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1,4-Dioxane is a widespread groundwater contaminant frequently co-occurring with chlorinated solvents. The group-6 propane monooxygenase (PRM) from Mycobacterium dioxanotrophicus PH-06 degrades dioxane efficiently, yet the molecular determinants underlying its broad substrate spectrum and inhibition behavior remain unresolved. Here, we combined AlphaFold2-based structure prediction, molecular docking, and alchemical free energy calculations to systematically characterize ligand binding in PH-06 PRM. The catalytic center (residues 87-265), coordinated by two histidines and four glutamates, exhibited calculated binding free energies for five substrates (C2-C4 alkanes and cyclic ethers) that significantly correlated with experimentally determined degradation rates (p < 0.05), supporting the ability of ligand binding thermodynamics to capture major substrate-recognition trends in PH-06 PRM. In addition, we identified a remote binding site (residues 329-446) approximately 30 &#xc5; from the catalytic center. Thermodynamic analysis indicates that this remote site can attract methane and ethane, potentially limiting their access to the catalytic center. Comparative binding analyses of three common chlorinated solvent inhibitors (i.e., trichloroethylene [TCE], 1,1-dichloroethylene [DCE], and 1,1,1-trichloroethane [TCA]) revealed distinct site preferences consistent with their experimentally observed inhibition modes. Noncompetitive inhibitors (DCE and TCA) displayed stronger affinity for the remote site, whereas the competitive inhibitor TCE exhibited comparable affinity for both binding regions. Sequence conservation, contact probability analysis, and Gene Ontology enrichment further suggest the structural relevance of the remote site and its possible role in ligand recognition and inhibitor selectivity. These findings demonstrate that the AlphaFold-guided free energy calculations can capture experimentally observed substrate and inhibitor trends in PH-06 PRM, while identifying a remote ligand-binding pocket that warrants further mechanistic investigation.

This study aimed to describe rural data from the Australian National Study of Mental Health and Wellbeing survey (2020-2022) to assess strengths-based questions, differences by rurality, and factors associated with excellent social connectedness. Survey questions were mapped to the Rural Strengths Socioecological Framework. Descriptive and logistic analyses assessed rural adults' use of strengths by remoteness and presence of affective/anxiety disorders in the past 12&#x2009;months. Logistic regression explored factors associated with social connectedness. Survey questions reflected some strengths within the Framework including self-management techniques, family and friend support, social connectedness, and health care personnel. However, questions were primarily framed using a deficit perspective and many strengths from the Framework (i.e. nature, rural norms, culture, and lay personnel) were absent. Most strengths did not differ significantly between levels of rurality, though making healthy diet choices (as a self-management technique) was significantly lower in remote areas. Adults without affective/anxiety disorders more often reported good social support and self-efficacy. Conversely, those with affective/anxiety disorders were more likely to self-manage and access consultations for mental health. Excellent social connectedness was associated with better mental health. The survey questions reflected limited strengths. Future surveys should include a broader range of strengths-based questions spanning the extent of the Rural Strengths Socioecological Framework. Healthy diet choices as a self-management tool in remote areas may need to be prioritised. Findings also suggest the need for targeted approaches to protect, improve, or leverage social connectedness for those with more severe illness in rural areas.

All 17 of Nevada's counties carry a federal Health Professional Shortage Area (HPSA) designation, straining the state's capacity to deliver care remotely. This narrative review examines four dimensions of that capacity. It asks how telehealth is regulated and used, how far health information exchange and electronic health records have spread, whether broadband can support remote care, and what role artificial intelligence (AI) and remote patient monitoring (RPM) now play. Throughout, it considers how the state's workforce shortages, geography, and demographic diversity shape both demand for digital health and the barriers to it, with attention to equity. Four databases (PubMed/MEDLINE, CINAHL, Scopus, Google Scholar) were searched alongside federal, state, and policy grey literature for English-language sources from January 2015 to March 2026, yielding 88 sources, 40 peer-reviewed. Nevada has enacted comparatively expansive telehealth legislation, including conditional payment parity made permanent under Senate Bill 119 (2023); however, the limited utilization evidence shows uptake varying by race, ethnicity, and language. The sole statewide HIE operates under an opt-in consent model that constrains data availability, and roughly 100,000 Nevadans lack wireline broadband at the federal benchmark speed, concentrated in rural areas. AI and RPM are being deployed in rural settings without published evaluation, and nearly all peer-reviewed evidence on Nevada's digital health derives from a single study. Nevada's policy framework has outpaced its infrastructure and equity conditions; closing that gap requires coordinated action across HIE consent reform, broadband-telehealth alignment, Medicaid RPM reimbursement, and community-level investment in digital literacy and language access.

Health-related quality of life (HRQoL) is frequently impaired in cirrhosis. Among the most critical components of reduced HRQoL in cirrhosis is disturbed sleep. Despite the importance of sleep in cirrhosis and overall health, sleep is rarely clinically assessed and the specific aspects of sleep which drive reduced wellbeing are understudied. Remote monitoring with wearable technology may facilitate sleep assessment and targeted intervention. We enrolled 119 participants with cirrhosis across two academic medical centers and collected baseline clinical, cognitive and laboratory assessment and 6 months of longitudinal wearable tracking with an Oura Ring. HRQoL was assessed with the Chronic Liver Disease Questionnaire (CLDQ) and subjective sleep quality with the Pittsburgh Sleep Quality Index. Association of sleep metrics with HRQoL and subjective sleep was assessed in multivariable mixed effects model, with mediation analysis further analyzing the relationship. Across analysis of 12516 sleep episodes in 88 participants who completed all assessments and &#x2265;14 valid sleep nights, there was a strong association between measured sleep and reported sleep quality as well as HRQoL, with reduction in sleep efficiency, overall sleep time, and sleep regularity index (SRI). In adjusted mediation analyses, SRI was the strongest mediator (49.9% total mediation effect, ACME = - 0.093, p<0.001) of the relationship between liver disease severity (as measured by Child-Turcotte-Pugh Score) and CLDQ. In a large prospective study of remote sleep monitoring in liver disease, we found that sleep regularity had a strong association with patient-reported sleep quality and wellbeing, and was the strongest sleep metric mediating the relationship between progressive liver disease and overall HRQoL. These findings suggest the potential for circadian-targeted interventions in patients with cirrhosis. Sleep impairment is a major contributor to reduced wellbeing in cirrhosis, but existing sleep assessments often are too cumbersome to be used clinically and fail to capture long-term sleep patterns and circadian disruption. Using six months of wearable-derived sleep data, this study identifies sleep irregularity, as captured by the Sleep Regularity Index, as the sleep metric most strongly associated with patient reported sleep and overall wellbeing impairment. These findings suggest that sleep regularity, a marker of circadian rhythm dysfunction, may be an important digital biomarker for progressive worsening in cirrhosis and highlight a possible target for future interventions. If validated in future studies, wearable monitoring of sleep could provide clinicians and researchers a scalable approach for identifying patients with cirrhosis at increased risk for impaired wellbeing through sleep disturbance and monitor response to treatment.

Plastic pollution is an ever-growing concern around the globe, with current research portraying the presence of contaminants even in previously pristine regions. Especially small particles, micro- and nanoplastics, can be dispersed over long stretches by atmospheric transport, reaching even the most remote areas of the planet. This study aims to portray current levels of nanoplastic contamination (<&#x2009;1&#xa0;&#x3bc;m) by analyzing snow samples from high-altitude glaciers in the European Alps (2300-3800&#xa0;m) via TD-PTR-MS. We were able to detect six common plastic pollutants, with PE and PP contributing over 60% of the total mass concentration measured across all sites. On average, nanoplastic concentrations of 85 ng mL-&#x2009;1 (range: 3.6&#x2009;&#xb1;&#x2009;12 ng mL-&#x2009;1 - 470&#x2009;&#xb1;&#x2009;76 ng mL-&#x2009;1) were detected at sampled glacier surfaces. Access to these remote regions was enabled through a citizen-science initiative, involving trained mountaineers for sample collection. The results were applied to atmospheric modelling, highlighting possible point sources of contamination. While agriculture and local plastic factories were revealed as potential sources of nanoplastics, spatial and temporal limitations complicated comparison inside the sample cluster.

To describe HPTN 094 study's peer navigation (PN) intervention, implemented in 5 urban US cities among people who inject drugs (PWID) at risk for or living with HIV, including guiding theories, core components, navigator training, available services, implementation challenges, and implications for future PN intervention research dissemination. This 2-arm, randomized, open-label study assessed outcomes for PWID receiving integrated care services delivered in a mobile health unit that provided medication for opioid use disorder (MOUD), HIV prevention/treatment, and other health care in addition to PN to community services compared with PN to community services alone. Participants were PWID with opioid use disorder (OUD) not receiving MOUD and were either at risk for HIV or living with HIV. The PN model was grounded in 5 complementary theories addressing individual, interpersonal, social, systemic, and structural determinants of care. Variables used to measure PN intervention utility were number of sessions attended, session length, session topics, and in-person versus remote navigation sessions. Across study sites, participants without HIV (PWOH; n = 409) completed 3390 PN sessions and participants with HIV (PWH; n = 38) completed 365 PN sessions; the median number of sessions per participant was 6 in both groups. Most sessions were conducted in person and commonly addressed MOUD, HIV prevention or HIV care, and other medical or social service needs. These findings support the feasibility of delivering a flexible, theory-informed PN model for urban PWID and help characterize how peer navigation was used to address substance use, HIV, and broader service needs within HPTN 094. The PN model is acceptable with urban PWID and potentially for people with other public health concerns in underserved communities. The findings have implications for future research examining the effectiveness and dissemination of the PN intervention.

About 3.5 million fishing vessels ply the world's oceans, providing livelihoods and food for millions of people. Sound management is key to fisheries' sustainability, but illegal fishing, along with fishing overcapacity generally and environmental change, are putting many fisheries at risk. Illegal fishing is a globally pervasive yet unevenly distributed phenomenon, manifesting in diverse forms across both small-scale and industrial-scale fleets, the latter accounting for about 82 to 93% of the 8.4 to 15.4 million metric tons global annual illicit marine wild fish seafood trade valued at US$6.2 to 12.2 billion. The massive rise in fishing effort since 1950 has not been matched by adequate regulations and enforcement, especially for industrial-scale fishing in the waters of developing countries. About two-thirds of the illicit trade by value originates from fishing grounds in West Africa (27%), East Asia (24%), and Southeast Asia (16%). Remote sensing and AI technologies are improving detection of illegal fishing, but enforcement remains an issue given its high costs and the relative ease of laundering illegal catch through transshipments at sea, poorly regulated ports, and fraudulent documentation along seafood supply chains. Illegal fishing markets require multilayered policy responses grounded in transparency, international cooperation, and socioeconomic justice. Proposed measures, ranging from mandatory electronic vessel identification and subsidy reform to artisanal fishery protections and stronger port controls, warrant further research into their implementation and effectiveness.

Achieving precise and on-demand steering of the oxygen reduction reaction (ORR) pathway between the efficient 4e- route to H2O and the valuable 2e- route to H2O2 remains a pivotal challenge in electrocatalysis. Herein, we address this challenge by designing a bioinspired molecular magnetic field-responsive catalyst (MMFR-C) via magnetic single-atom-anchored Salen-based covalent organic frameworks (MSA-Salen COFs) onto magnetic nanoparticles (single/multi-domain Fe3O4). Mimicking cytochrome c oxidase, the MMFR-C employs MSA-Salen COFs as an ordered proton-transfer channel and well-defined N2-M-O2 moieties as enzymatic O2 activation sites, with Fe3O4 providing a built-in magnetic field for remote regulation of the active-site electronic structure. The bioinspired MMFR-C exhibits switchable ORR pathways. Relative to the pristine Co-Salen COF (26% H2O2 selectivity, n&#x2009;=&#x2009;3.48), the MMFR-C integrated with a single-domain Fe3O4 exhibits a remarkably enhanced H2O2 selectivity of 63.9% (n&#x2009;=&#x2009;2.72), while that with a multi-domain Fe3O4 diverts the ORR pathway toward the 4e- route (n&#x2009;=&#x2009;3.67). (i) We elucidate that the uniform magnetic field from the single-domain Fe3O4 in MMFR-C favors orbital hybridization between its active N2-M-O2 moieties and the *OOH intermediate, with moderate *OOH adsorption suppressing O-O scission and thus steering ORR selectivity toward H2O2. (ii) In contrast, the enhanced specific magnetism from its multi-domain Fe3O4 core optimizes the d-band center of MMFR-C's active sites, stabilizes triplet O2 adsorption, and reduces spin-forbidden transition barriers, thereby facilitating O-O cleavage and diverting its ORR pathway to the 4e- route.

Despite clinical guidelines emphasising coordinated, person-centred care for pregnant women with epilepsy, preventable maternal deaths and suboptimal care continue. To explore the perspectives of women with epilepsy on pregnancy-related care and their views on how to improve it. We conducted semi-structured interviews with eleven women aged 27-39&#xa0;years who were currently pregnant or had given birth within the last two years. We recruited participants from across the UK. Data were analysed using reflexive thematic analysis. Three main themes were identified. Enabling and supportive care was characterised by supportive healthcare professionals as anchors, proactive preconception counselling, collaboration between providers, a single coordinator of care, and access to specialist expertise. Fragmented and inadequate care included absence of informed decision-making, poor coordination, women being left to correct errors in their own care, encounters lacking empathy, limited epilepsy knowledge among non-specialist staff, and over-reliance on remote contact. Priorities for service improvement included early and direct conversations about risks (including SUDEP), respectful and balanced communication, partnership-based adult-to-adult dialogue, in-person consultations, and coordinated, holistic care that includes mental health support. Despite longstanding guidelines, women with epilepsy continue to experience significant gaps between recommended standards of pregnancy care and service realities. Women describe deficits in early, proactive discussions about medication and risks, informed decision-making, and joined-up care, leaving some to perform unsupported "safety work", correcting errors and mediating between neurology, obstetric and midwifery teams. Improving care requires a commitment to holistic, person-centred support that embeds clear, respectful, two-way communication with women and across services as a core safety practice.

Behavioral weight loss interventions (BWL) consisting of remote coaching and self-monitoring have limited effectiveness in breast cancer (BC) survivors. We conducted a single-arm phase II study evaluating addition of Contrave&#xae; for <5% weight loss (%WL) after 2-months of BWL. Women with prior stage 0-III BC and BMI &#x2265;27 kg/m2 were eligible and initiated BWL. We collected weight, patient-reported outcomes, and labs at baseline, 2- and 6-months. At 2-months, participants with &#x2265;5%WL (FAST-BWL) continued BWL; those with <5%WL (SLOW-BWL) received BWL+Contrave&#xae;. The primary endpoint was proportion of SLOW-BWL with &#x2265;5%WL at 6-months, with 30 participants providing 80% power with 5% type I error. Paired t-tests, Kruskal-Wallis tests and mixed-effects models were utilized. Of 55 participants, 2 withdrew prior to 2-months. At 2-months, 15 (28.3%) were FAST-BWL with mean%WL (SD) of 7.2% (1.5); and 38 (71.7%) were SLOW-BWL with mean%WL of 1.2% (2.2). Mean%WL between 2-6 months was similar in SLOW-BWL (3.8%&#xb1;3.6) and FAST-BWL (3.6%&#xb1;2.6). At 6-months, mean%WL was 5.1% (2.9) for SLOW-BWL and 10.8% (3.5) for FAST-BWL; 13/15 (86.7%) FAST-BWL and 16/38 (42%) SLOW-BWL had &#x2265;5%WL. Physical function and pain improved with &#x2265;5%WL (p=0.03 and p=0.02, respectively). SLOW-BWL had improved HbA1c (p=0.003) and triglycerides (p=0.04). Gastrointestinal symptoms were reported in 74% of SLOW-BWL. Of six withdrawals on Contrave&#xae;, one was due to adverse events. Adding Contrave&#xae; for BC survivors with minimal initial benefit from BWL results in clinically meaningful weight loss (&#x2265;5%) in 42% following 6 months of treatment, which also improves selective cardiometabolic risk factors.

Mitochondrial oxidative damage is one of the factors that contributes to the pathological process of intestinal ischemia/reperfusion (II/R) injury. Glutaredoxin (GRX2), which serves as a crucial protein in maintaining mitochondrial redox homeostasis, affects the activity of downstream proteins through its deglutathionylation effect. Silent information regulator (SIRT3), a crucial deacetylase in mitochondria, has regulatory effects on the activity of various mitochondrial antioxidant enzymes. However, the precise regulatory mechanism underlying SIRT3 enzymatic activity is unknown. Our research is designed to explore GRX2-mediated SIRT3 deglutathionylation's role and mechanism in II/R injury. GRX2 levels decreased after II/R injury, and GRX2 overexpression alleviated II/R-induced intestinal mucosal injury, mitochondrial oxidative damage, damage to mitochondrial structure and function, remote organ injury, and the systemic inflammatory response. GRX2 overexpression substantially decreased the S-glutathionylation of SIRT3 and increased its activity. The results of the incubation of recombinant SIRT3 with glutathione and H2O2 indicated that the S-glutathionylation of SIRT3 inhibited SIRT3 activity. Subsequently, SIRT3 mutant plasmids with cysteine-to-serine substitutions were constructed to screen for the S-glutathionylation sites of SIRT3 among the four cysteine residues in its amino acid sequence. The results demonstrated that C280 and C283 are the SIRT3 S-glutathionylation sites. The results of experiments using ischemic intestines from clinical cases confirmed the relationship between GRX2 and SIRT3. This study demonstrates that GRX2 alleviates mitochondrial oxidative damage following II/R by reversing the S-glutathionylation of SIRT3. GRX2 is an important protective factor against II/R injury, and GRX2-mediated deglutathionylation of SIRT3 alleviates II/R-induced mitochondrial injury and intestinal damage. Antioxid. Redox Signal. 00, 000-000.

Salmonellosis contributes to a significant burden on global healthcare systems. The impact of this foodborne bacterium is more pronounced when the infection is invasive, leading to bacteraemia and sepsis. Studies on invasive salmonellosis are few, and there is an urgent need to understand the spatial distribution of bacteraemia and the different contributing serotypes. To describe the spatial and temporal distribution of Salmonella bacteraemia in Queensland from 2010 to 2019 and identify high-risk areas and demographic groups. A retrospective population-based spatiotemporal analysis was conducted using laboratory-confirmed Salmonella bacteraemia notifications. Standardised incidence ratios (SIRs) were estimated at the postcode level using indirect standardisation with age and sex as stratification variables. A Besag-York-Moll&#xe8; (BYM) Poisson model was used to estimate posterior mean relative risks (RRs), assess spatial clustering and identify hotspots. The highest risk was observed in children aged 0-10&#x2009;years (RR&#x2009;=&#x2009;2.36, 95% CI: 2.00-2.78), and males had a 24% higher risk than females (RR&#x2009;=&#x2009;1.24, 95% CI: 1.10-1.40). Across the study period, approximately 39% of postcode areas exceeded RR >&#x2009;1.5. The three most common Salmonella serotypes also exhibited notable spatial heterogeneity. We found that Tropical North QLD (RR ranges from 1.6 to 5.39) and the outback areas of Central QLD (RR ranges from 1.8 to 6.19) were high-risk areas for bacteraemia. Salmonella bacteraemia in QLD shows substantial spatial and demographic heterogeneity, with clear hotspots in remote and tropical regions, supporting targeted, serotype-informed surveillance and prevention strategies, particularly for children and males in high-risk areas.

The growing interest in studying Saccharomyces cerevisiae strains from previously unexplored niches is greatly expanding our understanding of this yeast's ecology and evolution. While strains involved in alcoholic fermentation are the most studied, S. cerevisiae has also been isolated from milk fermentations and their products, suggesting a potential evolutionary specialization for dairy environments. These fermentations are characterized by the predominant presence of lactose, a carbon source that S. cerevisiae cannot metabolize directly but can exploit through the enzymatic activity of co-occurring microorganisms that convert lactose into fermentable substrates, such as glucose and galactose. In this study, we analyzed S. cerevisiae strains isolated from an unexplored and remote niche: traditional goat fermented milk produced by the Yaghnob people, an ethnically and geographically partly isolated population living in the Upper Zarafshan area of the Republic of Tajikistan. Comparative analyses with published S. cerevisiae genomes positioned the Yaghnob strains at the base of the phylogenetic dairy clade. These strains revealed distinctive coding sequences and strain-specific single-nucleotide variants present in all Yaghnob strains but absent from the other 1,053 strains analyzed. Further investigation of variants in key genes involved in galactose metabolism provided insights into the genomic and protein-level evolution of Yaghnob strains, uncovering unique genomic signatures of adaptation to the dairy environment.

Little is known about dementia incidence and its risk factors in people older than 90 years, particularly in heterogeneous populations. We evaluated dementia incidence and examined the associations of sex, race and ethnicity, and APOE genotype with dementia risk after age 90 years using data from LifeAfter90, an ongoing prospective cohort study. LifeAfter90 is a prospective cohort study that enrolled Kaiser Permanente Northern California members, who were at least 90 years old, from the San Francisco Bay Area and Sacramento, USA. Participants were clinically evaluated every 6 months from July 17, 2018, to Nov 9, 2024, in person or remotely. Incident all-cause dementia was diagnosed by a combination of physician assessment, Clinical Dementia Rating, and a Functional Activities Questionnaire. Sex, race and ethnicity, and education were captured during in-person assessments; APOE genotyping was performed using salivary DNA. We estimated age-standardised dementia incidence rates and used age-adjusted Cox and Fine-Gray competing-risk models to study the association between sex, race and ethnicity, APOE genotype, and dementia. The Fine-Gray subdistribution hazard ratio (sHR) models treated death as a competing risk. Models were adjusted for age (time-scale) and individuals were followed until dementia diagnosis or end of follow-up. Of 1120 individuals initially available, 96 with prevalent dementia and 219 with only one clinical evaluation were excluded; 805 participants were included. Median age was 92 years (range 90-103), 494 (61%) were female, 209 (26%) Asian, 191 (24%) African American or Black, 157 (20%) Hispanic or Latinx, 228 (28%) White, and 20 (2%) from other racial or ethnic groups; 413 had APOE data. During mean follow-up of 2 years (SD 1&#xb7;7), 138 (17%) developed dementia and 295 (37%) died. The age-standardised incidence rate was 116&#xb7;82 cases per 1000 person-years (95% CI 93&#xb7;69-139&#xb7;96). In Fine-Gray models, dementia risk was higher in female than in male participants (subdistribution hazard ratio [sHR] 1&#xb7;89, 95% CI 1&#xb7;30-2&#xb7;76) and Black than Asian participants (sHR 1&#xb7;75, 1&#xb7;07-2&#xb7;88), lower in APOE &#x3b5;2 carriers than in non-carriers (sHR 0&#xb7;39, 0&#xb7;17-0&#xb7;88), and not significantly higher in APOE &#x3b5;4 carriers than in non-carriers (sHR 1&#xb7;51, 0&#xb7;92-2&#xb7;47). No significant differences were found by education. Ethnoracial disparities in dementia risk appear to persist after 90 years, and the association between APOE &#x3b5;4 and dementia might differ by sex. These findings reinforce the importance of dementia screening and surveillance, even among people with exceptional longevity. National Institute on Aging.