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  1. Ansari S, Ansari MS, Satsangee SP, Jain R
    Anal Chim Acta, 2019 Jan 10;1046:99-109.
    PMID: 30482307 DOI: 10.1016/j.aca.2018.09.028
    Ranolazine (RZ) is an anti-anginal drug with a distinct mechanism of action and widely employed in patients with chronic angina. Its measurement is essential in clinical environment to ensure adequate drug level and understand the redox mechanism which gives an idea of in-vivo fate of the drug. In view of this, an exemplary voltammetric approach is proposed here for determination of RZ utilizing glassy carbon electrode (GCE) fabricated with WO3 decorated graphene nanocomposite. The structural and morphological characterizations of modifier were made by employing XRD, FESEM, EDAX, HRTEM, XPS, Raman and FT-IR spectroscopy which revealed successful formation of the nanocomposite. As a result of high electrical conductivity and large effective surface area of WO3 nanoparticles and graphene nanosheets, the developed sensor WO3/Graphene/GCE displayed effectual and unrelenting electron interceding behavior exhibiting higher peak currents at lower potentials for RZ oxidation. Using square wave voltammetry, the drug showcased well-defined voltammetric response in Britton-Robinson buffer at pH 4.5 in concentration range from 0.2-1.4 μM and 1.4-14 μM with the low detection limit of 0.13 μM. The developed protocol was then implemented successfully to quantify RZ in commercially accessible pharmaceutical tablets with satisfactory recovery (99.8%-100.2%). The experimental results illustrated the applicability of the fabricated sensor for drug quality control and clinical analysis along with pharmacokinetic studies.
  2. Chung CCY, Ng YNC, Jain R, Chung BHY
    Orphanet J Rare Dis, 2021 03 05;16(1):119.
    PMID: 33673852 DOI: 10.1186/s13023-021-01766-9
    BACKGROUND: This study assesses the areas and extent of impact of the Coronavirus Disease of 2019 (COVID-19) pandemic on rare disease (RD) organisations in the Asia Pacific region. There is no existing literature that focuses on such impact on RD organisations in any jurisdictions, nor RD populations across multiple jurisdictions in the Asia Pacific region. A cross-sectional survey was distributed to RD organisations between April and May 2020. Quantitative and qualitative data on the impact of COVID-19 on RD organisations and patients were collected from the organisation representative's perspective. Qualitative data was analysed using thematic analysis. A follow-up focus group meeting was conducted in August 2020 to validate the survey findings and to discuss specific needs, support and recommendations for sustainable healthcare systems during the pandemic.

    RESULTS: A total of 80 RD organisations from Australia, Hong Kong Special Administrative Region of China, India, Japan, mainland China, Malaysia, New Zealand, the Philippines, Singapore and Taiwan participated in the study. Of all, 89% were concerned about the impact of pandemic on their organisations. Results indicate that 63% of the organisations functioned at a reduced capacity and 42% stated a decrease in funding as their biggest challenge. Overall, 95% believed their patients were impacted, particularly in healthcare access, social lives, physical health, psychological health and financial impact. Specifically, 43% identified the reduced healthcare access as their top impact, followed by 26% about the impact on daily living and social life. Focus group meeting discussed differential impact across jurisdictions and point towards telemedicine and digitalisation as potential solutions.

    CONCLUSIONS: This serves as the first study to assess the impact of COVID-19 on RD patients and organisations across multiple jurisdictions in the Asia Pacific region, identifying major themes on the impact on both RD patients and organisations. By including 80 organisations from ten jurisdictions, our study presents the most comprehensive assessment of the pandemic's impact to date. It highlights the need for mental health support and sheds light on moving towards telemedicine and digitalisation of organisation operation, which constitutes a sustainable model in times of pandemics and beyond.

  3. Singhai M, Jain R, Jain S, Bala M, Singh S, Goyal R
    Ann Glob Health, 2021;87(1):102.
    PMID: 34712599 DOI: 10.5334/aogh.3431
    Background: Nipah virus (NiV) first emerged in 1998 in Malaysia, causing an outbreak of respiratory illness and encephalitis in pigs. Pig-to-human transmission of NiV associated with severe febrile encephalitis was described, and it was thought to occur through close contact with infected animals. The first outbreak was reported in India in Siliguri, West Bengal in 2001 followed by Nadia, West Bengal and adjoining areas of Bangladesh in 2007, where an intermediate animal host was not identified, suggesting bat-to-human and human-to-human transmissions. Although it is extremely difficult to document the spillover event and ascertain crossing of trans-natural boundaries by bats and bringing new viruses in an unexposed population, efforts for source identification are important to understand the epidemiology of disease. As the disease transcends beyond one species and has shown to infect humans, it therefore requires the 'One Health approach' in which multiple sectors coordinate and work together to achieve better public health outcomes.

    Objective: We summarize the re-emergence and response of the Nipah virus outbreaks (NiVD) in Kerala, India, about 1800 kms away, a decade later in 2018 and 2019. The paper recapitulates involvement of various stakeholders from the Ministry of Health and Family Welfare, Directorate of Health Research, Indian Council of Agricultural Research, State Health Department, State Animal Husbandry, District Administration, and multidisciplinary response mechanism during the NiVD outbreaks of 2018 and 2019.

    Methods: Information was collected from the Press Information Bureau (PIB), media/weekly alerts from the Integrated Disease Surveillance Programme (IDSP), news articles from print and electronic media, newsletters, advisories from the National Centre for Disease Control (NCDC), Disease Outbreak News (DON), World Health Organization (WHO), and published papers from various stakeholders.

    Findings & Conclusion: The evidence of NiV in humans and bats, with samples collected from the outbreak sites, was laboratory confirmed. The multidisciplinary response mechanisms during the 2018 outbreak helped in further understanding the importance of the One Health approach for systemic and streamlined response utilizing existing surveillance systems. This was of utmost help in the subsequent outbreak of the disease that occurred during 2019, wherein there was no documented spread of disease from the index case and no mortality was observed. This success reiterates the need for institutionalizing the involvement and cooperation of various departments and organizations during public health emergencies, especially of Zoonotic diseases, using the One Health approach.

  4. Ansari S, Ansari MS, Satsangee SP, Jain R
    J Pharm Anal, 2021 Feb;11(1):57-67.
    PMID: 33717612 DOI: 10.1016/j.jpha.2020.03.013
    In the present work, a chemically modified electrode has been fabricated utilizing Bi2O3/ZnO nanocomposite. The nanocomposite was synthesized by simple sonochemical method and characterized for its structural and morphological properties by using XRD, FESEM, EDAX, HRTEM and XPS techniques. The results clearly indicated co-existence of Bi2O3 and ZnO in the nanocomposite with chemical interaction between them. Bi2O3/ZnO nanocomposite based glassy carbon electrode (GCE) was utilized for sensitive voltammetric detection of an anti-biotic drug (balofloxacin). The modification amplified the electroactive surface area of the sensor, thus providing more sites for oxidation of analyte. Cyclic and square wave voltammograms revealed that Bi2O3/ZnO modified electrode provides excellent electrocatalytic action towards balofloxacin oxidation. The current exhibited a wide linear response in concentration range of 150-1000 nM and detection limit of 40.5 nM was attained. The modified electrode offered advantages in terms of simplicity of preparation, fair stability (RSD 1.45%), appreciable reproducibility (RSD 2.03%) and selectivity. The proposed sensor was applied for determining balofloxacin in commercial pharmaceutical formulations and blood serum samples with the mean recoveries of 99.09% and 99.5%, respectively.
  5. Tassaneeyakul W, Kumar S, Gaysonsiri D, Kaewkamson T, Khuroo A, Tangsucharit P, et al.
    Int J Clin Pharmacol Ther, 2010 Sep;48(9):614-20.
    PMID: 20860915
    OBJECTIVES: To compare the bioavailability of two risperidone orodispersible tablet products, Risperidone 1 mg Mouth dissolving tablet, Ranbaxy (Malaysia) Sdn. Bhd., Malaysia, as a test product and Risperdal 1 mg Quicklet, Janssen Ortho LLC, Gurabo, Puerto Rico, as a reference product, in healthy male volunteers under fasting condition.

    MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover with a washout period of 2 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h following drug administration. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone were determined using a non-compartmental model.

    RESULTS: The geometric means ratios (%) and 90% confidence interval (CI) of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of risperidone were 104.49 % (92.79% - 117.66%), 100.96 % (92.15% - 110.61 %) and 97.99 % (90.72% - 105.85%). The 90% CI of geometric means ratios of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of 9-hydroxyrisperidone were 97.00%, 96.97% and 97.49%.

    CONCLUSIONS: The 90% CI for the geometric means ratios (test/reference) of the log-trasformed Cmax, AUC0-t and AUC0-inf of risperidone and its major active metabolite were within the bioequivalence acceptance criteria of 80% - 125% of the US-FDA.

  6. Mondal PP, Galodha A, Verma VK, Singh V, Show PL, Awasthi MK, et al.
    Bioresour Technol, 2023 Feb;370:128523.
    PMID: 36565820 DOI: 10.1016/j.biortech.2022.128523
    Machine Learning is quickly becoming an impending game changer for transforming big data thrust from the bioprocessing industry into actionable output. However, the complex data set from bioprocess, lagging cyber-integrated sensor system, and issues with storage scalability limit machine learning real-time application. Hence, it is imperative to know the state of technology to address prevailing issues. This review first gives an insight into the basic understanding of the machine learning domain and discusses its complexities for more comprehensive applications. Followed by an outline of how relevant machine learning models are for statistical and logical analysis of the enormous datasets generated to control bioprocess operations. Then this review critically discusses the current knowledge, its limitations, and future aspects in different subfields of the bioprocessing industry. Further, this review discusses the prospects of adopting a hybrid method to dovetail different modeling strategies, cyber-networking, and integrated sensors to develop new digital biotechnologies.
  7. Dixit R, Khambhati K, Supraja KV, Singh V, Lederer F, Show PL, et al.
    Bioresour Technol, 2023 Feb;370:128522.
    PMID: 36565819 DOI: 10.1016/j.biortech.2022.128522
    Machine learning (ML) applications have become ubiquitous in all fields of research including protein science and engineering. Apart from protein structure and mutation prediction, scientists are focusing on knowledge gaps with respect to the molecular mechanisms involved in protein binding and interactions with other components in the experimental setups or the human body. Researchers are working on several wet-lab techniques and generating data for a better understanding of concepts and mechanics involved. The information like biomolecular structure, binding affinities, structure fluctuations and movements are enormous which can be handled and analyzed by ML. Therefore, this review highlights the significance of ML in understanding the biomolecular interactions while assisting in various fields of research such as drug discovery, nanomedicine, nanotoxicity and material science. Hence, the way ahead would be to force hand-in hand of laboratory work and computational techniques.
  8. Yadav P, Sarkale P, Patil D, Shete A, Kokate P, Kumar V, et al.
    Infect Genet Evol, 2016 11;45:224-229.
    PMID: 27619056 DOI: 10.1016/j.meegid.2016.09.010
    Bat-borne viral diseases are a major public health concern among newly emerging infectious diseases which includes severe acute respiratory syndrome, Nipah, Marburg and Ebola virus disease. During the survey for Nipah virus among bats at North-East region of India; Tioman virus (TioV), a new member of the Paramyxoviridae family was isolated from tissues of Pteropus giganteus bats for the first time in India. This isolate was identified and confirmed by RT-PCR, sequence analysis and electron microscopy. A range of vertebrate cell lines were shown to be susceptible to Tioman virus. Negative electron microscopy study revealed the "herringbone" morphology of the nucleocapsid filaments and enveloped particles with distinct envelope projections a characteristic of the Paramyxoviridae family. Sequence analysis of Nucleocapsid gene of TioV demonstrated sequence identity of 99.87% and 99.99% nucleotide and amino acid respectively with of TioV strain isolated in Malaysia, 2001. This report demonstrates the first isolation of Tioman virus from a region where Nipah virus activity has been noticed in the past and recent years. Bat-borne viruses have become serious concern world-wide. A Survey of bats for novel viruses in this region would help in recognizing emerging viruses and combating diseases caused by them.
  9. Jeyaraman M, Muthu S, Bapat A, Jain R, Sushmitha ES, Gulati A, et al.
    Heliyon, 2021 Jul;7(7):e07635.
    PMID: 34312598 DOI: 10.1016/j.heliyon.2021.e07635
    The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
  10. Lau CS, Chia F, Dans L, Harrison A, Hsieh TY, Jain R, et al.
    Int J Rheum Dis, 2019 Mar;22(3):357-375.
    PMID: 30809944 DOI: 10.1111/1756-185X.13513
    AIM: To update recommendations based on current best evidence concerning the treatment of rheumatoid arthritis (RA), focusing particularly on the role of targeted therapies, to inform clinicians on new developments that will impact their current practice.

    MATERIALS AND METHODS: A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations. Recommendations were finalized through consensus using the Delphi technique.

    RESULTS: This update provides 16 RA treatment recommendations based on current best evidence and expert clinical opinion. Recommendations 1-3 deal with the use of conventional synthetic disease-modifying antirheumatic drugs. The next three recommendations (4-6) cover the need for screening and management of infections and comorbid conditions prior to starting targeted therapy, while the following seven recommendations focus on use of these agents. We address choice of targeted therapy, switch, tapering and discontinuation. The last three recommendations elaborate on targeted therapy for RA in special situations such as pregnancy, cancer, and major surgery.

    CONCLUSION: Rheumatoid arthritis remains a significant health problem in the Asia-Pacific region. Patients with RA can benefit from the availability of effective targeted therapies, and these updated recommendations provide clinicians with guidance on their use.

  11. Gokhale M, Sudeep AB, Mathapati B, Balasubramanian R, Ullas PT, Mohandas S, et al.
    PMID: 35390635 DOI: 10.1016/j.cimid.2022.101800
    Nipah virus (NiV) is one of the priority pathogens with pandemic potential. Though the spread is far slower than SARS-CoV-2, case fatality is the biggest concern. Fruit bats belonging to genus Pteropus are identified to be the main reservoir of the virus causing sporadic cases and outbreaks in Malaysia, Bangladesh and India. The sudden emergence of Nipah in Kerala, India during 2018-2019 has been astonishing with respect to its introduction in the unaffected areas. With this, active Nipah virus surveillance was conducted among bat populations in Southern part of India viz., Karnataka, Kerala, Tamil Nadu, Telangana, Puducherry and Odisha during January-November 2019. Throat swabs/rectal swabs (n = 573) collected from Pteropus medius and Rousettus leschenaultii bat species and sera of Pteropus medius bats (n = 255) were screened to detect the presence of Nipah viral RNA and anti-Nipah IgG antibodies respectively. Of 255 P. medius bats sera samples, 51 bats (20%) captured from Karnataka, Kerala, Tamil Nadu and Puducherry demonstrated presence of anti-Nipah IgG antibodies. However, the presence of virus couldn't be detected in any of the bat specimens. The recent emergence of Nipah virus in Kerala in September 2021 warrants further surveillance of Nipah virus among bat populations from the affected and remaining states of India.
  12. Jha NK, Ojha S, Jha SK, Dureja H, Singh SK, Shukla SD, et al.
    J Mol Neurosci, 2021 Nov;71(11):2192-2209.
    PMID: 33464535 DOI: 10.1007/s12031-020-01767-6
    The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
  13. Lau CS, Chia F, Harrison A, Hsieh TY, Jain R, Jung SM, et al.
    Int J Rheum Dis, 2015 Sep;18(7):685-713.
    PMID: 26334449 DOI: 10.1111/1756-185X.12754
    Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue.
  14. Abouelazayem M, Jain R, Wilson MSJ, Martinino A, Balasubaramaniam V, Biffl W, et al.
    Surg Endosc, 2024 Aug;38(8):4402-4414.
    PMID: 38886232 DOI: 10.1007/s00464-024-10881-0
    BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these.

    METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality.

    RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality.

    CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

  15. Ham H, Jing H, Lamborn IT, Kober MM, Koval A, Berchiche YA, et al.
    Science, 2024 Sep 20;385(6715):eadd8947.
    PMID: 39298586 DOI: 10.1126/science.add8947
    Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2, which encodes Gαi2, a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating Gαi2 mutations had clinical presentations that included impaired immunity. Mutant Gαi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant Gαi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)-activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT S6 signaling to drive cellular growth and proliferation.
  16. Tobias DK, Merino J, Ahmad A, Aiken C, Benham JL, Bodhini D, et al.
    Nat Med, 2023 Oct;29(10):2438-2457.
    PMID: 37794253 DOI: 10.1038/s41591-023-02502-5
    Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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