Mitochondrial epigenetic modifications and nuclear-mitochondrial communication: A new dimension towards understanding and attenuating the pathogenesis in women with PCOS.

Mitochondrial DNA (mtDNA) epigenetic modifications have recently gained attention in a plethora of complex diseases, including polycystic ovary syndrome (PCOS), a common cause of infertility in women of reproductive age. Herein we discussed mtDNA epigenetic modifications and their impact on nuclear-mitochondrial interactions in general and the latest advances indicating the role of mtDNA methylation in the pathophysiology of PCOS. We highlighted epigenetic changes in nuclear-related mitochondrial genes, including nuclear transcription factors that regulate mitochondrial function and may be involved in the development of PCOS or its related traits. Additionally, therapies targeting mitochondrial epigenetics, including time-restricted eating (TRE), which has been shown to have beneficial effects by improving mitochondrial function and may be mediated by epigenetic modifications, have also been discussed. As PCOS has become a major metabolic disorder and a risk factor for obesity, cardiometabolic disorders, and diabetes, lifestyle/behavior intervention using TRE that reinforces feeding-fasting rhythms without reducing caloric intake may be a promising therapeutic strategy for attenuating the pathogenesis. Furthermore, future perspectives in the area of mitochondrial epigenetics are described.

Effect of integrated people-centred eye care (IPEC) model on eye care seeking behaviour of community.

Background: World report on vision makes integrated people-centered eye care as care model of choice. Integrating eye care with the existing public health system makes services available, accessible, affordable, and sustainable. Being from the community, Accredited Social Health Activists (ASHAs) are better suited to improve people's eye health-seeking behavior. Objectives: This study aims to assess the eye care-seeking behavior of community and to understand their response toward the approach of integrated vision centers (VC) with ASHA involvement. Methods: A cross-sectional descriptive study was conducted in South Delhi district where integrated VC were functional for more than a year. These centers were supervised by medical officer in-charge, under whom ophthalmic assistants, ASHAs, auxiliary nurse midwives, and pharmacist work. ASHAs were trained in community-based primary eye care. The community survey was conducted on eye health-seeking behavior and utilization of VC services. Descriptive statistics were used for data analysis. Results: Out of 1571 study participants, 998 reported any ophthalmic illness in family in the past 6 months as against 1302 who reported nonophthalmic illness in family. The majority (1461, 90%) were aware about integrated VC and half of them (748, 51.2%) visited it. Of them, 64.2% were motivated through ASHAs. ASHAs spread awareness about eye diseases, eye treatment facility, and referred patients from the community. The majority (93%) were happy with the integrated VC and 87.8% were happy with ASHAs. Conclusion: Integrated VC with ASHA engagement could pave the way for universal eye health. Understanding people's needs and engaging community would increase the demand for eye care.

The mitochondrial landscape of ovarian cancer: emerging insights.

Ovarian cancer (OC) is known to be the most lethal cancer in women worldwide, and its etiology is poorly understood. Recent studies show that mitochondrial DNA (mtDNA) content as well as mtDNA and nuclear genes encoding mitochondrial proteins influence OC risk. This review presents an overview of role of mitochondrial genetics in influencing OC development and discusses the contribution of mitochondrial proteome in OC development, progression and therapy. A role of mitochondrial genetics in racial disparity is also highlighted. In-depth understanding of role of mitochondria in OC will help develop strategies toward prevention and treatment and improving overall survival in women with OC.

Choosing Plan B Over Plan A: Risk Compensation Theory and Contraceptive Choice in India.

Can women's contraceptive method choice be better understood through risk compensation theory? This theory implies that people act with greater care when the perceived risk of an activity is higher and with less care when it is lower. We examine how increased over-the-counter access to emergency contraceptive pills (ECPs) accompanied by marketing campaigns in India affected women's contraceptive method choices and incidence of sexually transmitted infections (STIs). Although ECPs substantially reduce the risk of pregnancy, they are less effective than other contraceptive methods and do not reduce the risk of STIs. We test whether an exogenous policy change that increased access to ECPs leads people to substitute away from other methods of contraception, such as condoms, thereby increasing the risk of both unintended pregnancy and STIs. We find evidence for risk compensation in terms of reduced use of condoms but not for increases in rates of STIs.

Diabetic retinopathy screening programme utilising non-mydriatic fundus imaging in slum populations of New Delhi, India.

OBJECTIVES: To develop and implement a community-based programme for screening of diabetic retinopathy (DR) in urban populations of Delhi. METHODS: Known diabetics (KDs) aged 40 years and older were identified through house-to-house surveys, volunteers and publicity. All KDs were referred to DR screening camps organised locally where procedures included brief medical history, ocular examination and non-mydriatic fundus photography using portable handheld camera. Fundal images were graded on the spot by trained optometrists for DR. Patients with DR were referred to tertiary centre for management. RESULTS: A total of 11 566 KDs were identified, of whom 9435 (81.6%) visited DR screening camps and 8432 (89.4%) had DR gradable images. DR was identified in 13.5% of subjects; 351 cases were mild NPDR, 567 moderate, 92 severe. Seventy-seven had PDR, and 49 had DME, and 2.7% of participants were blind (presenting visual acuity <3/60 in better eye). Non-use of lifestyle management, presence of systemic complications, BMI <18.5 kg/m2 , disease duration of >5 years and uncontrolled diabetes were associated with increased odds of DR. All cases with DR were referred, and 420 (37%) successful referrals to base hospital were observed. CONCLUSION: The programme of creating awareness about DR, identifying KDs and optometrist-led DR screening using non-mydriatic fundus camera based in slums was successful.

Perception of sex workers of Lucknow City, Uttar Pradesh, India towards sexually transmitted infections.

The prevention, control, and management of sexually transmitted infections/reproductive tract infection (STI/RTI) are well-recognized cost-effective strategies for controlling the spread of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). A cross-sectional descriptive study was done over a period of 1 year to assess the prevalence of STI, knowledge level about STI, and the STI-HIV link among the female sex workers (FSWs) of Lucknow city, Uttar Pradesh, India along with their biosocial characteristics. Most of the FSWs were illiterate, married, Hindus, and belonged to general category. The prevalence rates of STI among street-based and home-based FSWs were 50.6% and 29.8%, respectively. Knowledge about the role of condom in prevention of STI and the STI-HIV link was significantly less among home-based FSWs than those who are street-based. There is a great lack in the awareness among FSWs regarding STI and their prevention. Behavior change communication (BCC) and advocacy strategy were developed, especially for the home-based group, to strengthen their knowledge regarding the STI-HIV link.

Facile Fabrication of Sandalwood Oil-Based Nanoemulsion to Intensify the Fatty Acid Composition in Burned and Rough Skin.

The restoration process of burned and rough skin takes a long time and remains a critical challenge. It can be repaired through a combination of proper care, hydration, and topical therapies. In this study, a novel nanoemulsion was synthesized through the high-energy ultrasonication method. A total of five nanoemulsions (NE1-5) were prepared with varying concentrations of sandalwood oil, a nonionic surfactant (polysorbate 80), and water. Among them, NE3 had a number of appropriate physicochemical characteristics, such as physiological pH (5.58 ± 0.09), refractive index (∼1.34), electrical conductivity (115 ± 0.23 mS cm-1), and transmittance (∼96.5%), which were suitable for skin care applications. The NE3 had a strong surface potential of -18.5 ± 0.15 mV and a hydrodynamic size of 61.99 ± 0.22 nm with a polydispersity index of 0.204. The structural integrity and a distinct droplet size range between 50 and 100 nm were confirmed by transmission electron microscopic analysis. The skin regeneration and restoration abilities of synthesized nanoemulsions were examined by conducting an in vivo study on Sprague-Dawley rats. Exposure to NE3 significantly increased the healing process in burned skin as compared to untreated control and nonemulsified sandalwood oil. In another set of experiments, the NE3-treated rough skin became softer, smoother, and less scaly than all other treatments. Enhanced fatty acids, i.e., palmitic acid, stearic acid, and cholesterol, were recorded in NE3-supplemented burned and rough skin compared to the untreated control. The NE3 had outstanding compatibility with key components of skincare products without any stability issues. Its biocompatibility with the cellular system was established by the negligible generation of reactive oxygen species (ROS) and a lack of genotoxicity. Considering these results, NE3 can be used in cosmetic products such as creams, lotions, and serums, allowing industries to achieve improved product formulations and provide better healthcare benefits to humanity.

Sunset Yellow protects against oxidative damage and exhibits chemoprevention in chemically induced skin cancer model.

Skin cancer and other skin-related inflammatory pathologies are rising due to heightened exposure to environmental pollutants and carcinogens. In this context, natural products and repurposed compounds hold promise as novel therapeutic and preventive agents. Strengthening the skin's antioxidant defense mechanisms is pivotal in neutralizing reactive oxygen species (ROS) and mitigating oxidative stress. Sunset Yellow (SY) exhibits immunomodulatory characteristics, evidenced by its capacity to partially inhibit the secretion of proinflammatory cytokines, regulate immune cell populations, and modulate the activation of lymphocytes. This study aimed to investigate the antioxidant and anti-genotoxic properties of SY using in-silico, in vitro, and physiochemical test systems, and to further explore its potential role in 7,12-dimethylbenz(a) anthracene (DMBA)/ 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis. In vitro experiments showed that pre-treatment of SY significantly enhanced the cell viability of HaCaT cells when exposed to tertiary-Butyl Hydrogen Peroxide (tBHP). This increase was accompanied by reduced ROS levels, restoration of mitochondrial membrane potential, and notable reduction in DNA damage in (SY + tBHP) treated cells. Mechanistic investigations using DPPH chemical antioxidant activity test and potentiometric titrations confirmed SY's antioxidant properties, with a standard reduction potential ( E o ) of 0.211 V. Remarkably, evaluating the effect of topical application of SY in DMBA/TPA-induced two-step skin carcinogenesis model revealed dose-dependent decreases in tumor latency, incidence, yield, and burden over 21-weeks. Furthermore, computational analysis and experimental validations identified GSK3ß, KEAP1 and EGFR as putative molecular targets of SY. Collectively, our findings reveal that SY enhances cellular antioxidant defenses, exhibits anti-genotoxic effects, and functions as a promising chemopreventive agent.

Effective cataract surgical coverage in India: Evidence from 31 districts.

BACKGROUND: Effective Cataract Surgical Coverage (eCSC) is a core outcomes domain indicator to assess accessibility and quality of eye care services with limited available information. PURPOSE: To generate baseline estimates of eCSC for India. METHODS: We performed the analysis of data pooled from Rapid Assessment of Avoidable Blindness surveys conducted in 31 districts of India during 2015-2019 among persons aged 50+ years. eCSC was calculated at various thresholds, the primary being operable cataract at best corrected visual acuity <6/12, good outcome at presenting visual acuity of 6/12. RESULTS: Age-sex standardized and weighed eCSC in India was 36.7% (95% CI: 33.6, 39.9), and cataract surgical coverage (CSC) was 57.3% (95% CI: 53.3, 61.2), a relative quality gap in cataract surgery being 36.0%. eCSC in males was higher at 38.0% than females (35.6%). eCSC increased with education from 31.0% in illiterate participants to 59.7% in class 10 educated. On multivariate analysis, rural setting, increasing age, and residence in eastern or northeastern zones of India continued to be associated with poor/worse eCSC, while female gender was associated with higher eCSC. District-wide variations in eCSC were observed. CONCLUSION: Developmental factors have an important bearing on eCSC in India. Geographical variations point toward the need for targeted, locally relevant strategies.

DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.

Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA.

N-acetyltransferase and cytochrome P450 2E1 gene polymorphisms and susceptibility to antituberculosis drug hepatotoxicity in an Indian population.

Background. Antituberculosis drug hepatotoxicity (ATDH) is common in India. Isoniazid, a constituent of most anti- tuberculosis drug regimens, is metabolized by N-acetyltransferase (NAT2) and cytochrome P450 2E1 (CYP2E1) enzymes. We therefore studied the association of some single-nucleotide polymorphisms (SNPs) in these enzyme genes with ATDH. Methods. Allelic and genotypic frequencies at three SNP loci in the NAT2 gene (rs1799929, rs1799930 and rs1799931) and one locus (rs2031920) in the CYP2E1 gene were studied using restriction fragment length polymorphism in 33 patients who developed ATDH following an isoniazid- containing antituberculosis drug regimen and 173 healthy blood donors. After confirming adherence of the control data to the Hardy-Weinberg equilibrium model, genotype and allele frequencies in the two groups were compared. Results. For SNP rs1799930 in the NAT2 gene, 7 (21%), 21 (64%) and 5 (15%) patients, and 93 (54%), 62 (36%) and 18 (10%) controls had GG, GA and AA genotypes, respectively (p=0.003; odds ratio [OR] for GA v. GG=4.50 [95% CI 1.80-11.22] and for AA v. GG=3.69 [1.05-12.93]). Allele frequency for G nucleotides for this SNP was 0.53 among patients and 0.72 among controls (OR 2.24 [1.31-3.84], p=0.007). The allele and genotype frequencies of the other NAT2 SNPs and the CYP2E1 SNP showed no significant difference between cases and controls. All the 33 patients and 151 (87%) of 173 controls had mutant allele at one or more of the three NAT2 SNP loci (p=0.03). The presence of two or more mutant alleles, a marker of slow acetylator status, was more frequent in patients (23/33 [70%]) than in controls (73/173 [42%]; OR 3.23 [95% CI 1.45-7.19], p=0.004). Conclusion. In India, the risk of ATDH is increased in persons with 'A' allele at SNP rs1799930 in the NAT2 gene, but is not associated with rs2031920 polymorphism in the CYP2E1 gene.

Molecular characterization of variants in mitochondrial DNA encoded genes using next generation sequencing analysis and mitochondrial dysfunction in women with PCOS.

Emerging studies indicates mitochondrial dysfunction and involvement of mitochondrial DNA (mtDNA) variants in the pathogenesis of polycystic ovary syndrome (PCOS). Cumulative effect of mtDNA rare variants are now gaining considerable interest apart from common variants in the pathogenesis of complex diseases. Rare variants may modify the effect of polymorphism or in combination with the common variants may affect the risk of disease. With the evolution of high throughput sequencing techniques, which can be utilized to identify common as well as rare variants along with heteroplasmy levels, comprehensive characterization of the mtDNA variants is possible. Till date, few studies reported common mtDNA variants using traditional sequencing techniques but rare variants in mtDNA encoding genes remain unexplored in women with PCOS. These mtDNA variants may be responsible for mitochondrial dysfunction and may contribute in PCOS pathogenesis. In this study we determined mtDNA copy number, a biomarker of mitochondrial dysfunction and first time analysed variants in mtDNA encoded genes in women with PCOS using mitochondrial Next Generation sequencing (NGS) approach and compared allele frequency from mitochondrial 1000 genome dataset. Variant annotation and prioritization was done using highly automated pipeline, MToolBox that excludes reads mapped from nuclear mitochondrial DNA sequences (NumtS) to identify unique mtDNA reads. The present study identified significant reduction in mtDNA copy number in women with PCOS compared to non-PCOS women. A total of unique 214 prioritized common to rare variants were identified in mtDNA encoded genes, 183 variants in OXPHOS complexes, 14 variants in MT-tRNA and 17 variants in MT-rRNA genes that may be involved in mitochondrial dysfunction in PCOS. Numerous variants were heteroplasmic, pathogenic in nature and occurred in evolutionary conserved region. Heteroplasmic variants were more frequently occurred in MT-CO3 gene. Non-synonymous variants were more than synonymous variants and mainly occurred in OXPHOS complex I and IV. Few variants were found to be associated with diseases in MITOMAP database. The study provides a better understanding towards pathogenesis of PCOS from novel aspects focusing on mitochondrial genetic defects as underlying cause for contributing mitochondrial dysfunction in women with PCOS.

Readiness and Motivation of ASHAs towards Their Participation in Non-Communicable Disease Control Programmein North India:A Cross Sectional Study.

BACKGROUND: ASHAs (Accredited Social Health Activist)role is evolving beyond maternal and child health workers. They are engaged in NCD (Non-communicable Diseases)control activities. This study investigated their preparedness for this new task.The aim of the study was to assess the preparedness (knowledge, attitude, practices & patient navigation) of ASHAs in delivering community-based NCD prevention and control services under NPCDCS (National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases & Stroke)program. And the study also assessed the challenges faced by ASHAs in fulfilling their roles and responsibilities towards common NCDs. SETTINGS AND DESIGN: Cross sectional descriptive conducted in Delhi. METHOD: Total 464 ASHAs randomly selected from 54 Primary Health Centres from 3 districts of Delhi. A self-administered, pre-tested, validated and piloted semi structured questionnaire was filled by enrolled ASHAs. It assessed their knowledge, attitude and practices related to NCD screening. STATISTICAL ANALYSIS USED: descriptive statistics, chi square test and logistic regression analysis were used. RESULTS: Two-third ASHAs had moderate to good knowledge about NCDs. They had positive inclination towards NCD screening and risk mitigation. Their practices for hypertension and diabetes screening were adequate but common cancer screening practices were inadequate. Challenges encountered in performing these tasks were lack of appropriate referral linkages, minimal supportive supervision and no ear marked incentives. CONCLUSIONS: ASHAs showed willingness to work for NCD control provided they have optimum training, supportive supervision from their superiors, and screening facilities in functional state and appropriate incentives for the new tasks.

Endovascular Management of Falcine Dural Arteriovenous Fistula-A Case Report and Review of Literature.

Cranial dural arteriovenous (AV) fistulas are abnormal connections between the branches of dural arteries to dural veins or venous sinuses. They are most frequently located at the transverse sinus and cavernous sinus. They can occur at every cranial dural sinus. Dural AV fistula of falx cerebri is rare. A 62-year-old female presented with signs and symptoms of raised intracranial pressure. Radiological imaging revealed a dural AV fistula at the posterior one-third falx cerebri. She underwent transarterial embolization, and complete obliteration of the fistula was achieved. A detailed digital subtraction angiography study is warranted in patients with seemingly benign complaints like recurrent headaches, and falcine dural AV fistula should be identified and treated in the nick of time. We describe a very rare falcine dural AV fistula case and its management.

A Review of Sustainable Use of Biogenic Nanoscale Agro-Materials to Enhance Stress Tolerance and Nutritional Value of Plants.

Climate change is more likely to have a detrimental effect on the world's productive assets. Several undesirable conditions and practices, including extreme temperature, drought, and uncontrolled use of agrochemicals, result in stresses that strain agriculture. In addition, nutritional inadequacies in food crops are wreaking havoc on human health, especially in rural regions of less developed countries. This could be because plants are unable to absorb the nutrients in conventional fertilizers, or these fertilizers have an inappropriate or unbalanced nutrient composition. Chemical fertilizers have been used for centuries and have considerably increased crop yields. However, they also disrupt soil quality and structure, eventually impacting the entire ecosystem. To address the situation, it is necessary to develop advanced materials that can release nutrients to targeted points in the plant-soil environment or appropriate receptors on the leaf in the case of foliar applications. Recently, nanotechnology-based interventions have been strongly encouraged to meet the world's growing food demand and to promote food security in an environmentally friendly manner. Biological approaches for the synthesis of nanoscale agro-materials have become a promising area of research, with a wide range of product types such as nanopesticides, nanoinsecticides, nanoherbicides, nanobactericides/fungicides, bio-conjugated nanocomplexes, and nanoemulsions emerging therefrom. These materials are more sustainable and target-oriented than conventional agrochemicals. In this paper, we reviewed the literature on major abiotic and biotic stresses that are detrimental to plant growth and productivity. We comprehensively discussed the different forms of nanoscale agro-materials and provided an overview of biological approaches in nano-enabled strategies that can efficiently alleviate plant biotic and abiotic stresses while potentially enhancing the nutritional values of plants.

Chitosan fabricated biogenic silver nanoparticles (Ch@BSNP) protectively modulate the defense mechanism of tomato during bacterial leaf spot (BLS) disease.

Herein, the impact of chitosan fabricated biogenic silver nanoparticles (Ch@BSNP) has been evaluated for the protective management of bacterial leaf spot (BLS) disease in tomatoes caused by Xanthomonas campestris (NCIM5028). The Ch@BSNP originated by the Trichoderma viride (MTCC5661) derived extracellular compounds and subsequent chitosan hybridization. Spherical-shaped Ch@BSNP (30-35 nm) treated diseased plants were able to combat the biotic stress, as evidenced by the decreased elevated response of stress markers viz; anthocyanin (34.02%), proline (45.00%), flavonoids (20.26%), lipid peroxidation (10.00%), guaiacol peroxidase (36.58%), ascorbate peroxidase (41.50%), polyphenol oxidase (25.34%) and phenylalanine ammonia-lyase (2.10 fold) as compared to untreated diseased plants. Increased biochemical content specifically sugar (15.43%), phenolics (49.10%), chlorophyll, and carotenoids were measured in Ch@BSNP-treated diseased plants compared to untreated X. campestris-infested plants. The Ch@BSNP considerably reduced stress by increasing net photosynthetic rate and water use efficiency along with decreased transpiration rate and stomatal conductance in comparison to infected plants. Additionally, the expression of defense-regulatory genes viz; growth responsive (AUX, GH3, SAUR), early defense responsive (WRKYTF22, WRKY33, NOS1), defense responsive (PR1, NHO1, NPR1), hypersensitivity responsive (Pti, RbohD, OXI1) and stress hormones responsive (MYC2, JAR1, ERF1) were found to be upregulated in diseased plants while being significantly downregulated in Ch@BSNP-treated diseased plants. Furthermore, fruits obtained from pathogen-compromised plants treated with Ch@BSNP had higher levels of health-promoting compounds including lycopene and beta-carotene than infected plant fruits. This nano-enabled and environmentally safer crop protection strategy may encourage a sustainable agri-system towards the world's growing food demand and promote food security.

A study to assess the knowledge and skills of Accredited Social Health Activists and its retention after training in community-based primary eye care.

PURPOSE: Community volunteers like Accredited Social Health Activists (ASHAs) could be utilized for linking community and eye care services. Research is needed to effectively utilize them. This study was to assess whether ASHAs could imbibe new knowledge in eye care and conduct vision screening. METHODS: Settings and Design: A pre-post-intervention study in South Delhi Integrated Vision Centres. It was conducted from January 2016 to March 2017. One day of conceptual training followed by hands-on training in vision screening was imparted to ASHAs. The knowledge was assessed thrice: before, immediately after, and following 1 year after training. The vision screening skill was assessed twice. Descriptive analysis using percentages, mean and standard deviations. Paired t-test was used for assessing the change in scores. RESULTS: A total of 102 ASHAs were recruited. A significant increase in the knowledge score of ASHAs before (14.96) and after training (25.38) (P < 0.001) was noted. The knowledge score was sustained at 1 year (21.75). The satisfactory skill of vision screening was seen in 88 (86.3%) ASHAs after training, while 79 (77.5%) ASHAs still retained it after 1 year. CONCLUSION: The potential to involve ASHAs in community-based frontline eye care activities: awareness generation of eye diseases, identification of referrable conditions, and facilitating individuals to seek eye care facilities. This study informs about the duration, frequency, and content of the training. It also provides evidence on the improvement and sustainability of eye care knowledge and skills by ASHAs after conceptual and hands-on training.

ARID2 suppression promotes tumor progression and upregulates cytokeratin 8, 18 and ß-4 integrin expression in TP53-mutated tobacco-related oral cancer and has prognostic implications.

Mutations in ARID2 and TP53 genes are found to be implicated in the tobacco related tumorigeneses. However, the effect of loss of ARID2 in the TP53 mutated background in tobacco related cancer including oral cancer has not been investigated yet. Hence, in this study we knockdown ARID2 using shRNA mediated knockdown strategy in TP53 mutated oral squamous cell carcinoma (OSCC) cell line and studied its tumorigenic role. Our study revealed that suppression of ARID2 in TP53 mutated oral cancer cells increases cell motility and invasion, induces drastic morphological changes and leads to a marked increase in the expression levels of cytokeratins, and integrins, CK8, CK18 and ß4-Integrin, markers of cell migration/invasion in oral cancer. ARID2 suppression also showed early onset and increased tumorigenicity in-vivo. Interestingly, transcriptome profiling revealed differentially expressed genes associated with migration and invasion in oral cancer cells including AKR1C2, NCAM2, NOS1, ADAM23 and genes of S100A family in ARID2 knockdown TP53 mutated oral cancer cells. Pathway analysis of differentially regulated genes identified "cancer pathways" and "PI3K/AKT Pathway" to be significantly dysregulated upon suppression of ARID2 in TP53 mutated OSCC cells. Notably, decreased ARID2 expression and increased CK8, CK18 expression leads to poor prognosis in Head and Neck cancer (HNSC) patients as revealed by Pan-Cancer TCGA data analysis. To conclude, our study is the first to demonstrate tumor suppressor role of ARID2 in TP53 mutated background indicating their cooperative role in OSCC, and also highlights its prognostic implications suggesting ARID2 as an important therapeutic target in OSCC.

Arsenic Induces Differential Neurotoxicity in Male, Female, and E2-Deficient Females: Comparative Effects on Hippocampal Neurons and Cognition in Adult Rats.

We earlier reported that arsenic induced hippocampal neuronal loss, causing cognitive dysfunctions in male rats. This neuronal damage mechanism involved an altered bone morphogenetic protein (BMP2)/Smad and brain-derived neurotrophic factor (BDNF)/TrkB signaling. Susceptibility to toxicants is often sex-dependent, and hence we studied the comparative effects of arsenic in adult male and female rats. We observed that a lower dose of arsenic reduced learning-memory ability, examined through passive avoidance and Y-maze tests, in male but not female rats. Again, male rats exhibited greater learning-memory loss at a higher dose of arsenic. Supporting this, arsenic-treated male rats demonstrated larger reduction in the hippocampal NeuN and %-surviving neurons, together with increased apoptosis and altered BMP2/Smad and BDNF/TrkB pathways compared to their female counterparts. Since the primary female hormone, estrogen (E2), regulates normal brain functions, we next probed whether endogenous E2 levels in females offered resistance against arsenic-induced neurotoxicity. We used ovariectomized (OVX) rat as the model for E2 deficiency. We primarily identified that OVX itself induced hippocampal neuronal damage and cognitive decline, involving an increased BMP2/Smad and reduced BDNF/TrkB. Further, these effects appeared greater in arsenic + OVX compared to arsenic + sham (ovary intact) or OVX rats alone. The OVX-induced adverse effects were significantly reduced by E2 treatment. Overall, our study suggests that adult males could be more susceptible than females to arsenic-induced neurotoxicity. It also indicates that endogenous E2 regulates hippocampal BMP and BDNF signaling and restrains arsenic-induced neuronal dysfunctions in females, which may be inhibited in E2-deficient conditions, such as menopause or ovarian failure.

Vision Delhi: A study of primary eye care model operational in urban slums and resettlement colonies of Delhi.

Background: Family physicians (FPs) encounter numerous patients who need eye care services. For providing eye care services at the primary level, they need to be abreast with the common disorders, their management and appropriate referral. Objectives: The aim of this study was to describe the socio-demographic and ocular morbidity profile of the beneficiaries, seasonal pattern of few ocular disorders and to find the proportion of blindness that is avoidable at the primary level. Methodology: Study was conducted in 25 vision centers across Delhi. Chart review was done in each center and retrospective data of previous 4 years was analyzed. Socio-demographic, ocular morbidity profile and trend of selected diseases was deducted and causes of blindness were determined. Results: Around 62.76% of patients were women and 78.26% were new patients. A seasonal peak of conjunctivitis was observed during the spring season. The common conditions detected by optometrists were refractive errors (34.68%), presbyopia (14.15%), cataract (14.02%), conjunctivitis (9.84%) and diseases of ocular adnexa (1.35%). In the age group ≥50 years, the proportion of patients who were blind was 2.5%, 39.0% had VI. The proportion of VI patients in all the categories was higher in women as compared to men. In patients ages ≥50 years, 81.4% of the blindness was avoidable. Conclusions: Women outnumbered men in availing services at the center and the proportion of visual impairment was also higher in them. The major causes of blindness in the older population were cataract and corneal-opacity, and it is avoidable by strengthening primary eye care services by FPs.