Displaying publications 1 - 20 of 47 in total

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  1. Vignesh R, Pradeep P, Balakrishnan P
    Med J Malaysia, 2023 Jul;78(4):547-549.
    PMID: 37518931
    Chat Generative Pre-Trained Transformer (ChatGPT) is an artificial intelligence (AI) language model developed by OpenAI. It is trained to process vast amounts of text and engage in human-like conversational interaction with users. Being accessible by all, it is widely used and its capabilities range from language translation, summarising long texts and creative writing. This article explores the potential role of ChatGPT in medical education and the possible concerns about the misuse of this technology through a conversation with ChatGPT itself via text prompts. The implications of this technology in medical education as told by ChatGPT are interesting and seemingly helpful for both the students and the tutors. However, this could be a double-edged sword considering the risks of compromised students' integrity and concerns of over-reliance. This also calls for counter strategies and policies in place to mitigate these risks.
  2. Norshidah H, Leow CH, Ezleen KE, Wahab HA, Vignesh R, Rasul A, et al.
    Front Cell Infect Microbiol, 2023;13:1061937.
    PMID: 36864886 DOI: 10.3389/fcimb.2023.1061937
    An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.
  3. Swathirajan CR, Nandagopal P, Vignesh R, Srikrishnan AK, Goyal R, Qureshi H, et al.
    Pathog Dis, 2019 06 01;77(4).
    PMID: 31505637 DOI: 10.1093/femspd/ftz044
    HIV-1 vaccine functioning relies on successful induction of broadly neutralizing antibodies (bNAbs). CXCR3- circulatory T-follicular helper (cTfh) cells are necessary for inducing B-cells for generating bNAbs. Recent studies have suggested that CXCR3+ Tfh cells might also influence bNAb production. Plasma samples from 34 ART-Naïve HIV-1 infected individuals [long-term nonprogressors (LTNP)-19; Progressors-13] were tested against a heterologous virus panel (n = 11) from subtypes A, B, C, G, AC, BC and AE. Frequencies of CXCR3+ and CXCR3- cTfh-like cells in peripheral circulation were studied using flow cytometry. LTNP showed significantly lower CXCR3+ and higher CXCR3- cTfh-like cell frequencies, while neutralization breadth was observed to be broader in progressors. A positive correlation was observed between bNAb breadth and potency with CXCR3+PD-1+ cTfh-like cells in LTNP. Based on neutralization breadth, 9 HIV-1 infected individuals were classified as 'top neutralizers' and 23 as 'low neutralizers' and they did not show any correlations with CXCR3+ and CXCR3- cTfh-like cells. These preliminary data suggest that CXCR3+ similar to CXCR3- might possess significant functional properties for driving B-cells to produce bNAbs. Hence, an HIV vaccine which is capable of optimal induction of CXCR3+ cTfh cells at germinal centers might confer superior protection against HIV.
  4. Nandagopal P, Bhattacharya J, Srikrishnan AK, Goyal R, Ravichandran Swathirajan C, Patil S, et al.
    J Gen Virol, 2018 Mar;99(3):379-392.
    PMID: 29458681 DOI: 10.1099/jgv.0.001016
    Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.
  5. Barathan M, Mohamed R, Vadivelu J, Chang LY, Vignesh R, Krishnan J, et al.
    Cell Immunol, 2017 03;313:1-9.
    PMID: 28104239 DOI: 10.1016/j.cellimm.2016.12.002
    Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.
  6. Swathirajan CR, Rameshkumar MR, Solomon SS, Vignesh R, Balakrishnan P
    J Glob Antimicrob Resist, 2019 03;16:274-277.
    PMID: 30389636 DOI: 10.1016/j.jgar.2018.10.019
    OBJECTIVES: Pseudomonas aeruginosa is an important aetiological agent causing pneumonia, urinary tract infections and bacteraemia. High antibiotic use in nosocomial settings and for immunocompromised conditions results in increasing multidrug resistance. This study analysed the antimicrobial resistance profile of P. aeruginosa isolates in an HIV setting.

    METHODS: A total of 7386 clinical specimens were collected from HIV patients attending YRG CARE from 2010-2017. P. aeruginosa isolated from clinical specimens were identified conventionally, and antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method.

    RESULTS: A total of 260 P. aeruginosa strains were isolated, with 165 P. aeruginosa (63.5%) being isolated from hospitalised patients. A higher incidence of P. aeruginosa infection (25.8%) was observed in 2017, and most of the P. aeruginosa were isolated from sputum specimens (57.3%). A high level of resistance was noted to ceftazidime (49.6%), followed by ticarcillin (41.5%). Imipenem and meropenem resistance was observed in 15.0% and 16.9% of P. aeruginosa isolates, respectively. A high rate of imipenem resistance was noted in 2016 (46.2%) and a high rate of meropenem resistance was noted in 2017 (20.5%). An increasing resistance rate of P. aeruginosa was observed against aztreonam, cefepime, levofloxacin, meropenem, piperacillin, piperacillin/tazobactam, ticarcillin and tobramycin from 2010 to 2017.

    CONCLUSION: A constant increase in drug-resistant P. aeruginosa isolates from HIV patients was observed from 2010 to 2017. Findings from this study urge the need for periodical monitoring and surveillance of the P. aeruginosa resistance profile, especially in hospitalised and immunocompromised patients in resource-limited settings.

  7. Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  8. Selvavinayagam ST, Karishma SJ, Hemashree K, Yong YK, Suvaithenamudhan S, Rajeshkumar M, et al.
    PMID: 38076717 DOI: 10.1016/j.lansea.2023.100272
    BACKGROUND: Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India.

    METHODS: Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients.

    FINDINGS: Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population.

    INTERPRETATION: Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants.

    FUNDING: National Health Mission (India), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA).

  9. Balakrishnan P, Girija ASS, Kannan I, Vignesh R, Shankar EM, Sucharitha ST
    Indian J Med Microbiol, 2023;43:49-50.
    PMID: 36280566 DOI: 10.1016/j.ijmmb.2022.10.004
  10. Yong YK, Wong WF, Vignesh R, Chattopadhyay I, Velu V, Tan HY, et al.
    Front Immunol, 2022;13:889196.
    PMID: 35874775 DOI: 10.3389/fimmu.2022.889196
    The dynamics of host-virus interactions, and impairment of the host's immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.
  11. Ramesh Kumar MR, Arunagirinathan N, Srivani S, Dhanasezhian A, Vijaykanth N, Manikandan N, et al.
    Microb Drug Resist, 2017 Jul;23(5):602-608.
    PMID: 27854149 DOI: 10.1089/mdr.2016.0034
    The antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), is generally used for prophylaxis in HIV individuals to protect them from Pneumocystis jiroveci infection. Long-term use of TMP-SMX develops drug resistance among bacteria in HIV patients. The study was aimed to detect the TMP-SMX resistance genes among gram-negative bacteria from HIV patients. TMP-SMX-resistant isolates were detected by the Kirby-Bauer disc diffusion method. While TMP resistance genes such as dfrA1, dfrA5, dfrA7, and dfrA17 and SMX resistance genes such as sul1 and sul2 were detected by multiplex PCR, class 1 and class 2 integrons were detected by standard monoplex PCR. Of the 151 TMP-SMX-resistant bacterial isolates, 3 were positive for sul1 alone, 48 for sul2 alone, 11 for dfrA7 alone, 21 for sul1 and sul2, 1 for sul1 and dfrA7, 23 for sul2 and dfrA7, 2 for sul2 and dfrA5, 41 for sul1, sul2, and dfrA7, and 1 for sul2, dfrA5, and dfrA7. Of 60 TMP-SMX-resistant isolates positive for integrons, 44 had class 1 and 16 had class 2 integrons. It was found that the prevalence of sul genes (n = 202; p 
  12. Vignesh, R., Theingi, M.M., Soe, San, Ooi, P.C., Ma, Nwet
    MyJurnal
    Introduction: Congenital talipes equinovarus (CTEV), commonly known as the ‘club foot’ is a developmental disorder of the lower limb that is related with socioeconomic difficulties. Ponseti method is considered as the most popular and successful method of treatment for CTEV children. This study was aimed to evaluate the severity and monitoring the progress of initial treatment of CTEV children.

    Materials and methods: Forty two patients with 58 idiopathic CTEV feet treated at a hospital outpatient clinic from January 2017 to February 2018 were included in the study. Ponseti method and Pirani score system were used and the results were calculated after wearing brace for three months duration at the end of serial casting.

    Results: The patients in the study were in the age range of 14 days to 12 months. The mean number of changing of casting was 7.2 times. Casts were changed 1.9 times more in the severe cases than mild cases. Thirty six (85.7%) cases needed percutaneous tenotomy. There was no need to perform tenotomy for the mild cases. The initial achievement rate was 90.5 % and there were 9.5 % relapsed cases because of incorrect wearing of the brace. Statistically significant score differences were seen before and after treatment (P-value
  13. Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.
    J Med Virol, 2024 Feb;96(2):e29456.
    PMID: 38329187 DOI: 10.1002/jmv.29456
    A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
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