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Major depressive disorder emerges from the complex interactions of biological systems that span genes and molecules through cells, networks, and behavior. Establishing how neurobiological processes coalesce to contribute to depression requires a multiscale approach, encompassing measures of brain structure and function as well as genetic and cell-specific transcriptional data. Here, we examine anatomical (cortical thickness) and functional (functional variability, global brain connectivity) correlates of depression and negative affect across three population-imaging datasets: UK Biobank, Brain Genomics Superstruct Project, and Enhancing NeuroImaging through Meta Analysis (ENIGMA; combined n ≥ 23,723). Integrative analyses incorporate measures of cortical gene expression, postmortem patient transcriptional data, depression genome-wide association study (GWAS), and single-cell gene transcription. Neuroimaging correlates of depression and negative affect were consistent across three independent datasets. Linking ex vivo gene down-regulation with in vivo neuroimaging, we find that transcriptional correlates of depression imaging phenotypes track gene down-regulation in postmortem cortical samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data reveal somatostatin interneurons and astrocytes to be consistent cell associates of depression, through both in vivo imaging and ex vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS-derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multiscale approaches, the transcriptional correlates of depression-linked brain function and structure were enriched for disorder-relevant molecular pathways. These findings bridge levels to connect specific genes, cell classes, and biological pathways to in vivo imaging correlates of depression.
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Encéfalo/metabolismo , Corteza Cerebral/metabolismo , Trastorno Depresivo Mayor/genética , Regulación de la Expresión Génica/genética , Somatostatina/genética , Astrocitos/metabolismo , Astrocitos/patología , Autopsia , Encéfalo/patología , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Femenino , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Redes Reguladoras de Genes/genética , Estudio de Asociación del Genoma Completo , Genómica/métodos , Humanos , Interneuronas/metabolismo , Interneuronas/patología , Masculino , Herencia Multifactorial/genética , Neuroimagen/métodos , Transducción de Señal/genética , Análisis de la Célula Individual/métodosRESUMEN
BACKGROUND: The relationship between mercury (Hg) exposure and thyroid hormones (THs) levels in the general population has been inconclusive. We conducted a random effects model meta-analysis to identify the association between Hg exposure and THs levels in the general population. METHODS: This meta-analysis were performed based on the PECO questions (P = general population; E =1ug/L Hg in blood and urine; C =1ug/L incremental increase on; and O = variation of THs levels). We searched four electronic databases including PubMed, Web of Science, Embase, and Cochrane Library for studies published on or before 20th July 2020. Prospective and cross-sectional studies that evaluated the association between Hg exposure and the levels of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and free thyroxine (FT4) were included. We also assessed aggregate risks for the reliability of the included studies. RESULTS: Initially, we retrieved 4889 articles. 18 studies met our inclusion criteria after screening and 13 articles were eligible to be included in the meta-analysis. The meta-analysis results suggest that blood Hg may be significantly associated with THs levels. The presence of Hg in blood may significantly increase the levels of TSH (ß=0.55; 95%CI: 0.20,0.90; p < 0.001) and FT4 (ß=0.47; 95%CI: 0.11,0.82; p < 0.001), with the opposite association in T4 (ß=-0.02; 95%CI: 0.02, -0.01; p < 0.001). For the subgroup analysis, blood Hg was positively correlated with TSH levels in children and adolescents (ß=0.62; 95%CI: 0.09, 1.15; p < 0.001) and FT4 levels in pregnant women (ß=1.00; 95%CI: 0.99, 1.00; p < 0.001) respectively. CONCLUSIONS: This meta-analysis indicates that exposure to Hg in blood could significantly corrrelate with the levels of TSH, T4, and FT4 in the general population. Therefore, it is crucial to control the use of Hg and strengthen protection of the thyroid.
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Mercurio , Glándula Tiroides , Adolescente , Niño , Estudios Transversales , Femenino , Humanos , Mercurio/toxicidad , Embarazo , Estudios Prospectivos , Reproducibilidad de los Resultados , Hormonas Tiroideas , Tirotropina , Tiroxina , TriyodotironinaRESUMEN
AIMS/INTRODUCTION: To investigate the changes in the gut microbiome in the second trimester of pregnancy associated with later-diagnosed gestational diabetes mellitus (GDM) and their relationship with fasting serum levels of metabolites, especially glucose. MATERIALS AND METHODS: We carried out a case-control study with 110 GDM patients and 220 healthy pregnant women who provided fecal samples for 16S ribosomal ribonucleic acid sequencing in the second trimester of pregnancy. RESULTS: Our results showed that GDM patients had lower α-diversity that was significantly associated with glycemic traits. Principal coordinates analysis showed significantly different microbial communities, as within GDM patients, seven genera within the phylum Firmicutes and two within the phylum Actinobacteria were significantly decreased, and four genera within phylum Bacteroidetes were increased. In addition, microbiota co-occurrence network analysis was carried out, and decreased genera within the phylum Firmicutes in GDM patients showed a significant negative correlation with oral glucose tolerance test values. Finally, microbial gene functions related to glycan biosynthesis and metabolism were found to be enriched in GDM patients. CONCLUSIONS: Our results show the relationship between changed gut microbiota composition in the second trimester of pregnancy before the diagnosis of GDM and fasting serum levels of metabolites, which might inform the diagnosis, prevention and treatment of GDM.
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Diabetes Gestacional/microbiología , Microbioma Gastrointestinal , Adulto , Glucemia , Estudios de Casos y Controles , Diabetes Gestacional/sangre , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive. METHOD: This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR). RESULTS: In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data. CONCLUSION: The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.
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Objective: To quantitatively evaluate associations between exposure to triclosan during pregnancy and maternal thyroid hormone levels. Method: The databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched to identify relevant studies on the relationship between prenatal exposure to triclosan and maternal levels of serum thyroid hormone published before October 22, 2019. Stata 12.0 was used to examine the heterogeneity among the eligible studies. Results: Seven studies involving a total of 4,136 participants were included. Overall, descriptive analysis provided no indication that exposure to TCS during pregnancy was related to either maternal FT4 levels (ES = 0.01, 95% CI: -0.03 to 0.05, P = 0.00) or TSH levels (ES = -0.03, 95% CI: -0.13 to 0.07, P = 0.412). Although the results were statistically insignificant, with the increase of urine TCS concentration, maternal FT4 levels exhibited a tendency to increase while TSH levels had a tendency to decrease during pregnancy. Conclusion: The results indicated that exposure to triclosan during pregnancy has no significant influence on maternal levels of thyroid hormone. On account of the inconsistency of existing research designs and study locations, further studies and replication are necessary to confirm these findings.
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Antiinflamatorios no Esteroideos/efectos adversos , Efectos Tardíos de la Exposición Prenatal/sangre , Hormonas Tiroideas/sangre , Triclosán/efectos adversos , Adulto , Disruptores Endocrinos , Femenino , Humanos , Lactante , Recién Nacido , EmbarazoRESUMEN
With the accelerated pace of economic development and modernization, air pollution has become one of the most focused public health problems. However, the impact of particulate matter exposure during pregnancy on childhood asthma and wheezing remains controversial. We performed this meta-analysis to explore the relationship between prenatal exposure to PM2.5 and childhood asthma and wheezing. Candidate papers were searched on PubMed, Web of Science, Embase, and Cochrane Library before July 15, 2019. The main characteristics of the included studies were extracted, and the quality was evaluated by the Newcastle-Ottawa Scale (NOS). A sensitivity analysis was performed to assess the impact of individual studies on the combined effects. The Egger and Begg tests were conducted to examine the publication bias. Nine studies were included in the final analysis. Prenatal exposure to PM2.5 significantly increased the risk of childhood asthma and wheezing (OR = 1.06, 95% CI 1.02-1.11; per 5 µg/m3). Maternal exposure was more strongly related to childhood asthma and wheezing before age 3 (OR = 1.15, 95% CI 1.00-1.31; per 5 µg/m3) than after (OR = 1.04, 95% CI 1.00-1.09; per 5 µg/m3). Children in developed countries showed more severe effects (OR = 1.14, 95% CI 1.02-1.27; per 5 µg/m3). Children who were born to mothers with higher levels of prenatal exposure were at higher risk of asthma and wheezing (OR = 1.07, 95% CI 1.02-1.13; per 5 µg/m3). This meta-analysis indicated that the impact of PM2.5 on childhood asthma and wheezing begins as early as utero, so regulating pollutant emission standards and strengthening prenatal protection are crucial to maternal and child health.
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Contaminación del Aire , Asma , Efectos Tardíos de la Exposición Prenatal , Niño , Femenino , Humanos , Material Particulado , Embarazo , Ruidos RespiratoriosRESUMEN
BACKGROUND: During pregnancy, physiological systems and psychological perceptions vary across individuals. Prenatal physical activity has been linked to reduced anxiety symptoms and lower blood pressure values. However, whether anxiety symptoms can mediate the relationship between physical activity and blood pressure during pregnancy remains unclear. METHODS: In this prospective cohort study, 1275 pregnant women enrolled in Nanjing, China. Life behaviours and anxiety symptoms were investigated during the first trimester. Anxiety symptoms were measured by the Self-Rating Anxiety Scale. Blood pressure values were taken during the third trimester. Multivariate linear regression models were used to estimate the associations of physical activity with anxiety symptoms and blood pressure, and mediating effect models were used to detect the regulating effect by anxiety. RESULTS: The participants were assigned to 3 groups based on their frequency and intensity of physical activity, and those who engaged in regular physical activity had lower blood pressure values. Anxiety symptoms were milder in the regular group than in the insufficient group. Partial mediating effect of anxiety on the association between regular physical activity and systolic blood pressure was significant after accounting for some confounders. LIMITATIONS: The participants' physical activity and anxiety symptoms were self-reported, as well as the lack of details of physical activity during pregnancy may restrict the power of our findings. CONCLUSIONS: Regular physical activity might be beneficial for anxiety and blood pressure. Physical activity likely stabilises systolic blood pressure by alleviating anxiety symptoms. Our research could provide a positive theoretical reference for guiding prenatal care.
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Depresión , Complicaciones del Embarazo , Ansiedad , Presión Sanguínea , China , Ejercicio Físico , Femenino , Humanos , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: To find the correlation between exposure to PM2.5 (fine particulate matter) and hypertensive disorders in pregnancy (HDP), and provide medical evidence for decreasing the incidence of hypertensive disorders in pregnancy. METHOD: A combination of computer and manual retrieval was used to search for keywords in PubMed (385 records), Cochrane Library (20 records), Web of Science (419 records) and Embase (325 records). Finally, ten epidemiological articles were considered in this meta-analysis. Stata 13.0 was used to examine the heterogeneity among the studies and to calculate the combined effect value (OR, odds ratio) by selecting the corresponding models. Sensitivity analysis and publication bias test were also performed. RESULTS: Meta-analysis indicated that there was an association between PM2.5 exposure (per 10⯵g/m3 increase) and hypertensive disorders in pregnancy (ORâ¯=â¯1.52, 95% CI: 1.24-1.87). Exposure to PM2.5 (per 10⯵g/m3 increase) enhanced the risk of pre-eclampsia (ORâ¯=â¯1.31, 95% CI: 1.07-1.61), but there was no evidence relating exposure to PM2.5 to gestational hypertension (ORâ¯=â¯1.35, 95% CI: 0.98-1.87). CONCLUSION: There is a significant link between exposure to PM2.5 and hypertensive disorders in pregnancy. The first and the third trimester were more susceptible to PM2.5 exposure. It is recommended to further strengthen protective measures against PM2.5 during pregnancy.
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Contaminación del Aire/estadística & datos numéricos , Hipertensión Inducida en el Embarazo/epidemiología , Exposición Materna/estadística & datos numéricos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Femenino , Humanos , EmbarazoRESUMEN
This cohort study examines the utilization changes associated with the reintroduction of cost sharing for patients receiving telemental health services.
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Telemedicina , Humanos , Telemedicina/estadística & datos numéricos , Telemedicina/economía , Femenino , Masculino , Estados Unidos , Persona de Mediana Edad , Adulto , Cobertura del Seguro/estadística & datos numéricos , Servicios de Salud Mental/economía , Teleterapia de Salud MentalRESUMEN
Objective: Poor sleep has been associated with type 2 diabetes. Since racial/ethnic minorities experience a disproportionately high prevalence of poor sleep and type 2 diabetes, we sought to determine the relationships between multiple sleep dimensions and incident type 2 diabetes and to investigate if these relationships vary by race/ethnicity. Research design and methods: Prospective data were analyzed from the Sister Study, which enrolled 50 884 women from 2003 to 2009. Participants self-reported sleep duration, sleep latency, night awakenings, and napping at baseline, and a physician's diagnosis of type 2 diabetes at follow-up. Multivariable-adjusted HRs and 95% CIs were estimated using Cox proportional hazards models. Results: Among the 39 071 eligible participants, 87% self-identified as white, 8% black and 5% Hispanic/Latina. The mean follow-up period was 8.5±2.1 years and 1785 type 2 diabetes cases were reported. The incidence rate per 1000 person-years was 5.4 for whites, 13.3 for blacks and 11.6 for Hispanics/Latinas. There was a positive but non-significant increased risk of type 2 diabetes among women who reported short sleep, latency >30 min and frequent night awakenings. In fully-adjusted models, frequent napping was associated with a 19% (HR 1.19, 95% CI 1.04 to 1.37) higher type 2 diabetes risk in the overall sample. Poor sleep among racial/ethnic minorities ranged from a 1.4-fold to a 3.2-fold higher type 2 diabetes risk than whites with recommended sleep. Conclusions: Frequent napping was associated with higher type 2 diabetes risk. Racial/ethnic minorities with poor sleep had a higher type 2 diabetes risk than whites with recommended sleep.
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Diabetes Mellitus Tipo 2/epidemiología , Etnicidad/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Trastornos del Inicio y del Mantenimiento del Sueño/clasificación , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Over the last decade, many studies have indicated a therapeutic potential for treating diabetic lower extremity ulcers with autologous stem cells. The aim of the current study was to conduct a systematic review and meta-analysis of the treatment of diabetic foot ulcers (DFUs) with autologous stem cells. The search strategy included the Pubmed, EMBASE, Web of Science, and Cochrane's Library databases. The endpoint measured was the healing of DFUs.Six eligible randomized controlled trial (RCT) studies were screened from related published studies and reviewed for meta-analysis. The overall meta-analysis showed that stem cell administration was significantly favorable for healing diabetic ulcers (mean difference (MD) 0.52, 95% confidence interval (CI) 0.38-0.65; p < 0.00001). Subgroup analyses indicated that stem cells seemed to exert similar beneficial effects on patients with ulcer size ≥ 5 cm2 (MD 0.76, 95% CI 0.55-0.97; p < 0.00001) and < 5 cm2 (MD 0.43, 95% CI 0.31-0.54; p < 0.00001). Furthermore, stem cells had similar effects on patients aged ≥ 70 years (MD 0.61, 95% CI 0.14-1.08; p = 0.01) and < 70 years (MD 0.47, 95% CI 0.35-0.58; p < 0.00001). This systematic review and meta-analysis suggests a promising role for stem cells in DFU treatment. This review will pave the way to further study on the long-term effects of stem cell-based therapy and large-scale RCTs.