Biological evaluation of fruits from the Brazilian Cerrado : Guapeva, Gabiroba and Murici

Orientador: Glaúcia Maria PastoreTese (doutorado) - Universidade Estadua de Campinas, Faculdade de Engenharia de AlimentosResumo: A ingestão de muitas frutas convencionais, exóticas e nativas está associada com a redução do risco de doenças crônicas não transmissíveis e até mesmo o câncer. Neste contexto, o presente trabalho tem como proposta estudar atividades biológicas bem como identificar e quantificar os compostos fenólicos das frutas do Cerrado brasileiro, Guapeva (Pouteria cf. guardneriana Radlk.), Murici (Byrsonima verbascifolia Rich.) e Gabiroba (Compomanesia cambessedeana O. Berg.). Além dos compostos fenólicos, foram investigadas as atividades antioxidante, antiinflamatória, antimutagência, antigenotóxica, antiproliferativa e citotóxica. Os compostos fenólicos foram extraídos com etanol 95% e com água. Os fenólicos lipofílicos foram extraídos, a partir da fruta, com hexano. A quantificação dos compostos fenólicos foi realizada e os extratos etanólicos apresentaram melhores resultados quando comparados com os aquosos. O extrato etanólico da Gabiroba concentração de fenólicos de 4610,46 mg Ácido Gálico/100g fruta fresca, sendo superior a todos os outros extratos. Também foi realizada a quantificação dos flavonóides totais, mas apenas para os extratos etanólicos, e a semente da Guapeva apresentou o resultado mais relevante, no valor de 2915,62 mg Catequina/100g fruta fresca. Os extratos do Cerrados foram avaliados quanto a capacidade antioxidante in vitro através dos métodos 2,2- Diphenyl ¿ 1- picrylhydrazil (DPPH), Trolox Equivalent Antioxidant Capacity (TEAC), Oxygen Radical Absorbance Capacity (ORAC) e Peroxyl Radical cavenging Capacity (PSC). Os resultados do teste DPPH foram expostos de duas formas diferentes, como equivalentes de Trolox onde o extrato etanólico da casca da Guapeva destacou-se por apresentar maior potencial antioxidante nos 3 tempos analisados (30, 60 e 90 minutos) e também como IC50, onde o extrato etanólico da Gabiroba apresentou melhor resultado no valor de 11,10 µg/mL de fruta fresca. Para o teste TEAC os extratos etanólicos da casca da Guapeva e a Gabiroba apresentaram maior potencial antioxidante, com resultados de 1543,53 e 1014,25 µM Trolox Equivalentes/100g fruta fresca, respectivamente. Já para os ensaios ORAC e PSC o extrato etanólico da Gabiroba apresentou maior atividade, com resultados de 43780,00 µM TE/100g de fruta e 2342,52 µM Vitamina C/100 g fruta fresca, respectivamente. A identificação e quantificação dos compostos fenólicos presentes nos extratos foram realizadas por Cromatografia líquida de alta eficiência. Foram identificados Ácido ferrúlico, Resveratrol, Etil galato, Catequina, Propil galato e Epicatequina. Ratos foram tratados com os extratos de frutas e o plasma foi coletado 30, 60 e 90 minutos após a gavagem para análise pelos métodos ORAC, TEAC e fenóis totais. O extrato de casca da Guapeva apresentou maior concentração de fenóis totais após trinta minutos da ingestão e o Murici após 1 hora. Através da análise TEAC, todos os extratos apresentaram maior atividade antioxidante no tempo de 30 minutos quando comparado com os demais tempos. No ensaio ORAC todos os extratos apresentaram maior potencial nos períodos de 30 e 60 minutos. A identificação dos compostos fenólicos no plasma foi determinada por Espectrometria de Massas, sendo que apenas a Catequina foi identificada no grupo que foi tratado com Gabiroba. O potencial antimutagênico/mutagênico foi determinado pelo teste in vivo de Micronúcleos. Todos os extratos mostraram-se antimutagênicos e não mutagênicos. O extrato com maior efeito protetor contra a droga Ciclofosfamida foi o Murici 400 mg extrato/kg P.C. com efeito redutor de 97,71%. A avaliação do efeito antiinflamatório foi realizada pelo teste de Edema de pata, induzido por Carragenina e todos os extratos apresentaram ação antiinflamatória. Também verificou-se que a partir da segunda hora após a injeção da Carragenina, o efeito antiinflamatório apresentado por todos extratos, aumentou. O efeito antigenotóxico foi avaliado pelo ensaio Cometa in vivo. Todos os extratos avaliados não danificaram o DNA e os que apresentaram maior proteção contra dano/lesão no DNA foram a polpa, casca e semente da Guapeva na concentração de 200 mg extrato/kg P.C. e o Murici na concentração de 400 mg extrato/kg P.C. Oito linhagens tumorais humanas foram utilizadas na determinação do potencial antiproliferativo, apenas a Guapeva casca, polpa e o Murici apresentaram início de efeito citostático. A atividade citotóxica e antiproliferativa foi avaliada em hepatocarcinoma humano (HepG2), a semente da fruta Guapeva apresentou citotoxicidade, e a casca e polpa da fruta Guapeva, assim como a Gabiroba se destacaram no potencial antiproliferativo com valores de 11,75; 12,57 e 8,35 mg/mL. O potencial antioxidante celular foi avaliado e a casca da fruta Guapeva apresentou maior atividade, no valor de 99,91 µmol Quercetina/100g fruta de fresca. De acordo com nosso conhecimento, este foi o estudo mais aprofundado sobre as propriedades biológicas das frutas do Cerrado, e que possivelmente possibilitará a utilização destes como alimento funcionalAbstract: There is an association between the conventional intake of many fruits (exotic native species) with reduced risk of chronic diseases and even cancer. In this context, this work aims to study the biological activities, identify and quantify the phenolic compounds of Cerrado's fruits, the Guapeva (Pouteria cf. Guardneriana Radlk), Murici (verbascifolia Byrsonima Rich) and Gabiroba (Compomanesia cambessedeana O. Berg). In addition, we investigated the antioxidant, anti-inflammatory, antimutagenic, antigenotoxic, antiproliferative and cytotoxic properties of these fruits. Phenolic compounds were extracted with 95% ethanol and water. The lipophilic phenolics were extracted from the fruit with hexane. The quantification of phenolic compounds was performed and the ethanol extracts presented better results when compared with aqueous extracts. The Gabiroba extract showed the total phenolic concentration of 4610.46 mg Gallic acid/100g fresh fruit, higher than all other analyzed extracts. Total flavonoids were also quantified, but only the ethanol extracts were used. The seed of the Guapeva presented the most relevant results, amounting to 2915.62 mg Catechin /100g fresh fruit. The Cerrado's extracts were evaluated for antioxidant capacity in vitro using the methods 2,2- Diphenyl ¿ 1- picrylhydrazil (DPPH), Trolox Equivalent Antioxidant Capacity (TEAC), Oxygen Radical Absorbance Capacity (ORAC) e Peroxyl Radical cavenging Capacity (PSC). The DPPH test results were presented in two different ways, one as Trolox equivalents, in which the ethanol extract of the peel of the Guapeva resulted in the highest antioxidant potential for the three analyzed times (30, 60 and 90 minutes) and the other way as EC50, in which it was observed that the ethanol extract of Gabiroba had the best result with a value of 11.10 µg/mL of fresh fruit. From the TEAC test, ethanol extracts of the peel of Guapeva and Gabiroba showed higher antioxidant potential, the results were 1543.53 and 1014.25 uM Trolox Equivalents/100g of fresh fruit, respectively. For the ORAC and PSC tests, the ethanol extract of the Gabiroba presented the highest activity, with results of 43,780.00 µM TE/100g of fresh fruit and 2342.52 µM Vitamin C/100g of fresh fruit, respectively. The identification and quantification of phenolic compounds in the extracts were performed by high performance liquid chromatography. The following standards were identified: Ferrulic acid, resveratrol, ethyl gallate, catechin, Propyl gallate, and epicatechin. Rats were treated with the extract of fruits and plasma was collected 30, 60 and 90 min after gavage for analysis by the methods ORAC, TEAC and Total phenolics. The peel of the Guapeva extract showed the highest concentration of phenolics thirty minutes after treatment and the Murici presented the highest concentration after 1 hour of ingestion. For the TEAC test, all extracts showed higher antioxidant activity at 30 minutes compared to the other analyzed periods. For the ORAC assay, all the extracts had the greatest potential in periods between 30 and 60 minutes. The identification of phenolic compounds in plasma was determined by mass spectrometry, and only the Catechin was identified in the group of animals that received the Gabiroba extract. The antimutagenic / mutagenic test was determined by in vivo micronucleus test. None of the extracts show mutagenic properties. The extract with the greatest protective effect against Cyclophosphamide drug was the Murici at 400 mg extract / kg body weight, presenting reduction effect of 97.71%. The evaluation of anti-inflammatory effect was accomplished by testing the paw edema induced by the Carrageenan drug and it was observed that all extracts showed anti-inflammatory properties. It was also found that from the second hour after injection of Carrageenan, all extracts presented an increase of anti-inflammatory effects. The antigenotoxic effect was evaluated by Comet assay in vivo. All the extracts evaluated did not induce DNA damage, the extracts that provided greater protection against DNA damage were the pulp, peel and seed of Guapeva at 200 mg extract/kg body weight and Murici at 400 mg extract/kg body. Eight human tumor cell lines were used to determine the potential antiproliferative effects of the fruits, however just the peel, pulp of Guapeva and Murici showed cytostatic effects. The antiproliferative and cytotoxicity activities were evaluated in human hepatocellular carcinoma cells (HepG2). The seeds of Guapeva presented cytotoxicity, and the peel and pulp of Guapeva, and Gabiroba showed the highest antiproliferative potential with values of 11.75, 12.57 and 8.35 mg/mL, respectively. The cellular antioxidant potential was tested and the peel of the Guapeva showed the highest activity, amounting to 99.91 µmol Quercetin/100g fresh fruit. This study furthers the investigation of the biological properties of the fruits of the Cerrado, and possibly allow the use of these as functional foodDoutoradoTecnologia de AlimentosDoutor em Tecnologia de Alimento

Bullying in Brazilian schools: results from the National School-based Health Survey (PeNSE), 2009

O objetivo deste estudo é identificar e descrever a ocorrência do bullying, episódios de humilhação ou provocação perpetrados pelos colegas da escola, entre estudantes do 9º ano do ensino fundamental de escolas públicas e privadas das 26 capitais dos estados brasileiros e do Distrito Federal. Trata-se de estudo transversal feito com 60.973 escolares de 1.453 escolas públicas e privadas. A análise dos dados aponta que 5,4% (IC95%: 5,1%-5,7%) dos estudantes relataram ter sofrido bullying quase sempre ou sempre nos últimos 30 dias; 25,4% (IC95%: 24,8%-26,0%) foram raramente ou às vezes vítimas de bullying e 69,2% (IC95%: 68,5%-69,8%) não sentiram nenhuma humilhação ou provocação (bullying). A capital com maior frequência de foi Belo Horizonte-MG (6,9%; IC95%: 5,9%-7,9) e a menor foi Palmas-TO (3,5%; IC95%: 2,6%-4,5%). Meninos relatam mais bullying (6,0%; IC95%: 5,5%-6,5%) do que meninas (4,8%; IC95%: 4,4%-5,3%). Não houve diferença entre escolas públicas (5,5%; IC95%: 5,1%-5,8%) e privadas (5,2%; IC95%: 4,6%-5,8%), exceto em Aracaju-SE, onde foi registrada maior ocorrência de bullying em escolas privadas. Os dados mostram urgente necessidade de ações intersetoriais a partir de políticas e práticas educativas que efetivem redução e prevenção da ocorrência do bullying nas escolas.The aim of this study is to identify and describe the occurrence of bullying among students in the 9th year (8th grade) from public and private schools from 26 Brazilian state capitals and the Federal District. It is a cross-sectional study involving 60,973 students and 1,453 public and private schools. Data analysis indicates that 5.4% (IC95%: 5.1%-5.7%) of students reported having suffered bullying almost always or always in the last 30 days, 25.4% (IC95%: 24.8%-26.0%) were rarely or sometimes the victim of bullying and 69.2% (IC95%: 68.5%-69.8%) of students felt no humiliation or provocation at school. The capital with higher frequency of bullying was Belo Horizonte (6.9%; IC95%: 5,9%-7,9%), Minas Gerais, and the lowest was Palmas (3.5%; IC95%: 2.6%-4.5%), Tocantins. Boys reported more bullying (6,0%; IC95%: 5.5%-6.5%) compared with girls (4,8%; IC95%: 4.4%-5.3%). There was no difference between public schools 5.5% (IC95%: 5.1%-5.8%) and private (5.2%) (IC95%: 4.6%-5.8%), except in Aracaju, Sergipe, that show more bullying in private schools. The findings indicate an urgent need for intersectoral action from educational policies and practices that enforce the reduction and prevention of the occurrence of bullying in schools in Brazil

Crescimento inicial de cafeeiros cultivados em solução nutritiva sob diferentes doses de fósforo

The objective of this study was to evaluate growth alterations and water relations in coffee plants (Coffea arabica L.) at the initial stage of development, grown in nutritive solution (hydroponics) and submitted to a wide variation of P doses. The various doses of P applied to the coffee plants similarly affected the growth characteristics evaluated (number of leaves, height, total leaf area, and dry and green mass accumulation), fitting a logarithmic model, with a direct relationship between P doses and growth. The logarithmic model was also fitted to the leaf water potential module, evaluated in the pre-dawn period and at noon. However, the direct relationship between P doses and water potential was only verified for determinations made at noon; the opposite behavior occurred with readings made in the pre-dawn period, since values decreased as P doses increased. Interactions between P and N nutritional status as well as between P and the water status of plants are discussed, with emphasis on the importance of future investigations.Objetivou-se neste estudo avaliar as alterações no crescimento e relações hídricas de plantas de cafeeiros (Coffea arabica L.) na fase inicial de desenvolvimento, cultivadas em solução nutritiva e submetidas a uma ampla faixa de variação de doses de P. As características de crescimento avaliadas (número de folhas, altura, área foliar total e acúmulo de massa seca e fresca) foram afetadas de modo semelhante, em função das doses de P aplicadas, sendo definido o modelo logarítmico, com relação direta entre as doses de P e crescimento. O modelo logarítmico também foi delineado para o módulo de potencial hídrico foliar, avaliado no período antemanhã e ao meio-dia. Entretanto, a relação direta entre doses de P e o potencial hídrico foi verificada apenas para as determinações realizadas ao meio-dia; para as leituras realizadas no período antemanhã, ocorreu um comportamento inverso, sendo verificada redução de valores com aumento das doses de P.Interações entre status nutricional relativo a P e N, assim como relações com o status hídrico das plantas, foram discutidas, sendo ressaltada a importância de futuras investigações

Indicadores de la línea de atención a personas con diabetes en Brasil : Encuesta Nacional de Salud 2013 y 2019

Objetivo: Comparar indicadores de cuidado assistencial em adultos com diagnóstico médico de diabetes mellitus (DM) no Brasil em 2013 e 2019, e analisar esses indicadores, em 2019, segundo características sociodemográficas. Métodos: Estudo transversal com dados da Pesquisa Nacional de Saúde de 2013 e 2019. Foram avaliados os indicadores de cuidado em pessoas com diagnóstico médico de DM. Resultados: A prevalência de DM aumentou de 6,2% (2013) para 7,7% (2019). Entre 2013 e 2019, ocorreu aumento no uso de medicamentos (de 80,2% para 88,8%) e de assistência médica (de 73,2% para 79,1%), houve redução no uso de medicamentos da Farmácia Popular (de 57,4% para 51,5%) e no acompanhamento com mesmo médico (de 65,2% para 59,4%). Em 2019, pessoas do sexo masculino, mais jovens, de raça/cor da pele preta e parda, menores escolaridade e renda apresentaram pior desempenho nos indicadores. Conclusão: A maioria dos indicadores permaneceu semelhante durante os últimos cinco anos, com diferenças segundo características sociodemográficas em 2019Objective: To compare health care indicators for adults with medical diagnosis of diabetes mellitus (DM) in Brazil, in 2013 and 2019, and analyze the indicators for 2019 according to sociodemographic characteristics. Methods: Cross-sectional study using data from the 2013 and 2019 National Health Survey. Care indicators were evaluated in people with medical diagnosis of DM. Results: DM prevalence increased from 6.2% (2013) to 7.7% (2019). Between 2013 and 2019 there was an increase in the use of medications (80.2% to 88.8%) and of medical care (73.2% to 79.1%), a reduction in the use of Popular Pharmacy Program medications (57.4% to 51.5%) and in follow-up with the same physician (65.2% to 59.4%). In 2019, poorer indicators were observed for individuals who were male, younger, Black and Brown, and with lower education and income. Conclusion: Most indicators remained similar in the last five years, with differences according to sociodemographic characteristics in 2019.Objetivo: Comparar indicadores de atención de salud para adultos con diagnóstico médico de diabetes mellitus (DM) en Brasil, en 2013 y 2019, y analizar estos indicadores, en 2019, según características sociodemográficas. Métodos: Estudio transversal con datos de la Encuesta Nacional de Salud de 2013 y 2019. Se evaluaron indicadores de atención en personas con diagnóstico médico de DM. Resultados: La prevalencia de DM aumentó del 6,2% (2013) al 7,7% (2019). Entre 2013 y 2019 hubo aumento en uso de medicamentos (80,2% a 88,8%) y de atención médica (73,2% a 79,1%), reducción en uso de medicamentos de Farmacia Popular (57, 4% a 51,5%) y seguimiento con mismo médico (65,2% a 59,4%). En 2019, personas de sexo masculino, más jóvenes, de la raza/color de piel negra y mestiza, menor nivel educativo e ingresos mostraron un peor desempeño en los indicadores. Conclusión: La mayoría de los indicadores se mantuvieron similares durante los últimos cinco años, con diferencias según las características sociodemográficas en 2019

Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography–mass spectrometry

Abstract\ud \ud Background\ud Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers.\ud \ud \ud Methods\ud An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases.\ud \ud \ud Results\ud The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols.\ud \ud \ud Conclusions\ud UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.The Fleury SA Group supported this work and AMPC received a doctorate\ud scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo –\ud FAPESP (no. 2013/03701-0). The funding agencies did not interfere in the\ud scientific aspects of the study

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions