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.

Terbinafine resistance in dermatophytes: Time to revisit alternate antifungal therapy.

Resistant superficial dermatophytic infections of the skin and its appendages have emerged as a major health problem in India. Mutations in Squalene epoxidase gene have led to increasing incidence of resistance to terbinafine in dermatophytic isolates. We examined six patients with recalcitrant dermatophytosis attending Dermatology OPD at a tertiary care hospital and demonstrated terbinafine resistance by molecular method. Immediate hyperitivity (IH) reaction to Trichophytin antigen was highlighted in these patients. The patients were treated with alternate antifungals after demonstration of resistance to terbinafine based on the antifungal susceptibility testing (AFST). On follow up the patients responded well to the substitute but the duration of therapy had to be prolonged beyond six weeks.

Simultaneous administration of mifepristone and misoprostol for early termination of pregnancy: a randomized controlled trial.

AIM: To compare the efficacy of different intervals of misoprostol administration (simultaneously vis-à-vis 24 h), after mifepristone, in women undergoing medical termination of pregnancy up to gestation of 49 days. METHODS: Eighty eligible women with single intrauterine pregnancy of ≤ 7 weeks of gestation requesting abortion were randomized to receive either 200 mg of mifepristone orally and 400 µg of misoprostol vaginally simultaneously (Group 1) or at 24-h interval (Group 2).Women who had no bleeding after the drugs were offered a second dose of misoprostol 24 h after the first dose. All patients were followed up on day 14. Primary outcome measure was the complete abortion rate. Secondary outcome measures were the induction-abortion interval, adverse effects, especially bleeding, and treatment acceptability rate. Treatment was considered a failure if surgical intervention was needed for any indication. RESULTS: Complete abortion was achieved in 38 women [95%; 95% confidence interval (CI) 88%, 100%] in Group 1 and 39 women (97.50%; 95% CI 93%,100%) in Group 2 (p = 0.56). A second dose of misoprostol was needed in two patients in Group 1 and in only one patient in Group 2. The induction-abortion interval was 6.50 ± 1.48 h in Group 1 and 5.95 ± 1.81 h in Group 2 (p = 0.13). The difference in frequency of adverse effects in the two groups was statistically insignificant (p = 0.18). The treatment acceptability rate was 97.50% in Group 1 and 95% in Group 2 (p = 0.56). CONCLUSION: Simultaneous administration of mifepristone and 400 µg vaginal misoprostol is an effective alternative to standard regimens for medical abortion up to 49 days of gestation.

The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology.

The TB Structural Genomics Consortium is an organization devoted to encouraging, coordinating, and facilitating the determination and analysis of structures of proteins from Mycobacterium tuberculosis. The Consortium members hope to work together with other M. tuberculosis researchers to identify M. tuberculosis proteins for which structural information could provide important biological information, to analyze and interpret structures of M. tuberculosis proteins, and to work collaboratively to test ideas about M. tuberculosis protein function that are suggested by structure or related to structural information. This review describes the TB Structural Genomics Consortium and some of the proteins for which the Consortium is in the progress of determining three-dimensional structures.

Metal ions modulate the plastic nature of Mycobacterium tuberculosis chaperonin-10.

Chaperonin-10s possess a highly flexible segment of approximately 10 residues that covers their dome-like structure and closes the central cavity of the chaperonin assembly. The dome loop is believed to contribute to the plasticity of their oligomeric structure. We have exploited the presence of a single tryptophan residue occurring in the dome loop of Mycobacterium tuberculosis chaperonin-10 (cpn-10), and through intrinsic fluorescence measurements show that in the absence of metal ions, the tryptophan is almost fully solvent exposed at neutral pH. The dome loop, however, assumes a closed conformation in the presence of metal ions, or at low pH. These changes are fully reversed in the presence of chelating agents such as EDTA, confirming the role of cations in modulating the metastable states of cpn-10.

Conserved structural features and sequence patterns in the GroES fold family.

An irregular, all beta-class of proteins, comprising members of the chaperonin-10, quinone oxidoreductase, glucose dehydrogenase and alcohol dehydrogenase families has earlier been classified as the GroES fold. In this communication, we present an extensive analysis of sequences and three dimensional structures of proteins belonging to this family. The individual protein structures can be superposed within 1.6 A for more than 60 structurally equivalent residues. The comparisons show a highly conserved hydrophobic core and conservation of a few key residues. A glycyl-aspartate dipeptide is suggested as being critical for the maintenance of the GroES fold. One of the surprising findings of the study is the non-conservative nature of Ile to Leu mutations in the protein core, although Ile to Val mutations are found to occur frequently.

ROLE OF HYSTEROSCOPY IN DIAGNOSIS OF MENSTRUAL DISORDERS.

Hysteroscopic evaluation was carried out in 120 cases of menstrual disorders with no clinical positive findings. The ages of patients ranged from 20 years to 48 years. Abnormal findings on hysteroscopy were noted in 48.3 percent (58 cases) and histologically abnormal lesions were observed in 35.8 percent (43 cases). Histological correlation with hysteroscopy was 74.1 percent Lesions like submucous fibroid, polyps, and uterine synechiae were diagnosed with 100 percent accuracy. This study suggests that hysteroscopic evaluation increases the diagnostic precision in patients with intra-uterine lesions and should be done in cases of menstrual disorders alongwith other traditional methods of evaluation.

Controlled field trial of the effectiveness of cholera and cholera El Tor vaccines in Calcutta.

To assess the effectiveness of cholera vaccines, 2 controlled field trials were made in Calcutta-an endemic area-during 1964 and 1965. Three Indian vaccines of which 1 was grown on casein hydrolysate and 2 on agar, a freeze-dried vaccine from the Walter Reed Army Institute of Research (WRAIR), Washington, D.C., and an El Tor vaccine from the Philippines were used, with typhoid-paratyphoid (TAB) vaccine as a control. The 210 112 volunteers were vaccinated subcutaneously with a single dose of one of the vaccines.In the 1964 trial, the number of bacteriologically confirmed cases was not enough to show statistically significant differences in incidence between the 5 vaccine groups and the control group. However, the WRAIR freeze-dried vaccine protected about 40% of the vaccinees for 6 months after vaccination, although the efficacy was higher (57%) during the first 3 months than during the subsequent 3 months (28%). Agar-grown vaccine, produced by the Central Research Institute, Kasauli, was 37% efficacious.In the 1965 trial, owing to the small number of cases in the study area, the Kasauli vaccine was the only one to show statistically significant protection (40%).