Assessment of the Knowledge, Attitudes, and Practices of Indian Medical Students Towards Coronavirus Disease 2019 (COVID-19) After Two Doses of Vaccination and Their Approach Towards the Third (Booster) Dose.

Background and objectives Medical students not only directly impact coronavirus disease 2019 (COVID-19) transmission due to their behavior and perceptions but also play an important role in influencing the behavior and vaccine intentions of their families and the community at large. The study's objective was to assess the knowledge, attitudes, and practices of medical students who have completed two doses of the COVID-19 vaccine towards the disease and their approach towards the third (booster) dose. Methods A total of 705 individual responses were obtained from a cross-sectional web-based study deployed using Google Forms. After getting consent and basic information, data was obtained regarding knowledge of the disease, attitudes towards the disease, and practices regarding the same. The mean score was calculated for the above different categories and compared with their respective cut-offs using a one-sample t-test. Data was also collected regarding their approach towards the booster dose of the COVID-19 vaccine, and the proportion of each response for different categories of questions was calculated. Results Participants were found to have mean scores in the range of moderate knowledge in the first part (47.67±4.49) and the second part (6.96±1.10) of the questionnaire and moderate practices (30.6±4.27) regarding COVID-19 disease. However, they had a mean score in the range of low attitude (39.79±4.07). The majority of participants acknowledge the role of vaccines in preventing the severity and spread of the disease (71.95%) and its effect on workers and medical professionals (60.26%). Mixed opinions were obtained for concerns regarding its pre-market testing and adverse effects and the government's vaccination policy. Interpretation and conclusion Responses of the medical students obtained in this study were majorly positive and in accordance with pre-vaccination studies concerning knowledge and practices. However, the low mean score in attitude obtained can be possibly explained due to their lack of direct exposure to patient management during the pandemic. The majority of participants had a positive response towards the use of the vaccine and the effectiveness of the booster dose, but concerns regarding pre-market testing, adverse effects, and the government's vaccination policy suggested the role of awareness campaigns and government endeavors to curb the same.

Review of applications of artificial intelligence (AI) methods in crop research.

Sophisticated and modern crop improvement techniques can bridge the gap for feeding the ever-increasing population. Artificial intelligence (AI) refers to the simulation of human intelligence in machines, which refers to the application of computational algorithms, machine learning (ML) and deep learning (DL) techniques. This is aimed to generalise patterns and relationships from historical data, employing various mathematical optimisation techniques thus making prediction models for facilitating selection of superior genotypes. These techniques are less resource intensive and can solve the problem based on the analysis of large-scale phenotypic datasets. ML for genomic selection (GS) uses high-throughput genotyping technologies to gather genetic information on a large number of markers across the genome. The prediction of GS models is based on the mathematical relation between genotypic and phenotypic data from the training population. ML techniques have emerged as powerful tools for genome editing through analysing large-scale genomic data and facilitating the development of accurate prediction models. Precise phenotyping is a prerequisite to advance crop breeding for solving agricultural production-related issues. ML algorithms can solve this problem through generating predictive models, based on the analysis of large-scale phenotypic datasets. DL models also have the potential reliability of precise phenotyping. This review provides a comprehensive overview on various ML and DL models, their applications, potential to enhance the efficiency, specificity and safety towards advanced crop improvement protocols such as genomic selection, genome editing, along with phenotypic prediction to promote accelerated breeding.

Utilization of DNA and 2D metal oxide interaction for an optical biosensor.

The efficient monitoring and early detection of viruses may provide essential information about diseases. In this work, we have highlighted the interaction between DNA and a two-dimensional (2D) metal oxide for developing biosensors for further detection of viral infections. Spectroscopic measurements have been used to probe the efficient interactions between single-stranded DNA (ssDNA) and the 2D metal oxide and make them ideal candidates for detecting viral infections. We have also used fully atomistic molecular dynamics (MD) simulation to give a microscopic understanding of the experimentally observed ssDNA-metal oxide interaction. The adsorption of ssDNA on the inorganic surface was found to be driven by favourable enthalpy change, and 5'-guanine was identified as the interacting nucleotide base. Additionally, the in silico assessment of the conformational changes of the ssDNA chain during the adsorption process was also performed in a quantitative manner. Finally, we comment on the practical implications of these developments for sensing that could help design advanced systems for preventing virus-related pandemics.

A Comprehensive Roadmap Towards the Generation of an Influenza B Reporter Assay Using a Single DNA Polymerase-Based Cloning of the Reporter RNA Construct.

The mini-genome reporter assay is a key tool for conducting RNA virus research. However, procedural complications and the lack of adequate literature pose a major challenge in developing these assay systems. Here, we present a novel, yet generic and simple, cloning strategy for the construction of an influenza B virus reporter RNA template and describe an extensive standardization of the reporter RNP/polymerase activity assay for monitoring viral RNA synthesis in an infection-free setting. Using this assay system, we showed for the first time the effect of viral protein NS1 and host protein kinase C delta (PKCD) on influenza B virus RNA synthesis. In addition, the assay system showed promising results in evaluating the efficacy of antiviral drugs targeting viral RNA synthesis and virus propagation. Together, this work offers a detailed protocol for the standardization of the influenza virus minigenome assay and an excellent tool for screening of host factors and antivirals in a fast, user-friendly, and high-throughput manner.

Targeting an evolutionarily conserved "E-L-L" motif in the spike protein to develop a small molecule fusion inhibitor against SARS-CoV-2.

As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key towards sustenance. Here, we identify an evolutionary conserved E-L-L motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing the post-fusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this E-L-L motif resulting in effective inhibition of SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy towards blocking S protein-mediated viral entry, mutations within the E-L-L motif rendered the protein completely resistant to the drug, establishing its specificity towards this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective towards all major variants of concerns of SARS-CoV-2 including beta, kappa, delta, and omicron. Together, we show that this conserved essential E-L-L motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.

Green Light-Activated Single-Component Organic Fluorescence-Based Nano-Drug Delivery System for Dual Uncaging of Anticancer Drugs.

Developing green or red light-activated drug delivery systems (DDSs) for cancer treatment is highly desirable. Herein, we have reported a green light-responsive single component-based organic fluorescence nano-DDS by simply anchoring 2-hydroxy-6-naphthacyl (phototrigger) on both sides of the 1,5-diaminonaphthalene (DAN) chromophore. This green light (λ ≥ 500 nm)-activated DDS released two equivalents of the anticancer drug (valproic acid) in a spatio-temporally controlled manner. Our photoresponsive DDS [DAN-bis(HO-Naph-VPA)] exhibited interesting properties such as excited-state intramolecular proton transfer (ESIPT) accompanied with aggregation-induced emission (AIE) phenomena. AIE initiated the photorelease, and ESIPT enhanced the rate of the photorelease. Further, in vitro studies revealed that our green light-activated nano-DDS exhibited good cytocompatibility, excellent cellular internalization, and effective cancer cell killing ability.

The Species-Specific 282 Residue in the PB2 Subunit of the Polymerase Regulates RNA Synthesis and Replication of Influenza A Viruses Infecting Bat and Nonbat Hosts.

Bat influenza viruses are genetically distant from classical influenza A viruses (IAVs) and show distinct functional differences in their surface antigens. Nevertheless, any comparative analyses between bat and classical IAV RNA polymerases or their specific subunits are yet to be performed. In this work, we have identified signature residues present in the bat influenza virus polymerase which are responsible for its altered fitness in comparison to the classical IAVs. Through comparative sequence and structural analysis, we have identified specific positions in the PB2 subunit of the polymerase, with differential amino acid preferences among bat and nonbat IAVs. Functional screening helped us to focus upon the previously uncharacterized PB2-282 residue, which is serine in bat virus but harbors highly conserved glutamic acid in classical IAVs. Introduction of E282S mutation in the human-adapted PB2 (influenza A/H1N1/WSN/1933) drastically reduces polymerase activity and replication efficiency of the virus in human, bat, and canine cells. Interestingly, this newly identified PB2-282 residue within an evolutionary conserved "S-E-S" motif, present across different genera of influenza viruses and serving as a key regulator of RNA synthesis activity of the polymerase. In contrast, bat influenza viruses harbor an atypical "S-S-T" motif at the same position of PB2, alteration of which with the human-like "S-E-T" motif significantly enhances its (H17N10/Guatemala/164/2009) polymerase activity in human cells. Together, our data indicate that the PB2-S282 residue may serve as an inherent restriction element of the bat virus polymerase, limiting its activity in other host species. IMPORTANCE Influenza A viruses are known for their ability to perform cross-species transmission, facilitated by amino acid alterations either in the surface antigen hemagglutinin (HA) or in the polymerase subunit PB2. Recent isolation of influenza A-like viruses from bats raised concern about their epizootic and zoonotic potential. Here, we identify a novel species-specific signature present within the influenza virus polymerase that may serve as a key factor in adaptation of influenza viruses from bat to nonbat host species. The PB2-282 residue, which harbors a highly conserved glutamic acid for influenza viruses across all genera (A, B, C, and D), encompasses an atypical serine in the case of bat influenza viruses. Our data show that the human-adapted polymerase, harboring a bat-specific signature (PB2-S282,) performs poorly, while bat PB2 protein, harboring a human-specific signature (PB2-E282), shows increased fitness in human cells.

Targeting an evolutionarily conserved "E-L-L" motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2.

As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved "Ex3Lx6L" ("E-L-L") motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this "E-L-L" motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the "E-L-L" motif rendered the protein completely resistant to the drug, establishing its specificity toward this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective toward all major variants of concerns of SARS-CoV-2, including Beta, Kappa, Delta, and Omicron. Together, we show that this conserved essential "E-L-L" motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.

Piecewise Isothermal Nucleic Acid Testing (PINAT) for Infectious Disease Detection with Sample-to-Result Integration at the Point-of-Care.

We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagnosing pathogen-associated infections, empowered by an illustrative novel methodology that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse transcription cum amplification protocol for detecting viral RNA. In a point-of-care format, this test is executable in a unified single-step, single-chamber procedure, leading to seamless sample-to-result integration in an inexpensive, scalable, pre-programmable, and customizable portable device, with mobile-app-integrated interpretation and analytics involving minimal manually operative procedures. The test exhibited a high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection by the Indian Council of Medical Research (ICMR), and subsequently using 170 double-blind patient samples in a point-of-care format outside controlled laboratory settings as performed by unskilled technicians in an organized clinical trial. We also established its efficacy in detecting Influenza A infection by performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based molecular diagnostic procedures and the elegance of common rapid tests renders the method ideal for deployment in resource-limited settings towards catering the needs of the underserved.

Clinical outcomes of post-renal transplant patients with COVID-19 infection in the ICU: A single-center case series.

Most of the post-renal transplant patients are taking immunosuppressive medications, including calcineurin inhibitors, anti-proliferative agents, and steroids. This case series highlights the clinical characteristics and outcomes of eight post-renal transplant patients with severe COVID-19 infection admitted to the intensive care unit.

Understanding the molecular evolution of tiger diversity through DNA barcoding marker ND4 and NADH dehydrogenase complex using computational biology.

BACKGROUND: Currently, Tigers (the top predator of an ecosystem) are on the list of endangered species. Thus the need is to understand the tiger's population genomics to design their conservation strategies. OBJECTIVE: We analyzed the molecular evolution of tiger diversity using NADH dehydrogenase subunit 4 (ND4), a significant electron transport chain component. METHODS: We have analyzed nucleotide composition and distribution pattern of ND genes, molecular evolution, evolutionary conservation pattern and conserved blocks of NADH, phylogenomics of ND4, and estimating species divergence, etc., using different bioinformatics tools and software, and MATLAB programming and computing environment. RESULTS: The nucleotide composition and distribution pattern of ND genes in the tiger genome demonstrated an increase in the number of adenine (A) and a lower trend of A+T content in some place of the distribution analysis. However, the observed distributions were not significant (P > 0.05). Evolutionary conservation analysis showed three highly align blocks (186 to 198, 406 to 416, and 527 to 545). On mapping the molecular evolution of ND4 among model species (n = 30), we observed its presence in a broader range of species. ND4 based molecular evolution of tiger diversity and time divergence for a tiger (20 different other species) shows that genus Panthera originated more or less at a similar time. CONCLUSIONS: The nucleotide composition and nucleotide distribution pattern of tiger ND genes showed the evolutionary pattern and origin of tiger and Panthera lineage concerning the molecular clock, which will help to understand their adaptive evolution.

Prevalence of Intestinal Parasitosis among Under-Five Children in a Rural Community of Purba Bardhaman District, West Bengal.

CONTEXT: Intestinal parasitosis (IP), a group of diseases caused by one or more species of protozoa and helminths, is still considered a neglected tropical disease and a public health concern in India. Poor sanitation and unhygienic conditions largely contribute to sustained transmission, primarily among children, adversely affecting health and development. The problem needs area-specific assessment and interventions. AIMS: The present study aimed at determining the prevalence of IP and its correlates among under-five children in a rural community of Purba Bardhaman district, West Bengal, India. SETTINGS AND DESIGN: A descriptive cross-sectional study was conducted in Bhatar Block of Purba Bardhaman district. SUBJECTS AND METHODS: Mothers/caregivers of 294 under-five children (selected through multistage sampling) were interviewed for background characteristics at the household level, and stool samples from each child were collected, transported, and examined for ova/parasite/cysts following standard guidelines. STATISTICAL ANALYSIS USED: Statistical analysis of the data obtained was done using SPSS (V20). RESULTS: The overall prevalence of IP was 17.0%. Majority of the intestinal parasites were protozoa (42, 84%), of which the most common was Giardia lamblia (24, 48.0%). Age of the child and practice of defecation showed a significant association with IP on logistic regression. CONCLUSIONS: Protozoa, mainly G. lamblia, contributes for majority of intestinal parasitic infections among the study population, and children belonging to the age group of 25-60 completed months and with open-field defecation practice have higher risk of acquiring them.

Epigenetic modifications of DAPK and p16 genes contribute to arsenic-induced skin lesions and nondermatological health effects.

Over 26 million people in West Bengal, India, are exposed to very high levels of arsenic through drinking water, leading to several deleterious endpoints including cancers. To elucidate the role of promoter methylation in arsenic-induced dermatological and nondermatological health effects, methylation status of p16 and DAPK genes was determined. A case-control study was conducted involving 72 individuals with arsenic-induced skin lesions (cases) and 50 individuals without skin lesions (controls), having similar arsenic exposure through drinking water. Methylation status was determined by bisulfite conversion of genomic DNA and methylation-specific PCR. Expression of the genes was determined by real-time PCR and Western blot analysis. Associations between the promoter methylation status and nondermatological health effects were determined from epidemiological survey data. Significant hypermethylation was found in the promoters of both DAPK and p16 genes in the cases compared with the controls resulting in downregulation of both the genes in the cases. There was a 3.4-fold decrease in the expression of death-associated protein kinase and 2.2-fold decrease in gene expression of p16 in the cases compared to the controls, the lowest expression being in the cancer tissues. Promoter hypermethylation of the genes was also associated with higher risk of developing arsenic-induced skin lesions, peripheral neuropathy, ocular and respiratory diseases. This study for the first time makes an attempt to correlate epigenetic modifications of the tumor suppressor genes with dermatological and nondermatological health outcomes in a population chronically exposed to arsenic.

Association of NALP2 polymorphism with arsenic induced skin lesions and other health effects.

Prolonged consumption of arsenic-laden water above the threshold limit of 10µg/L causes a plethora of dermatological and non-dermatological multi-organ health problems, including cancer and death. Among several mechanisms of arsenic-induced toxicity and carcinogenicity studied so far, role of arsenic in impairment of immune system is less understood. Epidemiological data, animal model as well as cell line based studies have indicated that arsenic targets immune system and is associated with characteristic immunosupression, which may further adversely affect respiratory function. However, to the best of our knowledge, there is no study with respect to arsenic susceptibility investigating the role of genetic variation having immunological function. Hence, we have recruited a total of 432 arsenic-exposed individuals, of which 219 individuals with characteristic arsenic-induced skin lesions (cases) and 213 individuals without arsenic-induced skin lesion(controls), from arsenic-exposed districts of West Bengal, India. To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) in NALP2 gene, an important component of inflammasome complex, we screened the entire coding region (exon) in all the study participants. Among 9 SNPs found in NALP2 gene, the A1052E polymorphism (at least with one minor allele), was significantly overrepresented in controls and hence implies decreased risk toward the development of skin lesions [OR=0.67, 95% CI: 0.46-0.97]. Since, development of non-dermatological health effects are also important factor to properly look into, we have attempted to correlate the genetic variation of NALP2 with the extent of cytogenetic damage as measured by chromosomal aberration assay and adverse health effects including peripheral neuropathy, eye problem and respiratory diseases in the study population. We observed individuals with the protective genotype had less chromosomal aberration (p<0.05), and were also less susceptible toward arsenic-related respiratory diseases [OR=0.47; 95%CI: 0.23-0.89]. These findings suggest that NALP2 A1052E SNP plays an important role toward development of arsenic-induced skin lesions, chromosomal damage and respiratory diseases.

Arsenic-induced toxicity and carcinogenicity: a two-wave cross-sectional study in arsenicosis individuals in West Bengal, India.

In the state of West Bengal in India, over 26 million individuals are exposed to arsenic via drinking water. Dermatological, non-dermatological disorders and cancers are associated with arsenic toxicity. Of late, there has been a decrease in the arsenic concentration in drinking water owing to governmental efforts, raising the possibility of remediation. A cross-sectional study was conducted, where 189 arsenicosis and 171 unexposed individuals were recruited at two time points, (2005-06 and 2010-11) with concomitant decrease in the level of arsenic exposure via drinking water in the arsenicosis group in 2010-11. Parameters studied included dermatological, non-dermatological health status and cytogenetic damage. Decrease of arsenic exposure (190.1 µg/l to 37.94 µg/l) resulted in significant decline in the number of individuals having dermatological disorders (P<0.01) and in the severity of each dermatological outcome (P<0.0001). Micronucleus formation in urothelial cells and lymphocytes decreased significantly (P<0.001). However, there was a significant (P<0.001) rise in the incidence of each of the non-dermatological diseases, that is, peripheral neuropathy, conjunctivitis and respiratory distress over the period. Thirteen (6.87%) of the initially recruited arsenicosis individuals died of cancer, in this period. Remediation by arsenic-safe drinking water can reduce dermatological manifestations and cytogenetic insult; but is unable to counter the non-dermatological symptoms.

Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India.

BACKGROUND: Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. METHODS: Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. RESULTS: Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. CONCLUSIONS: Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

Polymorphisms in the TNF-α and IL10 gene promoters and risk of arsenic-induced skin lesions and other nondermatological health effects.

In West Bengal, India, at present, more than 26 million people are exposed to arsenic through drinking water. Among them, only 15-20% manifest arsenic-induced noncancerous, precancerous, and cancerous skin lesions, indicating that genetic variants play important role in arsenic susceptibility. Chronic arsenic exposure has been associated with impairment of immune systems in the exposed individuals. Because cytokines are important immune mediators, alteration in expression of these gene products may lead to arsenic-specific disease manifestations. The aim of the present work was to investigate the association between the TNF-α-308G>A (rs1800629) and IL10 -3575T>A (rs1800890) polymorphisms and arsenic-induced dermatological and nondermatological health outcomes. A case-control study was conducted in West Bengal, India, involving 207 cases with arsenic-induced skin lesions and 190 controls without skin lesions having similar arsenic exposure. The polymorphisms were determined using conventional PCR-sequencing method. ELISA was done to determine the serum levels of the two cytokines tumor necrosis factor α (TNF-α) and interleukin 10 (IL10). Associations between the polymorphisms studied and nondermatological health effects in the study subjects were determined from our epidemiological survey data. Individuals with GA/AA (-308 TNF-α) and TA/AA (-3575 IL10) genotypes were at higher risk of developing arsenic-induced skin lesions, ocular, and respiratory diseases. Also the -308 TNF A allele corresponded to a higher production of TNF-α, and -3575 IL10 A allele corresponded to a lower production of IL10. Thus, the polymorphisms studied impart significant risk toward development of arsenic-induced dermatological and nondermatological health effects in the chronically exposed population of West Bengal, India.

Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism.

Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR=0.45, 95% CI: 0.30-0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30-0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40-0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis.

Chronic arsenic exposure impairs macrophage functions in the exposed individuals.

INTRODUCTION: Owing to the established roles of human macrophages in immune defense, we investigated the effect of chronic arsenic exposure upon these major hematopoietic cells in 70 arsenic-exposed individuals with skin lesions and 64 unexposed individuals. METHODS: Human monocyte-derived macrophages were prepared from peripheral blood mononuclear cells, by culture of the adherent cells for 6 days in medium supplemented with granulocyte-monocyte colony stimulating factor. Parameters studied included cell adhesion capacity, expression of CD54 and F-actin, nitric oxide production, phagocytic capacity, and effect of arsenic on Rho A-ROCK pathway. RESULTS: In macrophages of exposed individuals when compared to unexposed group, there was cell rounding accompanied with a significant (p < 0.001) loss of cell adhesion capacity, decrease in nitric oxide production, impaired phagocytic capacity, and decreased CD 54 and F-actin expression. Additionally, chronic arsenic exposure affected Rho A-ROCK pathway which in turn impaired macrophage functions. DISCUSSION AND CONCLUSION: These altogether could contribute significantly to arsenic-induced immunosuppression observed in the arsenic-exposed individuals.