BMC Medicine最新文献

Background: Bulimia nervosa (BN) is a severe psychiatric disorder characterized by dysregulated eating behaviors and impaired cognitive-emotional control. Despite increasing recognition of brain network dysfunction in BN, the interplay between structural connectivity (SC) and functional connectivity (FC), termed SC-FC coupling, remains poorly understood. This study aimed to comprehensively characterize SC-FC coupling alterations in BN using multimodal neuroimaging and to evaluate the predictive value for disordered eating behaviors.

Methods: This study enrolled 79 patients with BN and 69 healthy controls who underwent high-resolution structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI). Functional and structural connectomes were constructed using the Schaefer-400 atlas. SC-FC coupling was quantified using eight biologically grounded similarity and communication metrics. A multivariate linear modeling framework was applied to estimate region-specific coupling profiles. Group comparisons and ridge regression-based leave-one-out cross-validation were used to identify altered coupling and predict symptom severity.

Results: The global topological properties of the SC and FC networks were preserved in BN. However, patients exhibited significantly reduced degree centrality and nodal efficiency in the inferior frontal gyrus within the FC network. SC-FC coupling, quantified using the matching index (MI), showed widespread regional alterations in BN, particularly within the default mode, control, and attention networks. Seventeen brain parcels demonstrated significant group differences in MI-based coupling (false discovery rate (FDR)-corrected, p < 0.05), with both hypercoupling and hypocoupling observed. Findings were parcellation-robust (Glasser-360 replication; Dice = 0.93 vs. Schaefer-400). Moreover, coupling features moderately predicted binge-eating frequency (r = 0.24, p < 0.001), but not questionnaire-based emotional or behavioral scores.

Conclusions: In BN, macroscale white-matter organization is preserved, yet focal prefrontal functional decentralization and widespread, parcellation-robust SC-FC coupling changes invisible to single-modality analyses were observed. Multidimensional SC-FC coupling provides a sensitive neurobiological marker that explains clinically relevant variance in binge-eating behavior, highlighting its potential as a target for personalized diagnosis and intervention in BN.

Background: Radon, a naturally occurring radioactive gas, is ubiquitous in the environment. Little is known about radon's impact on cardiovascular disease (CVD). This study aims to evaluate the association between residential radon exposure and incident myocardial infarction (MI) and stroke.

Methods: This cohort study included participants with electronic health records (EHR) and residential address information from the All of Us Research Program between May 31, 2017, and October 1, 2023. Residential radon exposures were estimated from a 2024 high-resolution model incorporating over six million measurements across the USA. The main outcome was MI and stroke diagnosis or condition, obtained from EHR. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of incident MI and stroke for log-2 transformed radon exposure and quartiles of radon exposure, adjusting for sociodemographic, behavioral, and clinical covariates. Sex- and smoker-stratified analyses were conducted. Penalized spline models were used to estimate the nonlinear association.

Results: A total of 304,050 participants were included. The mean (SD) age was 58.5 (12.9) years old. Among them, 59.2% were female, 18.2% non-Hispanic Black, and 59.0% non-Hispanic White. The median radon exposure was 1.14 pCi/L (interquartile range: 0.90-1.71 pCi/L). Over 950,895 person-years, 1334 MI and 1869 stroke cases were identified. Per doubling of radon exposure was associated with increased risks for incident MI (HR = 1.46, 95% CI 1.04-2.08) and stroke (HR = 1.60, 1.02-2.49). Participants in the third and fourth quartiles had a significantly higher risk for MI and stroke compared to the lowest quartile. Specifically, the fourth quartile was associated with HR = 2.20 (95% CI 1.18-4.10) for MI and HR = 2.38 (95% CI 1.16-4.89) for stroke. Associations persisted across sexes and current smoking status. Nonlinear analyses revealed steep risk increased starting at 1 pCi/L, plateauing at 1.5 pCi/L.

Conclusions: In this cohort study of 304,050 participants, residential radon exposure was significantly associated with elevated risks for incident MI and stroke. Our results suggest that risks may emerge at levels well below this action level. These findings call for further research incorporating household-level exposure measures and lifetime residential histories to confirm the association.

Background: Engaging in regular physical activity and obtaining recommended amounts of sleep are touted as strategies to promote healthy brain aging. However, as each day is only 24 h long, changing time spent in one activity must come at the expense or gain of another, making it necessary to understand how the whole 24-h activity composition is associated with dementia risk. We investigated the effect of substituting sleep duration for different levels of physical activity (i.e., inactivity, light activity, and moderate to vigorous physical activity; MVPA) in short sleepers (< 6 h) and normal sleepers (≥ 6 h and ≤ 9 h).

Methods: The study sample comprised 87,490 participants from the community-based UK Biobank, with 24-h behaviors estimated using up to 7 days of accelerometry. Participants were free from dementia or severe neurological disease at baseline. The main outcome was the risk of incident all-cause dementia over a median follow-up of 8.2 years.

Results: The mean age of the sample was 63 years (Q1, Q3, 56, 68); 56% were women. For short sleepers, increasing sleep duration was associated with a lowering of dementia risk when at the expense of inactivity or light activity, but not when at the expense of MVPA. For normal sleepers, the effect of increasing or decreasing sleep duration on dementia risk differed for all three substituted behaviors (i.e., inactivity, light, or MVPA). Most notably, increasing sleep at the expense of MVPA was associated with greater dementia risk, and increasing MVPA at the expense of sleep was associated with lower dementia risk. The interpretation of the results was broadly consistent when using MRI-based outcomes (e.g., hippocampal volume) in a subset with brain imaging (n = 15,180).

Conclusions: Our findings from this observational analysis suggest that personalized approaches that balance trade-offs between sleep duration and differing physical activity levels based on individual circumstances, such as habitual sleep duration, may be important for dementia risk reduction.

Background: This study aimed to explore associations between the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet and the risk of incident cardiovascular disease (CVD) and arrhythmias, together with comparing to three other pre-existing diet quality indices.

Methods: A prospective analysis was conducted using the UK Biobank. MIND diet score, Mediterranean Diet Adherence Screener (MEDAS), Recommended Food Score (RFS), and Healthy Diet Indicator (HDI) were computed using the Oxford WebQ. Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).

Results: 193,983 participants were included in the CVD analyses, and 190,529 for arrhythmias. Compared with participants in the lowest quartile of MIND diet score, participants in the highest quartile had a lower risk of CVD (HR 0.86; 95% CI 0.81-0.91), ischemic heart disease (0.92; 0.85-0.98), stroke (0.86; 0.75-0.97), heart failure (0.79; 0.71-0.88), and total arrhythmias (0.93; 0.88-0.99), after adjusting for demographics, lifestyle, and chronic conditions. With further adjustment for metabolic profiles, the associations remain significant for CVD and its subtypes but become non-significant for arrhythmias. Strengths of association varied across diet scores, with associations for MEDAS (CVD and arrhythmias) and MIND (CVD subtypes). The associations with CVD were linear for MIND and MEDAS and non-linear for RFS. The association between MEDAS and arrhythmias was non-linear. We observed significant interactions by age and obesity for CVD.

Conclusions: The MIND diet was associated with CVD and arrhythmias, relying on a single day of dietary data to derive dietary patterns. The findings suggest that following the MIND diet was associated with a lower risk of CVD, heart failure specifically, and arrhythmias.

Background: Digital technologies are crucial to drive the needed improvement in NHS primary care delivery and access. The impact of these digital interventions on health inequalities remains a critical area of concern and uncertainty. Transition to digital primary care services was rapidly accelerated during the COVID-19 pandemic. We explored what can be learnt from this transition to digital access by examining the patterns of remote general practice consultation before and after the pandemic and the influence of age, gender, social deprivation, and ethnicity on these patterns.

Methods: This is a longitudinal study in primary care settings involving data from19 million men and women aged 18 + years registered with general practices in England between January 2019 and February 2022 using the OpenSAFELY platform. The main outcome was remote consultation (telephone, video, or electronic) of all appointments recorded by GPs. Binomial regression models including marginal effect probabilities were used to analyse the proportion of remote consultations in all appointments. Covariates including age, gender, deprivation, and ethnicity were adjusted for in the models.

Results: Remote consultations increased from 10.1 million per annum (March 2019 to March 2020) to 32.7 million per annum during the pandemic (March 2020 to March 2022). Pre-pandemic, 85 + year olds had the highest probability of remote consultation (0.133, 95% CI [0.132-0.133]). In the pandemic period, the probability of remote consultation increased for all age groups with those aged 18-49 years having the highest probability of remote consultation and those aged 85 + having the second highest probability. Men were less likely to have remote consultations than women pre-pandemic and in the 2 years after the pandemic started. Before the pandemic, the most affluent group (5th deprivation quintiles) had the lowest probability of having consultation being held remotely (0.086, 95% CI [0.086-0.086]), a trend that was maintained through the first 2 years of the pandemic. White ethnic group had the highest probabilities of remote consultations across the study period.

Conclusions: There were significant variations in remote consultations by age, gender, socioeconomic group, and ethnicity during the pandemic. These factors should be considered when planning access to services especially for vulnerable patients.

Background: Antiretroviral therapy has extended the life expectancy of people with HIV (PWH), leading to a rapidly expanding ageing population of PWH worldwide, including in low- and middle-income countries. The interaction between ageing and chronic HIV infection is closely associated with immunosenescence, and PWH are widely regarded as a model of accelerated immune ageing. Immunosenescence, characterized by a progressive decline in immune function and increased susceptibility to infections, contributes to a higher burden of age-related comorbidities and cancers, posing a major long-term health challenge for this population.

Main body: The main focus of this review is on immunosenescence-related phenotypic and functional alterations in innate immune cells in PWH, including natural killer cells, monocytes, macrophages, and dendritic cells. It also outlines immunosenescence-related changes in T and B cells in the context of ageing and chronic HIV infection, such as thymic atrophy, loss of naïve T cell diversity, expansion of terminally differentiated and exhausted T-cell subsets, the impact of cytomegalovirus co-infection, and the emergence of age-associated B cells that impair humoral immunity and vaccine responsiveness. Furthermore, it discusses how persistent low-grade inflammation, mitochondrial damage induced by viral proteins and certain antiretroviral regimens, together with lifestyle factors such as cigarette smoking, accelerate systemic immune ageing, and summarizes emerging therapeutic and lifestyle strategies aimed at mitigating immunosenescence and improving long-term immune health, while noting that robust evidence remains limited.

Conclusion: Despite growing insights into HIV-associated immune ageing, there is still no universally applicable biomarker of immunosenescence. This gap underscores the need to develop robust, population-tailored biomarker panels and targeted interventions for PWH, to support integrated strategies that combine antiretroviral therapy with immune restoration and anti-ageing approaches, ultimately improving immune health and quality of life.

Background: Social determinants of health (SDOH) contribute significantly to geographical variations in cardiovascular disease (CVD) mortality in the USA. We aimed to develop and evaluate a SDOH-related social cardiovascular mortality index (SCMI) as a population-level tool for public health surveillance and planning to identify US counties at risk of high CVD mortality. We also sought to identify the leading SDOH-related variables associated with CVD mortality across US counties.

Methods: We used public registry data from 3141 US counties and applied machine learning techniques to screen 158 SDOH-related variables (centered around 2019), identifying 15 key determinants of total CVD mortality (2018-2020) to develop the SCMI, a composite score ranging from 0.00 to 100.00. We validated SCMI by comparing its predictive performance with social vulnerability index (SVI) for future total CVD mortality (2019-2021) in 1000 bootstrap resamples, based on R², root mean square error (RMSE), and mean absolute error (MAE). We also used geographical random forest models to identify leading SDOH variables associated with total CVD mortality at the county level.

Results: Counties in the highest SCMI quintile (80.01-100.00), reflecting the most disadvantaged community conditions, had on average 202.55 more predicted total CVD deaths per 100,000 population than those in the lowest quintile (0.00-20.00) (p < 0.001). SCMI consistently outperformed SVI in predicting future total CVD mortality, with higher R² [mean, 0.47 (95% confidence interval, 0.32, 0.57) versus 0.14 (- 0.15, 0.27)] and lower RMSE [72.93 (64.14, 80.69) versus 92.76 (81.14, 105.38)] and MAE [54.63 (48.37, 60.58) versus 72.15 (62.94, 82.94)]. Additionally, the proportion of individuals with frequent mental distress, receiving Supplemental Nutrition Assistance Program, and lower median household income were identified as the leading determinants of total CVD mortality, all positively associated with higher SCMI scores (p < 0.001).

Conclusions: Our novel SDOH-based SCMI consistently outperformed SVI in predicting US counties at risk of high CVD mortality. The identified leading county-level SDOH variables need further evaluation as potentially modifiable targets for community interventions. Our findings can improve county-level cardiovascular risk stratification and support efforts to mitigate geographical variations in cardiovascular mortality in the USA.

Background: Antiemetics are commonly prescribed for nausea and vomiting during pregnancy (NVP), affecting up to 80% of pregnant women. However, data on their long-term neurodevelopmental effects are limited. We therefore aimed to assess the risk of neurodevelopmental disorders and delays in children exposed to antiemetics commonly prescribed during pregnancy.

Methods: This nationwide cohort study, designed to emulate a pragmatic trial, used South Korea's National Health Insurance Service mother-child linked database, 2009-2023. The primary exposure of interest was metoclopramide, while pyridoxine, doxylamine, dimenhydrinate, domperidone, and ondansetron were included in secondary analyses. Non-exposed pregnancies within the cohort served as comparators. The outcomes included seven neurodevelopmental disorders-autism spectrum disorder, cerebral palsy, communication disorder, intellectual disorder, movement disorder, attention deficit hyperactivity disorder (ADHD), and epilepsy-as well as neurodevelopmental delays assessed using the validated Korean Developmental Screening Test. Overlap weights based on potential confounders were applied to a Cox proportional hazard model to estimate hazard ratios (HR) with 95% confidence intervals (CI).

Results: Among 630,904 children included, 281,476 (44.6%) were exposed to metoclopramide during pregnancy, while 131,837 (20.9%), 1383 (0.2%), 12,013 (1.9%), 14,531 (2.3%), and 5673 (0.9%) were respectively exposed to pyridoxine, doxylamine, dimenhydrinate, domperidone, and ondansetron. There was no substantial association between antiemetic exposure during pregnancy and neurodevelopmental disorders and delays. Findings were consistent across various subgroup and sensitivity analyses, except for a slightly elevated risk of attention-deficit hyperactivity disorder (HR 1.12, 95% CI 1.06-1.18) in children exposed to metoclopramide during the second half of pregnancy and neurodevelopmental delays in those exposed to metoclopramide for ≥ 7 days.

Conclusions: This large-scale study found no association between antiemetic exposure during pregnancy and the risk of neurodevelopmental disorders or delays in children, providing reassurance for the use of antiemetics in pregnancy to treat nausea and vomiting. However, the slightly elevated risks observed in certain subgroups warrant further investigation. Meanwhile, these findings may assist in guiding decisions when considering antiemetic treatment during pregnancy.

Background: Birth outcomes are linked to postnatal metabolic adaptation and long-term health, but their associations with neonatal metabolite profiles remain poorly understood. This study aimed to delineate the associations of key birth outcomes with a panel of 11 amino acids and 27 acylcarnitines in a large-scale newborn population.

Methods: This cross-sectional study analyzed data from 3,398,012 neonates across 14 regions in China from April 2013 to May 2019. We compared metabolite levels between preterm and full-term infants using the Wilcoxon rank-sum test, and among low, normal, and high birth weight groups using the Kruskal-Wallis test with Dunn's post hoc analysis. Multivariable linear regression was used to examine the associations of gestational age and sex-specific birth weight for gestational age z-scores (BWZ) with metabolite concentrations. Restricted cubic splines were employed to model potential nonlinear relationships. Pathway enrichment analysis was conducted to identify implicated metabolic pathways. Finally, we performed several sensitivity analyses to test the robustness of the findings.

Results: The cohort comprised 52.8% males, with 5.2% preterm births. The prevalence of low, normal, and high birth weight was 3.4%, 91.1%, and 5.6%, respectively. Small, appropriate, and large for gestational age accounted for 1.6%, 89.2%, and 9.2% of neonates. All 38 measured metabolites differed significantly across gestational age and birth weight categories (all P < 0.05). Gestational age was significantly associated with all metabolites, including alanine (β = 0.308; 95% CI, 0.306 to 0.310) and C3 (β = - 0.139; 95% CI, - 0.140 to - 0.137). Similarly, BWZ was associated with all metabolites, such as proline (β = - 0.026; 95% CI, - 0.026 to - 0.026) and C0 (β = - 0.030; 95% CI, - 0.030 to - 0.029). Most of these associations were linear and varied by neonatal age and sex. Pathway analysis implicated the urea cycle, phenylalanine and tyrosine metabolism, arginine and proline metabolism, and β-oxidation of very long-chain fatty acids.

Conclusions: Neonatal amino acid and acylcarnitine profiles are profoundly associated with birth outcomes, highlighting the importance of developing targeted early screening and intervention strategies.

Background: Emerging evidence highlights that diet dynamically shapes the gut microbiome, which in turn influences cognitive function through bidirectional gut-brain communication, offering a promising target for mitigating cognitive decline and neurodegenerative disorders. While the Mediterranean diet (MedDiet) is a well-established dietary pattern with demonstrated neuroprotective benefits, the interplay between MedDiet adherence, gut microbiota, and longitudinal cognitive trajectories remains poorly understood. We aimed to identify a gut microbial signature of the MedDiet adherence and prospectively examine the associations of MedDiet adherence and MedDiet gut microbial signature (MedDiet-GMS) with cognitive changes over time in older adults at high risk of cognitive decline.

Methods: This study included 746 participants (mean age 65 ± 5 years, 48% women) with overweight/obesity and metabolic syndrome. Adherence to the MedDiet was assessed using a validated 14-item Mediterranean Diet Adherence Screener (MEDAS). Baseline gut microbiota composition was profiled via 16S rRNA sequencing. Cognitive function was evaluated at baseline, 2, 4, and 6 years using a comprehensive neuropsychological battery. Elastic net regressions were applied to derive a MedDiet-GMS, and linear mixed models were used to assess associations of both MEDAS and MedDiet-GMS with trajectories of cognitive function, adjusting for potential confounders.

Results: Higher adherence to the MedDiet was associated with greater gut microbial diversity (p < 0.05) and distinct microbial composition (PERMANOVA, p = 0.001). The MedDiet-GMS comprised 20 taxa, including short-chain fatty acid-producers (e.g., Barnesiella, Butyricicoccus) positively weighted and pro-inflammatory taxa (e.g., Eggerthella) negatively weighted. Both higher MEDAS scores (p = 0.007) and MedDiet-GMS (p = 0.036) were independently associated with slower global cognitive decline. The MedDiet-GMS was additionally linked to preserved executive function (p = 0.049), while MEDAS was associated with attenuated general cognitive decline (p = 0.028). Eggerthella, inversely associated with MedDiet adherence, was linked to greater executive function decline (FDR < 0.05).

Conclusions: Greater adherence to the MedDiet was associated with a favorable gut microbiota profile and slower cognitive decline over 6-year of follow-up. A microbiome-derived signature of MedDiet adherence was prospectively associated with favorable cognitive trajectories in older adults at risk of cognitive decline. External validation and experimental research are warranted to translate these findings into targeted microbiome-based dietary interventions for healthy cognitive aging.