Pregnancy outcomes among Indian women: increased prevalence of miscarriage and stillbirth during 2015-2021.

BACKGROUND: Pregnancy outcome is an important health indicator of the quality of maternal health. Adverse pregnancy outcomes is a major public health problem, which can lead to poor maternal and neonatal outcomes. This study investigates the trends in pregnancy outcomes prevalent during 2015-2021 in Indian women. METHODS: The study analysed the data presented in the fourth (2015-16) and fifth (2019-21) rounds of National Family Health Survey (NFHS). The absolute and relative changes in the birth outcomes of last pregnancy during the five years preceding the surveys were estimated using data collected from 195,470 women in NFHS-4 and from 255,549 women in NFHS-5. RESULTS: Livebirth decreased by 1.3 points (90.2% vs. 88.9%), and nearly half of the Indian states/UTs (n = 17/36) had lower than the national average of livebirth (88.9%) reported during 2019-21. A higher proportion of pregnancy loss was noted, particularly miscarriages increased in both urban (6.4% vs. 8.5%) and rural areas (5.3% vs. 6.9%), and stillbirth increased by 28.6% (0.7% vs. 0.9%). The number of abortions decreased (3.4% vs. 2.9%) among Indian women. Nearly half of the abortions were due to unplanned pregnancies (47.6%) and more than one-fourth (26.9%) of abortions were performed by self. Abortions among adolescent women in Telangana was eleven times higher during 2019-21 as compared to 2015-16 (8.0% vs. 0.7%). CONCLUSION: Our study presents evidence of a decrease in the livebirth and an increase in the frequency of miscarriage and stillbirth among Indian women during 2015-2021. This study emphasises that there is a need of regional-specific, comprehensive and quality maternal healthcare programs for improving livebirth among Indian women.

Dysregulation of X-ray repair cross-complementing 4 expression in the eutopic endometrium of women with endometriosis.

Recent data suggest that the DNA damage response (DDR) is altered in the eutopic endometrium (EE) of women with endometriosis and this probably ensues in response to higher DNA damage encountered by the EE in endometriosis. DDR operates in a tissue-specific manner and involves different pathways depending on the type of DNA lesions. Among these pathways, the non-homologous end joining (NHEJ) pathway plays a critical role in the repair of dsDNA breaks. The present study was undertaken to explore whether NHEJ is affected in the EE of women with endometriosis. Toward this, we focused on the X-ray repair cross-complementing 4 (XRCC4) protein, one of the core components of the NHEJ pathway. Endometrial XRCC4 protein levels in the mid-proliferative phase were found significantly (P < 0.05) downregulated in women with endometriosis, compared to control women. Investigation of a microarray-based largest dataset in the Gene Expression Omnibus database (GSE51981) revealed a similar trend at the transcript level in the EE of women with endometriosis, compared to control women. Further in vitro studies were undertaken to explore the effects of H2O2-induced oxidative stress on DNA damage, as assessed by γ-H2AX and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunolocalization, and XRCC4 protein levels in endometrial stromal (hTERT immortalized human endometrial stromal cell line (ThESCs)) and epithelial (Ishikawa) cells. A significant decrease in XRCC4 protein levels and significantly higher localization of γ-H2AX and 8-OHdG were evident in ThESCs and Ishikawa cells experiencing oxidative stress. Overall, the study demonstrates that the endometrial XRCC4 expression is dysregulated in women with endometriosis and this could be due to higher oxidative stress in endometriosis.

Outcomes in neonates born to mothers with COVID-19 during the second wave in India.

COVID-19 pandemic has affected all age groups globally including pregnant women and their neonates. The aim of the study was to understand outcomes in neonates of mothers with COVID-19 during the first and second waves of COVID-19 pandemic. A retrospective analysis of 2524 neonates born to SARS-CoV-2-infected mothers was conducted during the first wave (n = 1782) and second wave (n = 742) of the COVID-19 pandemic at five study sites of the PregCovid registry in Maharashtra, India. A significant difference was noted in preterm birth, which was higher in the second wave (15.0%, 111/742) compared to the first wave (7.8%, 139/1782) (P < 0.001). The proportion of neonates requiring NICU admission was significantly higher in the second wave (19.0%, 141/742) as compared to that in the first wave (14.8%, 264/1782) (P < 0.05). On comparing regional differences, significantly higher neonatal complications were reported from Mumbai metropolitan region (P < 0.05). During the second wave of COVID-19, birth asphyxia and prematurity were 3.8- and 2.1-fold higher respectively (P < 0.001). Neonatal resuscitation at birth was significantly higher in second wave (3.4%, 25/742 vs 1.8%, 32/1782) (P < 0.05). The prevalence of SARS-CoV-2 infection in neonates was comparable (4.2% vs 4.6%) with no significant difference between the two waves. CONCLUSION: Higher incidence of adverse outcomes in neonates born to SARS-CoV-2-infected mothers in the second wave of COVID-19 as compared to the first wave. TRIAL REGISTRATION: PregCovid study is registered with the Clinical Trial Registry of India (CTRI/2020/05/025423, Registered on 28/05/2020). WHAT IS KNOWN: • The second wave of COVID-19 was more lethal to pregnant women than the first wave. Newborns are at risk of developing complications. WHAT IS NEW: • Birth asphyxia, prematurity, and neonatal resuscitation at birth were significantly higher in the second wave as compared to those in the first wave of the COVID-19 pandemic in India.

Co-infection of malaria and early clearance of SARS-CoV-2 in healthcare workers.

Healthcare workers (HCWs) are at higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Information regarding co-infection of SARS-CoV-2 with vector-borne diseases (malaria and dengue) is crucial especially for the countries wherein malaria and dengue are endemic. The objective was to study the prevalence, demographic, clinical presentations among HCWs with coronavirus disease 2019 (COVID-19) and to compare the viral clearance in HCWs with COVID-19 and co-infection of malaria and dengue. This retrospective study was conducted at a dedicated COVID-19 hospital, BYL Nair Charitable Hospital (NH), Mumbai, India April 6th-October 31st 2020. The SARS-CoV-2 infection in HCWs was confirmed by reverse transcription-plymerase chain reaction. Out of 491 HCWs infected with SARS-CoV-2, analysis of viral clearance was carried out in 467 HCWs over seven month periods, The prevalence of SARS-CoV-2 infection in HCWs was 13% (491 out of 3711). Out of the HCWs with COVID-19, prevalence of SARS-CoV-2 infection was higher among security guards (25%) with 1% mortality. The co-infection of malaria or dengue was reported in 31 HCWs (6.3%). The mean duration of virus clearance was longer (12 days) in symptomatic HCWs as compared to asymptomatic (8 days, p < .005). The recovery of SARS-CoV-2 infection in HCWs was faster (mean 8 days) with co-infection of malaria than without malaria (p < .005). We recommend universal testing of HCWs, to optimize staffing levels during the current pandemic as HCWs are the most precious resource. There is a need to effectively implement standard protocols for prevention of vector-borne diseases, especially in the hospital settings.

Persistence of SARS-CoV-2 in the first trimester placenta leading to transplacental transmission and fetal demise from an asymptomatic mother.

Coronavirus disease 2019 (COVID-19) is caused by infection of the respiratory tract by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which survives in the tissues during the clinical course of infection but there is limited evidence on placental infection and vertical transmission of SARS-CoV-2. The impact of COVID-19 in first trimester pregnancy remains poorly understood. Moreover, how long SARS-CoV-2 can survive in placenta is unknown. Herein, we report a case of a pregnant woman in the first trimester who tested positive for SARS-CoV-2 at 8 weeks of gestation, although her clinical course was asymptomatic. At 13 weeks of gestation, her throat swab tested negative for SARS-CoV-2 but viral RNA was detected in the placenta, and the Spike (S) proteins (S1 and S2) were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. Histologically, the villi were generally avascular with peri-villus fibrin deposition and in some areas the syncytiotrophoblast layer appeared lysed. The decidua also had fibrin deposition with extensive leukocyte infiltration suggestive of inflammation. The SARS-CoV-2 crossed the placental barrier, as the viral RNA was detected in the amniotic fluid and the S proteins were detected in the fetal membrane. Ultrasonography revealed extensively subcutaneous edema with pleural effusion suggestive of hydrops fetalis and the absence of cardiac activity indicated fetal demise. This is the first study to provide concrete evidence of persistent placental infection of SARS-CoV-2 and its congenital transmission is associated with hydrops fetalis and intrauterine fetal demise in early pregnancy.

Endometrial DNA damage response is modulated in endometriosis.

STUDY QUESTION: Is the DNA damage response (DDR) dysregulated in the eutopic endometrium of women with endometriosis? SUMMARY ANSWER: Endometrial expression of genes involved in DDR is modulated in women with endometriosis, compared to those without the disease. WHAT IS KNOWN ALREADY: Ectopic endometriotic lesions are reported to harbour somatic mutations, thereby hinting at dysregulation of DDR and DNA repair pathways. However, it remains inconclusive whether the eutopic endometrium also manifests dysregulated DDR in endometriosis. STUDY DESIGN, SIZE, DURATION: For this case-control study conducted between 2015 and 2019, eutopic endometrial (E) samples (EE- from women with endometriosis, CE- from women without endometriosis) were collected in either mid-proliferative (EE-MP, n = 23; CE-MP, n = 17) or mid-secretory (EE-MS, n = 17; CE-MS, n = 9) phases of the menstrual cycle. This study compares: (i) DNA damage marker localization, (ii) expression of DDR genes and (iii) expression of DNA repair genes in eutopic endometrial samples from women with and without endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included (i) 40 women (aged 31.9 ± 0.81 years) with endometriosis and (ii) 26 control women (aged 31.4 ± 1.02 years) without endometriosis. Eutopic endometrial samples from the two groups were divided into different parts for histological analysis, immunohistochemistry, RNA extraction, protein extraction and comet assays. Eighty-four genes of relevance in the DNA damage signalling pathway were evaluated for their expression in eutopic endometrial samples, using RT2 Profiler PCR arrays. Validations of the expression of two GADD (Growth Arrest DNA Damage Inducible) proteins - GADD45A and GADD45G were carried out by immunoblotting. DNA damage was assessed by immunohistochemical localization of γ-H2AFX (a phosphorylated variant of histone H2AX) and 8-OHdG (8-hydroxy-2'-deoxyguanosine). RNA sequencing data from mid-proliferative (EE-MP, n = 4; CE-MP, n = 3) and mid-secretory phase (EE-MS and CE-MS, n = 4 each) endometrial samples were scanned to compare the expression status of all the genes implicated in human DNA repair. PCNA (Proliferating Cell Nuclear Antigen) expression was determined to assess endometrial proliferation. Residual DNA damage in primary endometrial cells was checked by comet assays. Public datasets were also scanned for the expression of DDR and DNA repair genes as our RNASeq data were limited by small sample size. All the comparisons were made between phase-matched endometrial samples from women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: Endometrial expression of DDR genes and intensity of immunolocalized γ-H2AFX were significantly (P < 0.05) higher in EE, compared to CE samples. DDR proteins, especially those belonging to the GADD family, were found to be differentially abundant in EE, as compared to CE. These patterns were evident in both mid-proliferative and mid-secretory phases. Intriguingly, higher DDR was associated with increased cell proliferation in EE-MP, compared to CE-MP. Furthermore, among the differentially expressed transcripts (DETs) encoded by DNA repair genes, the majority showed up-regulation in EE-MP, compared to CE-MP. Interestingly, CE-MP and EE-MP had a comparable percentage (P > 0.05) of cells with residual DNA damage. However, unlike the mid-proliferative phase data, many DETs encoded by DNA repair genes were down-regulated in EE-MS, compared to CE-MS. An analysis of the phase-matched control and endometriosis samples included in the GSE51981 dataset available in the Gene Expression Omnibus database also revealed significant (P < 0.05) alterations in the expression of DDR and DNA repair genes in EE, compared to CE. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The study was conducted on a limited number of endometrial samples. Also, the study does not reveal the causes underlying dysregulated DDR in the eutopic endometrium of women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Alterations in the expression of DDR and DNA repair genes indirectly suggest that eutopic endometrium, as compared to its healthy counterpart, encounters DNA damage-inducing stimuli, either of higher strength or for longer duration in endometriosis. It will be worthwhile to identify the nature of such stimuli and also explore the role of higher genomic insults and dysregulated DDR/DNA repair in the origin and/or progression of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Department of Biotechnology and Indian Council of Medical Research, Government of India. No conflict of interest is declared.

Clinical characteristics, outcomes, & mortality in pregnant women with COVID-19 in Maharashtra, India: Results from PregCovid registry.

Background & objectives: The PregCovid registry was established to document the clinical presentations, pregnancy outcomes and mortality of pregnant and post-partum women with COVID-19. Methods: The PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across the State of Maharashtra, India. Data of 4203 pregnant women collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) was analyzed. Results: There were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The proportion of pregnancy/foetal loss including stillbirths was six per cent. Five hundred and thirty-four women (13%) were symptomatic, of which 382 (72%) had mild, 112 (21%) had moderate, and 40 (7.5%) had severe disease. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications. The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths. Interpretation & conclusions: The study demonstrates the adverse outcomes including severe COVID-19 disease, pregnancy loss and maternal death in women with COVID-19 in Maharashtra, India.

Clinical Characteristics, Management, and Short-Term Outcome of Neonates Born to Mothers with COVID-19 in a Tertiary Care Hospital in India.

INTRODUCTION: We describe the clinical characteristics, management, and short-term outcomes of SARS-CoV-2 neonates born to mothers with COVID-19 in a tertiary care hospital in Mumbai, India. METHODS: The study is a retrospective analysis of 524 neonates born to mothers with COVID-19 admitted from 14th April 2020 to 31st July 2020. RESULTS: SARS-CoV-2 infection was detected in 6.3% of the newborns of the mothers with COVID-19. No significant differences were observed between maturity at gestation, birth weight and sex of SARS-CoV-2 infected and noninfected newborns. The risk of sepsis was 4.09 [95% confidence interval (95% CI) 1.28-13.00] fold higher in the neonates with SARS-CoV-2 as compared to the noninfected group (p = 0.031). Poor feeding was significantly more common among SARS-CoV-2 infected neonates (12.1%) as compared to the noninfected neonates (2.7%) (p = 0.017). There was a total of 13 neonatal deaths, of which 3 deaths occurred in SARS-CoV-2 infected neonates (9%) while 10 (2.04%) in the SAR-CoV-2 negative group. The risk of neonatal death was higher in SARS-CoV-2 infected newborns [odds ratio (OR) 4.8; 95% CI 1.25-18.36]. CONCLUSION: Neonatal SARS-CoV-2 infection is observed in almost 6% of neonates born to mothers with perinatal COVID-19. There is a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates.

The current pandemic of COVID-19 has affected all the countries globally. However, the adverse impact of the pandemic is more seen in the low-income and middle-income countries (LMICs). Although there is evidence on the adverse impact of the SARS-CoV-2 on the health of mothers and neonates, the evidence is mainly from high-income countries. For reducing the mortality and morbidity due to COVID-19 in LMICs, there is a need to generate evidence from the LMICs. The present study is a part of the National Registry of pregnant women with COVID-19 in India (PregCovid registry). Our study demonstrates a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates. The study also showed the risk of SARS-CoV-2 infection in 6.3% of neonates born to mothers with COVID-19.

Clinical Presentation of Cases with SARS-CoV-2 Reinfection/ Reactivation.

BACKGROUND: Reinfection/reactivation of SARS-CoV-2 has been a matter of great interest from the immunological and vaccine perspective. However, little is known about the clinical presentation of such reinfection/reactivation. We report a case series of 9 COVID-19 patients having experienced two clinically- and/or virologically-confirmed episodes of COVID-19. METHODS: Epidemiological and clinical characteristics of 9 healthcare workers (HCWs) with two episodes of SARS-CoV-2 are described. RESULTS: The incidence of reinfection/reactivation amongst the HCWs was 2% (9 out of 491) with an average remission period of 66 days (range 43-78 days). Amongst the cases of reinfection 4/9 were asymptomatic in first episode were symptomatic in second episode. There is negative correlation between numbers of days the patients took to become SARS-CoV-2 negative by RT-CPR and/or clinically recover in the first episode and the second episode irrespective for the time spent in remission. CONCLUSION: Shorter durations of SARS-COV-2 infection in the first episode are associated with longer time to recovery in the second episode in patients with re-infection/reactivation.

Cystic fibrosis transmembrane conductance regulator-related male infertility: Relevance of genetic testing & counselling in Indian population.

BACKGROUND & OBJECTIVES: Due to limited information available on the frequency and spectrum of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens (CBAVD) in Indian population, it is difficult to provide accurate genetic counselling to couples. The present study was undertaken to investigate the spectrum and frequency of CFTR gene mutations in Indian men with CBAVD and to determine the female CF carrier status. METHODS: Direct DNA sequencing of the CFTR gene was carried out in eighty CBAVD men, their female partners and fifty controls from the general population. Pathological significance of the identified novel CFTR gene variants was carried out using in silico tools. Appropriate genetic counselling was provided to the couples prior to intracytoplasmic sperm injection (ICSI). RESULTS: A significant association was observed for CFTR gene variants in Indian CBAVD men versus controls (odds ratio: 12.1; 95% confidence interval: 4.8-30.4; P<0.0001). A total of 20 CFTR gene variants were identified in 53 CBAVD men. Eight novel missense CFTR gene variants (L214V, A238P, E379V, L578I, F587L, L926W, R1325K and R1453Q); two novel splice-site gene variants (c.1-30C>G and IVS1+2T>G) and ten previously reported mutations (R75Q, c.1210-12[5], F508del, A309G, R334W, I444T, R668C, R709X, A1285V and Q1352H) were detected in CBAVD men. The novel and reported CFTR gene mutations were L926W (2.5%, P=0.26), R1453Q (2.5%, P=0.26), F508del (8.75%, P=0.03) and c.1210-12[5] (42.5%, P=0.002). A total of 13 (16.2%) female partners were found to be a CF carrier. Nine couples had a risk of transmitting mutant CFTR allele to the offspring. INTERPRETATION & CONCLUSIONS: The heterogeneous spectrum of CFTR gene in Indian population suggests the necessity of screening CBAVD men and female partners for accurate genetic counselling prior to undergoing ICSI.

LC-QTOF-MS-based metabolite profiling and evaluation of α-glucosidase inhibitory kinetics of Coccinia grandis fruit.

Coccinia grandis is an important food crop of the Cucurbitaceae family, widely used for culinary purposes in India. It is reported to possess hypoglycemic, hypolipidemic and antioxidant activities. The current study was aimed to explore the inhibition kinetics as well as major constituents of the active fraction of C. grandis against α-glucosidase. The kinetic study was performed through spectrophotometric assay, with p-nitrophenyl-α-d-glucopyranoside as a substrate with varying concentrations. An in vitro antioxidant study was performed by DPPH assay. In addition, UPLC-QTOF-MS analysis was carried out for metabolite profiling of the bioactive fraction of C. grandis. The results showed that the difference between the α-glucosidase inhibitory activity of the ethyl acetate fraction of C. grandis (EFCG) (IC50 2.43 ± 0.27 mg/ml), and standard inhibitor, acarbose (2.08 ± 0.19 mg/ml), was not statistically significant at a P-value of 0.05. The enzyme kinetics confirmed the inhibition mode in a mixed manner. The EFCG also showed the highest antioxidant activity (101.74 ± 1.95 µg/ml) among all of the fractions. A significant correlation between antioxidant and α-glucosidase inhibitory activity of EFCG was observed. The LC-QTOF-MS study of the EFCG putatively identified 35 metabolites, which may be responsible for its antioxidant and α-glucosidase inhibitory properties. Thus, C. grandis fruits can serve as a functional food to address diabetes-related disorders associated with α-glucosidase.

Newly Developed Correlations to Predict the Rheological Parameters of High-Bentonite Drilling Fluid Using Neural Networks.

High-bentonite mud (HBM) is a water-based drilling fluid characterized by its remarkable improvement in cutting removal and hole cleaning efficiency. Periodic monitoring of the rheological properties of HBM is mandatory for optimizing the drilling operation. The objective of this study is to develop new sets of correlations using artificial neural network (ANN) to predict the rheological parameters of HBM while drilling using the frequent measurements, every 15 to 20 min, of mud density (MD) and Marsh funnel viscosity (FV). The ANN models were developed using 200 field data points. The dataset was divided into 70:30 ratios for training and testing the ANN models respectively. The optimized ANN models showed a significant match between the predicted and the measured rheological properties with a high correlation coefficient (R) higher than 0.90 and a maximum average absolute percentage error (AAPE) of 6%. New empirical correlations were extracted from the ANN models to estimate plastic viscosity (PV), yield point (YP), and apparent viscosity (AV) directly without running the models for easier and practical application. The results obtained from AV empirical correlation outperformed the previously published correlations in terms of R and AAPE.

Prevalence and Clinical Presentation of COVID-19 among Healthcare Workers at a Dedicated Hospital in India

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading in India and across the world. Healthcare workers (HCWs) are at increased risk of contracting COVID-19 due to direct or indirect exposure to COVID-19 patients, and require special attention. Limited information is available about its effect in HCWs. Secondary transmission from HCWs is a possibility among patients, family members, and the community. Therefore, it is important to investigate the infection risk of HCWs and the clinical characteristics of affected cases and possible source of infection with exposure details. Methods: The aim of this study is to analyze the medical records of HCWs with COVID-19 retrospectively and carry out the analysis of the data of HCWs with COVID-19 at TNMC and BYL Nair Charitable Hospital (NH, COVID-19 Hospital) in Mumbai. Results: Interim analysis was carried out for the data collected from 6th April to 20th August 2020. Total 3711 HCWs (frontline, 74.32%, non-frontline, 25.68%) are working at NH Mumbai. We observed 11% prevalence of SARS-CoV-2 infection among HCWs, 4% co-infection and 1% mortality. Majority (85%) of the HCWs with COVID-19 were symptomatic and 15% were asymptomatic. Comorbidities were reported in 19% of HCWs with COVID-19. Hypertension and Diabetes Mellitus were the most common co-morbidities reported. More than 4% percent of HCWs with COVID-19 were also positive for plasmodium vivax Malaria. Conclusion: The results of the study will be useful for determining the impact of COVID-19 and adverse outcomes in HCWs, identifying probable mode of acquiring SARS-CoV-2 infection in HCWs. This is required for planning the strategies to handle the epidemic of COVID-19 among HCWs in Mumbai region, and at Maharashtra state level.

Incidence & management practices of snakebite: A retrospective study at Sub-District Hospital, Dahanu, Maharashtra, India.

This study was undertaken to know the incidence and management practices of snakebite envenomation at the First Referral Unit - Sub-District Hospital, Dahanu, Maharashtra, India. Retrospective analysis of snakebite case records (n=145) was carried out for one-year period (January to December 2014). The annual incidence of snakebite was 36 per 100,000 population with case fatality rate of 4.5 per cent. Venomous snakebites were 76 per cent and non-venomous snakebites were 24 per cent. Overall, snakebites were more common in males (52.4%) than females (47.6%). Majority of the snakebites (66%) were in the age group of 18-45 yr. Seasonal variation was observed with highest snakebites in monsoon (58%). Lower extremities were the most common site of bites (63%). Neurotoxic and vasculotoxic envenomation were reported in 19 and 27 per cent snakebite cases, respectively. Anti-snake venom (ASV) was administered at an average dose of 7.5±0.63 vials (range 2-40, median 6). There was no uniform protocol followed for ASV administration as per the National Snakebite Management Protocol of Government of India (2009).

Orcinol Glucoside Loaded Polymer - Lipid Hybrid Nanostructured Lipid Carriers: Potential Cytotoxic Agents against Gastric, Colon and Hepatoma Carcinoma Cell Lines.

PURPOSE: Orcinol glucoside (OG) - loaded nanostructured lipid carrier (NLC), coated with polyethylene glycol-25/55-stearate (PEG-25/55-SA), were explored for delivering OG to improve in vitro cytotoxicity against gastrointestinal tract (GIT), colon and hepatoma carcinoma cell lines. It is being expected that the PEGylated formulations would possess the sustainability in withstanding the adverse physiological extremities like the most significant metabolic activities and phase I / II enzymatic activities in the intestines. METHODS: NLCs were prepared using tristearin, oleic acid and PEG-25/55-stearate by hot homogenization-ultrasonic dispersion; characterized by DLS, TEM, SEM, AFM, entrapment efficiency and drug loading capacity studies. RESULTS: NLC diameter ranged from 160 to 230 nm with negative zeta potential of -8 to -20 mV. TEM/SEM and AFM studies suggest spherical and smooth surface morphologies. Differential scanning calorimetry studies reveal the loss of crystallinity when OG was incorporated into the NLC. NLCs showed initial burst release, followed by sustained release of OG. PEG-NLC exhibited superior anticancer activity against GIT and also in hepatoma cancer cell lines. CONCLUSIONS: This is the first report demonstrating a practical approach for possible oral delivery of OG in GIT and targeting hepatoma cancer, warranting further in vivo studies for superior management of GIT cancer.

Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry.

BACKGROUND & OBJECTIVES: Bisphenol-A (BPA) and phthalates are utilized widely in consumer products. Due to their ubiquitous presence in the environment, a concern is expressed worldwide about their possible effect on human reproductive health. This study was conducted to compare the internal exposure of BPA and phthalates (using their metabolites as biomarkers) in plasma samples of infertile and fertile women. METHODS: A sensitive gas chromatographic-mass spectrometric (GC-MS) method was developed to simultaneously quantify BPA and four phthalate monoester metabolites [namely mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] in human plasma. The method was validated using charcoal-stripped human plasma. Activated charcoal was also utilized to reduce contamination from reagents. The method was designed to account for and/or eliminate background contamination from all sources. RESULTS: The limit of quantification for the method was 5 ng/ml for MMP and MBzP, while 1 ng/ml for BPA, MEHP and MEHHP, respectively. The precision and accuracy were well within the acceptable range. BPA was detectable in 77 per cent of plasma samples of infertile women and 29 per cent of fertile women. All the four phthalate metabolites were detected in plasma samples of both fertile and infertile women. INTERPRETATION & CONCLUSIONS: A GC-MS was developed and validated to estimate the BPA and four phthalate monoester metabolites in human plasma. It was utilised to analyse the plasma samples from fertile and infertile women. The infertile women showed significantly higher plasma concentrations of MBzP, BPA and MEHHP as compared to fertile women. The levels of MMP and MEHP were not significantly different between the two groups. Further studies need to be done to confirm these preliminary findings.