Lactate is a key biomarker of tissue metabolism and oxygenation, yet clinical assessment still relies on intermittent blood tests that overlook rapid metabolic dynamics and disrupt clinical workflows. Continuous transdermal monitoring of lactate in interstitial fluid (ISF) offers a minimally invasive approach for real-time monitoring of metabolic status, particularly in conditions associated with metabolic syndrome such as obesity and diabetes. Here we report a proof-of-concept transdermal lactate biosensor based on a fenestrated microneedle array (F-MNA), consisting of a polymeric MNA enclosed within a fenestrated polymeric shell that protects the biosensing layer while retaining access to ISF. Under controlled anesthetized conditions, the biosensor differentiated ISF lactate profiles between healthy and diabetic-obese (db/db) mice, with the db/db group exhibiting higher baseline lactate concentrations. In fasted healthy mice subjected to subcutaneous glucose challenge, the biosensor captured transient increases in ISF lactate followed by partial recovery over the 2 h monitoring period. Biosensor-derived ISF lactate showed strong temporal association with paired blood lactate measurements while exhibiting a systematic positive ISF-to-blood concentration offset. These findings establish proof-of-concept continuous transdermal ISF lactate monitoring under controlled in vivo conditions.

BACKGROUND Unintentional poisoning is a preventable cause of injury-related morbidity and mortality, yet global patterns, trends, and inequalities remain incompletely characterised. Within the Global Burden of Disease (GBD) framework, unintentional poisoning includes poisoning by carbon monoxide and poisoning by other means, a category largely informed by pesticide poisoning codes plus some indirect capture of other poisoning as part of the GBD re-distribution process. Poisonings by pharmaceuticals and illicit substances are not captured in the GBD definition of poisoning. We aimed to quantify this GBD-defined burden and assess regional variation, sociodemographic gradients, and case fatality between 1990 and 2023. METHODS We analysed GBD 2023 estimates for 204 countries and territories, modelling deaths, incidence, and disability-adjusted life-years (DALYs) using standard GBD cause-of-death and non-fatal estimation methods with 95% uncertainty intervals. We stratified results by age, sex, region, and Socio-demographic Index (SDI), and derived case fatality from modelled deaths and incidence. FINDINGS In 2023, unintentional poisoning from carbon monoxide and other means caused 2·54 million incident poisonings, 69 805 deaths, and 3·68 million DALYs globally, with age-standardised DALY rates declining by 47·5% since 1990. Carbon monoxide accounted for 641 932 poisonings, 30 890 deaths and 1·34 million DALYs, with the highest burdens in central and eastern Europe and central Asia. Most regions showed substantial long-term declines, and the global age-standardised DALY rate for carbon monoxide poisoning declined by 58·2% since 1990. Poisoning by other means caused 1·90 million incident cases, 38 914 deaths, and 2·34 million DALYs, with the greatest burden in sub-Saharan Africa. Most regions showed declining age-standardised DALY rates for poisoning by other means; however, there was no clear change (with the 95% uncertainty interval including zero) in the global estimate, driven by wide uncertainty intervals in several regions (including sub-Saharan Africa). Mortality and DALYs were inversely associated with SDI, and derived case fatality was highest in low-SDI regions. INTERPRETATION Global reductions in GBD-defined unintentional poisoning by carbon monoxide and other means are consistent with decades of regulatory and environmental interventions. These include bans of highly toxic pesticides, improved heating and ventilation systems, emissions controls, and adoption of carbon monoxide alarms. Stark inequalities persist in some regions and in low-SDI settings. Compared with previous GBD publications, this study provides a detailed global assessment of unintentional poisoning by carbon monoxide and other means up to 2023, integrating incidence, DALYs, and comparative case fatality across regions. FUNDING Gates Foundation and the Australian National Health and Medical Research Council.

Summary Background Second-hand smoke (SHS) exposure remains a major source of morbidity and mortality among non-smokers. This study presents the first dedicated Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) publication to systematically quantify SHS prevalence and evaluate its effect as a global risk factor across a broader range of outcomes. Methods Using the GBD 2023 comparative risk assessment framework, we estimated SHS exposure prevalence and attributable disease burden across 204 countries and territories from 1990 to 2023, stratified by age and sex. Exposure estimates were derived by synthesising population-based surveys and household composition data through spatiotemporal Gaussian process regression. Relative risks for nine health outcomes, now including asthma, were estimated using the Burden of Proof methodology, and applied to calculate attributable deaths and disability-adjusted life-years (DALYs). Findings In 2023, an estimated 2·71 billion (95% UI 2·44–3·02) people worldwide were exposed to SHS, including 767 million (687–858) children aged 0–14 years. Age-standardised prevalence was highest in southeast Asia, east Asia, and Oceania (48·4% [44·0–53·4]), with female individuals in some countries experiencing nearly 1·8 times the exposure prevalence of male individuals. Despite a 22·2% (10·6–32·4) decline in global age-standardised prevalence since 1990, this progress has not been sufficient to reduce the absolute number of exposed individuals, which has remained stable globally and has risen sharply in sub-Saharan Africa (98·5% [62·0–144·4] increase) and North Africa and the Middle East (72·1% [47·8–101·8] increase). In 2023, SHS exposure accounted for 1·66 million (1·33–2·07) deaths and 44·8 million (35·8–54·3) DALYs globally. Ischaemic heart disease was the leading contributor to SHS-attributable DALYs (12·0 million [9·31–15·2]) overall, while lower respiratory infections predominated among children (5·16 million [3·48–7·12]). Interpretation We estimated that SHS remains a substantial driver of global health loss, particularly through cardiovascular and paediatric respiratory diseases. Persistent geographical disparities and growing absolute numbers of exposed individuals in several regions underscore the urgent need for accelerated implementation and enforcement of comprehensive tobacco control measures, particularly to protect women and children in both public and domestic environments. Funding Bloomberg Philanthropies and the Gates Foundation.

Cell therapies are increasingly manufactured in closed, automated culture systems, yet decisions about cell quality, safety, and release still rely largely on sparsely executed, destructive, and offline assays. Over the past 5 years, significant progress has been made in developing biosensors capable of real-time measurement of key biochemical and physicochemical indicators including metabolites, ionic species, and protein-associated stress indicators within cell culture environments. However, most systems remain disconnected from manufacturing workflows and fail to support actionable process control. This opinion article discusses the next phase of innovation and the need to reposition biosensors as process analytical technology, shifting the field from descriptive monitoring toward integrated, decision-driven control of cell therapy manufacturing.

Summary Background Understanding the size, gender composition, and cadre mix of the health workforce and how it has evolved across time and locations can inform policies for planning, recruitment, training, and retention of human resources for health (HRH), and improvement of access to the health-care workforce among populations. Using comparable and standardised data sources, we aim to describe the composition and density of health workers by sex among 20 cadres for 204 countries and territories over 1990–2023 and quantify workforce shortfalls relative to universal health coverage (UHC) attainment. Methods We used 1816 country-years of data from population-based surveys, 82 from censuses, 3888 from administrative sources, and 96 from scientific literature. We harmonised reported occupation in all sources with the International Standard Classification of Occupations 2008. We produced estimates for 20 cadres and the total health workforce disaggregated by sex using spatiotemporal Gaussian process regression, a standardised method in the Global Burden of Diseases, Injuries, and Risk Factors study. Finally, stochastic frontier meta-regression was used to estimate the minimum density of doctors, nurses and midwives, dentists, and pharmacists required to reach a score of 80 out of 100 on the UHC effective coverage index. Findings In 2023, there were 122·1 million (95% uncertainty interval 115·4–130·5) health workers across 20 cadres, an increase of 81·2 million (72·0–90·5) or 198·5% (161·9–245·6) relative to 1990. Of that total, there were 15·1 million (13·1–18·2) doctors, 33·2 million (30·8–36·3) nurses, 2·4 million (2·0–2·9) midwives, and 7·6 million (6·7–8·6) community health workers (CHWs). 68·9% (66·9–70·6) of all health workers in 2023 were female, and female health workers accounted for 71·4% (64·5–77·4) of net HRH workforce growth. Less than half of doctors were female (43·9%, 34·5–53·2) and most nurses (80·7%, 76·2–83·1), midwives (96·0%, 83·9–98·5), and CHWs (89·5%, 83·6–93·7) were female. Substantial differences in HRH density remained into 2023: sub-Saharan Africa had the lowest HRH densities across cadres, with the exception of CHWs, while high-income countries had the highest HRH densities. To reach 80 out of 100 on the UHC index, an additional 7·1 million (6·6–7·5) doctors, 23·9 million (21·8–26·1) nurses and midwives, 1·8 million (1·6–1·9) dentists, and 1·6 million (1·4–1·9) pharmacists are required globally. Interpretation The global health workforce has expanded substantially since 1990, largely due to women entering the formal health workforce. However, this expansion has been uneven across regions and persistent shortfalls remain in doctors, nurses and midwives, dentists, and pharmacists relative to moderate UHC attainment. Addressing these gaps will require expansion of training capacity, retention and remuneration policies for early-career workers, and gender-responsive workforce arrangements. Funding Gates Foundation.

BACKGROUND Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. METHODS We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. FINDINGS In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04-10·3) incident cases of all-form TB, 1·22 million (0·98-1·49) deaths, and 54·6 million (43·8-65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000-879 000) incident cases and 210 000 (142 000-279 000) deaths, contributing 11·0 million (7·56-14·3) DALYs. MDR-TB accounted for 466 000 (198 000-1 080 000) incident cases, 102 000 (31 700-238 000) deaths, and 3·96 million (1·31-9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8-20·5) and deaths declined by 22·6% (4·7-35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000-970 000) and DALYs to 34·9 million (27·8-43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400-183 000) and DALYs to 3·12 million (1·03-7·29). INTERPRETATION Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. FUNDING Gates Foundation.

Ensuring the quality, safety, and functional performance of stem cell cultures remains a critical challenge in biomedical research, drug development, and emerging cell-based therapies, as early metabolic disturbances can compromise outcomes and therapeutic efficacy. Glucose (Glu) consumption and L-lactate (LA) production serve as central indicators of cellular bioenergetic state, stress, and viability. However, conventional analytical approaches rely on discontinuous, labor-intensive assays that disrupt workflows and limit early intervention. Here, we report a miniaturized electrochemical biosensing platform for serial time-resolved analysis of Glu and LA in human induced pluripotent stem cell (hiPSC) culture media using a micropillar array (MPA)-based microfluidic electrochemical device (MED). The device exhibits linear detection ranges of 0.5-35 mM for Glu and 0.5-40 mM for LA, with limits of detection (LODs) of 0.18 ± 0.01 mM and 0.19 ± 0.01 mM, respectively. Using serially collected culture media, the MED quantifies dose-dependent metabolic responses to mitochondrial inhibition with oligomycin, revealing suppressed metabolic turnover and altered Glu-LA coupling prior to observable morphological changes. By enabling paired metabolic readouts from small-volume, undiluted culture-media samples, this platform provides a practical analytical route toward earlier recognition of culture-state deviations and more informed monitoring of stem-cell culture quality and drug-induced metabolic responses.

BACKGROUND Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. METHODS We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. FINDINGS In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963-1·68) deaths globally, declining from 3·69 million (3·04-4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0-92·9) per 100 000 population to 16·4 (12·6-21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811-1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000-882 000) and 501 000 (373 000-648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0-21·5]), followed by norovirus (10·2% [2·4-17·0]) and Shigella spp (9·3% [5·4-15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5-48·5) for rotavirus, 24·0% (15·1-36·7) for Shigella spp, and 23·4% (13·7-34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290-49 000) and 18 800 (4650-44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. INTERPRETATION Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. FUNDING Gates Foundation.

Wildlife–vehicle collisions (WVCs) represent a growing safety, ecological, and economic challenge, with direct consequences for human lives, material damage, and biodiversity conservation. In the Federation of Bosnia and Herzegovina, systematic analyses that link traffic accidents caused by collisions with wildlife are lacking. This research identifies high-risk locations of WVCs and applies geospatial analysis to the main roads of the Federation of Bosnia and Herzegovina. The analysis is based on official police reports documenting 14,169 traffic accidents between 2021 and 2023, of which 104 cases (0.73%) were classified as animal-related. Although species were not specified in the reports, these accidents predominantly occurred in areas where wildlife crossings are expected, and thus are treated as potential wildlife–vehicle collisions. The results indicate a concentration of WVCs in nine municipalities, with eight critical road segments identified on main roads. Additional analyses explored the relationship between collisions, road infrastructure (bridges, tunnels), and ecological features of habitats (Emerald Network, Natura 2000, Red List of FBiH, IUCN). Based on the findings, it can be concluded that spatially targeted prevention is essential, with priority given to infrastructural measures (wildlife overpasses, fencing, signage) and strategic measures (improved databases, continuous monitoring, and integration into spatial planning). The obtained results provide a foundation for policies that simultaneously enhance traffic safety and contribute to the protection of wildlife populations.