Understanding Acquired Brain Injury: A Review.

Any type of brain injury that transpires post-birth is referred to as Acquired Brain Injury (ABI). In general, ABI does not result from congenital disorders, degenerative diseases, or by brain trauma at birth. Although the human brain is protected from the external world by layers of tissues and bone, floating in nutrient-rich cerebrospinal fluid (CSF); it remains susceptible to harm and impairment. Brain damage resulting from ABI leads to changes in the normal neuronal tissue activity and/or structure in one or multiple areas of the brain, which can often affect normal brain functions. Impairment sustained from an ABI can last anywhere from days to a lifetime depending on the severity of the injury; however, many patients face trouble integrating themselves back into the community due to possible psychological and physiological outcomes. In this review, we discuss ABI pathologies, their types, and cellular mechanisms and summarize the therapeutic approaches for a better understanding of the subject and to create awareness among the public.

Structural changes, increased hypoxia, and oxidative DNA damage in placenta due to maternal smokeless tobacco use.

BACKGROUND: Smokeless tobacco (SLT) consumption during pregnancy is a well-recognized health risk that causes placental damage including hypoxia and oxidative damage. Although consumption of SLT by women varies from region to region, majority of tea leave pluckers consume SLT for relieving stress and pain. Still, the effects of SLT consumption have not been evaluated in tea garden workers (TGW). While previous studies have attempted to report effects of cigarette smoke using in vitro model, hypoxia-inducible factor (HIF)-1α expression in human placentae from pregnant women exposed to SLT has not been previously studied. This study was aimed to explore the effects of SLT consumption on placental structure, expression of HIF-1α and oxidative DNA damage in sample population of TGW. METHODS: A total of 51 placentae were collected from SLT users and nonusers (n = 30 and 21, respectively) with full-term normal delivery, who were involved in the plucking of tea leaves during pregnancy in tea plantation. Low birth weight (LBW, i.e., weight <2,500 g) and normal birth weight (NBW) groups among both SLT user and nonuser were compared for the stated parameters. Placental tissues were processed for transmission electron microscopy (TEM) study and immunohistochemical analysis for the expression of HIF-1α and 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: Altered ultrastructural characteristics were observed in the tertiary villi of LBW group among SLT users which included endothelial cells protrusion into capillary lumen, degenerated nuclei, significant thickening of trophoblast basement membrane and vasculo-syncytial membrane, abnormalities of the microvilli, swollen or damaged mitochondria, and dilatation in endoplasmic reticulum cisternae. Furthermore, significant reduction in the perimeter, area, and number of the stromal capillary of the tertiary villi of placenta were found in LBW group as compared with NBW group from the SLT users. Enhanced expression for HIF-1α and oxidative DNA damage (8-OHdG) biomarker was observed in SLT users as compared with nonusers. CONCLUSIONS: Maternal SLT exposure during pregnancy may be associated with villus hypoxia and consequently oxidative DNA damage. It is presumed that deleterious effect of SLT exposure on placenta could result in impairment of placental barrier, and restrict nutrient and oxygen supply from mother to fetus, and thus could be a cause of fetal growth restriction.

Transcriptomic landscaping of core genes and pathways of mild and severe psoriasis vulgaris.

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)­Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG­encoded proteins and a protein­protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine­cytokine receptor interaction and rheumatoid arthritis, whereas cytokine­cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our understanding of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.

Occupational exposure to pesticides in female tea garden workers and adverse birth outcomes.

Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia-inducible factor (HIF)-1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom-like structures, were observed during scanning electron microscopy along with increased HIF-1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF-1α expression, which also contributes to placental insufficiency and fetal growth restriction.

Predicting risk of low birth weight offspring from maternal features and blood polycyclic aromatic hydrocarbon concentration.

Prenatal exposure to organic pollutants increases the risk of low birth weight (LBW) offspring. Women involved in the plucking of tea leaves can be exposed to polycyclic aromatic hydrocarbons (PAHs) during pregnancy through inhalation and diet. Therefore, the aim of the study was to investigate the association of maternal socio-demographic features and blood PAH concentration with LBW; also to develop a model for predicting LBW risk. The study was performed by recruiting 55 women who delivered LBW and 120 women with NBW (normal birth weight) babies from Assam Medical College. The placental tissue, maternal and cord blood samples were collected. A total of sixteen PAHs and cotinine were analysed by HPLC and GC-MS. Association of PAH concentration with weight was determined using correlation and multiple logistic regression analyses. Predictive model was developed using SVMlight and Weka software. Maternal features such as age, education, food habits, occupation, etc. were found to be associated with LBW deliveries (p-value<0.05). Overall, 9 PAHs and cotinine were detected in the samples. A multiple logistic regression depicted an increased likelihood of LBW by exposure to PAHs (pyrene, di-benzo (a,h) anthracene, fluorene and fluoranthene) and cotinine. Models based on the features and PAHs/ cotinine predicted LBW offspring with 84.35% sensitivity and 74% specificity. LBW prediction models are available at http://dev.icmr.org.in/plbw/ webserver. With machine learning gaining more importance in medical science; our webserver could be instrumental for researchers and clinicians to predict the state of the fetus.

Association of maternal determinants with low birth weight babies in tea garden workers of Assam.

AIM: This study was aimed to evaluate the association of maternal determinants with birth weight (BW) of babies in tea garden workers (TGW) and housewives (HW). METHODS: A total of 175 subjects were recruited from Assam Medical College, Dibrugarh, India. In this cross-sectional study, maternal determinants, BW of babies and placental weight were explored in TGW (n = 102) and HW (n = 73). These factors were assessed and correlated by logistic regression models. RESULTS: A higher incidence of low birth weight (LBW) was found in mothers working in the tea garden (48.04%) as compared to HW (10.96%). Activity of plucking of leaves in tea garden by women had a higher risk for LBW babies (adjusted odd ratio [AOR] 4.33, 95% confidence interval [CI] 1.38-13.57, P = 0.012) and decreased placental weight (AOR 11.42, 95% CI 1.18-126.02, P = 0.036) as compared to HW considered as reference group. Women who worked continuously in the tea garden during 9 months of pregnancy also revealed an elevated risk for LBW (AOR 5.32, 95% CI 1.34-21.09, P = 0.017). CONCLUSION: This study suggests the activity of plucking of tea leaves by women is associated with LBW of babies and decreased placental weight. Particularly, if mothers worked continuously in the tea garden during 9 months of pregnancy, it also increased the risk of delivering LBW babies. This exploratory study provides an important platform for further prospective studies, which could be focused on the potential consequences of maternal occupational exposures during pregnancy on fetal development.

Up-regulation of fibroblast growth factor receptor 1 due to prenatal tobacco exposure can lead to developmental defects in new born.

Introduction: Tobacco-smoking is one of the most important risk factor for preterm delivery, pregnancy loss, low birth weight, and fetal growth restriction. It is estimated that approximately 30% of growth-restricted neonates could be independently associated with maternal smoking.Methods: In this study, gene expression profile, GSE11798, was chosen from GEO database with an aim to perceive change in gene expression signature in new born due to maternal smoking. Enrichment analysis was performed to annotate differentially expressed genes (DEGs) through gene ontology and pathway analysis using DAVID. Protein-protein interactions and module detection of these DEGs were carried out using cytoscape v3.6.0. Thirty umbilical cord tissue samples from 15 smokers and 15 non-smokers pregnant women were included in this analysis.Results: Twenty-six differentially expressed genes (DEGs) between two groups were selected using GEO2R tool. The DEGs were observed to be participating in biological processes/pathways related to growth releasing hormone, angiogenesis, embryonic skeletal, and cardiac development. Fibroblast growth factor receptor-1 (FGFR1) was identified to be the hub node with 348 interacting partners, which regulates transcription, cell growth, differentiation, and apoptosis. The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.Conclusion: The findings manifests the possibility of overcoming these adverse health effects in new born through FGFR1 modulating treatments during pregnancy.