Wiley最新文献

Objective: Transportation noise is increasingly recognized as a cardiometabolic stressor, but its relationship with type 2 diabetes mellitus (T2DM) remains poorly defined. We examined whether transportation noise exposure was associated with incident T2DM in a large, diverse U.S. healthcare system cohort.

Methods: We identified adults without baseline T2DM from the Houston Methodist Learning Health System Registry (2016-2023). Transportation noise exposure was assigned at the census block group level using the 2020 U.S. Department of Transportation National Transportation Noise Map. Five noise categories were examined: Road, Rail, Aviation, Road plus Aviation and Total. Cox proportional hazards models estimated associations across predefined categories, Quiet (≤45 dB), Moderate (45-54 dB) and Loud (≥55 dB), and per 10 dB increase, adjusting for demographics, cardiometabolic risk factors, socioeconomic vulnerability and PM₂.₅.

Results: Among 984 658 adults (2.1 million person-years), 39 587 developed T2DM (1.88 per 100 person-years). Loud rail noise (HR 1.14; 95% CI: 1.01-1.29) and loud total noise (HR 1.17; 95% CI: 1.03-1.33) were associated with higher T2DM risk. Continuous models showed similar patterns, with each 10 dB increase in rail noise (HR 1.09; 95% CI: 1.05-1.13) and road noise (HR 1.04; 95% CI: 1.01-1.08) associated with a higher hazard of incident T2DM. Effect sizes were modest but internally consistent and aligned with prior environmental noise studies.

Conclusion: Transportation noise, particularly rail noise, was associated with higher T2DM risk. Given plausible mechanisms involving sleep disruption and stress-related neuroendocrine activation, these findings add to evidence linking environmental noise to metabolic health and motivate further studies to evaluate causality and potential benefits of noise mitigation.

Aims: The current study measured the extent to which different neurobehavioral indices of incentive-motivational salience attribution to alcohol cues predict alcohol craving and consumption in the natural environment.

Design, setting, and participants: Laboratory study at a university in Missouri, USA, followed by a smartphone-based 21-day ecological momentary assessment (EMA) protocol. Participants were emerging adults (N = 218-268 [52-56% female], age 18-20).

Measurements: Participants completed an alcohol cue approach-avoidance task while their electroencephalogram (EEG) was recorded. Behavioral measures (response time) indexed the strength of cue-activated approach vs. avoidance tendency. Cue-locked event-related potentials provided EEG-based neural measures of motivated attention (P3 amplitude) and approach-avoidance conflict (N450 amplitude). From EMA, measures of alcohol consumption dynamics (as indexed by estimated blood alcohol concentration [eBAC], g/dL) during real-world drinking episodes were obtained, as were measures of alcohol craving (7-point visual analogue scale) dynamics during and outside these episodes.

Findings: Different approach-avoidance task-derived behavioral and neural measures rank-ordered participants differently. Participants who approached alcohol cues more rapidly in lab subsequently showed steeper increases in craving (∆B ± standard error [SE] = 1.042 ± 0.499 point/hr), and eBAC (∆B ± SE = 0.046 ± 0.017 g/dl/hr), during real-world drinking episodes. Participants who avoided alcohol cues more slowly in lab also showed steeper increases in eBAC (∆B ± SE = 0.056 ± 0.017 g/dl/hr). Participants with larger P3 during alcohol cue approach in lab subsequently showed steeper increases in eBAC (∆B ± SE = 0.048 ± 0.017 g/dl/hr), as did those with smaller P3 during alcohol cue avoidance (∆B ± SE = 0.025 ± 0.017 g/dl/hr). Participants with smaller N450 during alcohol cue approach in lab subsequently showed steeper increases in craving during drinking episodes (∆B ± SE = 1.465 ± 0.607 point/hr). Tests examining lab-based neurobehavioral measures as predictors of craving dynamics during nondrinking moments, such as following incidental cue exposure, generally were inconclusive.

Conclusions: Incentive salience toward alcohol may influence alcohol seeking (including craving) and alcohol consumption through distinct behavioral risk pathways in different people.

Background and aims: Smokers quitting successfully with the help of e-cigarettes often continue vaping. It is not known whether this promotes or prevents relapse back to smoking. This study aimed to determine whether use of e-cigarettes after successful smoking cessation affects the probability of relapse later on.

Design: Secondary analysis of a randomised controlled trial where participants received combination nicotine replacement therapy (NRT) or e-cigarettes to compare relapse rates in the two study arms and in abstainers who did and did not use e-cigarettes.

Setting: Four stop-smoking services in the United Kingdom.

Participants: 886 smokers (median age 41, smoking on average 15 cigarettes per day, 48% female) seeking help with stopping smoking.

Measurements: Main outcome was relapse to smoking by 12 months in participants who were abstinent at 4 weeks or at 6 months. Relapse was defined as abstinence at 4 weeks but not at one year or abstinence at 6 months but not at one year. Abstinence from smoking was defined as no smoking over the past 7 days. E-cigarette use was defined as using e-cigarettes at the time of abstinence on at least one day per week.

Findings: Abstainers in the e-cigarette arm were less likely to relapse than abstainers in the NRT arm [relative risk (RR) = 0.78, 95% confidence interval (CI) = 0.64-0.96 for relapse between 4 weeks and 1 year; RR = 0.71, 95% CI = 0.55-0.93 for relapse between 6 months and 1 year). Relapse rates over both time periods were also lower in abstainers who used e-cigarettes compared with abstainers who did not use e-cigarettes (RR = 0.79, 95% CI = 0.65-0.97 and RR = 0.75, 95% CI = 0.57-0.98, respectively).

Conclusions: Use of e-cigarettes after stopping smoking is associated with a reduced risk of relapse.

Objective: The pharmacological treatment of temporal lobe epilepsy (TLE), a disorder characterized by recurrent seizures and cognitive dysfunction, is limited to symptomatic control. Identifying novel targets to modify disease progression is of great clinical and translational interest. Cellular senescence has been recently implicated in the development and progression of other neurodegenerative diseases, but its role in TLE is unstudied.

Methods: We first investigated cellular senescence markers in resected hippocampi from patients with medically intractable TLE through multiplexed immunofluorescence. We next used a mouse model of TLE (pilocarpine induced status epilepticus [SE]) for a combination of immunohistochemistry, behavioral testing, and electroencephalogram (EEG) monitoring. We implemented 2 strategies for removal of senescent cells (SCs), a genetic mouse model allowing for targeted senolysis, and a pharmacological approach using dasatinib and quercetin.

Results: We found a 5-fold elevation of senescent glia in human TLE cases as compared with controls. In mice, we found increases in senescence markers at both the transcript and protein level and predominantly expressed in microglia, which developed within 2 weeks following SE. Senolytic treatment produced a 50% reduction in SCs, rescued long-term potentiation deficits, normalized spatial memory impairments, reduced seizures, and protected a third of animals from epilepsy.

Interpretation: Our data demonstrate that SCs accumulate in both human TLE and in a mouse model of TLE and suggest that clearing SCs may be a viable strategy to reduce seizures and associated cognitive comorbidities. ANN NEUROL 2026;99:1059-1075.

Objective: Parkinson's disease (PD) is one of the rare diseases in which sleep alteration is a true marker of disease outcome. Yet, how the association between sleep and PD emerges over the healthy lifetime is not established. We examined the association between the polygenic risk score (PRS) for PD and the variability in the electrophysiology of rapid eye movement (REM) sleep in 433 younger (18-31 years) healthy individuals and 85 late-midlife (50-69 years) healthy individuals.

Methods: In this prospective cross-sectional study, in-lab electroencephalography recordings of sleep were recorded to extract REM sleep metrics. PRS was computed using SBayesR approach.

Results: Generalized additive model for location, scale, and shape analysis showed significant association of REM duration (p_corrected = 0.03) and theta energy in REM (p_corrected = 0.004) with PRS for PD in interaction with the age group. In the younger subsample, REM duration and theta energy were positively associated with PD PRS. In contrast, in the late-midlife subsample, the same associations were negative (although only qualitatively for REM theta energy) and may differ between men and women.

Interpretation: REM sleep is associated with the PRS for PD in early adulthood, 2 to 5 decades before typical symptoms onset. The association changes from positive in younger individuals, presumably free of alpha-synuclein, to negative in late-midlife individuals, possibly because of the progressive presence of alpha-synuclein aggregates or of the repeated increased oxidative metabolism imposed by REM sleep. Our findings may unravel core associations between PD and sleep and may contribute to novel intervention targets to prevent or delay PD. ANN NEUROL 2026;99:922-934.

Objective: The objective of this study was to determine whether missing individual doses of anti-seizure medications (ASMs) elevate short-term seizure risk in people with drug-resistant epilepsy.

Methods: In a prospective, community-based cohort, adults with drug-resistant epilepsy (≥ 3 seizures/month) or their caregivers recorded seizures and ASM intake with smartphone applications for 10 months each. Individual level analysis modeled the relationships between ASM adherence with seizure occurrence, as well as with a simplified seizure forecast via a 90-day moving average ("Napkin method"). Group-level analysis with a mixed-effects model was performed to examine the relationship between ASM adherence and simplified forecasts, while controlling for differences in individual seizure frequency via random effects.

Results: Twenty-seven participants (median age = 29 years) contributed 7,853 person-days. Individual analysis showed that only a small (n = 2) number of participants had a weak relationship between ASM adherence with seizure occurrence. Group-level analysis showed that seizure occurrence was highly linked to the Napkin method, but not ASM adherence.

Interpretation: Among individuals with frequent, drug-resistant epilepsy, occasional missed ASM doses did not measurably raise immediate seizure risk. Whereas sustained nonadherence remains a clinical concern, clinicians may reassure patients that infrequent brief lapses are unlikely to trigger seizures acutely, yet they should continue emphasizing overall adherence for long-term seizure control. ANN NEUROL 2026;99:1076-1082.

Background and aims: The global rise in dementia, including early-onset cases, imposes a growing burden on patients and caregivers. While midlife obesity is a recognized risk factor, the role of body weight fluctuation in dementia and cognitive decline remains uncertain. This systematic review and meta-analysis examined the association between weight variability and the risk of dementia, including Alzheimer's disease, vascular dementia, and cognitive decline.

Methods: We systematically searched PubMed, Scopus, Web of Science, and PsycINFO, supplemented by manual searches, up to July 2024. Pooled hazard ratios (HRs) were estimated through pairwise meta-analysis, with subgroup analyses conducted to explore heterogeneity. Additionally, the quality of the included studies and the certainty of the evidence were assessed using the "Risk of Bias in Non-randomized Studies of Interventions" (ROBINS-I) tool and the GRADE Tool, respectively.

Results: Sixteen studies met the inclusion criteria. Compared with the lowest levels of weight fluctuation, the highest levels were associated with an increased risk of all-cause dementia (HR 1.40, 95% CI 1.29-1.52), Alzheimer's disease (HR 1.33, 95% CI 1.21-1.45), and vascular dementia (HR 1.39, 95% CI 1.16-1.67). No significant association was observed with cognitive decline. No clear source of heterogeneity was identified.

Conclusion: High body weight fluctuation is associated with an elevated risk of dementia, particularly Alzheimer's disease and vascular dementia. These findings highlight weight stability as a potential target for dementia prevention strategies. Further high-quality studies are warranted to clarify underlying mechanisms and long-term implications.

The mechanisms of selenium (Se) oxyanion transformation in endophytic bacteria remain poorly understood, which limits their application in biofortification and phytoremediation. Here, we investigated these mechanisms using the plant-growth-promoting (PGP) endophyte Erwinia sp. PSI-03. Under 2 mM selenite stress, the strain intracellularly and extracellularly produced spherical selenium nanoparticles (SeNPs; ab57 nm average diameter). Multi-omics analyses revealed that these SeNPs were formed through parallel enzymatic (mediated by sulfite reductase, cysI) and non-enzymatic (via glutathione and l-cysteine) reduction pathways. Additionally, γ-glutamyl-Se-methylselenocysteine was identified as a key organo-selenium metabolite. Selenite exposure induced extensive reprogramming of the metabolome and transcriptome, highlighting key roles for glutathione metabolism and stress response systems related to cell wall/membrane maintenance, oxidative phosphorylation, two-component signaling systems, and DNA repair. Intriguingly, selenite stress concurrently stimulated bacterial synthesis of PGP compounds, including the auxin precursor indole-3-pyruvate, the defense hormone salicylic acid, and acetate. Consistent with this, under selenite-free and high-selenite (12 mg kg^-1 Se) conditions, inoculation with Erwinia sp. PSI-03 significantly promoted tea plant growth. Compared to uninoculated controls, the leaf biomass increased by 52.8% and 51.7%, and the total biomass by 82.9% and 49.6%, respectively. These findings establish a paradigm where endophytic bacteria simultaneously detoxify Se and promote plant health, offering a robust strategy for agricultural and environmental Se management.

Global climate warming has significantly increased plant diseases prevalence. In subtropical regions, high temperature frequently co-occurs with bacterial wilt caused by Ralstonia solanacearum, creating compound stress conditions that severely compromise eggplant productivity. However, the molecular mechanisms governing eggplant's response to combined heat and pathogen stress remain poorly characterized. In this study, we conducted the temperature analyses of Guangzhou, China, and isolated a thermotolerant strain PSS219-GZ under high temperatures in eggplant. Phenotypic analysis of eggplants inoculated with PSS219-GZ at different temperature, indicated that PSS219-GZ have maximal pathogenicity at 37°C. SmWRKY6 is a WRKY transcription factor activated by both high temperatures and Ralstonia solanacearum infection. Genetic evidence from silencing of SmWRKY6 via VIGS in eggplants and overexpression of SmWRKY6 in tomato demonstrated that SmWRKY6 is essential for enhancing resistance to Ralstonia solanacearum under high-temperature stress. SmWRKY6 directly binds to and transcriptionally activates the SmPR1b promoter, forming a key regulatory node in bacterial wilt resistance pathways. This study provides novel insights into plant responses to combined heat and R. solanacearum stress and highlights potential resistance genes for mitigating compound stress effects.