D.Y. Patil University

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Abstract Pearl millet [ Cenchrus americanus (L.) Morrone] is a staple food for more than 90 million farmers in arid and semi-arid regions of sub-Saharan Africa, India and South Asia. We report the ∼1.79 Gb draft whole genome sequence of reference genotype Tift 23D 2 B 1 -P1-P5, which contains an estimated 38,579 genes. We highlight the substantial enrichment for wax biosynthesis genes, which may contribute to heat and drought tolerance in this crop. We resequenced and analyzed 994 pearl millet lines, enabling insights into population structure, genetic diversity and domestication. We use these resequencing data to establish marker trait associations for genomic selection, to define heterotic pools, and to predict hybrid performance. We believe that these resources should empower researchers and breeders to improve this important staple crop.

Laccases (benzenediol:oxygen oxidoreductase, EC 1.10.3.2) are multi-copper oxidases that are widely distributed among plants, insects, and fungi. They have been described in different genera of ascomycetes, some deuteromycetes, and mainly in basidiomycetes. These enzymes catalyze the one-electron oxidation of a wide variety of organic and inorganic substrates, including mono-, di-, and polyphenols, aminophenols, methoxyphenols, aromatic amines, and ascorbate, with the concomitant four electron reduction of oxygen to water. Laccase is currently the focus of much attention because of its diverse applications, such as delignification of lignocellulosics, crosslinking of polysaccha-rides, bioremediation applications, such as waste detoxification, and textile dye transformation, food technologic uses, personal and medical care applications, and biosensor and analytical applications. This review helps to understand the properties of this important enzyme for efficient utilization for its biotechnological and environmental applications.

Curcumin induces cancer cell growth arrest and apoptosis in vitro, but its poor bioavailability in vivo limits its antitumor efficacy. We have previously evaluated the bioavailability of novel analogues of curcumin compared with curcumin, and we found that the analogue CDF exhibited greater systemic and pancreatic tissue bioavailability. In this study, we evaluated the effects of CDF or curcumin alone or in combination with gemcitabine on cell viability and apoptosis in gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer (PC) cell lines. Mechanistic investigations revealed a significant reduction in cell viability in CDF-treated cells compared with curcumin-treated cells, which were also associated with the induction of apoptosis, and these results were consistent with the downregulation of Akt, cyclooxygenase-2, prostaglandin E(2), vascular endothelial growth factor, and NF-kappaB DNA binding activity. We have also documented attenuated expression of miR-200 and increased expression of miR-21 (a signature of tumor aggressiveness) in gemcitabine-resistant cells relative to gemcitabine-sensitive cells. Interestingly, CDF treatment upregulated miR-200 expression and downregulated the expression of miR-21, and the downregulation of miR-21 resulted in the induction of PTEN. These results prompt further interest in CDF as a drug modality to improve treatment outcome of patients diagnosed with PC as a result of its greater bioavailability in pancreatic tissue.

Background and objectives The rapid and extensive spread of the COVID-19 pandemic has become a major cause of concern for the healthcare profession. The aim of this study is to assess the awareness of COVID-19 disease and related infection control practices among healthcare professionals and students in the Mumbai Metropolitan Region. Materials and methods A total of 1562 responders from the Mumbai Metropolitan Region completed a questionnaire-based survey on the awareness, knowledge, and infection control practices related to COVID-19 infection in the healthcare setting. The questionnaire was adapted from the current interim guidance and information for healthcare workers published by the US Centers for Disease Control and Prevention (CDC). Convenient sampling method was used for data collection and the distribution of responses was presented as frequencies and percentages. Descriptive statistics were performed for all groups and subgroups based on the percentage of correct responses. Individual pairwise comparisons were done using the median test for the percentage of correct responses. Results The overall awareness for all subgroups was adequate with 71.2% reporting correct answers. The highest percentage of correct responses were from undergraduate medical students and the lowest was from non-clinical/administrative staff. Less than half of the total respondents could correctly define "close contact." More than three-fourths of the responders were aware of the various infection control measures like rapid triage, respiratory hygiene, and cough etiquette and having a separate, well ventilated waiting area for suspected COVID-19 patients. However, only 45.4% of the responders were aware of the correct sequence for the application of a mask/respirator, and only 52.5% of the responders were aware of the preferred hand hygiene method for visibly soiled hands. Conclusion There is a need for regular educational interventions and training programs on infection control practices for COVID-19 across all healthcare professions. Occupational health and safety are of paramount importance to minimize the risk of transmission to healthcare students and professionals and provide optimal care for patients.

-antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.

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. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Plumbagin is one of the simplest plant secondary metabolite of three major phylogenic families viz. Plumbaginaceae, Droseraceae, and Ebenceae, and exhibits highly potent biological activities, including antioxidant, antiinflammatory, anticancer, antibacterial, and antifungal activities. Recent investigations indicate that these activities arise mainly out of its ability to undergo redox cycling, generating reactive oxygen species and chelating trace metals in biological system. The compound is endowed with a property to inhibit the drug efflux mechanism in drug-resistant bacteria, thereby allowing intracellular accumulation of the potent drug molecules. An interesting bioactivity exhibited by this compound is the elimination of stringent, conjugative, multidrug-resistant plasmids from several bacterial strains including opportunistic bacteria, such as Acinetobacter baumannii. Moreover, plumbagin effectively induces apoptosis and causes cell cycle arrest, which is, in part, due to the inactivation of NF-κB in cancer cells. Therefore, it has been suggested that designing "hybrid drug molecules" of plumbagin by combining it with other appropriate anticancer agents may lead to the generation of novel and potent anticancer drugs with pleiotropic action against human cancers. This comprehensive review is an attempt to understand the chemistry of plumbagin and catalog its biological activities reported to date.

Silver nanoparticles (AgNPs) are widely recognized for their unique optical, electronic, and antibacterial properties, enabling their use in biosensing, photonics, electronics, drug delivery, and antimicrobial treatments. Green chemistry-based biological synthesis methods offer an eco-friendly alternative to traditional chemical techniques. Among metallic nanoparticles (NPs) and metal oxides, those derived from plant extracts exhibit notable medicinal properties. Due to their exceptional stability and low chemical reactivity, AgNPs are particularly well-suited for various biological applications. AgNPs can be synthesized through chemical, physical, or biological methods, each with distinct benefits and challenges. Chemical and physical approaches often involve complex purification, reactive reagents, and high energy demands, while biological methods, though slower, provide sustainable solutions. The chosen synthesis method strongly influences the stability, size, and purity of the resulting NPs. This review emphasizes the importance of selecting appropriate synthesis methods to optimize the characteristics and functionality of silver NPs. It consolidates research spanning the past two decades, including the most recent findings from 2024. A comprehensive electronic search of databases such as PubMed, Scopus, ScienceDirect, Cochrane, and Google Scholar was conducted to provide an up-to-date overview of advances in the synthesis and applications of silver nanoparticles.

studies. Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity. Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients.

Strategies to bridge the gap between magnetic nanoparticles for their nano bio applications.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused great financial and psychological havoc. Healthcare professionals (HCPs) are among the many groups of people who are in the frontline and facing a risk of direct exposure to the virus. This study aimed to assess the prevalence and predictors of stress, depressive, and anxiety symptoms among HCPs of India. METHODS: It was a cross-sectional, online survey conducted in April 2020 among HCPs who are directly involved in the triage, screening, diagnosing, and treatment of COVID-19 patients and suspects. Stress was estimated using Cohen's perceived stress scale. Depression and anxiety were assessed using the tools Public Health Questionnaire-9 and Generalized Anxiety Disorder-7. Predictors were analyzed using univariate and multivariate binary logistic regression. RESULTS: A total of 433 online responses were obtained, and N = 350 were finally included. The prevalence (95% CI) of HCPs with high-level stress was 3.7% (2.2, 6.2), while the prevalence rates of HCPs with depressive symptoms requiring treatment and anxiety symptoms requiring further evaluation were 11.4% (8.3, 15.2) and 17.7% (13.9, 22.1), respectively. Women had approximately two times the increased odds of developing moderate- or high-level stress, depressive symptoms requiring treatment, and anxiety symptoms requiring further evaluation. Similarly, women staying in a hostel/temporary accommodation had two times the increased odds of developing depression or anxiety symptoms. CONCLUSION: The prevalence of stress, depressive, and anxiety symptoms among HCPs in India during the pandemic is comparable with other countries.

Recent advances in development of potential magnetic nanoparticles for magnetic fluid hyperthermia are summarized. This review covers relation between various size dependent physical properties and their applications subject to modification in synthesis methods. Brief discussion on different heating mechanism of magnetic nanoparticles is provided. This review covers recent progress of various magnetic nanoparticles including core shell type for in vitro, in vivo and pre-clinical trials. The highlight of this review is to build up a bridge between synthesis, surface modification and in vivo- pre-clinical in magnetic fluid hyperthermia. Keywords: In vitro, In vivo and Pre-clinical trials of MFH, magnetic nanoparticles, synthesis, magnetic fluid hyperthermia (MFH).

(NCIM 2613). The antibacterial and antibiofilm activity was inversely proportional to the size of the synthesized ZnO nanoparticles. Among all prepared particles, ZnO nanoparticles with least size (~ 15 nm) prepared by refluxing zinc acetate dihydrate in diethylene glycol for 3 h exhibited remarkable antibacterial and antibiofilm activity which may serve as potential alternatives in biomedical application.

Crystal structure of CoFe₂O₄where green atoms are Co, pink atoms are Fe and blue atoms are O.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Recently lots of efforts have been taken to develop superparamagnetic iron oxide nanoparticles (SPIONs) for biomedical applications. So it is utmost necessary to have in depth knowledge of the toxicity occurred by this material. This article is designed in such way that it covers all the associated toxicity issues of SPIONs. It mainly emphasis on toxicity occurred at different levels including cellular alterations in the form of damage to nucleic acids due to oxidative stress and altered cellular response. In addition focus is been devoted for in vitro and in vivo toxicity of SPIONs, so that a better therapeutics can be designed. At the end the time dependent nature of toxicity and its ultimate faith inside the body is being discussed.

BACKGROUND: Dermatophytosis management has become an important public health issue, with a large void in research in the area of disease pathophysiology and management. Current treatment recommendations appear to lose their relevance in the current clinical scenario. The objective of the current consensus was to provide an experience-driven approach regarding the diagnosis and management of tinea corporis, cruris and pedis. METHODS: Eleven experts in the field of clinical dermatology and mycology participated in the modified Delphi process consisting of two workshops and five rounds of questionnaires, elaborating definitions, diagnosis and management. Panel members were asked to mark "agree" or "disagree" beside each statement, and provide comments. More than 75% of concordance in response was set to reach the consensus. RESULT: KOH mount microscopy was recommended as a point of care testing. Fungal culture was recommended in chronic, recurrent, relapse, recalcitrant and multisite tinea cases. Topical monotherapy was recommended for naïve tinea cruris and corporis (localised) cases, while a combination of systemic and topical antifungals was recommended for naïve and recalcitrant tinea pedis, extensive lesions of corporis and recalcitrant cases of cruris and corporis. Because of the anti-inflammatory, antibacterial and broad spectrum activity, topical azoles should be preferred. Terbinafine and itraconazole should be the preferred systemic drugs. Minimum duration of treatment should be 2-4 weeks in naïve cases and > 4 weeks in recalcitrant cases. Topical corticosteroid use in the clinical practice of tinea management was strongly discouraged. CONCLUSION: This consensus guideline will help to standardise care, provide guidance on the management, and assist in clinical decision-making for healthcare professionals.

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. FUNDING: Gates Foundation.

Silver nanoparticles (SNPs), owing to their wide range of biomedical applications, have recently attracted remarkable interest for use in cancer nanomedicine. The present research work investigated the anticancer activity of phytosynthesized SNPs against human cancer cell lines. Phytosynthesis of SNPs was achieved by using an aqueous extract of Salacia chinensis (SC) bark as a green source to reduce silver nitrate to silver nanoparticles. Characterization of synthesized nanoparticles demonstrated a UV–visible peak at 443 nm, ζ-potential (zetasizer) of −25.6 ± 0.34 and particle size (transmission electron microscopy analysis) in the range of 40–80 nm, which validates formation of stable silver nanoparticles. The absence of cytotoxicity against normal human fibroblasts and blood erythrocytes confirms the biocompatible nature of green synthesized SNPs. In vitro anticancer assay demonstrated IC50 values of 6.31, 4.002, 5.228, 8.452, 14.37, 7.46, and 6.55 μg/mL against liver (Hep G2), lungs (L-132), pancreas (MIA-Pa-Ca-2), breast (MDA-MB-231), oral (KB cells), prostate (PC-3), and cervical (HeLa) cancer cell lines respectively, which confirms its potent anticancer action. The results of the present study give an experimental proof that the SC mediated green synthesized SNPs could serve as a promising anticancer agent to overcome limitations of existing conventional cancer chemotherapeutics.