Incidence, Pattern, Causes, and Outcome of Acute Chest Pain Among Patients Presenting in the Emergency Department of a Tertiary Care Hospital in North India.

BACKGROUND: Acute chest pain is a common presentation in emergency departments worldwide. Differentiating between cardiac and non-cardiac chest pain is crucial for patient management and resource allocation. METHODS: This study analyzed 714 patients presenting with acute chest pain in a tertiary care hospital in North India. We investigated demographic characteristics, chief complaints, risk factors, ECG findings, and final diagnoses to identify patterns associated with cardiac (CCP) and non-cardiac chest pain (NCCP). RESULTS: CCP was diagnosed in 53.7% (n=383) and NCCP in 46.3% (n=331). Significant predictors of CCP included age (OR=1.05, p<0.001), smoking (OR=2.22, p<0.001), diabetes (OR=1.57, p=0.003), hypertension (OR=1.82, p<0.001), and family history of ischemic heart disease (IHD) (OR=1.42, p=0.01). Central chest pain was more common in CCP (60% vs. 40%, p<0.001), as were abnormal ECG findings such as ST-segment depression (35% vs. 10%, p<0.001) and elevation (29% vs. 6%, p<0.001). Normal ECG was more prevalent in NCCP (60%, p<0.001). CONCLUSION: Traditional cardiovascular risk factors remain strongly associated with CCP. Smoking has a particularly high odds ratio, suggesting the need for targeted interventions. ECG findings significantly aid in differentiating CCP from NCCP. This study underscores the importance of a comprehensive approach in evaluating acute chest pain to ensure accurate diagnosis and effective treatment.

Interactions between diabetic and hypertensive drugs: a pharmacogenetics approach.

Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.

Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity.

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

Structural interactions of phytoconstituent(s) from cinnamon, bay leaf, oregano, and parsley with SARS-CoV-2 nucleocapsid protein: A comparative assessment for development of potential antiviral nutraceuticals.

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin > catechin > apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin > cinnamic acid > catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.

Prevalence of Comorbidities in Survivors and Non-Survivors of Severe COVID-19 at a Dedicated COVID Care Centre.

Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. Diseases such as diabetes, hypertension, cardiovascular and pulmonary diseases are common comorbidities in COVID-19 patients and have been correlated with increased disease severity. Comorbidities lead the COVID-19 patient into a vicious infectious circle and are substantially associated with significant morbidity and mortality. This study was aimed to estimate prevalence of comorbidities in severe category of COVID survivors and non survivors. More than 90% patients with multiple comorbidities admitted to ICU did not survive compared to those with one or two comorbidities. Diabetes followed by hypertension was the most common comorbidity in these patients. Thus comorbid individuals must adopt vigilant preventive measures including vaccination and they require intensive management for better outcome.

Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis.

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.

A Clinical Study to Evaluate the Association Between Metabolic Syndrome and Sensorineural Hearing Loss.

Metabolic syndrome is considered to be a triggering factor for deterioration of health related quality of life. In present study we assessed hearing loss consequent to metabolic syndrome. A total of 100 patients diagnosed for metabolic syndrome (IDF criteria) were included in the study. All the patients underwent pure tone audiometry and impedance audiometry. All the patients underwent anthropometric measurements, lipid profile, blood sugar and blood pressure assessments. Data was analyzed using SPSS 21.0 software. A total of 62% patients had sensorineural hearing loss. Maximum (35%) had mild hearing loss, followed by moderate hearing loss (23%). Only 4 (4%) cases had severe hearing loss. Older age, wider waist circumference, higher fasting blood glucose levels and lower blood pressure were found to be significantly associated with sensorineural hearing loss and its severity on univariate analysis. However, on multivariate assessment only age and waist circumference showed a significant association with hearing loss.

Study of Association of Metabolic Syndrome and Risk Factors of Nephrolithiasis.

BACKGROUND AND AIM: The increasing incidence of nephrolithiasis in recent decades is coinciding with rising epidemic of obesity, metabolic syndrome, and type 2 diabetes. This temporal concordance suggests that a link might exist between these metabolic abnormalities and urinary stone disease. Therefore, the present study was aimed to investigate the association between presence of risk factors of nephrolithiasis and metabolic syndrome. METHODS: In a hospital-based, case control study, hundred patients of metabolic syndrome diagnosed according to IDF criteria and hundred age and matched controls were studied for presence of risk factors of nephrolithiasis. RESULTS: Patients with metabolic syndrome had significantly higher uricosuri a,hypercalciuria,oxaluria and hypocitraturia. The prevalence of risk factors of nephrolithiasis was also higher in patients with metabolic syndrome. The most prevalent was low urinary pH in 40% patients with mean pH of 5.8±1.6. Amongst other factors, 33% had hyperuricemia, 29% had hypercalciuria, 15% had oxaluria 13% had hypocitraturia and 10% had hyperuricosuria. Significant correlation was observed between risk factors of nephrolithiasis and components of metabolic syndrome. CONCLUSION: The present study provides an evidence of association between risk factors of nephrolithiasis and metabolic syndrome and suggests that nephrolithiasis may be a systemic disorder representing the interaction of multiple metabolic derangements. Determining common modifiable risk factors for the development of kidney stones might uncover new preventive strategies.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

Association of Genetic Non-alcoholic Fatty Liver Disease with Insulin Resistance-Are we Different?

INTRODUCTION: Metabolic risk factors such as obesity, insulin resistance, type 2 diabetes mellitus and dyslipidemia are associated with non-alcoholic fatty liver disease (NAFLD). In the development and progression of NAFLD genetic mutations also play a significant role. NAFLD associated with the rs 738409 polymorphism of patatin-like phospholipase domain containing 3 gene (PNPLA3) G allele does not feature the typical metabolic abnormalities of NAFLD, including insulin resistance. In the light of rising epidemic of metaobesity in our population this study aimed to evaluate the relation of PNPLA3 polymorphism with insulin resistance. METHODS: In this case control hospital based study, 100 patients of NAFLD were recruited based on ultrasound findings of hepatic steatosis. Healthy subjects age and gender matched(n = 100) from the institute who volunteered to be part of the study were recruited as controls based on the sole criteria of the absence of fatty liver on ultrasonography and normal alanine and aspartate transaminases (ALT and AST) levels. Anthropometry, biochemical profiles and insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. RESULTS: A higher frequency of CG and GG genotypes of rs738409 polymorphism of PNPLA3 was observed in patients with NAFLD than controls. These patients with G allele had increased ALT, dyslipidemia and insulin resistance. The polymorphism had positive correlation with severity of hepatic steatosis. CONCLUSION: The presence of the PNPLA3 G allele is associated with a risk of NAFLD. Our study shows that subjects with variant PNPLA3 are not only at increased risk for the development and progression of NAFLD, but also have increased insulin resistance.

Cerebrospinal Fluid Lactate in Tubercular Meningitis: Diagnostic or Prognostic Marker?

Introduction/Background: Diagnosis of tubercular meningitis (TBM) continues to be a clinical challenge and available microbiological tests fail to attain the required accuracy standards. As a result, most guidelines for the diagnosis and management of TBM depend on clinical setting, cerebrospinal fluid (CSF) analyses including adenosine deaminase activity (ADA), and imaging to guide decisionmaking. Delay in diagnosis leads to high mortality and morbidity. As there is scarcity of data on CSF lactate in TBM and its role as a diagnostic and prognostic marker, study of CSF Lactate in TBM Patients was undertaken. Methods: In this hospital based cross sectional study all admitted patients of meningo-encephalitis aged more than 15 years who fulfilled the diagnostic criteria for TBM were included. Routine haematological and biochemical investigations were done in all the patients. The CSF analysis was done including all routine microscopic parameters, lactate, Gram's stain, AFB and culture. Patients included were classified as definite, probable, or possible TBM as per WHO diagnostic criteria and were classified into three clinical stages using criteria laid down by the British Medical Research Council. Results: Fifty five patients fulfilling the diagnostic criteria for tubercular meningitis were studied. Most of the patients were in stage II according to severity. An increase in CSF lactate and CSF ADA levels with increase in severity of clinical stage of TBM was observed. Other CSF parameters and imaging were not significantly different in various groups. Conclusion: CSF lactate levels of study patients were higher than normal and showed increasing trend from possible to definite diagnosis of TBM suggesting that CSF lactate could be a predictor of definite diagnostic class of TBM though more studies with large number of patients are needed to prove its utility as prognostic tool.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as early markers of diabetic nephropathy.

INTRODUCTION: Diabetes mellitus (DM) is a major cause of concern because of its increasing prevalence rate and related microvascular as well as macrovascular complications, including kidney disease. Microalbuminuria has been accepted as the earliest marker for diabetic nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. We planned to investigate the serum and urinary levels of the tubular damage markers (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C [Cys C]) in patients of type 2 diabetes to detect early kidney injury. MATERIALS AND METHODS: This cross-sectional hospital-based study included 180 patients with type 2 DM according to the American Diabetes Association criteria. Serum NGAL (S.NGAL) and urine NGAL (U.NGAL) and Cys C were measured in all study participants and investigated for correlation with microalbuminuria. RESULTS: Our results showed that U.NGAL and S.NGAL levels were significantly high in patients with microalbuminuria as compared to normoalbuminuric controls. Serum Cys C was also higher in microalbuminuric patients than who had normoalbuminuria. A positive correlation of urinary albumin excretion with S.NGAL and U.NGAL was noted. U.NGAL also showed positive correlation with duration of diabetes, glycated hemoglobin, and dyslipidemia. Receiver operating characteristic curve analysis showed that the area under the curve for U.NGAL and S.NGAL were 1 and 0.8, respectively, which indicates that they are sensitive markers for early renal damage. CONCLUSION: Urinary biomarkers were significantly elevated in normoalbuminuric type 2 diabetic patients compared with nondiabetic controls and could be used as markers of nephropathy at a very early stage even before the development of microalbuminuria, the current gold standard for early diagnosis. Despite the promise of these new biomarkers, further large, multicenter prospective studies are still needed.

Soft Drinks Consumption and the Risk of Nonalcoholic Fatty Liver Disease.

INTRODUCTION: The increased consumption of sugar-sweetened beverages (SSBs) has been implicated in the increased incidence of obesity and metabolic syndrome Little of the research on sugar-sweetened beverage intake has examined the consumption patterns of sugared beverages by college students, despite the vulnerabilities of this population to weight gain. The current study sought to characterize sugar-sweetened beverage intake of undergraduate students who belong to high socio-economic strata and to study its correlation with presence of non-alcoholic fatty liver disease. MATERIAL AND METHODS: In a cross sectional, a self reported questionnaire based study about soft drink consumption (≥2/day, 1/day, <1/day). That included undergraduate medical students. Anthropometry and blood pressure were recorded and fasting glucose, insulin and lipid profile and abdominal ultrasonography for the presence of fatty liver was assessed. RESULTS: A total of 242 students were studied. The students in group 1 (≥2/day) had significantly higher BMI, waist circumference and diastolic blood pressure than students of other groups. They also had higher triglycerides, fasting insulin, HOMA-IR and significantly lower levels of HDL-cholesterol. Overall (40%) students had metabolic syndromes in group 1 compared to 8% and 3% in other groups while presence of NAFLD was observed in 75%, 16% and 4% in three groups respectively. Duration of soft drink consumption had positive correlation with presence of NAFLD. CONCLUSIONS: Substantial consumption of soft drinks is leading to increased obesity and cardio-metabolic risk factors in young adults. Artificially sweetened diet soft drinks have been posed as a healthier alternative due to their lack of calories but they do not guarantee protection against non-alcoholic fatty liver disease.

The relationship between Multidrug Resistance Protein 1(rs1045642) and Cholesterol 24-hydroxylase (rs754203) genes polymorphism with type 2 diabetes mellitus.

BACKGROUND: The involvement of genetic factors like gene polymorphisms has been found to contribute significantly to the development and progression of type 2 diabetes (T2DM). Thousands of single nucleotide polymorphisms in various genes have been found to be associated with risk of T2DM. The present study was aimed to investigate association of Multidrug resistance 1 (MDR1) (rs1045642) and CYP46A1 (rs754203) genes polymorphism with T2DM. SUBJECTS & METHODS: Study includes 333 subjects, 183 T2DM cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by PCR-PFLP. Alleles and genotype frequencies between cases and controls were compared using χ2 and Student's t-tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. RESULTS: In case of CYP46A1 gene, CC (p < 0.001) and CT (p = 0.001) genotypes and C allele (p < 0.001) were found to be a positive risk factor and TT genotype (p < 0.001) and T allele (p < 0.001) as negative risk factor for T2DM whereas, no association of MDR1 gene was found with T2DM (P values of all genotypes and alleles were greater than 0.001). MDR1 (rs1045642) and CYP46A1 (rs754203) genes polymorphism was not found associated with Fasting Blood Sugar (FBS), Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP). CONCLUSION: CYP46A1 gene polymorphism is associated with the risk of T2DM whereas, MDR1 gene polymorphism was not found to confer any risk of T2DM in North Indian Ethnic group.

Study of Vitamin D Status in Patients with Dilated Cardiomyopathy at a Teaching Hospital in North India.

BACKGROUND/INTRODUCTION: Recent studies have indicated a much broader role to Vitamin D than simply the regulation of calcium metabolism alone. Vitamin D likely confers physiologically relevant pleiotropic functions that include cardioprotective and immunomodulatory effect, and its deficiency could lead to increased risk of cardiovascular disease and heart failure. AIM: The aim of our work was to evaluate the presence of hypovitaminosis D in patients with dilated cardiomyopathy (DCMP) and to study any correlation of echocardiographic parameters with Vitamin D deficiency. PATIENTS AND METHODS: In an observational case-control hospital-based study, 56 patients diagnosed to have DCMP and 60 age-, gender-, and body mass index-matched controls who were patients of other medical illnesses were included in the study. Each subject underwent transthoracic two-dimensional guided M-mode echocardiography, and Vitamin D, parathyroid hormone (PTH), and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were assessed. RESULTS: Mean 25-hydroxyvitamin D3 [25(OH) D3] levels were significantly lower (14.5 ± 7.4 ng/ml vs. 28.2 ± 12 ng/ml, P = 0.001), whereas PTH (90.5 ± 28.5 pg/ml vs. 57 ± 20.2 pg/ml, P = 0.02) and NT-proBNP levels were significantly greater in patients with DCMP than controls. In DCMP group, 24/56 patients had severe Vitamin D deficiency, whereas in control group, 10/60 patients had severe hypovitaminosis D. There was a significant negative correlation between 25(OH) D3 concentrations and left ventricular (LV) end-diastolic and LV end-systolic dimensions. CONCLUSION: Patients with DCMP had lower Vitamin D levels than controls, and Vitamin D deficiency had a significant correlation with cardiac function. Therefore, screening for Vitamin D deficiency along with prompt treatment is recommended in patients with DCMP.

Association of Angiotensin-Converting Enzyme and Glutathione S-Transferase Gene Polymorphisms with Body Mass Index among Hypertensive North Indians.

OBJECTIVES: This study aimed to examine the association of angiotensin-converting enzyme (ACE) and glutathione S-transferase (GST) gene polymorphisms with body mass index (BMI) in hypertensive North Indians. METHODS: This case-control study was carried out between May 2013 and November 2014 at the Era's Lucknow Medical College & Hospital, Lucknow, India, and included 378 subjects divided into three groups. One group constituted 253 hypertensive individuals (sustained diastolic blood pressure of >90 mmHg and systolic blood pressure of >140 mmHg) who were subcategorised according to normal (<25 kg/m(2)) or high (≥25 kg/m(2)) BMI. The third group consisted of 125 age-, gender- and ethnically-matched normotensive controls with a normal BMI. Gene polymorphisms were evaluated by polymerase chain reaction. The genotypic and allelic frequency distribution among both groups were analysed. RESULTS: A significant difference was found between GST theta 1-null and GST mu 1-positive genotype frequencies among the hypertensive overweight/obese individuals and controls (P = 0.014 and 0.033, respectively). However, no difference was observed in the frequency of ACE polymorphisms. ACE insertion/insertion genotype (P = 0.006), insertion and deletion alleles (P = 0.007 each) and GST theta 1-null and GST theta 1-positive genotypes (P = 0.006 each) were found to differ significantly between hypertensive cases and controls, regardless of BMI. CONCLUSION: ACE and GST gene polymorphisms were not associated with BMI but were significantly associated with hypertension among the studied group of North Indians.

Assessment of noninvasive risk markers of subclinical atherosclerosis in premenopausal women with previous history of gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is state of carbohydrate intolerance detected first time during pregnancy. GDM represents a significant risk factor for the development of CVD in women. The degree to which women with histories of gestational diabetes are at risk for cardiovascular disease, beyond their predisposition to future diabetes, is still unclear. The aim of our study was to assess the presence of surrogate markers of subclinical atherosclerosis which can be present in them even without developing type 2 diabetes. SUBJECTS AND METHODS: In this descriptive cross-sectional hospital based study, 50 patients 20-45 yrs of age, premenopausal, at least 1 yr past her most recent pregnancy, and not more than 5 yr past her index pregnancy with GDM. These patients and controls who did not have GDM were assessed for carotid intima media thickness,endothelial dysfunction, epicardial fat thickness and other cardiovascular risk factors. RESULTS: Women with pGDM were found to have unfavourable cardiovascular risk parameters. They also demonstrated more frequent occurrence of metabolic syndrome(64% vs 10%) than control subjects. Individual components of MS increased with increasing BMI in both the groups. As far as markers of subclinical atherosclerosis were concerned women with pGDM had significantly higher CIMT, FMD and epicardial fat thickness than control group. CONCLUSION: Women with pGDM, even before development of diabetes have significant differences in CVD risk factors when compared to those who do not have such history. Postpartum screening for glucose intolerance and efforts to minimize modifiable cardiovascular risk factors, including hypertension, viscerall adiposity, and dyslipidemia should be the most effective measures for lowering of cardiovascular risk.

A case of cerebellar dysarthria as the presenting symptom of HIV infection.

A 37 year old man presented with progressive dysarthria for 2 weeks. A week later he developed ataxia and bilateral cerebellar signs including intention tremors, dysmetria and dysdiadokokinesia. During evaluation for aetiology of cerebellar dysarthria, MRI brain revealed asymmetric altered signal intensities in bilateral cerebellar hemispheres and right side of pons suggesting demyelinating lesions. ELISA for Human Immune Deficiency virus-1 was positive. We kept a presumptive diagnosis of Progressive Multifocal Leukoencephalopathy (PML) on the basis of clinico-radiological picture. PML is an under investigated and under diagnosed CNS infection seen in HIV patients with advanced disease. We present an unusual case report where isolated cerebellar involvement occurred as the first AIDS defining event in the absence of appreciable immunodeficiency in a patient with previously undiagnosed HIV infection.