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Objectives: The persistence and outcomes following myocardial injury subsequent to coronavirus disease-2019 (COVID-19) infection has not been properly elucidated. We assessed sub-clinical bi-ventricular dysfunction using speckle tracking echocardiography (STE) in post COVID-19 patients., Methods: A total of 189 subjects following recovery from COVID-19 infection were enrolled. Detailed echocardiography including STE along with clinical, hematological, biochemical and inflammatory parameters were assessed for all. Patients were divided into four groups (asymptomatic, mild, moderate and severe) based on severity of COVID-19 infection. Additionally, 90 healthy individuals were enrolled as controls. All these patients were followed up for one year following enrolment., Results: Subclinical LV and right ventricle (RV) dysfunction were seen in 58 (30.7 %) and 55 (29.1 %) patients respectively at baseline. Significant difference was observed in mean LVGLS values among the three groups (mild: -21.5 ± 2.8 %; moderate: -17 ± 7.1 %; severe: -12.1 ± 4 %; P < 0.0001). Over a year of follow-up, significant improvement in LVGLS from baseline (-19.1 ± 5.8 %) was observed (-19.9 ± 4.6 %; P < 0.0001). Similarly, RVFWS (-23.5 ± 6.3 % vs -23.8 ± 5.8 %; P = 0.03) had significant improvement from baseline to one year of follow-up. Reduced LVGLS was reported in 12 (6.3 %) subjects while impaired RVFWS was documented in 10 (5.3 %) subjects at one year of follow-up., Conclusions: Subclinical LV and RV dysfunction were seen in nearly a third of recovered COVID-19 patients. Over a year of follow-up, significant improvement in subclinical LV and RV dysfunction was noted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Despite significant progress in primary prevention, rates of myocardial infarction (MI) in South Asian population is alarmingly high., Objectives: We sought to compare risk factor profiles and outcomes between individuals with ST-Segment Elevation Myocardial Infarction (STEMI) in young (<50 years) and old (≥50 years) age groups., Methods: North India STEMI Registry (NORIN-STEMI) is a prospective observational registry of patients hospitalised with STEMI. We conducted a study of young patients (<50 years) regarding their risk factors for coronary artery disease (CAD), in-hospital and 30-day mortality and compared with their older counterpart., Results: Among 5335 patients enrolled, 1752 (32.8%) were young and were 19 years younger than the older cohort. Major risk factors in young patients were physical inactivity (75.1%) and alcohol intake (67.8%). Higher prevalence of tobacco use (66.6% vs 52.4%), but lower prevalence of diabetes (16% vs 26.3%) and hypertension (18.5% vs 29.9%) were seen in young STEMI. Young patients were less likely to die both in-hospital (5.9% vs 10.0%) and at 30-days (11.1% vs 16.2%). Left ventricular ejection fraction (LVEF) < 30% at admission [OR: 8.00, 95% confidence interval (CI): 4.60-13.90, P < 0.001 in-hospital, OR: 3.92, 95% CI: 2.69-5.73 at 30-days] and female sex were strongest predictors of mortality., Conclusions: Young STEMI patients constituted one-third of total cohort. Most of them were tobacco consumers with lesser prevalence of diabetes and hypertension. They were less likely to die both in-hospital and at 30 days because of earlier presentation to a health care facility and hence a relatively preserved LVEF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Genetic polymorphism in endothelial Nitric Oxide Synthase (eNOS) are associated with occurrence of multiple cardiovascular diseases (CVDs)., Methods: This study included 300 young ST-segment elevation myocardial infarction (STEMI) patients and 300 healthy controls. STEMI patients were divided into two groups: premature coronary artery disease [CAD] (STEMI<40 years of age) and older STEMI (>40 years of age). Genetic polymorphisms in the eNOS gene (894G/T) was evaluated in both subjects and controls. Plasma levels of nitric oxide (NO) were estimated for both patients as well as controls., Results: Mean age of the study population was 49.7 ± 9.2 years with premature CAD being present in 58 (19.3 %) patients. No significant difference at genotypic (P = 0.589, odds ratio (OR) = 0.9, 95 % CI = 0.6-1.6) and allelic level (P = 0.173, OR = 1.2, 95 % CI = 0.9-1.4) was observed between STEMI patients and healthy controls. Genotype 894 TT had significantly higher frequency in STEMI patients >40 years (P = 0.047, OR: 2.5; 95 % CI = 1.0-6.0). No significant difference at genotypic (P = 0.279) and allelic level (P = 0.493) was observed between premature CAD (STEMI age <40 years) and healthy controls. NO levels (131 ± 59.6 μM vs 118.11 ± 49.96 μM; P = 0.001) was significantly higher in healthy controls as compared to STEMI patients >40 years of age (P= 0.001)., Conclusion: There was significant association of eNOS gene polymorphism Glu298Asp with STEMI patients > 40 years. However, this association was not observed in premature CAD patients. Lower levels of NO in STEMI patients >40 years suggests its potential role as a marker of CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Psychosocial factors such as stress have been previously implicated as a risk factor for cardiovascular diseases (CVDs). There is little evidence regarding the prevalence of stress among patients with acute myocardial infarction (AMI)., Methods: A total of 903 patients with AMI enrolled in the North Indian ST-Segment Elevation Myocardial Infarction (NORIN-STEMI) registry were included in this study. Perceived stress in these subjects was evaluated using the Perceived Stress Scale-10 questionnaire while the World health Organization (WHO-5) Well-being Index was used to evaluate psychological well-being. All these patients were followed up for one month and major adverse cardiac events (MACE) were determined., Results: A majority of patients with AMI had either severe (478 [52.9%]) or moderate stress (347 [38.4%]) while low stress levels were observed in 78 [8.6%] patients. Additionally, most of the patients with AMI (478 [53%]) had WHO-5 well-being index <50%. Subjects with severe stress were younger (50.86 ± 13.31; P < 0.0001), more likely to be males (403 [84.30%]; P = 0.027), were less likely to have optimal level of physical activity (P < 0.0001) and had lower WHO-5 well-being score (45.54 ± 1.94%; P < 0.0001) as compared to those with low and moderate stress levels. On 30-days follow-up, subjects with moderate/severe stress had higher MACE however, the difference was non-significant (2.1% vs 1.04%; P = 0.42)., Conclusion: A high prevalence of perceived stress and low well-being index was observed in patients presenting with AMI in India., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Introduction: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution., Hypothesis/objective: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred., Study Design: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021., Results: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB)., Discussion: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy., Conclusion: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Genetic polymorphism in MMPs are associated with multiple adverse CV events. There is little evidence regarding role of MMPs and their genetic polymorphisms in young (<50 years) ST-segment elevation myocardial infarction (STEMI) patients., Methods: This study included 100 young (18-50 years) STEMI patients and 100 healthy controls. Serum levels of MMP-3, MMP-9 and TIMP were estimated for both patients as well as controls. Additionally, genetic polymorphisms in the MMP-9 gene (-1562 C/T and R279Q) & MMP-3 gene (5A/6A-1612) was evaluated. All these patients were followed up for one year and major adverse cardiac events (MACE) were determined., Results: Serum levels of MMP-3 (128.16 ± 115.81 vs 102.3 ± 57.28 ng/mL; P = 0.04), MMP-9 (469.63 ± 238.4 vs 188.88 ± 94.08 pg/mL; P < 0.0001) and TIMP (5.84 ± 1.93 vs 2.28 ± 1.42 ng/mL; P < 0.0001) were significantly higher in patients as compared to controls. Additionally, patients with genetic polymorphisms in the MMP genes (5A/5A, 6A/6A and the AG genotypes) had an increased risk of STEMI. Patients with MACE had significantly higher levels of MMP-9 (581.73 ± 260.93 vs 438.01 ± 223.38 pg/mL; P = 0.012). A cutoff value of 375.5 pg/mL of MMP-9 was best able to discriminate patients with STEMI and MACE with sensitivity of 77.3% and specificity of 57%., Conclusion: Novel biomarkers such as MMP-3, MMP-9 and TIMP and their genetic polymorphism are associated with the susceptibility for STEMI in young individuals. Higher MMP-9 levels in STEMI patients with MACE suggests its potential role in predicting cardiac remodeling and left ventricular dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier, a division of RELX India, Pvt. Ltd.)

Background: Risk prediction following ST-Elevation Myocardial Infarction (STEMI) in resource limited countries is critical to identify patients at an increased risk of mortality who might benefit from intensive management., Methods: North India ST-Elevation Myocardial Infarction (NORIN-STEMI) is an ongoing registry that has prospectively enrolled 3,635 STEMI patients. Of these, 3191 patients with first STEMI were included. Patients were divided into two groups: development (n=2668) and validation (unseen) dataset (n=523). Various ML strategies were used to train and tune the model based on validation dataset results that included 31 clinical characteristics. These models were compared in sensitivity, specificity, F1-score, receiver operating characteristic area under the curve (AUC), and overall accuracy to predict mortality at 30 days. ML model decision making was analyzed using the Shapley Additive exPlanations (ShAP) summary plot., Results: At 30 days, the mortality was 7.7%. On the validation dataset, Extra Tree ML model had the best predictive ability with sensitivity: 85%, AUC: 79.7%, and Accuracy: 75%. ShAP interpretable summary plot determined delay in time to revascularization, baseline cardiogenic shock, left ventricular ejection fraction <30%, age, serum creatinine, heart failure on presentation, female sex, and moderate-severe mitral regurgitation to be major predictors of all-cause mortality at 30 days (P<0.001 for all)., Conclusion: ML models lead to an improved mortality prediction following STEMI. ShAP summary plot for the interpretability of the AI model helps to understand the model's decision in identifying high-risk individuals who may benefit from intensified follow-up and close monitoring., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Current risk scores to estimate atherosclerotic cardiovascular disease (ASCVD) risk and allocate statins in at-risk persons have largely been developed in Western populations; their applicability in India is uncertain., Objective: To assess eligibility for primary prevention statin therapy using the 2018 U.S Multisociety Guideline and other contemporary cholesterol guidelines in patients presenting with ST-elevation myocardial infarction (STEMI) in the North India STEMI (NORIN-STEMI) registry., Methods: NORIN-STEMI registry prospectively enrolled 3,635 patients at 2 tertiary care centers in Delhi, India from January 2019 to February 2020. Pooled cohort risk equations were used to estimate ASCVD risk at presentation. Patients were evaluated for statin eligibility using the 2018 U.S Multisociety Guideline, United States Preventive Services Task Force (USPSTF), and National Cholesterol Education Program (NCEP) III cholesterol guidelines., Results: A total of 2,551 met the inclusion criteria. The median age was 54 years; 17% were women. The median ASCVD risk was 7.0%. At the time of MI, 54% of patients were eligible for primary prevention statin therapy by Multisociety Guideline, 46% by USPSTF, and 30% by NCEP III guidelines. These findings were applicable in both women and men. Compared with patients aged ≥50 years, those <50 years were less likely to be recommended statin therapy by all the three guidelines., Conclusion: A significant proportion of patients with STEMI in India did not meet the current guideline-based threshold for statin therapy for primary prevention. Novel risk stratification tools are needed to identify patients for primary prevention statin therapy in this population., (Copyright © 2021. Published by Elsevier Inc.)

Background: Overt left ventricular (LV) dysfunction and congestive heart failure are known entities in Takayasu arteritis (TA). Subclinical LV dysfunction may develop in these patients despite normal LV ejection fraction (LVEF). Moreover, effect of treatment of aortic or renal artery narrowing in such patients is unknown., Methods: This study included 15 angiographically confirmed TA patients undergoing aortic and/or renal intervention. A comprehensive clinical, biochemical and echocardiographic (2-dimensional, speckle tracking and tissue doppler imaging) evaluation were done at baseline, 72 h, and six months post intervention., Results: Six patients (40%) had reduced LVEF (<50%) at baseline while rest 9 (60%) patients had reduced global longitudinal strain (GLS) but normal EF. Diastolic filling pattern was abnormal in all the patients. In patients with baseline reduced EF, mean EF improved from 24.62 ± 12.14% to 45.6 ± 9.45% (p = 0.001), E/e' ratio decreased from 15.15 ± 3.19 to 10.8 ± 2.56 (p = 0.005) and median NT pro BNP decreased from 1673 pg/ml (970-2401 pg/ml) to 80 pg/ml (40-354 pg/ml) (p = 0.001) at 6 months after interventional procedure. In patients with baseline normal EF, median NT pro BNP decreased from 512 pg/ml (80-898.5 pg/ml) to 34 pg/ml (29-70.8 pg/ml) (p < 0.01), mean GLS improved from -8.80 ± 0.77% to -16.3 ± 0.78% (p < 0.001) and mean E/e' decreased from 12.93 ± 2.63 to 7.8 ± 2.73 (p = 0.005) at 6 months follow up., Conclusion: LV dysfunction is common in patients with TA and obstructive lesions in aorta or renal arteries. GLS can be used to assess subclinical systolic dysfunction in these patients. Timely intervention can improve LV dysfunction and can even reverse the subclinical changes., Competing Interests: Declaration of competing interest Authors have no conflict of interest to disclose., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Objectives: COVID-19 pandemic has led to unprecedented increase in rates of stress and burn out among healthcare workers (HCWs). Heart rate variability (HRV) has been shown to be reflective of stress and burnout. The present study evaluated the prevalence of burnout and attempted to develop a HRV based predictive machine learning (ML) model to detect burnout among HCWs during COVID-19 pandemic., Methods: Mini-Z 1.0 survey was collected from 1615 HCWs, of whom 664, 512 and 439 were frontline, second-line and non-COVID HCWs respectively. Burnout was defined as score ≥3 on Mini-Z-burnout-item. A 12-lead digitized ECG recording was performed and ECG features of HRV were obtained using feature extraction. A ML model comprising demographic and HRV features was developed to detect burnout., Results: Burnout rates were higher among second-line workers 20.5% than frontline 14.9% and non-COVID 13.2% workers. In multivariable analyses, features associated with higher likelihood of burnout were feeling stressed (OR = 6.02), feeling dissatisfied with current job (OR = 5.15), working in a chaotic, hectic environment (OR = 2.09) and feeling that COVID has significantly impacted the mental wellbeing (OR = 6.02). HCWs with burnout had a significantly lower HRV parameters like root mean square of successive RR intervals differences (RMSSD) [p < 0.0001] and standard deviation of the time interval between successive RR intervals (SDNN) [p < 0.001]) as compared to normal subjects. Extra tree classifier was the best performing ML model (sensitivity: 84%) CONCLUSION: In this study of HCWs from India, burnout prevalence was lower than reports from developed nations, and was higher among second-line versus frontline workers. Incorporation of HRV based ML model predicted burnout among HCWs with a good accuracy., Competing Interests: Declaration of competing interest Dr. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. Dr Qamar is supported by institutional grant support from the North Shore Auxiliary research scholar fund and has received funding from Daiichi-Sankyo, American Heart Association and fees for educational activities from the American College of Cardiology, Society for Vascular Medicine, Society for Cardiovascular Angiography and Interventions, Janssen and Janssen, Pfizer, Medscape, and Clinical Exercise Physiology Association. The remaining authors have no disclosures to report., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Aim: Genetic contribution in acute rheumatic fever (ARF)/rheumatic heart disease (RHD) has been suggested but not according to severity of the valve involvement. This study attempts to identify the relevance of CTLA-4 polymorphism with severity of the disease., Methods: In a case-control design, 291 healthy controls and 83 patients were genotyped for association between RHD and single-nucleotide polymorphisms -1661A/G of CTLA-4., Results: Segregation of patients on the basis of severity i.e., MVL (Mitral Valve Lesion) and CVL (Combined Valve Lesion) revealed that the frequency of CTLA-4 -1661G allele depleted as the disease progressed to CVL (p < 0.05). Patients in the age group of 31-45 years were significantly more susceptible (p < 0.046). Whereas, female patients were more susceptible than the male patients., Conclusion: Our study suggests the risk associated with decreased frequency of CTLA-4 -1661G allele in the CVL group and in females., Competing Interests: Declaration of competing interest All the authors state that they have no conflict interest to declare with respect to the present article titled “Susceptibility of CTLA-4 −1661A/G polymorphism towards severity of Rheumatic Heart Disease”., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: There is no large contemporary data from India to see the prevalence of burnout in HCWs in covid era. Burnout and mental stress is associated with electrocardiographic changes detectable by artificial intelligence (AI)., Objective: The present study aims to estimate the prevalence of burnout in HCWs in COVID-19 era using Mini Z-scale and to develop predictive AI model to detect burnout in HCWs in COVID-19 era., Methods: This is an observational and cross-sectional study to evaluate the presence of burnout in HCWs in academic tertiary care centres of North India in the COVID-19 era. At least 900 participants will be enrolled in this study from four leading premier government-funded/public-private centres of North India. Each study centre will be asked to recruit HCWs by approaching them through various listed ways for participation in the study. Interested participants after initial screening and meeting the eligibility criteria, will be asked to fill the questionnaire (having demographic and work related with Mini Z questionnaire) to assess burnout. The healthcare workers will include physicians at all levels of training, nursing staff and paramedical staff who are involved directly or indirectly in COVID-19 care. The analysis of the raw electrocardiogram (ECG) data and development of algorithm using convolutional neural networks (CNN) will be done by experts., Conclusions: In Summary, we propose that ECG data generated from the people with burnout can be utilized to develop AI-enabled model to predict the presence of stress and burnout in HCWs in COVID-19 era., Competing Interests: Declaration of competing interest None declared for all authors., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: While the pro-inflammatory and pro-coagulant effects of cigarette smoking have been well described, the effect of smokeless tobacco (ST) on inflammatory and coagulation markers is still not clear. The study aimed to evaluate impact of smokeless tobacco use on systemic markers of inflammation [(TLC), neutrophil-lymphocyte ratio (NLR) (ESR), interleukin (IL) IL-1β, IL-6 and tumor necrosis factor alpha (TNFα)] and hypercoagulable state [fibrinogen and d-dimer] leading to increased cardiovascular risk in ST users as compared to non-users., Methods: 150 healthy young adults using oral tobacco products for at least 1 year were included in the case group and 50 age-matched non-consumers as controls. Subjects with any known chronic illness or comorbidity were excluded from the study. Blood samples were tested for TLC, NLR, ESR, IL-1β, IL-6, TNFα, fibrinogen and d-dimer. Statistical analysis was done using SPSS 17.0 software., Results: The baseline clinical and cardio-metabolic characteristics were comparable between the two groups. ST users had significantly elevated serum IL-6 [59.29 ± 124.69 pg/mL (n = 149) vs 8.21 ± 27.27 pg/mL (n = 47), p-value = 0.005], TNFα [77.18 ± 236.10 pg/mL (n = 149) vs 8.32 ± 9.36 pg/mL (n = 47), p-value = 0.041], fibrinogen [310.53 ± 129.05 mg/dL (n = 143) vs 282.82 ± 65.23 mg/dL (n = 42), p-value = 0.045] and d-dimer [0.28 ± 0.42 mg/L (n = 144) vs 0.17 ± 0.09 mg/L (n = 45), p-value = 0.043] levels as compared to non-users. Serum TLC, NLR, ESR and IL-1β remained unchanged in ST users and were similar to that of controls., Conclusions: Chronic use of ST is associated with systemic inflammation and coagulation, which may increase the risk of athero-thrombotic cardiovascular events among ST users., Competing Interests: Conflict of interest All authors have none to declare., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Cardiovascular disease is the leading cause of death in India. Previously it was thought to be a disease of the elderly but now an epidemiological transition is being seen with increasing incidence in the very young adults as well. Such patterns are not well studied in the South East Asian population., Objective: To study the epidemiological profile of very young (≤35 years) adults presenting with an acute myocardial infarction (AMI) in comparison with an older cohort., Methodology: The present study included all patients presenting with AMI to the emergency or to the out-patient department of the G B Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi between January 2014 and October 2015. A total of 102 subjects ≤35 years with AMI comprised the study subjects (cases) and were compared with 104 subjects >35 years old with AMI (Controls)., Results & Conclusion: Most of the very young AMI patients presented with an anterior wall ST segment elevation myocardial infarction, a stable hemodynamic profile, single vessel disease and better left ventricular ejection fraction as compared with controls. Most of the patients were from urban and semi-urban areas, middle and lower middle socioeconomic status and were smokers but lacked other traditional risk factors., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: Incidence rate of acute myocardial infarction (MI) has increased in younger population over the years. The young patients have a different risk profile, presentation, and prognosis than the elderly. Hence, it is essential to understand the risk factors in young patients for proper treatment., Methods: Apolipoprotein E (ApoE) polymorphism and biochemicals such as total cholesterol, serum triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a), insulin, interleukin-6, homocysteine, fibrinogen, and highly sensitive C-reactive protein were investigated in very young MI (yMI patients; age ≤ 35 years; n = 125), in old MI (oMI patients; age >35 and < 80 years; n = 111), and healthy controls (age ≤35 years; n = 103)., Results: HDL-C was significantly lower in yMI patients than in controls (p = 2.63E-04) and oMI patients (p = 1.29E-05). ApoA1 was also lowest in yMI patients, but significant only in comparison to controls (p = 2.62E.04). The yMI group had the highest ratios of total cholesterol:HDL-C (p = 0.027 in yMI patients versus controls and p = 0.018 in yMI patients versus oMI patients), LDL-C:HDL-C (p = 0.002 in yMI patients versus controls and p = 0.005 in yMI patients versus oMI patients), and ApoB:ApoA1 (p = 8.75E-05 in yMI patients versus controls and p > 0.05 in yMI patients versus oMI patients). No significant pattern of ApoE polymorphisms was observed., Conclusion: The lower level of HDL-C and ApoA1 and higher ratios of total cholesterol:HDL-C, LDL-C:HDL-C, and ApoB:ApoA1 are risk factors for MI in young patients., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Purpose: Currently, most high-grade glioma patients undergo a 1.5T brain magnetic resonance (MR) for radiation treatment planning. We hypothesized that 3T MR imaging (MRI) scanning is superior to 1.5T due to higher signal-to-noise ratio (SNR), and thus will result in more accurate quantification of tumor volumes. The purpose of this prospective study was to determine differences in radiation planning volumes for high-grade gliomas when scanned on 3T MR versus 1.5T MR., Methods and Materials: In this prospective controlled trial, 23 patients with high-grade gliomas underwent brain MRI scanning in both 1.5T and 3T field strengths within a 24-hour period; no steroids or treatment changes were made in-between scans. After 3 investigators contoured the T2 fast low-angle inversion recovery (FLAIR) abnormality (gross tumor volumes or [GTV]) for all patients, clinical target volume (CTV) and planning treatment volumes (PTV) were defined. Calculations by an independent investigator included volumes, standard deviations, SNRs, and contrast-to-noise ratios (CNRs); statistical analysis was performed on raw data., Results: Planning treatment volume ratios (3T:1.5T) for each investigator were 0.95 ± 0.12 (range, 0.64-1.10), 0.98 ± 0.10 (range, 0.64-1.16), and 0.99 ± 0.06 (range, 0.86-1.13). By paired 2-tailed t test, these volumes were not statistically different (P = .051), although there is a trend to 3T producing smaller volumes than 1.5T. Dice similarity coefficients were 0.90 ± 0.05, 0.90 ± 0.06, and 0.91 ± 0.05 for the investigators., Conclusions: Planning target volumes for high-grade gliomas were similar at 3T and 1.5T MR using our standard imaging protocols. However, in some patients, the 3T MR may reveal substantially smaller tumor volume due to inferior conspicuity of the lesion. These findings imply that while overall the radiation target volumes are comparable, there are differences in CNR and SNR that lead to differences in individual patients. The 1.5T may be better for gaining conspicuity of the tumor., (Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. The objective of the present study was to investigate dietary nicotinamide enrichment dependent adaptive response to potential cytotoxic effect of (60)Co γ-radiation. To elucidate the possible underlying mechanism(s), male Swiss mice were maintained on control diet (CD) and nicotinamide supplemented diet (NSD). After 6 weeks of CD and NSD dietary regimen, we exposed the animals to γ-radiation (2, 4 and 6Gy) and investigated the profile of downstream metabolites and activities of enzymes involved in NAD(+) biosynthesis. Increased activities of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNAT) were observed up to 48h post-irradiation in NSD fed irradiated mice. Concomitant with increase in liver NAMPT and NMNAT activities, NAD(+) levels were replenished in NSD fed and irradiated animals. However, NAMPT and NMNAT-mediated NAD(+) biosynthesis and ATP levels were severely compromised in liver of CD fed irradiated mice. Another major finding of these studies revealed that under γ-radiation stress, dietary nicotinamide supplementation might induce higher and long-lasting poly(ADP)-ribose polymerase 1 (PARP1) and poly(ADP-ribose) glycohydrolase (PARG) activities in NSD fed animals compared to CD fed animals. To investigate liver DNA damage, number of apurinic/apyrimidinic sites (AP sites) and level of 8-hydroxy-2'-deoxyguanosine (8-oxo-dG) residues were quantified. A significant increase in liver DNA AP sites and 8-oxo-dG levels with concomitant increase in caspase-3 was observed in CD fed and irradiated animals compared to NSD fed and irradiated mice. In conclusion present studies show that under γ-radiation stress conditions, dietary nicotinamide supplementation restores DNA excision repair activity via prolonged activation of PARP1 and PARG activities. Present results clearly indicated that hepatic NAD(+) replenishment might be a novel and potent approach to reduce radiation injury., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A characterization study detailing the phase transformations and microstructural nature of the carbon deposited during methane decomposition over red mud has been undertaken. In situ XRD was carried out to study the phase transformation sequences of red mud during the reaction. Scanning electron microscopy, high resolution transmission electron microscopy, thermogravimetric analysis, BET surface area determination and CHN analysis were carried out to investigate the properties of the post-reaction samples. Exposure to methane with increasing temperature caused a stepwise reduction of iron oxides in red mud and promoted methane cracking leading to carbon deposition. The presence of carbon nanostructures was confirmed by HRTEM observations. The carbon formed was graphitic in nature and the spent red mud, rich in Fe and Fe(3)C formed as a result of the reduction of the iron oxide, was magnetic in nature. The surface area of the material was enhanced upon reaction. In addition, reactivity comparisons between goethite and red mud were carried out to study the formation of carbon oxides during reaction., (Copyright 2010 Elsevier B.V. All rights reserved.)

Radiation exposure poses a major risk for workers in the nuclear power plants and other radiation related industry. In this context, we demonstrate that gamma-radiation is an efficient DNA demethylating agent and its injurious effect can be minimized by dietary methyl supplements (folate, choline and vitamin B12). To elucidate the possible underlying mechanism(s), male Swiss mice were maintained on normal control diet (NCD) and methyl-supplemented diet (MSD). After 2 weeks of NCD and MSD dietary regimen, we exposed the animals to gamma-radiation (2, 4 and 6Gy) and investigated the profile of downstream metabolites and activity levels of one-carbon (C(1)) flux generating enzymes. In MSD fed and irradiated animals, hepatic folate levels increased (P<0.01), while hepatic homocysteine levels decreased (P<0.01) compared to NCD fed and irradiated animals. Although hepatic folate level increased significantly in MSD fed animals (P<0.01), it showed a decrease in response to high doses of gamma-irradiation. Under these conditions, a marked suppression of S-adenosylmethionine (SAM) levels occurred in NCD fed and irradiated animals, suggesting reduced conversion of homocysteine to SAM. Concomitant with decline in liver SAM Pool, activities of DNA methyltransferase (Dnmt, that methylates DNA) and methionine synthase (MSase, that regenerates methionine from homocysteine) were both decreased in NCD fed and irradiated mice. However, in MSD fed and irradiated mice, they were increased. These results strongly indicated that increased levels of dnmt and MSase may enhance C(1) flux towards DNA methylation reactions in MSD fed animals. These results were confirmed and further substantiated by measuring genomic DNA methylation levels, which were maintained at normal levels in MSD fed and irradiated mice compared to NCD fed and irradiated animals (P<0.01). In conclusion, our results suggest that maintenance of genomic DNA methylation under gamma-radiation stress might be a very dynamic, progressive diet dependent process that could involve increased one-carbon flux through various C(1) metabolites., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

The search for non-toxic radio-protective drugs has yielded many potential agents but most of these compounds have certain amount of toxicity. Recent studies have indicated that bio-molecules such as folate and choline might be of radio-protective value as they are, within broad dose ranges, non-toxic to humans and experimental animals. The objective of the present study was to investigate choline dependent adaptive response to potential synergistic cytotoxic effect of folate deficiency and gamma-radiation. Male Swiss mice maintained on folate sufficient diet (FSD) and folate free diet (FFD) based on AIN-93M formula, were subjected to 1-4Gy total body gamma-irradiation. To investigate liver DNA damage, apurinic/apyrimidinic sites (AP sites) were quantified. A significant increase in liver DNA AP sites with concomitant depletion of liver choline reserves was observed when gamma-radiation was combined with folate deficiency. Further work in this direction suggested that cytotoxic interaction between folate deficiency and gamma radiation might induce utilization of choline and choline containing moieties by modifying levels of key regulatory enzymes dihydrofolate reductase (DHFR) and choline oxidase (ChoOx). Another major finding of these studies is that significant liver damage at higher doses of radiation (3-4Gy), might release considerable amounts of choline reserves to serum. In conclusion, a plausible interpretation of the present studies is that folate deprivation and gamma-radiation interact to mobilize additional choline reserves of hepatic tissue, for redistribution to other organs, which could not be utilized by folate deficiency alone. Present results clearly indicated a distinct choline pool in liver and kidney tissues that could be utilized by folate deficient animals only under radiation stress conditions.

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of piperaquine, an antimalarial drug, in human plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method involved a simple protein precipitation with methanol followed by rapid isocratic elution of analytes with 10mM ammonium acetate buffer/methanol/formic acid/ammonia solution (25/75/0.2/0.15, v/v) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and quantification by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 535.3-->288.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 1.0-250.2 ng/mL for piperaquine in plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) in plasma were 0.2 and 1.0 ng/mL, respectively. Acceptable precision and accuracy (+/-20% deviation for LLOQ standard and +/-15% deviation for other standards from the respective nominal concentration) were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully applied to analyze human plasma samples from phase-1 clinical studies. The mean pharmacokinetic parameters of piperaquine following 1000 mg oral dose: observed maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (T1/2) were 46.1 ng/mL, 3.8h and 13 days, respectively.

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of chloroquine, an antimalarial drug, in plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method is based on simple protein precipitation with methanol followed by a rapid isocratic elution with 10 mM ammonium acetate buffer/methanol (25/75, v/v, pH 4.6) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 320.3-->247.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 2.0-489.1 ng/mL for chloroquine in dog plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.4 and 2.0 ng/mL, respectively in 0.05 mL plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range of 2.0-489.1 ng/mL. A run time of 2.0 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully used to analyze samples of dog plasma during non-clinical study of chloroquine.

Objective: The approach and credibility of future physicians and nurses as treatment providers for smoking- and tobacco-related diseases may be influenced by their smoking habits. We compared smoking habits among medical and nursing students, and examined whether these habits changed during the course of education for each cohort., Method: Over 1,100 medical and nursing students from a university were surveyed in year 2000 using a questionnaire that included the Fagerstrom test for nicotine dependence (FTND)., Results: A total of 397 medical students and 126 nursing students completed the survey. Significantly fewer medical students (3.3%) smoked compared to nursing students (13.5%). Also, significantly more nursing students were former smokers (17.8%) than medical students (9.8%). The severity of nicotine dependence, as indicated by the total FTND score as well as scores on five of the six items on the FTND, was significantly lower among medical students compared to nursing students. Smoking or quit rates did not differ across class years in both groups; however, unlike nursing students, time since quitting significantly differed across class years for medical students. Although smoking habits appear to change little during the course of education for both medical and nursing students, many smokers may have quit just prior to entering medical school but not nursing school., Conclusions: The findings confirm the continuing decline in smoking among medical students in the United States; however, increased efforts to promote tobacco education and intervention among nursing students seem necessary. Nevertheless, both groups appear to have the potential to be credible advisors to patients and public regarding smoking cessation.

Dependence on tobacco, like many other drug dependencies, is a complex behavior with both genetic and environmental factors contributing to the variance. The heritability estimates for smoking in twin studies have ranged from 46 to 84%, indicating a substantial genetic component to smoking. Candidate gene studies have detected functional polymorphisms in genes coding for the cytochrome P450 enzymes, and variations in these genes that lead to more rapid nicotine metabolism have been implicated in smoking. Similarly, smoking has been associated with polymorphisms in dopaminergic genes that may influence the dopamine receptor number and/or function. Animal experiments have localized specific subunits of the nicotinic receptors that may mediate the reinforcing properties of nicotine and have investigated their role in nicotine dependence. However, environmental factors have also been found to contribute to the risk of initiation and persistence of smoking. We review the scientific evidence that supports a role for genetic influences on smoking, discuss the specific genetic and neurobiological mechanisms that may mediate susceptibility to nicotine dependence, identify possible gene/environmental interactions that may be important in understanding smoking behavior, and suggest directions for future research. Insights into the genetic contributions to smoking can potentially lead to more effective strategies to reduce smoking.

Despite availability of effective treatments for nicotine addiction, smoking remains prevalent with serious health consequences. Most smokers recognize the ill effects of smoking but are unable to quit. Nicotine addiction may be viewed as any other chronic illness that results from exposure to a recognizable agent (tobacco) and manifests with a well-documented set of signs and symptoms. Much like any chronic disease, both environmental and genetic factors determine the occurrence and severity of this affliction. There has been recent focus on uncovering the genetic basis of nicotine addiction. In this article, we have attempted to briefly review the current evidence for the role of genetics in smoking as well as comment on available pharmacotherapeutic options for treating nicotine dependence.

Background: Tobacco use remains the most preventable cause of death and disability in the United States. Public opinion regarding tobacco use is not only an important barometer of the likelihood of effective tobacco-control legislation, but also identifies ongoing public health educational needs. Because > 63,000 children become new smokers annually in Pennsylvania, we chose to evaluate the statewide public health tobacco perspective in order to help tailor future public policy interventions., Study Design and Setting: Registered voters were randomly contacted in a statewide telephone survey. To reduce response bias, an independent polling firm conducted the 643 structured interviews., Results: Most respondents were >or= 45 years old (55%), female (54%), and had at least some college education (62%). Twenty-eight percent (95% confidence interval [CI], 25 to 32%) were current tobacco users, and 38% (95% CI, 34 to 42%) had lost family members or friends to smoking-related disease. Ninety-two percent (95% CI, 90 to 94%) expressed "concern" about adolescent tobacco use, but only 46% (95% CI, 42 to 50%) believed that government needed to do more. Of respondents opposed to government involvement, 65% (95% CI, 61 to 68%) believed it was an improper role for government, or that there are more important non-health government priorities. When framed more personally, 80% (95% CI, 77 to 83%) indicated that elected officials have a responsibility to "dedicate a significant portion of tobacco settlement" to prevention. Still, 28% (95% CI, 25 to 32%) would oppose laws restricting smoking in establishments frequented by youth., Conclusions: Prior public health education initiatives have been effective in shaping the tobacco-related health concerns of Pennsylvania voters. As expected, the overwhelming majority of respondents are concerned about youth tobacco use and agree that money should be spent on tobacco-control initiatives. In contrast, many are reluctant to support "government" involvement in what is still seen as a personal issue. Future public health initiatives should focus on this dichotomy and should highlight the utility of an integrated policy approach to tobacco control.

Sustained release of ferrous sulfate (FeSO4) from gum arabica pellets has been achieved for 7 h. Release is further sustained for 12 to 600 h by coating the pellets with polyvinyl acetate and ethylene vinyl acetate, respectively. An increase in the amount of gum arabica in the pellets decreases the rate of release due to the gelling property of gum arabica. The gel layer acts as a barrier and retards the rate of diffusion of FeSO4 through the pellet. In coated pellets, an increase in thickness of membrane helps to sustain the release of FeSO4 for a longer duration. Thus, the release of FeSO4 can be sustained for the required duration by adjusting the amount of gum arabica in the pellet and the composition and thickness of polymeric coat. The mechanism of release accordingly varies from Fickian to zero-order and super case II transport.

97 patients with symptoms of early tetanus at the time of admission to hospital were treated with sedation, antibiotics, and human tetanus immune globulin (TIG). After intrathecal TIG 250 IU 3 patients out of 49 got worse but only 1 died while in a closely similar group of 48 patients in whom TIG was administered intramuscularly in dose of 1000 IU, the clinical features of the disease became severer in 15 (31%) and 10 (21%) died. The intrathecal use of TIG was devoid of side effects.

Piperacillin sodium was administered intravenously to dogs, alone or in combination with gentamicin, twice a day (approximately 5 hr apart) for 36-37 days. The pharmacokinetics of neither drug changed in the presence of the other; however, the percentage of the gentamicin dose recovered in the urine decreased significantly when coadministered with piperacillin. The data demonstrate that interaction between the two drugs in urine is feasible.

A new topically active antihypertensive agent, the methyl ester of 15-deoxy-16-hydroxy-16-vinylprostaglandin E2 (1), rapidly hydrolyzes in blood to the carboxylic acid 2, which also has antihypertensive activity. A capillary gas chromatographic-mass spectrometric method is described for measuring 2 in human plasma or serum at expected experimental blood levels of 75-1500 pg/mL. The assay is based on selected-ion monitoring of the carboxylate anion formed from negative ion chemical ionization of the trimethylsilylpentafluorobenzyl ester of 2, using a trideuterated analogue of 2 as internal standard. The method has been used to analyze samples from subjects following topical application of 1-2 mg of 1. Sample preparation included isolation from 1 mL of plasma or serum and purification of the ester derivative with C18 cartridges, followed by a two-step trimethylsilylation.

This investigation generated data characterize a specific electron-capture GLC assay reported previously for naltrexone and applied the method to a determination of naltrexone pharmacokinetics. Extraction efficiencies are reported for the assay, and mass spectral evidence indicates that naltrexone forms a triester when derivatized for electron-capture GLC with pentafluoropropionic anhydride and a base catalyst. Plasma level-time data for intravenous naltrexone at two dose levels in monkeys yielded no evidence of dose-dependent kinetics. A two-compartment open pharmacokinetic model was fitted to plasma level-time data for naltrexone in two dogs and yielded a total body clearance of 51-55 ml/min/kg. Urine collected for 0-24 hr contained 36% of the dose as naltrexone conjugates with less than 1% as unchanged naltrexone. Plasma level-time data for intravenous naltrexone in six monkeys yielded an average terminal half-life of 7.8 hr and a total body clearance of 64 ml/min/kg. The total body clearance for naltrexone was greater than the hepatic plasma or blood flow in both dogs and monkeys. This finding, together with the extremely low renal excretion of naltrexone, suggests the existence of elimination mechanisms besides liver metabolism and renal excretion.