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Causal effects between gut microbiota and endometriosis: a two-sample Mendelian randomisation study.Journal of Obstetrics and Gynaecology :... Dec 2024Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship...
BACKGROUND
Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.
METHOD
Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.
RESULT
A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.
CONCLUSIONS
This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
Topics: Endometriosis; Humans; Female; Mendelian Randomization Analysis; Genome-Wide Association Study; Gastrointestinal Microbiome; Polymorphism, Single Nucleotide; Causality
PubMed: 38885114
DOI: 10.1080/01443615.2024.2362415 -
JAMA Network Open Jun 2024Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial...
IMPORTANCE
Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.
OBJECTIVE
To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.
EXPOSURE
Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.
MAIN OUTCOMES AND MEASURES
Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.
RESULTS
Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.
CONCLUSIONS AND RELEVANCE
In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.
Topics: Humans; COVID-19; Female; Male; Middle Aged; SARS-CoV-2; Prospective Studies; Aged; Adult; Post-Acute COVID-19 Syndrome; Pandemics; United States
PubMed: 38884994
DOI: 10.1001/jamanetworkopen.2024.17440 -
International Journal of Cardiology Jun 2024The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
BACKGROUND
The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
METHODS
Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs.
RESULTS
There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785-6.826), isolated CHDs (aOR 4.044, 95%CI 1.803-9.070), multiple CHDs (aOR 2.625, 95%CI 1.137-6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443-5.756), atrial septal defects (aOR 3.067, 95%CI 1.406-6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414-38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta.
PubMed: 38880423
DOI: 10.1016/j.ijcard.2024.132270 -
Multiple Sclerosis and Related Disorders Jun 2024This study aimed to investigate the factors contributing to the variability of Multiple Sclerosis (MS) among individuals born and residing in France. Geographical...
BACKGROUND
This study aimed to investigate the factors contributing to the variability of Multiple Sclerosis (MS) among individuals born and residing in France. Geographical variation in MS prevalence was observed in France, but the role of genetic and environmental factors in explaining this heterogeneity has not been yet elucidated.
METHODS
We employed a heritability analysis on a cohort of 403 trios with an MS-affected proband in the French population. This sample was retrieved from REFGENSEP register of MS cases collected in 23 French hospital centers from 1992 to 2017. Our objective was to quantify the proportion of MS liability variability explained by genetic variability, sex, shared environment effects, region of birth and year of birth. We further considered gene x environment (GxE) interaction effects between genetic variability and region of birth. We have implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias.
RESULTS
Our analysis revealed that GxE interaction effects between genetic variability and region of birth represent the primary significant explanatory factor for MS liability variability in French individuals (29 % [95 %CI: 5 %; 53 %]), suggesting that additive genetic effects are modified by environmental factors associated to the region of birth. The individual contributions of genetic variability and region of birth explained, respectively, ≈15 % and ≈16 % of MS variability, highlighting a significantly higher MS liability in individuals born in the Northern regions compared to the Southern region. Overall, the joint contribution of genetic variability, region of birth, and their interaction was then estimated to explain 65 % [95 %CI: 35 %; 92 %] of MS liability variability. The remaining proportion of MS variability is attributed to environmental exposures associated with the year of birth, shared within the same household, and specific to individuals.
CONCLUSION
Overall, our analysis highlighted the interaction between genetic variability and environmental exposures linked to the region of birth as the main factor explaining MS variability within individuals born and residing in France. Among the environmental exposures prevalent in the Northern regions, and potentially interacting with genetic variability, lower vitamin D levels due to reduced sun exposure, higher obesity prevalence and higher pollution levels represent the main risk factors in influencing MS risk. These findings emphasize the importance of accounting for environmental factors linked to geographical location in the investigation of MS risk factors, as well as to further explore the influence of GxE interactions in modifying genetic risk.
PubMed: 38880029
DOI: 10.1016/j.msard.2024.105730 -
Ecotoxicology and Environmental Safety Jun 2024Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM) is related to the occurrence and development of...
Both epidemiological and experimental studies increasingly show that exposure to ambient fine particulate matter (PM) is related to the occurrence and development of chronic diseases, such as metabolic diseases. However, whether PM has "exposure memory" and how these memories affect chronic disease development like hepatic metabolic homeostasis are unknown. Therefore, we aimed to explore the effects of exposure transition on liver cholesterol and bile acids (BAs) metabolism in mice. In this study, C57BL/6 mice were exposed to concentrated ambient PM or filtered air (FA) in a whole-body exposure facility for an initial period of 10 weeks, followed by another 8 weeks of exposure switch (PM to FA and FA to PM) comparing to non-switch groups (FA to FA and PM to PM), which were finally divided into four groups (FF of FA to FA, PP of PM to PM, PF of PM to FA, and FP of FA to PM). Our results showed no significant difference in food intake, body composition, glucose homeostasis, and lipid metabolism between FA and PM groups after the initial exposure before the exposure switch. At the end of the exposure switch, the mice switched from FA to PM exposure exhibited a high sensitivity to late-onset PM exposure, as indicated by significantly elevated hepatic cholesterol levels and disturbed BAs metabolism. However, the mice switched from PM to FA exposure retained a certain memorial effects of previous PM exposure in hepatic cholesterol levels, cholesterol metabolism, and BAs metabolism. Furthermore, 18-week PM exposure significantly increased hepatic free BAs levels, which were completely reversed by the FA exposure switch. Finally, the changes in small heterodimeric partner (SHP) and nuclear receptor subfamily 5 group A member 2 (LRH1) in response to exposure switch mechanistically explained the above alterations. Therefore, mice switching from PM exposure to FA showed only a weak memory of prior PM exposure. In contrast, the early FA caused mice to be more susceptible to subsequent PM exposure.
PubMed: 38878334
DOI: 10.1016/j.ecoenv.2024.116589 -
International Journal For Equity in... Jun 2024The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However,...
BACKGROUND
The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China.
METHODS
Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores.
RESULTS
From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou.
CONCLUSIONS
This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.
Topics: Humans; Rabies; China; Post-Exposure Prophylaxis; Health Services Accessibility; Incidence; Spatial Analysis; Healthcare Disparities; Animals
PubMed: 38877457
DOI: 10.1186/s12939-024-02207-2 -
Communications Biology Jun 2024Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an...
Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.
Topics: Fear; Animals; Benzodiazepines; Hippocampus; Extinction, Psychological; Male; Midline Thalamic Nuclei; Rats; Anti-Anxiety Agents; Mice
PubMed: 38877285
DOI: 10.1038/s42003-024-06417-w -
Scientific Reports Jun 2024OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs...
OPFRs are emerging environmental pollutants with reproductive and endocrine toxicity. This study aimed to examine the association between environmental exposure to OPFRs during early pregnancy and GDM. This nested case-control study was based on a birth cohort that was constructed at a maternal and child health hospital, including 74 cases of GDM among 512 pregnant women. The OPFRs, including TBP, TBEP, TCEP, TDCPP, TMCP, TOCP, and TPHP during 10-14 weeks of pregnancy were determined using GC-MS. The association between the OPFRs and GDM was assessed using WQS and BKMR models. The levels of OPFRs were significantly elevated in GDM patients (60) compared with the controls (90). The WQS analysis showed that mixtures of the OPFRs were significantly associated with GDM (OR 1.370, 95% CI 1.036-1.810, P = 0.027), and TBP, TPHP, and TMCP were the major contributors to the mixed exposure effect. In the BKMR model, individual exposure to TBP, TPHP, and TMCP, and the interaction of TMCP with TBP and TPHP were significantly associated with GDM. Environmental exposure to OPFRs is positively associated with GDM. These findings provide evidence for the adverse effects of OPFR exposure on the health of pregnant women.
Topics: Humans; Pregnancy; Female; Diabetes, Gestational; Case-Control Studies; Flame Retardants; Adult; Environmental Exposure; Maternal Exposure; Organophosphorus Compounds; Environmental Pollutants; Risk Factors; Pregnancy Trimester, First
PubMed: 38877153
DOI: 10.1038/s41598-024-64557-9 -
Environmental Research Jun 2024Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain...
Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.
PubMed: 38876423
DOI: 10.1016/j.envres.2024.119411 -
Ecotoxicology and Environmental Safety Jun 2024Selenium (Se), as a vital stress ameliorant, possesses a beneficial effect on mediating detrimental effects of environmental threats. However, the mechanisms of Se in...
Selenium (Se), as a vital stress ameliorant, possesses a beneficial effect on mediating detrimental effects of environmental threats. However, the mechanisms of Se in mitigating the deleterious effects of drought are still poorly understood. Gentiana macrophylla Pall. is a well-known Chinese medicinal herb, and its root, as the main medicinal site, has significant therapeutic effects. The purpose of this experiment was to investigate the functions of Se on the seedling growth and physiobiochemical characteristics in G. macrophylla subjected to drought stress. The changes in microstructure and chloroplast ultrastructure of G. macrophylla leaves under drought exposure were characterized by scanning electron microscopy (SEM), scanning electron microscopes and energy dispersive X-Ray spectroscope (SEM-EDX), and transmission electron microscopy (TEM), respectively. Results revealed that drought stress induced a notable increase in oxidative toxicity in G. macrophylla, as evidenced by elevated levels of hydrogen peroxide (HO), lipid peroxidation (MDA), enhanced antioxidative response, decreased plant photosynthetic function, and inhibited plant growth. Chloroplasts integrity with damaged membranes and excess osmiophilic granule were observed in the drought-stressed plants. Se supplementation notably recovered the stomatal morphology, anatomical structure damage, and chloroplast ultrastructure of G. macrophylla leaves caused by drought exposure. Exogenous Se application markedly enhanced SPAD, photosynthetic stomatal exchange parameters, and photosystem II activity. Se supplementation significantly promoted the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), while reducing levels of MDA, superoxide anion (O) and HO, and improving membrane integrity. Furthermore, the ameliorative effects of Se were also suggested by increased contents of osmotic substances (soluble sugar and proline), boosted content of gentiopicroside and loganinic acid in roots, and alleviated the inhibition in plant growth and biomass. Fourier transform infrared (FTIR) analysis of Se-treated G. macrophylla roots under drought stress demonstrated that Se-stimulated metabolites including O-H, C-H, N-H, C-N, and CO functional groups, were involved in resisting drought stress. Correlation analysis indicated an obvious negative correlation between growth parameters and MDA, O and HO content, while a positive correlation with photosynthetic gas exchange parameters. Principal component analysis (PCA) results explained the total variance into two principal components contributing the maximum (93.50 %) among the drought exposure with or without Se due to the various experiment indexes. In conclusion, Se exerts beneficial properties on drought-induced detrimental effects in G. macrophylla by relieving oxidative stress, improving photosynthesis indexes, PSII activity, regulating anatomical changes, altering levels of gentiopicroside and loganinic acid, and promoting growth of drought-stressed G. macrophylla.
PubMed: 38875819
DOI: 10.1016/j.ecoenv.2024.116591