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Browsing by Author "Dharmendra Jain"

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    PublicationArticle
    A gain-of-function mutation in CITED2 is associated with congenital heart disease
    (Elsevier B.V., 2021) Manohar Lal Yadav; Dharmendra Jain; Neelabh; Damyanti Agrawal; Ashok Kumar; Bhagyalaxmi Mohapatra
    CITED2 is a transcription co-activator that interacts with TFAP2 and CBP/ P300 transcription factors to regulate the proliferation and differentiation of the cardiac progenitor cells. It acts upstream to NODAL-PITX2 pathways and regulates the left-right asymmetry. Both human genetic and model organism studies have shown that altered expression of CITED2 causes various forms of congenital heart disease. Therefore, we sought to screen the coding region of CITED2 to identify rare genetic variants and assess their impact on the structure and function of the protein. Here, we have screened 271 non-syndromic, sporadic CHD cases by Sanger's sequencing method and detected a non-synonymous variant (c.301C>T, p.P101S) and two synonymous variants (c.21C>A, p.A7A; c.627C>G, p.P209P). The non-synonymous variant c.301C>T (rs201639244) is a rare variant with a minor allele frequency of 0.00011 in the gnomAD browser and 0.0018 in the present study. in vitro analysis has demonstrated that p.P101S mutation upregulates the expression of downstream target genes Gata4, Mef2c, Nfatc1&2, Nodal, Pitx2, and Tbx5 in P19 cells. Luciferase reporter assay also demonstrates enhanced activation of downstream target promoters. Further, in silico analyses implicate that increased activity of mutant CITED2 is possibly due to phosphorylation of Serine residue by proline-directed kinases. Homology modeling and alignment analysis have also depicted differences in hydrogen bonding and tertiary structures of wild-type versus mutant protein. The impact of synonymous variations on the mRNA structure of CITED2has been analyzed by Mfold and relative codon bias calculations. Mfold results have revealed that both the synonymous variants can alter the mRNA structure and stability. Relative codon usage analysis has suggested that the rate of translation is attenuated due to these variations. Altogether, our results from genetic screening as well as in vitro and in silico studies support a possible role of nonsynonymous and synonymous mutations in CITED2contributing to pathogenesis of CHD. © 2021
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    PublicationArticle
    Association of lifestyle risk factors with metabolic syndrome components: A cross‑sectional study in eastern India
    (Wolters Kluwer Medknow Publications, 2018) Pragya Verma; Ratan K Srivastava; Dharmendra Jain
    Background: Approximately 20%-25% of the world adult population and nearly 30% of Indians have metabolic syndrome disorder. Our objective was designed to find out the association between important nutrients and potential lifestyle risk factors such as diet, physical inactivity, and smoking and alcohol consumption with the number of metabolic syndrome components. Methods: This was a cross‑sectional study. A total of 205 patients of metabolic syndrome were enrolled for this study. Diagnosis of metabolic syndrome was done on the basis of National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III 2004). Dietary data were collected with the validated food frequency questionnaire and 24 h dietary recall method, and the nutrient intake was calculated with the specially designed software. Results: Unhealthy dietary habits were seen more among the participants who had more than 3 risk factors. Results showed the odds of taking >5 times junk foods was 3 times higher (odds ratio [OR]: 2.97; 95% confidence interval [CI]: 1.61-5.47), and sweet dishes was 2.3 times higher (OR: 2.33; 95% CI: 1.28-4.24) among the participants who had 4-5 risk factors. However, milk and dairy products > 4 servings/ day (OR: 0.54; 95% CI: 0.175-1.67) and pulses and legumes more than 2 servings/day (OR: 0.57; 95% CI: 0.25-1.29) was protective against hypertension. Mean carbohydrate, saturated fat, and sodium intake was significantly higher in the participants who had 4-5 metabolic risk factors compared to 3 risk factors (P < 0.0001). Conclusions: It was concluded that low intake of fruits, vegetables, and higher intake of flesh food and inadequate physical activity significantly associated with the metabolic syndrome risk factors. © 2018 International Journal of Preventive Medicine | Published by Wolters Kluwer - Medknow.
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    PublicationArticle
    Cardiac changes in children hospitalized with severe acute malnutrition: A prospective study at tertiary care center of northern India
    (Elsevier B.V., 2019) Dharmendra Jain; Sunil Kumar Rao; Dhilip Kumar; Ashok Kumar; Bhupendra Kumar Sihag
    Severe acute malnutrition (SAM) may affect cardiac structure and function. Cardiac changes in sick children with SAM have received little attention in the literature. Children aged 6–60 months with SAM were cases, and age and sex matched children were controls. Cardiac biomarker levels were measured by the quantitative the Enzyme- linked immunosorbent assay (ELISA) method, and echocardiography was used to assess cardiac changes in all children. The study included 76 children in each group. Children with SAM had less left ventricular mass and increased myocardial performance index as compared with controls (p < 0.0001). Cardiac biomarker levels were increased in children with SAM (p < 0.0001). Cardiac changes and biomarker levels were comparable in children with edema and children without edema except creatine kinase-MB (p = 0.01). © 2020 Cardiological Society of India
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    PublicationArticle
    Comparative study of scores for prediction of coronary artery disease severity: Evaluation of a newly formulated CHA2DS2-VASc-HSLp(a) score
    (Journal of Clinical and Diagnostic Research, 2018) Bhupendra Kumar Sihag; Dharmendra Jain; Geetha Subramanian
    Introduction: The Framingham Risk Score (FRS) and CHA2DS2-VASc scores include risk factors for the development of Coronary Artery Disease (CAD). On review of literature, one study concluded that CHADS2, CHA2DS2-VASc, and especially CHA2DS2-VASc-HS scores could be considered predictive of the risk of severe CAD. CHA2DS2-VASc-HS score was made by adding hyperlipidaemia and smoking to CHA2DS2-VASc score. In developing countries like India, other than hyperlipidemia and smoking, Lipoprotein-(a) is an independent risk factor of CAD and adding Lipoprotein-(a) to CHA2DS2-VASc-HS score could be a better predictor of CAD in Indians. Aim: To formulate a new CHA2DS2-VASc-HSLp(a)) score by including hyperlipidemia, smoking and Lipoprotein-(a) and to compare it with FRS and CHA2DS2-VASc score. Hence to better predict CAD severity especially in developing countries like India. Materials and Methods: A total of 516 consecutive patients who underwent coronary angiography were enrolled in the study. Presence of >50% stenosis in a coronary artery was assessed as significant CAD. This study investigated whether these three scores can be used to predict CAD severity. Statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS version 16.0) for Windows (SPSS Inc., Chicago, Illinois). Results: Out of 516 patients, 31 had normal coronary angiograms or mild CAD. The remaining 485 patients with coronary stenosis were further classified into single, double and triple vessel disease. The FRS, CHA2DS2-VASc, and CHA2DS2-VASc-HSLp(a) Scores correlated significantly with the number of significant diseased vessels and highest predictive ability was found with CHA2DS2-VASc-HSLp(a) score (r=0.157, r=0.279, and r=0.461, p<0.001, respectively). The diagnostic accuracy and Positive predictive value were 87.2% and 97.7% obtained for CHA2DS2-VASc-HSLp(a) score with optimum Lp(a) cut-off ≥19 mg/dL. In addition, these three scores correlated significantly with the Gensini score and highest predictive ability was found with CHA2DS2-VASc-HSLp(a) score (r=0.194, r=0.459, and r=0.587, p<0.001 respectively). Conclusion: FRS, CHA2DS2-VASc, and especially CHA2DS2-VASc-HSLp(a) scores could be considered predictive of the risk of severe CAD. The CHA2DS2-VASc-HSLp(a) score was found to be the better scoring scheme to predict CAD severity in Indian population. © 2018, Journal of Clinical and Diagnostic Research. All rights reserved.
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    PublicationArticle
    Comparative study of two ionotropes levosimendan and dobutamine in critically ill patients suffering from heart failure
    (Faculty of Anaesthesia, Pain and Intensive Care, AFMS, 2018) Dharmendra Jain; Sandeep Loha; Dhirendra Chandrakar; Manimoy Debburma; Dinesh Kumar Singh
    Objective: Acute heart failure frequently happens in critically ill patients due to myocardial injury, cardiac dysfunction, arrhythmias, and inflammatory mediators. Till now, the outcomes of studies comparing levosimendan with dobutamine for patients requiring inotropic support remain controversial and ambiguous. The present study was aimed to compare the effects of levosimendan and dobutamine in the management of critically ill patients in ICU and establish preference of one over the other drug. Methodology: In this study 100 critically ill patients with clinical diagnosis of heart failure or impending heart failure due to any cause of age between 21 years to 80 years (left ventricular ejection fraction < 35%) in ICU were included and randomly divided into 2 groups; Group-1 (n=50) received inj levosimendan and Group-2 (n=50) which received inj dobutamine. The parameters recorded during study were: heart rate (beats/min), systolic blood pressure (mmHg), stroke volume (ml), cardiac output (l/min), cardiac index (l/min/m2), brain natriuretic peptide (pg/ml), requirement of ionotropic agent and 7 day survival. Baseline parameters of the patient at “0” h was recorded, then the ionotrope (levosimendan or dobutamine) was started. After this the parameters were recorded at 24 h, 48 h and 5th day of study and follow-up of patient was done upto 7 days. SPSS for Windows version 16.0 software was used for statistical analysis. For non-continuous data Chi-square test was used. The mean and standard deviation of the parameters compared using student “t” test. The p < 0.05 was considered as significant. Results: The distribution of patients according to age, sex and body surface area was comparable (p > 0.05) in both the groups. Heart rate decreased significantly in both the groups at 24 h and 5th day, although it remained higher in Group-1 patients receiving levosimendan. Systolic blood pressure and Cardiac Index (CI) increased significantly in both the groups but was more in Group-1 patients receiving levosimendan at all times. Cardiac output increased significantly in Group-1 pts whereas in Group-2, after an initial increase for first 48 hrs ultimately decrease in cardiac output was observed on 5th day. 7 Day survival was more (56%) in Group-1 patients as compared to 52% in Group-2 patients. Conclusion: Based upon the results of our study, we conclude that levosimendan shows better results than dobutamine in maintaining hemodynamic stability in critically ill patients. Larger, multi-center studies may have to be done for confirming or discrediting our results. © 2018 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.
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    PublicationErratum
    Corrigendum to “Cardiological Society of India position statement on management of heart failure in India” (Indian Heart Journal (2018) 70(S1) (S1–S72), (S0019483218303006) (10.1016/j.ihj.2018.05.003))
    (Elsevier B.V., 2018) Santanu Guha; S. Harikrishnan; Saumitra Ray; Rishi Sethi; S. Ramakrishnan; Suvro Banerjee; V.K. Bahl; K.C. Goswami; Amal Kumar Banerjee; S. Shanmugasundaram; P.G. Kerkar; Sandeep Seth; Rakesh Yadav; Aditya Kapoor; Ajaykumar U. Mahajan; P.P. Mohanan; Sundeep Mishra; P.K. Deb; C. Narasimhan; A.K. Pancholia; Ajay Sinha; Akshyaya Pradhan; R. Alagesan; Ambuj Roy; Amit Vora; Anita Saxena; Arup Dasbiswas; B.C. Srinivas; B.P. Chattopadhyay; B.P. Singh; J. Balachandar; K.R. Balakrishnan; Brian Pinto; C.N. Manjunath; Charan P. Lanjewar; Dharmendra Jain; Dipak Sarma; G. Justin Paul; Geevar A. Zachariah; H.K. Chopra; I.B. Vijayalakshmi; J.A. Tharakan; J.J. Dalal; J.P.S. Sawhney; Jayanta Saha; Johann Christopher; K.K. Talwar; K. Sarat Chandra; K. Venugopal; Kajal Ganguly; M.S. Hiremath; Milind Hot; Mrinal Kanti Das; Neil Bardolui; Niteen V. Deshpande; O.P. Yadava; Prashant Bhardwaj; Pravesh Vishwakarma; Rajeeve Kumar Rajput; Rakesh Gupta; S. Somasundaram; S.N. Routray; S.S. Iyengar; G. Sanjay; Satyendra Tewari; G. Sengottuvelu; Soumitra Kumar; Soura Mookerjee; Tiny Nair; Trinath Mishra; U.C. Samal; U. Kaul; V.K. Chopra; V.S. Narain; Vimal Raj; Yash Lokhandwala
    In the article titled ‘Cardiological Society of India Position Statement on Management of Heart Failure in India’ below is the list of corrections to be included. The authors would like to apologise for any inconvenience caused. Fig. 14 ECG of a patient with RVEMF and atrial fibrillation, qR in V1 and R/S ratio in lead V2 more than V1. Fig. 15 ECG of a patient with LVEMF showing LVH with strain pattern. Fig. 16. Fluoroscopy showing the presence of LV apical calcium. Fig. 17. LV angiogram in a patient with LVEMF showing the obliteration of the LV apex, transverse diameter more than the longitudinal diameter and no MR (primary diastolic HF). Fig. 18. RV angiogram in a patient with RVEMF showing obliteration of the RV apex and body, RVOF dilatation and significant TR. Fig. 19. Echocardiogram, apical 4-chamber view, showing the presence of calcium at the LV apex. Fig. 20. Perfusion MRI, 4-chamber view in diastole showing fibrosis and obliteration of RV apex (white arrow) [RV – right ventricle, RA – Right atrium, LA – left atrium]. In the text – Page S 48 Column 2 Section 3.10.3 Figs. 13 and 14 – Corrected as Figs. 14 and 15. Figs. 16–18 – Corrected as Figs. 16–19. Fig 19 – Corrected as Fig 20 References: The references are changed as given below (Page S 66). 240. K Balakrishnan, Ratnagiri R, S. Rao, M. Tungaturu Limiting the Number of Endomyocardial Biopsies does not impact one year survival after Heart Transplant. J heart Lung Transplant. Supplement. April 2016 Volume 35; Issue 4, Supplement: S210. 241. Stehlik J, Starling RC, Movsesian MA, et al. Utility of long-term surveillance endomyocardial biopsy: a multi-institutional analysis. J Heart Lung Transplant. 2006; 25:1402–1409. To be added at the end of references (Can be given as reference in the heading 2.8). Status of Cardiac Transplantation in India.(583) 583. Dr KR Balakrishnan, R Ravi Kumar; - “Status of Cardiac Transplantation in India” Pages 599–606 in Chapter 44 of CSI TEXT BOOK OF CARDIOLOGY. (Ed) PK Deb 2018 Jaypee Brothers, New Delhi. © 2018 Cardiological Society of India
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    PublicationReview
    CSI position statement on management of heart failure in India
    (Elsevier B.V., 2018) Santanu Guha; S. Harikrishnan; Saumitra Ray; Rishi Sethi; S. Ramakrishnan; Suvro Banerjee; V.K. Bahl; K.C. Goswami; Amal Kumar Banerjee; S. Shanmugasundaram; P.G. Kerkar; Sandeep Seth; Rakesh Yadav; Aditya Kapoor; Ajaykumar U. Mahajan; P.P. Mohanan; Sundeep Mishra; P.K. Deb; C. Narasimhan; A.K. Pancholia; Ajay Sinha; Akshyaya Pradhan; R. Alagesan; Ambuj Roy; Amit Vora; Anita Saxena; Arup Dasbiswas; B.C. Srinivas; B.P. Chattopadhyay; B.P. Singh; J. Balachandar; K.R. Balakrishnan; Brian Pinto; C.N. Manjunath; Charan P. Lanjewar; Dharmendra Jain; Dipak Sarma; G. Justin Paul; Geevar A. Zachariah; H.K. Chopra; I.B. Vijayalakshmi; J.A. Tharakan; J.J. Dalal; J.P.S. Sawhney; Jayanta Saha; Johann Christopher; K.K. Talwar; K. Sarat Chandra; K. Venugopal; Kajal Ganguly; M.S. Hiremath; Milind Hot; Mrinal Kanti Das; Neil Bardolui; Niteen V. Deshpande; O.P. Yadava; Prashant Bhardwaj; Pravesh Vishwakarma; Rajeeve Kumar Rajput; Rakesh Gupta; S. Somasundaram; S.N. Routray; S.S. Iyengar; G. Sanjay; Satyendra Tewari; G. Sengottuvelu; Soumitra Kumar; Soura Mookerjee; Tiny Nair; Trinath Mishra; U.C. Samal; U. Kaul; V.K. Chopra; V.S. Narain; Vimal Raj; Yash Lokhandwala
    [No abstract available]
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    PublicationReview
    Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders
    (American Chemical Society, 2023) Aseem Setia; Abhishesh Kumar Mehata; Vishnu Priya; Datta Maroti Pawde; Dharmendra Jain; Sanjeev Kumar Mahto; Madaswamy S. Muthu
    Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents. © 2023 American Chemical Society.
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    PublicationArticle
    Do gender differences matter in Acute Heart Failure? Insights from Indian College of Cardiology – National Heart Failure Registry, India
    (Elsevier B.V., 2025) Pathiyil Balagopalan Jayagopal; Chollenahally Nanjappa Manjunath; Jabir Abdullakutty; Sridhar Lakshmana Sastry; Veena Nanjappa; Peruvamba Raman Vaidyanathan; Johny Kutty Joseph; Soma Sekhar Ghanta; Panchanatham Manokar; Nitin Kabra; Dharmendra Jain; Vinod Kumar Sharma; Trinath Kumar Mishra; R. Badri Narayanan; Narendra Jathappa; Gautam M. Rege; Sunil Kumar Modi; S. N. Routray; Thagachagere Ramegowda Raghu; Rabin Chakraborty; Dayasagar Rao; Shantanu P. Sengupta; Khandenahally Shankarappa Ravindranath; Budanuru Chikkaswamy Srinivas; Vijay Kumar Chopra
    Background: Real-world investigations focused on gender-associated characteristics of Acute Heart failure (AHF) are lacking. The current study, from a national heart failure registry, aims to investigate gender-based patterns and outcomes among AHF patients in India. Methods: This prospective Indian College of Cardiology National Heart Failure Registry enrolled patients admitted with AHF in 17 centres from 2019 to 2021. Demographics, aetiology, co-morbidities, laboratory investigations, electrocardiogram, and echo parameters were captured. In-hospital 30-day and one-year mortality rates were recorded. The prescription and adherence to the three Guideline Directed Medical Therapy (GDMT) prescription in 2019–2021 were also captured at discharge. Mortality rate Gender-based comparisons were tested at a 5 % level of significance. Results: The study enrolled 5182 AHF patients, 66.7 % male (M) and 33.3 % female (F). The mean age of the male (M) population was 60.9 ± 13.3, and the female (F) population was 62.8 ± 14 years. Women had a higher prevalence of heart failure with preserved ejection fraction (HFpEF)(F:12.9 %, M:7.3 %;P < 0.0001), hypertension (F: 57.2 %, M: 52.4 %; P = 0.0011) and arrhythmia (F:15.2 %, M:11.7 %;P = 0.0005). Men had a higher incidence of ischemic heart disease (M:76.2 %, F:67.5 %; P < 0.001). Adherence to Renin-angiotensin-aldosterone system (RAAS) inhibitors, Beta-blockers and Mineralocorticoid receptor antagonists (MRAs) was low (18.8 % (M); 15.9 % (F)). The mortality rate, in-hospital mortality was 6.9 % (M:6.5 %, F:7.7 %), up to one-month was 11.8 % (M:11.6 %, F:12.3 %) or one-year was 18.1 % (M:17.8 %, F:18.6 %). Conclusion: Women represent one-third of the population with AHF. Hypertension and HFpEF were more common in women, while ischemic heart disease was more prevalent in men. No gender-based differences were observed in the mortality outcomes. Both groups had low GDMT adherence. This calls for effective strategies to improve HF care in the country. © 2025 The Authors
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    PublicationLetter
    Early marker of left ventricular dysfunction in echocardiography and cardiac biomarkers in sick children with severe acute malnutrition
    (Elsevier B.V., 2020) Sunil Kumar Rao; Dharmendra Jain; Tej Bali Singh
    [No abstract available]
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    PublicationArticle
    Echocardiography versus cardiac biomarkers for myocardial dysfunction in children with scorpion envenomation: An observational study from tertiary care center in northern India.
    (Elsevier B.V., 2020) Rajniti Prasad; Anil Kumar; Dharmendra Jain; B.K. Das; Utpal Kant Singh; T.B. Singh
    Objective: This study was done to evaluate myocardial function by 2D Echocardiography and Cardiac biomarkers (cTnI, CK-MB, BNP) changes in patients of scorpion envenomation of grade II-IV and correlate mortality of envenomed children with myocardial dysfunction. Methods: A total of 40 patients admitted consecutively with grade II and more scorpion envenomation from October 2015 to July2018 were enrolled in the study. The data included demographics, the time of presentation, clinical features, echocardiographic findings, electrocardiographic findings, cardiac biomarker levels at admission and discharge, use of inotropic medication, oral prazosin, time of discharge, and their outcome. Results: The most common ECG abnormality was sinus tachycardia 28 (70%) followed by low voltage complex 13 (32.5%) which got normalized at the time of discharge in majority. Cardiac troponin I (cTnI) levels were more than 0.1 ng/mL, suggesting myocarditis was present in 25 (62.5%) and got normalized at discharge. CK-MB levels were increased in 26 (65%) patients suggesting myocardial involvement. BNP levels were also increased in 24 (60%) patients suggesting heart failure and its value got normalized at discharge. Abnormal 2D Echo findings as reduced left ventricular ejection fraction (LVEF) was present in 18 (45%) cases suggesting myocardial dysfunction and became normal at discharge. The sensitivity, specificity, positive predictive value and negative predictive value of Cardiac troponin I (cTnI) considering ECHO cardiograph as gold standard were 100, 68.1, 72 and 100% respectively. One patient had died whose Ejection fraction was less than 30%. Conclusion: Echocardiography and cTnI can identify subgroup of patients, who require early aggressive therapy. Echocardiography, if not available, cardiac troponin I level can guide early therapy and indicates the prognosis. © 2020 Cardiological Society of India
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    Efficient delivery of abciximab using mesoporous silica nanoparticles: In-vitro assessment for targeted and improved antithrombotic activity
    (Elsevier B.V., 2022) Vishnu Priya; Vikas; Abhishesh Kumar Mehata; Dharmendra Jain; Sanjeev K. Singh; Madaswamy S. Muthu
    Abciximab (ABX) is a chimeric monoclonal antibody reported for antithrombotic activity but their delivery remains challenging due to its poor stability in a biological system. The purpose of this research was to deliver ABX on the target efficiently using mesoporous silica nanoparticles (MSN). ABX coated mesoporous silica nanoparticles (MSN-ABX) were formulated and analyzed for particle size, shape, zeta-potential, surface morphology and surface chemistry. XPS analysis confirmed the presence of ABX on the surface of amino functionalized mesoporous silica nanoparticles (MSN-NH2). The degree of ABX attachment was 67.53 ± 5.81 % which was demonstrated by the Bradford assay. Furthermore, the targeting efficiency of the targeted nanoparticles has been evaluated by capturing the fluorescent images in-vitro which showed the significant accumulation of the ABX coated nanoparticles towards activated platelets. The significant (P < 0.05) increase in affinity of DiD dye loaded nanoparticles towards the activated platelets was confirmed by using an in-vitro imaging through photon imager optima. The hemolysis study of the nanoparticle formulations revealed that they were non-hemolytic for healthy human blood. The in-vitro antithrombotic effects of MSN-ABX were observed by blood clot assay which revealed its superior antithrombotic activity over clinical injection of ABX and could be a promising carrier for improved ABX targeted delivery. © 2022 Elsevier B.V.
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    PublicationArticle
    Evaluation of cardiac biomarkers in children with acute severe bronchial Asthma-A prospective study from tertiary care center in northern India
    (Elsevier B.V., 2018) Meghna Jain; Dharmendra Jain; B.K. Das; Rajniti Prasad; Bhupendra Kumar Sihag
    Objectives: During the attacks of acute severe bronchial asthma there are marked cardiopulmonary changes leading to hypoxia. The study aims to find the incidence of myocardial dysfunction in patients of acute severe bronchial asthma based on cardiac enzyme levels at admission and see whether the myocardial damage is transient or persistent even after stabilization of the patient based on enzyme levels at discharge. Materials and methods: This prospective, case control study was done at Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University between October 2016 to May 2018. Sixty pediatric patients of acute severe bronchial asthma were taken as cases and 15 age and sex matched children served as controls. Blood samples were collected in Ethylene diamine tetra acetic acid vials before the start of treatment, for measurement of cardiac biomarkers Troponin I (TnI), Brain natriuretic peptide (BNP) and Creatine Kinase-muscle/brain (CK-MB) and repeat samples were taken before discharge. Results: Fifty percent of the cases had abnormal TnI levels, 15% had abnormal CK-MB levels and 8.3% had abnormal BNP levels at admission. At discharge, only 1 (1.7%) case had abnormal levels of CK-MB, whereas the levels of TnI and BNP normalized in all. The level of cardiac biomarkers were significantly raised at admission when compared to discharge values (p value < 0.001). Conclusions: The raised cardiac biomarkers suggest myocardial stress during acute exacerbation of bronchial asthma. Though, the present study showed that the changes are of transient nature, larger follow up studies are required to document any permanent damage to myocardium. © 2018 Cardiological Society of India
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    PublicationArticle
    Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study
    (SAGE Publications Inc., 2024) Ashish Gautam; Prashant Raghav; Vijay Subramaniam; Sunil Kumar; Sudeep Kumar; Dharmendra Jain; Ashish Verma; Parminder Singh; Manphoul Singhal; Vikash Gupta; Samir Rathore; Srikanth Iyengar; Sudhir Rathore
    To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P <.001) and high limits of agreement (±1.96 SD; −2000, 2000) in Bland–Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources. © The Author(s) 2024.
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    Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study
    (SAGE Publications Inc., 2025) Ashish Gautam; Prashant Raghav; Vijay Subramaniam; Sunil Kumar; Sudeep Kumar; Dharmendra Jain; Ashish Verma; Parminder D. Singh; Manphool Singhal; Vikash Gupta; Samir Rathore; Srikanth R.S. Iyengar; Sudhir Rathore
    To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P <.001) and high limits of agreement (±1.96 SD; −2000, 2000) in Bland–Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources. © The Author(s) 2024.
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    Identification and in silico characterization of CSRP3 synonymous variants in dilated cardiomyopathy
    (Springer Science and Business Media B.V., 2023) Prerna Giri; Dharmendra Jain; Ashok Kumar; Bhagyalaxmi Mohapatra
    Background: Synonymous variations have always been ignored while studying the underlying genetic mechanisms for most of the human diseases. However, recent studies have suggested that these silent changes in the genome can alter the protein expression and folding. Methods and results: CSRP3, which is a well-known candidate gene associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), was screened for 100 idiopathic DCM cases and 100 controls. Three synonymous variations were identified viz., c.96G > A, p.K32=; c.336G > A, p.A112=; c.354G > A, p.E118=. A comprehensive in silico analysis was performed using various web based widely accepted tools, Mfold, Codon Usage, HSF3.1 and RNA22. Mfold predicted structural changes in all the variants except c.96 G > A (p.K32=), however it predicted changes in the stability of mRNA due to all the synonymous variants. Codon bias was observed as evident by the Relative Synonymous Codon Usage and Log Ratio of Codon Usage Frequencies. The Human Splicing Finder also predicted remarkable changes in the regulatory elements in the variants c.336G > A and c.354 G > A. The miRNA target prediction using varied modes available in RNA22 revealed that 70.6% of the target sites of miRNAs in CSRP3 were altered due to variant c.336G > A while 29.41% sites were completely lost. Conclusion: Findings of the present study suggest that synonymous variants revealed striking deviations in the structural conformation of mRNA, stability of mRNA, relative synonymous codon usage, splicing and miRNA binding sites from the wild type suggesting their possible role in the pathogenesis of DCM, either by destabilizing the mRNA structure, or codon usage bias or else altering the cis-acting regulatory elements during splicing. © 2023, The Author(s), under exclusive licence to Springer Nature B.V.
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    Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population
    (Elsevier Inc., 2021) Manohar Lal Yadav; Prashant Ranjan; Parimal Das; Dharmendra Jain; Ashok Kumar; Bhagyalaxmi Mohapatra
    NODAL signaling plays an essential role in vertebrate embryonic patterning and heart development. Accumulating evidences suggest that genetic mutations in TGF-β/NODAL signaling pathway can cause congenital heart disease in humans. To investigate the implication of NODAL signaling in isolated cardiovascular malformation, we have screened 300 non-syndromic CHD cases and 200 controls for NODAL and ACVR1B by Sanger sequencing and identified two rare missense (c.152C > T; p.P51L and c.981 T > A; p.D327E) variants in NODAL and a novel missense variant c.1035G > A; p.M345I in ACVR1B. All these variants are absent in 200 controls. Three-dimensional protein-modelling demonstrates that both p.P51L and p.D327E variations of NODAL and p.M345I mutation of ACVR1B, affect the tertiary structure of respective proteins. Variants of NODAL (p.P51L and p.D327E) and ACVR1B (p.M345I), significantly reduce the transactivation of AR3-Luc, (CAGA)12-Luc and (SBE)4-Luc promoters. Moreover, qRT-PCR results have also deciphered a reduction in the expression of cardiac-enriched transcription factors namely Gata4, Nkx2-5, and Tbx5 in both the mutants of NODAL. Decreased expression of, Gata4, Nkx2-5, Tbx5, and lefty is observed in p.M345I mutant of ACVR1B as well. Additionally, reduced phosphorylation of SMAD2/3 in response to these variants, suggests impaired NODAL signaling and possibly responsible for defective cell fate decision and differentiation of cardiomyocytes leading to CHD phenotype. © 2021 Elsevier Inc.
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    Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: A rare case report
    (2013) Dharmendra Jain; Vikas Kumar; Deba P. Kar; Shashi R. Prasad
    A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC) like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed. © 2012, Cardiological Society of India. All rights reserved.
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    Poor emotional responsiveness in clinical hypertension: Reduced accuracy in the labelling and matching of emotional faces amongst individuals with hypertension and prehypertension
    (Routledge, 2018) Meenakshi Shukla; Rakesh Pandey; Dharmendra Jain; Jennifer Y. F. Lau
    Psychological factors are known to play an important part in the origin of many medical conditions including hypertension. Recent studies have reported elevated blood pressure (even in the normal range of variation) to be associated with a reduced responsiveness to emotions or ‘emotional dampening’. Our aim was to assess emotional dampening in individuals with more extreme blood pressure levels including prehypertensives (N = 58) and hypertensives (N = 60) by comparing their emotion recognition ability with normotensives (N = 57). Participants completed novel facial emotion matching and facial emotion labelling tasks following blood pressure measurement and their accuracy of emotion recognition and average response times were compared. The normotensives demonstrated a significantly higher accuracy of emotion recognition than the prehypertensives and the hypertensives in labelling of facial emotions. This difference generalised to the task where two facial halves (upper & lower) had to be matched on the basis of emotions. In neither the labelling nor matching emotion conditions did the groups differ in their speed of emotion processing. Findings of the present study extend reports of ‘emotional dampening’ to hypertensives as well as to those at-risk for developing hypertension (i.e. prehypertensives) and have important implications for understanding the psychological component of such medical conditions as hypertension. © 2017 Informa UK Limited, trading as Taylor & Francis Group.
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    PublicationLetter
    Reply to “Letter to the Editor: Comments on gender differences in acute heart failure study”
    (Elsevier B.V., 2025) Pathiyil Balagopalan Jayagopal; Chollenahally Nanjappa Manjunath; Jabir Abdullakutty; Sridhar Lakshmana Sastry; Veena Nanjappa; Peruvamba Raman Vaidyanathan; Johny Kutty Joseph; Soma Sekhar Ghanta; Panchanatham Manokar; Nitin Kabra; Dharmendra Jain; Vinod Kumar Sharma; Trinath Kumar Mishra; R. Badri Narayanan; Narendra Jathappa; Gautam M. Rege; Sunil Kumar Modi; S. N. Routray; Thagachagere Ramegowda Raghu; Rabin Chakraborty; Dayasagar Rao; Shantanu P. Sengupta; Khandenahally Shankarappa Ravindranath; Budanuru Chikkaswamy Srinivas; Vijay Kumar Chopra
    [No abstract available]
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