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Understanding the pathophysiology of idiopathic central precocious puberty (ICPP) is essential, in view of its consequences on reproductive health and metabolic disorders in later life. Towards this, estimation of circulating levels of the neuropeptides, viz; Kisspeptin (Kp-10), Neurokinin B (NKB) and Neuropeptide Y (NPY), acting upstream to Gonadotropin-Releasing Hormone (GnRH), has shown promise. Insights can also be gained from functional studies on genetic variations implicated in ICPP. This study investigated the pathophysiology of ICPP in a girl by exploring the therapeutic relevance of the circulating levels of Kp-10, NKB, NPY and characterizing the nonsynonymous KISS1R variant, L364H, that she harbours, in a homozygous condition. Plasma levels of Kp-10, NKB and NPY before and after GnRH analog (GnRHa) treatment, were determined by ELISA. It was observed that GnRHa treatment resulted in suppression of circulating levels of Kp-10, NKB and NPY. Further, the H364 variant in KISS1R was generated by site directed mutagenesis. Post transient transfection of either L364 or H364 KISS1R variant in CHO cells, receptor expression was ascertained by western blotting, indirect immunofluorescence and flow cytometry. Kp-10 stimulated signalling response was also determined by phospho-ERK and inositol phosphate production. Structure-function studies revealed that, although the receptor expression in H364 KISS1R was comparable to L364 KISS1R, there was an enhanced signalling response through this variant at high doses of Kp-10. Thus, elevated levels of Kp-10, acting through H364 KISS1R, contributed to the manifestation of ICPP, providing further evidence that dysregulation of Kp-10/KISS1R axis impacts the onset of puberty.
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Puberdade Precoce , Animais , Cricetinae , Feminino , Humanos , Cricetulus , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Kisspeptinas/genética , Neurocinina B/genética , Neurocinina B/metabolismo , Puberdade Precoce/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Kisspeptina-1/genéticaRESUMO
The emergence and evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that could compromise vaccine efficacy (VE) with re-infections in immunized individuals have necessitated continuous surveillance of VE. Here, the occurrence and dynamics of SARS-CoV-2 infections in the context of vaccination during the second wave of infection in Mumbai were evaluated. RT-PCR cycle threshold (Ct) values of the open reading frame (ORF)/envelope (E)/nucleocapsid (N) genes obtained from a total of 42415 samples, comprising unvaccinated (96.88%) and vaccinated cases (3.12%) were analyzed between December 28, 2020, and August 30, 2021. A lower incidence of SARS-CoV-2 infection in fully vaccinated cases (5.07%) compared to partially vaccinated cases (6.5%) and unvaccinated cases (13.453%) was recorded. VE was significant after the first dose of vaccination (ORF gene p-value = 0.003429, and E/N gene p-value = 0.000866). Furthermore, VE was observed to be significant when the post-immunization (first dose) period was stratified to within 30 days (ORF gene p-value = 0.0094 and E/N gene p-value = 0.0023) and to 60 days following the second dose of vaccination (ORF gene p-value = 0.0238). Also, significantly higher efficacy was observed within individuals receiving two doses compared to a single dose (ORF gene p-value = 0.0132 and E/N gene p-value = 0.0387). The emergence of breakthrough infections was also evident (odds ratio= 0.34; 95% confidence interval= 0.27-0.43). Interestingly, viral loads trended towards being higher in some groups of partially vaccinated individuals compared to completely vaccinated and unvaccinated populations. Finally, our results delineated a significantly higher incidence of SARS-CoV-2 acquisition in males, asymptomatic individuals, individuals with comorbidities, and those who were unvaccinated.
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COVID-19 , Masculino , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2/genética , Índia/epidemiologia , Vacinação , Infecções IrruptivasRESUMO
OBJECTIVE: To estimate incidence, risk of early and late-onset preeclampsia (PE) and understand their relationship with severity of COVID-19. METHODS: Pregnant women with COVID-19 (n = 1929) were enrolled from 1 April 2020 to 24 February 2022. Primary outcome measure was incidence and risk of early onset PE in women with COVID-19. RESULTS: The incidence of early and late-onset PE was 11.4% and 5.6%. Moderate to severe COVID-19 was associated with eight times higher risk of early onset PE [aOR = 8.13 (1.56-42.46), p = 0.0129] compared to asymptomatic group. CONCLUSIONS: Risk of early onset PE was higher in pregnant women with symptomatic COVID-19 as compared to asymptomatic women.
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COVID-19 , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/etiologia , Gestantes , COVID-19/complicações , Terceiro Trimestre da Gravidez , IncidênciaRESUMO
BACKGROUND: Snakebite envenoming (SBE) is an acute, life-threatening emergency in tropical and subtropical countries. It is an occupational hazard and a major socioeconomic determinant. Limited awareness, superstitions, lack of trained health providers, poor utilization of anti-venom results in high mortality and morbidity. India is the snakebite capital of the world. Yet, information on awareness, knowledge, and perceptions about snakebite is limited. Data on capacity building of health systems and its potential impact is lacking. Recommended by the National Task Force on snakebite research in India, this protocol describes the National Snakebite Project aiming for capacity building of health systems on prevention and management of snakebite envenomation in Maharashtra and Odisha states. METHODS: A cross-sectional, multi-centric study will be carried out in Shahapur, Aheri blocks of Maharashtra, and Khordha, Kasipur blocks of Odisha. The study has five phases: Phase I involves the collection of retrospective baseline data of snakebites, facility surveys, and community focus group discussions (FGDs). Phase II involves developing and implementing educational intervention programs for the community. Phase III will assess the knowledge and practices of the healthcare providers on snakebite management followed by their training in Phase IV. Phase V will evaluate the impact of the interventions on the community and healthcare system through FGDs and comparison of prospective and baseline data. DISCUSSION: The National Snakebite Project will use a multi-sectoral approach to reduce the burden of SBE. It intends to contribute to community empowerment and capacity building of the public healthcare system on the prevention and management of SBE. The results could be useful for upscaling to other Indian states, South Asia and other tropical countries. The findings of the study will provide critical regional inputs for the revision of the National Snakebite Treatment protocol. TRIAL REGISTRATION: Registered under the Clinical Trials Registry India no. CTRI/2021/11/038137.
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Mordeduras de Serpentes , Humanos , Mordeduras de Serpentes/epidemiologia , Mordeduras de Serpentes/prevenção & controle , Índia/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Fortalecimento Institucional , Estudos ProspectivosRESUMO
OBJECTIVE: To study clinical presentation, disease severity, pregnancy complications, and maternal outcomes in women affected with coronavirus disease 2019 (COVID-19) during the third wave compared with the first and second waves of COVID-19. METHODS: A retrospective, observational cohort study was conducted among 2058 pregnant and postpartum women with COVID-19 admitted during three wave periods at a tertiary care COVID-19-dedicated hospital. RESULTS: The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -infected pregnant and postpartum women with symptoms of COVID-19 was four times higher during the third wave compared with the first (odds ratio [OR] 4.6, 95% confidence interval [CI] 3.5-6.0, P < 0.001). There was a significantly lower proportion of pregnant and postpartum women with moderate to severe COVID-19 during the third wave (0.6%, 2/318) compared with those during the first wave (2.4%, 27/1143, P < 0.001) and second wave (14.4%, 86/597, P < 0.001). The intensive care/high dependency unit admissions during the third wave were significantly lower (2.5%, 8/318) than during the second wave (14.7%, 88/597; OR 0.2, 95% CI 0.1-0.3, P < 0.001) but similar to the first wave (2.4%, 27/1143). CONCLUSIONS: Decreased severity of COVID-19, reduced maternal mortality, and morbidity were reported in the third wave compared with the first wave and second wave of COVID-19 in the Mumbai Metropolitan Region, India. TRIAL REGISTRATION: The study is registered with the Clinical Trial Registry of India (Registration no: CTRI/2020/05/025423).
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COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Gravidez , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Gestantes , Estudos Retrospectivos , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez/epidemiologiaRESUMO
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.
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COVID-19 , Doenças do Recém-Nascido , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Asfixia/epidemiologia , COVID-19/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Mães , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Ressuscitação , Estudos Retrospectivos , SARS-CoV-2RESUMO
PURPOSE: To evaluate the association of single-nucleotide polymorphisms (SNPs) in the anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) genes with ovarian response and clinical pregnancy outcomes in women undergoing controlled ovarian hyperstimulation. METHODS: In this prospective study, we genotyped AMH polymorphisms (c. -649 T > C, c. 146 T > G, c. 252 G > A, and c. 303 G > A) in 365 women and AMHR2 polymorphisms (c. -482 A > G, c. 622-6 C > T, c. 4952 G > A, c. 10 A > G) in 80 women undergoing controlled ovarian hyperstimulation for IVF. RESULTS: Higher doses of exogenous FSH and lower numbers of preovulatory follicles were noted in women having AMH c. -649 T > C and AMH c. -146 T > G polymorphisms, respectively. Overall, we found that the presence of a polymorphic genotype (homozygous or heterozygous) at positions c. -649 T > C, c. 146 T > G, c. 252 G > A, and c. 303 G > A in the AMH gene was associated with higher doses of FSH for ovulation induction (p < 0.001). Interestingly, a higher live birth rate was noted in women with a homozygous polymorphic genotype for all four AMH SNPs investigated while none of the women showing a homozygous polymorphic genotype at all AMHR2 SNPs investigated in this study had a live birth. CONCLUSION: Our results show that presence of AMHR2 SNPs (c. 482 A > G, c. 622-6 C > T, c. 4952 G > A, and c. 10 A > G) negatively correlate with live birth rate. However, these findings need to be validated by using larger sample size.
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Hormônio Antimülleriano , Polimorfismo de Nucleotídeo Único , Receptores de Peptídeos/genética , Receptores de Fatores de Crescimento Transformadores beta/genética , Hormônio Antimülleriano/genética , Feminino , Hormônio Foliculoestimulante/genética , Humanos , Indução da Ovulação , Gravidez , Resultado da Gravidez , Estudos ProspectivosRESUMO
INTRODUCTION: Pregnant women are at increased risk of contracting COVID-19 due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, postpartum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India. METHODS AND ANALYSIS: PregCovid is a hospital-based registry for capturing information of pregnant, postpartum women with COVID-19 and their newborns in India. Medical case records of pregnant and postpartum women with a laboratory-confirmed diagnosis of COVID-19 will be captured in real-time using an online electronic patient record software. The data analysis will be carried out for symptoms, the severity of COVID-19, pregnancy complications, maternal morbidity and mortality, neonatal complications, mother-to-child transmission, etc. Data analysis will be carried out for different waves of the COVID-19 pandemic for rapid response and developing strategies well in advance to manage pregnant women infected with SARS-CoV-2. The evidence generated from the registry will be regularly shared with the appropriate authorities for policy decisions. Thus, the registry data may be useful for planning the strategies for better management of pregnant women with COVID-19. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Ethics Committees of all the participating study sites under the Medical Education and Drugs Department, Government of Maharashtra, Topiwala National Medical College & BYL Nair Charitable Hospital, Mumbai and ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India. The results from this study will be disseminated with local, state, and national health authorities, collaborators and the general population on the study website (https://pregcovid.com) as well as dissemination through scientific meetings and publications. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025423.
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COVID-19 , Gestantes , COVID-19/epidemiologia , Feminino , Hospitais , Humanos , Índia/epidemiologia , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Pandemias , Gravidez , Estudos Prospectivos , Sistema de Registros , SARS-CoV-2RESUMO
Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.
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COVID-19 , Interleucina-15/sangue , Linfopenia , Linfócitos T CD8-Positivos , Moléculas de Adesão Celular , Citocinas , Humanos , Interleucina-6 , Linfopenia/etiologia , SARS-CoV-2RESUMO
OBJECTIVE: To compare spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB) rates during both waves of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Retrospective analysis of the PregCovid registry of pregnant women with COVID-19 was performed at a dedicated COVID-19 hospital in Mumbai, India. The data of 1630 women were analyzed for this study between April 4, 2020 and July 4, 2021. Prepandemic data were analyzed and compared with pandemic data. Main outcome measure was spontaneous preterm birth rate. RESULTS: Preterm deliveries were higher during the second wave (46/329; 14%) compared with the first wave (82/807; 10.2%) of the COVID-19 pandemic (P = 0.065). Higher SPTBs were reported during the second wave than the first wave (12.5% versus 8.3%) (P = 0.03) as well as the prepandemic period (12.5% versus 10.5%) (P = 0.286). IPTBs were significantly lower in the pandemic period than in the prepandemic period (1.8 versus 3.3) (P = 0.012). CONCLUSION: In Mumbai, India, we found an unusual change in SPTBs during the 6 months of the second wave of COVID-19 compared with the previous 10 months of the first wave of pandemic and 1 year of prepandemic.
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COVID-19 , Nascimento Prematuro , COVID-19/epidemiologia , Feminino , Humanos , Recém-Nascido , Pandemias , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
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.
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COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Humanos , Índia/epidemiologia , Recém-Nascido , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Gestantes , Sistema de Registros , SARS-CoV-2Assuntos
COVID-19 , Natimorto , Feminino , Humanos , Índia/epidemiologia , Pandemias , Gravidez , SARS-CoV-2 , Natimorto/epidemiologiaRESUMO
INTRODUCTION: Endometriosis is one of the common, gynaecological disorders associated with chronic pelvic pain and subfertility affecting ~10% of reproductive age women. The clinical presentation, etiopathogenesis of endometriosis subtypes and associated risk factors are largely unknown. Genome-Wide Association (GWA) Studies (GWAS) provide strong evidence for the role of genetic risk factors contributing to endometriosis. However, no studies have investigated the association of the GWAS-identified single-nucleotide polymorphism (SNPs) with endometriosis risk in the Indian population; therefore, one-sixth of the world's population is not represented in the global genome consortiums on endometriosis. The Endometriosis Clinical and Genetic Research in India (ECGRI) study aims to broaden our understanding of the clinical phenotypes and genetic risks associated with endometriosis. METHODS AND ANALYSIS: ECGRI is a large-scale, multisite, case-control study of 2000 endometriosis cases and 2000 hospital controls to be recruited over 4 years at 15 collaborating study sites across India covering representative Indian population from east,north-east, north, central, west and southern geographical zones of India. We will use the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project (WERF-EPHect) data collection instruments for capturing information on clinical, epidemiological, lifestyle, environmental and surgical factors. WERF-EPHect standard operating procedures will be followed for the collection, processing and storage of biological samples. The principal analyses will be for main outcome measures of the incidence of endometriosis, disease subtypes and disease severity determined from the clinical data. This will be followed by GWAS within and across ethnic groups. ETHICS AND DISSEMINATION: The study is approved by the Institutional Ethics Committee of Indian Council of Medical Research-National Institute for Research in Reproductive Health and all participating study sites. The study is also approved by the Health Ministry Screening Committee of the Government of India. The results from this study will be actively disseminated through discussions with endometriosis patient groups, conference presentations and published manuscripts.
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Endometriose , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Endometriose/epidemiologia , Endometriose/genética , Feminino , Pesquisa em Genética , Estudo de Associação Genômica Ampla , Humanos , FenótipoRESUMO
INTRODUCTION: India has remarkably the highest number of snakebite cases contributing to nearly 50% of the global snakebite deaths. Despite this fact, there is limited knowledge and awareness regarding the management practices for snakebite in the Indian population. The study aimed to explore the knowledge, awareness, and perception of snakes and snakebites, first aid, and treatment amongst the community and the frontline health workers in a tribal block of Dahanu, Maharashtra, India. METHODS: A cross-sectional study was carried out from June 2016 to October 2018 in the Dahanu Block, Maharashtra. Perceptions, knowledge, awareness, and first-aid practices on the snakebites among the community were studied through focus group discussions (FGDs). Semi-structured questionnaires were used to assess the knowledge, awareness, and experience of the traditional faith healers, snake rescuers, frontline health workers on the snakebites and their management. A facility check survey was conducted using pre-tested questionnaires for different levels of the government health care facilities. RESULTS: Most of the tribal community was aware of the commonly found snakes and their hiding places. However, there was inadequate knowledge on the identification and classification of venomous snakes. Belief in a snake god, the perception that snakes will not come out during thunderstorms, change in taste sensation, the ability of tamarind seeds or magnet to reduce the venom effect were some of the superstitions reported by the tribal community. The application of a harmful method (Tourniquet) as the first aid for snakebite was practiced by the tribal community. They preferred herbal medicines and visiting the traditional faith healers before shifting the patient to the government health facility. The knowledge on the ability to identify venomous snakebites and anti-venom was significantly higher amongst nurses and accredited social health activists (ASHAs) than auxiliary nurse midwives (ANMs) and multi-purpose workers (MPWs) (p < 0.05). None of the traditional faith healers; but nearly 60% of snake rescuers were aware of anti-venom. Fifty percent of the medical officers in Dahanu block did not have correct knowledge about the Krait bite symptoms, and renal complications due to the Russell viper bite. CONCLUSIONS: Inappropriate perception, inadequate awareness, and knowledge about snakes and snakebites may predispose the tribal community to increased risks of venomous snakebites. Unproven and harmful methods for snakebite treatment practiced by the community and traditional faith healers could be dangerous leading to high mortality. Therefore, a multi-sectoral approach of community awareness, mapping of vulnerable populations, capacity building of health care facility, empowerment of health care workers (HCWs) could be useful for reducing the mortality and morbidity due to snakebite envenoming in India.
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Primeiros Socorros/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Mordeduras de Serpentes/psicologia , Adulto , Feminino , Pessoal de Saúde/psicologia , Pessoal de Saúde/normas , Humanos , Índia , Masculino , Medicina Tradicional/psicologia , População Rural/estatística & dados numéricos , Mordeduras de Serpentes/terapiaRESUMO
Male infertility is a multifactorial condition that contributes to around one-third of cases of infertility worldwide. Several chromosomal aberrations, single-gene and polygenic associations with male factor defects have been reported. These defects manifest as sperm number or sperm quality defects leading to infertility. However, in almost 40% of cases, the genetic etiology of male infertility remains unexplained. Understanding the causal genetic factors is crucial for effective patient management and counseling. Integrating the vast amount of available omics data on male infertility is a first step towards understanding, delineating and prioritizing genes associated with the different male reproductive disorders. The Male Infertility Knowledgebase (MIK) is a manually curated repository developed to boost research on the elusive genetic etiology of male infertility. It integrates information on â¼17 000 genes, their associated pathways, gene ontology, diseases and gene and sequence-based analysis tools. In addition, it also incorporates information on reported chromosomal aberrations and syndromic associations with male infertility. Disease enrichment of genes in MIK indicate a shared genetic etiology between cancer, male and female infertility disorders. While the genes involved in cancer pathways were found to be common causal factors for sperm number and sperm quality defects, the interleukin pathways were found to be shared and enriched between male factor defects and non-reproductive conditions like cardiovascular diseases, metabolic diseases, etc. Disease information in MIK can be explored further to identify high-risk conditions associated with male infertility and delineate shared genetic etiology. Utility of the knowledgebase in predicting novel genes is illustrated by identification of 149 novel candidates for cryptorchidism using gene prioritization and network analysis. MIK will serve as a platform for review of genetic information on male infertility, identification pleiotropic genes, prediction of novel candidate genes for the different male infertility diseases and for portending future high-risk diseases associated with male infertility. Database URL: http://mik.bicnirrh.res.in/.
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Infertilidade Masculina , Feminino , Humanos , Infertilidade Masculina/genética , Bases de Conhecimento , Masculino , EspermatozoidesRESUMO
The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker-sMIL index (sMAdCAM/IL-6 ratio)-these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.
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COVID-19/imunologia , Moléculas de Adesão Celular/sangue , Interleucina-6/sangue , Mucoproteínas/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , COVID-19/fisiopatologia , Estudos de Coortes , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Intestinos/imunologia , Masculino , Pessoa de Meia-Idade , Ressonância de Plasmônio de Superfície , Adulto Jovem , Tratamento Farmacológico da COVID-19Assuntos
COVID-19/mortalidade , Complicações Infecciosas na Gravidez/mortalidade , Resultado da Gravidez/epidemiologia , SARS-CoV-2 , Adulto , COVID-19/complicações , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Índia/epidemiologia , Recém-Nascido , Unidades de Terapia Intensiva , Mortalidade Materna , Gravidez , Complicações Infecciosas na Gravidez/virologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/virologia , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Retrospectivos , Natimorto/epidemiologiaRESUMO
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.