Physical Activity With the Risk of All-Cause Mortality Among Chinese Adults: A Prospective Cohort Study.

ObjectiveThis study was conducted to evaluate the association of the risk of all-cause mortality with habitual physical activity (HPA) and its different domains among Chinese adults.MethodsA total of 11,994 participants from the Guangzhou Heart Study were followed up until 1 January 2020. Information on HPA, including leisure-time physical activity (LTPA) and commute activity, was collected using a modified Global Physical Activity Questionnaire. Individual cause of death was obtained from the National Death Registry of China. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for covariates.ResultsDuring 37,715 person-years of follow-up, 208 deaths (1.73%) were observed. When compared with the highest with the lowest exposure tertiles, HPA and LTPA were associated with 34% (HR: 0.66, 95% CI: 0.46–0.95) and 30% (HR: 0.70, 95% CI: 0.49–0.99) reduced risk of all-cause mortality after adjustment for covariates. Commute activity was not associated with mortality risk. For the specific component of LTPA, we found that every 1 MET-h/week increment of the housework was associated with a 1% (HR: 0.99, 95% CI: 0.98–0.99) decreased mortality risk, and performing brisk walking/health exercises/Yangko was associated with a 46% reduced mortality risk (HR: 0.54, 95% CI: 0.29–0.99).ConclusionThis study suggests that a higher level of HPA and LTPA was associated with a lower risk of all-cause mortality. Our findings suggest people to perform HPA, especially LTPA, as a strategy for mortality reduction and health promotion.

Mortality burden attributable to high and low ambient temperatures in China and its provinces: Results from the Global Burden of Disease Study 2019

SummaryBackgroundNon-optimal temperatures are associated with mortality risk, yet the heterogeneity of temperature-attributable mortality burden across subnational regions in a country was rarely investigated. We estimated the mortality burden related to non-optimal temperatures across all provinces in China in 2019.MethodsThe global daily temperature data were obtained from the ERA5 reanalysis dataset. The daily mortality data and exposure–response curves between daily temperature and mortality for 176 individual causes of death were obtained from the Global Burden of Disease Study 2019 (GBD 2019). We estimated the population attributable fraction (PAF) based on the exposure-response curves, daily gridded temperature, and population. We calculated the cause- and province-specific mortality burden based on PAF and disease burden data from the GBD 2019.FindingsWe estimated that 593·9 (95% UI:498·8, 704·6) thousand deaths were attributable to non-optimal temperatures in China in 2019 (PAF=5·58% [4·93%, 6·28%]), with 580·8 (485·7, 690·1) thousand cold-related deaths and 13·9 (7·7, 23·2) thousand heat-related deaths. The majority of temperature-related deaths were from cardiovascular diseases (399·7 [322·8, 490·4] thousand) and chronic respiratory diseases (177·4 [141·4, 222·3] thousand). The mortality burdens were observed significantly spatial heterogeneity for both high and low temperatures. For instance, the age-standardized death rates (per 100 000) attributable to low temperature were higher in Western China, with the highest in Tibet (113·7 [82·0, 155·5]), while for high temperature, they were greater in Xinjiang (1·8 [0·7, 3·3]) and Central-Southern China such as Hainan (2·5 [0·9, 5·4]). We also observed considerable geographical variation in the temperature-related mortality burden by causes of death at provincial level.InterpretationA substantial mortality burden was attributable to non-optimal temperatures across China, and cold effects dominated the total mortality burden in all provinces. Both cold- and heat-related mortality burden showed significantly spatial variations across China.FundingNational Key Research and Development Program.

Prevention and monitoring of metabolic syndrome in patients with severe mental ilness - presentation of our study protocol

IntroductionCardiovascular diseases are the leading cause of death in individuals with SMI. The sedentary lifestyle that usually guides these individuals associated with the use of some psychotropic drugs increases the risk of adverse events related to these pathologiesObjectivesPresentation of the Study Protocol for the Implementation of a Psychoeducational Group directed to Prevention and Monitoring Metabolic Syndrome (MS) in patients with SMIMethodsIt is intended to implement a psychoeducational program, which includes a 30-minute walk, focused on healthy lifestyle habits, for 16 weeks.It is intended to include SMI individuals, from a convenience sample, who present any of these criteria: Excess weight; At risk or diagnosed with DM; Sedentary lifestyle; Smoker. Data regarding socio-demographic, clinical and motivational for and about physical activity will be collected from the intervention group. Patients who refuse to join the study will only receive information about lifestyle changes at the beginning and will continue with their usual care.ResultsAccording to available literature, it is expected that the monitoring and control of these parameters will translate into a benefit in reducing cardiovascular risk factors and optimizing the treatment of MS, contributing to the empowerment of patients in managing their disease and increasing their quality and years of life.ConclusionsThe impact of lifestyle changes proved to be effective and are sometimes lasting, with objective gains in quality of life of these patients. The main measure to face this issue, improve the well-being and physical health of these individuals, is to reduce weight and increase baseline physical activity.DisclosureNo significant relationships.

Sex Differences and Cardiovascular Diseases in Down Syndrome

Congenital heart disease and cardiovascular disease are the leading causes of death for individuals with Down Syndrome (Ds) (Zhu, J.L., et al, 2013). A systematic review was conducted in June 2021 to address the research question “Are there reported sex differences for cardiovascular disease and cardiovascular physiological function in Ds”. Since there are significant sex differences in the risk of congenital heart and cerebrovascular disease in the general population, we hypothesized that these differences are present in the Ds population. Four domains were developed: congenital heart disease, baseline physiology and risk factors, heart disease and hypertension, and cerebrovascular disease. Exclusion criteria were applied to identify studies that addressed sex differences. The systematic review shows that women with Ds have a higher rate of congenital heart disease, coronary and cerebrovascular events and Moyamoya. Following the systematic review, a retrospective medical chart review of the University of Iowa Hospitals and Clinics was conducted using the platform TriNetX to identify the incidence of congenital and cardiovascular diseases in males and females. Relative risk was computed comparing Ds to general patient counts as well as men and women within each population. Ds patients did not share most of the sex differences in risk factors observed in the general population, however there are important sex differences in each domain that may contribute to earlier mortality in women with Ds. Several studies report women have an increased probability of developing risk factors for cardiovascular disease, such as obesity. Therefore, future research to understand the mechanism underlying these sex differences is necessary.ReferencesZhu, J.L., et al., Survival among people with Down syndrome: a nationwide population‐basedstudy in Denmark. Genetics in Medicine, 2013. 15(1): p. 64‐69.

Clinical and biochemical profile of COVID-19 patients admitted in a tertiary care hospital in Visakhapatnam, India during post unlock 2.0 - a retrospective study.

There have been more than 31378143 confirmed coronavirus disease 2019 (COVID-19) cases in India. It was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Because the risk of severe COVID-19 is not consistent across all individuals, uncertainty is linked to disease development. COVID-19 results have been related to systemic inflammation as a predictor. In COVID-19, increased levels of inflammatory markers have been associated with cytokine storm, coagulopathy, and endothelial dysfunction. A significant amount of research suggests that these results have a role in the cause of death in individuals suffering from a severe form of COVID-19. We aim to show our experience of COVID-19 at GITAM Institute of Medical Sciences and Research (GIMSR), Visakhapatnam. We analyzed data on 558 patients admitted to our dedicated COVID hospital during post unlock (UL) 2.0 in India from August 2 to August 31, 2020. The mean age was 43.65 years; 69% of them were male. Using MoHFW India severity guidelines, 68.10% were mild, 18.64% were moderate, and 13.26% were severe cases. Fatigue (66.13%) was the most common complaint, followed by anosmia (63.80%), fever (57.53%), diarrhea (56.09%), shortness of breath (22.40%), and others. The most common preexisting comorbidity seen in our patients was diabetes mellitus and hypertension, respectively. Laboratory parameters revealed mean hemoglobin of 13.04±1.91 gm/dl, mean total leukocyte count of 7378.49±3229 cells/cumm, mean platelet count of 2.3±0.8 lakhs/cumm, mean erythrocyte sediment rate of 40±30 mm/hr, mean ferritin level of 335.96 ng/ml, mean D-dimer level of 794.88 ng/ml and mean CRP of 23.27 mg/l. Severity was associated with higher age, symptomatic presentation, elevated leucocytes, and elevated inflammatory markers.

ВЛИЯНИЕ ОСНОВНЫХ ПРИЧИН СМЕРТНОСТИ НА ОЖИДАЕМУЮ ПРОДОЛЖИТЕЛЬНОСТЬ ЖИЗНИ НАСЕЛЕНИЯ ИРКУТСКОЙ ОБЛАСТИ

Significance. The study on life expectancy of the population and its impact on the indicator of the leading causes of death is an important stage in the assessment and forecasting of socio-economic processes in individual administrative-territorial entities. Analysis of the dynamics in the indicator of average life expectancy provides the necessary information for developing an evidence-based demographic policy in the subject of the Russian Federation. Purpose of the study: to identify and explore the potential for increasing average life expectancy in the Irkutsk region. Material and methods. A continuous method was used to observe deaths by sex, age group, cause of death for 2005, 2010, 2019 in the Irkutsk region. We used methodology that included the indirect method of constructing tables of average life expectancy (ALE) or survival tables. We determined intensive indicators of mortality by class of causes and by individual nosological form. Based on the decomposition method we carried out calculations of ALE and the elimination reserve of the number of years of increase in life, subject to a 50% decrease in mortality rate with regard to classes 2,9,20 of the International Classification of Diseases No. 10 revision. Results. Dynamics in life expectancy among male and female population demonstrate the following: increase in life expectancy at birth among males equals to 6.6 years, and 4.2 years in females. Accordingly, the gap in life expectancy between women and men has narrowed from 14.2 years to 11.8 years. Assessment of the contribution of individual causes of death to the overall mortality and life expectancy among males and females shows that the following three classes play the leading role: diseases of the circulatory system, neoplasms, and external causes of death. Calculation of the demographic gain (elimination reserve) shows that the class of diseases of diseases of the circulatory system is of highest significance for increasing life expectancy, while control over cerebrovascular diseases and acute myocardial infarction makes the highest contribution to increasing life expectance in the Irkutsk region Conclusion. The presented results made it possible to study age and gender characteristics of the most important demographic indicator of average life expectancy in male and female population. They are an important component in the development and substantiation of scientific programs aimed at improving demographic situation in the region.

Determining causes of death among individuals with haemophilia in Afghanistan.

Haemophilia is a well-known bleeding disorder that affects people worldwide. The main therapeutic strategy is regular infusion of exogenous factor VIII to ensure an optimal haemostatic standard. Morbidity and mortality of individuals with haemophilia has decreased in developing countries due to improvement in early detection, advanced treatments, and comprehensive population outreach efforts. However, individuals with bleeding disorders in developing countries like Afghanistan do not have access to such therapeutic facilities. The goals of this study were to determine the causes of death and findings related to death among in individuals with bleeding disorders in Afghanistan. This study conducted as a retrospective cross-sectional study of 387 individuals with bleeding disorders (mainly haemophilia) in Afghanistan. All registered individuals with bleeding disorders in Afghanistan were interviewed by telephone. Among the 387 individuals with bleeding disorders, there were 136 deaths. Most deaths occurred in individuals aged 1-15 years (66.2%). Intracranial haemorrhage was the leading cause of death in individuals with haemophilia A and B. These findings revealed that supply of coagulation factor concentrates, facilities for haemostasis diagnosis, and trained haematologists is inadequate in Afghanistan.

Small Extracellular Vesicles Propagate the Inflammatory Response After Trauma.

Trauma is the leading cause of death in individuals under 44 years of age. Thorax trauma (TxT) is strongly associated with trauma‐related death, an unbalanced innate immune response, sepsis, acute respiratory distress syndrome, and multiple organ dysfunction. It is shown that different in vivo traumata, such as TxT or an in vitro polytrauma cytokine cocktail trigger secretion of small extracellular nanovesicles (sEVs) from endothelial cells with pro‐inflammatory cargo. These sEVs transfer transcripts for ICAM‐1, VCAM‐1, E‐selectin, and cytokines to systemically activate the endothelium, facilitate neutrophil‐endothelium interactions, and destabilize barrier integrity. Inhibition of sEV‐release after TxT in mice ameliorates local as well as systemic inflammation, neutrophil infiltration, and distant organ damage in kidneys (acute kidney injury, AKI). Vice versa, injection of TxT‐plasma‐sEVs into healthy animals is sufficient to trigger pulmonary and systemic inflammation as well as AKI. Accordingly, increased sEV concentrations and transfer of similar cargos are observed in polytrauma patients, suggesting a fundamental pathophysiological mechanism.

Risk stratification in patients with Brugada syndrome: the role of the late potentials evaluated by signal-averaged ECG

Abstract Introduction Brugada syndrome (BS) is a relevant cause of sudden death in individuals without structural heart disease. The accuracy of the available methods for risk stratification is very limited and the investigation of new methodologies to improve the identification of patients at risk is under intensive investigation. Recently the pathophysiological relevance of anomalous, fragmented and prolonged electrograms on the epicardial surface of the right ventricular outflow tract (RVOT) has been described. Therefore, the study of signal-averaged ECG (SA-ECG) has become attractive since it may allow the non-invasive evaluation of these electrical anomalies. In order to maximize the detection capacity and to focus the evaluation in the RVOT, we developed an alternative methodology of electrode positioning directed to this area of interest. Purpose To characterize the study of late potentials (LP) by SA-ECG in patients with SB and to evaluate its association with the occurrence of arrhythmia events. Methods Prospective single centre study of patients (pts) with BS. LP were evaluated by SA-ECG with determination of the total filtered QRS duration (fQRS), root mean square voltage of the 40 ms terminal portion of the QRS (RMS40) and duration of the low amplitude electric potential component (40 microV) of the terminal portion of the QRS (LAS40) in conventional and modified leads (addressed to RVOT). The association of LP with the risk of definite malignant dysrhythmias due to sudden death, ventricular fibrillation, ventricular tachycardia or appropriate shock of the implantable cardioverter defibrillator (ICD) was evaluated and the acuity of the prognostic stratification was determined by the area under the receiver operator characteristic curve (ROC). Results A total of 76 pts (69.7% men, age 48±12 years) were studied, of which 33 had a spontaneous type 1 pattern and 43 had a type 1 pattern induced by flecainide. During a median follow-up of 1.6 years, 13 pts (17.1%) had symptoms potentially related to BS and 6 (10.5%) had malignant arrhythmias [including two pts who suffered sudden death (2.6%). The pts who had malignant dysrhythmias presented higher values of fQRS (125±23 vs. 108±18, p=0.046) and LAS40 (54±13 vs. 40±11, p=0.014), and lower values of RMS40 only in the modified leads (11±5 vs. 22±19, p=0.041). The parameters of the SA-ECG were significant prognostic predictors. The acuity of each of the parameteres alone was moderate and the parameters that were identified as more powerful predictors of risk were those derived from the modified leads (Figure). Conclusion The LP evaluated by SA-ECG may be relevant in the prognostic stratification of patients with BS, since it seems to be associated with the risk of malignant ventricular arrhythmias. Funding Acknowledgement Type of funding sources: None.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality

Objectives Suicide is the fourth leading cause of death for individuals aged 15–29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. Methods Sixty-four college students with high suicidal ideation (aged 18–30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. Results Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. Conclusions BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Unsound sleep, wound-up mind: a longitudinal examination of acute suicidal affective disturbance features among an eating disorder sample.

Suicide is one of the most commonly reported causes of death in individuals with eating disorders. However, the mechanisms underlying the suicide and disordered eating link are largely unknown, and current assessments are still unable to accurately predict future suicidal thoughts and behaviors. The purpose of this study is to test the utility of two promising proximal risk factors, sleep quality and agitation, in predicting suicidal ideation in a sample of individuals with elevated suicidal thoughts and behaviors, namely those with eating disorders. Women (N = 97) receiving treatment at an eating disorder treatment center completed weekly questionnaires assessing suicidal ideation, agitation, and sleep. General linear mixed models examined whether agitation and/or sleep quality were concurrently or prospectively associated with suicidal ideation across 12 weeks of treatment. There was a significant interaction between within-person agitation and sleep quality on suicidal ideation [B(s.e.) = -0.02(0.01), p < 0.05], such that on weeks when an individual experienced both higher than their average agitation and lower than their average sleep quality, they also experienced their highest levels of suicidal ideation. However, neither agitation nor sleep quality prospectively predicted suicidal ideation. This study was the first to examine dynamic associations between interpersonal constructs and suicidal ideation in individuals with eating disorders. Results suggest that ongoing assessment for overarousal symptoms, such as agitation and poor sleep quality, in individuals with eating disorders may be warranted in order to manage suicidal ideation among this vulnerable population.

Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study

SummaryBackgroundAssociations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure.MethodsIn part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure–response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990–2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws.FindingsWe included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10–8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1–1·4) in Brazil to 35·1 deaths (29·9–40·3) per 100 000 and a PAF of 4·7% (4·3–5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9–4·7) and attributable rates of 32·0 deaths (27·2–36·8) per 100 000 and in New Zealand with 3·4% (2·9–3·9) and 26·4 deaths (22·1–30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3–0·6) and attributable rates of 3·25 deaths (2·39–4·24) per 100 000 and in Brazil with 0·4% (0·3–0·5) and 2·71 deaths (2·15–3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52–1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia.InterpretationAcute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health.FundingBill & Melinda Gates Foundation.

PDL1-positive exosomes suppress antitumor immunity by inducing tumor-specific CD8+ T cell exhaustion during metastasis.

Metastasis is the main cause of death in individuals with cancer. Immune checkpoint blockade (ICB) can potentially reverse CD8+ cytotoxic T lymphocytes (CTLs) dysfunction, leading to significant remission in multiple cancers. However, the mechanism underlying the development of CTL exhaustion during metastatic progression remains unclear. Here, we established an experimental pulmonary metastasis model with melanoma cells and discovered a critical role for melanoma‐released exosomes in metastasis. Using genetic knockdown of nSMase2 and Rab27a, 2 key enzymes for exosome secretion, we showed that high levels of effector‐like tumor‐specific CD8+ T cells with transitory exhaustion, instead of terminal exhaustion, were observed in mice without exosomes; these cells showed limited inhibitory receptors and strong proliferation and cytotoxicity. Mechanistically, the immunosuppression of exosomes depends on exogenous PD‐L1, which can be largely rescued by pretreatment with antibody blockade. Notably, we also found that exosomal PD‐L1 acts as a promising predictive biomarker for ICB therapies during metastasis. Together, our findings suggest that exosomal PD‐L1 may be a potential immunotherapy target, suggesting a new curative therapy for tumor metastasis.

Management of solid organ injury in patient of blunt abdominal trauma

Background: In this ongoing era of 21st century, trauma is the leading cause of death in individuals between age 1 and 44. In trauma, also road traffic accidents (RTAs) are the major cause of death. Blunt abdominal trauma is a frequent emergency and is associated with significant morbidity and mortality.Methods: A prospective analysis of 50 patients of blunt abdominal trauma admitted in SMIMER hospital Surat within a span of 12 months was done. Unstable patients with initial resuscitation underwent focused assessment sonography for trauma (FAST). Failed resuscitation with free fluid in abdomen confirmed by FAST immediately shifted to operation theatre for laparotomy and proceed. Hemodynamically stable patients underwent computerized tomography of abdomen.Results: Most of the patients in our study were in the age group of 21-45 years with M:F ratio of 4:1. RTAs (62%) was the most common mechanism of injury. Spleen (38%) was the commonest organ injured and the most common surgery performed was splenectomy. In total non-operative management (NOM) was done in 58% of cases and surgical management was done in 42% of cases.Conclusions: Appropriate patient selection, early diagnosis and repeated clinical examination and use of appropriate investigations forms the key in management of blunt abdominal trauma. To conclude, initial resuscitation measures and correct diagnosis forms the most vital part of blunt abdominal trauma management.