Summary Background Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. Methods GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. Findings The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6–47·0) in 1990 to 63·4 years (63·1–63·7) in 2023. For males, mean age increased from 45·4 years (45·1–45·7) to 61·2 years (60·7–61·6), and for females it increased from 48·5 years (48·1–48·8) to 65·9 years (65·5–66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9–81·0) and for males 74·8 years (74·8–74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5–38·4) for females and 35·6 years (35·2–35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. Interpretation We examined global mortality patterns over the past three decades, highlighting—with enhanced estimation methods—the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales

Summary Background For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010–23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings Total numbers of global DALYs grew 6·1% (95% UI 4·0–8·1), from 2·64 billion (2·46–2·86) in 2010 to 2·80 billion (2·57–3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0–14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31–1·61) global DALYs in 2010, increasing to 1·80 billion (1·63–2·03) in 2023, alongside a concurrent 4·1% (1·9–6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176–209] DALYs), stroke (157 million [141–172]), and diabetes (90·2 million [75·2–107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0–107·5]), depressive disorders (26·3% [11·6–42·9]), and diabetes (14·9% [7·5–25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837–917) in 2010 to 681 million (642–736) in 2023, and a 25·8% (22·6–28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7–61·0) for diarrhoeal diseases, 42·9% (38·0–48·0) for HIV/AIDS, and 42·2% (23·6–56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6–22·0) and 24·8% (7·4–36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7–19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18–1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation—with high SBP accounting for 8·4% (6·9–10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories—behavioural, metabolic, and environmental and occupational—risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8–37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0–11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023—eg, declining by 54·4% (38·7–65·3) for unsafe sanitation, 50·5% (33·3–63·1) for unsafe water source, and 45·2% (25·6–72·0) for no access to handwashing facility, and by 44·9% (37·3–53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [–2·7 to 15·6]; non-significant). Interpretation Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors—eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG—including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic—the complex interaction of multiple health risks, social determinants, and systemic challenges—will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity.

Background Age-related macular degeneration (AMD) is a common retinal disorder, causing blindness in aged individuals. One of the traditional Chinese medicines, modified Zhujing pill (MZP), has been widely used to treat various ocular disorders, including AMD; however, its protective mechanisms remain elusive. In this study, we explored the functional role of MZP in high-fat-diet-fed mice, a commonly used model for AMD. Methods Compounds of MZP water extract were identified by high-performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS. The mice were divided into three groups: group 1 mice fed with control diet (CD), group 2 mice fed with high-fat diet (HFD), and group 3 mice fed with HFD for 12 weeks; groups 1 and 2 were then treated with physiological saline, while group 3 was treated with MZP for 4 weeks. The cholesterol level and expression of cholesterol homeostasis-associated genes, antioxidant genes, and proinflammatory cytokines in mouse tissues were measured using biochemical approaches. Mouse cecum microbiota compositions and metabolic functions were analyzed using 16rRNA sequencing and bioinformatics approach. Results HFD-fed mice had high levels of cholesterol in the retinal pigment epithelial (RPE) cells, liver, and serum, a decreased expression of cholesterol homeostasis-associated genes and antioxidant genes in the RPE and liver, and an increased expression of proinflammatory cytokines. MZP treatment counteracted HFD-induced pathologic effects. Additionally, HFD altered cecum bacterial compositions and diversities associated with individual metabolic pathways. These metabolic pathways are involved in the biosynthesis of bacterial metabolites, mitochondrial function, oxidative stress, and inflammation. MZP reversed most of the changes back to control characteristics. Conclusion We postulate that the beneficial effects of MZP against AMD are possibly related to lowering the cholesterol level, suppressing oxidative stress and inflammation, and modulating gut microbiota and associated functions.

Background Age-related macular degeneration (AMD) is the commonest cause of retinal disorders in the aged population. Ziyin-Mingmu decoction (ZD) has been widely used to treat AMD patients over thousands of years, however the underlying functional mechanisms of ZD are largely elusive. In this study, we aim to elucidate the therapeutic mechanisms of ZD in AMD models. Methods An in vivo AMD mouse model and an in vitro AMD model were established. Cholesterol level in mouse tissues was measured. Expression of antioxidant genes and proinflammatory cytokines in mouse tissues and in human retinal pigment epithelial (RPE) cells were detected using biochemical approaches. Gut microbiota community and functional pathways were analysed using bioinformatics approach. Compounds in ZD were identified using HPLC/MS. Results High fat diet (HFD)-fed mice had significantly higher levels of cholesterol in the retina, RPE, liver and serum, and markedly decreased expression of cholesterol metabolism-associated genes in those tissues, compared to mice fed with normal diet. Similarly, expression of antioxidant and inflammation genes was dysregulated in HFD-fed mouse tissues. ZD treatment reversed these HFD-induced pathological effects. HFD also altered the composition of cecum bacterial communities and associated metabolic pathways, which returned to control levels by ZD. In vitro assays showed that H2O2 significantly increased oxidative stress and enhanced expression of proinflammatory cytokines. Co-treatment with ZD significantly counteracted these changes. HPLC/MS identified 105 compound in water extracted ZD and most are polyphenols. Conclusion Our data suggests that protection of ZD against AMD is possibly through mitigating cholesterol level, oxidative stress and inflammation, and modulating gut microbiota by polyphenols.

Summary Background Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Findings Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1–77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6–20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6–17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Interpretation Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO’s Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals

Abstract Background Since its inception in 1974, the Expanded Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, persistent coverage inequities and stagnating progress in recent decades have been further amplified by the COVID-19 pandemic. Methods This study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories, comprehensive assessment of the pandemic’s impact on coverage, and forecasts to 2030. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and pandemic-related disruptions. Findings Global coverage for original EPI vaccines against diphtheria-tetanus-pertussis (DTP1 and DTP3, ie, first and third doses), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, coverage gains slowed between 2010 and 2019 in many countries, including declines in 23 of 36 high-income countries for at least one of these vaccine-doses. The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-pandemic levels as of 2023. Coverage for newer vaccines, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series, RotaC), saw continued increases globally during the pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of COVID-19. Forecasts to 2030 for DTP3, PCV3 and MCV2 suggest that only DTP3 would reach 90% global coverage, and only under an optimistic scenario. The number of “zero-dose children”—those presumed not to have received a single vaccine dose—fell by 74·9% (95% uncertainty interval [UI] 72·1–77·3) globally between 1980 and 2019, but rose during the pandemic, remaining concentrated in conflict-affected, under-resourced regions, particularly sub-Saharan Africa. As of 2023, more than 50% of zero-dose children resided in just eight countries, emphasising persistent inequities. Interpretation Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving Immunization Agenda 2030 (IA2030) targets, such as halving zero-dose children compared to 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recovery to past coverage levels will be necessary in Latin America and Caribbean. These findings underscore the critical need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation, and adapting to local contexts are essential to advancing coverage. Pandemic recovery efforts, such as WHO’s “Big Catch-Up” initiative, must prioritise vulnerable populations and target subnational geographies to regain lost ground and achieve global immunisation goals.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer globally, and is a significant contributor to both morbidity and mortality rates. Emerging research has promptly highlighted the potential role of the gut microbiome in the development and progression of CRC. This study aims to investigate the differences in gut microbiota between CRC patients and healthy individuals in Iraq, using 16S rRNA metagenomic sequencing on Illumina NovaSeq (PE250-Seq). A total of 21 stool samples were analyzed: 12 from early-stage CRC patients and nine from healthy controls. Bacterial DNA was extracted, followed by 16S rRNA amplicon sequencing to profile the microbial communities. The results indicated significant differences between the fecal microbiome of the two groups. Remarkably, CRC patients exhibited a marked reduction in Bacteroidota and an increase in Verrucomicrobiota compared to healthy controls. At the genus level, Prevotella, Faecalibacterium, Roseburia, Barnesiella, Eubacterium Lachnospiraceae_UCG_004, and Lachnospira were significantly less abundant in CRC patients compared to the healthy individuals, while Actinomyces, Monoglobus, Desulfovibrio, Akkermansia, and Bacteroides were highly enriched. In addition, diversity analyses further indicated decreased α-diversity and distinct β-diversity patterns in the CRC patients, suggesting significant shifts in the gut microbial composition. These findings underscore the potential of microbiome-based diagnostics and therapeutic strategies, with microbial alterations serving as biomarkers for CRC diagnosis. Further research needs to focus on elucidating the causal relationships and therapeutic potential of these microbiome changes in CRC management.

Helicobacter pylori (H. pylori) is a globally prevalent bacterium, infecting roughly half the global population, with higher prevalence rates in developing countries. This study aimed to investigate the prevalence of H. pylori among symptomatic dyspeptic patients in Zakho City, Iraq, evaluate its association with various risk factors, as well as evaluate the effectiveness of treatment in curing this bacterium. Of a total of 150 dyspeptic patients, 50 who had received antibiotics were excluded, leaving 100 patients without antibiotics enrolled in this study. These participants, aged 11-67 years, visited the private Nawroz Laboratory in Zakho City, Kurdistan, Iraq, between June 2021 and October 2022. These patients were tested using the Helicoprobe 14C-Urea breath test and data on various factors, including age, gender, smoking, family size, drinking water source, education level, BMI, hemoglobin levels, and blood group, were collected through structured interviews. In this study, the prevalence of this bacterium was 50%, with no significant difference observed between males and females as well as BMI, smoking, source of drinking water, and blood groups while significant associations were found between infection and increasing age, low Hb levels, and educational level. Notably, 46.7% of patients failed to respond to standard triple therapy, possibly due to antibiotic resistance. The ineffectiveness of standard triple therapy for H. pylori highlights the need for tailored treatments based on local antibiotic resistance patterns to improve prevention and treatment strategies with further investigation studies

Background Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates— with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sexlocation-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration causeof-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere.

Sepsis is a life-threating complication among pediatric patients. This study aims primarily to investigate sepsis causative bacteria, their antimicrobial resistance profile, and to check the change of antimicrobial resistance trend for some selected bacteria.In addition, to evaluate the incidence of sepsis and related mortality rate. Besides, to evaluate the effectiveness and outcome of the treatment regimes in sepsis pediatric patients. A retrospective analysis was conducted on a four-year data (2018)(2019)(2020)(2021) collected from three Intensive Care Units of Hevi Pediatric Teaching Hospital. Sepsis screening involved clinical detection and confirmed by blood culture. A total of 520 out of 1098 (47.35%) blood samples showed positive microbial growth. Sepsis rate's reduction noticed during COVID-19 pandemic period. Coagulase-Negative Staphylococci (CoNS) and Klebsiella pneumonia were the most common isolated bacteria. A notable variation of antimicrobial resistance trend observed among sepsis causing bacteria. Obviously, the sepsis empirical treatment recommended by WHO was ineffective, as certain bacteria exhibited 100% resistance to every antibiotic tested. The mortality rate significantly increased from 1.3% in 2018 to 16.5% in 2021.The antimicrobial resistance profile for sepsis causing bacteria sending an alarm for expecting the worst. Thus, to avoid treatment failure, it is essential to monitor antimicrobial resistance in pediatric patient.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is a multinational collaborative research study with >10,000 collaborators around the world. GBD generates a time series of summary measures of health, including prevalence, cause-specific mortality (CSMR), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) to provide a comprehensive view of health burden for a wide range of stakeholders including clinicians, public and private health systems, ministries of health, and other policymakers. These estimates are produced for 371 causes of death and 88 risk factors according to mutually exclusive, collectively exhaustive hierarchies of health conditions and risks. The study is led by a principal investigator and governed by a study protocol, with oversight from a Scientific Council, and an Independent Advisory Committee.1 GBD is performed in compliance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).2 GBD uses de-identified data, and the waiver of informed consent was reviewed and approved by the University of Washington Institutional Review Board (study number 9060).

Traditional Chinese Medicine (TCM) has been used for thousands of years but without any sound empirical basis. One TCM preparation is the Qijudihuang pill (QP), a mixture of eight herbs, which has been used in China for the treatment of various conditions including age-related macular degeneration (AMD), the most common cause of blindness in the elderly population. In order to explain the mechanism behind the effect of QP, we used an AMD model of high-fat diet (HFD) fed mice to investigate cholesterol homeostasis, oxidative stress, inflammation, and gut microbiota. Cholesterol levels in the retina, retinal pigment epithelium (RPE), liver, and serum were determined as was the expression of enzymes involved in cholesterol metabolism, inflammation, and oxidative stress. In the majority of the lipid determinations, analytes were elevated by HFD but this was reversed by QP. Cholesterol metabolism, including the enzymes of bile acid (BA) formation, was suppressed by HFD but again this was reversed by QP. Bas play a major role in signaling between host and microbiome and this is disrupted by HFDs, resulting in major changes in the composition of colonic bacterial communities. Associated with these changes are predictions of the metabolic pathway complexity and abundance of individual pathways. These concerned substrate breakdowns, energy production, and the biosynthesis of pro-inflammatory factors but were changed back to control characteristics by QP. We propose that the ability of QP to reverse these effects is related to mechanisms acting to lower cholesterol levels, oxidative stress, and inflammation and those that modulate gut microbiota.

ABSTRACT The prevalence of Staphylococcus aureus (S. aureus) among patients with urinary tract infections (UTIs) has become a significant cause of morbidity in all age groups. The aim of the current study was to identify S. aureus with methicillin-resistant S. aureus (MRSA). Moreover, it aimed to determine their antimicrobial susceptibility patterns and to detect the presence of the mecA, lukPV and icaA genes in isolated S. aureus among UTIs patients. A total of 402 urine samples were collected from patients diagnosed with UTIs aged (less than 80 years) at Zakho General Hospital in Zakho City, from August 2021 to March 2022. From these samples, a total of 37 (12.6%) S. aureus was identified and molecularly confirmed by the nuc gene. A high prevalence of MRSA 28 (75.7%) was identified from these isolates S. aureus by Oxacillin sensitive test and confirmed by mecA gene. Females were highly infected with UTIs than males, and most cases were in chronic condition and married. In addition, 18 (64.3%) and 21 (75%) of these isolates S. aureus were harbored luk-PV and icaA genes, respectively. There were widespread of antimicrobial resistance patterns for these bacteria. Isolated MRSA were highly sensitive to Imipenem. Interestingly, a significant positive correlation between mecA and both virulence marker genes (luk-PV and icaA) found in MRSA with UTIs. Conclusion, the data demonstrated, for the first time, alarming emergence of multidrug-resistant MRSA isolated from UTIs of community-acquired in Kurdistan Region-Iraq. Further studies are required in other cities to report whether or not MRSA is the cause of UTI patients in Iraqi Kurdistan.

Background: The presence of extended-spectrum β-lactamase (ESBL)-producing bacteria among uropathogens is significantly increasing in children all over the world. Thus, this research was conducted to investigate the prevalence of E. coli and their antimicrobial susceptibility pattern, and both genes of ESBL-producing E. coli resistant and virulence factor in UTIs patients among children in Duhok Province, Kurdistan, Iraq. Method: a total of 67 E. coli were identified from 260 urine samples of pediatric patients diagnosed with UTIs aged (0–15 years) which were collected from Heevi Pediatric Teaching Hospital, from August 2021 to the end of February 2022. Result: a high proportion of UPEC infections at ages <5 years and the rates among girls (88%) were significantly higher than those among the boys. A wide variety of E. coli are resistant to most antibiotics, such as Amoxicillin, Ampicillin and Tetracycline, and 64% of them were positive for ESBL. Interestingly, the presence of both the ESBL marker genes (blaTEM, and blaCTX-M) as well as both virulence marker genes (pai and hly) were detected in above 90% of E. coli. Conclusion: the data illustrate an alarming increase in UPEC with ESBL production and the emergence of multidrug-resistant drugs in the early age of children. The public health sectors should further monitor the guidelines of using antibiotics in Kurdistan, Iraq.

Dysbiosis of gut microbiota has adverse effects on host health. This study aimed to determine the effects of changes of faecal microbiota in obese and diabetic rats on the imputed production of enzymes involved in the metabolism of glutamate, gamma-aminobutyric acid (GABA), and succinate. The levels of glutamate decarboxylase, GABA transaminase, succinate-semialdehyde dehydrogenase, and methylisocitrate lyase were reduced or absent in diabetic rats compared with controls and obese rats. Glutamate decarboxylase (GAD) was significantly reduced in obese rats compared with control rats, while the other enzymes were unaltered; different bacterial taxa are suggested to be involved. Levels of bacterial enzymes were inversely correlated with the blood glucose level. These findings suggest that the absence of GABA and reduced succinate metabolism from gut microbiota contribute to the diabetic state in rats.

This research aimed to find out the prevalence of theileriosis by Giemsa stained blood films and to deal with hemato-biochemical changes in naturally infected cattle. The overall prevalence rates were 32.75% (95/290) for Theileria infection by Giemsa stained blood smears. Clinical examination of infected cattle showed signs of fever, anorexia, congested mucous membranes, corneal opacity, emaciation, enlargement of superficial lymph nodes, pale mucous membrane, respiratory signs, yellowish diarrhea and brown coffee urine were common clinical findings. There was no significant difference associated with prevalence between gender and age (P < 0.05). The hematological parameter revealed the microcytic anemia which was associated with large reductions in RBCs (4.48±0.11) 1012/l, Hb (7.15±0.18) g/dl, PCV (17.63±0.40) %, MCV (39.69±0.58) fl, MCHC (36.98±0.67) g/l and neutrophils (3.21±0.203) %. While a significant increase in the WBCs (13.24±0.32)109 /l and lymphocytes (61.42±1.84) % were found. The biochemical parameter revealed a significant increase in active serum enzyme AST (87.60± 0.12), ALT (21.70±0.07), ALP (119±0.06), and total serum bilirubin (1.13±0.01); whereas, a significant decrease in the total serum protein (6.10±0.03), albumin (2.70±0.03), calcium (7.40±0.02) and glucose (19.9±0.05) were recorded. According to the findings of this study, bovine theileriosis is a serious infectious disease in Erbil province. A more effective control program should be created to confine and manage the disease’s prevalence in the area

Age-related Macular Degeneration (AMD) is a major cause of sight impairment in the elderly with complex aetiology involving genetics and environment and with limited therapeutic options which have limited efficacy. We have previously shown in a mouse-model of the condition, induced by feeding a high fat diet, that adverse effects of the diet can be reversed by co-administration of the TSPO activator, etifoxine. We extend those observations showing improvements in retinal pigment epithelial (RPE) cells with decreased lipids and enhanced expression of cholesterol metabolism and transport enzymes. Further, etifoxine decreased levels of reactive oxygen species (ROS) in RPE and inflammatory cytokines in RPE and serum. With respect to gut microbiome, we found that organisms abundant in the high fat condition (e.g. in the genus Anaerotruncus and Oscillospira) and implicated in AMD, were much less abundant after etifoxine treatment. The changes in gut flora were associated with the predicted production of metabolites of benefit to the retina including tryptophan and other amino acids and taurine, an essential component of the retina necessary to counteract ROS. These novel observations strengthen earlier conclusions that the mechanisms behind improvements in etifoxine-induced retinal physiology involve an interaction between effects on the host and the gut microbiome.

Although many pharmaceutical compounds (and their metabolites) can induce harmful impacts at the molecular, physiological and behavioural levels, their underlying mechanistic associations have remained largely unexplored. Here, we utilized RNA-Seq to build a whole brain transcriptome profile to examine the impact of a common endocrine disrupting pharmaceutical (17α-ethinyl estradiol, EE2) on reproductive behaviour in wild guppies (Poecilia reticulata). Specifically, we annotated 16,791 coding transcripts in whole brain tissue in relation to the courtship behaviour (i.e. sigmoid display) of EE2 exposed (at environmentally relevant concentration of 8 ng/L for 28-days) and unexposed guppies. Further, we obtained 10,960 assembled transcripts matching in the non-coding orthologous genomes. Behavioural responses were assessed using a standard mate choice experiment, which allowed us to disentangle chemical cues from visual cues. We found that a high proportion of the RNAseq reads aligned back to our de novo assembled transcriptome with 80.59% mapping rate. Behavioural experiments showed that when males were presented only with female visual cues, there was a significant interaction between male treatment and female treatment in the time spent in the preference zone. This is one of the first studies to show that transcriptome-wide changes are associated with the reproductive behaviour of fish: EE2 exposed male guppies that performed high levels of courtship had a gene profile that deviated the most from the other treatment groups, while both non-courting EE2 and control males had similar gene signatures. Using Gene Ontology pathway analysis, our study shows that EE2-exposed males had gene transcripts enriched for pathways associated with altered immunity, starvation, altered metabolism and spermatogenesis. Our study demonstrates that multiple gene networks orchestrate courting behaviour, emphasizing the importance of investigating impacts of pharmaceuticals on gene networks instead of single genes.

Various studies have suggested that the gut microbiome interacts with the host and may have a significant role in the aetiology of obesity and Type 2 Diabetes (T2D). It was hypothesised that bacterial communities in obesity and T2D differ from control and compromise normal interactions between host and microbiota. Obesity and T2D were developed in rats by feeding a high-fat diet or a high-fat diet plus a single low-dose streptozotocin administration, respectively. The microbiome profiles and their metabolic potentials were established by metagenomic 16S rRNA sequencing and bioinformatics. Taxonomy and predicted metabolism-related genes in obesity and T2D were markedly different from controls and indeed from each other. Diversity was reduced in T2D but not in Obese rats. Factors likely to compromise host intestinal, barrier integrity were found in Obese and T2D rats including predicted, decreased bacterial butyrate production. Capacity to increase energy extraction via ABC-transporters and carbohydrate metabolism were enhanced in Obese and T2D rats. T2D was characterized by increased proinflammatory molecules. While obesity and T2D show distinct differences, results suggest that in both conditions Bacteroides and Blautia species were increased indicating a possible mechanistic link.

Obesity is intimately associated with diet and dysbiosis of gut microorganisms but anxiolytics, widely used in treatment of psychiatric conditions, frequently result in weight gain and associated metabolic disorders. We are interested in effects of the anxiolytic etifoxine, which has not been studied with respect to weight gain or effects on gut microorganisms. Here we induced obesity in mice by feeding a high-fat diet but found that intraperitoneal administration of etifoxine resulted in weight loss and decreased serum cholesterol and triglycerides. Obese mice had increased hepatic transcripts associated with lipid metabolism (cyp7a1, cyp27a1, abcg1 and LXRα) and inflammatory factors (TNFα and IL18) but these effects were reversed after etifoxine treatment other than cyp7a1. Taxonomic profiles of the organisms from the caecum were generated by 16S rRNA gene sequencing and Obese and etifoxine mice show differences by diversity metrics, Differential Abundance and functional metagenomics. Organisms in genus Oscillospira and genera from Lachnospiraceae family and Clostridiales order are higher in Control than Obese and at intermediate levels with etifoxine treatment. With respect to community metabolic potential, etifoxine mice have characteristics similar to Control and particularly with respect to metabolism of butanoate, sphingolipid, lipid biosynthesis and xenobiotic metabolism. We suggest mechanisms where-by etifoxine influences processes of host, such as on bile acid synthesis, and microbiota, such as signalling from production of butanoate and sphingosine, resulting in decreased cholesterol, lipids and inflammatory factors. We speculate that the indirect effect of etifoxine on microbial composition is mediated by microbial β-glucuronidases that metabolise excreted etifoxine glucuronides.

A total of 41 sorbitol non fermentative E. coli from previous work were used in this study. Among these isolates 5 were positive serologically by anti-O157 serum. All isolates were tested by PCR technique. No E. coli O157 were detected in all isolates by PCR. The results revealed that gene based method such as PCR technique is more reliable than biochemical and serological tests for diagnosis of E. coli O157

This study was carried out for the first time to investigate the occurrence of E. coliO157 in sheep and goats in Duhok province, Iraq. A total of 320 samples were collected from April to July2009 as following: 100 fecal samples from sheep, 100 fecal samples from goats, 60 samples from sheep milk and 60 samples from goat milk. E coliO157 was isolated from 3 (3%) sheep fecal samples and 2 (2%) from goat fecal samples, while no E. coliO157 was detected in the milk samples from sheep and goats. E. coliO157 was detected only among E. coli isolates which were sorbitol non fermentative but MUG positive, while no E. coliO157 was detected among E. coli isolates which were negative for both sorbitol and MUG. All E. coliO157 isolates were resistant to 6 among 12 antimicrobial agents used in vitro drug sensitivity test.

This study was conducted to determine the prevalence of Salmonella species in slaughtered animals and abattoir sewage from Zakho Abattoir, Kurdistan Region, Iraq. A total of 500 samples were collected including 200 from healthy sheep (100 rectal swabs and 100 gallbladder contents), 100 from healthy goats (50 rectal swabs and 50 gallbladder contents), 100 from cattle (50 rectal swabs and 50 gallbladder contents), and 100 sewage samples from the abattoir drains. From the total of 400 animals examined, 9 (2.25%) were positive for Salmonella spp., in which 5 (2.5%) were from sheep [ 2 (2%) from rectal swabs and 3 (3%) from gallbladder], 2 (2%) were from rectal swabs of goats, and 2 (2%) were from cattle [1 (2%) from rectal swabs and 1 (2%) from gallbladder]. Whereas, only 3 (3%) were positive for Salmonella spp., obtained from 100 sewage samples. Only three serotypes of Salmonella were detected in 12 (2.4%) samples from the total 500 samples. The isolated Salmonella serotypes were Salmonella hato 8 (66.66%), Salmonella anatum 3 (25%), and Salmonella enteritidis 1 (8.33%). The antimicrobial sensitivity test of all 12 isolates against 13 antibiotics was studied. Results revealed that all isolates were 100% sensitive to amoxicillin, amikacin, gentamicin, and ciprofloxacin, and 100% resistant to clindamycin, rifampin, vancomycin, cephalothin, lincomycin, and trimethoprim and sulfamethoxazole, chloramphinicol, doxycycline and tetracycline except S. hato. Collapse

The objective of the current study involved determination chemical composition (including lipid, protein ash, moisture and glycogen) in four fish species from Tigris River in North of Iraq. The chemical analysis revealed that the lipids in muscles of four fish species Carassius carassius, Mastacembleus mastacembleus, Barbas luteus and Silurus triostegus were 8.573 ±0.841 %, 7.715±0.736 %, 8.532± 0.685 %, and 14.650±0.554 % respectively. Proteins content in Carassius carassius, Mastacembleus mastacembleus, Barbas luteus and Silurus triostegus were 310.4 ± ٣.٦٤٩ mg/g, 380.5 ± ٢.٥٣٠ mg/g, 305.1 ± ١.٨٠٠ mg/g and 321.7 ± 3.٥٨٧ mg/g of the fresh weight, respectively. The study also shows that ash content and moisture ranged from 1.55±٠.٠٧٨ and 2.99±٠.٣٦٣ %, 76.05±٠.٥٤٠ and 80.73±٠.١٤٧ % of the fresh weight, correspondingly. The concentrations of protein in the fishes were significantly different among the species. Concentration of protein was the highest in muscle of Mastacembleus mastacembleus and lowest in the muscle of Barbas luteus. The highest concentrations of glycogen was found in the Carassius carassius among the four species (p<0.001).

Branchiomycosis is a fungal disease that infects fish gills. It was identified by isolation and histopathological changes of examined gills in common carp fish (Cyprinus carpio) which, were obtained from fish farm in Duhok Governorate, Iraq. The infected fish were suffering from respiratory disorders; gulping air at the water surface, rapid movement of operculum and massive mortality, which resulted in the loss of 95% of fish pond. The gills appear marbled appearance with necrotic areas on the localized damage gills. The causal pathogen was identified as Branchiomyces sanguinis, in which the diameter of spores and non-septated hyphae are 5-7 µm and 12 – 20 µm, respectively. In histopathological preparation, the spores and the non-septated hyphae have been shown to be embedded in the gill tissues contained undivided and sporulating stages.