Assessment of Vitamin D Levels and Other Bone Related Biochemical Markers in Healthy Adults in Rural Population of Uttarakhand, India.

Despite being close to equator and receiving sufficient sun rays, evidences revealed that Indians have severe deficiency of vitamin D (vit D) ranging from 41 to 100% in different geographical locations. Therefore, in this study levels of 25(OH)D (physiologically measurable form) along with other bone metabolism associated biochemical markers were determined in serum sample of 300 apparently healthy study subjects (rural) from Doiwala block of Dehradun district in the state of Uttarakhand. Demographic data was also obtained based on a structured questionnaire to establish an association between 25(OH)D levels and various dietary and socio-cultural factors. Results demonstrated that of all study subjects, 197 (65%) had 25(OH)D levels below < 12 ng/mL (deficient) and 65 (21%) had 25(OH)D levels between 12 and 20 ng/mL (insufficient) with all other markers falling within respectively established reference ranges. Further, in univariate analysis, gender, occupation (indoor and outdoor), education were independently associated with vitamin D status. Additionally, parathyroid hormone associated significantly with gender and occupation, while calcium associated significantly with gender, occupation and education. Lastly, regression analysis revealed that gender and occupation independently associated with vitamin D status of subjects. In conclusion, apparently healthy subjects showed considerable vitamin D deficiency thereby generating an urgent need for formulating and implementing better government policies for enrichment of vitamin D levels among rural adults of Uttarakhand in future. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01048-6.

Single-Point Insulin Sensitivity Estimator (SPISE) as a Feasible Marker of Insulin Resistance in Adult Metabolic Syndrome: Evaluated in a Hospital Based Cross-Sectional Pilot Study at Tertiary Care Centre of Uttarakhand.

Insulin resistance (IR) plays an important role as a major determinant of Metabolic syndrome (MetS). Various methods are available for measuring insulin resistance but they are laborious, time-consuming, and costly. Therefore various surrogate markers and indices have been devised to simplify and improve the determination of insulin resistance. Recently, a new index, single point insulin sensitivity estimator (SPISE) was proposed in the European population and was found comparable to the gold standard test (hyperinsulinemic euglycemic glucose clamp).This study was planned to evaluate whether SPISE could be a useful potential low-cost indicator for predicting MetS with IR patients in Indian population. Eighty-three participants from outpatient care of AIIMS Rishikesh were evaluated after informed consent. They were divided into Metabolic syndrome (n = 56) and Non Metabolic Syndrome(n = 27), using South Asian Modified National Cholesterol Education Program- ATP-III criteria for metabolic syndrome. SPISE index, HOMA-IR, Insulin Resistance Index, Triglycerides to high-density lipoproteins cholesterol ratio (TG/HDL-C) were calculated for all the subjects. Receiver operating characteristic (ROC) curve was plotted to assess discriminatory ability of SPISE, HOMA-IR, TG/HDL-C ratio, IRI and hs-CRP to differentiate between IR(Metabolic syndrome) and non-IR (Non-Metabolic syndrome) subjects. SPISE has greater area under curve with better sensitivity and specificity compared to HOMA-IR, IRI, TG/HDL-C ratio and hs CRP. So, SPISE has better predictive ability than HOMA-IR, IRI, TG/HDL-C ratio and hs CRP to discriminate IR from non-IR cases. SPISE could be a useful potential low-cost indicator with high sensitivity and specificity for predicting IR in MetS patients.

Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.

INTRODUCTION: Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization. MATERIALS AND METHODS: This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC. RESULTS: Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters. CONCLUSION: SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.

COVID-19 and Gut Microbiota: A Potential Connection.

Currently, world is facing a global outbreak causing a pandemic threat known as COVID-19. This infectious disease is triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Gut microbiota harbours multi species community with a strong impact on host immune homeostasis. However, our knowledge about this gut microbiota and its symbiotic relationship with immune activation in association with SARS-CoV-2 is limited. Unbalanced bacterial flora with too many opportunistic infections can shift immune system towards a cascade of inflammatory responses leading to multi organ damage. This review will highlight immune-regulation via various mechanisms in SARS-CoV-2 infection. Diet has an unbelievable influence on gut microbiome that allows a new state of homeostasis to be reached through timing, frequency and duration of intake. This review article focuses on gut, lung microbiota and immunomodulation with specific attention on immune activation by gut microbiota.

Review on COVID-19 Etiopathogenesis, Clinical Presentation and Treatment Available with Emphasis on ACE2.

In December 2019, Wuhan city in the Hubei province of China reported for the first time a cluster of patients infected with a novel coronavirus, since then there has been an outburst of this disease across the globe affecting millions of human inhabitants. Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), is a member of beta coronavirus family which upon exposure caused a highly infectious disease called novel coronavirus disease-2019 (COVID-19). COVID-19, a probably bat originated disease was declared by World Health Organization (WHO) as a global pandemic in March 2020. Since then, despite rigorous global containment and quarantine efforts, the disease has affected nearly 56,261,952 laboratory confirmed human population and caused deaths of over 1,349,506 lives worldwide. Virus passes in majority through respiratory droplets and then enters lung epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and there it undergoes replication and targeting host cells causing severe pathogenesis. Majority of human population exposed to SARS-CoV-2 having fully functional immune system undergo asymptomatic infection while 5-10% are symptomatic and only 1-2% are critically affected and requires ventilation support. Older people or people with co-morbidities are severely affected by COVID-19. These categories of patients also display cytokine storm due to dysfunctional immune response which brutally destroys the affected organs and may lead to death in some. Real time PCR is still considered as standard method of diagnosis along with other serology, radiological and biochemical investigations. Till date, no specific validated medication is available for the treatment of COVID-19 patients. Thus, this review provides detailed knowledge about the different landscapes of disease incidence, etiopathogenesis, involvement of various organs, diagnostic criteria's and treatment guidelines followed for management of COVID-19 infection since its inception. In conclusion, extensive research to recognize novel pathways and their cross talk to combat this virus in precarious settings is our future positive hope.

Quantifying the Homeostatic Model Assessment of Insulin Resistance to Predict Mortality in Multi-organ Dysfunction Syndrome.

BACKGROUND: Insulin resistance is an integral component of a multi-organ dysfunction syndrome (MODS) associated with increased mortality. We determined a cutoff value for the homeostatic model assessment of insulin resistance (HOMA-IR) during an ICU admission that could predict 28-day mortality of nondiabetic MODS patients. MATERIALS AND METHODS: In this prospective, outcome assessor blinded cohort design, we evaluated 82 such patients for fasting blood glucose (FBG)/insulin levels (FIL) during an ICU admission and followed their outcome for 28 days. The primary outcome variable was the HOMA-IR score calculated from the above variables. The statistical tool included receiver operating characteristic curve, Youden index, and correlation and regression analysis. RESULTS: Overall, 38 patients succumbed to their illness. The optimal cutoff value for HOMA-IR was ≥1.61 (area under curve: 0.684, sensitivity: 36.8%, specificity: 95.5%). The 28-day survival was significantly lower (p = 0.001) at HOMA-IR threshold ≥1.61 (odds ratio: 12.25, hazard ratio: 2.98). The mean HOMA-IR among survivors vs nonsurvivors was 0.76 ± 0.61 and 1.38 ± 1.14, respectively (p = 0.004). Except for FIL and FBG, HOMA-IR values did not correlate with any other baseline or outcome parameters (demographics, APACHE II/sequential organ failure assessment score, vasopressor needs, or ICU/hospital stay). On comparing these parameters across the HOMA-IR threshold, only FIL and the hospital stay varied significantly. Most of the outcome parameters, however, varied significantly among nonsurvivors vs survivors. CONCLUSION: The HOMA-IR is a significant predictor of mortality in MODS. Its cutoff value may assist in determining a reference range for critically ill patients. Its routine use in the light of other disease severity scores may serve in their better prognostication. HOW TO CITE THIS ARTICLE: Sama S, Jain G, Kant R, Bhadoria AS, Naithani M, Kumar A. Quantifying the Homeostatic Model Assessment of Insulin Resistance to Predict Mortality in Multi-organ Dysfunction Syndrome. Indian J Crit Care Med 2021;25(12):1364-1369.

An intercontinental comparison of the influence of smoking on the occurrence of nonsyndromic cleft lip and palate: a meta-analysis and systematic review.

BACKGROUND: The influence of smoking on nonsyndromic clefts has been a topic of research for many years. However, few studies have investigated the effect of smoking on causing clefts in different gene pools. METHODS: A meta-analysis was conducted of case-control studies related to smoking. Keywords such as "clefts," "cleft lip," "cleft palate," "orofacial cleft," and "smoking" were used to search the MEDLINE, Embase, and Cochrane databases. RESULTS: In total, 51 articles were reviewed. The RevMan software was utilized for the analysis, and the Mantel-Haenszel method was employed to pool the odds ratios (ORs) and 95% confidence intervals. Although the overall OR, a measure of the association between exposure and outcome, was higher for smokers than for non-smokers, this association was significantly stronger in individuals from Asia and South America (1.73), and lowest in Europe (1.31). Among active and passive smokers in Asia, the OR was approximately 0.93, indicating an equivalent impact from both types of smoking. CONCLUSION: This analysis indirectly suggests that restriction measures targeting both active and passive smoking are crucial in Asia.

Wound pH and Surface Temperature as a Predictive Biomarker of Healing in Diabetic Foot Ulcers.

AIM: To monitor wound pH and surface temperature as predictors of wound healing in diabetic foot ulcers (DFU). METHODS: Prospective, observational, time-bound study of 18 months, enrolling patients aged 18 to 60 years with uninfected DFU. The wound was assessed at baseline and after that, every week for 4 weeks according to the leg ulcer measurement tool (LUMT). Concurrently, wound surface pH and temperature were measured. The data were analyzed using descriptive statistics, and a P-value < .05 was considered statistically significant. RESULTS: Fifty-four patients with DFU were included in the study with a mean age of 55 years and a male to female ratio of 1.57. The wound showed progressive improvement, a maximum mean LUMT score of 48.89 (± 2.81) at the initial evaluation and decreased progressively to the mean of 19.80 at week 4 (± 3.43), both of which were statistically significant (P-value < .001). Similarly, the median wound pH progressively reduced from 7.7 at baseline to 7.20 in the fourth week, and median wound temperature decreased from 90°F (32.22 °C) at baseline to 85°F (29.44 °C) in the fourth week, both of which were statistically significant (P-value < .001). CONCLUSION: Progressive and significant change in wound pH to acidic and drop in wound surface temperature, both corresponding to improvement in the status of DFU, maximum at 4 weeks, make them valuable predictors of wound healing. However, further, more extensive studies are required to establish a concrete relationship.

Metabolic Syndrome and Its Association with Menopausal Symptoms among Postmenopausal Women: A Cross-sectional Study.

Background: With increase in postmenopausal population, screening for MetS and its relationship with menopausal symptoms needs evaluation. Objective: To identify the frequency of metabolic syndrome (MetS) and assess its relationship with menopausal symptoms in postmenopausal women. Methods: This was a cross sectional study performed at a tertiary care centre in Uttarakhand India over a period of 18 months. All postmenopausal women >40 years with natural menopause included in the study sample. We used the Consensus Definition IDF and AHA/NHLBI (2009) criteria to classify subjects as having metabolic syndrome. Menopausal symptoms were assessed using Menopause Rating Scale (MRS) questionnaire. Results: The frequency of metabolic syndrome in our study was 34.38% (55 out of 160 patients). We observed sleeping problems (36.88%) followed by physical & mental exhaustion (33.75%) and hot flushes (33.13%) to be the commonest menopausal symptoms. Significant association was seen for MRS along with its subscales in women with metabolic syndrome (P value <.05). Significant positive correlation was observed between total Menopause rating scale scores as well as all three subscales for triglycerides in patients with metabolic syndrome. Conclusion: Hyper triglyceridemia was associated with severe menopausal symptoms among postmenopausal women with MetS in our study.

Comparison of Human Epididymis Protein 4, Cancer Antigen 125, and Ultrasound Prediction Model in Differentiating Benign from Malignant Adnexal Masses.

Background: This study aimed to compare the diagnostic performance of carcinogenic antigen (CA) 125, (HE)-4 (Human epididymis protein 4), and ultrasound (International Ovarian Tumor Analysis [IOTA]) Simple Rules individually and to derive a composite score in the differentiating ovarian cancer from benign ovarian mass. Subjects and Methods: Consecutive patients (n = 100) with pelvic mass admitted during February 2018-August 2019 were included prospectively. Patients with either known case of epithelial ovarian cancer (EOC) or metastatic EOC were excluded. The primary outcome was to assess the sensitivity and specificity of CA-125, HE-4, and IOTA Simple Rules in predicting benign from malignant mass independently, while secondary outcome was derivation of a new model incorporating these variables using multivariate logistic regression analysis to predict benign from malignant lesions. Receiver operator curve (ROC) was drawn to redefine the best-performing cutoff values and difference between area under the ROC (AUROC) were compared by DeLong's method. Results: Out of 100 cases of adnexal mass selected, the sensitivity and specificity of CA-125 were 73.8% and 77.6%, HE-4 were 90.5% and 87.9%, and IOTA Simple Rules were 92.9% and 81.0%. CA-125, HE-4, and IOTA Simple Rules were independently associated with the likelihood of malignancy/borderline (P < 0.001). The area under the curve for the "composite score" (AUC = 0.93) was the highest and was significantly better than that of CA-125 (AUC = 0.786) (P = 0.004 using DeLong's test) and comparable with HE-4 (AUROC = 0.90; P = 0.128 using DeLong's Test). Conclusion: The sensitivity and specificity of HE-4 and IOTA Simple Rules for predicting malignant ovarian tumor was better than those of CA-125. The diagnostic performance of "composite score" was comparable to those of either HE-4 or IOTA Simple Rules and significantly better than CA-125.

The Role of Yoga in Hospitalized COVID-19 Patients: An Exploratory Randomized Controlled Trial.

Introduction The unpredictable course and sheer magnitude of coronavirus disease 2019 (COVID-19) have sparked a search for novel and repurposed pharmacological interventions. Non-pharmacological interventions may also play a role in the management of this multifaceted disease. This study aimed to evaluate the safety, feasibility, and effect of yoga in hospitalized patients with moderate COVID-19. Methods Twenty patients satisfying the inclusion criterion were randomized (1:1 ratio) into Intervention and Control groups. Patients in the intervention arm performed a one-hour yoga session that included pranayama and Gayatri mantra (GM) chant for up to 14 days. Sessions were fully supervised by a trained yoga trainer via an online platform. Patients in both groups received the normal treatment as per national guidelines. Outcome parameters were recorded on the 14th day/end of the hospital stay. Results Yoga is safe and feasible in hospitalized patients with COVID-19. The decline of high-sensitivity C-reactive protein (hs-CRP) levels was significantly greater in the Intervention Group. Quality of life (QOL), depression, anxiety, and fatigue severity scale (FSS) showed a decline in both groups with a significant decline observed in FSS scores of the Intervention Group. Median chest X-ray score values, duration of hospital stay, and reverse transcription-polymerase chain reaction (RT-PCR) conversion days were observed to be lower in the Intervention Group but were not significant (p>0.05). Conclusion The study found that incorporating pranayama and GM practices in hospitalized patients with moderate COVID-19 pneumonia was safe and feasible. It showed a notable reduction in hs-CRP levels and FSS scores in the Intervention Group, but the study was not powered to detect statistically significant results. Further research with larger sample sizes is needed for conclusive findings.

Genetic Variations in IL-1ß, TNF-α, and TGF-ß Associated with the Severity of Chronic Cervical Spondylitis in Patients.

Chronic cervical spondylitis (CCS), a degenerative disorder of the spine, is known for causing disability among old and young people. Single-nucleotide polymorphisms (SNPs) in various cytokine genes have demonstrated an impactful association with several inflammatory disorders. In the present study, we have investigated the SNPs and allelic distribution of the three most prevalent cytokines genes, IL-1ß (-511C/T), TNF-α (-308G/A), and TGF-ß (-509C/T), along with serum levels of these cytokines in 252 subjects. SNPs were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and digested fragments were separated and visualized using agarose gel electrophoresis and Native Polyacrylamide gel electrophoresis (PAGE). The serum cytokine levels were analyzed with a flow cytometer using a customized multiplex bead-based assay. It was observed that these SNPs did not reflect the susceptibility to CCS but were associated with susceptibility to CCS. We found a significant association between the C/C and G/G genotypes and the C and G alleles of IL-1ß and TNF-α, respectively, suggesting a lower risk of CCS. The frequency distribution of risk alleles (-511T) and (-308A) were simultaneously higher in CCS compared to the control, reflecting the susceptibility to CCS. TGF-ß showed a significant association with disease susceptibility, along with a significant correlation between age and the chronicity of CCS. The serum cytokine levels were significantly different in CCS and controls.

Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review.

To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug discovery. Only four studies used AI technology for vaccine development, whereas one study generated stable antibodies against SARS-CoV-2. Approx. 50% of studies exclusively targeted 3CLpro of SARS-CoV-2, and only two studies targeted ACE/TMPSS2 for inhibiting host viral interactions. Around 16% of the identified drugs are in different phases of clinical evaluation against COVID-19. AI has emerged as a promising solution of COVID-19 therapeutics. During this current pandemic, many of the researchers have used AI-based strategies to process large databases in a more customized manner leading to the faster identification of several potential targets, novel/repurposing of drugs and vaccine candidates. A number of these drugs are either approved or are in a late-stage clinical trial and are potentially effective against SARS-CoV2 indicating validity of the methodology. However, as the use of AI-based screening program is currently in budding stage, sole reliance on such algorithms is not advisable at this current point of time and an evidence based approach is warranted to confirm their usefulness against this life-threatening disease. Communicated by Ramaswamy H. Sarma.

Plastic bottle feeding produces changes in biochemical parameters in human infants - A pilot study.

BACKGROUND: Plastic bottles are widely used by people to feed their infants when breastfeeding is not possible. Bisphenol A (BPA), an endocrine disruptor is widely used in the manufacturing of plastic wares and is leached out from these plastic wares on exposure to high temperature, changed pH, or cleaning the plastic wares by harsh detergents. PURPOSE: Feeding through plastic bottles over prolong duration is expected to expose the infants to leached BPA. Hence the present study was taken up to compare the effects of breastfeeding and plastic bottle feeding on biochemical parameters in infants and also detect for the presence of free BPA or its metabolite in the infants. METHODS: Biochemical tests like lipid profile, liver function tests, creatine-kinase-MB (CK-MB), serum urea, serum electrolytes were performed on blood samples obtained from infants who were breastfed and plastic bottle fed. Further, plasma and urine samples of the infants were subjected to Liquid chromatography-mass spectrometry analysis for detecting free BPA and BPA glucuronide. RESULTS: Biochemical changes in form of raised triglycerides, cholesterol, low-density lipoproteins, very low-density lipoproteins and increase in CK-MB, serum urea were observed in plastic bottle fed infants. BPA glucuronide was also detected in the urine of these infants. Free BPA was not detected in plasma or urine samples of the infants except in one plasma sample from bottle-fed group. CONCLUSION: Plastic bottle feeding may lead to toxic changes in the functioning of organs which manifest as altered biochemical parameters.

Assessment of Dyslipidemia, Lipid Ratios, and Atherogenic Indices as Cardiovascular Risk Factors in Prediabetic and Diabetic Subjects.

Background Uttarakhand is a small state in northern India that comprises mixed population with people dwelling in both hilly and plain areas. Globally, diabetes mellitus (DM) has already been considered to be a pandemic. Furthermore, cardiovascular diseases (CVD) significantly increase mortality and morbidity in patients suffering from DM. Additionally, dyslipidemia has been identified as an important marker in the development of atherosclerosis and ultimately CVD in patients of prediabetes and diabetes. Thus, the identification of subjects with dyslipidemia in prediabetes might be fruitful in lowering their progression to diabetes and ultimately in decreasing incidences of CVD. Hence, this study was undertaken to assess dyslipidemia via the calculation of atherogenic indices (AI) and lipid ratios in prediabetic and diabetic groups attending tertiary care hospital in Uttarakhand. Materials and Methods This study reviewed retrospective biochemical data of 500 study subjects from e-hospital software of the All India Institute of Medical Sciences, Rishikesh. All study subjects were divided into three groups: 122 controls, 137 prediabetics, and 241 diabetics based on the American Diabetes Association criteria. Study subjects were evaluated for glycated hemoglobin (HbA1c), lipid profile, and AI (total cholesterol [TC]/high-density lipoprotein cholesterol [HDLc], low-density lipoprotein cholesterol [LDLc]/HDLc, TC-HDLc/HDLc, triglycerides [TG]/HDLc). Results Results showed that TC, TG, LDLc, and AI were significantly higher, and HDLc was significantly decreased in prediabetic and diabetic groups compared with controls. Furthermore, HbA1c showed significant positive correlation with lipid profile and AI except atherogenic coefficient (TC-HDL/HDL). Conclusion In conclusion, the current study showed the presence of dyslipidemia in both prediabetic and diabetic groups underlining their importance for screening at the prediabetic stage. Hence, we also recommend screening of the prediabetic group for dyslipidemia to arrest the development of early cardiovascular complications.

An Insight Into the Association of Sclerostin With Insulin Sensitivity and Glycemic Parameters in Male Indian Prediabetic and Diabetic Population.

Background Type 2 diabetes (T2D) is increasing day by day and creating a huge financial and social burden on the Indian population. Insulin resistance results in hyperglycemia, a condition that eventually causes prediabetes and Type 2 diabetes. The etiopathogenesis of T2D is still not clearly defined. Wnt signaling pathway is involved in pancreas development, islet function, insulin production, and secretion. Recent studies show that sclerostin, a Wnt signaling inhibitor, is associated with diabetes. The sclerostin level is altered as a function of race and ethnicity. However, no study has been conducted to observe the sclerostin level in prediabetic and diabetic individuals in the Indian population. Objectives The main objectives of the study are: to determine whether sclerostin is associated with glycemic parameters, serum insulin levels, insulin resistance/ sensitivity, beta-cell function, and adipose tissue insulin resistance (Adipo-IR). Methods This observational study was carried out at a tertiary care hospital, in Rishikesh, Uttarakhand, India. Individuals with T2D and prediabetes and healthy references were included in this study. Sclerostin and free fatty acids (FFA) were measured with the enzyme-linked immunosorbent assay (ELISA), and blood sugar, insulin, and glycated haemoglobin (HbA1c) were measured by the hexokinase, chemiluminescent, and chromatography methods, respectively. Messenger RNA (mRNA) was quantified by real-time polymerase chain reaction (PCR) using the SYBR Green protocol. Adipo-IR, homeostasis model assessment-estimated insulin resistance (HOMA-IR), homeostasis model assessment of ß-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), and single point insulin sensitivity estimator (SPISE) indices were calculated. Results A total of 171 study participants were enrolled in type 2 diabetes, prediabetes, and controls groups, having 57 each in the group. There was a gradual increase in sclerostin levels from healthy [242.12(158.44)] to prediabetes [256.06(299.65)] and diabetes [465.76 (735.71)] with a significant (<0.001) difference from healthy reference. Sclerostin showed a significant positive correlation with fasting blood sugar (r=0.200; p=0.009), HbA1c (r=0.394; p<0.001) and free fatty acids (r=0.205; p=0.007) in total study participants. The SPISE index showed a significant positive correlation (r=0.269, p=0.043) in the prediabetic group. SOST, GLUT4, and insulin receptor (IR) mRNA expression all corroborate with the glycemic status. Conclusion Significantly higher expression of sclerostin (both protein and gene) in newly diagnosed T2D and prediabetes male patients, as well as significant association with SPISE index, suggest that sclerostin might be an indicator of pathophysiology related to insulin resistance, which is a characteristic feature of diabetes mellitus. However, the identification of causal relationships would warrant a large-scale prospective cohort study.

Preparedness of Undergraduate Medical Students to Combat COVID-19: A Tertiary Care Experience on the Effectiveness and Efficiency of a Training Program and Future Prospects.

Introduction Due to the nature of the coronavirus disease 2019 (COVID-19) pandemic, final year medical undergraduate students have had to be involved in patient management in different countries. The same was the case with India. This study was conducted with the objective to analyze the effectiveness and efficiency of preparedness training to combat COVID-19 in pre-final and final-year medical students at a tertiary care institute in North India. Methods A pre-post study was conducted among final and pre-final year medical undergraduate students. Data was collected as pre-test and post-test multiple-choice questions (MCQs) and clinical vignettes. Results A total of 179 medical undergraduate students attended the training. Scores on general instructions, personal protective equipment (PPE) donning and doffing, hand hygiene, biomedical waste management, contact tracing, cleaning and disinfection, ECG, and COVID-19 management improved significantly after the training. Pre-test scores on ECG, simulation, COVID-19 management were 21.58±5.311, 17.05±4.501, and 23.84±4.067, respectively. Post-test scores on ECG, simulation, COVID-19 management were 28.01±6.826, 23.84±4.067, and 6.93±1.726, respectively. Pre-test and post-test scores were statistically significant (p=0.0001).  Discussion Our preparedness training program was effective in delivering the intended skills. The efficiency of the training program was demonstrated through simulation. We created a trained pool of medical undergraduate students to assist clinicians in COVID-19-related supportive care.

Diffuse large B-cell lymphoma and new insights into its pathobiology and implication in treatment.

The most common non-Hodgkin lymphoma (NHL) subtype is diffuse large B-cell lymphoma (DLBCL). It accounts for roughly 30% of all cases of NHL affecting both nodal and extra nodal sites. There are molecular subtypes of DLBCL, germinal centre subtype (GCB), and activated B-cell (ABC), based on gene expression profiling (GEP), in accumulation to distinct morphological and clinicopathological subtypes. To prognosticate patients, the International Prognostication Index (IPI) and its variants are used. In ABC type DLBCL, limited stage disease is treated with a combination of abbreviated systemic chemotherapy (three cycles) and field radiation therapy. Although advanced stage disease is treated with a full course of chemotherapy as well as novel agents (Bortezomib, Ibrutinib, Lenalidomide). In this review study, we looked at the role of multiple aspects of genetic and microenvironment changes which have effects in DLBCL tumours.

Detection of differential expression of miRNAs in computerized tomography-guided lung biopsy.

Aims: Nonsmall-cell lung carcinoma comprises 85% of lung malignancies and is usually associated with a poor prognosis due to diagnosis at advanced stages. Molecular diagnosis of computerized tomography (CT)-guided biopsy has the potential to identify subtypes of lung carcinoma like adenocarcinoma (AC) and squamous cell carcinoma (SCC) along with its molecular stratification. This approach will help predict the genetic signature of lung cancer in individual patients. Subjects and Methods: Histopathologically proved a CT-guided biopsy sample of lung cancer cases was used to screen for the expression of microRNA (miRNA) earlier quantitated in blood plasma. Primers against hsa-miR2114, hsa-miR2115, hsa-miR2116, hsa-miR2117, hsa-miR449c, and hsa-miR548q with control RNU6 were used to screen 30 AC, 30 SCC, 5 nonspecific granulomatous inflammation, and 8 control samples. Reverse transcription polymerase chain reaction (RT-PCR) data revealed expression of hsa-miR2114 and hsa-miR548q in AC as well as SCC. Results: RT-PCR data revealed that the expression of hsa-miR2116 and hsa-miR449c was found upregulated in AC while hsa-miR2117 was expressed in SCC cases. Bioinformatic analysis revealed that genes, where these miRNAs are located, were also upregulated while targets of these miRNAs were downregulated. Conclusions: miRNAs expression pattern in the CT-guided biopsy samples can be used as a potential tool to differentially diagnose lung cancer subtypes. The expression pattern of miRNAs matches very well in blood plasma and tissue samples, albeit levels were very low in the earlier case than later. This approach can also be used for screening mutations and other molecular markers in a personalized manner for the management of lung cancer patients.