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.

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 a-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.

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.

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.

Introduction Sarcopenia has drawn considerable attention as a predictor of postoperative risk, although the relationship between sarcopenia and postoperative risk is contentious. This meta-analysis was conducted to evaluate this relationship. Methods A systematic literature search up to May 2020 was carried out and 43 studies were identified (with 16,716 patients) reporting on the relationship between sarcopenia and postoperative risk. In order to evaluate this relationship, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the dichotomous and continuous method with a random or fixed effects model. Results Compared with non-sarcopenic patients, those with sarcopenia have a higher major complications rate (OR: 4.03, 95% CI: 2.49–5.57, p<0.001), a higher total complications rate (OR: 1.77, 95% CI: 1.40–2.24, p<0.001), a higher 30-day mortality rate (OR: 2.38, 95% CI: 1.56–3.63, p<0.001) and a longer hospital stay (mean difference: 4.54 days, 95% CI: 2.49–6.59 days, p<0.001). Conclusions Sarcopenia significantly increases the risk of major complications, total complications, 30-day mortality and length of hospital stay. For this reason, it is recommended that sarcopenia is added to preoperative risk evaluation to avoid any possible negative outcomes following gastrointestinal oncological surgery.