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Objective: To investigate whether induction/augmentation of labor in pregnant women with anemia increases the risk of postpartum hemorrhage (PPH) and whether this risk varied by indications for labor induction/augmentation and by anemia severity in pregnancy., Methods: In a prospective cohort study of 9420 pregnant women from 13 hospitals across India, we measured hemoglobin concentrations at recruitment (≥28 weeks of gestation) and blood loss after childbirth during follow-up and collected clinical information about PPH. Clinical obstetric and childbirth information at both visits were extracted from medical records. Anemia severity in the third trimester was categorized using hemoglobin concentrations (no/mild anemia: hemoglobin ≥10 g/dL; moderate: hemoglobin 7 to 9.9 g/dL; severe: hemoglobin <7 g/dL), while PPH was defined based on blood loss volume (vaginal births: ≥500 mL or cesarean sections: ≥1000 mL) and clinical diagnosis. Indications for labor induction/augmentation were classified as clinically indicated and elective as per guidelines. We performed multivariable modified Poisson regression analyses to investigate the associations of anemia severity and indications for labor induction/augmentation, including their interaction, with PPH, adjusted for potential confounders., Results: PPH was associated with anemia but not with indications for labor induction/augmentation. However, there was a significant interaction between the two factors in relation to PPH (P = 0.003). Among pregnant women with severe anemia, a higher risk of PPH was associated with elective (adjusted risk ratio, 3.44 [95% confidence interval, 1.29-9.18]) but not with clinically indicated (adjusted risk ratio, 1.22 [95% confidence interval, 0.42-3.55]) labor induction/augmentation. No associations were observed among pregnant women with no/mild and moderate anemia., Conclusion: The risk of PPH is higher in women who have moderate-severe anemia in late pregnancy. Induction/augmentation of labor is generally safe for women with anemia, but it can increase the risk of PPH in women with severe anemia if performed electively., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Guidelines for labour induction/augmentation involve evaluating maternal and fetal complications, and allowing informed decisions from pregnant women. This study aimed to comprehensively explore clinical and non-clinical factors influencing labour induction and augmentation in an Indian population., Methods: A prospective cohort study included 9305 pregnant women from 13 hospitals across India. Self-reported maternal socio-demographic and lifestyle factors, and maternal medical and obstetric histories from medical records were obtained at recruitment (≥28 weeks of gestation), and women were followed up within 48 h after childbirth. Maternal and fetal clinical information were classified based on guidelines into four groups of clinical factors: (i) ≥2 indications, (ii) one indication, (iii) no indication and (iv) contraindication. Associations of clinical and non-clinical factors (socio-demographic, healthcare utilisation and lifestyle related) with labour induction and augmentation were investigated using multivariable logistic regression analyses., Findings: Over two-fifths (n = 3936, 42.3%, 95% confidence interval [CI] 41.3-43.3%) of the study population experienced labour induction and more than a quarter (n = 2537, 27.3%, 95% CI 26.4-28.2%) experienced augmentation. Compared with women with ≥2 indications, those with one (adjusted odds ratio [aOR] 0.50, 95% CI 0.42-0.58) or no indication (aOR 0.24, 95% CI 0.20-0.28) or with contraindications (aOR 0.12, 95% CI 0.07-0.20) were less likely to be induced, adjusting for non-clinical characteristics. These associations were similar for labour augmentation. Notably, 34% of women who were induced or augmented did not have any clinical indication. Several maternal demographic (age at labour, parity and body mass index in early pregnancy), healthcare utilization (number of antenatal check-ups, duration of iron-folic acid supplementation and individuals managing childbirth) and socio-economic factors (religion, living below poverty line, maternal education and partner's occupation) were independently associated with labour induction and augmentation., Interpretation: Although decisions about induction and augmentation of labour in our study population in India were largely guided by clinical recommendations, we cannot ignore that more than a third of the women did not have an indication. Decisions could also be influenced by non-clinical factors which need further research., Funding: The MaatHRI platform is funded by a Medical Research Council Career Development Award (Grant Ref: MR/P022030/1) and a Transition Support Award (Grant Ref: MR/W029294/1)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population., Methods: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018-September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve., Results: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2-25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25-2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12-45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97-6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03-2.36), preterm birth (aRR: 4.41, 95% CI: 3.21-6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02-1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%-81.4%) of the risk of stillbirth in the population., Conclusion: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: According to WHO, hypertensive disease is the leading cause of direct maternal mortality accounting for 10-25% in developing countries (James in Heart, 90(12):1499-504). This study compares the combinations of mean arterial pressure (MAP) and uterine artery doppler (UAD) versus serum-free β HCG, pregnancy-associated plasma protein-A, and placental growth factor (PlGF) versus a combination of all variables at 11 to 13 +6 as long-term predictors of pregnancy-induced hypertension (PIH)., Materials and Methods: A prospective, observational cohort study recruited 97 primigravidae at 11 to 13 +6  weeks gestation at GMCH. Follow-up was done at 32-34 weeks and before delivery. Development of PIH, mode of delivery, birthweight, maternal and fetal adverse outcomes were documented, analyzed and compared among three groups. In Group A-biophysical markers, Group B-biochemical markers and in Group C all variables were used., Results: The mean age, maternal weight, height and BMI of patients developing gestational hypertension were 30 ± 5 years, 64.3 ± 12.5 kg, 155.8 ± 5.5 cm and 26.4 ± 4.1, respectively. Out of the 3, Group C is the best screening test for predicting the overall chance of development of gestational hypertension with a sensitivity of 97.37% and specificity of 38.98% ( p  < 0.0001). A mild negative correlation is seen between PlGF levels and severity of PIH ( p -0.0382)., Conclusion: MAP and UAD can be easily incorporated into the infrastructure of most hospitals. If the biochemical test kits are made available at a low cost through available programs such as JSSK, it can bring down the MMR by preventing gestational hypertension., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Microorganisms are integral components of ecosystems, exerting profound impacts on various facets of human life. The recent United Nations General Assembly (UNGA) Science Summit emphasized the critical importance of comprehending the microbial world to address global challenges, aligning with the United Nations Sustainable Development Goals (SDGs). In agriculture, microbes are pivotal contributors to food production, sustainable energy, and environmental bioremediation. However, decades of agricultural intensification have boosted crop yields at the expense of soil health and microbial diversity, jeopardizing global food security. To address this issue, a study in West Bengal, India, explored the potential of a novel multi-strain consortium of plant growth promoting (PGP) Bacillus spp. for soil bioaugmentation. These strains were sourced from the soil's native microbial flora, offering a sustainable approach. In this work, a composite inoculum of Bacillus zhangzhouensis MMAM, Bacillus cereus MMAM3), and Bacillus subtilis MMAM2 were introduced into an over-exploited agricultural soil and implications on the improvement of vegetative growth and yield related traits of Gylcine max (L) Meril. plants were evaluated, growing them as model plant, in pot trial condition. The study's findings demonstrated significant improvements in plant growth and soil microbial diversity when using the bacterial consortium in conjunction with vermicompost. Metagenomic analyses revealed increased abundance of many functional genera and metabolic pathways in consortium-inoculated soil, indicating enhanced soil biological health. This innovative bioaugmentation strategy to upgrade the over-used agricultural soil through introduction of residual PGP bacterial members as consortia, presents a promising path forward for sustainable agriculture. The rejuvenated patches of over-used land can be used by the small and marginal farmers for cultivation of resilient crops like soybean. Recognizing the significance of multi-strain PGP bacterial consortia as potential bioinoculants, such technology can bolster food security, enhance agricultural productivity, and mitigate the adverse effects of past agricultural activities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SH declared a shared affiliation with the authors MM and AM to the handling editor at the time of review., (Copyright © 2023 Mukhopadhyay, Mukherjee, Ganguli, Chakraborti, Roy, Choudhury, Subramaniyan, Kumarasamy, Sayed, El-Demerdash, Almutairi, Şuţan, Dhara and Mitra.)

Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low-and-middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12-72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] -0.0004, 95% confidence interval [CI] -0.001, 0.001; postnatal: aCoef -0.0001, 95% CI -0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef -0.04, 95% CI -0.07, -0.01), TSAT (aCoef -0.005, 95% CI -0.008, -0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non-anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: Notch signaling is crucial during pregnancy with ability to regulate angiogenesis and inflammatory response. Considering the enigmatic importance of Notch signaling in pregnancy including placenta development, gestational disorders and adverse pregnancy; we performed experimental analysis to identify the Notch receptor-ligands association with Preterm delivery (PTD) and linked complication., Method: A total of 245 cases [Term n = 135 and Preterm n = 110] were enrolled for the study from Northeast Indian Population. The differential mRNA expression of Notch receptors , ligands, its downstream target Hes1 and Immune markers (IL-10, IL-12 and TNF-α) was studied by real time polymerase chain reaction. Further the protein study of Notch1 and 4, Hes1, VEGF and TNF-α was performed by immunofluorescence., Results: Placental mRNA expression of all the four notch receptors [Notch1 = 2.15 ± 1.02 fold, Notch2 = 6.85 ± 2.70 fold, and Notch3 = 1.74 ± 0.90 fold and Notch4 = 14.15 ± 6.72 fold]; ligands [JAG1 = 2.71 ± 1.22, JAG2 = 4.41 ± 2.31, DLL1 = 3.55 ± 1.38, DLL3 = 4.31 ± 2.82 and DLL4 = 3.07 ± 1.30 folds] and downstream target [Hes1 = 6.09 ± 2.89 folds] was elevated in PTD cases compared to Term delivery (TD) cases. The mRNA expression of pro-inflammatory marker (IL-12 = 3.99 ± 1.02 fold and TNF-α = 16.83 ± 2.97), was upregulated. The upregulated expression of Notch1(p < 0.001), JAG1 (p = 0.006), JAG2 (p = 0.009), DLL1 (p = 0.001), DLL4 (p < 0.001) Hes1 (p < 0.001), TNF-α (p < 0.001) and IL-12 (p = 0.006) were associated with the baby death; and Notch4 significantly inversely correlated with low birth weight (LBW). Consistently higher protein level expression of Notch1, Hes1, VEGFA and TNF-α was observed in preterm with highest expression in negative outcome cases., Discussion: To conclude, the increased Notch1 expression and angiogenesis linked inflammation holds key in understanding the pathogenesis of PTD and linked complications and underlines its potential as therapeutic target for PTD interventions., Competing Interests: Declaration of competing interest Authors have no conflict of interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Hypertensive hemorrhage is a leading cause of intracerebral haemorrhage (ICH), although some of these patients may not present with high blood pressure (BP) at the time of ICH., Materials and Methods: This retrospective study included patients with history of hypertension presenting with ICH. Patients with systolic BP recording of more than 140 mmHg were included in hypertension group (group I). Patients whose BP rose to hypertension range after fluid correction were included in group II and patients with BP <140 mmHg on consecutive 1-week BP recordings were included in group III. Clinical features including volume of ICH of all the three groups were noted. Outcome in the form of mortality was analyzed. Chi-square test was used for categorical variables and independent t -test for continuous variables. P < 0.05 was considered significant., Results: Ninety-two ICH patients with history of hypertension were included in the study. Of them, 20 patients (22%) presented with BP <140 mmHg systolic at the time of ICH. After fluid correction, it rose to hypertensive range in 9 (10%) but remained normal in 11 patients (12%) during consecutive recordings for 1-week post-admission. On comparing normotensive and hypertensive groups, significant difference was seen in survival and volume of ICH., Conclusion: There is a subset of hypertensive patients who may present with normal BP recording during acute ICH. The BP rises subsequently with the correction of hypovolemia in some. The volume of hemorrhage in normotensives is relatively small but whether this translates into better prognosis needs further studies., Competing Interests: There are no conflicts of interest., (© 2023 Published by Scientific Scholar on behalf of Journal of Neurosciences in Rural Practice.)

Background: Hiccups are characterized by involuntary, intermittent, repetitive, myoclonic, and spasmodic contractions of the diaphragm. Hiccups are termed "intractable" when they last for over 1 month., Observations: A rare case of intractable hiccups due to an uncommon location of cavernous hemangioma in the dorsal medulla is illustrated. With respect to the management, surgical excision was performed, and postsurgical complete recovery was witnessed, which has been reported only in six cases worldwide to date., Lessons: A mechanism of the hiccups reflex arc is discussed in detail with special reference to the need for equal emphasis on evaluating central nervous system causes and peripheral etiologies for pertinent hiccups.

Background: Cardiac complications are a leading cause of maternal death. Cardiac imaging with echocardiography is important for prompt diagnosis, but it is not available in many low-resource settings. The aim of this study was to determine whether focused cardiac ultrasound performed by trained obstetricians and interpreted remotely by experts can identify cardiac abnormalities in pregnant women in low-resource settings., Methods: A cross-sectional study was conducted among 301 pregnant and postpartum women recruited from 10 hospitals across three states in India. Twenty-two obstetricians were trained in image acquisition using a portable cardiac ultrasound device following a simplified protocol adapted from focus-assessed transthoracic echocardiography protocol. It included parasternal long-axis, parasternal short-axis, and apical four-chamber views on two-dimensional and color Doppler. Independent image interpretation was performed remotely by two experts, in the United Kingdom and India, using a standard semiquantitative assessment protocol. Interrater agreement between the experts was examined using Cohen's κ. Diagnostic accuracy of the method was examined in a subsample for whom both focused and conventional scans were available., Results: Cardiac abnormalities identified using the focused method included valvular abnormalities (27%), rheumatic heart disease (6.6%), derangements in left ventricular size (4.7%) and function (22%), atrial dilatation (19.5%), and pericardial effusion (30%). There was substantial agreement on the cardiac parameters between the two experts, ranging from 93.6% (κ = 0.84) for left ventricular ejection fraction to 100% (κ = 1) for valvular disease. Image quality was graded as good in 79% of parasternal long-axis, 77% of parasternal short-axis and 64% of apical four-chamber views. The chance-corrected κ coefficients indicated fair to moderate agreement (κ = 0.28-0.51) for the image quality parameters. There was good agreement on diagnosis between the focused method and standard echocardiography (78% agreement), compared in 36 participants., Conclusions: The focused method accurately identified cardiac abnormalities in pregnant women and could be used for screening cardiac problems in obstetric settings., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Enzyme function can be altered via modification of its amino acid residues, side chains and large-scale domain modifications. Herein, we have addressed the role of residue modification in catalytic activity and molecular recognition of an enzyme alpha-chymotrypsin (CHT) in presence of a covalent cross-linker formalin. Enzyme assay reveals reduced catalytic activity upon increased formalin concentration. Polarization gated anisotropy studies of a fluorophore 8-Anilino-1-naphthalenesulfonic acid (ANS) in CHT show a dip rise pattern in presence of formalin which is consistent with the generation of multiple ANS binding sites in the enzyme owing to modifications of its local amino acid residues. Molecular docking study on amino acid residue modifications in CHT also indicate towards the formation of multiple ANS binding site. The docking model also predicted no change in binding behavior for the substrate Ala-Ala-Phe-7-amido-4-methylcoumarin (AMC) at the active site upon formalin induced amino acid cross-linking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Biswas, Adhikari, Pal, Mondal, Mukherjee, Ghosh, Obaid, Moussa, Choudhury, Ahmed, Das and Pal.)

Understanding the noncovalent interactions (NCIs) among the residues of proteins and nucleic acids, and between drugs and proteins/nucleic acids, etc. , has extraordinary relevance in biomolecular structure and function. It helps in interpreting the dynamics of complex biological systems and enzymatic activity, which is esential for new drug design and efficient drug delivery. NCIs like hydrogen bonding (H-bonding) and π-stacking have been researchers' delight for a long time. Prominent among the recently discovered NCIs are halogen, chalcogen, pnictogen, tetrel, carbo-hydrogen, and spodium bonding, and n → π* interaction. These NCIs have caught the imaginations of various research groups in recent years while explaining several chemical and biological processes. At this stage, a holistic view of these new ideas and findings lying scattered can undoubtedly trigger our minds to explore more. The present review attempts to address NCIs beyond H-bonding and π-stacking, which are mainly n → σ*, n → π* and σ → σ* type interactions. Five of the seven NCIs mentioned earlier are linked to five non-inert end groups of the modern periodic table. Halogen (group-17) bonding is one of the oldest and most explored NCIs, which finds its relevance in biomolecules due to the phase correction and inhibitory properties of halogens. Chalcogen (group 16) bonding serves as a redox-active functional group of different active sites of enzymes and acts as a nucleophile in proteases and phosphates. Pnictogen (group 15), tetrel (group 14), triel (group 13) and spodium (group 12) bonding does exist in biomolecules. The n → π* interactions are linked to backbone carbonyl groups and protein side chains. Thus, they are crucial in determining the conformational stability of the secondary structures in proteins. In addition, a more recently discovered to and fro σ → σ* type interaction, namely carbo-hydrogen bonding, is also present in protein-ligand systems. This review summarizes these grand epiphanies routinely used to elucidate the structure and dynamics of biomolecules, their enzymatic activities, and their application in drug discovery. It also briefs about the future perspectives and challenges posed to the spectroscopists and theoreticians.

Objective: 1. To study the clinical profile, progression and outcome of GBS during peripartum period in a tertiary care hospital. 2. To identify the determinants of outcome in GBS during peripartum period., Background: Guillain-Barré Syndrome (GBS) is an acute, autoimmune disorder of the peripheral nervous system triggered by a bacterial or viral infection or other antecedent events. Modern day critical care has dramatically improved the outcome of GBS. GBS during pregnancy is rare with an annual incidence of 2.8/100,000 population. Pregnancy itself is a life-threatening condition and full of complications. GBS during pregnancy makes its more complicated in terms of both maternal and fetal care during peripartum period., Methods: This was a prospective study conducted by the Department of Neurology, Gauhati Medical College including 36 patients of GBS presenting during peripartum period in between December 2019 and November 2021. Their clinical and electrophysiological features were analyzed. Hughes grading, EGRIS, mEGOS, MRC sum score were used. The fetal outcome was observed and patients were followed up for GBS outcome at 3 months and 6 months., Results: The mean age of patients was 25.97 years. AIDP was the most common subtype found in 21 (58.33%) patients followed by AMAN in 7 (19.4%), AMSAN in 3 (8.33%). In 3 cases NCS was equivocal and in 3 cases inexcitable. Respiratory distress was found in 13 (36.1%) cases, out of which 4 (11.1%) required mechanical ventilation and 1 (2.8%) died. The pre-term birth rate and stillbirth rate were 35.7% (n = 10) and 8.33% (n = 3), respectively with 66.7% (n = 24) spontaneous vaginal delivery(SVD). At 3 month 26 (72.2%) had complete recovery. 5 (13.9%) and 4 (11.1%) had partial and poor recovery, respectively. 78.9% of primigravidae had complete recovery in comparison to 64.7% in multigravidae indicating better outcome in primigravidae in this study., Conclusion: The outcome of GBS during peripartum period is favorable. Primigravidae are more commonly affected but have better outcome than the multigravidae. The risk of developing GBS in pregnancy decreases significantly after delivery and is minimal after 2 weeks. GBS is not an indication for LSCS. Stillbirth rate and preterm birth rate is higher in pregnancy associated with GBS without fearsome neonatal complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Objectives: To investigate the association between coagulation parameters and severity of anaemia (moderate anaemia: haemoglobin (Hb) 7-9.9 g/dL and severe anaemia: Hb <7 g/dL) during pregnancy and relate these to postpartum haemorrhage (PPH) at childbirth., Design: A prospective cohort study of pregnant women recruited in the third trimester and followed-up after childbirth., Setting: Ten hospitals across four states in India., Participants: 1342 pregnant women., Intervention: Not applicable., Methods: Hb and coagulation parameters: fibrinogen, D-dimer, D-dimer/fibrinogen ratio, platelets and international normalised ratio (INR) were measured at baseline. Participants were followed-up to measure blood loss within 2 hours after childbirth and PPH was defined based on blood loss and clinical assessment. Associations between coagulation parameters, Hb, anaemia and PPH were examined using multivariable logistic regression models., Outcomes Measures: Adjusted OR with 95% CI., Results: In women with severe anaemia during the third trimester, the D-dimer was 27% higher, mean fibrinogen 117 mg/dL lower, D-dimer/fibrinogen ratio 69% higher and INR 12% higher compared with women with no/mild anaemia. Mean platelets in severe anaemia was 37.8×10 9 /L lower compared with women with moderate anaemia. Similar relationships with smaller effect sizes were identified for women with moderate anaemia compared with women with no/mild anaemia. Low Hb and high INR at third trimester of pregnancy independently increased the odds of PPH at childbirth, but the other coagulation parameters were not found to be significantly associated with PPH., Conclusion: Altered blood coagulation profile in pregnant women with severe anaemia could be a risk factor for PPH and requires further evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

The products of the Friedlander reaction, i.e., 1,8-naphthyridines, have far-reaching impacts in materials science, chemical biology, and medicine. The reported synthetic methodologies elegantly orchestrate the diverse synthetic routes of naphthyridines but require harsh reaction conditions, organic solvents, and expensive metal catalysts. Here, we introduce gram-scale synthesis of 1,8-naphthyridines in water using an inexpensive and biocompatible ionic liquid (IL) as a catalyst. This is the first-ever report on the synthesis of naphthyridines in water. This is a one-step reaction, and the product separation is relatively easy. The choline hydroxide (ChOH) is used as a metal-free, nontoxic, and water-soluble catalyst. In comparison to other catalysts reported in the literature, ChOH has the advantage of forming an additional hydrogen bond with the reactants, which is the vital step for the reaction to happen in water. Density functional theory (DFT) and noncovalent interaction (NCI) plot index analysis provide the plausible reaction mechanism for the catalytic cycle and confirm that hydrogen bonds with the IL catalyst are pivotal to facilitate the reaction. Molecular docking and molecular dynamics (MD) simulations are also performed to demonstrate the potentialities of the newly synthesized products as drugs. Through MD simulations, it was established that the tetrahydropyrido derivative of naphthyridine ( 10j ) binds to the active sites of the ts3 human serotonin transporter (hSERT) (PDB ID: 6AWO) without perturbing the secondary structure, suggesting that 10j can be a potential preclinical drug candidate for hSERT inhibition and depression treatment., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The data represents the bacterial community profile obtained through metagenomic sequencing of soil sample, collected from the 'Rarh' region of West Bengal, which is characterized by the lateritic badlands dating back to the late Pleistocene. Taxonomic binning and operational taxonomic unit (OTU) prediction of the Illumina sequencing data indicated the abundance Proteobacteria (61%) followed closely by Bacterioidetes (35%). The top two most abundant genera identified, were Sphingobacterium and Acinetobacter respectively. Chemical properties of soil, such as pH, organic carbon content, available nitrogen, phosphorus, and potassium were also analyzed for enabling future researchers to correlate the abundance of microbial taxa with the prevalent conditions. These findings can be effectively used to formulate strategic microbiome engineering through bioaugmentation for a sustainable agricultural system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Inc.)

Surface-based biosensing devices benefit from a dedicated design of the probe layer present at the transducing interface. The layer architecture, its physicochemical properties, and the embedding of the receptor sites affect the probability of binding the analyte. Here, the enhancement of the probe density at the sensing interface by tuning the exponential growth regime of polyelectrolyte multilayers (PEMs) is presented. PEMs were made of poly-l-lysine (PLL), with appended clickable dibenzocyclooctyne (DBCO) groups and oligo(ethylene glycol) chains, and poly(styrene sulfonate) (PSS). The DNA probe loading and target hybridization efficiencies of the PEMs were evaluated as a function of the PLL layer number and the growth regime by a quartz crystal microbalance (QCM). An amplification factor of 25 in the target DNA detection was found for a 33-layer exponentially grown PEM compared to a monolayer. A Voigt-based model showed that DNA probe binding to the DBCO groups is more efficient in the open, exponentially grown films, while the hybridization efficiencies appeared to be high for all layer architectures. These results show the potential of such engineered gel-like structures to increase the detection of bio-relevant analytes in biosensing systems., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Objective: To examine the risk factors for pregnancy-related death in India's nine Empowered Action Group (EAG) states., Design: Secondary data analysis of the Indian Annual Health Survey (2010-2013)., Setting: Nine states: Assam, Bihar, Chhattisgarh, Jharkhand, Madhya Pradesh, Odisha, Rajasthan, Uttar Pradesh and Uttarakhand., Participants: 1 989 396 pregnant women., Methods: Maternal mortality ratio (MMR), overall and for each state, with 95% CI was calculated. Stepwise multivariable logistic regression was used to investigate the association of risk factors with maternal mortality. Area under the receiver-operating characteristic (AUROC) curve was used to assess the prediction of the model., Outcome Measures: MMR adjusted for survey design, adjusted OR (aOR)with 95% CI and C-statistic with 95% CI., Results: MMR calculated for the nine states was 383/100 000 live births (95% CI 346 to 423 per 100 000). Age exhibited a U-shaped association with maternal mortality. Not having a health scheme and belonging to a scheduled caste or scheduled tribe group were significant risk factors for maternal death with aOR of 2.72 (95% CI 2.41 to 3.07), 1.10 (95% CI 1.02 to 1.18) and 1.43 (95% CI 1.31 to 1.56), respectively. Socioeconomic status and rural residence were not associated with maternal mortality after adjusting for access to a healthcare facility. Complications of pregnancy and medical comorbidities were the strongest risk factors for maternal death (aOR 50.2, 95% CI 44.5 to 56.6). Together, the risk factors identified accounted for 89% (95% CI 0.887 to 0.894) of the AUROC., Conclusions: Maternal mortality in India's EAG states greatly exceeds the national average. The identified risk factors demonstrate the importance of improving the quality of pregnancy care. Notably, the study showed that the risk conferred by poor socioeconomic status could be mitigated by universal access to healthcare during pregnancy and childbirth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The conceptual development of aromaticity is essential to rationalize and understand the structure and behavior of aromatic heterocycles. This work addresses for the first time, the interconnection between aromaticity and sulfur/selenium centered hydrogen bonds (S/SeCHBs) involved in representative heterocycle models of canonical nucleobases (2-Pyridone; 2PY) and its sulfur (2-Thiopyridone; 2TPY) and selenium (2-Selenopyridone; 2SePY) analogs. The nucleus-independent chemical shift (NICS) and gauge induced magnetic current density (GIMIC) values suggested significant reduction of aromaticity upon replacement of exocyclic carbonyl oxygen with sulfur and selenium. However, we observed two-fold (57 %) and three-fold (80 %) enhancement in the aromaticity for 2TPY dimer, and 2SePY dimer, respectively which are connected through S/SeCHBs. Aromaticity enhancement was also noticed in 1 : 1 H-bonded complexes (heterodimers), micro hydrated clusters and for bulk hydration. It is expected that exocyclic S and Se incorporation into heterocycles without compromising aromatic loss would definitely reinforce to design new supramolecular building blocks via S/SeCH-bonded complexes., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Maternal and perinatal Health Research collaboration, India (MaatHRI) is a research platform that aims to improve evidence-based pregnancy care and outcomes for mothers and babies in India, a country with the second highest burden of maternal and perinatal deaths. The objective of this paper is to describe the methods used to establish and standardise the platform and the results of the process. Methods: MaatHRI is a hospital-based collaborative research platform. It is adapted from the UK Obstetric Surveillance System (UKOSS) and built on a pilot model (IndOSS-Assam), which has been extensively standardised using the following methods: (i) establishing a network of hospitals; (ii) setting up a secure system for data collection, storage and transfer; (iii) developing a standardised laboratory infrastructure; and (iv) developing and implementing regulatory systems. Results: MaatHRI was established in September 2018. Fourteen hospitals participate across four states in India - Assam, Meghalaya, Uttar Pradesh and Maharashtra. The research team includes 20 nurses, a project manager, 16 obstetricians, two pathologists, a public health specialist, a general physician and a paediatrician. MaatHRI has advanced standardisation of data and laboratory parameters, real-time monitoring of data and participant safety, and secure transfer of data. Four observational epidemiological studies are presently being undertaken through the platform. MaatHRI has enabled bi-directional capacity building. It is overseen by a steering committee and a data safety and monitoring board, a process that is not normally used, but was found to be highly effective in ensuring data safety and equitable partnerships in the context of low and middle income countries (LMICs). Conclusion: MaatHRI is the first prototype of UKOSS and other similar platforms in a LMIC setting. The model is built on existing methods but applies new standardisation processes to develop a collaborative research platform that can be replicated in other LMICs., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Nair M et al.)

Introduction: Approximately 35% of NSCLC patients in East Asia have EGFR mutations. Next-generation sequencing (NGS) provides a comprehensive mutational profile in lung cancer patients., Material and Method: Clinicopathologic characteristics and mutational profiling data was analyzed from nonsmall cell lung carcinoma /Adenocarcinoma over a duration of 42 months (October 2014 to March 2018) using next-generation sequencing Ion Ampliseq Cancer Hotspot panel v2 (Ampliseq, Life Technologies) on the Ion torrent PGM platform., Results: A total of 154 cases were processed during this period. The average number of mutations/case varied from one to four 72.07% (111/154), of these cases had minimum one genetic alteration. The most common mutated gene was TP53 gene (37.6%, n = 58) followed by EGFR (32.4%, n = 50), KRAS (18.18%, n = 28), ERBB2 (3.2%, n = 5), BRAF (1.94%, n = 3). EGFR positivity was more in females (43.3%) and non-smokers (52.08%) in comparison to males (26.7%) and smokers (16.1%)., Conclusion: In this paper, we have described the comprehensive mutational profiling of a large cohort of advanced lung adenocarcinoma patients from the eastern part of India. To the best of our knowledge, this is one of the largest studies from the country describing mutations in BRAF, ERBB2, TP53 genes and their clinicopathologic/histopathologic associations in lung cancers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Enzymes are dynamical macromolecules and their conformation can be altered via local fluctuations of side chains, large scale loop and even domain motions which are intimately linked to their function. Herein, we have addressed the role of dynamic flexibility in the catalytic activity of a thermostable enzyme almond beta-glucosidase (BGL). Optical spectroscopy and classical molecular dynamics (MD) simulation were employed to study the thermal stability, catalytic activity and dynamical flexibility of the enzyme. An enzyme assay reveals high thermal stability and optimum catalytic activity at 333 K. Polarization-gated fluorescence anisotropy measurements employing 8-anilino-1-napthelenesulfonic acid (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. A study of the atomic 3D structure of the enzyme shows the presence of four loop regions (LRs) strategically placed over the catalytic barrel as a lid. MD simulations have indicated that the flexibility of BGL increases concurrently with temperature through different fluctuating characteristics of the enzyme's LRs. Principal Component Analysis (PCA) and the Steered Molecular Dynamics (SMD) simulation manifest the gatekeeper role of the four LRs through their dynamic fluctuations surrounding the active site which controls the catalytic activity of BGL.

Despite common clinical features to suggest encephalitis, different viral encephalitides are known to have some specific clinical features, which if present, may suggest infection by a particular virus. West Nile viral (WNV) encephalitis has not been described with any specific diagnostic feature so far. In this context, we describe three patients of West Nile encephalitis (WNE) who had behavioural and cognitive impairment with acute irreversible bilaterally symmetrical sensorineural deafness. Clinical profiles of these cases suggest that the patients who present with prominent behavioural and cognitive changes and have in addition features of bilateral sensorineural deafness may be considered as the possible case of WNE.

Introduction: Unsafe abortion is a preventable cause of maternal mortality. While studies report high number of abortions in India, the population-level rates of unsafe abortion and their risk factors are not well understood. Our objective was to analyse the rates of and risk factors for unsafe abortion and abortion-related maternal death in India., Methods: We conducted a secondary analysis of data from 1 876 462 pregnant women aged 15-58 years from nine states in the Indian Annual Health Survey (2010-2013). We calculated the rate of unsafe abortion and abortion-related mortality with 95% CI. Multivariable logistic regression models examined the associations of sociodemographic characteristics, health seeking behaviours and family planning with unsafe abortion and abortion-related mortality., Results: There were 89 447 abortions among 1 876 462 pregnant women in 2007-2011 (4.8%; 95% CI 4.8 to 4.9). Of these, 58 266 were classified as unsafe (67.1%; 95% CI 66.7 to 67.5). There were 253 abortion-related maternal deaths (0.3%; 95% CI 0.2 to 0.3). Factors associated with unsafe abortion: maternal age 20-24 years (adjusted OR (aOR): 1.13; 95% CI 1.09 to 1.18), illiteracy (aOR: 1.48; 95% CI 1.39 to 1.59), rural residence (aOR: 1.26; 95% CI 1.21 to 1.32), Muslim religion (aOR: 1.16; 95% CI 1.12 to 1.22), Schedule caste social group (aOR: 1.08; 95% CI 1.04 to 1.12), poorest asset quintile (aOR: 1.45; 95% CI 1.38 to 1.53), antenatal care (aOR: 0.69; 95% CI 0.67 to 0.72), no surviving children (aOR: 1.30; 95% CI 1.16 to 1.46), all surviving children being female (aOR: 1.12; 95% CI 1.07 to 1.17), use of family planning methods (aOR: 0.69; 95% CI 0.66 to 0.71). Factors associated with abortion-related deaths: maternal age 15-19 (aOR: 7.79; 95% CI 2.73 to 22.23), rural residence (aOR: 3.28; 95% CI 1.76 to 6.11), Schedule tribe social group (aOR: 4.06; 95% CI 1.39 to 11.87)., Conclusion: Despite abortion being legal, the high estimated prevalence of unsafe abortion demonstrates a major public health problem in India. Socioeconomic vulnerability and inadequate access to healthcare services combine to leave large numbers of women at risk of unsafe abortion and abortion-related death., Competing Interests: Competing interests: None declared.

A 26-year-old patient of limited cutaneous sclerosis presented to us with insidious-onset posterior fossa symptoms of headache, vomiting, vertigo and gait imbalance, progressing over a period of 3 weeks. A diagnosis of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids was made by combining the clinical features with radiological evidence showing punctate infiltration of the pons, brainstem and cerebellum. Relevant differentials in the form of neurosarcoid, infections, central nervous system (CNS) lymphoma and Neuro-Behcet's disease were ruled out by history and investigations. The patient responded dramatically to steroid therapy, and had no neurological deficits after 18 months of follow-up. This case highlights the rare association of a not-so-common immunological disease with a rare neurological disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the rate of stillbirth and associated risk factors across nine states in India., Design: Secondary analysis of cross-sectional data from the Indian Annual Health Survey (2010-2013)., Setting: Nine states in India: Madhya Pradesh, Chhattisgarh, Rajasthan, Uttarakhand, Jharkhand, Odisha, Bihar, Assam and Uttar Pradesh., Participants: 886 505 women, aged 15-49 years., Main Outcome Measures: Stillbirth rate with 95% CI. Adjusted OR to examine the associations between stillbirth and (1) socioeconomic, behavioural and biodemographic risk factors and (2) complications in pregnancy (anaemia, eclampsia, other hypertensive disorders, antepartum and intrapartum haemorrhage, obstructed labour, breech presentation, abnormal fetal position)., Results: The overall rate of stillbirth was 10 per 1000 total births (95% CI 9.8 to 10.3). Indicators of socioeconomic deprivation were strongly associated with an increase in stillbirth: rural residence (adjusted OR (aOR) 1.27, 95% CI 1.16 to 1.39), female illiteracy (aOR 1.43, 95% CI 1.17 to 1.74), low socioeconomic status (aOR 2.42, 95% CI 1.82 to 3.21), schedule caste background (aOR 1.11, 95% CI 1.04 to 1.19) and woman not in paid employment (aOR 1.15, 95% CI 1.07 to 1.24). Women from minority religious groups were at higher risk than the Hindu majority (Muslim (aOR 1.33, 95% CI 1.25 to 1.43); Christian (aOR 1.42, 95% CI 1.19 to 1.70)). While a few women smoked (<1%), around 9% reported chewing tobacco, which was associated with an increased odds of stillbirth (aOR 1.11, 95% CI 1.02 to 1.21). Adverse pregnancy and birth characteristics were also associated with stillbirth: antenatal care visits <4 (aOR 1.08, 95% CI 1.01 to 1.15), maternal age <25 years (aOR 1.29, 95% CI 1.21 to 1.37) and ≥35 years (aOR 1.16, 95% CI 1.04 to 1.29), multigravida (aOR 3.06, 95% CI 2.42 to 3.86), multiple pregnancy (aOR 1.77, 95% CI 1.47 to 2.15), assisted delivery (aOR 3.45, 95% CI 3.02 to 3.93), caesarean section (aOR 1.73, 95% CI 1.58 to 1.89), as were pregnancy complications (aOR 1.42, 95% CI 1.33 to 1.51)., Conclusion: India is an emerging market economy experiencing a rapid health transition, yet these findings demonstrate the marked disparity in risk of stillbirth by women's socioeconomic status. Tobacco chewing and maternal and fetal complications were each found to be important modifiable risk factors. Targeting the 'at-risk' population identified here, improved recording of stillbirths and the introduction of local reviews would be important steps to reduce the high burden of stillbirths in India., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Introduction:: Several extracranial symptoms, including somatic pain syndormes, are known to occur in migraine. Though neck pain has been occasionally described with migraine, its precise association and nature is not yet clear., Objective:: To study the incidence and characteristics of neck pain in migraine with particular emphasis on its occurrence as a trigger or a part of the symptom complex of migraine, as well as its association with different phases of the migraine attack., Materials and Methods:: We interviewed 391 migraine patients for 18 months. All patients who reported neck pain anytime during the migraine phase were analyzed for their demographic profile, headache and neck pain characteristics, the associated conditions, and other clinical features., Results:: One hundred and sixty-six (42.5%) patients reported neck pain anytime during the attack (61.5% were female patients and the mean age was 35.8 years). A total of 82.7% patients had migraine without aura and 75.3% had episodic migraine at the onset. In 53 patients (32%), neck pain was a trigger, and in the rest (n = 113, 68%), neck pain was a part of migraine symtomatology. Fifty-seven patients (34.3%) noticed neck pain before the onset of headache; 148 patients (89.2%) reported neck pain at the onset of headache, and 46 patients (27.7%) experienced neck pain after the resolution of headache. The characteristic feature of migraine, such as the unilateral side shifting type of headache, was seen in only 54.2% of the patients, and the throbbing pain quality was seen in 75.2% of the patients. There was no significant difference in the nonheadache symptoms (P = 0.587) and cranial autonomic symptoms (P = 0.596) between the neck pain triggered migraine patients and those having neck pain as a part of the attack., Conclusion:: These data indicate that neck pain is a very common feature of migraine attacks and is likely to be either a trigger or a part of the migraine attack. Contrary to the established concept, however, neck pain as a prodromal or postdromal migraine symptom was less common. Careful history taking is required to diagnose neck pain as a feature of migraine and to differentiate it from secondary headache due to a cervical pathology for avoiding unnecessary imaging or other investigations., Competing Interests: The authors declare no conflict of interest issues

Objective: To assess the feasibility of establishing a simple maternal morbidity surveillance system in Assam (Indian Obstetric Surveillance System-Assam (IndOSS-Assam)) to investigate the incidence and trends in severe maternal complications. This study presents the surveillance platform of IndOSS-Assam., Design: Four tasks were undertaken: (1) setting up of a steering committee; (2) establishing priorities for the region; (3) mapping of surveillance sites; (4) piloting case-notification systems in selected centres., Setting: Two government tertiary hospitals in the state., Study Population: Pregnant women delivering in the hospitals between March and August 2015., Main Outcome Measures: Incidence and case fatality rates with 95% CIs., Results: Local stakeholder ownership and a simple uncomplicated anonymous system for case notification were the key strengths of this project. Cases and deaths were reported for six conditions: eclampsia, postpartum haemorrhage, puerperal sepsis, septic abortion, uterine rupture and anaemic heart failure. Among 10 475 women delivering over 6 months, 402 had one of these conditions and 66 died (case fatality 16%). The incidence of eclampsia was 17 per 1000 deliveries (95% CI 14 to 19), postpartum haemorrhage was 11 per 1000 deliveries (95% CI 10 to 13) and anaemic heart failure was 3 per 1000 deliveries (95% CI 2 to 5). For each of the other three conditions-puerperal sepsis, septic abortion and uterine rupture-the incidence rate was 2 per 1000 deliveries., Conclusions: IndOSS-Assam was shown to be a feasible and simple system for ongoing surveillance of maternal morbidity that can be used to monitor the trends in the incidence of specific severe life-threatening conditions during pregnancy., Competing Interests: Competing interests: None declared.

Objectives: To examine the association between maternal anaemia and adverse maternal and infant outcomes, and to assess the feasibility of conducting epidemiological studies through the Indian Obstetric Surveillance System-Assam (IndOSS-Assam)., Design: Retrospective cohort study using anonymised hospital records. Exposure: maternal iron deficiency anaemia; outcomes: postpartum haemorrhage (PPH), low birthweight, small-for-gestational age babies, perinatal death., Setting: 5 government medical colleges in Assam., Study Population: 1007 pregnant women who delivered in the 5 medical colleges from January to June 2015., Main Outcome Measures: ORs with 95% CIs to estimate the association between maternal iron deficiency anaemia and the adverse maternal and infant outcomes. Potential interactive roles of infections and induction of labour on the adverse outcomes were explored., Results: 35% (n=351) pregnant women had moderate-severe anaemia. Women with severe anaemia had a higher odds of PPH (adjusted OR (aOR) =9.45; 95% CI 2.62 to 34.05), giving birth to low birthweight (aOR=6.19; 95% CI 1.44 to 26.71) and small-for-gestational age babies (aOR=8.72; 95% CI 1.66 to 45.67), and perinatal death (aOR=16.42; 95% CI 4.38 to 61.55). Odds of PPH increased 17-fold among women with moderate-severe anaemia who underwent induction of labour, and 19-fold among women who had infection and moderate-severe anaemia., Conclusions: Maternal iron deficiency anaemia is a major public health problem in Assam. Maternal anaemia was associated with increased risks of PPH, low birthweight, small-for-gestational age babies and perinatal death. While the best approach is prevention, a large number of women present with severe anaemia late in pregnancy and there is no clear guidance on how these women should be managed during labour and delivery., Competing Interests: Competing interests: None declared.

We report a patient with progressive supranuclear palsy and incidentally detected the absence of right middle cerebral artery (MCA) without any old or acute infarct in its territory. The magnetic resonance angiography and computed tomography angiography failed to detect any significant collateral circulation. We discuss the embryogenesis of brain circulation and offer a possible explanation for the nonvisualization of the right MCA in our patient.

The aim of this study was to assess the regional impacts of heavy metals (Mn, Fe, Mg, Ca, Cu, Zn, Cd, Cr, Pb and Ni) on water, sediment and a native, teleost fish species, Labeo angra, inhabiting a flood plain wetland of Barak River in Assam, India. Heavy metal concentrations in the water, sediments and fish were measured; bioaccumulation factor, metal pollution index as well as condition indices were calculated, to assess the pollution load and health status of the fish. Multivariate statistical analysis was used on wetland water and sediment heavy metals to ascertain the possible sources and seasonal variations of the pollutants. Results showed that most heavy metals in the wetland water and sediments exceeded the water (drinking and irrigation) and sediment quality guidelines, respectively. Seasonal variations were observed for geogenic heavy metals, Mn, Fe, Mg and Ca while no seasonal variations were observed for anthropogenic heavy metals, Cu, Cd, Cr, Pb and Ni. Multivariate statistical analysis showed that there was strong correlation between geogenic and anthropogenic heavy metals in water and sediment, both originating from the common anthropogenic sources. Accumulation of most of the metals in all the tissues was above the safe limits as recommended by the Food and Agriculture Organization. High bioaccumulation factors and metal pollution index for these metals in the different tissues revealed that metals were extensively bio-accumulated and bioconcentrated. Condition indices in fish from the wetland suggested metabolic abnormalities.

Backgrounds and Aims: 4-6 million people die of enteric infections each year. After invading intestinal epithelial cells, enteric bacteria encounter phagocytes. However, little is known about how phagocytes internalize the bacteria to generate host responses. Previously, we have shown that BAI1 (Brain Angiogenesis Inhibitor 1) binds and internalizes Gram-negative bacteria through an ELMO1 (Engulfment and cell Motility protein 1)/Rac1-dependent mechanism. Here we delineate the role of ELMO1 in host inflammatory responses following enteric infection., Methods: ELMO1-depleted murine macrophage cell lines, intestinal macrophages and ELMO1 deficient mice (total or myeloid-cell specific) was infected with Salmonella enterica serovar Typhimurium. The bacterial load, inflammatory cytokines and histopathology was evaluated in the ileum, cecum and spleen. The ELMO1 dependent host cytokines were detected by a cytokine array. ELMO1 mediated Rac1 activity was measured by pulldown assay., Results: The cytokine array showed reduced release of pro-inflammatory cytokines, including TNF-α and MCP-1, by ELMO1-depleted macrophages. Inhibition of ELMO1 expression in macrophages decreased Rac1 activation (~6 fold) and reduced internalization of Salmonella . ELMO1-dependent internalization was indispensable for TNF-α and MCP-1. Simultaneous inhibition of ELMO1 and Rac function virtually abrogated TNF-α responses to infection. Further, activation of NF-κB, ERK 1/2 and p38 MAP kinases were impaired in ELMO1-depleted cells. Strikingly, bacterial internalization by intestinal macrophages was completely dependent on ELMO1. Salmonella infection of ELMO1-deficient mice resulted in a 90% reduction in bacterial burden and attenuated inflammatory responses in the ileum, spleen and cecum., Conclusion: These findings suggest a novel role for ELMO1 in facilitating intracellular bacterial sensing and the induction of inflammatory responses following infection with Salmonella ., Competing Interests: The authors declare no conflicts of interest.

Ethnopharmacological Relevance: Ocimum sanctum (OS), commonly known as Holy basil/Tulsi, has been traditionally used to treat cardiovascular diseases (CVD) and manage general cardiac health. The present study is designed to evaluate the antiinflammatory effect of O. sanctum and its phenolic compound and eugenol (EUG) in human monocytic (THP-1) cells and validate its traditional use for treating cardiovascular diseases., Materials and Methods: The phytochemical analysis of alcoholic and water extracts of OS-dry leaves (OSAE and OSWE) was done using LC-QTOF-MS. A phenolic compound, EUG was quantified in both OSAE and OSWE by an LC-MS technique using a mass hunter work station software quantitative analysis system. The effect of both OSAE, OSWE, pure compound EUG and positive control imatinib (IMT) was investigated in THP-1 cells by studying the following markers: lipopolysaccharide (LPS) induced tumor necrosis factor alpha (TNF-α) secretion by ELISA, gene expression of inflammatory markers (TNF-α, IL-6, MIP-1α and MCP-1) by real time PCR and translocation of nuclear factor kappa B (NF-κB) by confocol microscopy. Furthermore, the effect of the extracts, EUG and IMT, was studied on phorbol-12-myristate-13-acetate (PMA) induced monocyte to macrophage differentiation and gene expression of CD14, TLR2 and TLR4., Results: The LC-MS analysis of OSAE and OSWE revealed the presence of several bioactive compounds including eugenol. Quantitative analysis revealed that OSAE and OSWE had EUG of 12 ng/mgdwt and 19 ng/mgdwt respectively. OSAE, OSWE (1 mg dwt/mL) pure compound EUG (60 µg/mL) and positive control IMT (20 µg/mL) showed marked inhibition on LPS induced TNF-α secretion by THP-1 cells. At the selected concentration, the plant extracts, EUG and IMT inhibited gene expression of cytokines and chemokines (IL-6, TNF-α, MIP-1α, MCP-1) and translocation of NF-κB-p65 to the nuclei. In addition, they showed significant inhibition on PMA induced monocyte to macrophage differentiation and the gene expression of CD14, TLR2 and TLR4 markers., Conclusion: The result of the present study validated traditional use of Ocimum sanctum for treating cardiovascular disease for the first time by testing antiinflammatory activity of Ocimum sanctum in acute inflammatory model, LPS induced THP-1 cells. The plant extracts showed significant antiinflammatory activity, however, further to be evaluated using chronic inflammatory animal models like diabetic or apolipoprotein E-deficient mice to make it evidence based medicine. The phenolic compound eugenol (60 µg/mL) showed significant antiinflammatory activity. However the amount of eugenol present in 1mg of OSAE and OSWE (12 ng/mg and 19 ng/mg dwt respectively) used for cell based assays was very low. It suggests that several other metabolites along with eugenol are responsible for the efficacy of the extracts., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)