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Pharmacological therapies for the prevention of fractures in men.

RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.

Humans

Air Pollution and Heat Impacts on Respiratory Morbidity and Mortality Outcomes in Africa: A Systematic Review Towards a Meta-analysis.

PURPOSE OF THE REVIEW: This review synthesised evidence on associations between air pollution and respiratory morbidity in Africa. Following PRISMA guidelines, we systematically searched PubMed, ScienceDirect and Elicit for case-control studies published between 2015 and 2025. RECENT FINDINGS: Thirteen studies from ten African countries reported pollutant levels far exceeding WHO guidelines. Indoor PM₂.₅ in biomass-using homes ranged from 96 to 177 µg/m³, and ambient PM₂.₅ reached 259 µg/m³. Nitrogen oxides were consistently associated with reduced lung function in children, while household air pollution increased risks of under-five mortality and low birthweight. Associations with acute respiratory infections varied across settings. Vulnerability was greatest among young children, those with airway hyperresponsiveness, and households with poor ventilation. Only three studies included temperature, and none examined heat-respiratory interactions. Across African case-control studies, particulate matter and household air pollution remain consistently linked to adverse respiratory outcomes, highlighting urgent needs for cleaner fuels, improved ventilation, and stronger evidence on combined pollution and heat exposures.

Humans

To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans

Review: The African turquoise killifish as a model for the integrative physiology of vertebrate aging.

With increasing emphasis on extending healthy lifespan, aging research requires vertebrate models that permit efficient mechanistic investigation and intervention testing within practical time and cost constraints. The African turquoise killifish (Nothobranchius furzeri) has attracted growing attention because it combines an exceptionally short life cycle with an intact vertebrate physiological context and an expanding genetic toolkit, enabling relatively rapid evaluation of candidate aging interventions and mechanistic analysis across molecular, tissue, and organismal levels. This review assesses N. furzeri from an integrative-physiology perspective, focusing on germline-soma interactions, gut microbiota-host crosstalk, nutrient sensing and metabolic remodeling, temperature responsiveness, and AMPK-mTOR-linked programs. It also examines expanding genome-engineering and reporter approaches that support mechanistic and tissue-resolved investigation of these physiological processes. Building on recent reviews of killifish biology, disease modeling, regeneration, and the hallmarks of aging, we synthesize evidence across major intervention domains, distinguish established phenotypic effects from incompletely resolved mechanisms, and highlight functional endpoints, methodological standardization, and the appropriate interpretation of the model's translational relevance. Together, these features position N. furzeri as a strategically useful vertebrate platform for rapid mechanistic testing, intervention evaluation, and prioritization of aging-related pathways. Future progress will require improved methodological standardization, tissue-resolved causal studies, and question-driven cross-species validation where appropriate.

Animals

Messaging Strategies for Tobacco Prevention and Cessation Among People with Depression: A Scoping Review.

INTRODUCTION: Depression is strongly associated with higher tobacco use and lower quit rate; few communication campaigns have been designed with these mental health factors in mind. This scoping review compiles existing research on tobacco prevention and cessation messaging involving people with depression to identify gaps and opportunities for future message development. METHODS: Sources included PubMed, PsycINFO, Scopus, Academic Search Premier, and ProQuest Central (November - December 2024). The 55 studies included examined tobacco prevention or cessation messages and measured depression, depressive symptoms, or mental health as a primary outcome or analytic covariate. Study characteristics, target population, delivery format, message content, theoretical frameworks, outcomes, and gaps were extracted. RESULTS: RCTs made up half (51%) of the included studies, and most (78%) were conducted in the U.S. Nearly half (46%) required participants to have a mental health condition. Interventions most often used interactive (65.5%) or text-based (47.3%) communication and focused on tobacco cessation (89%) rather than vaping (9%). Common outcomes included feasibility or acceptability (37.7%) and point prevalence abstinence (37.7%). Mental health-specific messages showed mixed effectiveness. CONCLUSIONS: Despite progress in integrating mental health into tobacco messaging, targeted interventions for people with depression remain limited. Few studies tested long-term outcomes or used biochemical verification; many relied on untargeted generalized messaging.

Journal Article

Spatially resolved multi-omics analysis of indigenous Bacillus-fortified high-temperature Daqu.

Layer-dependent patterns associated with indigenous Bacillus fortification on high-temperature Daqu remain unclear. Here, six indigenous functional Bacillus strains were combined to fortify Daqu at three inoculation levels (QH4, QH5, QH6), with non-fortified as the control (CK). Upper, middle, and lower shelf-layer samples were profiled by physicochemical measurements, volatilomics, organic acid analysis, untargeted metabolomics, 16S/ITS amplicon sequencing, and metagenomics. PERMANOVA showed significant effects of treatment, spatial layer, and their interaction on physicochemical, volatile, bacterial, and fungal profiles (P = 0.001). Among the three inoculation levels, QH5 showed the most balanced performance: QH5_M exhibited the highest observed mean peak temperature (63.3 °C; +4.5 °C relative to CK_M), and its group-mean temperature remained ≥ 60 °C for seven consecutive days. Multi-omics analyses indicated coordinated, non-linear, and layer-dependent differences associated with indigenous Bacillus fortification, with QH5_M showing the most pronounced combined thermal, pyrazine, substrate, microbial, and predicted functional profile. These findings indicate that moderate indigenous Bacillus fortification was associated with distinct layer-dependent thermal and flavor profiles and coordinated microbial, metabolic, and predicted functional differences.

Bacillus

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults ≥18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, ≥3 months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Humans

Behind the Curtain of Care. Nurses' Experiences Providing Care to Consumers With Alcohol and Other Drug Issues: A Qualitative Scoping Review.

AIM: To scope and synthesise qualitative literature relating to nurses' experiences of providing care to consumers with alcohol and other drug issues and explore how meaning is constructed in practice. DESIGN: Scoping review. METHODS: A scoping review was conducted following Arksey and O'Malley's framework. Findings were analysed using thematic analysis. DATA SOURCES: Systematic searches were conducted between September and November 2025 across Medline, Emcare, CINAHL and Google Scholar, using controlled vocabulary and keywords relevant to nurses' experiences of providing care to consumers with alcohol and other drug issues. RESULTS: Twenty-four studies from 12 countries were included. Seven themes were identified: emotional aspects of care, education, training and skills in practice, the spectrum of stigma, ethical issues in professional practice, navigating pain management, limited support, and how meaning is constructed in practice. CONCLUSION: Nurses' experiences of providing care to consumers with alcohol and other drug issues are shaped by multiple intersecting factors influencing care delivery and professional practice. Further research is needed to examine how workplace culture, language and interpersonal interactions influence healthcare experiences, and inform education, service development and support needs. REPORTING METHOD: Reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

alcohol and other drugs

Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.

In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F₁ and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F₁-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F₁ hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.

cis-regulation

Multiscale Modeling Primer: Focus on Chromatin and Epigenetics.

A central challenge in modern biology is to understand how molecular interactions produce cellular and organismal functions across vast spatiotemporal scales. Nowhere is this challenge more apparent than in the study of chromatin, where meters of DNA compact into a micron-sized nucleus. How this polymer folds is a dynamic process, regulated by epigenetic modifications-chemical changes to DNA and histones that involve only a handful of atoms. These small changes cooperate to produce emergent, higher-order structures that define cellular identity and function. To explain this system, we must integrate static, high-resolution snapshots from techniques like cryo-EM with dynamic, lower-resolution data from microscopy and genomics. Multiscale computational models are essential tools that bridge these experimental gaps and reveal the mechanisms of emergent behavior. However, the communication divide between experimental biologists and quantitative modelers often hampers progress. This primer addresses that gap. It first introduces the fundamental biology of chromatin and epigenetics at an introductory level for non-biologists audiences. We then survey the landscape of computational approaches, from atomistic to systems-level models, and connect them to the experimental data that inform and validate them at an introductory level for non-computationalists. We argue that the next frontier will require us to build integrative models that can predict how molecular perturbations mechanistically alter cellular phenotypes, which will open a new era of chromatin-targeted therapeutics.

Chromatin Dynamics

Handle with care: packaging the oocyte epigenome for the next generation.

During oocyte growth, substantial epigenetic programming occurs to establish a distinctive epigenome including appropriately patterned DNA methylation and histone modifications. Oocyte epigenetic programming must be tightly spatiotemporally regulated to ensure that a wide variety of epigenetic modifiers correctly establish their respective modifications to mediate precise control of gene expression. Furthermore, epigenetic modifications in oocytes include canonical and non-canonical genomic imprints, which are transmitted through meiosis to offspring. Significantly, disruptions in oocyte epigenetic programming can cause aberrant developmental outcomes in the next generation mediated by altered imprinting. Polycomb repressive complex 2 is an important epigenetic modifier that establishes histone 3 lysine 27 trimethylation and non-canonical imprints during mouse oogenesis, which are important for normal offspring development. While it is widely recognised that altered oocyte epigenetic programming can disrupt offspring development, mechanisms controlling maternal epigenetic inheritance remain poorly understood. The possibility remains that non-canonical imprinting exists in humans, although this requires confirmation. This review discusses mouse and human oocyte epigenetic programming including interactions between various epigenetic modifiers and modifications that form the unique oocyte epigenome. Understanding how oocyte epigenetic programming is regulated will be crucial in discerning how changes to the oocyte epigenome can disrupt epigenetic memory and alter developmental outcomes in offspring.

Animals

Psychological consequences of AI-assisted training and the buffering role of mindfulness.

The integration of artificial intelligence (AI) into athletic training is accelerating, yet its psychological implications for athletes remain insufficiently understood. Drawing on the transactional model of stress and the stress-buffering framework of mindfulness, this study examined whether mindfulness training can mitigate adverse psychological responses associated with AI-assisted training. Using a randomized controlled factorial design, 160 collegiate athletes were assigned to AI-assisted training or standard training, with or without concurrent mindfulness intervention, and assessed at baseline, week 4, and week 8. Athletes exposed to AI-assisted training without psychological support exhibited increases in perceived stress and AI dependence over time. In contrast, these stress increases were substantially attenuated when mindfulness training was implemented alongside AI-assisted training. A significant AI × Mindfulness × Time interaction emerged for perceived stress at post-intervention, and difference-in-differences analyses corroborated a robust buffering effect. Mediation analyses further indicated that mindfulness training reduced stress partially through enhancing mindful awareness; a three-wave cross-lagged analysis showed that mindful awareness and stress were reciprocally related over time, with the hypothesized awareness-to-stress pathway remaining robust. Together, these findings suggest that AI-assisted training introduces a distinct form of evaluative pressure, and that mindfulness training may serve as an effective psychological buffer during the adoption of continuous algorithmic performance evaluation systems.

Humans

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials

Gut microbiota and metabolic alterations in participants with flatulence identify Faecalibacterium prausnitzii as a key microbial target for clinical intervention.

Flatulence is closely associated with gut dysbiosis, yet the characteristic microbial signatures, metabolic alterations, and actionable intervention targets remain unclear. This limited mechanistic understanding has hindered the development of precise microbiota-based strategies for managing flatulence. Here, we found that participants with flatulence exhibited marked shifts in gut microbial functions and fecal metabolic profiles compared with healthy controls, characterized by enhanced abnormal fermentation, enrichment of oxidative stress-related functions, elevated low-grade inflammatory signatures, and reduced anti-inflammatory and mucosal-protective metabolic features. Faecalibacterium prausnitzii was significantly negatively associated with the high-gas-producing phenotype. In vitro replenishment experiments further validated the role of F. prausnitzii in reducing gas production, promoting butyrate generation, and remodeling butyrate-associated microbial communities. Based on microbial interaction analysis, we identified Bifidobacterium longum CCFM1319 as a candidate strain for targeting F. prausnitzii. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with B. longum CCFM1319 significantly increased intestinal F. prausnitzii abundance and improved flatulence-related symptoms. Collectively, these findings reveal the microbiota and metabolic dysbiosis underlying flatulence, highlight the key regulatory role of F. prausnitzii, and lays the foundation for targeted microbiota-based intervention strategies for flatulence.

Humans

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries

The spatial and temporal distribution of Staphylococcus aureus along a tropical Hawaiian watershed.

Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.

Staphylococcus aureus

Vortex-assisted liquid-liquid microextraction based on natural deep eutectic solvents for the determination of pyrethroid pesticides in urine.

A novel, facile, and environmentally friendly analytical method was developed based on vortex-assisted liquid-liquid microextraction and high-performance liquid chromatography with diode-array detection for detecting pyrethroid pesticides (PPs) in urine. Natural deep eutectic solvents (NADESs) were prepared using plant essential oil-derived monoterpenoids (thymol, carvacrol, and menthol) combined with aromatic primary alcohols (benzyl alcohol, phenethyl alcohol, and phenylpropyl alcohol) as hydrogen bond donors and acceptors. These solvents served as environmentally benign extraction media, thereby avoiding the use of conventional volatile, toxic organic solvents. NADESs are naturally derived, easy to prepare, biodegradable, and environmentally friendly solvents. Hydrophobic and π-π interactions between the NADESs and PPs may contribute to enhancing the affinity of PPs toward the NADESs phase. Vortex technology, accelerating mass transfer between the sample and extractant phases, enables fast extraction of PPs. Under optimized conditions, the method achieved a low detection limit (0.002 mg L-1), satisfactory precision with relative standard deviations (0.3%-2.4%), and acceptable recovery (80.7%-86.2%). The method demonstrated excellent performance in urine analysis and was feasible as a facile and green strategy for monitoring the content of PPs in biological matrices and assessing exposure risk.

Liquid Phase Microextraction

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (±1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans