Epigenetic modifications in Parkinson's disease: A critical review.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder expected to increase by over 50% by 2030 due to increasing life expectancy. The disease's hallmarks include slow movement, tremors, and postural instability. Impaired protein processing is a major factor in the pathophysiology of PD, leading to the buildup of aberrant protein aggregates, particularly misfolded α-synuclein, also known as Lewy bodies. These Lewy bodies lead to inflammation and further death of dopaminergic neurons, leading to imbalances in excitatory and inhibitory neurotransmitters, causing excessive uncontrollable movements called dyskinesias. It was previously suggested that a complex interplay involving hereditary and environmental variables causes the specific death of neurons in PD; however, the exact mechanism of the association involving the two primary modifiers is yet unknown. An increasing amount of research points to the involvement of epigenetics in the onset and course of several neurological conditions, such as PD. DNA methylation, post-modifications of histones, and non-coding RNAs are the primary examples of epigenetic alterations, that is defined as alterations to the expression of genes and functioning without modifications in DNA sequence. Epigenetic modifications play a significant role in the development of PD, with genes such as Parkin, PTEN-induced kinase 1 (PINK1), DJ1, Leucine-Rich Repeat Kinase 2 (LRRK2), and alpha-synuclein associated with the disease. The aberrant epigenetic changes implicated in the pathophysiology of PD and their impact on the design of novel therapeutic approaches are the primary focus of this review.

Obesity and Depression: Common Link and Possible Targets.

Depression is among the main causes of disability, and its protracted manifestations could make it even harder to treat metabolic diseases. Obesity is linked to episodes of depression, which is closely correlated to abdominal adiposity and impaired food quality. The present review is aimed at studying possible links between obesity and depression along with targets to disrupt it. Research output in Pubmed and Scopus were referred for writing this manuscript. Obesity and depression are related, with the greater propensity of depressed people to gain weight, resulting in poor dietary decisions and a sedentary lifestyle. Adipokines, which include adiponectin, resistin, and leptin are secretory products of the adipose tissue. These adipokines are now being studied to learn more about the connection underlying obesity and depression. Ghrelin, a gut hormone, controls both obesity and depression. Additionally, elevated ghrelin levels result in anxiolytic and antidepressant-like effects. The gut microbiota influences the metabolic functionalities of a person, like caloric processing from indigestible nutritional compounds and storage in fatty tissue, that exposes an individual to obesity, and gut microorganisms might connect to the CNS through interconnecting pathways, including neurological, endocrine, and immunological signalling systems. The alteration of brain activity caused by gut bacteria has been related to depressive episodes. Monoamines, including dopamine, serotonin, and norepinephrine, have been widely believed to have a function in emotions and appetite control. Emotional signals stimulate arcuate neurons in the hypothalamus that are directly implicated in mood regulation and eating. The peptide hormone GLP-1(glucagon-like peptide- 1) seems to have a beneficial role as a medical regulator of defective neuroinflammation, neurogenesis, synaptic dysfunction, and neurotransmitter secretion discrepancy in the depressive brain. The gut microbiota might have its action in mood and cognition regulation, in addition to its traditional involvement in GI function regulation. This review addressed the concept that obesity-related low-grade mild inflammation in the brain contributes to chronic depression and cognitive impairments.

SMAC Mimetics for the Treatment of Lung Carcinoma: Present Development and Future Prospects.

BACKGROUND: Uncontrolled cell growth and proliferation, which originate from lung tissue often lead to lung carcinoma and are more likely due to smoking as well as inhaled environmental toxins. It is widely recognized that tumour cells evade the ability of natural programmed death (apoptosis) and facilitates tumour progression and metastasis. Therefore investigating and targeting the apoptosis pathway is being utilized as one of the best approaches for decades. OBJECTIVE: This review describes the emergence of SMAC mimetic drugs as a treatment approach, its possibilities to synergize the response along with current limitations as well as future perspective therapy for lung cancer. METHOD: Articles were analysed using search engines and databases namely Pubmed and Scopus. RESULT: Under cancerous circumstances, the level of Inhibitor of Apoptosis Proteins (IAPs) gets elevated, which suppresses the pathway of programmed cell death, plus supports the proliferation of lung cancer. As it is a major apoptosis regulator, natural drugs that imitate the IAP antagonistic response like SMAC mimetic agents/Diablo have been identified to trigger cell death. SMAC i.e. second mitochondria activators of caspases is a molecule produced by mitochondria, stimulates apoptosis by neutralizing/inhibiting IAP and prevents its potential responsible for the activation of caspases. Various preclinical data have proven that these agents elicit the death of lung tumour cells. Apart from inducing apoptosis, these also sensitize the cancer cells toward other effective anticancer approaches like chemo, radio, or immunotherapies. There are many SMAC mimetic agents such as birinapant, BV-6, LCL161, and JP 1201, which have been identified for diagnosis as well as treatment purposes in lung cancer and are also under clinical investigation. CONCLUSION: SMAC mimetics acts in a restorative way in the prevention of lung cancer.

The fluorosis conundrum: bridging the gap between science and public health.

Fluorosis, a chronic condition brought on by excessive fluoride ingestion which, has drawn much scientific attention and public health concern. It is a complex and multifaceted issue that affects millions of people worldwide. Despite decades of scientific research elucidating the causes, mechanisms, and prevention strategies for fluorosis, there remains a significant gap between scientific understanding and public health implementation. While the scientific community has made significant strides in understanding the etiology and prevention of fluorosis, effectively translating this knowledge into public health policies and practices remains challenging. This review explores the gap between scientific research on fluorosis and its practical implementation in public health initiatives. It suggests developing evidence-based guidelines for fluoride exposure and recommends comprehensive educational campaigns targeting the public and healthcare providers. Furthermore, it emphasizes the need for further research to fill the existing knowledge gaps and promote evidence-based decision-making. By fostering collaboration, communication, and evidence-based practices, policymakers, healthcare professionals, and the public can work together to implement preventive measures and mitigate the burden of fluorosis on affected communities. This review highlighted several vital strategies to bridge the gap between science and public health in the context of fluorosis. It emphasizes the importance of translating scientific evidence into actionable guidelines, raising public awareness about fluoride consumption, and promoting preventive measures at individual and community levels.

Older PLHIV are at Higher Cardiovascular Risk with Poor Quality of Life.

BACKGROUND: People with HIV (PLHIV) face increased cardiovascular disease (CVD) risk due to inflammation and immune activation. Aging further amplifies this risk. Limited data exist on CVD risk in older PLHIV in India despite 2.14 million PLHIV with higher CVD risk factors. METHODS: In a cross-sectional study in Bihar, India, 73 PLHIV and 30 control participants were enrolled. Demographics, social factors, clinical information, and CVD risk factors were collected. HbA1c levels and lipid profiles were analyzed, and 10-year CVD risk scores were calculated using the Framingham risk score (FRS) and Qrisk3. Quality of life (QoL) was assessed using WHOQOL- HIV-BREF. RESULTS: Results showed higher LDL levels in non-HIV older participants and higher HDL levels in younger PLHIV participants. BMI differed significantly, with higher BMI in non-HIV older individuals and lower BMI in younger PLHIV individuals. Older PLHIV participants had significantly higher mean FRS and Q-Risk scores compared to older non-PLHIV and younger PLHIV groups. Among older PLHIV participants, six had higher CVD risk per FRS, while none in the other groups were classified as high CVD risk. Psychological, social relations and spirituality domains were highly deteriorated in older PLHIV, scoring 44.48, 42.72, and 41.2, respectively. The physical domain scored 57.6, and the environment scored 52.72 in the WHOQOL-HIV bref. CONCLUSION: In conclusion, older PLHIV in Bihar, India, face higher CVD risk compared to younger PLHIV and non-HIV individuals. FRS and Q-Risk scores effectively assessed CVD risk, identifying higher risk in older PLHIV. Age and BMI were significant predictors of high CVD risk. These findings emphasize CVD risk assessment and tailored management for older PLHIV. The QoL assessment findings indicate moderate deterioration in psychological, social relations, and spirituality domains among older PLHIV individuals. These results suggest greater challenges in psychological well-being, social interactions, and spirituality compared to the overall sample. Further research with larger samples and longitudinal designs is needed to confirm and extend these findings.

Arsenic Exposure and Amyloid Precursor Protein Processing: A Focus on Alzheimer's Disease.

BACKGROUND: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition. AIMS: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease. METHODS: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer's disease through the published article from Pubmed and Scopus. DESCRIPTION: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by ß-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article. CONCLUSION: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer's disease.

Development and Validation of Knowledge Attitudes and Practices Questionnaire (Nu-KAPQ): for the assessment of Knowledge, Attitudes, and Practices Associated with Arsenic.

More than 70 million individuals have been exposed to environmental arsenic toxicity, worldwide. United Nation Children's Fund (UNICEF) policy brief -2018 report to mitigate arsenic in drinking water, emphasizes assessing, and changing the knowledge, attitudes, and practices (KAP) as one of the long-term effective solutions to be implemented as a part of surveillance strategies. This study aims to develop a valid and reliable tool to assess knowledge, attitude, and practices of arsenic and its risk in general health. A cross-sectional survey of N=449 general population was conducted in the outpatient department of Rajendra Memorial Research Institute of Medical Sciences-Indian Council for Medical Research for data collection. The construct validation of the questionnaire was done using Exploratory Factor Analysis, Confirmatory factor analysis. The Item-Content Validity Index(I-CVI) and Scale-Content Validity Index (S-CVI) Kappa scores were used to analyze the content validity of the items. The I-CVI ranges from 0.70 to 1, the and the moderate to high cumulative content validity is S-CVI/Universal Agreement=0.84; S-CVI/Average =0.96. Following the principal component analysis, the cumulative Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) was 0.91 and the three domains in the tool (Kaiser-Meyer-Olkin measure of sampling adequacy for Knowledge (0.917), Attitude (0.825) & Practices (0.80)) were within the acceptable range. The Barret's test for sphericity was (P <0.001) and was highly acceptable. The Confirmatory Factor Analysis model of Nu-KAP has demonstrated excellent model fit where, majority of fit indices has sown good fit (X2/df=1.88, Root Mean Square Error of Approximation = 0.04, Comparative Fit Index=0.98, Goodness of Fit Index = 0.93, and Tucker Lewis Index=0.977). The Cronbach's alpha of 19 item tool was 0.72. The Nu-KAPQ questionnaire demonstrated exceptional validity and reliability while also capturing and integrating all pertinent psychometric analytic domains. Conclusively, this questionnaire can be used to assess psychometric properties associated with arsenic bridging the gap in current research to understand people's perception towards arsenic, since it is a crucial component of arsenic mitigation.

Barriers to the effective management and prevention of post kala-azar dermal leishmaniasis (PKDL) in the Indian subcontinent.

Post kala-azar dermal leishmaniasis (PKDL) is a skin disease that usually occurs among individuals with a past history of visceral leishmaniasis (VL). PKDL cases act as a reservoir of parasites and may play a significant role in disease transmission. Hence, prompt detection and complete treatment of PKDL cases are crucial for the control and elimination of VL. The purpose of this review was to highlight the barriers to effective control and prevention of VL/PKDL as well as potential solutions in India. Main obstacles are lack of knowledge about the disease and its vector, poor treatment-seeking behaviours, ineffective vector control measures, lack of confirmatory diagnostics in endemic areas, limited drug choices, treatment noncompliance among patients, drug resistance, and a lack of an adequate number of trained personnel in the health system. Therefore, in order to control and successfully eliminate VL in the Indian subcontinent, early detection of PKDL cases, improved diagnosis and treatment, raising awareness, and effective vector control mechanisms are necessary.

Targeting Histone 3 Variants Epigenetic Landscape and Inhibitory Immune Checkpoints: An Option for Paediatric Brain Tumours Therapy.

Despite little progress in survival rates with regular therapies, which do not provide complete care for curing pediatric brain tumors (PBTs), there is an urgent need for novel strategies to overcome the toxic effects of conventional therapies to treat PBTs. The co-inhibitory immune checkpoint molecules, e.g., CTLA-4, PD-1/PD-L1, etc., and epigenetic alterations in histone variants, e.g., H3K27me3 that help in immune evasion at tumor microenvironment have not gained much attention in PBTs treatment. However, key epigenetic mechanistic alterations, such as acetylation, methylation, phosphorylation, sumoylation, poly (ADP)-ribosylation, and ubiquitination in histone protein, are greatly acknowledged. The crucial checkpoints in pediatric brain tumors are cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PDL1), OX-2 membrane glycoprotein (CD200), and indoleamine 2,3-dioxygenase (IDO). This review covers the state of knowledge on the role of multiple co-inhibitory immunological checkpoint proteins and histone epigenetic alterations in different cancers. We further discuss the processes behind these checkpoints, cell signalling, the current scenario of clinical and preclinical research and potential futuristic opportunities for immunotherapies in the treatment of pediatric brain tumors. Conclusively, this article further discusses the possibilities of these interventions to be used for better therapy options.

4-Methylesculetin ameliorates LPS-induced depression-like behavior through the inhibition of NLRP3 inflammasome.

The pathophysiology of depression is heavily dependent on inflammation. Evidence suggests that the etiology of depression is linked with NLRP3 inflammasome-induced inflammation. Therefore, blocking the activated NLRP3 inflammasome may be beneficial for treating depression. Due to the limitations of currently available antidepressants, it is necessary to develop novel, safe, and affordable drugs for the treatment of depression. A natural coumarin derivative named 4-methylesculetin (4-MESC) possesses anti-inflammatory properties. However, the role of 4-MESC as an antidepressant has not been elucidated. Therefore, in this study, we explored the antidepressant-like effects of 4-MESC and its underlying molecular mechanism through the modulation of the NLRP3 inflammasome. The docking and molecular dynamic simulation studies revealed that 4-MESC has a higher affinity for the NLRP3 PYD. Blood-brain barrier permeability was confirmed using the SwissADME pharmacokinetic tool. High doses (50 mg/kg) of 4-MESC significantly reduced the immobility duration in the tail-suspension test (TST) and forced swim test (FST) without changing the overall locomotor activity in the female Swiss albino mice that were subjected to lipopolysaccharide (LPS). LPS-induced pro-inflammatory cytokines such as IL-6 and TNF-α were reduced in serum and brain tissues using 4-MESC. 4-MESC's neuroprotective effects are mediated by increased brain-derived neurotrophic factor (BDNF) and decreased cortisol levels. 4-MESC markedly reduced LPS-induced elevated levels of ROS and lipid peroxidation (malondialdehyde levels) and enhanced the superoxide dismutase (SOD) activity and glutathione levels, which revealed its anti-oxidant potential against oxidative stress. 4-MESC diminished the expression levels of NF-κBp65, IL-6, NLRP3, caspase-1, gasdermin D, and IL-1ß in the hippocampus. These findings demonstrated that 4-MESC exhibited antidepressant-like effects by inhibiting the NLRP3 inflammasome. However, other antidepressant mechanisms might also be involved which require further studies.

CD4 + Count: a Variable to Be Considered to Prioritize COVID-19 Vaccination in PLHIV.

The outbreak of the COVID-19 propagates, pressurizing the healthcare system by emphasizing and worsening the inequities. While many vaccines have shown excellent efficacy in protecting the general public from the COVID-19 infection, the efficacy of these vaccines for people living with HIV (PLHIV), especially those having a different range of CD4 + T-cell, has yet to be thoroughly investigated. Few studies have uncovered the escalated infection and death rates due to the COVID-19 infection in individuals with low CD4 + T-cells. Additionally, PLHIV has a low CD4 + count; furthermore, specific CD4 + T cells for coronavirus have a vigorous Th1 role and are related to the protective antibody responses. Follicular helper T cells (TFH) are vulnerable to HIV and virus-specific CD4 & CD8 T-cells which are essential for viral infection clearance and defective immune responses which further contributes to the development of illness. The specific CD8 & CD4 + T-cell reaction to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was identified in almost all COVID-19 recovered individuals, which is related to the size of antibodies of immunoglobulin G. It has previously been demonstrated that PLHIV has decreased responses to certain vaccines and that these responses are reliant on CD4 + T-cell levels. COVID-19 vaccines will likely have a lower response or limited effect, in PLHIV having low CD4 + T-cells.

Targeting Ion Channels for the Treatment of Glioma.

BACKGROUND: Glioma refers to the most aggressive tumor in the central nervous system that starts from support cells or glial cells. The glial cell is the most common cell type in the CNS, and they insulate, surround, as well as feed, oxygen, and nutrition to the neurons. Seizures, headaches, irritability, vision difficulties, and weakness are some of the symptoms. Targeting ion channels is particularly helpful when it comes to glioma treatment because of their substantial activity in glioma genesis through multiple pathways. OBJECTIVE: In this study, we explore how distinct ion channels can be targeted for glioma treatment and summarize the pathogenic ion channels activity in gliomas. RESULTS: Current research found several side effects such as bone marrow suppression, alopecia, insomnia, and cognitive impairments for presently done chemotherapy. The involvement of research on ion channels in the regulation of cellular biology and towards improvements of glioma have expanded recognition of their innovative roles. CONCLUSION: Present review article has expanded knowledge of ion channels as therapeutic targets and detailed cellular mechanisms in the roles of ion channels in gliomas pathogenesis.

Epigenetic basis for PARP mutagenesis in glioblastoma: A review.

Several modifications in the glioblastoma genes are caused by epigenetic modifications, which are crucial in appropriate developmental processes such as self-renewal and destiny determination of neural stem cells. Poly (ADP-ribose)polymerase (PARP) is an essential cofactor involved in DNA repair as well as several other cellular functions such as transcription and chromatin shape modification. Inhibiting PARP has evolved for triggering cell damage in cancerous cells when paired with certain other anticancer drugs including temozolomide (TMZ). PARP1 is involved with in base excision repair (BER) pathway, however its functionality differs across types of tumours. Epigenomics as well as chromosomal statistics have contributed to the growth of main subgroups of glioma, which serve as foundation for the categorization of central nervous system (CNS) tumours as well as a unique classification based only on DNA methylation information, which demonstrates extraordinary diagnostic accuracy. Unfortunately, not all patients respond to PARP inhibitors (PARPi), and there is no way to anticipate who will and who will not. In this field, PARPi are one of the innovative medicines currently being explored. As a result, cancer cells that also have a homologous recombination defect become fatal synthetically. As well as preparing the tumour microenvironment for immunotherapy, PARPi may enhance the lethal effects of chemotherapy and radiotherapy. This article analyzes the justification and clinical evidence for PARPi in glioma to offer potential therapeutic approaches. Despite the effectiveness of these targeted drugs, researchers have looked into a number of resistance mechanisms as well as the growing usage of PARPi in clinical practice for the treatment of various malignancies.

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis.

Leishmaniasis is a protozoal disease declared as an endemic in areas suffering from severe malnutrition and poverty. The factors associated with poverty like low income, ecological factors, and malnutrition cause disruption in immunity and host defense increasing risk of infection. Altered resistance to infection and host susceptibility are associated with low micronutrient levels in undernourished patients. Malnutrition has been recognized as a poor predictive marker for leishmaniasis, in particular the deficiency of trace elements like zinc, iron, and vitamin A, B, C, D which has a prominent function in the regulation of innate and adaptive immunity, cell proliferation, human physiology, etc. Malnourishment can exacerbate host sensitivity and pathophysiologic intensity to infection in variety of ways, whereas infection can enhance underlying poor nutrition or enhance host vulnerability and sandfly's urge to attack specific hosts. The intensity of leishmaniasis can be influenced by body mass and micronutrient availability in the blood. Vitamin D, C, zinc, and iron are proved effective in inhibiting the growth of leishmaniasis in both amastigote or promastigote forms, either directly or by acting as precursor for a pathway which inhibits the parasite growth. This article elucidates a new perception to the crucial role of micronutrients and their probable role in the therapeutic outcomes of leishmaniasis. Since there is requirement of novel drugs to fight drug resistance and relapse of leishmaniasis, this article may pave way to understand the importance of micronutrients and their role in therapeutic outcomes of leishmaniasis.

Nutritional Aspects of People Living with HIV (PLHIV) Amidst COVID-19 Pandemic: an Insight.

Purpose of Review: This review elaborates the role of malnutrition in PLHIV (people living with HIV) in the context of COVID-19 and emphasis the need of supplementation, dietary intervention, and nutritional counselling in the post-COVID era. One of the most critical challenges among HIV/AIDS patients is malnutrition since it weakens the immune system and increases risk to opportunistic infections. In HIV (human immunodeficiency virus) infection, weight loss is prevalent due to reduced nutritional consumption, malabsorption, abnormal metabolism, and antiretroviral therapy. Sufficient nutrition is required for optimal immune function, as a result, food therapy is now considered an important adjuvant in the treatment of HIV patients. Recent Findings: Nutritional intervention, such as the use of dietary supplements, can help to prevent nutrient deficiency, lowering the death risk among malnourished HIV population. Immunocompromised individuals are at very high risk for COVID-19 and malnutrition increases the risk of infection by multiple folds. Interventions, such as nutrition education and counselling are important, to improve the condition of HIV Patients by optimising their nutritional status. Summary: A balanced diet should be one of the most important priorities in preventing PLHIV against the potentially deadly consequences of COVID-19. It is to be ensured that HIV-positive persons continue to get enough and appropriate assistance, such as nutrition and psychological counselling, in the context of COVID-19 infection. The use of telemedicine to maintain nutritional intervention can be beneficial. To meet their nutritional needs and minimise future difficulties, PLHIV infected with COVID-19 should get specialised nutritional education and counselling.

Knowledge, Attitude, and Practices among HIV/Leishmaniasis Co-Infected Patients in Bihar, India.

Visceral leishmaniasis (VL) is a serious public health concern in the Indian state of Bihar, which has been exacerbated by an increasing HIV/AIDS incidence that has resulted in poor clinical outcomes. So far, there has been no investigation into the knowledge, attitude, and practices (KAP) of people who have been subjected to hospital-based supervision for VL or HIV/VL co-infection. This study assessed the KAP toward VL infection among 210 VL-infected patients (126 participants with VL and 84 participants with HIV/VL) using a pretested standard questionnaire. The findings are summarized descriptively and KAP scores are classified dichotomously (good/poor). Multivariable logistic regression and bivariate correlation were used in the analysis. The study showed that both VL-infected and co-infected patients exhibited similar deficits in KAP scores toward VL. The HIV/VL participants who had a personal or family history of VL were more likely to have appropriate awareness of and preventive practices toward VL. The independent predictors of attitude index in HIV/VL participants were education, VL family history, and marital status. There was a weak but significant positive correlation between knowledge and practice (rs = 0.321, p<0.001), and attitude and practice (rs = 0.294, p<0.001), while knowledge was strongly correlated with attitude (rs = 0.634, p<0.001). Based on the study findings, it is recommended that treatment programs in Bihar should concentrate on strengthening KAP among VL and HIV/VL co-infected patients to prevent reinfection-related complications. Behavior change communication intervention is ideal for tackling this problem. This proposal entails building a comprehensive public health program in endemic regions.

Impact of COVID-19 on Antimicrobial Resistance in Paediatric Population: a Narrative Review.

Purpose of Review: Irrational use of antimicrobials has been reported in paediatric population during the COVID-19 time period. This may lead to potential development of antimicrobial resistance and increased morbidity and mortality among this vulnerable population. The purpose of this review is to ascertain the impact of COVID-19 pandemic on antimicrobial resistance among paediatrics and the possible strategies to minimize the menace of antimicrobial resistance. Recent Findings: Recent findings indicate that the COVID-19 pandemic has direct as well as indirect impact on the development of antimicrobial resistance among paediatric population. Summary: This review article shows the impact of COVID-19 on the development of antimicrobial resistance and strategies to prevent it with special reference to antimicrobial stewardship programmes among paediatric population.

Nasal vaccine as a booster shot: a viable solution to restrict pandemic?

The coronavirus disease 2019 (COVID-19) pandemic revolutionized the vaccine market and initiated the momentum for alternative routes of administration for vaccines. The intranasal route of immunization is one such possibility that appears to be the most promising since it has some significant advantages, particularly in the prevention of respiratory infection. To analyze and summarize the role of nasal vaccines over conventional vaccines during COVID-19 and the need for the nasal vaccine as a booster shot. In this narrative review, the required data was retrieved using keywords "COVID-19," "Intranasal," "Immunity," "Nasal spray," and "Mucosal" in databases including PubMed, Scopus, Embase, Science Direct, and Web of Sciences. The results of the study showed that the nasal vaccines were both effective and protective according to the current researches approaching during the COVID-19 period and the preclinical and clinical phase trials prove the intranasal vaccination elicits more robust and cross-protective immunity than conventional vaccines. In this narrative review article, mechanisms across the nasal mucosa will be briefly presented and the current status of nasal vaccines during the COVID-19 pandemic is summarized, and advantages over traditional vaccines are provided. Furthermore, after exploring the primary benefits and kinetics of nasal vaccine, the potential for consideration of nasal vaccine as a booster dose is also discussed.

Arsenic: a Culpable Element and a Possible Menace for HIV/AIDS Patients.

Arsenic contamination has long been recognized as one of the most harmful environmental pollutants resulting from anthropogenic activity. Apart from being an environmental toxicant or pollutant, this culpable heavy metal also has detrimental effects on human health. People throughout the world are exposed to arsenic (As) mostly through polluted drinking water. Acute inorganic arsenic (iAs) poisoning causes nausea, vomiting, stomach discomfort, and severe diarrhea. As on long-term exposure is a potent carcinogen, characterized by IARC (International Agency for Research on Cancer). As levels are high mainly in Gangetic regions due to which the people living around are suffering the consequences. The carcinogenicity of As is well established but the immunotoxicity caused by it is still unknown. Some animal model supports the toxicity of As in the immune system as well, but in humans, mainly suffering from human immunodeficiency virus (HIV), it is not well established. iAs suppresses the immune system by acting on different targets and exacerbating infections. Although animal studies have demonstrated that arsenic trioxide (As2O3) reduces viral rebound and restores CD4 + count in vivo when coupled with antiretroviral medications, elemental AS may have devastating effects on the immune system of HIV patients, making them more prone to opportunistic infections (OIs). It is well known that in later stages of HIV infection, neurological problems also complicate the conditions such as cognitive impairment and AIDS dementia complex (ADC). Along with immunotoxicity, As has the potential to damage HIV patients' brains. This article addresses the immunotoxicity of arsenic and exacerbations caused by it, along with the neurotoxicity, particularly in HIV patients residing near the Gangetic belt.

Assessment of disease burden in the arsenic exposed population of Chapar village of Samastipur district, Bihar, India, and related mitigation initiative.

Fast growing arsenic menace is causing serious health hazards in Bihar, India, with an estimated 10 million people at risk. The exposed population is often unaware of the problem, which only amplifies the burden of arsenic health effects. In the present study, we have assessed the current situation of arsenic exposure in Chapar village of Samastipur district, Bihar. The health of the inhabitants was assessed and correlated with (1) arsenic concentrations in the groundwater of individual wells and (2) arsenic concentration found in their hair and urine. Altogether, 113 inhabitants were assessed, and 113 hair, urine and groundwater samples were collected. The health study reveals that the exposure to arsenic has caused serious health hazard amongst the exposed population with pronounced skin manifestations, loss of appetite, anaemia, constipation, diarrhoea, general body weakness, raised blood pressure, breathlessness, diabetes, mental disabilities, diabetes, lumps in the body and few cancer incidences. It was found that 52% of the total collected groundwater samples had arsenic levels higher than the WHO limit of 10 µg/l (with a maximum arsenic concentration of 1212 µg/l) and the reduced arsenite was the predominant form in samples tested for speciation (N = 19). In the case of hair samples, 29% of the samples had arsenic concentrations higher than the permissible limit of 0.2 mg/kg, with a maximum arsenic concentration of 46 µg/l, while in 20% exposed population, there was significant arsenic contamination in urine samples > 50 µg/l. In Chapar village, the probability of carcinogenic-related risk in the exposed population consuming arsenic contaminated water is 100% for children, 99.1% for females and 97.3% for male subjects. The assessment report shared to the government enabled the village population to receive two arsenic filter units. These units are currently operational and catering 250 households providing arsenic-free water through piped water scheme. This study therefore identified a significant solution for this arsenic-exposed population.