Determinants of public institutional births in India: An analysis using the National Family Health Survey (NFHS-5) factsheet data.

Background: Institutional births ensure deliveries happen under the supervision of skilled healthcare personnel in an enabling environment. For countries like India, with high neonatal and maternal mortalities, achieving 100% coverage of institutional births is a top policy priority. In this respect, public health institutions have a key role, given that they remain the preferred choice by most of the population, owing to the existing barriers to healthcare access. While research in this domain has focused on private health institutions, there are limited studies, especially in the Indian context, that look at the enablers of institutional births in public health facilities. In this study, we look to identify the significant predictors of institutional birth in public health facilities in India. Method: We rely on the National Family Health Survey (NFHS-5) factsheet data for analysis. Our dependent variable (DV) in this study is the % of institutional births in public health facilities. We first use Welch's t-test to determine if there is any significant difference between urban and rural areas in terms of the DV. We then use multiple linear regression and partial F-test to identify the best-fit model that predicts the variation in the DV. We generate two models in this study and use Akaike's Information Criterion (AIC) and adjusted R2 values to identify the best-fit model. Results: We find no significant difference between urban and rural areas (P = 0.02, α =0.05) regarding the mean % of institutional births in public health facilities. The best-fit model is an interaction model with a moderate effect size (Adjusted2 = 0.35) and an AIC of 179.93, lower than the competitive model (AIC = 183.56). We find household health insurance (ß = -0.29) and homebirth conducted under the supervision of skilled healthcare personnel (ß = -0.56) to be significant predictors of institutional births in public facilities in India. Additionally, we observe low body mass index (BMI) and obesity to have a synergistic impact on the DV. Our findings show that the interaction between low BMI and obesity has a strong negative influence (ß = -0.61) on institutional births in public health facilities in India. Conclusion: Providing households with health insurance coverage may not improve the utilisation of public health facilities for deliveries in India, where other barriers to public healthcare access exist. Therefore, it is important to look at interventions that minimise the existing barriers to access. While the ultimate objective from a policy perspective should be achieving 100% coverage of institutional births in the long run, a short-term strategy makes sense in the Indian context, especially to manage the complications arising during births outside an institutional setting.

Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review.

Developmental signalling pathways such as Wnt/ß-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term 'embryonic' might appear to be a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. Therefore, any aberration in these pathways or their associated components may contribute towards a detrimental outcome in the form of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke. In the last decade, researchers have extensively studied these pathways to decipher disease-related interactions, which can be used as therapeutic targets to improve outcomes in patients with neurological abnormalities. However, a lot remains to be understood in this domain. Nevertheless, there is strong evidence supporting the fact that embryonic signalling is indeed a crucial mechanism as is manifested by its role in driving memory loss, motor impairments and many other processes after brain trauma. In this review, we explore the key roles of three embryonic pathways in modulating a range of homeostatic processes such as maintaining blood-brain barrier integrity, mitochondrial dynamics and neuroinflammation. In addition, we extensively investigated the effect of these pathways in driving the pathophysiology of a range of disorders such as Alzheimer's, Parkinson's and diabetic neuropathy. The concluding section of the review is dedicated to neurotherapeutics, wherein we identify and list a range of biological molecules and compounds that have shown enormous potential in improving prognosis in patients with these disorders.

Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.

Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.

The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.

BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like ßTrcP1 and ßTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.

Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

Deciphering the SSR incidences across viral members of Coronaviridae family.

Presence of Simple Sequence Repeats (SSRs), both in genic and intergenic regions, have been widely studied in eukaryotes, prokaryotes, and viruses. In the current study, we undertook a survey to analyze the frequency and distribution of microsatellites or SSRs in multiple genomes of Coronaviridae members. We successfully identified 919 SSRs with length ≥12 bp across 55 reference genomes majority of which (838 SSRs) were found abundant in genic regions. The in-silico analysis further identified the preferential abundance of hexameric SSRs than any other size-based motif class. Our analysis shows that the genome size and GC content of the genome had a weak influence on SSR frequency and density. However, we find a positive correlation of SSRs GC content with genomic GC content. We also report relatively low abundances of all theoretically possible 501 repeat motif classes in all the genomes of Coronaviridae. The majority of SSRs were AT-rich. Overall, we see an underrepresentation of SSRs across the genomes of Coronaviridae. Besides, our integrative study highlights the presence of SSRs in ORF1ab (nsp3, nsp4, nsp5A_3CLpro and nsp5B_3CLpro, nsp6, nsp10, nsp12, nsp13, & nsp15 domains), S, ORF3a, ORF7a, N & 3' UTR regions of SARS-CoV-2 and harbours multiple mutations (3'UTR and ORF1ab SSRs serving as major mutational hotspots). This indicates the genic SSRs are under selection pressure against mutations that might alter the reading frame and at the same time responsible for rapid protein evolution. Our preliminary results indicate the significance of the limited repertoire of SSRs in the genomes of Coronaviridae.

A "NOTCH" Deeper into the Epithelial-To-Mesenchymal Transition (EMT) Program in Breast Cancer.

Notch signaling is a primitive signaling pathway having various roles in the normal origin and development of each multicellular organisms. Therefore, any aberration in the pathway will inevitably lead to deadly outcomes such as cancer. It has now been more than two decades since Notch was acknowledged as an oncogene in mouse mammary tumor virus-infected mice. Since that discovery, activated Notch signaling and consequent up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. Moreover, consistent over-expression of Notch ligands and receptors has been shown to correlate with poor prognosis in human breast cancer. Notch regulates a number of key processes during breast carcinogenesis, of which, one key phenomenon is epithelial-mesenchymal transition (EMT). EMT is a key process for large-scale cell movement during morphogenesis at the time of embryonic development. Cancer cells aided by transcription factors usurp this developmental program to execute the multi-step process of tumorigenesis and metastasis. In this review, we recapitulate recent progress in breast cancer research that has provided new perceptions into the molecular mechanisms behind Notch-mediated EMT regulation during breast tumorigenesis.

ABC Transporters in Neurological Disorders: An Important Gateway for Botanical Compounds Mediated Neuro-Therapeutics.

Neurodegeneration is a distinguishing feature of many age related disorders and other vector borne neuroinflammatory diseases. There are a number of factors that can modulate the pathology of these disorders. ATP-binding cassette (ABC) transporters are primarily involved in the maintenance of normal brain homeostasis by eliminating toxic peptides and compounds from the brain. Also, ABC transporters protect the brain from the unwanted effects of endogenous and exogenous toxins that can enter the brain parenchyma. Therefore, these transporters have the ability to determine the pathological outcomes of several neurological disorders. For instance, ABC transporters like P-glycoprotein (ABCB1), and BCRP (ABCG2) have been reported to facilitate the clearance of peptides such as amyloid-ß (Aß) that accumulate in the brain during Alzheimer's disease (AD) progression. Other members such as ABCA1, ABCA2, ABCC8, ABCC9, ABCG1 and ABCG4 also have been reported to be involved in the progression of various brain disorders such as HIV-associated dementia, Multiple sclerosis (MS), Ischemic stroke, Japanese encephalitis (JE) and Epilepsy. However, these defective transporters can be targeted by numerous botanical compounds such as Verapamil, Berberine and Fascalpsyn as a therapeutic target to treat these neurological outcomes. These compounds are already reported to modulate ABC transporter activity in the CNS. Nonetheless, the exact mechanisms involving the ABC transporters role in normal brain functioning, their role in neuronal dysfunction and how these botanical compounds ensure and facilitate their therapeutic action in association with defective transporters still remain elusive. This review therefore, summarizes the role of ABC transporters in neurological disorders, with a special emphasis on its role in AD brains. The prospect of using botanical/natural compounds as modulators of ABC transporters in neurological disorders is discussed in the latter half of the article.

Nuclear factor-kappa ß as a therapeutic target for Alzheimer's disease.

Alzheimer's disease (AD) is a typical progressive, chronic neurodegenerative disorder with worldwide prevalence. Its clinical manifestation involves the presence of extracellular plaques and intracellular neurofibrillary tangles (NFTs). NFTs occur in brain tissues as a result of both Aß agglomeration and Tau phosphorylation. Although there is no known cure for AD, research into possible cures and treatment options continues using cell-cultures and model animals/organisms. The nuclear factor-kappa ß (NF-κß) plays an active role in the progression of AD. Impairment to this signaling module triggers undesirable phenotypic changes such as neuroinflammation, activation of microglia, oxidative stress related complications, and apoptotic cell death. These imbalances further lead to homeostatic abnormalities in the brain or in initial stages of AD essentially pushing normal neurons toward the degeneration process. Interestingly, the role of NF-κß signaling associated receptor-interacting protein kinase is currently observed in apoptotic and necrotic cell death, and has been reported in brains. Conversely, the NF-κß signaling pathway has also been reported to be involved in normal brain functioning. This pathway plays a crucial role in maintaining synaptic plasticity and balancing between learning and memory. Since any impairment in the pathways associated with NF-κß signaling causes altered neuronal dynamics, neurotherapeutics using compounds including, antioxidants, bioflavonoids, and non-steroidal anti-inflammatory drugs against such abnormalities offer possibilities to rectify aberrant excitatory neuronal activity in AD. In this review, we have provided an extensive overview of the crucial role of NF-κß signaling in normal brain homeostasis. We have also thoroughly outlined several established pathomechanisms associated with NF-κß pathways in AD, along with their respective therapeutic approaches.

p38 MAPK and PI3K/AKT Signalling Cascades inParkinson's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring Alzheimer's disease (AD). Currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of PD. Out of the several factors contributing to PD prognosis, the role of p38 MAPK (Mitogen activated protein-kinase) and PI3K/AKT signalling module in PD brains is crucial because the impaired balance between the pro- apoptotic and anti-apoptotic pathways trigger unwanted phenotypes such as microglia activation, neuroinflammation, oxidative stress and apoptosis. These factors continue challenging the brain homeostasis in initial stages thereby essentially assisting the dopaminergic (DA) neurons towards progressive degeneration in PD. Neurotherapeutics against PD shall then be targeted against the misregulated accomplices of the p38 and PI3K/AKT cascades. In this review, we have outlined many such established mechanisms involving the p38 MAPK and PI3K/AKT pathways which can offer therapeutic windows for the rectification of aberrant DA neuronal dynamics in PD brains.