Molecular mechanism and health effects of 1,2-Naphtoquinone

Extensive literature regarding the health side effects of ambient pollutants (AP) are available, such as diesel exhaust particles (DEPs), but limited studies are available on their electrophilic contaminant 1,2-Naphthoquinone (1,2-NQ), enzymatically derived from naphthalene. This review summarizes relevant toxicologic and biological properties of 1,2-NQ as an environmental pollutant or to a lesser degree as a backbone in drug development to treat infectious diseases. It presents evidence of 1,2-NQ-mediated genotoxicity, neurogenic inflammation, and cytotoxicity due to several mechanistic properties, including the production of reactive oxygen species (ROS), that promote cell damage, carcinogenesis, and cell death. Many signal transduction pathways act as a vulnerable target for 1,2-NQ, including kappaB kinase b (IKKbeta) and protein tyrosine phosphatase 1B (PTP1B). Antioxidant molecules act in defense against ROS/RNS-mediated 1,2-NQ responses to injury. Nonetheless, its inhibitory effects at PTP1B, altering the insulin signaling pathway, represents a new therapeutic target to treat diabetes type 2. Questions exist whether exposure to 1,2-NQ may promote arylation of the Keap1 factor, a negative regulator of Nrf2, as well as acting on the sepiapterin reductase activity, an NADPH-dependent enzyme which catalyzes the formation of critical cofactors in aromatic amino acid metabolism and nitric oxide biosynthesis. Exposure to 1,2-NQ is linked to neurologic, behavioral, and developmental disturbances as well as increased susceptibility to asthma. Limited new knowledge exists on molecular modeling of quinones molecules as antitumoral and anti-microorganism agents. Altogether, these studies suggest that 1,2-NQ and its intermediate compounds can initiate a number of pathological pathways as AP in living organisms but it can be used to better understand molecular pathways

Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter

Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. In vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. The expression of nuclear factor-kappa B (p65-NF-kappa B) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kappa B pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis

Determinantes de saúde em crianças dos 3 aos 10 anos

RESUMO 1: Introdução: Os estilos de vida atuais sugerem comportamentos de risco que estão na base do perfil de saúde do país. Objetivo: Avaliar os estilos de vida e sua associação com dados sociodemográficos numa amostra de crianças portuguesas dos 3 aos 10 anos de idade. Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: Constatou-se que as crianças com mais idade apresentavam uma menor adesão a comportamentos alimentares saudáveis, uma maior prevalência de atividade física (49,2%), no entanto, foram, também aquelas que apresentaram um maior índice de atividades sedentárias (27,1%). Os rapazes apresentaram maiores níveis de atividade física (51,6%) e índices mais elevados de comportamentos sedentários (28,6%). Relativamente à zona de residência, existiu uma maior prevalência de consumo de legumes (73,2%) e fastfood (24,0%) e de comportamentos sedentários (26,1%) em zonas urbanas. As crianças que pertenciam a agregados familares de rendimentos mais favoráveis e com maior nível de habilitações literárias consumiam mais leite e derivados, legumes e praticavam mais atividade física. No entanto, apresentaram maior prevalência de consumo de fastfood e comportamentos sedentários. Conclusões:Torna-se perceptível a necessidade de se intervir nos grupos mais vulneráveis no sentido de uma mais eficaz equidade em saúde. Palavras-chave: Crianças; estilos de vida; dados sociodemográficos; escolas.ABSTRACT 1: Introduction: The current lifestyles suggests risk behaviors that are the basis of a country's health profile. Objective: Assess the lifestyles and its association with sociodemographic variables among a sample of Portuguese children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: It was found that the older children had a lower adherence to healthy eating habits and a higher prevalence of physical activity (49.2%). However, there were also those with higher rate of sedentary activities (27.1%). The boys had higher levels of physical activity (51.6%) and higher rates of sedentary behaviors (28.6%). With regard to residence area, there was a higher prevalence of consumption of vegetables (73.2%), fastfood (24.0%) and sedentary behaviors (26.1%) in urban areas. Children belonging to households of more favorable monthly earnings and a higher level of educational qualifications consumed more dairy product, vegetables and practiced more physical activity. However, they had a higher prevalence of fastfood consumption and sedentary behaviors. Conclusions: It becomes noticeable the need to make an intervention on the most vulnerable groups to obtain more effective health equity. Keywords: Children; lifestyles; sociodemographic data; schools.RESUMO 2: Introdução: As iniquidades de género na distribuição de recursos estão ainda profundamente associadas à saúde precária e à diminuição do bem-estar das mulheres e das crianças. Objetivo: Analisar a influência dos fatores materno-fetais nos estilos de vida numa amostra de crianças portuguesas dos 3 aos 10 anos de idade Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: As crianças que habitam em meio rural apresentavam um peso à nascença superior comparativamente às do meio urbano (93,7%). As grávidas com mais idade obtiveram uma prevalência de antecipação da primeira consulta de gravidez mais elevada (96,5%) assim como uma prevalência mais elevada de consultas de vigilância durante a gravidez (97,2%) quando comparadas com as grávidas mais novas. As mães com habilitações literárias superiores ao 9.º ano de escolaridade apresentavam uma prevalência de amamentação superior (58,0%) e os seus filhos uma prevalência de consumo de fastfood superior (64,9%) quando comparadas com as mães com habilitações literárias inferiores. Conclusões: Denota-se a importância da maturidade, formação e capacitação das mães para os cuidados maternos e neonatais. Palavras-chave: crianças; estilos de vida; fatores materno-fetais.ABSTRACT 2: Introduction: Gender inequalities in the distribution of resources is still deeply associated with poor health and reduced welfare of women and children. Objective: To analyze the influence of maternal and fetal factors in lifestyles of children, in a sample of children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: Children who live in rural areas presented a higher birth weight compared to those who live in urban areas (93.7%). Older pregnant women obtained a higher prevalence of the first medical appointment antecipation (96.5%) as well as a higher prevalence of medical appointments during pregnancy (97.2%) when compared with younger pregnant women. Mothers with qualifications higher than the 9th grade showed a higher prevalence of breastfeeding (58.0%) and their children presented a higher prevalence of fastfood consumption (64.9%) when compared with mothers with lower educational qualifications. Conclusion: To denote the importance of maturity and training of mothers in maternal and neonatal care. Keywords: children; lifestyles; maternal fetal factors

Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch

Evaluation and comparison between methods of measurement of systolic blood pressure in healthy conscious cats

Após validação de dois diferentes métodos de mensuração de pressão arterial sistólica (PAS) não invasivos ou indiretos (oscilométrico e Doppler vascular) com o invasivo ou direto (cateterização arterial padrão ouro) em 12 gatos hígidos anestesiados de mesma faixa etária, os métodos não invasivos foram avaliados e comparados em 24 gatos hígidos e conscientes, divididos em quatro grupos de idade. Em cada animal, procedeu-se à mensuração da pressão pelos métodos Doppler e oscilométrico. O método oscilométrico foi o primeiro a ser realizado, e, logo em seguida, o método Doppler. Os valores considerados foram obtidos das médias de sete medidas consecutivas para cada método, com intervalo de 30 segundos entre elas. A primeira medida e as medidas discrepantes (variação ˃ 20% PAS), obtidas com sinais óbvios de estresse e/ou com movimentação do animal, foram descartadas. Os métodos de mensuração oscilométrico e Doppler, embora tenham apresentado médias estatisticamente diferentes em todos os grupos, quando comparados em cada grupo, apresentaram uma correlação significativa, alta e positiva. Ou seja, sempre que for obtido um valor elevado por um método, o mesmo fato ocorrerá com o outro método e vice-versa. Clinicamente, a diferença observada não é relevante, uma vez que a diferença média dos valores obtida pelos dois métodos, em cada grupo, foi menor que 1,1%.After two different validation systolic blood pressure measurement methods (PAS), not invasive or indirect (oscillometric and doppler vascular) with invasive or direct (arterial catheterization - Gold Standard) in 12 anesthetized healthy cats of the same age group, not invasive methods were evaluated and compared in 24 healthy conscious cats, divided into four age groups. In each animal, we proceeded to measure the pressure by Doppler and oscillometric methods. The oscillometric method was the first to be performed, and, shortly thereafter, the doppler method. The values considered were obtained from averages from seven consecutive measurements for each method with an interval of thirty seconds between them. The first measurement and disparate measurements (range ˃ 20% PAS) obtained with obvious signs of stress and / or animal movement were discarded. Methods of oscillometric and doppler measurement, although statistically different averages were shown in all groups when compared, each group showed a significant high positive correlation, meaning that when a high value is obtained by a method, the same occurs with the other method, and vice versa. Clinically, the observed difference is not relevant since the mean difference values obtained by the two methods, in each group was lower than 1.1%

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic