High imperforate transverse vaginal septum with vaginal cicatrisation: a surgical tribulation.

An early adolescent girl was referred to us with cryptomenorrhoea, and pelvic pain consistent with obstructed menstruation. Originally presumed to be a case of imperforate hymen, she was referred to our centre after two failed surgical misadventures at correcting the obstruction. MRI revealed a haematometrocolpos, high transverse complete vaginal septum and an occluded vagina. She underwent a laparoscopic drainage of the collection, septal resection and a vaginoplasty with an absorbable Interceed graft. Postoperative recovery was smooth and she was sent with instructions to use a vaginal mould daily. Successful surgical treatment requires precise preoperative planning with MRI. A vaginal-assisted laparoscopic approach turned out to be advantageous in resecting the septum to a large extent due to the associated cicatrised vagina. The use of Interceed, a novel mould and harnessing system, ensured a favourable postoperative outcome by bolstering patient motivation due to its less challenging technique of use.

Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer.

Cervical cancer (CC) is a key contributor to cancer-related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR-379/miR-656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5-aza-2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation-regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral-based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post-transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer-related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca2+ levels, and lipid peroxidation rates, and inhibits epithelial-mesenchymal transition (EMT). C14MC targets pyruvate dehydrogenase kinase-3 (PDK3) according to the luciferase reporter assay. PDK3 is overexpressed in CC and is inversely correlated with C14MC. Both miR-494-mimic transfection and C14MC activation inhibited PDK3 expression. Reduced glucose uptake and lactate production, and upregulation of PDK3 upon C14MC activation suggest the potential role of these proteins in metabolic reprogramming. Finally, we showed that C14MC activation may inhibit EMT signaling. Thus, C14MC is a tumor-suppressive and methylation-regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC.

Potent antifungal properties of gallic acid in Sarcochlamys pulcherrima against Candida auris.

Candida auris is a major public health concern due to its high transmission and mortality rates, as well as the emergence of pan-resistant strains. This study aimed to identify an antifungal compound from Sarcochlamys pulcherrima , an ethnomedicinal plant, that can inhibit the growth of C. auris. Methanol and ethyl acetate extracts of the plant were obtained, and high-performance thin-layer chromatography (HPTLC) analysis was conducted to identify the major compounds in the extracts. The major compound detected by HPTLC was subjected to in vitro antifungal activity testing, and its antifungal mechanism was determined. The plant extracts inhibited the growth of both C. auris and Candida albicans. HPTLC analysis revealed the presence of gallic acid in the leaf extract. Furthermore, the in vitro antifungal assay showed that gallic acid inhibited the growth of different C. auris strains. In silico studies indicated that gallic acid can bind to the active sites of carbonic anhydrase (CA) proteins in both C. auris and C. albicans, affecting their catalytic activities. Compounds that target virulent proteins such as CA can aid in the reduction of drug-resistant fungi and the development of novel antifungal compounds with unique modes of action. However, additional in vivo and clinical studies are required to conclusively determine gallic acid's antifungal properties. Gallic acid derivatives may be developed in the future to possess more potent antifungal properties and target various pathogenic fungi.

An audit of hysterectomy in a teaching hospital in India: Story of a decade.

BACKGROUND: The appropriateness of hysterectomy has gained an interest in scrutiny and debate. Periodic audits of the prevailing clinical practices are imperative for insight, and to formulate recommendations and guidelines. We report the temporal trends of hysterectomies, over the last 10 years in a teaching hospital. METHODS: Present study involved all patients who underwent hysterectomy at a teaching hospital, from January 1, 2012 to December 31, 2021. Patients were identified by medical record tracking using International Classification of Diseases-9 codes. Case records were reviewed for demography, indication for surgery, approach, complications, hospital stay, and histopathological correlation. RESULTS: Over the years the absolute number of hysterectomies in our hospital has ranged from 414 to 597 (mean 476), barring the coronavirus 19 pandemic year. The proportion of hysterectomy among all gynaecological admissions has ranged from 6% to 9%, except in 2020 where this proportion dropped down to 4%. The indications, age distribution, surgical approach, and complications have remained almost same. CONCLUSION: We report a static trend in hysterectomy over the past 10 years. This audit provides an insight for the need of shifting the abdominal to vaginal route, in carefully chosen patients. This will be beneficial for the patients, and for the trainees, where they can learn under supervision. Availability and patient education about the nonsurgical management options for benign gynecological conditions, as well as awareness about sequelae of hysterectomy, will bring down the rate in countries such as India.

BacARscan: an in silico resource to discern diversity in antibiotic resistance genes.

Antibiotic resistance has escalated as a significant problem of broad public health significance. Regular surveillance of antibiotic resistance genes (ARGs) in microbes and metagenomes from human, animal and environmental sources is vital to understanding ARGs' epidemiology and foreseeing the emergence of new antibiotic resistance determinants. Whole-genome sequencing (WGS)-based identification of the microbial ARGs using antibiotic resistance databases and in silico prediction tools can significantly expedite the monitoring and characterization of ARGs in various niches. The major hindrance to the annotation of ARGs from WGS data is that most genome databases contain fragmented genes/genomes (due to incomplete assembly). Herein, we describe an insilicoBacterial Antibiotic Resistance scan (BacARscan) (http://proteininformatics.org/mkumar/bacarscan/) that can detect, predict and characterize ARGs in -omics datasets, including short sequencing, reads, and fragmented contigs. Benchmarking on an independent non-redundant dataset revealed that the performance of BacARscan was better than other existing methods, with nearly 92% Precision and 95% F-measure on a combined dataset of ARG and non-ARG proteins. One of the most notable improvements of BacARscan over other ARG annotation methods is its ability to work on genomes and short-reads sequence libraries with equal efficiency and without any requirement for assembly of short reads. Thus, BacARscan can help monitor the prevalence and diversity of ARGs in microbial populations and metagenomic samples from animal, human, and environmental settings. The authors intend to constantly update the current version of BacARscan as and when new ARGs are discovered. Executable versions, source codes, sequences used for development and usage instructions are available at (http://www.proteininformatics.org/mkumar/bacarscan/downloads.html) and GitHub repository (https://github.com/mkubiophysics/BacARscan).

Stress incontinence combined score (SICS): A novel combined grading system to assess the severity of stress urinary incontinence in women.

INTRODUCTION: Natural history of urinary incontinence (UI) in women is a less understood domain. Stratifying severity of stress urinary incontinence (SUI) can be an important tool to understand the natural history, prognosticate the disease and plan optimal management. Present study was aimed to test a novel score (Stress Incontinence Combined score: SICS) with the currently popular tools International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and Incontinence Symptom Index (ISI) scores. MATERIAL AND METHODS: This was a prospective study conducted at a university teaching hospital, over a period of 2 years. After screening women for SUI, SICS was administered. The novel SICS score was then compared with ICIQ-UI SF and ISI. RESULTS: A total of 1750 women, attending various OPDs in a tertiary care hospital, were screened for urinary incontinence. The prevalence of UI and SUI was 26.6% and 12.8% respectively. The agreement between ISI and SICS was 81.7%, while the ICIQ- UI SF agreed with the SICS in 80.8% of the cases. AUROC analysis done showed that a score of 10 or more on the SICS (total score 16) could diagnose high-grade SUI with a sensitivity of 97%, specificity of 96% (Reference: ISI), and a sensitivity of 100%, and specificity of 93% (Reference: ICIQ- UI SF) CONCLUSION: SICS is the first of its kind tool, developed to specifically grade the severity of SUI, while incorporating both subjective and objective measures, with excellent reliability and reproducibility.

Co-pyrolysis of petroleum coke and banana leaves biomass: Kinetics, reaction mechanism, and thermodynamic analysis.

Insights into thermal degradation behaviour, kinetics, reaction mechanism, possible synergism, and thermodynamic analysis of co-pyrolysis of carbonaceous materials are crucial for efficient design of co-pyrolysis reactor systems. Present study deals with comprehensive kinetics and thermodynamic investigation of co-pyrolysis of petroleum coke (PC) and banana leaves biomass (BLB) for realizing the co-pyrolysis potential. Thermogravimetric non-isothermal studies have been performed at 10, 20, and 30 °C/min heating rates. Synergistic effect between PC and BLB was determined by Devolatilization index (Di) and mass loss method. Kinetic parameters were estimated using seven model-free methods. Standard activation energy for PC + BLB blend from FWO, KAS, Starink, and Vyazovkin methods was ≈165 kJ/mol and that from Friedman and Vyazovkin advanced isoconversional methods was ≈171 kJ/mol. The frequency factor calculated for the blend from Kissinger method was found to be in the range of 106-1016s-1. Devolatilization index (Di) showed synergistic effect of blending. The data pertaining to co-pyrolysis was found to fit well with R2 (second order) and D3 (three dimensional) from Z(α) master plot. Thermodynamic parameters, viz. ΔH ≈ 163 kJ/mol and ΔG ≈ 151 kJ/mol were calculated to determine the feasibility and reactivity of the co-pyrolysis process. The results are expected to be useful in the design of petcoke and banana leaves biomass co-pyrolysis systems.

ß-LacFamPred: An online tool for prediction and classification of ß-lactamase class, subclass, and family.

ß-Lactams are a broad class of antimicrobial agents with a high safety profile, making them the most widely used class in clinical, agricultural, and veterinary setups. The widespread use of ß-lactams has induced the extensive spread of ß-lactamase hydrolyzing enzymes known as ß-lactamases (BLs). To neutralize the effect of ß-lactamases, newer generations of ß-lactams have been developed, which ultimately led to the evolution of a highly diverse family of BLs. Based on sequence homology, BLs are categorized into four classes: A-D in Ambler's classification system. Further, each class is subdivided into families. Class B is first divided into subclasses B1-B3, and then each subclass is divided into families. The class to which a BL belongs gives a lot of insight into its hydrolytic profile. Traditional methods of determining the hydrolytic profile of BLs and their classification are time-consuming and require resources. Hence we developed a machine-learning-based in silico method, named as ß-LacFamPred, for the prediction and annotation of Ambler's class, subclass, and 96 families of BLs. During leave-one-out cross-validation, except one all ß-LacFamPred model HMMs showed 100% accuracy. Benchmarking with other BL family prediction methods showed ß-LacFamPred to be the most accurate. Out of 60 penicillin-binding proteins (PBPs) and 57 glyoxalase II proteins, ß-LacFamPred correctly predicted 56 PBPs and none of the glyoxalase II sequences as non-BLs. Proteome-wide annotation of BLs by ß-LacFamPred showed a very less number of false-positive predictions in comparison to the recently developed BL class prediction tool DeepBL. ß-LacFamPred is available both as a web-server and standalone tool at http://proteininformatics.org/mkumar/blacfampred and GitHub repository https://github.com/mkubiophysics/B-LacFamPred respectively.

Investigating the OXA Variants of ESKAPE Pathogens.

ESKAPE pathogens are the leading cause of nosocomial infections. The Global Priority List of WHO has categorized ESKAPE as priority 1 and 2 pathogens. Even though several mechanisms contribute to antimicrobial resistance, OXA ß-lactamase has emerged as a new threat in combating nosocomial infections. In the present study we have investigated the presence of OXA and their variants, copy number, distribution on chromosomes/plasmids, subfamilies, phylogenetic relationships, amino acid identities and variabilities in ESKAPE pathogens. Our results revealed that a total of 929 OXA were present in 2258 completely assembled genomes, which could be further subdivided into 16 sub-families. Among all the ESKAPE pathogens, OXA were highly prevalent in A. baumannii, followed by P. aeruginosa and K. pneumoniae but completely absent in E. faecium and S. aureus while, only a few copies were found in Enterobacter spp. Most of the OXA variants belonged to the OXA-51-like subfamily (200 proteins), followed by OXA-50-like subfamily (189 proteins), OXA-23-like subfamily (156 proteins) and OXA-1-like subfamily (154 proteins). OXA-51-like, OXA-213-like, OXA-134-like, OXA-58-like, OXA-24-like and OXA-20-like subfamilies were present exclusively in A. baumannii. Phylogenetic tree of the subfamilies revealed that OXA-1-like and OXA-33-like, OXA-51-like and OXA-213-like and, OXA-5-like and OXA-10-like belonged to the same branches with amino acid identities as 100%, 97.10% and 80.90% respectively. This indicates that the members of these subfamily-pairs might have evolved from the same ancestor or have recently diverged. Thus, a judicious use of carbapenems is warranted to curtail the rise of new OXA enzymes and preserve them. This is the first detailed report about the OXA of ESKAPE pathogens.

Pyrolysis of mustard oil residue: A kinetic and thermodynamic study.

Critical analysis of thermogravimetric data, characterization of the biomass, and kinetic and thermodynamic analyses are crucial in the design of efficient biomass pyrolysis systems. In this study, characterization, kinetic and thermodynamic analysis was performed for pyrolysis of mustard oil residue (MOR). Thermogravimetric analysis (TGA) with differential thermal analysis (DTA) was applied to study thermal decomposition behaviour of MOR at 10, 20, and 30 °C/min. FTIR and XRD analyses were used to characterize MOR. Average activation energy estimated from employed isoconversional methods was ≈155 kJ/mol. Variation in activation energy was found to be statistically insignificant as suggested by p-value of 0.992 by one-way ANOVA method. The pyrolytic temperature for MOR ranged from 234 to 417 °C. Reaction mechanism predicted as R3 (third order) and D3 (three dimensional). Thermodynamic parameters (ΔHα, ΔGα, and ΔSα) showed that endothermicity increased from 0.2 to 0.8 conversion and product had highest energy at 0.8 conversion.

Post-operative tension adjustment-A simple technical modification in mid-urethral slings (MUS) for stress urinary incontinence (SUI).

INTRODUCTION: Mid-urethral sling (MUS) surgeries have revolutionized the management of stress urinary incontinence (SUI). However, MUS is a delicate balance of tension on the mid urethral segment with a 12 % risk of failure to achieve complete continence; and up-to 20 % chance of post-operative voiding dysfunction. We propose a simple technical modification in which the long ends of the tape at suprapubic or groin area are not cut immediately and are covered with a sterile dressing. After 48-72 h post-surgery the patient is checked for continence and voiding difficulties. Following this an ultrasonographic assessment of post-void residual urine is performed. Keeping in mind these 3 criteria the tape is adjusted. After complete subjective as well as objective satisfaction the long ends of tape are cut. MATERIAL AND METHODS: This is a retrospective analysis of women who underwent MUS surgery for the management of SUI, with our simple technical modification of tape adjustment in the postoperative period. A total of 17 patients operated by single surgeon in one year were included. RESULTS: Our results show that 58.8 % of our patients who underwent MUS procedures required post-operative tape adjustment. The number was significantly higher in the MUS - Retropubic group (85.7 %) as compared to the MUS - Obturator group (40 %). Three patients in the MUS - Retropubic group required a second time tape adjustment. Following tape adjustment all patients had complete continence (subjective and objective), with no voiding dysfunction. CONCLUSION: The incidence of postoperative voiding dysfunction is significant following MUS surgery for SUI. A simple technical modification of delaying the cutting of the tape for two to three days gives the opportunity for perfect tension adjustment.

Cervical cytology and associated factors among tribal women of Karnataka, India.

BACKGROUND: Reproductive well-being is a crucial element of women's health. Due to the asymptomatic nature of gynaecological morbidities, women rarely seek medical advice in the initial period leading to delayed diagnosis and poor prognosis of subsequent disease. The present study aimed to explore the cervical cytology and its associated risk factors among women from tribal communities of the southern part of coastal Karnataka, India. METHODS: Papanicolaou (Pap) smear test was performed among 1140 women from three tribal populations, to detect cervical lesions, infections and reactive changes. A semi-structured questionnaire was administered to collect data on socio-demographic and reproductive characteristics of the study population. RESULTS: The most predominant gynaecological complaint among the participants was severe lower back ache (77.6%), followed by white discharge per vagina (29.0%) and menstrual irregularities (25.9%). Of the 1140 women screened, 12.4% showed cervical microbial infections, 23.6% were reported to have reactive changes, and 0.2% had epithelial cell abnormalities in the cervix. Cervical microbial infections were found to be associated with younger age group, low socio-economic status and younger age at sexual debut. CONCLUSION: Most of the symptoms suggestive of gynaecological morbidities reported in this study are preventable or treatable. Strengthening ongoing cervical cancer screening programme and implementation of health education programmes among tribal population would be the right policy approach to prevent, detect and treat these symptoms at an early stage and to achieve acceptable health outcomes among tribal women.

ZNF471 modulates EMT and functions as methylation regulated tumor suppressor with diagnostic and prognostic significance in cervical cancer.

Cervical cancer (CC) is a leading cause of cancer-related death among women in developing countries. However, the underlying mechanisms and molecular targets for therapy remain to be fully understood. We investigated the epigenetic regulation, biological functions, and clinical utility of zinc-finger protein 471 (ZNF471) in CC. Analysis of cervical tissues and five independent public datasets of CC showed significant hypermethylation of the ZNF471 gene promoter. In CC cell lines, promoter DNA methylation was inversely correlated with ZNF471 expression. The sensitivity and specificity of the ZNF471 hypermethylation for squamous intraepithelial lesion (SIL) vs tumor and normal vs tumor was above 85% with AUC of 0.937. High methylation and low ZNF471 expression predicted poor overall and recurrence-free survival. We identified -686 to +114 bp as ZNF471 promoter, regulated by methylation using transient transfection and luciferase assays. The promoter CpG site methylation of ZNF471 was significantly different among cancer types and tumor grades. Gal4-based heterologous luciferase reporter gene assays revealed that ZNF471 acts as a transcriptional repressor. The retroviral mediated overexpression of ZNF471 in SiHa and CaSki cells inhibited growth, proliferation, cell migration, invasion; delayed cell cycle progression in vitro by increasing cell doubling time; and reduced tumor growth in vivo in nude mice. ZNF471 overexpression inhibited key members of epithelial-mesenchymal transition (EMT), Wnt, and PI3K-AKT signaling pathways. ZNF471 inhibited EMT by directly targeting vimentin as analyzed by bioinformatic analysis, ChIP-PCR, and western blotting. Thus, ZNF471 CpG specific promoter methylation may determine the prognosis of CC and could function as a potential tumor suppressor by targeting EMT signaling.

Knowledge, Attitude and Practices Towards Cervical Cancer and its Screening Among Women from Tribal Population: a Community-Based Study from Southern India.

BACKGROUND: Cervical cancer continues to be a leading cancer among women in India. Despite availability of various screening techniques, majority of Indian women remain unscreened for cancer cervix. The increasing incidence could be attributed to the lack of awareness regarding cervical cancer screening and paucity of organized screening facilities in the country. This study assessed the knowledge, attitude and practices (KAP) towards cervical cancer screening among tribal women of coastal Karnataka, southern India. METHODS: A community-based cross-sectional study was conducted among 1140 women aged 20-65 years from three tribes. Information on their KAP towards cervical cancer screening was collected using a semi-structured questionnaire. RESULTS: Mean age of the participants was 39.8 ± 10.1 years. Although 82.9% of the participants reported to have heard of cervical cancer, 51% were aware that the disease could be prevented, and only 2.3% knew that it can be detected at an early stage. Over 75% of the participants did not have adequate knowledge regarding cervical cancer. However, majority of them (99.9%) had a favourable attitude towards cervical cancer screening. None of them had undergone cervical cancer screening prior to the study. The knowledge scores were significantly associated with age group, marital status, education level, socioeconomic status and tribal community of the participants (p < 0.05). CONCLUSION: Overall knowledge regarding cervical cancer among the surveyed women was poor, though they exhibited a positive attitude. This calls for a sustained health education and screening program to create awareness and improve the uptake of cervical cancer screening among these women.

Molecular landscape of recurrent cervical cancer.

Cervical cancer (CC) is a major gynecological problem in developing and underdeveloped countries. Despite the significant advancement in early detection and treatment modalities, several patients recur. Moreover, the molecular mechanisms responsible for CC recurrence remains obscure. The patients with CC recurrence often show poor prognosis and significantly high mortality rates. The clinical management of recurrent CC depends on treatment history, site, and extent of the recurrence. Owing to poor prognosis and limited treatment options, recurrent CC often presents a challenge to the clinicians. Several in vitro, in vivo, and patient studies have led to the identification of the critical molecular changes responsible for CC recurrence. Both aberrant genetic and epigenetic modifications leading to altered cell signaling pathways have been reported to impact CC recurrence. Researchers are currently trying to dissect the molecular pathways in CC and translate these findings for better management of disease. This article attempts to review the existing knowledge of disease relapse, accompanying challenges, and associated molecular players in CC.

Mitochondrial DNA copy number variation - A potential biomarker for early onset preeclampsia.

OBJECTIVES: Oxidative stress has been hypothesized as a central component of both placental and endothelial dysfunction, leading to PE. This oxidative stress leading to mitochondrial dysfunction may be due to variations in mtDNA copy numbers as an adaptive response. In the present study we aimed to analyse mtDNA copy numbers in the placenta obtained after delivery from the women with PE as compared to the controls. STUDY DESIGN: It was a prospective case control study. A total of 32 placental samples were analyzed (Cases: 17; Controls: 15). Samples were collected ex vivo, after childbirth. MtDNA content was determined useing real-time quantitative PCR qRT-PCR) using TaqMan probes designed for two genes: MT-ND1 and a mitochondrial gene encoding for the NADH dehydrogenase 1 protein. RESULTS: We found that the median (IQR) mtDNA copy number was higher in PE cases 24.32 (9.260-33.51) as compared with controls 20.32 (13.33-26.22). On subgroup analysis, the median (IQR) mtDNA copy number was higher in early onset PE 28.06 (20.80-36.87) as compared to late onset PE 9.215 (4.150-56.45) as well as the controls 20.32 (13.33-26.22). CONCLUSION: Our findings support a higher mtDNA copy number in early onset PE as compared to late onset PE and control population. Although, mtDNA may only be increased in very severe cases of early onset preeclampsia. Future research may be directed to ascertain if mtDNA copy numbers can be a novel biomarker to predict or prognosticate early onset preeclampsia.

Psychological impact of mass quarantine on population during pandemics-The COVID-19 Lock-Down (COLD) study.

BACKGROUND: Quarantine often is an unpleasant experience. The aim of this study is to explore the degree of psychological distress in terms of-Depression, Anxiety and Stress among the adult population in India during the strict 21 days mandatory lockdown. We hypothesize that quantification of psychological impact of current situation will help us to modify the policies and implementation strategies. This assessment might also help in future to keep targeted services in place, to cope up with the psychological distress of the quarantined population. METHOD: A cross sectional survey design was adopted to assess the psychological state of general population in India, during the COVID-19 mandatory lockdown period, with the help of a validated questionnaire. FINDINGS: The reported prevalence of depression was around 30.5%, which was the highest among the variables of psychological health. Anxiety was reported by 22.4%, followed by stress which was seen in 10.8% of respondents. In the third week the incidence of depression (37.8% versus 23.4%; p<0.001), anxiety (26.6% versus 18.2%; p<0.001) and stress (12.2% versus 9.3%; p<0.045) was reported to be significantly higher as compared to second week. INTERPRETATION: Our results suggest a progressively detrimental impact of lockdown on various aspects of psychological health. We noticed around eight to ten fold increase in the prevalence of depression (30.5%) and anxiety (22.4%) during lockdown, as compared to baseline statistics in Indian population (3·1-3·6% for depressive disorders and 3·0-3·5% for anxiety disorders).

Placental mitochondrial DNA mutations and copy numbers in intrauterine growth restricted (IUGR) pregnancy.

Intrauterine Growth Restriction (IUGR) is a common and significant complication that arises during pregnancy wherein the fetus fails to attain its full growth potential. Mitochondria being one of the primary sources of energy, plays an important role in placentation and fetal development. In IUGR pregnancy, increased oxidative stress due to inadequate oxygen and nutrient supply could possibly alter mitochondrial functions and homeostasis. In this study, we evaluated the biochemical and molecular changes in mitochondria as biosignature for early and better characterization of IUGR pregnancies. We identified significant increase in mtDNA copy number in both IUGR (p = 0.0001) and Small for Gestational Age (SGA) but healthy (p = 0.0005) placental samples when compared to control. Whole mitochondrial genome sequencing identified novel mutations in both coding and non-coding regions of mtDNA in multiple IUGR placental samples. Sirtuin-3 (Sirt3) protein expression was significantly downregulated (p = 0.027) in IUGR placenta but there was no significant difference in Nrf1 expression in IUGR when compared to control group. Our study provides an evidence for altered mitochondrial homeostasis and paves a way towards interrogating mitochondrial abnormalities in IUGR pregnancies.

BacEffluxPred: A two-tier system to predict and categorize bacterial efflux mediated antibiotic resistance proteins.

Efflux proteins are transport proteins, which are involved in transporting different substrates from the cell to the external environment, including antibiotics. The efflux mechanism and efflux pumps are a major reason underlying emerging rampant antibiotic resistance (AR) in microbes. To reduce the resources required and time of identification, characterization and classification of bacterial efflux proteins, we have developed a fast and accurate support vector machine based two-tier prediction system, BacEffluxPred, which can predict bacterial efflux proteins responsible for AR and identify their corresponding families. A leave-one-out cross-validation also called jackknife procedure was used for performance evaluation. The accuracy to discriminate bacterial AR efflux from non-AR efflux was obtained as 85.81% (at tier-I) while accuracies for prediction of efflux pump families like ABC, MFS, RND and MATE family were found 92.13%, 85.39%, 91.01% and 99.44%, respectively (at tier-II). Benchmarking on an independent dataset also showed that BacEffluxPred had comparable accuracy for prediction of bacterial AR efflux pumps and their families. This is the first in-silico tool for predicting bacterial AR efflux proteins and their families and is freely available as both web-server and standalone versions at http://proteininformatics.org/mkumar/baceffluxpred/.

Exploring the genetic determinants underlying the differential production of an inducible chromosomal cephalosporinase - BlaB in Yersinia enterocolitica biotypes 1A, 1B, 2 and 4.

Yersinia enterocolitica is an enteric bacterium which can cause severe gastroenteritis. Beta-lactams are the most widely used antibiotics against Y. enterocolitica. Y. enterocolitica produces two chromosomal ß-lactamases, BlaA and BlaB. BlaB is an Ambler Class C inducible broad spectrum cephlaosporinase which showed differential enzyme activity in different biotypes of Y. enterocolitica. The expression of blaB is mainly regulated by ampR- the transcriptional regulator and, ampD - which helps in peptidoglycan recycling. The aim of this study was to identify and characterize genetic determinants underlying differential enzyme activity of BlaB in Y. enterocolitica biotypes 1 A, IB, 2 and 4. Thus, ampR, blaB and ampD were PCR-amplified and modeled in silico. The intercistronic region containing promoters of ampR and blaB was also investigated. Our results indicated that blaB was more inducible in biotypes 2 and 4, than in biotypes 1 A and 1B. Superimposition of in silico modeled proteins suggested that variations in amino acid sequences of AmpR, BlaB and AmpD were not responsible for hyper-production of BlaB in biotypes 2 and 4. Analysis of promoter regions of ampR and blaB revealed variations at -30, -37 and -58 positions from blaB transcription start site. Studies on relative expression levels of blaB in different biotypes by qRT-PCR indicated that nucleotide variations at these positions might contribute to a higher enzyme activity of BlaB in biotypes 2 and 4. However, this is a preliminary study and further studies including more strains of each biotype are required to strengthen our findings. Nevertheless, to the best of our knowledge, this is the first study which has investigated the genetic determinants underlying differential inducible production of BlaB in different biotypes of Y. enterocolitica.