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Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India., (© Journal of the Association of Physicians of India 2024.)

Background: A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response., Aim: To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response., Methods: The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1β, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis., Results: AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1β and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1β and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy., Conclusion: SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance., Competing Interests: Conflict-of-interest statement: All authors declared no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The lymphocyte to monocyte ratio (LMR) is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease., Aim: To investigate the predictive role of LMR in diabetic coronary artery disease patients., Methods: This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi, India. A total of 200 angiography-proven coronary artery disease (CAD) patients were enrolled and grouped into two categories: Group I [CAD patients with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) levels ≥ 6.5%], and Group II (CAD patients without T2DM and HbA1c levels < 6.5%). Serum lipoproteins, HbA1c, and complete blood count of enrolled patients were analyzed using fully automatic analyzers., Results: The logistic regression analysis showed an odds ratio of 1.48 (95%CI: 1.28-1.72, P < 0.05) for diabetic coronary artery disease patients (Group I) in unadjusted model. After adjusting for age, gender, diet, smoking, and hypertension history, the odds ratio increased to 1.49 (95%CI: 1.29-1.74, P < 0.01) in close association with LMR. Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49 (95%CI: 1.27-1.75, P < 0.01). Receiver operating characteristic curve analysis revealed 74% sensitivity, 64% specificity, and 0.74 area under the curve (95%CI: 0.67-0.80, P < 0.001), suggesting moderate predictive accuracy for diabetic CAD patients., Conclusion: LMR showed positive association with diabetic coronary artery disease, with moderate predictive accuracy. These findings have implications for improving CAD management in diabetics, necessitating further research and targeted interventions., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: This study aimed to assess the validity of external quality assessment (EQA) laboratory results across various cultural and environmental contexts and to identify potential improvement areas., Methods: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a 2-year study (2022 and 2023) in which EQA materials, related software and online training was provided by a commercial vendor to 100 laboratories in ten IFCC member society countries. The results were analysed on a monthly basis by the TF-GLQ, to show the number of submissions per country, tests per lab, acceptability rates, random failures and to get a measure of which analytes performed poorly., Results: The EQA material was dispatched on a quarterly basis. Some countries had problems with customs releasing the material in a timely manner, resulting in laboratories not receiving them on time leading to no submission. We report here the results for the second year of the survey. The number of examinations varied between laboratories, ranging from seven to 84 analytes. Of the ten countries surveyed, six averaged greater than 90 % acceptable results over the whole 12-months cycle, one had unacceptable results for two of the nine months they returned results and the other four were considered to not perform to an acceptable standard., Conclusions: All 100 participating laboratories indicated satisfaction with the EQA survey and related services, including on-site training, and report handling. However, specimen receiving issues, suggest benefits in dispatching materials for a full 12-month cycle. Significant discrepancies in EQA performance indicate that four countries require long-term assistance, training and guidance. To ensure reliable patient results, promoting EQA in certain countries is essential to achieve the required level of quality., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM)., Methods: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA 1c ), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and β2M were measured and compared in cases and controls., Results: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA 1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike β2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA 1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA 1c <10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and β2M/creatinine (r=0.42, p=0.009)., Conclusions: Urinary biomarkers NGAL and β2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: It is increasingly common to find patients affected by a combination of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), and studies are able to correlate their relationships with available biological and clinical evidence. The aim of the current study was to apply association rule mining (ARM) to discover whether there are consistent patterns of clinical features relevant to these diseases. ARM leverages clinical and laboratory data to the meaningful patterns for diabetic CAD by harnessing the power help of data-driven algorithms to optimise the decision-making in patient care., Aim: To reinforce the evidence of the T2DM-CAD interplay and demonstrate the ability of ARM to provide new insights into multivariate pattern discovery., Methods: This cross-sectional study was conducted at the Department of Biochemistry in a specialized tertiary care centre in Delhi, involving a total of 300 consented subjects categorized into three groups: CAD with diabetes, CAD without diabetes, and healthy controls, with 100 subjects in each group. The participants were enrolled from the Cardiology IPD & OPD for the sample collection. The study employed ARM technique to extract the meaningful patterns and relationships from the clinical data with its original value., Results: The clinical dataset comprised 35 attributes from enrolled subjects. The analysis produced rules with a maximum branching factor of 4 and a rule length of 5, necessitating a 1% probability increase for enhancement. Prominent patterns emerged, highlighting strong links between health indicators and diabetes likelihood, particularly elevated HbA1C and random blood sugar levels. The ARM technique identified individuals with a random blood sugar level > 175 and HbA1C > 6.6 are likely in the "CAD-with-diabetes" group, offering valuable insights into health indicators and influencing factors on disease outcomes., Conclusion: The application of this method holds promise for healthcare practitioners to offer valuable insights for enhancing patient treatment targeting specific subtypes of CAD with diabetes. Implying artificial intelligence techniques with medical data, we have shown the potential for personalized healthcare and the development of user-friendly applications aimed at improving cardiovascular health outcomes for this high-risk population to optimise the decision-making in patient care., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. All authors declare no conflict of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals., Methods: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned., Results: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions., Conclusions: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide., Competing Interests: Declaration of competing interest Raman Puri: Boehringer Ingelheim, Novartis Manish Bansal: Sun Pharmaceuticals, USV, Dr Reddy's Labs, Cipla, Eris Lifesciences, Intas Pharmaceuticals, AstraZeneca Pharma India, Novartis Vimal Mehta: Institutional research grants from Amgen, Boehringer Ingelheim, Novo Nordisk, Eli Lilly, LIB Therapeutics, AstraZeneca, Torrent P Barton Duell: Advisory activities: Akcea/Ionis, Esperion, Regeneron, Kaneka, Novo Nordisk. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere Nathan Wong: Research support through UC Irvine: Regeneron, Novo Nordisk, Novartis, Eli Lilly, Consultant: Novartis, Ionis, Agepha SS Iyengar: Reddy's Lab, Amgen, Emcure, Glenmark, Boehringer Ingelheim, Pfizer, Novartis Devaki Nair: Novartis, Daichi Sankyo Krishnaswami Vijayaraghavan: Amgen, AstraZeneca, Boehringer Ingelheim, Esperion, Novo Nordisk, Pfizer V Mohan: Servier, MSD, Novo Nordisk, Novartis, Eli Lilly, USV, Lifescan J & J, Sanofi Aventis, Merck, Boehringer Ingelheim, Abbott, Several Indian Pharmaceutical companies Shashank Joshi: Biocon, Cadilla, Twin Health, Glenmark, Torrent, Marico, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, Abbott, AstraZeneca, USV, Alkem, Serdia Saumitra Ray: Merck, Novartis, Boehringer Ingelheim, Astra Zeneca, Novartis Sandeep Bansal: Novo Nordisk, Vascular Innovations Co. Ltd, Bayer, Portico India, ICMR SN Narasingan: IPCA, Novartis, USV, Torrent, SUN Pharma J C Mohan: Novartis, Lupin, Sun pharmaceuticals, Astra Zeneca, Intas, Le Servier, Sanofi Other authors report no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Advances in technology have transformed healthcare and laboratory medicine. Biosensors have emerged as a promising technology in healthcare, providing a way to monitor human physiological parameters in a continuous, real-time, and non-intrusive manner and offering value and benefits in a wide range of applications. This position statement aims to present the current situation around biosensors, their perspectives and importantly the need to set the framework for their validation and safe use. The development of a qualification framework for biosensors should be conceptually adopted and extended to cover digitally measured biomarkers from biosensors for advancing healthcare and achieving more individualized patient management and better patient outcome., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Aim: To evaluate the associations of the pathogenic variants in Kruppel-like Factor 14 (KLF 14) and Adiponectin (ADIPOQ) with susceptibility to type 2 diabetes mellitus (T2DM)., Background: Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease characterized by increased blood sugar and caused by resistance to insulin in peripheral tissues and damage to pancreatic beta cells. Kruppel-like Factor 14 (KLF-14) is proposed to be a regulator of metabolic diseases, such as diabetes mellitus (DM) and obesity. Adiponectin (ADIPOQ) is an adipocytokine produced by the adipocytes and other tissues and was reported to be involved in T2DM., Objectives: To study the possible association of the KLF-14 rs972283 and ADIPOQ-rs266729 with the risk of T2DM in the Saudi population., Methods: We have evaluated the association of KLF-14 rs972283 C>T and ADIPOQ-rs266729 C>G SNV with the risk to T2D in the Saudi population using the Amplification Refractory Mutation System PCR (ARMS-PCR), and blood biochemistry analysis. For the KLF-14 rs972283 C>T SNV we included 115 cases and 116 healthy controls, and ADIPOQ-rs266729 C>G SNV, 103 cases and 104 healthy controls were included., Results: Results indicated that the KLF-14 rs972283 GA genotype and A allele were associated with T2D risk with OR=2.14, p-value= 0.014 and OR=1.99, p-value=0.0003, respectively. Results also ADIPOQ-rs266729 CG genotype and C allele were associated with an elevated T2D risk with an OR=2.53, p=0.003 and OR=1.66, p-value =0.012, respectively., Conclusion: We conclude that SNVs in KLF-14 and ADIPOQ are potential loci for T2D risk. Future large-scale studies to verify these findings are recommended. These results need further verifications in protein functional and large-scale case control studies before being introduced for genetic testing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Coronary artery disease (CAD) is a major cause of death worldwide, and India contributes to about one-fifth of total CAD deaths. The development of CAD has been linked to the accumulation of Nε-carboxymethyl-lysine (CML) in heart muscle, which correlates with fibrosis., Aim: To assess the impact of CML and inflammatory markers on the biochemical and cardiovascular characteristics of CAD patients with and without diabetes., Methods: We enrolled 200 consecutive CAD patients who were undergoing coronary angiography and categorized them into two groups based on their serum glycosylated hemoglobin (HbA1c) levels (group I: HbA1c ≥ 6.5; group II: HbA1c < 6.5). We analyzed the levels of lipoproteins, plasma HbA1c levels, CML, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nitric oxide., Results: Group I (81 males and 19 females) patients had a mean age of 54.2 ± 10.2 years, with a mean diabetes duration of 4.9 ± 2.2 years. Group II (89 males and 11 females) patients had a mean age of 53.2 ± 10.3 years. Group I had more severe CAD, with a higher percentage of patients with single vessel disease and greater stenosis severity in the left anterior descending coronary artery compared to group II. Group I also exhibited a larger left atrium diameter. Group I patients exhibited significantly higher levels of CML, TNF-α, and IL-6 and lower levels of nitric oxide as compared with group II patients. Additionally, CML showed a significant positive correlation with IL-6 ( r = 0.596, P = 0.001) and TNF-α ( r = 0.337, P = 0.001) and a negative correlation with nitric oxide ( r =-4.16, P = 0.001). Odds ratio analysis revealed that patients with CML in the third quartile (264.43-364.31 ng/mL) were significantly associated with diabetic CAD at unadjusted and adjusted levels with covariates., Conclusion: CML and inflammatory markers may play a significant role in the development of CAD, particularly in diabetic individuals, and may serve as potential biomarkers for the prediction of CAD in both diabetic and non-diabetic patients., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. All authors declare no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: The trueness and precision of clinical laboratory results are ensured through total quality management systems (TQM), which primarily include internal quality control (IQC) practices. However, quality practices vary globally. To understand the current global state of IQC practice and IQC management in relation to TQM the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC member countries on IQC practices and management., Methods: The survey included 16 questions regarding IQC and laboratory TQM practices and was distributed to IFCC full and affiliate member countries (n=110). A total of 46 (41.8 %) responses were received from all regions except North America., Results: Of the responding countries, 78.3 % (n=36) had legislative regulations or accreditation requirements governing medical laboratory quality standards. However, implementation was not mandatory in 46.7 % (n=21) of responding countries. IQC practices varied considerably with 57.1 % (n=28) of respondents indicating that they run 2 levels of IQC, 66.7 % (n=24) indicating they run IQC every 24 h and 66.7 % (n=28) using assay manufacturer IQC material sources. Only 29.3 % (n=12) of respondents indicated that every medical laboratory in their country has written IQC policies and procedures. By contrast, 97.6 % (n=40) of responding countries indicated they take corrective action and result remediation in the event of IQC failure., Conclusions: The variability in TQM and IQC practices highlights the need for more formal programs and education to standardize and improve TQM in medical laboratories., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease of impaired glucose utilization. Imbalance in generation and elimination of free radicals generate oxidative stress which modulates glucose metabolism and insulin regulation, resulting in the occurrence and progression of diabetes and associated complications. Antioxidant supplements in T2DM can be seen as a potential preventive and effective therapeutic strategy., Aim: To compare randomized controlled trials (RCTs) in which antioxidants have been shown to have a therapeutic effect in T2DM patients., Methods: We systematically searched the electronic database PubMed by keywords. RCTs evaluating the effect of antioxidant therapy on glycaemic control as well as oxidant and antioxidant status as primary outcomes were included. The outcomes considered were: A reduction in blood glucose; changes in oxidative stress and antioxidant markers. Full-length papers of the shortlisted articles were assessed for the eligibility criteria and 17 RCTs were included., Results: The administration of fixed-dose antioxidants significantly reduces fasting blood sugar and glycated hemoglobin and is associated with decreased malondialdehyde, advanced oxidation protein products, and increased total antioxidant capacity., Conclusion: Antioxidant supplements can be a beneficial approach for the treatment of T2DM., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Clinical laboratory results are required for critical medical decisions, underscoring the importance of quality results. As part of total quality management, external quality assessment (EQA) is a vital component to ensure laboratory accuracy. The goal of this survey was to evaluate the current status of global laboratory quality systems and assess the need for implementation, expansion, or harmonization of EQA programs (EQAP) for Clinical Chemistry and Laboratory Medicine., Methods: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC full and affiliate members (n=110) on laboratory quality practice. A total of 41 (37.3%) countries representing all IFCC regions except North America provided responses about EQA availability and practices., Results: All 41 countries perform EQA, 38 reported that their laboratories had EQA policies and procedures, and 39 further act/evaluate unacceptable EQA results. 39 countries indicated they have international and/or national EQAP and 30 use alternative performance assessments. EQA frequency varied among countries. Generally, an EQAP provided the EQA materials (40/41) with four countries indicating that they did not have an EQAP in their country., Conclusions: Globally, most laboratories participate in an EQAP and have defined quality procedures for EQA. There remain gaps in EQA material availability and implementation of EQA as a part of a total laboratory quality system. This survey highlights the need for education, training, and harmonization and will guide efforts of the IFCC TF-GLQ in identifying areas for enhancing global laboratory quality practices., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background and Aims: To assess the hospitalized sick children admitted to the pediatric emergency department (ED) and to find new patterns of clinical and laboratory attributes using association rule mining (ARM)., Methods: In this observational study, 158 children with median (IQR) age 11 months and a PRISM III score of 5 (2-9) were enrolled. Hotspot data mining method was applied to assess clinical attributes, lab investigations and pre-defined outcome parameters of children and their association in sick hospitalized children aged 1 month to 12 years., Results: We obtained 30 rules with value for outcome as discharge is given attributes as follows: duration of hospitalization > 4 days, lactate > 1.2 mmol/L, platelet = 3.67/μL, dur&#95;ventil = 0 h, serum K  = 5.2 mmol/L, SBP = 120 mmHg, pCO 2  = 41.9 mmHg, PaO 2  = 163 mmHg, age = 92 months, heart rate > 114-159 per minute, temperature > 98 °F, GCS (Glasgow Coma Scale) > 7-14, gas K  = 4.14 mmol/L, gas Na = 138.1 mmol/L, BUN (Blood Urea Nitrogen) = 18.69 mg/dL, Diagnosis > 1-718, Creatinine = 1.2 mg/dL, serum Na = 148 mmol/L, shock = 2, Glucose = 144 mg/dL, Mg(i) > 0.23 meq/L, BUN > 6.54 mg/dL., Conclusion: ARM is an effective data analysis technique to find meaningful patterns using clinical features with actual numbers in pediatric critical illness. It can prove to be important while analysing the association of clinical attributes with disease pattern, its features, and therapeutic or intervention success patterns.

Introduction: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males., Aim: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ET A ) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD)., Methods: We compared prevalence of ET-1 gene (Lys198Asn) and ET A gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls., Results: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females., Conclusions: ET-1 and ET A gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VIMAL MEHTA reports financial support was provided by SERB, Department of Science & Technology, Govt of India., (Copyright © 2022 Cardiological Society of India. All rights reserved.)

The aim of the study was to compare the efficacy of daily v . weekly oral vitamin D 3 therapy in radiological healing of nutritional rickets. Children 6 months to 12 years ( n 132) diagnosed with nutritional rickets were randomised into three groups ( n 44): group A - 2000 IU daily vitamin D 3 for 12 weeks, B - 60 000 IU weekly for 3 weeks, C - 60 000 IU weekly for 6 weeks. Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and X-ray score were estimated at baseline and 12 weeks (endline). The proportion of children who achieved complete radiological healing at endline was compared between three groups by χ 2 and delta change in laboratory parameters by ANOVA (parametric data) or Kruskal Wallis test (non-parametric data), respectively. Baseline 25(OH)D ≤ 20 ng/ml was seen in 119 (90·2 %), hyperparathyroidism in 90 (68·8 %) and hypocalcaemia in 96 (72·7 %). A total of 120/132 children completed the study. Complete radiological healing seen in 30 (75 %) in group A, 23 (60·5 %) in group B and 26 (61·9 %) in group C; P = 0·15, with comparable endline X-ray scores; P = 0·31. The median (interquartile range (IQR)) delta X-ray score (baseline-endline) was 7 (4,9), 5 (2·25, 6) and 6 (4,7) in groups A, B and C, respectively; P = 0·019. Median (IQR) 25(OH)D endline levels in groups A, B and C were 50·0 (26·5, 66·5), 42·1 (28·4, 54·4) and 53·5 (33·7, 71·2) ng/ml, respectively; P = 0·045. Radiological scores were comparable at endline among daily and weekly vitamin D groups with greater change from baseline in daily supplemented group.

Introduction: Magnesium is a less frequently monitored electrolyte in critically ill patients. Hypomagnesemia is associated with increased need for mechanical ventilation, mortality and prolonged ICU stay. The present study was undertaken to identify the proportion of children with abnormal magnesium levels and correlate it with disease outcome., Methods: This observational study included children aged 1 month to 12 years hospitalized at the emergency room. Heparinized blood was collected for determination of ionized magnesium, ionized calcium, sodium, potassium and lactate using Stat Profile Prime Plus (Nova Biomedical, Waltham, MA, USA). Clinical outcomes for duration of hospitalization, and death or discharge were recorded., Results: A total of 154 (102 males) children with median (IQR) age of 11 (4, 49.75) months were enrolled. Sixty one (39.6%) had ionized magnesium levels below 0.42 mmol/l, 63 (40.9%) had normal levels and 30 (19.4%) had hypermagnesemia (>0.59 mmol/l). Hypomagnesemia was associated with hypocalcemia (p < 0.001), hyponatremia (p < 0.001) and hypokalemia (p < 0.02). A higher proportion of children with hypermagnesemia required ventilation than hypomagnesemia (26% vs. 9%) and succumbed (35% vs. 20%), respectively; p > 0.05. Ninety-three (60.3%) had hypocalcemia and 10 (6.5%) children had hypercalcemia. There was good correlation between ionized calcium and magnesium values (r = 0.72, p < 0.001)., Conclusion: Both hypomagnesemia and hypermagnesemia were seen in critically ill children. Patients with hypomagnesemia had significantly higher proportion of other electrolyte abnormalities., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Epileptic patients have to continue anti-epileptic drugs (AED) over a long period of time which can have deleterious effects on the endocrine system including the thyroid hormones with rare check. Risk factors for the development of thyroid dysfunction are still unclear. Therefore the aim of study was to evaluate thyroid functions in epileptic patients receiving anti-epileptic drugs (AED) as monotherapy and polytherapy and to determine potential risk of low thyroid function in epileptic patients receiving treatment. This cross-sectional study included 100 epilepsy patients more than 12 years of age. Serum levels of free thyroxin (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were evaluated in all subjects in addition to serum AED levels. TSH levels were found to be significantly higher in the polytherapy subgroup ( p  < 0.05) in comparison to the monotherapy group. 44% of the patients in the VPA monotherapy group had raised TSH levels and 41.2% of the patients on CBZ had low FT4. A significant negative correlation was observed between CBZ and FT4 ( p  < 0.05). Female sex and old age were additional risk factors detected for deranged thyroid function. Female patients with epilepsy, an older age and AED polytherapy were found to be associated with a higher risk of thyroid dysfunction. Thus, Thyroid function in these patients should be monitored closely. In conclusion, we observed significant changes in thyroid hormone levels in patients receiving antiepileptic treatment in both monotherapy and polytherapy. Elevated CBZ levels were significantly associated with decreased FT4 levels., Competing Interests: Conflict of interestAll of the authors declare that they have no competing interests., (© Association of Clinical Biochemists of India 2021.)

We studied left atrial (LA) function in severe rheumatic mitral stenosis (MS) patients using two-dimensional speckle tracking echocardiography (STE). Eighty patients with isolated severe MS in sinus rhythm and 40 controls underwent comprehensive echocardiography including STE derived LA strain [reservoir strain (LAS r ), conduit strain (LAS cd ) and contractile strain (LAS ct )]. The mean MVA was 0.93 ± 0.21 cm 2 . The mean values of LAS r (14.73 ± 8.59%), LAS cd (-7.61 ± 4.47%) and LAS ct (-7.16 ± 5.15%) in patients were significantly lower (p < 0.001) vs. controls 44.11 ± 10.44%, -32.45 ± 7.63%, -11.85 ± 6.77% respectively and showed decreasing trend with increasing MS severity and higher NYHA class. In conclusion, LA dysfunction is prevalent in severe MS irrespective of NYHA functional class., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest with respect to the present submission., (Copyright © 2021 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Frailty is a conglomerated elderly disorder that includes multiple abnormalities, like anemia, an increased titer of catabolic hormones, and compromised physiology of most of the body systems. Many studies have established the biomarkers that correlate with physical function and immune aging; however, people can age differently, so chronological age is not a sufficient marker of susceptibility to disabilities, morbidities, and mortality. The pathophysiology of frailty is not clearly understood, but a critical role of enhanced inflammation in the body is hypothesized. Many factors contribute to the development of frailty syndrome, such as pro-inflammatory cytokines, inflammatory markers, inflammatory cytokines, and secosteroids, like vitamin D. This review aims to highlight the role of inflammatory and cytokine biomarkers and vitamin D in the pathogenesis of Frailty Syndrome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different ( p -value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, p -value < 0.05. In addition results showed that there were significant differences ( p -value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a p -values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, p -value < 0.05. We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity.

Objective: To evaluate the electrolyte and lactate abnormalities in hospitalized children using a point of care testing (POCT) device and assess the agreement on the electrolyte abnormalities between POCT and central laboratory analyzer with venous blood., Methods: This observational study recruited hospitalized children aged 1 month to 12 years within two hours of admission. A paired venous sample and heparinized blood sample were drawn and analyzed by the central laboratory and POCT device (Stat Profile Prime Plus-Nova Biomedical, Waltham, MA, USA) for sodium and potassium. Lactate was measured on the POCT device only. The clinical and outcome parameters of children with electrolyte abnormalities or elevated lactate (>2mmol/L), and the agreement between POCT values and central laboratory values were assessed., Results: A total of 158 children with median (IQR) age 11 (6-10) months and PRISM score 5 (2-9) were enrolled. The proportion of children with abnormal sodium and potassium levels, and acidosis on POCT were 87 (55.1%), 47 (29.7%) and 73 (46.2%), respectively. The interclass coefficient between POCT and laboratory values of sodium and potassium values was 0.74 and 0.71 respectively; P<0.001. Children with hyperlactatemia (81, 51.3%) had higher odds of shock (OR 4.58, 95% CI: 1.6-12.9), mechanical ventilation (OR 2.7, 95% CI 1.1-6.6, P=0.02) and death (OR 3.1, 95% CI 1.3-7.5 P=0.01) compared to those with normal lactate., Conclusion: POCT can be used as an adjunct for rapid assessment of biochemical parameters in sick children. Lactate measured by POCT was a good prognostic indicator., Competing Interests: Nova Biomedical for their supporting the studyConflict of Interest: None, (Copyright © 2021 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

SARS-CoV-2, the new coronavirus causing COVID-19, is one of the most contagious disease of past decades. COVID-19 is different only in that everyone is encountering it for the first time during this pandemic. The world has gone from complete ignorance to a blitz of details in a matter of months. The foremost challenge that the scientific community faces is to understand the growth and transmission capability of the virus. As the world grapples with the global pandemic, people are spending more time than ever before living and working in the digital milieu, and the adoption of Artificial Intelligence (AI) is propelled to an unprecedented level especially as AI has already proven to play an important role in counteracting COVID-19. AI and Data Science are rapidly becoming important tools in clinical research, precision medicine, biomedical discovery and medical diagnostics. Machine learning (ML) and their subsets, such as deep learning, are also referred to as cognitive computing due to their foundational basis and relationship to cognition. To date, AI based techniques are helping epidemiologists in projecting the spread of virus, contact tracing, early detection, monitoring, social distancing, compiling data and training of healthcare workers. Beside AI, the use of telemedicine, mobile health or mHealth and the Internet of Things (IOT) is also emerging. These techniques have proven to be powerful tools in fighting against the pandemic because they provide strong support in pandemic prevention and control. The present study highlights applications and evaluations of these technologies, practices, and health delivery services as well as regulatory and ethical challenges regarding AI/ML-based medical products., (Copyright © 2021 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Artificial Intelligence (AI) is a broad term that combines computation with sophisticated mathematical models and in turn allows the development of complex algorithms which are capable to simulate human intelligence such as problem solving and learning. It is devised to promote a significant paradigm shift in the most diverse areas of medical knowledge. On the other hand, Cardiology is a vast field dealing with diseases relating to the heart, the circulatory system, and includes coronary heart disease, cerebrovascular disease, rheumatic heart disease and other conditions. AI has emerged as a promising tool in cardiovascular medicine which is aimed in augmenting the effectiveness of the cardiologist and to extend better quality to patients. It has the ability to support decision‑making and improve diagnostic and prognostic performance. Attempt has also been made to explore novel genotypes and phenotypes in existing cardiovascular diseases, improve the quality of patient care, to enablecost-effectiveness with reducereadmissionand mortality rates. Our review addresses the integration of AI and laboratory medicine as an accelerator of personalization care associated with the precision and the need of value creation services in cardiovascular medicine., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest and do not have to declare any funding to support this article., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Vitamin B12 deficiency in early life can adversely affect the growth of developing brain with myriad of neurodevelopmental manifestations. At this age, the deficiency is usually the result of low maternal levels., Objectives: To assess the vitamin B12 status of healthy exclusively breast-fed Indian infants aged 1 to 6 months and their mothers., Methods: One hundred term exclusively breast-fed infants aged 1 to 6 months attending pediatric outpatient department were recruited. Hemogram, serum B12, folate, and ferritin levels were obtained from each infant-mother pair., Results: The prevalence of B12 deficiency in infants was found to be 57%. Forty-six percent of mothers were deficient. There was a positive correlation ( r = .23) between the B12 levels of the infants and their mothers., Conclusion: There is a high prevalence of vitamin B12 deficiency in Indian infants and their mothers. There is an urgent need to supplement our population with vitamin B12, and the best time to do this would be antenatal.

Purpose: To assess the nutritional status in 31 patients of congenital pouch colon (CPC) who had undergone definitive surgery and closure of a protective stoma, if any, at least 1 year earlier and were below 14 years age., Materials and Methods: The clinical history, demographic details, anthropometric measurements, and results of hematological and biochemical tests were recorded. In addition to collective data, analysis was also performed after grouping by age, subtype of CPC (Types I/II and Types III/IV CPC), and in Types I/II CPC patients, by whether the colonic pouch had been completely excised or else a segment preserved by tubular colorraphy (TC)., Results: Severe fecal incontinence (FI) was common (64.52%). Anthropometry showed a significant malnutrition in 53.85-95.45% patients, especially stunting which was most prevalent in the 0-5 years age-group. Serum Vitamin B 12 , folate, and Vitamin D were lower than normal in 38.71%, 22.58%, and 74.19% patients, respectively, without statistically significant difference among the various groups studied. Patients with Types I/II CPC had a statistically significant higher incidence of anemia, low serum ferritin, and severe FI than patients with Types III/IV CPC. Patients with Types I/II CPC, managed by excision of the colonic pouch, had a higher incidence of severe FI, wasting, and thinness than those undergoing TC., Conclusions: On follow-up of the patients of CPC, anthropometry shows a high incidence of malnutrition, especially stunting in the 0-5 years age-group. There is an adequate adaptation of fluid-electrolyte homeostasis. Although Types I/II CPC patients have a significantly higher incidence of anemia and severe FI than Types III/IV CPC patients, long-term anthropometric parameters are similar. In Types I/II CPC, preservation of the colonic pouch by TC offers long-term benefit., Competing Interests: There are no conflicts of interest.

Objectives: It is still unknown whether altered vitamin D levels observed with osteoarticular tuberculosis change during treatment in a child or modify the disease course. To find a possible answer to the above query, we investigated serial serum 25 hydroxy vitamin D concentrations in children suffering from osteoarticular tuberculosis treated with multidrug antitubercular drugs., Methods: The prospective study enrolled 19 untreated immunocompetent children with an established diagnosis of osteoarticular tuberculosis. None of the patients were offered any therapeutic vitamin D supplementation at initiation or during the treatment. The patients were followed for response to multidrug antitubercular therapy (DOTS) at 2 months interval. Mean values of vitamin D were calculated at 0, 2, and 6 months and statistically compared. The following laboratory references for defining the vitamin D status were used: <30 nmol/L = deficiency; 30-75 nmol/L = insufficiency; >75 nmol/L = sufficiency., Results: All the patients responded to antitubercular therapy. Out of the enrolled children, 73.67% had low vitamin D levels at initial presentation. There was no statistically significant difference in vitamin D levels in affected children at either 0-2 ( p  = 0.452), 2-6 ( p  = 0.240), or 0-6 months ( p  = 0.854) following antitubercular treatment. Although the mean vitamin D levels were higher in male patients when compared to female patients at all times, there was no statistically significant difference in vitamin D levels during treatment stages in either sex., Conclusions: Vitamin D levels were low at initiation of treatment and did not significantly improve during multidrug antitubercular treatment. Further, tuberculosis healed well with antitubercular therapy despite persistence of low serum levels of vitamin D.

Objectives: We prospectively investigated serum 25 hydroxy vitamin D concentrations in children suffering from osteoarticular tuberculosis. The age or sex correlation to vitamin D levels in affected subjects was also calculated., Methods: Twenty five untreated children with osteoarticular tuberculosis were taken as cases along with equal number of age and sex matched 'healthy' controls. The following laboratory references for defining the vitamin D status were used (<30 nmol/L = deficiency; 30-75 nmol/L = insufficiency; > 75 nmol/L = sufficiency). The cases were further grouped based on gender differences and age (<5 or >5 years)., Results: Out of 25 cases, there were 14 (56%) with deficiency of vitamin D. In 'apparently' healthy subjects, all 25 controls (100%) had hypovitaminosis D. The osteoarticular tuberculosis patients had significant lower levels of vitamin D when compared with their healthy peers irrespective of gender or age differences., Conclusions: The osteoarticular tuberculosis cases had low serum vitamin D levels compared to healthy controls. The low vitamin D levels were persistent irrespective of gender and age in osteoarticular tuberculosis children. There was widespread vitamin D insufficiency in apparently healthy controls.

Background: Tubercular patients, in general, have been demonstrated with lower serum levels of vitamin D, but the levels in osteoarticular tuberculosis (TB) in children are largely unknown. We aimed to determine serum vitamin D status in pediatric cases with osteoarticular TB., Methods: The values of serum vitamin D were estimated in 100 children with osteoarticular TB. The patients were divided into three groups based on gender, age, and site to assess variations of vitamin D levels in pediatric osteoarticular TB., Results: Hypovitaminosis D was associated with active osteoarticular TB in children. The mean vitamin D levels were 42.165 nmol/L. There were no statistical difference between mean vitamin D levels in boys and girls (p value = 0.6143); age groups <5 and 5-12 years (p value = 0.3857); or spinal and non-spinal osteoarticular groups (p value = 0.8350)., Conclusions: Active osteoarticular TB in children was also associated with hypovitaminosis D. The correlation between hypovitaminosis D and osteoarticular TB appears to be more disease specific rather than host specific.

Extensive data from animal and human studies indicate a role of vitamin D in erythropoiesis. Iron and vitamin D deficiencies are implicated with adverse health effects in children even if they are asymptomatic. The potential relationship between the two remains poorly understood. A cross-sectional study was performed in the period from 1st May 2012 through 30th April 2013 and subjects were classified into vitamin D deficiency (VDD), vitamin D insufficiency (VDI) and vitamin D sufficiency (VDS) groups according to their 25(OH) D levels. A total of 263 children were included in the analysis. Anaemia was present in 66 % of 25(OH) D deficient subjects compared with 35 % in vitamin D sufficient individuals (p < 0.0001). The association of breast feeding and development of VDD was also significant (p < 0.05). Serum levels of 25(OH) D were found lower in female sex and if the analysis was performed in the winter/spring season. Physicians should therefore assess vitamin D levels in all anaemic children and ensure adequate supplementation to prevent deficiencies.

Background: Steroid resistant nephrotic syndrome (SRNS) has a chronic and progressive course. Limited data is available evaluating thyroid function parameters in SRNS patients. The aim of the present study was to evaluate the thyroid hormone status in Indian children with SRNS., Materials & Methods: The present cross-sectional study included 50 patients aged 1-12 years with SRNS. As per Up:Uc ratio divided into three groups: Group A) 16 patients of SRNS in complete remission Group B) 14 patients of SRNS in partial remission Group C) 20 patients of SRNS in relapse. Serum levels of FT3, FT4 and TSH were measured in all., Results: 20% of the children (n=10) with SRNS had hypothyroidism (7 subclinical hypothyroidism and 3 with overt hypothyroidism). One child was found to be in complete remission, 4 in partial remission and 5 in relapse phase. TSH levels were found to be significantly elevated in children with relapse (p = 0.042). Serum albumin showed a significant negative correlation with Up:Uc ratio ( p < 0.0001) whereas total cholesterol showed a significant positive correlation (p < 0.001). On correlating TSH level with Up:Uc ratio a significant positive correlation ( p = 0.0098) was observed., Conclusion: Subclinical hypothyroidism in SRNS is temporary and may improve with remission. However prolonged proteinuria in SRNS patients may lead to progressive damage of the renal tubules and impaired absorption of Low Molecular Weight (LMW) proteins which may further exhaust the thyroid reserve and lead to overt hypothyroidism. Therefore thyroid examination should be routinely advocated in these children.

Free radicals or reactive oxygen species (ROS) are generated by oxygen metabolism which is balanced by the rate of oxidant formation and the rate of oxidant elimination. Oxidative stress is a result of imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defence systems. Hypertension is one of the major risk factors for cardiovascular diseases and is considered as a leading cause of mortality and morbidity. These diseases affect more than 600 million people and it has been estimated that 29% of the world population will be suffering from hypertension by 2025. It has been indicated by experimental evidence that reactive oxygen species (ROS) play an important role in the pathophysiology of hypertension. The vasculature is a rich source of NADPH oxidase which produces most of the reactive oxygen species and plays an important role in renal dysfunction and vascular damage. Recent studies indicate that increased oxidative stress is the important mediator of endothelial injury in the pathology of hypertension associated to increased production of pro oxidants such as superoxideanion hydrogen peroxide, reduced nitric oxide synthesis and decreased bioavailability of antioxidants. Oxidative stress is found to be associated with endothelial dysfunction, inflammation, hypertrophy, apoptosis, cell migration, fibrosis, and angiogenesis in relation to vascular remodelling of hypertension. Results in humans are still less conclusive inspite of data available that involve oxidative stress as a causative factor of essential hypertension. The aim of this review is to present a novel focus on the role of oxidative stress in the pathophysiology of hypertension and recent biomarkers which are found to be associated with reactive oxygen species and the role of antioxidants as therapy of hypertension.

Prostasin is a glycophosphatidylinositol-anchored protein which is found in prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary glands. It is a serine protease with trypsin-like substrate specificity which was first purified from seminal fluid in 1994. In the last decade, its diverse roles in various biological and physiological processes have been elucidated. Many studies done to date suggest that prostasin is one of several membrane peptidases regulating epithelial sodium channels in mammals. A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature and the National Library of Medicine. The data was also assessed from journals and books that published relevant articles in this field. Understanding the mechanism by which prostasin and its inhibitors regulate sodium channels has provided a new insight into the treatment of hypertension and some other diseases like cystic fibrosis. Prostasin plays an important role in epidermal growth factor receptor (EGFR) signal modulation. Extracellular proteases have been implicated in tumor metastasis and local tissue invasion because of their ability to degrade extracellular matrices.

Background: Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes its routine use. Co-peptin is the C-terminal part of the AVP precursor which plays an important role in the correct structural formation of the AVP precursor and its efficient proteolytic maturation. Because of its stoichiometric generation, co-peptin mirrors the release of AVP and measurement of more stable co-peptin may be an indicator of AVP levels., Method: A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field., Result: Recent and ongoing research indicates the diagnostic and prognostic roles of co-peptin in various clinical settings especially in critically ill patients., Conclusion: Co-peptin levels are altered in various physiological and pathological conditions indicating its possible role as a biomarker. However, further research using co-peptin in various clinical settings will prove its cost-effectiveness and clinical usefulness., (Copyright © 2010. Published by Elsevier B.V.)

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease.

Reactive oxygen species (ROS), especially superoxide anion and hydrogen peroxide, are important signaling molecules in cardiovascular cells. ROS participate in growth, apoptosis, and migration of vascular smooth muscle cells, in the modulation of endothelial function, including endothelium-dependent relaxation and expression of proinflammatory phenotype, and in the modification of the extracellular matrix. They have also been linked to hypertension and to pathological states associated with uncontrolled growth and inflammation leading to coronary artery disease (CAD). The NAD(P)H oxidase is a multisubunit enzyme that catalyzes the reduction of molecular oxygen to form superoxide (O2*-). Although first described in phagocytes, NAD(P)H oxidases have also been demonstrated as major sources of superoxide in vascular cells and myocytes. Enhanced superoxide production increases nitric oxide inactivation and leads to an accumulation of peroxynitrites and hydrogen peroxide. An entire new family of NAD(P) H oxidase (Nox) homologs has emerged, which vary widely in cell and tissue distribution as well as in function and regulation. Recent and ongoing research tends to highlight the biochemical characters, activation paradigms, structure, and function of this enzyme. In this review, we provide a brief overview of structural features of NAD(P)H oxidases and then discuss their role in pathophysiology of CAD.