Detection of HbD Punjab Trait in Saurashtra Region of Gujarat by HPLC Method.

The HbD Punjab trait is a less common hemoglobin variant in the Saurashtra region of Gujarat. This patient presented to the General Medicine and Biochemistry Department at All India Institute of Medical Sciences, Rajkot, Hospital, for the HbA1c analysis by high-performance liquid chromatography (HPLC). The patient was 52 years old, a known case of type 2 diabetes mellitus and hypertension, and presented with complaints of generalized malaise and fatigability for the previous ten to twelve months. On physical examination, there was no evidence of pallor, lymphadenopathy, splenomegaly, or hepatomegaly. Peripheral blood smear revealed normocytic normochromic RBC, and platelets were adequate and normal in morphology. The HPLC analysis revealed heterozygous for hemoglobin D (HbD Punjab trait), and false high HbA1c corresponds to fasting plasma glucose (FPG) levels due to abnormal separation. However, genetic counseling is highly recommended to detect any potential reproductive risk factors.

Effects of Wearing Personal Protective Equipment on Serum Cortisol Levels and Physiological Variables in Healthcare Workers: A Randomised Controlled Trial in a Simulated Pandemic Environment.

INTRODUCTION: The COVID-19 pandemic has necessitated the widespread use of personal protective equipment (PPE), particularly in high-risk environments. Full-body PPE is favoured for its comprehensive protection against the virus but poses challenges to the body's thermoregulatory system as it inhibits air exchange. This randomised trial was undertaken to investigate the effects of wearing a commonly used gown-type full-body PPE kit in a simulated environment. METHODS: Initially, 65 healthy males were recruited and randomly divided into two groups: a study group wearing a full-body PPE kit (gown-type, full-body PPE kit with trousers, a gown-type shirt with a hood, a shoe cover, an N95 face mask, and an optional face shield) and a control group without PPE. They remained seated for three hours while wearing the PPE kit. Room conditions mimicked non-air-conditioned hospital scenarios, with temperature and humidity recorded and ventilation provided through open doors and windows, along with ceiling fan cooling. Activities with minimal physical exertion were allowed, and access to the toilet was kept to a minimum. Subjects underwent assessments of heart rate, respiratory rate, temperature, blood pressure, heart rate variability (HRV), and blood samples for serum cortisol before donning the PPE kit and entering a simulated ICU/WARD environment and after doffing. RESULTS: A total of 60 participants completed the study (30 in each group). Compared to the controls, serum cortisol levels significantly increased in the PPE groups, and HRV data indicated increased sympathetic activity in the PPE group. CONCLUSION:  Wearing a full-body PPE kit (gown-type upper garment with trousers) was found to have a significant impact on cortisol levels and physiological variables in a simulated environment. This suggests that in situations like the COVID-19 pandemic that warrant the use of such PPE kits, appropriate measures should be taken to provide better thermal stability for maintaining the well-being of healthcare workers.

Evaluation of Laboratory Performance in Consideration with Pre analytical and Post analytical Quality Indicators.

Implementation of Quality indicators (QIs) plays an imperative role in improving the total testing process, as it provides a quantitative basis for evaluating the laboratory performance. Besides monitoring of analytical quality specifications, several lines of experimental and clinical evidence have alluded a pivotal role of extra-analytical phases in improving the quality of laboratory services and therefore a relevance of pre- and post-analytical steps have been speculated on the overall quality in the total testing process and consequently on clinical decision-making. This was a retrospective study designed to evaluate and review different extra-analytical quality indicators in NABL accredited clinical biochemistry laboratory at BJ Medical College and Civil Hospital, Ahmedabad, Gujarat in an endeavour to ameliorate the performance of the laboratory. All Clinical Chemistry Laboratory test requests with their respective samples from January 2018 to December 2021 were included in the study. A total of 1,439,011samples were processed, and were evaluated for seven QIs [(% of number of suitable samples not received; QI-8), (% of number of samples received in inappropriate container; QI-9), (% of number of samples hemolysed; QI-10), (% of number of samples with inadequate sample volume; QI 12) (% of number of samples received mismatched; QI 15), (% of number of samples reported after turnaround time; QI 21) and (% of number of samples with critical values informed; QI 22)] based on defined criteria of Quality Specification given by International Federation of Clinical Chemistry. Total number of preanalytical errors was 53,669 (3.72%). Among the preanalytical errors, inadequate sample volume (2.37% of total samples; 63.49% of total pre-analytical errors) was the most common anomaly followed by Not received samples (24.18%) hemolysis (8.26%) mismatched (3.91%) and 0.14% samples were received in Inappropriate container; manifesting that the error frequency was unacceptable for QI 21 and QI 8, acceptable for QI 10, minimally acceptable for QI 15 and optimum for QI QI 9. Furthermore, there was year-wise progressive decline in error rate of inadequate sample volume, hemolysed sample received and mismatched samples. Total number of post analytical errors were 19,002 (1.32%). TAT outlier and critical values communicated were the two QIs evaluated for this phase and results of both QI were within acceptable limits. Quality indicators serve as a tool to monitor process performance and consequently derived error rates warrant active intervention to improve the laboratory services and patient health care. Dissemination of certified documents, regular staff training and evaluation needs to be conducted.

Maternal Obesity and Neonatal Metabolic Health: Insights Into Insulin Resistance.

Background Maternal obesity is a global health concern that leads to metabolic alterations in the offspring, making them vulnerable to metabolic disorders in adulthood. Early identification of such neonates would provide opportunities to positively alter modifiable risk factors for non-communicable diseases (NCDs) to prevent their occurrence later in life. Objectives This study aimed to assess and contrast insulin resistance (IR) levels in neonates born to mothers with obesity and those born to healthy, non-obese mothers.  Methods This case-control study was conducted after approval from the institutional ethics committee. A total of 98 healthy, non-obese pregnant females were included in Group 1, and 68 obese pregnant females were included in Group 2. The participants were followed up until delivery and cord blood samples were collected after delivery. Neonatal glucose and insulin concentrations were estimated, and indices of IR such as homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), and glucose-to-insulin ratio were calculated. Neonatal IR indices and anthropometric measurements were compared between the groups using the Z test and correlated with the maternal pre-pregnancy body mass index (BMI) using Pearson's correlation. Additionally, Pearson's correlations were examined between neonatal IR indices and anthropometric measurements. Statistical significance was set at p <0.05. Results Neonates in Group 2 exhibited significantly higher anthropometric parameters and IR indices than those in Group 1. A statistically significant positive correlation was identified between maternal pre-pregnancy BMI, neonatal anthropometric parameters, and IR. Furthermore, a statistically significant positive correlation was observed between neonatal IR and the anthropometric parameters. Conclusion Neonates born to obese mothers exhibited higher anthropometric parameters and insulin resistance than those born to non-obese, healthy mothers. Assessment of IR at birth can help identify neonates who are at higher risk of developing NCD in later life. Timely promotion of a healthy lifestyle can reduce the occurrence of NCDs in later life.

Heart Rate Variability in Patients of Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

Patients with ankylosing spondylitis (AS) have a significantly higher risk of cardiovascular morbidities. The participation of the autonomic nervous system (ANS) in AS is still unknown and inconclusive. Heart rate variability (HRV) is defined as the variability of the time interval between two consecutive heartbeats. This meta-analysis aims to detect the association of HRV and its various parameters with AS patients by comparing them to healthy controls. Research literature was searched in PubMed, Embase, and Cochrane Library databases from inception to April 2022. The Review Manager 5 (RevMan) Version 5.4 software was used to analyze the data. In addition, the protocol of systematic review is registered in the PROSPERO database with ID CRD42022336484. This study includes a total of nine case-control studies with a total of 923 patients; 409 with AS and 514 healthy controls. The root mean square of successive differences between normal heartbeats (RMSSD) [standardized mean difference (SMD); -0.47, 95% CI: -0.69 to -0.25, p < 0.0001], proportion of NN50 (pNN50) (SMD; -0.89, 95% CI: -1.74 to -0.04, p = 0.04) and HRV (SMD; -1.11, 95% CI: -1.53 to 0.69, P < 0.00001) were significantly low in AS cases compared to healthy controls. The HRV value was also significantly low in patients with high Bath ankylosing spondylitis disease activity (BASDAI) index (SMD: -1.45, 95% CI: -2.45 to -0.36, p < 0.009). HRV (parasympathetic activity) was significantly lowered in AS patients compared to healthy controls.

Bexagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for improvement of glycemia in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2 diabetes mellitus (T2DM). AREAS COVERED: We examined RCTs with T2DM comparing the clinical effectiveness and safety of 20 mg once daily oral dose of bexagliflozin with placebo for managing glycemia till 28 May 2023, published on databases like ClinicalTrials.gov, PubMed, Embase, and Cochrane Library. Furthermore, reduction of body weight, fasting plasma sugarr(FPG), systolic blood pressure (SBP) and the percentage of individuals who achieved glycated hemoglobin (HbA1c) of < 7% from baseline were also evaluated. The Review Manager 5 was utilized to investigate the retrieved data. EXPERT OPINION: We involved eight RCTs. Bexagliflozin was significantly superior in reducing HbA1c[least squares mean difference(LSMD) = -0.45,95% confidence interval (CI =-0.55 to -0.34,p < 0.00001], FPG [LSMD= -1.37, 95%CI =-1.73 to -1.00, p < 0.00001], body weight (LSMD= -1.77, 95%CI =-2.44 to-1.10, p < 0.00001), and SBP(LSMD= -4.11,95%CI = -6.18 to -2.03,p = 0.0001) in comparison to placebo. The safety outcomes of bexagliflozin were consistent with the placebo arm. This study concluded that bexagliflozin seems to be a promising oral anti-diabetic drug for enhancing glycemic management in adult patients with T2DM.

Bexagliflozin, a novel hypoglycemic agent, is an extremely effective SGLT2 inhibitor developed by TheracosBio to manage glycemia in T2DM. The United States Food and Drug Administration (USFDA) granted first approval of bexagliflozin on 20 January 2023, for usage as an adjunctive therapy agent alongside lifestyle changes and exercise in T2DM. All included RCTs have investigated the therapeutic efficacy and safety of bexagliflozin 20 mg concerning glycemic and extra-glycemic effects in T2DM. Bexagliflozin 20 mg significantly reduces HbA1c, FPG (glycemic effect), body weight, and SBP (extra-glycemic effect) compared to the placebo arm in T2DM. Safety data show that bexagliflozin was comparable to placebo arm and polyuria, urinary tract infection (UTI), nasopharyngitis or upper respiratory tract infection (URTI), hypoglycemia, nausea, and diarrhea were the most common non-serious adverse effects. Bexagliflozin 20 mg seems to be an effective SGLT2 inhibitor compared to the placebo arm to manage glycemia in patients with T2DM along with favorable extra-glycemic effects.

Integrating Cutting-Edge Methods to Oral Cancer Screening, Analysis, and Prognosis.

Oral cancer (OC) has become a significant barrier to health worldwide due to its high morbidity and mortality rates. OC is among the most prevalent types of cancer that affect the head and neck region, and the overall survival rate at 5 years is still around 50%. Moreover, it is a multifactorial malignancy instigated by genetic and epigenetic variabilities, and molecular heterogeneity makes it a complex malignancy. Oral potentially malignant disorders (OPMDs) are often the first warning signs of OC, although it is challenging to predict which cases will develop into malignancies. Visual oral examination and histological examination are still the standard initial steps in diagnosing oral lesions; however, these approaches have limitations that might lead to late diagnosis of OC or missed diagnosis of OPMDs in high-risk individuals. The objective of this review is to present a comprehensive overview of the currently used novel techniques viz., liquid biopsy, next-generation sequencing (NGS), microarray, nanotechnology, lab-on-a-chip (LOC) or microfluidics, and artificial intelligence (AI) for the clinical diagnostics and management of this malignancy. The potential of these novel techniques in expanding OC diagnostics and clinical management is also reviewed.

Association of the Human Leptin Receptor Gene (rs1137101; Gln223Arg) Polymorphism and Circulating Leptin in Patients with Metabolic Syndrome in the Indian Population.

Phenotypic expression of metabolic syndrome is precipitated by environmental variables along with the individual genetic susceptibility to the obesogenic environment and growing body of evidence suggest a paramount role of adipocytokines. Therefore, identifying the genetic influence on circulation leptin levels and clarifying genotype-phenotype correlation of rs1137101 {Leptin receptor gene (LEPR) Gln223Arg (Q223R; A668G)} in metabolic syndrome were the primary objective of this study. A total of 447 adult participants, including 214 metabolic syndrome patients and 233 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci {Leptin receptor gene; Gln223Arg (Q223R; A668G); rs1137101} on the occurrence of metabolic syndrome in consort with circulation leptin levels. Suitable descriptive statistics was used for different variables. The genotype frequencies were found to be in Hardy-Weinberg equilibrium for both cases (p > 0.2722) as well as in controls (p > 0.2331). However, genotype (x2: 11.26, 2 d.f. p = 0.0036) and allele distribution (x2: 10.51, 2 d.f. p: 0.0012) of the LEPR Gln223Arg (Q223R; A668G) differed significantly between cases and controls. Gln/Arg genotype (OR = 1.6099; 95% CI = 1.0847-2.3893; p value = 0.0181), Arg/Arg genotype (OR = 2.8121; 95% CI = 1.4103-5.6074; p value = 0.0033) and R allele (OR = 1.5875; 95% CI = 1.1996-2.1008; p value = 0.0012) were significantly associated with increased risk of metabolic syndrome in univariate analysis. Further a multivariate logistic regression adjusted for potential confounders showed that Arg/Arg genotype (OR = 1.9; 95% CI = 1.271-2.639; p-value < 0.05) and Gln/Arg (OR: 1.3; 95% CI = 0.873-2.034; p value < 0.05) have a significant risk for the occurrence of the metabolic syndrome. A progressive increase in the serum leptin levels from major homozygous alleles to minor homozygous alleles were observed indicating that rs1137101 modify the serum leptin concentrations in patients with metabolic syndrome. These findings provide enough evidence of a significant association of LEPR Gln223Arg (Q223R; A668G) polymorphism in the LepR gene in Indian patients with increased risk of metabolic syndrome for R allele and Arg/Arg homozygote. Thus, rs1137101 might be a pleiotropic locus for metabolic syndrome and its components in studied population.

Verification of Reference Interval of Thyroid Hormones With Manual and Automated Indirect Approaches: Comparison of Hoffman, KOSMIC and refineR Methods.

INTRODUCTION: The interpretation of quantitative test results requires the availability of appropriate reference intervals (RIs). Every laboratory has been advised by scientific literature and reagent manufacturers to establish RIs for all analytes. Measuring RIs using direct methods is very costly, and it poses ethical and practical challenges. To overcome these challenges, indirect methods, such as Hoffman, and newer automated approaches, such as KOSMIC and refineR, are used to verify RIs for thyroid hormones. OBJECTIVE: To verify RIs for thyroid hormones in adult patients using Hoffman, KOSMIC and refineR methods and to compare these with reference ranges given in kit literature or standard textbooks. MATERIALS AND METHODS: The observed values (results) of thyroid hormone were collected from the LIS (Laboratory Information System) of the Biochemistry Department at the B. J. Medical College and Civil Hospital in Ahmedabad between 1 January 2021 and 31 May 2022. Hoffman, KOSMIC and refineR methods were used to verify the RIs. The computerised Hoffman approach, which Katayev et al. describe, is a simple method for determining RI from hospital data. Zierk et al. pre-validated and suggested the KOSMIC method based on Python programming, whereas refineR was proposed by Tatjana et al. based on R programming language. RESULTS: Hoffman, KOSMIC and refineR's indirect RI techniques revealed comparable results with kit literature in free T3 and T4, whereas higher upper reference limits of thyroid-stimulating hormone (TSH) compared to kit literature were observed with KOSMIC and refineR methods. However, the computerised Hoffman method revealed comparable results with TSH also. CONCLUSION: Indirect approaches, such as Hoffman, KOSMIC and refineR, provide reliable RI verification for free T3 and T4 utilising patient samples obtained from LIS. However, the manual Hoffman method provides reliable RI verification for TSH data derived from the hospital population as compared to automated approaches, such as KOSMIC and refineR.

COVID-19-related liver injury: Focus on genetic and drug-induced perspectives.

BACKGROUND: Empirical use of potentially hepatotoxic drugs in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is considered as one of the major etiopathogenetic factors for liver injury. Recent evidence has shown that an underlying genetic factor may also occur. Hence, it is important to understand the host genetics and iatrogenic-based mechanisms for liver dysfunction to make timely remedial measures. AIM: To investigate drug-induced and genetic perspectives for the development of coronavirus disease 2019 (COVID-19)-related liver injury. METHODS: Reference Citation Analysis, PubMed, Google Scholar and China National Knowledge Infrastructure were searched by employing the relevant MeSH keywords and pertaining data of the duration, site and type of study, sample size with any subgroups and drug-induced liver injury outcome. Genetic aspects were extracted from the most current pertinent publications. RESULTS: In all studies, the hepatic specific aminotransferase and other biochemical indices were more than their prescribed upper normal limit in COVID-19 patients and were found to be significantly related with the gravity of disease, hospital stay, number of COVID-19 treatment drugs and worse clinical outcomes. In addition, membrane bound O-acyltransferase domain containing 7 rs641738, rs11385942 G>GA at chromosome 3 gene cluster and rs657152 C>A at ABO blood locus was significantly associated with severity of livery injury in admitted SARS-CoV-2 patients. CONCLUSION: Hepatic dysfunction in SARS-CoV-2 infection could be the result of individual drugs or due to drug-drug interactions and may be in a subset of patients with a genetic propensity. Thus, serial estimation of hepatic indices in hospitalized SARS-CoV-2 patients should be done to make timely corrective actions for iatrogenic causes to avoid clinical deterioration. Additional molecular and translational research is warranted in this regard.

Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND AND AIMS: This study was carried out to analyze the clinical safety and efficacy of dasiglucagon for the treatment of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: We searched PubMed, Cochrane Library, Embase, and ClinicalTrials.gov for randomized controlled trials (RCTs) investigating the safety and efficacy of dasiglucagon in the treatment of hypoglycemia in patients with T1DM. Furthermore, time required for the recovery of blood glucose or to elevate blood glucose levels ≥20.0 mg/dL from baseline was analyzed. The data was analyzed in version 5.4 of review manager 5 (RevMan). RESULTS: We included five published RCTs with a total of 347 patients . Dasiglucagon was significantly better at reducing the recovery time of blood glucose or increasing blood glucose levels 20.0 mg/dL from baseline compared to glucagon [pooled mean difference (PMD): 1.08%, 95% confidence interval (CI): 1.96 to 0.21, p = 0.02] and placebo (PMD: - 23.30%, 95% CI: 23.97 to 22.63, p < 0.00001). Overall, the safety outcome results of dasiglucagon were comparable with the native glucagon. CONCLUSIONS: Dasiglucagon appears to be a promising human glucagon analog peptide for the safe and effective treatment of severe hypoglycemia in T1DM.

Growth differentiation factor 15 as an emerging novel biomarker in SARS-CoV-2 infection.

BACKGROUND: Growth differentiation factor (GDF)-15 is a member of a transforming growth factor-ß cytokine superfamily that regulates metabolism and is released in response to inflammation, hypoxia and tissue injury. It has evolved as one of the most potent cytokines for predicting the severity of infections and inflammatory conditions, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIM: To investigate the utility of GDF-15 in predicting the severity of SARS-CoV-2 infection. METHODS: PubMed, Reference Citation Analysis, CNKI, and Goggle Scholar were explored by using related MeSH keywords and data such as the first author's name, study duration, type and place of study, sample size and subgroups of participants if any, serum/plasma GDF- 15 level in pg/mL, area under the curve and cut-off value in receiver operating characteristic analysis, method of measurement of GDF-15, and the main conclusion were extracted. RESULTS: In all studies, the baseline GDF-15 level was elevated in SARS-CoV-2-infected patients, and it was significantly associated with severity, hypoxemia, viral load, and worse clinical consequences. In addition, GDF-15 levels were correlated with C-reactive protein, D-dimer, ferritin and procalcitonin, and it had superior discriminatory ability to detect severity and in-hospital mortality of SARS-CoV-2 infection. Hence, GDF-15 might be used to predict the severity and prognosis of hospitalized patients with SARS-CoV-2. CONCLUSION: Serial estimation of GDF-15 levels in hospitalized patients with SARS-CoV-2 infection appeared to have useful prognostic value and GDF-15 can be considered a clinically prominent sepsis biomarker for SARS-CoV-2 infection.

Analysis of Prediagnostic Circulating Levels of Gonadotropins and Androgens with Risk of Epithelial Ovarian Cancer.

Background Prevailing experimental and epidemiological evidence supports the role of circulating endogenous sex steroid hormones in the pathogenesis of ovarian carcinogenesis by dysregulation of cell differentiation, proliferation, and apoptosis but is scarce and inconclusive. Objectives This article evaluates the role of circulating levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and androgens (testosterone, dehydroepiandrosterone-sulfate [DHEA-S]) for the risk of epithelial ovarian cancer in a case-control approach using samples collected in advance of clinical diagnosis. Materials and Methods A total of 100 epithelial ovarian cancer (EOC) patients and 100 healthy female controls were consequently enrolled in this hospital-based case-control study. Serum FSH, LH, testosterone, and DHEA-S were measured based on the principle of electrochemiluminescence immunoassay. Suitable descriptive statistics were used for different variables. Results Median values of FSH (58.9 vs. 45.5 IU/L, p = 0.02) and DHEA-S (163.43 vs. 142.2 ug/dL, p = 0.03) were significantly high in EOC patients compared with controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH and DHEA-S concentrations, and the results revealed that the highest third tertile of FSH (> 72.6 IU/L; OR = 3.0, confidence interval [CI] = 1.24-7.29, p trend = 0.04) and DHEA-S (> 194.2 ug/dL; OR = 3.8, CI = 1.26-11.61, p trend = 0.03) were significantly associated with increased risk of ovarian cancer in postmenopausal and premenopausal women, respectively. The statistically significant trend observed for FSH in postmenopausal women, remained only for the subgroup with menopause duration greater than 10 years (OR = 5.9, CI = 1.33-26.66, p trend = 0.04). FSH and DHEA-S concentrations and ovarian cancer risk were internally consistent with groups defined by oral contraceptive pill use, hormone replacement therapy, and smoking. However, no evidence was found for the association between serum LH and testosterone level with the occurrence of ovarian tumorigenesis. Conclusion Prediagnostic circulating concentration of FSH and DHEA-S unveiled a significant positive association with augmented risk of EOC, thus might serve as a predictive marker for the susceptibility to ovarian carcinogenesis and should be added in the screening profile of EOC for early recognition and scheduling necessary interventions/management strategies.

Analysis of the Prevalence and Severity of Dysregulated Bone Mineral Homeostasis in Nondialyzed Chronic Kidney Disease Patients.

Background Progressive loss of kidney function in chronic kidney disease (CKD) leads to altered mineral homeostasis, reflected by the imbalance in calcium and phosphorus, and has been associated with progression of renal failure. Aims The aim of this study was to investigate CKD-mineral bone disorder (CKD-MBD)-associated candidate variables and its relationship with parathyroid hormone (PTH), as well as to quantify the prevalence of CKD-associated mineral disturbances in nondialyzed CKD patients. Materials and Methods This cross-sectional analytical study included 124 CKD patients and 157 control participants. Blood samples were analyzed for serum total calcium, phosphorus, PTH, electrolytes, and other hematological/hemodynamic parameters by standard methods. Suitable descriptive statistics was used for different variables. Results The 124 patients had a mean age of 50.2 ± 7.8 years with male to female ratio of 1.58; majority of patients had stage 3 CKD (40.32%), and the most common comorbid conditions were diabetes mellitus ( n = 78 [62.9%]) and hypertension ( n = 63 [50.8%]). A high prevalence of mineral metabolite abnormalities was observed in a patient cohort; overall prevalence of hyperparathyroidism was found in 57.25% patients, hypocalcemia in 61.29%, and hyperphosphatemia in 82.25% patients. Prevalence of abnormal homeostasis (with regard to total calcium, phosphate, and PTH) increased progressively with the severity of disease (analysis of variance; p < 0.05). Significant differences in the mean values of total calcium, phosphorus, alkaline phosphatase, and PTH were seen compared with healthy participants ( p < 0.0001). Furthermore, there was a significant positive correlation between serum PTH with serum phosphorous ( R 2 : 0.33; p < 0.0001), serum creatinine ( R 2 : 0.084; p < 0.0259), serum potassium ( R 2 : 0.068; p < 0.0467), and a significant negative correlation with serum total calcium ( R 2 : 0.37; p < 0.0001). Conclusions CKD patients are at risk of or may already have developed secondary hyperparathyroidism apparent from PTH-linked derangements in mineral metabolism in predialysis CKD patients. These abnormalities start in early stages of CKD and worsen with disease progression. This accentuates the significance of early recognition of mineral bone disorder, understanding its pathophysiological consequences and scheduling necessary interventions/management strategies to protect the CKD patients from a plethora of complications.

A Molecular Insight of the Role of PIN-1 Promoter Polymorphism (- 667C > T; rs2233679) in Chronic Kidney Disease Patients with Secondary Hyperparathyroidism.

Murine studies stipulate Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN-1) as a key mediator of PTH mRNA stability and is acknowledged by genome-wide-association-studies as secondary hyperparathyroidism defining trait in chronic kidney disease. Therefore, we hypothesize that molecular variants of the PIN-1 gene might affect the incidence and predisposition to secondary hyperparathyroidism in chronic renal insufficiency. A total of 281 adult participants, including 124 chronic kidney disease patients with secondary hyperparathyroidism and 157 healthy controls, were genotyped using polymerase chain reaction-restriction fragment length polymorphism method to unravel the effects of genetic risk loci (PIN-1 gene; - 667C > T; rs2233679) on the susceptibility to secondary hyperparathyroidism in chronic kidney disease. Suitable descriptive statistics was used for different variables. The genotype (x2: 8.03, 2 d. f. p = 0.0181) and allele distribution (x2: 7.27, 2 d. f. p: 0.007) of the - 667C > T variant differed significantly in cases and controls, with no deviation from Hardy-Weinberg equilibrium in either affected or control group. The observed frequencies of T allele of PIN-1 - 667 C > T SNP was significantly high in CKD-SHPT group compared to control group (52.41% vs. 41.71%; p: 0.0118). TT variant of PIN-1 - 667C > T SNP was associated with increased risk for occurrence of CKD-SHPT in univariate analysis (OR: 4.6, p: 0.0032, 95% CI: 1.66-12.76). Further in multivariate analysis, both TT (OR: 3.84, p: 0.002, 95% CI: 0.79-9.26) and CT + TT (OR: 2.51, p: 0.031, 95% CI: 0.64-8.68) variants were independently associated with increased risk for CKD-SHPT, emphasizing the deleterious effect of minor T allele. Serum PTH, phosphorus levels were significantly high in CT and TT genotypes compared to CC genotype of PIN-1 - 667C > T SNP (p = 0.001). PIN-1 promoter functional SNP (- 667C > T; rs2233679) appeared to be an important genetic determinant in etiopathogenesis of CKD-SHPT and genetic variants of this SNP influences the risk stratification and might serve as a predictive marker. Thus, rs2233679 can be useful for outcome predictions during diagnostic processes.

Analysis of the Pattern, Alliance and Risk of rs1799752 (ACE I/D Polymorphism) with Essential Hypertension.

Studies in spontaneously hypertensive rat had revealed an elevated level of ACE gene expression in the tissues and is substantiated by experimental clinical studies for a positive correlation between ACE I/D polymorphism and hypertension. Aim: To determine whether the polymorphic variant of ACE gene in intron 16 confers susceptibility to essential hypertension. I/D polymorphism at the locus intron 16 of the ACE gene were amplified from the genomic DNA of the total 571 (hypertensive patients, n: 279; controls, n: 292) participants using polymerase chain reaction and gel electrophoresis methods and were examined in a case-control approach. Suitable descriptive statistics was used for different variables. Result revealed significant heterogeneity under the allele (p: 0.0002) and genotype (p: 0.0001) contrast in hypertensive patients than in normal controls, with an increased frequency of D allele (62.72%; p < 0.0001; OR: 1.8144; 95% CI: 1.4327-2.2979) and DD genotype (41.93%; p: < 0.0001). A significant association was found in the DD variant with disease phenotype (p: 0.0018, 95% CI: 1.3303-3.4907; OR: 2.1549; Table 31) and is substantiated by the data of multivariate analysis, demonstrating a statistically significant increase in odds of hypertension with the ACE D/D genotype (OR: 2.09; 95% CI: 1.24-2.91). Conspicuously, subgroup analysis by gender did not change this pattern of results. Albeit the allele distribution resulted in a higher frequency of the D/D genotype in the cases than controls, testing genetic equilibrium between the observed and expected genotypes using Hardy-Weinberg equilibrium showed ACE gene variants were confirming to the law in hypertensive as well as in non-hypertensive participants. I/D polymorphism in the angiotensin-I-converting enzyme gene at the 16th intron can be useful for outcome predictions during diagnostic processes can be implicated in an individual's propensity for hypertension and thus implies that genetic variants of ACE I/D might serve as a predictor for the susceptibility to hypertension.

CRISPR/Cas9: A Molecular Tool for Ovarian Cancer Management beyond Gene Editing.

Ovarian cancer manifests with early metastases and has an adverse outcome, impacting the health of women globally. Currently, this malignancy is often treated with cytoreductive surgery and platinum-based chemotherapy. This treatment option has a limited success rate due to tumor recurrence and chemoresistance. Consequently, the fundamental objective of ovarian cancer treatment is the development of novel treatment approaches. As a new robust tool, the CRISPR/Cas9 gene-editing system has shown immense promise in elucidating the molecular basis of all the facets of ovarian cancer. Due to the precise gene editing capabilities of CRISPR-Cas9, researchers have been able to conduct a more comprehensive investigation of the genesis of ovarian cancer. This gained knowledge can be translated into the development of novel diagnostic approaches and newer therapeutic targets for this dreadful malignancy. There is encouraging preclinical evidence that suggests that CRISPR/Cas9 is a powerful versatile tool for selectively targeting cancer cells and inhibiting tumor growth, establishing new signaling pathways involved in carcinogenesis, and verifying biomolecules as druggable targets. In this review, we analyzed the current research and progress made using CRISPR/Cas9-based engineering strategies in the diagnosis and treatment, as well as the challenges in bringing this method to clinics. This comprehensive analysis will lay the basis for subsequent research in the future for the treatment of ovarian cancer.

Role of the Tumor Microenvironment and the Influence of Epigenetics on the Tumor Microenvironment in Oral Carcinogenesis: Potential Implications.

Oral cancer has become a significant problem throughout the world, particularly in countries that are still developing. Recent literature supports the contribution of components of the tumor microenvironment (TME) and the effect of epigenetic changes happening in the cells of the TME on oral cancer development and progression. In this review, we comprehensively examine the significance of TME in the development of OC along with the current understanding of the epigenetic modifications that regulate the TME and their cohesive impact on tumor traits and their potential as therapeutic targets.

Utility of P-SEP, sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection.

The coronavirus disease 2019 is a highly contagious viral infection caused by SARS-CoV-2 virus, member of coronaviridae family. It causes life threatening complications due to complexity and rapid onset course of the disease. Early identification of high-risk patients who require close monitoring and aggressive treatment remains challengeable till date. Novel biomarkers which help to identify high risk patients at the early stage is high priority. Objective of this review to find utility of P-SEP, sTREM-1 and suPAR for diagnosis, risk stratification and prognosis of SARS-CoV-2 infected cases. Soluble receptors like, P-SEP, sTREM-1 and suPAR have been involved in immune regulation in SARS-CoV-2 infection and elevate more in severe cases. A comprehensive research of databases like PubMed, EMBASE, CNKI and Web of Science was performed for relevant studies. A total of nine out of fifteen research literature in initial screening were included for this review. Interestingly all studies have reported high levels of P-SEP, sTREM-1 and suPAR in SARS-CoV-2 infected cases and the biomarkers positively correlated with severity of infection. This implies that P-SEP, sTREM-1 and suPAR can be implemented as surrogate marker in blood profile for early diagnosis, risk stratification and prognosis in SARS-CoV-2 for better management in Indian population at the current situation.

Notable and Emerging Variants of SARS-CoV-2 Virus: A Quick Glance.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease-2019 (COVID-19), is a highly contagious pathogenic coronavirus to emerge and spread in human populations. Although substantial exertions have been laid to avert spread of COVID-19 by therapeutic and preventive countermeasures, but emergence of SARS-CoV-2 variants as a result of mutations make the infection more ominous. New viral confers a higher nasopharyngeal viral load, increased viral transmissibility, higher infectiousness, immune escape, increased resistance to monoclonal/polyclonal antibodies from convalescence sera/vaccine, and an enhanced virulence. Thus, it is pertinent to monitor evolving mutations and genetic diversity of SARS-CoV-2 as it is decisive for understanding the viral variants. In this review we provide an overview of colloquial nomenclature and the genetic characteristics of different SARS-CoV-2 variants in the context of mutational changes of the circulating strains, transmissibility potential, virulence and infectivity.