Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Lambda cyhalothrin toxicity induces alterations in lipogenic genes and inflammatory factors in rat liver

The present study aims to elucidate the molecular basis of lambda cyhalothrin (LCT) toxicity. Thirty-two mature male albino rats were randomly classified into four equal groups. The first group was orally administered normal saline, the second group was orally administered dimethylsulfoxide (DMSO). The third group was orally administered 1/100 LD50 (6.12 mg/kg b. wt) of a commercial formulation containing 2.5% LCT (i.e., a net dose LCT corresponding to 0.15 mg/kg b. wt). The fourth group was orally administered 1/100 LD50 (0.64 mg/kg b. wt) of a pure form of LCT. The results indicated that exposure to LCT is capable of inducing an up-regulation in the mRNA expression levels of peroxisome proliferative activated receptor α and γ (PPAR α and PPAR γ), tumor necrosis factor (TNF-α), fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c). Additionally, our study revealed a significant increase in serum levels of ALT, AST, ALP, γGT as well as the inflammatory cytokines TNF-α and monocyte chemoattractant protein-1 (MCP-1). A significant elevation in total lipids, total cholesterol, triacylglycerol, LDL-c and leptin with a corresponding significant decrease in HDL-c was also noted. Moreover, our results depicted that LCT treatment exhibits a significant increase in hepatic MDA levels concurrent with a significant decrease in GSH levels and the activities of CAT, SOD, and GPx. An immunohistochemical investigation also revealed a strong up-regulation of hepatic FAS in the LCT treated groups. The histopathological findings were marked by evidence in support of periportal fatty changes and interstitial aggregation of round cells

Impact of prenatal and postnatal exposure to bisphenol A on female rats in a two generational study: Genotoxic and immunohistochemical implications

Environmental xenoestrogen contaminant bisphenol A (BPA), widely used as a monomer in the manufacture of epoxy, polycarbonate plastics and polystyrene resins. However, exposure to BPA has raised concerns, and the negative impacts of its exposure on reproduction have been controversial. The purpose of this work was directed to assess the potential adverse effects of BPA on dam rats and their first generation females in a comparative toxicological study. Fifteen pregnant female rats were classified into three equal groups; first group was orally administered corn oil and served as control (group1), second and third groups were orally administered BPA at dose levels of 50 and 200 mg/kg b.wt respectively (groups 2 & 3). The administration was carried out daily from zero day through the gestation period (21 days) until the last day of the lactation period (21days) and was extended after weaning for three months, in which female off springs of first generation (F1) of the three groups of dams were classified into; F1control group (group 4), F1 group treated with low dose of BPA (group 5) and F1 group treated with high dose of BPA (group 6) which continued in daily oral administration of BPA at the same previously mentioned doses for three months. The results elucidated a clear marked DNA fragmentation in the ovary of both dam and F1 female groups especially at higher examined concentration. Also, the data demonstrated a significant increase in the serum levels of GGT, ALP, glucose, total cholesterol, triglycerides, LDH and also in the serum level of estrogen hormone. Meanwhile, our study recorded a significant decrease in total protein, catalase, GST, HDL and FSH hormone in both treated dam and F1 female groups which was more significantly decreased in F1 female rats. Moreover, our experiment illustrated up-regulation in the immunoexpression of ERβ in ovary, uterus and liver of dam and F1 female groups. The histopathological investigation showed degeneration in the epithelial lining of ovarian follicles, submucosal leukocytic infiltration and increase in vaculation of hepatic cells with proliferation of kupffer cells. The lesions were more sever in groups 3 & 6 of both dam and their F1 females. Our data speculated that long- term exposure to BPA at 50 and 200 mg/kg.b.wt. depicted total genomic damage, significant alterations in liver enzymes, lipid profile, antioxidant enzymes and reproductive hormones with up-regulation in the expression of ERβ which were more significantly perturbed in group 3 and group 6 of both dam and F1 female rats. Keywords: DNA damage, Estrogen receptors, Reproductive organs, Female rat

Downregulation of male-specific cytochrome P450 by profenofos

The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide

Immunotoxicological, biochemical, and histopathological studies on Roundup and Stomp herbicides in Nile catfish (Clarias gariepinus)

Aim: The current study was directed to investigate the immunotoxic and oxidative stress effects of Roundup and Stomp herbicides and their combination on Nile catfish (Clarias gariepinus). Materials and Methods: The experiment was carried out on 120 fish that randomly divided into four equal groups with three replicates: The first group kept as control, the second group exposed to 1/2 96 h lethal concentration 50 (LC50) of Roundup, the third group exposed to 1/2 96 h LC50 of Stomp, and the fourth one exposed to a combination of Roundup and Stomp at previously-mentioned doses. The experiment was terminated after 15 days; blood samples were obtained at 1st, 8th, and 15th days of treatment where the sera were separated for estimation of antioxidant enzymes. Meanwhile, at 15th day of exposure part of blood was collected from all groups with an anticoagulant for evaluation of phagocytic activity, then the fish were sacrificed, and specimens from the liver of all groups were obtained for histopathological examination. Results: Our results indicated that both herbicides either individually or in combination elucidated significant decrease in phagocytic activity that was highly marked in group exposed to both herbicides. Furthermore, our data elicited an obvious elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Meanwhile, the data depicted reduction in levels of reduced glutathione (GSH) and glutathione-S-transferase (GST). Histopathological investigation of liver proved the aforementioned results. Conclusion: It could be concluded that either Roundup or Stomp alone cause significant deleterious effects on aquatic vertebrates. However, the use of their combination enhanced their toxic effects. Toxicity can end up in humans through the food chain

Sustained Functioning Impairments and Oxidative Stress with Neurobehavioral Dysfunction Associated with Oral Nicotine Exposure in the Brain of a Murine Model of Ehrlich Ascites Carcinoma: Modifying the Antioxidant Role of <i>Chlorella vulgaris</i>

Background: This study provides a model for studying the mechanism(s) responsible for the nervous tissue damage and misfunctioning that occurred due to oral nicotine exposure, considered a stress factor, during the presence of Ehrlich ascites carcinoma bearing in the mouse model (EAC). The mitigating role of Chlorella vulgaris (CV) against nicotine-induced brain damage was evaluated. Methods: Eighty Swiss female mice were classified into four groups, these were the control, the CV group, the nicotine group(100 µg/kg), and the combination group. Oxidant/antioxidant status, proinflammatory cytokines levels, DNA damage, quantitative microscopical lesions, and Caspase 3, Bcl-2 proteins were assessed in the current study. Levels of dopamine (DA) and gamma-aminobutyric acid (GABA) were also evaluated. Results: Nicotine was found to cause pronounced neurobehavioral alterations, increase the mortalities oxidative stress DNA damage, and augment the inflammatory response in brain tissue alongside the microstructural alteration. The administration of CV with nicotine in EAC-bearing mice rescued the detrimental effects of nicotine. Conclusions: CV aids in reducing the harmful effects of nicotine and returns the conditions caused by nicotine to near-control levels. Thus, we are in favor of giving it to cancer patients who are taking daily dosages of nicotine even by smoking cigarettes or being exposed to second-hand smoke