Single-Molecule Imaging Reveals Translation of mRNAs Localized to Stress Granules.

Cellular stress leads to reprogramming of mRNA translation and formation of stress granules (SGs), membraneless organelles consisting of mRNA and RNA-binding proteins. Although the function of SGs remains largely unknown, it is widely assumed they contain exclusively non-translating mRNA. Here, we re-examine this hypothesis using single-molecule imaging of mRNA translation in living cells. Although we observe non-translating mRNAs are preferentially recruited to SGs, we find unequivocal evidence that mRNAs localized to SGs can undergo translation. Our data indicate that SG-associated translation is not rare, and the entire translation cycle (initiation, elongation, and termination) can occur on SG-localized transcripts. Furthermore, translating mRNAs can be observed transitioning between the cytosol and SGs without changing their translational status. Together, these results demonstrate that mRNA localization to SGs is compatible with translation and argue against a direct role for SGs in inhibition of protein synthesis.

Single-molecule imaging reveals translation-dependent destabilization of mRNAs.

The relationship between mRNA translation and decay is incompletely understood, with conflicting reports suggesting that translation can either promote decay or stabilize mRNAs. The effect of translation on mRNA decay has mainly been studied using ensemble measurements and global transcription and translation inhibitors, which can have pleiotropic effects. We developed a single-molecule imaging approach to control the translation of a specific transcript that enabled simultaneous measurement of translation and mRNA decay. Our results demonstrate that mRNA translation reduces mRNA stability, and mathematical modeling suggests that this process is dependent on ribosome flux. Furthermore, our results indicate that miRNAs mediate efficient degradation of both translating and non-translating target mRNAs and reveal a predominant role for mRNA degradation in miRNA-mediated regulation. Simultaneous observation of translation and decay of single mRNAs provides a framework to directly study how these processes are interconnected in cells.

Nonlinear control of transcription through enhancer-promoter interactions.

Chromosome structure in mammals is thought to regulate transcription by modulating three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated loops and topologically associating domains (TADs)1-4. However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. Here, to address this question, we use an assay to position an enhancer at large numbers of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. A quantitative analysis of hundreds of cell lines reveals that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship. Mathematical modelling suggests that nonlinearity might arise from transient enhancer-promoter interactions being translated into slower promoter bursting dynamics in individual cells, therefore uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism of how distal enhancers act from large genomic distances, and of how topologically associating domain boundaries block distal enhancers. Finally, we show that enhancer strength also determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation. Our measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.

Single-Molecule Imaging of mRNA Localization and Regulation during the Integrated Stress Response.

Biological phase transitions form membrane-less organelles that generate distinct cellular environments. How molecules are partitioned between these compartments and the surrounding cellular space and the functional consequence of this localization is not well understood. Here, we report the localization of mRNA to stress granules (SGs) and processing bodies (PBs) and its effect on translation and degradation during the integrated stress response. Using single mRNA imaging in living human cells, we find that the interactions of mRNAs with SGs and PBs have different dynamics, very few mRNAs directly move between SGs and PBs, and that specific RNA-binding proteins can anchor mRNAs within these compartments. During recovery from stress, we show that mRNAs that were within SGs and PBs are translated and degraded at similar rates as their cytosolic counterparts. Our work provides a framework for using single-molecule measurements to directly investigate the molecular mechanisms of phase-separated compartments within their cellular environment.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Life Expectancy for White, Black, and Hispanic Race/Ethnicity in U.S. States: Trends and Disparities, 1990 to 2019.

BACKGROUND: Life expectancy (LE) differences within and between states by race/ethnicity have not been examined. OBJECTIVE: To estimate LE for selected race/ethnicity groups in states from 1990 to 2019. DESIGN: Cross-sectional time-series analysis. SETTING: United States. PARTICIPANTS: Deidentified death records and Census data were used to construct regression models with smoothed time series of mortality from 1990 to 2019. MEASUREMENTS: LE at birth, by sex and year, for subgroups of people reporting Hispanic, non-Hispanic Black, or non-Hispanic White race/ethnicity. RESULTS: Disparities in LE across states were 8.0 years for females and 12.2 years for males in 1990 and 7.9 years for females and 7.8 years for males in 2019. When race/ethnicity groups were accounted for, disparities across states were 20.7 years for females and 24.5 years for males in 1990, decreasing to 18.5 years for females and 23.7 years for males in 2019. Disparities across states increased within each race/ethnicity group between 1990 and 2019, with the largest increase for non-Hispanic White males and the smallest for Hispanic females. The disparity between race/ethnicity groups within states decreased for most of the 23 states with estimates for all 3 groups but increased for females in 7 states and males in 5 states. LIMITATION: Because of small sample size, LE was not estimated for 37 of 153 state-race/ethnicity groups. CONCLUSION: Disparity in LE across states was greater when race/ethnicity groups were considered. Disparities across all state-race/ethnicity groups in general have decreased over the past 3 decades. Within each race/ethnicity group, disparities across states have increased. Although racial/ethnic disparities decreased in most of the 23 states for which LE was estimated for all 3 groups, they increased for females in 7 states and males in 5 states. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Trends in State-Level Maternal Mortality by Racial and Ethnic Group in the United States.

Importance: Evidence suggests that maternal mortality has been increasing in the US. Comprehensive estimates do not exist. Long-term trends in maternal mortality ratios (MMRs) for all states by racial and ethnic groups were estimated. Objective: To quantify trends in MMRs (maternal deaths per 100 000 live births) by state for 5 mutually exclusive racial and ethnic groups using a bayesian extension of the generalized linear model network. Design, Setting, and Participants: Observational study using vital registration and census data from 1999 to 2019 in the US. Pregnant or recently pregnant individuals aged 10 to 54 years were included. Main Outcomes and Measures: MMRs. Results: In 2019, MMRs in most states were higher among American Indian and Alaska Native and Black populations than among Asian, Native Hawaiian, or Other Pacific Islander; Hispanic; and White populations. Between 1999 and 2019, observed median state MMRs increased from 14.0 (IQR, 5.7-23.9) to 49.2 (IQR, 14.4-88.0) among the American Indian and Alaska Native population, 26.7 (IQR, 18.3-32.9) to 55.4 (IQR, 31.6-74.5) among the Black population, 9.6 (IQR, 5.7-12.6) to 20.9 (IQR, 12.1-32.8) among the Asian, Native Hawaiian, or Other Pacific Islander population, 9.6 (IQR, 6.9-11.6) to 19.1 (IQR, 11.6-24.9) among the Hispanic population, and 9.4 (IQR, 7.4-11.4) to 26.3 (IQR, 20.3-33.3) among the White population. In each year between 1999 and 2019, the Black population had the highest median state MMR. The American Indian and Alaska Native population had the largest increases in median state MMRs between 1999 and 2019. Since 1999, the median of state MMRs has increased for all racial and ethnic groups in the US and the American Indian and Alaska Native; Asian, Native Hawaiian, or Other Pacific Islander; and Black populations each observed their highest median state MMRs in 2019. Conclusion and Relevance: While maternal mortality remains unacceptably high among all racial and ethnic groups in the US, American Indian and Alaska Native and Black individuals are at increased risk, particularly in several states where these inequities had not been previously highlighted. Median state MMRs for the American Indian and Alaska Native and Asian, Native Hawaiian, or Other Pacific Islander populations continue to increase, even after the adoption of a pregnancy checkbox on death certificates. Median state MMR for the Black population remains the highest in the US. Comprehensive mortality surveillance for all states via vital registration identifies states and racial and ethnic groups with the greatest potential to improve maternal mortality. Maternal mortality persists as a source of worsening disparities in many US states and prevention efforts during this study period appear to have had a limited impact in addressing this health crisis.

Spending on Cardiovascular Disease and Cardiovascular Risk Factors in the United States: 1996 to 2016.

BACKGROUND: Spending on cardiovascular disease and cardiovascular risk factors (cardiovascular spending) accounts for a significant portion of overall US health care spending. Our objective was to describe US adult cardiovascular spending patterns in 2016, changes from 1996 to 2016, and factors associated with changes over time. METHODS: We extracted information on adult cardiovascular spending from the Institute for Health Metrics and Evaluation's disease expenditure project, which combines data on insurance claims, emergency department and ambulatory care visits, inpatient and nursing care facility stays, and drug prescriptions to estimate >85% of all US health care spending. Cardiovascular spending (2016 US dollars) was stratified by age, sex, type of care, payer, and cardiovascular cause. Time trend and decomposition analyses quantified contributions of epidemiology, service price and intensity (spending per unit of utilization, eg, spending per inpatient bed-day), and population growth and aging to the increase in cardiovascular spending from 1996 to 2016. RESULTS: Adult cardiovascular spending increased from $212 billion in 1996 to $320 billion in 2016, a period when the US population increased by >52 million people, and median age increased from 33.2 to 36.9 years. Over this period, public insurance was responsible for the majority of cardiovascular spending (54%), followed by private insurance (37%) and out-of-pocket spending (9%). Health services for ischemic heart disease ($80 billion) and hypertension ($71 billion) led to the most spending in 2016. Increased spending between 1996 and 2016 was primarily driven by treatment of hypertension, hyperlipidemia, and atrial fibrillation/flutter, for which spending rose by $42 billion, $18 billion, and $16 billion, respectively. Increasing service price and intensity alone were associated with a 51%, or $88 billion, cardiovascular spending increase from 1996 to 2016, whereas changes in disease prevalence were associated with a 37%, or $36 billion, spending reduction over the same period, after taking into account population growth and population aging. CONCLUSIONS: US adult cardiovascular spending increased by >$100 billion from 1996 to 2016. Policies tailored to control service price and intensity and preferentially reimburse higher quality care could help counteract future spending increases caused by population aging and growth.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Stroke Among Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry. METHODS: In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death. RESULTS: Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality. CONCLUSIONS: Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.

The enrichment paradox in adaptive radiations: Emergence of predators hinders diversification in resource rich environments.

Adaptive radiations are known for rapid niche diversification in response to ecological opportunity. While most resources usually exist prior to adaptive radiation, novel niches associated with novel resources can be created as a clade diversifies. For example, in African lake cichlid radiations some species prey upon other species of the clade (intraclade consumers). Using a trait-based eco-evolutionary model, we investigate the evolution of intraclade consumers in adaptive radiations and the effect of this novel trophic interaction on the diversification process of the radiating clade. We find that the evolutionary emergence of intraclade consumers halts the diversification processes of other ecomorphs as a result of increased top-down control of density. Because high productivity enables earlier evolution of intraclade consumers, highly productive environments come to harbour less species-rich radiations than comparable radiations in less productive environments. Our results reveal how macroevolutionary and community patterns can emerge from ecological and microevolutionary processes.

The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2020 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, metrics to assess and monitor healthy diets, an enhanced focus on social determinants of health, a focus on the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors, implementation strategies, and implications of the American Heart Association's 2020 Impact Goals. RESULTS: Each of the 26 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

US Health Care Spending by Race and Ethnicity, 2002-2016.

Importance: Measuring health care spending by race and ethnicity is important for understanding patterns in utilization and treatment. Objective: To estimate, identify, and account for differences in health care spending by race and ethnicity from 2002 through 2016 in the US. Design, Setting, and Participants: This exploratory study included data from 7.3 million health system visits, admissions, or prescriptions captured in the Medical Expenditure Panel Survey (2002-2016) and the Medicare Current Beneficiary Survey (2002-2012), which were combined with the insured population and notified case estimates from the National Health Interview Survey (2002; 2016) and health care spending estimates from the Disease Expenditure project (1996-2016). Exposure: Six mutually exclusive self-reported race and ethnicity groups. Main Outcomes and Measures: Total and age-standardized health care spending per person by race and ethnicity for each year from 2002 through 2016 by type of care. Health care spending per notified case by race and ethnicity for key diseases in 2016. Differences in health care spending across race and ethnicity groups were decomposed into differences in utilization rate vs differences in price and intensity of care. Results: In 2016, an estimated $2.4 trillion (95% uncertainty interval [UI], $2.4 trillion-$2.4 trillion) was spent on health care across the 6 types of care included in this study. The estimated age-standardized total health care spending per person in 2016 was $7649 (95% UI, $6129-$8814) for American Indian and Alaska Native (non-Hispanic) individuals; $4692 (95% UI, $4068-$5202) for Asian, Native Hawaiian, and Pacific Islander (non-Hispanic) individuals; $7361 (95% UI, $6917-$7797) for Black (non-Hispanic) individuals; $6025 (95% UI, $5703-$6373) for Hispanic individuals; $9276 (95% UI, $8066-$10 601) for individuals categorized as multiple races (non-Hispanic); and $8141 (95% UI, $8038-$8258) for White (non-Hispanic) individuals, who accounted for an estimated 72% (95% UI, 71%-73%) of health care spending. After adjusting for population size and age, White individuals received an estimated 15% (95% UI, 13%-17%; P < .001) more spending on ambulatory care than the all-population mean. Black (non-Hispanic) individuals received an estimated 26% (95% UI, 19%-32%; P < .001) less spending than the all-population mean on ambulatory care but received 19% (95% UI, 3%-32%; P = .02) more on inpatient and 12% (95% UI, 4%-24%; P = .04) more on emergency department care. Hispanic individuals received an estimated 33% (95% UI, 26%-37%; P < .001) less spending per person on ambulatory care than the all-population mean. Asian, Native Hawaiian, and Pacific Islander (non-Hispanic) individuals received less spending than the all-population mean on all types of care except dental (all P < .001), while American Indian and Alaska Native (non-Hispanic) individuals had more spending on emergency department care than the all-population mean (estimated 90% more; 95% UI, 11%-165%; P = .04), and multiple-race (non-Hispanic) individuals had more spending on emergency department care than the all-population mean (estimated 40% more; 95% UI, 19%-63%; P = .006). All 18 of the statistically significant race and ethnicity spending differences by type of care corresponded with differences in utilization. These differences persisted when controlling for underlying disease burden. Conclusions and Relevance: In the US from 2002 through 2016, health care spending varied by race and ethnicity across different types of care even after adjusting for age and health conditions. Further research is needed to determine current health care spending by race and ethnicity, including spending related to the COVID-19 pandemic.

Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years.

BACKGROUND AND PURPOSE: Prediction of stroke impact provides essential information for healthcare planning and priority setting. We aim to estimate 30-year projections of stroke epidemiology in the European Union using multiple modeling approaches. METHODS: Data on stroke incidence, prevalence, deaths, and disability-adjusted life years in the European Union between 1990 and 2017 were obtained from the global burden of disease study. Their trends over time were modeled using 3 modeling strategies: linear, Poisson, and exponential regressions-adjusted for the gross domestic product per capita, which reflects the impact of economic development on health status. We used the Akaike information criterion for model selection. The 30-year projections up to 2047 were estimated using the best fitting models, with inputs on population projections from the United Nations and gross domestic product per capita prospects from the World Bank. The technique was applied separately by age-sex-country groups for each stroke measure. RESULTS: In 2017, there were 1.12 million incident strokes in the European Union, 9.53 million stroke survivors, 0.46 million deaths, and 7.06 million disability-adjusted life years lost because of stroke. By 2047, we estimated an additional 40 000 incident strokes (+3%) and 2.58 million prevalent cases (+27%). Conversely, 80 000 fewer deaths (-17%) and 2.31 million fewer disability-adjusted life years lost (-33%) are projected. The largest increase in the age-adjusted incidence and prevalence rates are expected in Lithuania (average annual percentage change, 0.48% and 0.7% respectively), and the greatest reductions in Portugal (-1.57% and -1.3%). Average annual percentage change in mortality rates will range from -2.86% (Estonia) to -0.08% (Lithuania), and disability-adjusted life years' from -2.77% (Estonia) to -0.23% (Romania). CONCLUSIONS: The number of people living with stroke is estimated to increase by 27% between 2017 and 2047 in the European Union, mainly because of population ageing and improved survival rates. Variations are expected to persist between countries showing opportunities for improvements in prevention and case management particularly in Eastern Europe.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND: Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS: We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS: We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally. CONCLUSIONS: We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).

Trends in prevalence, mortality, and morbidity associated with high systolic blood pressure in Brazil from 1990 to 2017: estimates from the "Global Burden of Disease 2017" (GBD 2017) study.

BACKGROUND: Hypertension remains the leading risk factor for cardiovascular disease (CVD) worldwide, and its impact in Brazil should be assessed in order to better address the issue. We aimed to describe trends in prevalence and burden of disease attributable to high systolic blood pressure (HSBP) among Brazilians ≥ 25 years old according to sex and federal units (FU) using the Global Burden of Disease (GBD) 2017 estimates. METHODS: We used the comparative risk assessment developed for the GBD study to estimate trends in attributable deaths and disability-adjusted life-years (DALY), by sex, and FU for HSBP from 1990 to 2017. This study included 14 HSBP-outcome pairs. HSBP was defined as ≥ 140 mmHg for prevalence estimates, and a theoretical minimum risk exposure level (TMREL) of 110-115 mmHg was considered for disease burden. We estimated the portion of deaths and DALYs attributed to HSBP. We also explored the drivers of trends in HSBP burden, as well as the correlation between disease burden and sociodemographic development index (SDI). RESULTS: In Brazil, the prevalence of HSBP is 18.9% (95% uncertainty intervals [UI] 18.5-19.3%), with an annual 0.4% increase rate, while age-standardized death rates attributable to HSBP decreased from 189.2 (95%UI 168.5-209.2) deaths to 104.8 (95%UI 94.9-114.4) deaths per 100,000 from 1990 to 2017. In spite of that, the total number of deaths attributable to HSBP increased 53.4% and HSBP raised from 3rd to 1st position, as the leading risk factor for deaths during the period. Regarding total DALYs, HSBP raised from 4th in 1990 to 2nd cause in 2017. The main driver of change of HSBP burden is population aging. Across FUs, the reduction in the age-standardized death rates attributable to HSBP correlated with higher SDI. CONCLUSIONS: While HSBP prevalence shows an increasing trend, age-standardized death and DALY rates are decreasing in Brazil, probably as results of successful public policies for CVD secondary prevention and control, but suboptimal control of its determinants. Reduction was more significant in FUs with higher SDI, suggesting that the effect of health policies was heterogeneous. Moreover, HSBP has become the main risk factor for death in Brazil, mainly due to population aging.

Root cortical anatomy is associated with differential pathogenic and symbiotic fungal colonization in maize.

Root anatomical phenotypes vary among maize (Zea mays) cultivars and may have adaptive value by modifying the metabolic cost of soil exploration. However, the microbial trade-offs of these phenotypes are unknown. We hypothesized that nodal roots of maize with contrasting cortical anatomy have different patterns of mutualistic and pathogenic fungal colonization. Arbuscular mycorrhizal colonization in the field and mesocosms, root rots in the field, and Fusarium verticillioides colonization in mesocosms were evaluated in maize genotypes with contrasting root cortical anatomy. Increased aerenchyma and decreased living cortical area were associated with decreased mycorrhizal colonization in mesocosm and field experiments with inbred genotypes. In contrast, mycorrhizal colonization of hybrids increased with larger aerenchyma lacunae; this increase coincided with larger root diameters of hybrid roots. F. verticillioides colonization was inversely correlated with living cortical area in mesocosm-grown inbreds, and no relation was found between root rots and living cortical area or aerenchyma in field-grown hybrids. Root rots were positively correlated with cortical cell file number and inversely correlated with cortical cell size. Mycorrhizae and root rots were inversely correlated in field-grown hybrids. We conclude that root anatomy is associated with differential effects on pathogens and mycorrhizal colonization of nodal roots in maize.