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Background: Caesarean section (C-section) delivery is a serious maternal health concern in the long run. Notedly, there is a lack of studies dealing with understanding the ways and reasons of C-section deliveries becoming a public health issue in today’s time in India and the measures to reduce the unnecessary caesarean sections. We have conducted this study to study the changes in the state-wise prevalence of C-section deliveries in India and understand C-section delivery’s socioeconomic and biomedical predictors. Materials and Methods: The study uses data from the fourth and fifth rounds of the National Family Health Surveys (NFHS). The per cent differences in the C-section deliveries from NFHS-4 to NFHS-5 across the states were measured through relative changes. The association between the C-section delivery and socioeconomic and biomedical factors were assessed using multiple logistic regression. Results: This study revealed that the C-section deliveries are higher in the southern states than in the other parts of India. Literacy plays a vital role in C-section deliveries. The probabilities of C-section deliveries are more in 30–40 and 40 + years. The women belonging to the median wealth index category were more likely (OR–CI, 1.62 [1.55–1.66]) to undergo the C-section followed by the women from wealthy households (OR–CI, 1.46 [1.41–1.52]). Conclusion: The Government’s health policymakers should take the initiative to reduce the C-section section delivery by means of building maternal health literacy and awareness among women and the community so that its future implications can be minimised. It is crucial to formulate a mandate and implement it in the states where C-sections are too high through community health workers and primary care providers.

Background The impact of infertility on mental, emotional, physical and sexual health is grave, particularly in a pronatalist society. Literature is replete with evidence of wide ranging psychosocial consequences of infertility in women, indicating the need for identifying the gaps and designing appropriate context specific interventions to improve access and utilization of services. Data that are accessible, primarily from infertility clinics and women visiting hospitals for infertility treatment; information from community settings is rare. This is a protocol paper for a study to understand women’s experiences and actions taken by them to cope with delayed conception. Methods Mixed-methods cross-sectional design is used to obtain deep insights into the experiences of delayed conception, coping mechanisms, medical assistance and other help sought. Information is also being obtained on socio-demographic profile, fertility intentions, fertility quality of life, general medical history, obstetric, gynecological and sexual history, substance use and mental health status. A sample of 1530 women will be administered 4 modules of a quantitative survey. Focus group discussions, about four or till saturation point, will be conducted using purposive sampling. The study is recruiting from a population of women who previously participated in the ‘Women and Infants Integrated Interventions for Growth Study (WINGS) and failed to conceive during 18 months follow up period. Data collected through questionnaire will be assembled, cleaned, analyzed and reported. The findings will be disseminated through reports with the ethics review committee, government entities, academic and research publications. Discussion This study will provide insights on the experiences and coping strategies of women with delayed conception in the study community. Results will assist in designing appropriate interventions to meet the holistic health and psychosocial needs of women with delayed conception and promote sexual and reproductive health within the broader framework of Sustainable Development Goals and Universal health coverage. Trial registration Trial registration number: CTRI/2020/03/023955.

The level and relationship of child health, wealth, and basic amenities are changing fast in India. How strong are the relationships of state wealth, i.e., state Gross Domestic Product and basic household amenities like sanitation facilities with child health? Using the published National Family Health Survey 2015-16 at a macro level, the paper compares the change of stunting, underweight and under-five mortality over ten years (National Family Health Survey 2005-06 to 2015-16) and explores how far child health indices are associated with state Gross Domestic Product. Though wealth and child health are positively associated in India, the strength of the relationship is declining over time, indicating that wealth per se may not guarantee the betterment of child health. Undertaking a case study with 510 children in a low-income community of Mumbai, we further establish that the availability of basic facilities and recent infections play a stronger role in determining child nutrition status when household wealth is controlled. Higher-income, more years of schooling, less crowding in a household, covered drainage system, the non-occurrence of Gastro intestine, and infectious disease are significantly associated with better child nutrition status. Sincere attention to policy on improving basic facilities and living environment to address child health issues has become mandatory. National Health Mission or health programs like Swachh Bharat Abhiyan are good initiatives to focus on improving basic facilities and living environment to address child health issues. Key Words: Wealth, Child health, Stunting, Slum, Mumbai

Objectives: To study the changes in Anemia among women and to study the association between anemia and socio-demographic and economic predictors, also estimating the percentage contribution of selected predictors to Anemia among women belonging to poor and non-poor households.Methods: The State-wise percentages were taken from the extracted factsheets of National Family Health Survey 2015-2016 and 2019-2020. Absolute and relative percent changes to understand the changes in prevalence have been calculated. Multiple logistic regression was done to understand the associated varying predictors of Anemia among women. Percentage contribution of selected varying predictors through multivariate decomposition analysis have also been estimated. Results: Anemia prevalence was found the highest among the women in Goa and least in Lakshwadeep. The relative change in prevalence of Anemia was highest in Assam and lowest in Lakshwadeep. Socio-economic factors like marriage at a young age, lack of education, exposure to media, malnutrition, and poor economic status contribute significantly to the prevalence of Anemia among women of age 15-49 years.Conclusion: It is seen that the socio-demographic and economic burden on Anemia still continues to be higher than other medical predictors. The focus should be made more on education, malnutrition, and economic status to reduce the prevalence of Anemia.

Background: During the COVID pandemic, migrant workers had experienced harsh livelihood and socio-economic crises which amplified their challenges of life and significantly affected their mental health. However, there is a lack of in-depth evidence on how the mental trauma and shock of the loss of job and livelihood crisis affected men and women migrant workers differently. This study aimed to explore the impact of the COVID pandemic and lockdown on migrant workers who had faced psycho-social and financial challenges during the pandemic and lockdown and the effects of these challenges on their health. Methods: A formative research method comprising of iterative approach was used by conducting in-depth interviews of men and women migrant workers residing in randomly selected 2 blocks of a slum called Madanpur Khadar JJ Colony of Delhi, India. The respondents were chosen using a respondent driven purposive sampling depending on those who had faced severe loss during the pandemic. The migrant workers were interviewed about their challenges until saturation point was reached. In total 25 men and 25 women migrant workers were interviewed. Results: The financial constraints due to loss of employment, closing down of small scale self employment ventures, salary cuts and loans, threw life out of gear, further marginalizing the already disadvantaged community, who live from hand to mouth. To further aggravate the damage, COVID brought with it social stigma, discrimination, fear, stress, and anxiety. Women migrant workers bore the brunt of the burden of household responsibilities, increased demand without support and emotional abuse at home. Conclusions: There is an urgent need for unified social protection system with preventive, promotion-stricken, protective, and transformational measures designed through a crisis-responsive lens is required to provide an ecosystem of support to migrant workers.

Leishmania donovani, an obligate intracellular parasite, the causative agent of visceral leishmaniasis is known to subvert the host immune system for its own survival. Although the precise mechanism is still unknown, emerging evidences indicate that L. donovani efficiently suppress MHC I mediated antigen presentation, rendering inadequate CD8

Immunomodulation is an emerging concept to combat infection in recent years. Immunomodulators like arabinosylated-lipoarabinomannan (Ara-LAM) and glycyrrhizic-acid (GA) possess anti-leishmanial property, whereas sodium-antimony-gluconate (SAG) is still considered as the first choice for chemotherapy against leishmaniasis. During infection, invasion of Leishmania donovani needs the potential requirement of Ca2+, which is further responsible for apoptosis in intracellular amastigotes. However, suppression of elevated intracellular calcium by the activation of plasma-membrane-calcium-ATPase (PMCA4) facilitates survival of L. donovani in the host. In the present study, SAG, Ara-LAM, and GA were found to evoke significant increase in intracellular Ca2+ in L. donovani infected macrophages by inhibiting PMCA4. Moreover, PMCA4 inhibition by TFP or PMCA4 siRNA elevated the level of PKCβ, whereas calcium-independent upregulation of PKCζ remained unchanged in infected macrophages. Furthermore, application of immunomodulators in infected macrophages resulted in down-regulation of PKCζ, conversion of anti-inflammatory to pro-inflammatory cytokines and inhibition of PMCA4. Plasma membrane-associated ceramide which is known to be elevated during leishmaniasis, triggered upregulation of PMCA4 via PKCζ activation. Interestingly, immunomodulators attenuated ceramide generation, which resulted into reduced PKCζ activation leading to the decreased PMCA expression in infected macrophages. Therefore, our study elucidated the efficacy of SAG, Ara-LAM, and GA in the reduction of parasite burden in macrophages by suppressing PMCA activation through inhibition of ceramide mediated upregulation of PKCζ.

Background and Aims: Human fetal olfactory bulbs have a six layered laminar architecture where mitral cells are the largest neurons. Volume of the bulbs is considered as an indicator of olfactory function. Fetal bulb cell transplants are used to treat many diseases of the central nervous system. The present study aims to trace the development of the fetal bulbs with respect to it’s gross appearance, volume, arrangement and the number of mitral cells. Materials and Methods: Sixty two normal fresh aborted fetuses were collected from Obstetrics and Gynaecology department of Regional Institute of Medical Sciences, Imphal. The fetuses were dissected and olfactory bulbs were gently taken out and fixed in 10& formal saline. Once fixed, the volume of the bulbs were measured using a measuring cylinder and insulin syringe. This was followed by tissue processing and staining with Toluidine Blue and Cresyl Violet. Stained slides were photographed and number of mitral cells were counted using Image J software. The correlation of bulb volume with fetal age, crown rump length [CRL 1 and fetal body weight was analysed using SPSS software. Similar analysis was also done between mitral cell number and fetal age. Result: Fetal bulbs attained adult morphology at 20 weeks. Bulb volume was found to rise significantly with advancing fetal age until it slowed down 32 weeks onwards. Mitral cells were identifiable at 16 weeks and maintained a laminar arrangement and showed progressive increase in number until 28 weeks. There after the orderly arrangement of cells as well their number declined. Conclusion: Very few studies have been conducted so far regarding the fetal olfactory bulbs in India. The present study is expected to supplement known data and knowledge regarding the development of the fetal bulbs and the mitral cell population and help in the diagnosis and treatment of central nervous system diseases.

In urban areas, social interaction has done the job of reducing the intensity of discrimination, more than the anti-discrimination movements. Also, positive discrimination, like the reservation system, has given the opportunity to the lower caste to become active in social interaction. The objective of this study is to explore various changes in the caste system and to know the experience of migrated people in urban areas, especially who are Dalit and of other Scheduled Castes, in terms of their social interaction. The theme of the interview was their experiences in terms of social interaction with people from higher caste background. Six informal and unstructured in-depth interviews were conducted in Mumbai. Three among the six interviewees were students, one of the students being a Dalit and other two were of Scheduled Caste from Nagaland and Manipur, two taxi drivers, both being Dalit and a street vendor of scheduled caste, was interviewed. Caste system is not visually prominent in the traditional sense, but, the caste mindset still prevails and it influences the social interactions in urban area. Due to secularization, the higher caste people in the urban area seems to be away from their caste identity, but, when it comes to social interaction, they choose to maintain a prominent distance from lower caste people, only if they are in the knowledge of the caste background.

Acute Vibrio cholerae infection triggers significant inflammatory response and immense fluid secretion in the intestine. In the present study, methyl gallate (MG) isolated from Terminalia chebula was evaluated to determine the in vivo fluid accumulation-inhibitory, anticolonization and anti-inflammatory and in vitro biofilm-inhibitory activities against multi-drug resistant (MDR) V. cholerae. Bacterial membrane-damaging and biofilm-inhibitory activities were determined by membrane perturbation and transmission electron microscopy (TEM); and microdilution assays, respectively. Fluid accumulation-inhibitory and anticolonization activities of MG (23.80-95.23 mg/kg body weight) were determined in 4-5 days old BALB/c mice with an incubation time of 18 h. The effect of MG (1, 50 and 500 mg/kg body weight) on intestinal inflammatory reaction induced by V. cholerae was studied by performing histology in Swiss albino mice. MIC and MBC of MG against the test strains were 32-64 and 64-256 μg/ml, respectively. MG showed the fluid accumulation-inhibitory activity with inhibition values of 42.86-89.08% at doses between 23.80 and 95.23 mg/kg body weight and significant anticolonization activity (p 0.0001) against V. choleare in the suckling mouse intestine. MG (500 mg/kg body weight) significantly inhibited the inflammatory reactions induced by V. cholerae compared to the vehicle control. MG exhibited 70% minimum biofilm inhibition concentration of 64 μg/ml and bacterial membrane damaging activity at 1 × MBC. The results obtained in the present study suggest that MG has potential as an effective agent for the treatment of severe secretory and inflammatory diarrheal disease caused by MDR V. cholerae.

We show here that oral immunization with purified outer membrane vesicles (OMVs) of Vibrio cholerae induces a prolonged high rise in the protective antibody titre. Rabbit immune sera were vibriocidal against the homologous and against several heterologous V. cholerae strains in vitro. In addition, OMV immunization conferred significant protective immunity against subsequent bacterial challenges. Thirty OMV-immunized rabbits were challenged with different V. cholerae strains; each challenged group contained five immunized and three unimmunized animals. All the immunized rabbits survived bacterial challenges and were healthy after 24 h, except the two from each group that received the SG24 and SG06 strains, respectively, which developed watery diarrhoea. In contrast, all the unimmunized animals developed cholera-like symptoms, with a death toll of eight within 24 h of challenge. This is the first report of the induction of protective immunity by V. cholerae OMVs in a rabbit model (removable intestinal tie-adult rabbit diarrhoea) that mimics the human disease. Finally, OMVs were found to be significantly less reactogenic than the live and the heat-killed bacteria. Our studies show that oral immunization with OMVs of V. cholerae may induce long-term immunity and may be useful as a 'nonliving' vaccine candidate for the future.

In our earlier studies, we constructed a hybrid strain of Shigella dysenteriae type 1 by introducing a plasmid vector pPR 1347. After introduction of a lipopolysaccharide (LPS) biosynthesis gene, virulent Shigella dysenteriae type 1 strain became avirulent. In our present study, we have evaluated the immune response and protective efficacy of avirulent live transconjugant Shigella hybrid (LTSH) strain against wild type Shigella dysenteriae type 1, after four doses of oral (rabbit) and intranasal (mouse) immunizations. Serum IgG titers showed exponential increase during immunization and peaking on the 28th day and remained at that level till the 35th day in both the rabbit and the mouse models. When tested, serum IgG titers persisted for 63 days in mice and relatively high for 150 days in case of rabbits. Protection studies showed 100% protection against the challenge with wild type Shigella dysenteriae type 1 strain in rabbits and 80% protection in mice. Our results suggested that the LTSH strain could be a useful vaccine candidate strain in the future.

The nuclear protein NIPP1 (nuclear inhibitor of protein Ser/Thr phosphatase-1) interacts with the splicing factors SAP155 and CDC5L and is involved in a late step of spliceosome assembly. In addition, NIPP1 is an interactor of protein phosphatase-1 and a COOH-terminal NIPP1 fragment displays an RNase E like endoribonuclease activity. A yeast two-hybrid screening resulted in the identification of the Polycomb group protein EED (embryonic ectoderm development), an established transcriptional repressor, as a novel NIPP1 interactor. NIPP1 only interacted with full-length EED, whereas two EED interaction domains were mapped to the central and COOH-terminal thirds of NIPP1. The NIPP1-EED interaction was potentiated by the binding of (d)G-rich nucleic acids to the central domain of NIPP1. Nucleic acids also decreased the potency of NIPP1 as an inhibitor of PP1, but they did not prevent the formation of a ternary NIPP1.EED.PP1 complex. EED had no effect on the function of NIPP1 as a splicing factor or as an endoribonuclease. However, similar to EED, NIPP1 acted as a transcriptional repressor of targeted genes and this NIPP1 effect was mediated by the EED interaction domain. Also, the histone deacetylase 2 was present in a complex with NIPP1. Our data are in accordance with a role for NIPP1 as a DNA-targeting protein for EED and associated chromatin-modifying enzymes.

Guanylate cyclase C is the receptor for the bacterial heatstable enterotoxins and guanylin family of peptides, and mediates its action by elevating intracellular cGMP levels. Potentiation of ligand-stimulated activity of guanylate cyclase C in human colonic T84 cells is observed following activation of protein kinase C as a result of direct phosphorylation of guanylate cyclase C. Here, we show that prolonged exposure of cells to phorbol esters results in a decrease in guanylate cyclase C content in 4b-phorbol 12-myristate 13-acetate-treated cells, as a consequence of a decrease in guanylate cyclase C mRNA levels. The reduction in guanylate cyclase C mRNA was inhibited when cells were treated with 4b-phorbol 12-myristate 13-acetate (PMA) in the presence of staurosporine, indicating that a primary phosphorylation event by protein kinase C triggered the reduction in RNA levels. The reduction in guanylate cyclase C mRNA levels was not due to alterations in the half-life of guanylate cyclase C mRNA, but regulation occurred at the level of transcription of guanylate cyclase C mRNA. Expression in T84 cells of a guanylate cyclase C promoter-luciferase reporter plasmid,containing 1973 bp of promoter sequence of the guanylate cyclase C gene, indicated that luciferase activity was reduced markedly on PMA treatment of cells, and the protein kinase C-responsive element was present in a 129-bp region of the promoter, containing a HNF4 binding element. Electrophoretic mobility shift assays using an oligonucleotide corresponding to the HNF4 binding site, indicated a decrease in binding of the factor to its cognate sequence in nuclear extracts prepared from PMA-treated cells. We therefore show for the first time that regulation of guanylate cyclase C activity can be controlled at the transcriptional level by cross-talk with signaling pathways that modulate protein kinase C activity. We also suggest a novel regulation of the HNF4 transcription factor by protein kinase C.

We show here that oral immunization with purified outer membrane vesicles (OMVs) of Vibrio cholerae induces a prolonged high rise in the protective antibody titre. Rabbit immune sera were vibriocidal against the homologous and against several heterologous V. cholerae strains in vitro. In addition, OMV immunization conferred significant protective immunity against subsequent bacterial challenges. Thirty OMV-immunized rabbits were challenged with different V. cholerae strains; each challenged group contained five immunized and three unimmunized animals. All the immunized rabbits survived bacterial challenges and were healthy after 24 h, except the two from each group that received the SG24 and SG06 strains, respectively, which developed watery diarrhoea. In contrast, all the unimmunized animals developed cholera-like symptoms, with a death toll of eight within 24 h of challenge. This is the first report of the induction of protective immunity by V. cholerae OMVs in a rabbit model (removable intestinal tie-adult rabbit diarrhoea) that mimics the human disease. Finally, OMVs were found to be significantly less reactogenic than the live and the heat-killed bacteria. Our studies show that oral immunization with OMVs of V. cholerae may induce long-term immunity and may be useful as a 'nonliving' vaccine candidate for the future.

The control of RNA stability is an important post-transcriptional event. While neural development is known to require proteins that bind AU-rich elements (ARE) and affect RNA half-life, the role of specific RNA stability in this process remains elusive. In the Drosophila embryo, glial fate acquisition is triggered by glial cells missing (gcm) master gene, which is transiently expressed in all gliogenic stem cells and submitted to tight transcriptional regulation. By using in vitro and in vivo site directed mutagenesis, we have discovered that gcm RNA is unstable and that its 3'UTR confers labile properties to RNA due to the presence of an ARE motif. Moreover, we show that the gliogenic potential of Gcm transcription factor increases when ARE is abolished and demonstrate the importance of gcm RNA stability in the acquisition of the glial fate. Thus, control of a single RNA half-life is crucial for nervous system differentiation.

NIPP1 is a ubiquitously expressed nuclear protein that represses the transcription of targeted genes. Here we show that the transcriptional repression by NIPP1 is alleviated by the RNAi-mediated knockdown of EED and EZH2, two core components of the Polycomb Repressive Complex 2 (PRC2), and by the overexpression of a catalytically dead mutant of the histone methyltransferase EZH2. NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins. These data disclose an essential role for the PRC2 complex in the transcriptional repression by NIPP1. © 2007 Elsevier B.V. All rights reserved.

Summary Objectives To determine whether Vibrio cholerae strains with similar phage types are also genetically homogeneous or heterogeneous by molecular typing methods like PFGE and RAPD-PCR employed in this study. Methods A total of 26 V. cholerae O1 and O139 strains received from different parts of India were analyzed by using conventional phage typing method, antibiogram and molecular typing methods such as PFGE and RAPD-PCR. Results Both O1 and O139 strains were resistant against two antibiotics (Ampicillin and Furazolidone) were detected. All of these strains were clustered in a single phage type, i.e., Type 27 for V. cholerae O1 and Type 1 for V. cholerae O139. Extensive molecular characterization by RAPD and PFGE showed that six sets of O1 and O139 strains, each comprising two strains, had identical PFGE and RAPD profiles. Only one O139 strain (PL-4) had unique RAPD and PFGE profile among all the 26 V. cholerae strains used in this study. Conclusion Apart from serology, the strains of V. cholerae can be discriminated by this conventional phage typing system that offers the basic information on identification, biotyping and discrimination of strains. But, a high level of heterogeneity was observed in RAPD and PFGE profiles indicating the clonal diversity of V. cholerae O1 and O139 strains. It was concluded that these strains were phenotypically identical through phage typing system and antibiogram but genetically dissimilar, as shown in molecular typing systems.

Neuronal differentiation relies on proneural factors that also integrate positional information and contribute to the specification of the neuronal type. The molecular pathway triggering glial specification is not understood yet. In Drosophila, all lateral glial precursors and glial-promoting activity have been identified, which provides us with a unique opportunity to dissect the regulatory pathways controlling glial differentiation and specification. Although glial lineages are very heterogeneous with respect to position, time of differentiation, and lineage tree, they all express and require two homologous genes, glial cell deficient/glial cell missing (glide/gcm) and glide2, that act in concert, with glide/gcm constituting the major glial-promoting factor (Hosoya et al., 1995; Jones et al., 1995; Kammerer and Giangrande, 2001; Vincent et al., 1996). Here, we show that glial specification resides in glide/gcm transcriptional regulation. The glide/gcm promoter contains lineage-specific elements as well as quantitative and turmoil elements scattered throughout several kilobases. Interestingly, there is no correlation between a specific regulatory element and the type of glial lineage. Thus, the glial-promoting factor acts as a naive switch-on button that triggers gliogenesis in response to multiple pathways converging onto its promoter. Both negative and positive regulation are required to control glide/gcm expression, indicating that gliogenesis is actively repressed in some neural lineages.

Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis.