Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common clinical manifestation of a perturbed vaginal ecology associated with adverse sexual and reproductive health outcomes if left untreated. The existing diagnostic modalities are either cumbersome or require skilled expertise, warranting alternate tests. Application of machine-learning tools to heterogeneous and high-dimensional multi-omics datasets finds promising potential in data integration and may aid biomarker discovery. OBJECTIVES: The present study aimed to evaluate the potential of the microbiome and metabolome-derived biomarkers in BV diagnosis. Interpretable machine-learning algorithms were used to evaluate the utility of an integrated-omics-derived classification model. METHODS: Vaginal samples obtained from reproductive-age group women with (n = 40) and without BV (n = 40) were subjected to 16S rRNA amplicon sequencing and LC-MS-based metabolomics. The vaginal microbiome and metabolome were characterized, and machine-learning analysis was performed to build a classification model using biomarkers with the highest diagnostic accuracy. RESULTS: Microbiome-based diagnostic model exhibited a ROC-AUC (10-fold CV) of 0.84 ± 0.21 and accuracy of 0.79 ± 0.18, and important features were Aerococcus spp., Mycoplasma hominis, Sneathia spp., Lactobacillus spp., Prevotella spp., Gardnerella spp. and Fannyhessea vaginae. The metabolome-derived model displayed superior performance with a ROC-AUC of 0.97 ± 0.07 and an accuracy of 0.92 ± 0.08. Beta-leucine, methylimidazole acetaldehyde, dimethylethanolamine, L-arginine and beta cortol were among key predictive metabolites for BV. A predictive model combining both microbial and metabolite features exhibited a high ROC-AUC of 0.97 ± 0.07 and accuracy of 0.94 ± 0.08 with diagnostic performance only slightly superior to the metabolite-based model. CONCLUSION: Application of machine-learning tools to multi-omics datasets aid biomarker discovery with high predictive performance. Metabolome-derived classification models were observed to have superior diagnostic performance in predicting BV than microbiome-based biomarkers.

Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis.

BACKGROUND: Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions. AIMS: To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis. METHODS: Microvesicles originating from different cells were studied pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30 nonresponders) and 20 healthy controls. Microvesicles and cells were determined in peripheral and hepatic vein samples using flow cytometry and correlated with outcomes. Inflammatory signalling pathways and functional alterations of immune cells after stimulation with microvesicles were also investigated. RESULTS: Microvesicles mean levels were higher in nonresponders for T cells (CD3+ CD4+ ; 10.1 MV/µL vs 5.4; P = 0.06), macrophages (CD68+ CD11b+ ; 136.5 vs 121.9 MV/µL; P = 0.01), haematopoietic stem-cells (CD45+ CD34+ ; 116.8 vs 13.4 MV/µL; P = 0.0001) and hepatocytes (ASGPR+ ; 470 vs 361 MV/µL; P = 0.01); the latter two predicting steroid nonresponse in 94% patients at baseline in peripheral plasma. Microvesicle levels correlated with histological and liver disease severity indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P = 0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting impaired regeneration. Also, microvesicles of 0.2-0.4 µm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro. CONCLUSIONS: Pre-therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis.

Some psychological characteristics of adolescents hospitalized following a suicide attempt.

BACKGROUND: In most countries, suicide is second or third leading cause of death in youth. Suicidal tendencies among youth have been the subject of extensive research. Reports of increased rate of suicide attempts in the past few decades indicate that this phenomenon has not been fully understood. AIM: The aim of this study was to better understand the phenomenon of adolescent suicide behavior by defining some specific psychological characteristics of adolescents who were hospitalized at the psychiatric ward because of the suicide attempt. METHODS: 62 participants were assigned to two groups: clinical (adolescents who were hospitalized after a suicide attempt) and non-clinical (adolescents without psychiatric symptoms). They filled in a series of instruments: a questionnaire examining adolescents' demographic characteristics, Rosenberg's Self-Esteem Scale, Youth Self Report. RESULTS: Compared to the non-clinical populaton adolescents attempting suicide had significantly more frequent suicidal thoughts (χ2 = 18.627, df = 1, p < .01), higher incidence of earlier attempts (χ2 = 10.008, df = 1, p < .01), they abused substances more often (χ2 = 7.398, df=1, p < .01), had higher incidence of fathers' psychopathology (χ2 = 11.77, df = 1, p < .01), lower level of self-esteem (t = 4.23, p < .01), and more significant expression of internalized (F/1.60/ = 19.02; p < .01) as well as externalized problems (F/1.60/ = 4.41; p < .05). CONCLUSIONS: This study point to some of the characteristics of adolescents who were hospitalized after a suicide attempt.  

Unconjugated hyperbilirubinemia in patients with non-alcoholic fatty liver disease: a favorable endogenous response.

The clinical significance of increased frequency of unconjugated hyperbilirubinemia in patients with non-alcoholic fatty liver disease (NAFLD) is unknown. Serum bilirubin is an endogenous anti-oxidant, and oxidative stress plays an important role in the pathogenesis of NAFLD. In this study, we have documented 25.4% prevalence of unconjugated hyperbilirubinemia in 204 consecutive NAFLD patients. These patients had a significantly less severe liver disease on histopathology and/or fibroScan which may be attributed to anti-oxidant effect of bilirubin.