Exploring the burden of mixed dyslipidemia in patients with type 2 diabetes mellitus: A cross-sectional study in Kashmir, India.

BACKGROUND: Diabetes-related dyslipidemia is a multifaceted, complicated disorder characterized by an abnormal lipid profile in individuals with diabetes. The incidence of different types of dyslipidemia, however, was not a focus of prior investigations. The patients were characterized into three categories of dyslipidemia. Different patterns of dyslipidemia were combined into single dyslipidemia (7 patterns), mixed dyslipidemia (16 patterns), and triple dyslipidemia (4 patterns). METHODS: In this cross-sectional study, 586 people suffering from type 2 diabetes mellitus (T2DM) were included. We assessed the serum lipid profile and used log (TG/HDL-C) to determine the atherogenic index of plasma (AIP). Dyslipidemia was examined as a categorical variable, and the findings were presented as percentages and numbers. To compare categorical variables, we either utilized Fisher exact tests or Chi square tests. RESULTS: The study comprised of 586 T2DM patients, with 310 (52.9%) women and 276 (47.1%) men. Women have significantly higher hypertension (33.6%) as compared to men (23.2%). 18.94% (111) of patients were having coronary artery disease (CAD) history consisting of 12.28% (72) females and 6.66% (39) males, a difference which is statistically significant. 98.12% of total individuals had as a minimum of one lipid abnormality. 4.61% (27) of study subjects were having isolated dyslipidemia and 93.51% (548) had dual or triple pattern of dyslipidemia (mixed dyslipidemia). High AIP >0.24 (94.8%) was the most predominant trend of dyslipidemia. The dual combination of AIP (>0.24) and HDL (<50 mg/dL in Females and <40 mg/dL in Males) was found to be the most common pattern of mixed dyslipidemia (68.08%). The most prevalent trend of isolated dyslipidemia was found to be high AIP (>0.24), In patients with CAD history. Among the mixed dyslipidemia, the common pattern of dyslipidemia (71.17%) was the dual combination of high AIP (>0.24) and low HDL (<50 mg/dL women and <40 mg/dL males). The triple combination of TG (≥200 mg/dL) and HDL (<40 and <50 mg/dL) and LDL (≥100 mg/dL) was only found in females. CONCLUSION: In conclusion, dyslipidemia is highly prevalent in T2DM patients, with mixed dyslipidemia being the most common type observed in the community of Kashmir valley, India. High AIP was the most prevalent pattern in the current investigation.

Vitamin D receptor gene variations and their haplotypic association: Possible impact on gastric cancer risk.

Background: Vitamin D receptor (VDR) gene alterations have been associated with the occurrence and prognosis of various types of cancers, but only few studies have focussed on gastric cancer (GC) risk. Objectives: This case-control study was conceived to evaluate possible association of VDR polymorphisms (Fok1, Taq1, and Cdx2) with GC risk. Materials and Methods: A total of 293 subjects, including 143 GC patients and 150 controls were included in this study. The genotypes were elucidated by polymerase chain reaction-restriction fragment length polymorphism followed by DNA sequencing. Results: The frequency of Fok1 genotypes (TC and TT) was found higher in GC cases compared to controls (P ≤ 0.05). In the stratified analysis, we observed a significant association of the (CT + TT) variant with GC risk in males, rural dwellers, smokers, and preobese cases, and those having no family history of Gastrointestinal cancer (P ≤ 0.05). In silico analysis predicted that the Fok1 variant impacts the stability and functional efficiency of the protein. Some exact haplotypes (CCG and CCA) of the VDR gene may act as low penetrance alleles in inclination to GC. Conclusion: VDR Fok1 polymorphism is significantly associated with GC risk in the Kashmiri population. Specific haplotypes in the VDR gene could act synergistically in the development of GC.

Impact of clinico-biochemical and inflammatory biomarkers on the immunogenicity and efficacy of SARS-CoV-2 adenoviral vaccine: a longitudinal study.

Purpose: Due to a lack of effective antiviral treatment, several vaccines have been put forth to curb SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and to reduce the mortality and morbidity rate by eliciting a protective immune response, primarily through virus-neutralizing antibodies specific for SARS-CoV-2 spike protein. This longitudinal study was designed to evaluate the vaccine effectiveness and immune response following the administration of adenoviral vaccine, COVISHIELD, in Indian population who were previously uninfected with SARS-CoV-2 and to reveal the effect of various sociodemographic, inflammatory and biochemical factors on antibody response. Methods: Briefly, the total immunoglobulin G (IgG) against SARS-CoV-2 spike and nucleocapsid protein along with the immunological markers were estimated by chemiluminescent microparticle immunoassay (CMIA) technology. Biochemical parameters were estimated by spectrometry. Results: A total of 348 subjects received two doses of COVISHIELD (224 males, 124 females). The mean age of the study subjects was 42.03 ± 13.54 years. Although both the doses of COVISHIELD against SARS-CoV-2 spike protein induced a robust immune response that lasted for months in all the subjects, the total IgG titer against SARS-CoV-2 spike protein was found significantly higher in subjects ≥50 years of age, and those with obesity, elevated triglycerides and elevated lactate dehydrogenase levels. Conclusions: There is a definite effect of age and biochemical factors on the immunogenicity of COVISHIELD. An understanding of these factors could not only impact the design of vaccines and help improve vaccine immunogenicity and efficacy but also assist in decisions on vaccination schedules, in order to combat this deadly pandemic.

Impact of Age and Clinico-Biochemical Parameters on Clinical Severity of SARS-CoV-2 Infection.

INTRODUCTION: The surge in novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease-2019 (COVID-19) has overwhelmed the health system. To help health-care workers and policy makers prioritize treatment and to decrease the burden on health systems caused by COVID-19, clinical severity along with various clinico-biochemical parameters was evaluated by designing a cross-sectional study comprising 236 SARS-CoV-2-infected individuals from Kashmir Valley, India. METHODS: Briefly, real-time polymerase chain reaction (RT-PCR) was used for the confirmation of SARS-CoV-2 infection. The principles of spectrophotometry and chemiluminescent microparticle immunoassay (CMIA) were employed to estimate the levels of glucose, TSH, and 25-hydroxy vitamin D levels in serum of infected patients. RESULTS: A total of 236 patients infected with SARS-CoV-2 were taken for this cross-sectional study. Patients with COVID-19 had a male predominance (72.9 vs. 27.1%) and a higher prevalence of 25-hydroxy vitamin D deficiency (72.0 vs. 28.0%) with a mean 25-hydroxy vitamin D levels of 24.0 ± 13.9 in ng/mL. We observed a varied clinical spectrum of SARS-CoV-2 infection with 36.4%, 23.7%, and 29.7% patients having mild, moderate, and severe disease, respectively. We observed that severity of SARS-CoV-2 infection was significantly associated with older age group, hypertension, low TSH levels, and 25-hydroxy vitamin D deficiency. CONCLUSION: We conclude that not only old age but also hypertension and low levels of TSH and 25-hydroxy vitamin D levels could significantly lead to clinical severity of SARS-CoV-2 infection.

Understanding the potential immunogenetic role of TNFα-308 polymorphism in the pathogenesis of recurrent miscarriage.

Background: Recurrent miscarriage (RM) represents the spontaneous termination of two or more successive pregnancies. TNFα is a proinflammatory cytokine that is often considered harmful for embryonic development when expressed beyond normal levels. Aim: The study was conducted to assess the association between TNFα-308 polymorphism and RM pathogenesis. Methods: Samples of blood were obtained from patients and controls through venipuncture. The levels of TNFα in serum were measured by ELISA. TNFα gene promoter-associated single-nucleotide polymorphism was investigated with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques with precise primers and the restriction endonuclease, NcoI. Results: Serum TNFα levels in patients were considerably high (p < 0.05) than controls. The genotype and allele frequencies for TNFα gene polymorphism differs significantly (p = 0.0089; p = 0.0043 respectively) between patients and controls. The TNFα-308 SNP exhibited a link with higher RM risk in heterozygous (GG vs. GA; OR: 3.086, 95% CI: 1.475-6.480; p: 0.0027), dominant (GG vs. GA + AA; OR: 2.919, 95% CI: 1.410-6.056, p: 0.0038), and allelic/codominant (G vs. A; OR: 2.449, 95% CI: 1.313-4.644, p: 0.0064) models. However, this SNP showed an insignificant association with higher and lower RM risk in homozygous (GG vs. AA; OR: 1.915, 95% CI: 0.3804-10.99, p: 0.6560) and recessive (AA vs. GA + GG; OR: 0.6596, 95% CI: 0.1152-3.297, p: >0.9999) models, respectively. Further, the TNFα-308G/A genotype frequencies were in concord with HWE both in the controls (χ2 = 3.235; p = 0.1985) and the patients (χ2 = 0.0117; p = 0.9942). Conclusion: The serum TNFα levels were significantly higher in the patients than the controls. The genotyping analysis also demonstrated that TNFα-308G/A SNP significantly increases the overall risk of RM, suggesting that the SNP modulates the TNFα gene expression and thereby increases serum TNFα levels that adversely affect the pregnancy outcome.

TGF-ß signaling pathway: Therapeutic targeting and potential for anti-cancer immunity.

Transforming growth factor-ß (TGFß) is a pleiotropic secretory cytokine exhibiting both cancer-inhibitory and promoting properties. It transmits its signals via Suppressor of Mother against Decapentaplegic (SMAD) and non-SMAD pathways and regulates cell proliferation, differentiation, invasion, migration, and apoptosis. In non-cancer and early-stage cancer cells, TGFß signaling suppresses cancer progression via inducing apoptosis, cell cycle arrest, or anti-proliferation, and promoting cell differentiation. On the other hand, TGFß may also act as an oncogene in advanced stages of tumors, wherein it develops immune-suppressive tumor microenvironments and induces the proliferation of cancer cells, invasion, angiogenesis, tumorigenesis, and metastasis. Higher TGFß expression leads to the instigation and development of cancer. Therefore, suppressing TGFß signals may present a potential treatment option for inhibiting tumorigenesis and metastasis. Different inhibitory molecules, including ligand traps, anti-sense oligo-nucleotides, small molecule receptor-kinase inhibitors, small molecule inhibitors, and vaccines, have been developed and clinically trialed for blocking the TGFß signaling pathway. These molecules are not pro-oncogenic response-specific but block all signaling effects induced by TGFß. Nonetheless, targeting the activation of TGFß signaling with maximized specificity and minimized toxicity can enhance the efficacy of therapeutic approaches against this signaling pathway. The molecules that are used to target TGFß are non-cytotoxic to cancer cells but designed to curtail the over-activation of invasion and metastasis driving TGFß signaling in stromal and cancer cells. Here, we discussed the critical role of TGFß in tumorigenesis, and metastasis, as well as the outcome and the promising achievement of TGFß inhibitory molecules in the treatment of cancer.

Mitochondrial uncoupling protein 2 (UCP2) gene polymorphism - 866 G/A in the promoter region is associated with type 2 diabetes mellitus among Kashmiri population of Northern India.

OBJECTIVE: The study aimed to evaluate the association of UCP2 gene polymorphism - 866 G/A and its expression with diabetes predisposition in the North Indian population. METHODS: The study involved 850 subjects, including 425 each T2DM and control subjects. The serum metabolic and clinical parameters were estimated using standard protocols. The PCR-RFLP based genotyping was performed to determine UCP2 gene polymorphism, while the expression was measured by real-time quantitative PCR. RESULTS: The genotypic and allelic frequencies showed a significant difference in cases compared to controls (p < 0.05). The diabetes patients had a 4.2-fold decrease in UCP2 gene expression. The expression was 29.8 and 8.4 fold lower in diabetes patients with homozygous (AA) and heterozygous (GA) mutation at - 866 locus of UCP2 nucleotide sequence, respectively. When categorized according to age and BMI, the T2DM subjects with age ≥ 50 and BMI ≥ 25 had a 5.53 and 8.2-fold decrease in UCP2 expression, respectively. The diabetes subjects with homozygous and heterozygous mutation demonstrated a pathological increase in serum metabolic and clinical parameters, which corroborated with UCP2 gene expression, indicating a strong association between the two. Intriguingly, we did not find any association between - 866 G/A polymorphism of UCP2 with serum insulin levels. CONCLUSION: Our investigation is the first among the studies conducted in Jammu and Kashmir to work on adipose tissue and UCP2 gene polymorphism. The association of - 866 G/A SNP of the UCP2 gene with its expression in diabetes patients appears to be an important genetic determinant in the progression of T2DM. Moreover, age ≥ 50 years and BMI ≥ 25 could be considered risk factors for developing T2DM in the studied population.

Immunogenetic Role of IL17A Polymorphism in the Pathogenesis of Recurrent Miscarriage.

Interleukin-17A (IL17A) is a proinflammatory cytokine and is assumed to play an important role in fetal rejection. In order to evaluate the potential role of IL17A polymorphism in the pathogenesis of recurrent miscarriage (RM), serum IL17A levels were estimated by ELISA. Single-nucleotide polymorphism was assessed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using gene-specific primers and the EcoNI restriction enzyme. Serum IL17A levels were nonsignificantly (p > 0.5) low in RM patients compared with the control group. IL17A gene amplification by PCR yielded the undigested product of 815 bp, and its digestion with EcoNI enzyme produced 815, 529, 286, and 270 bp fragments for the GG genotype; 529, 286, and 270 bp fragments for the GA genotype; and 529 and 286 bp fragments for the AA genotype. The genotype frequency between the RM and control groups exhibited a significant difference (p = 0.001), whereas no significant difference was observed between allele frequencies in the two groups (p = 0.0954). These data suggest that the IL17A gene polymorphism exhibits no significant effect on IL17A gene expression. However, it significantly decreases and increases RM risk in the homozygous and recessive models, suggesting its potential pregnancy-protecting and -harming roles in the AA and GA + GG genotypes, respectively.

Inter-relationship of Pro- and Anti- inflammatory Biomarkers with the development of Type 2 Diabetes Mellitus.

Purpose: There has been growing evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) in the etiopathogenesis of T2DM. Basic procedures: A total of 480 T2DM cases and 540 healthy controls were recruited for the study. Blood samples were collected from each study subject to measure the serum levels of CRP, TNFα, IL-6 and IL-10. Main findings: We found that serum levels of CRP in mg/dl (4.2 ± 0.9), TNFα in pg/ml (34.5 ± 8.8), IL-6 in pg/ml (19.2 ± 7.2) in T2DM patients were significantly high as compared to control participants (CRP; 1.4 ± 0.6, TNFα; 12.7 ± 3.4, IL-6; 3.1 ± 1.4; P < 0.0001). The serum levels of IL-10 in pg/ml were lower in T2DM cases compared to controls (4.35 ± 1.2 vs. 9.6 ± 1.2). In addition, we observed a significant association of CRP levels with insulin resistance, obesity and dyslipidemia. Increased TNFα levels were strongly associated with female gender, Poor glycemic control and strong family history of diabetes. Poor glycemic control was significantly associated with elevated IL-6 levels. Moreover, significantly reduced IL-10 levels were found in T2DM patients with sedentary lifestyle; low educational and rural background. Conclusions: This study showed a strong relationship between TNFα, IL-6, CRP, IL-10 and T2DM patients of Kashmiri ethnicity, treated at SMHS Hospital. Thus, supporting other studies and showing that cytokines may be good markers for T2DM development.

Seroprevalence of SARS-CoV-2-specific anti-spike IgM, IgG, and anti-nucleocapsid IgG antibodies during the second wave of the pandemic: A population-based cross-sectional survey across Kashmir, India.

Background: Within Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley. Methods: We conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used. Findings: The data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51-85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45-59 years (odds ratio of 0.73; 95% CI 0.67-0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33-1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79-0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32-1.57) for age more than 60 years, 1.21 (95% CI 1.15-1.27) for the female gender, 0.87 (95% CI 0.82-0.92) for urban residents, 0.86 (95% CI 0.76-0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08-1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034-0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies. Interpretation: During the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51-85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.

MiRNAs in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Potential.

Lung cancer is the dominant emerging factor in cancer-related mortality around the globe. Therapeutic interventions for lung cancer are not up to par, mainly due to reoccurrence/relapse, chemoresistance, and late diagnosis. People are currently interested in miRNAs, which are small double-stranded (20-24 ribonucleotides) structures that regulate molecular targets (tumor suppressors, oncogenes) involved in tumorigeneses such as cell proliferation, apoptosis, metastasis, and angiogenesis via post-transcriptional regulation of mRNA. Many studies suggest the emerging role of miRNAs in lung cancer diagnostics, prognostics, and therapeutics. Therefore, it is necessary to intensely explore the miRNOME expression of lung tumors and the development of anti-cancer strategies. The current review focuses on the therapeutic, diagnostic, and prognostic potential of numerous miRNAs in lung cancer.

Clinical variables accompanying salt-sensitive essential hypertension in ethnic Kashmiri population.

BACKGROUND: Salt sensitivity is actually a measure of an individual's blood pressure response to salt intake. It has been reported that people who are salt sensitive have high prevalence of hypertension and target organ damage. The link between dietary salt intake and hypertension is well established, and a reduction in salt intake has been shown to lower blood pressure. SCOPE: In Kashmir, this achieves significance because of a high incidence of hypertension along with a high salt intake among ethnic Kashmiris. DESIGN AND METHODS: We analysed clinical variables accompanying salt sensitive hypertension among Kashmiri population in our on-going salt sensitivity study on 770 Kashmiri patients (250 men, 520 women) of age group 18years and above from March 2020 to June 2021. We studied the clinical variables accompanying salt sensitivity and the difference in their blood pressure on. a low salt diet (mean = 2 g/day) vs. their usual salt intake (mean = 11 g/day). To document compliance of salt-restricted diet, we used 24-h urinary NaCl estimation as a surrogate marker for salt intake estimation. RESULTS: We observed, a huge drop in SBP (-28.9 mmHg), DBP (-17.6 mmHg) and mean arterial pressure (-21.3mmHg) in this cohort of 770 ethnic Kashmiris on a strict salt restricted diet. And that women, urban inhabitants, and nonsmokers are more prone to the risk of developing salt sensitive hypertension. Physical activity had no effect on salt sensitivity. CONCLUSION: As per our study, salt restriction has a major role in treatment of Hypertension in Kashmiri Population. More studies need to be focused on this vital area.

Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer.

AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of ARID1A and elevated mRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.

The burden of SARS-CoV-2 among healthcare workers across 16 hospitals of Kashmir, India-A seroepidemiological study.

SARS-CoV-2 pandemic has greatly affected healthcare workers because of the high risk of getting infected. The present cross-sectional study measured SARS-CoV-2 antibody in healthcare workers of Kashmir, India. METHODS: Serological testing to detect antibodies against nucleocapsid protein of SARS-CoV-2 was performed in 2003 healthcare workers who voluntarily participated in the study. RESULTS: We report relatively high seropositivity of 26.8% (95% CI 24.8-28.8) for SARS-CoV-2in healthcare workers, nine months after the first case was detected in Kashmir. Most of the healthcare workers (71.7%) attributed infection to the workplace environment. Among healthcare workers who neither reported any prior symptom nor were they ever tested for infection by nasopharyngeal swab test, 25.5% were seropositive. CONCLUSION: We advocate interval testing by nasopharyngeal swab test of all healthcare workers regardless of symptoms to limit the transmission of infection within healthcare settings.

Seroprevalence of SARS-CoV-2-specific IgG antibodies in Kashmir, India, 7 months after the first reported local COVID-19 case: results of a population-based seroprevalence survey from October to November 2020.

OBJECTIVES: We designed a population-based survey in Kashmir to estimate the seroprevalence of SARS-CoV-2-specific IgG antibodies in the general population aged 18 years and above. SETTING: The survey was conducted among 110 villages and urban wards across 10 districts in Kashmir from 17 October 2020 to 4 November 2020. PARTICIPANTS: Individuals aged 18 years and above were eligible to be included in the survey. Serum samples were tested for the presence of SARS-CoV-2-specific IgG antibodies using the Abbott SARS-CoV-2 IgG assay. PRIMARY AND SECONDARY OUTCOME MEASURES: We labelled assay results equal to or above the cut-off index value of 1.4 as positive for SARS-CoV-2-specific IgG antibodies. Seroprevalence estimates were adjusted for the sampling design and assay characteristics. RESULTS: Out of 6397 eligible individuals enumerated, 6315 (98.7%) agreed to participate. The final analysis was done on 6230 participants. Seroprevalence adjusted for the sampling design and assay characteristics was 36.7% (95% CI 34.3% to 39.2%). Seroprevalence was higher among the older population. Among seropositive individuals, 10.2% (247/2415) reported a history of COVID-19-like symptoms. Out of 474 symptomatic individuals, 233 (49.2%) reported having been tested. We estimated an infection fatality rate of 0.034%. CONCLUSIONS: During the first 7 months of the COVID-19 epidemic in Kashmir Valley, approximately 37% of individuals were infected. The reported number of COVID-19 cases was only a small fraction of the estimated number of infections. A more efficient surveillance system with strengthened reporting of COVID-19 cases and deaths is warranted.

Metastatic Breast Cancer, Organotropism and Therapeutics: A Review.

The final stage of breast cancer involves spreading breast cancer cells to the vital organs like the brain, liver lungs and bones in the process called metastasis. Once the target organ is overtaken by the metastatic breast cancer cells, its usual function is compromised causing organ dysfunction and death. Despite the significant research on breast cancer metastasis, it's still the main culprit of breast cancer-related deaths. Exploring the complex molecular pathways associated with the initiation and progression of breast cancer metastasis could lead to the discovery of more effective ways of treating the devastating phenomenon. The present review article highlights the recent advances to understand the complexity associated with breast cancer metastases, organotropism and therapeutic advances.

Analysis of Intrinsic and Extrinsic Coagulation Pathway Factors in OCP Treated PCOS Women.

Human polycystic ovary syndrome (PCOS)-a cluster of diseases displays various symptoms associated with endocrine and gynecological disorders in childbearing women. Oral contraceptive pills (OCP) being a drug of choice minimizes symptoms and complications associated with the disorder. But, the controversial data available in literature regarding use of OCPs compels us to setup a study design regarding effect of OCP treatment in PCOS subjects and the possible outcomes specifically regarding coagulation pathways. Two PCOS study groups have been selected according to Rotterdam Criteria: one with OCP treatment (n = 50) and other without any drug treatment i.e., drug naive (n = 50). Anthropometry, Biochemistry, Hormones, Insulin and various clotting factors like Factor XI, Factor V, tPA, TAT-III and D-dimer were analyzed in both groups. The results showed worsening of IR, Metabolic parameters and coagulopathy in OCP group comparative to drug naive group indicating adverse effects of the OCP treatment which puts these women at risk for number of future clinical implications especially Cardiovascular and metabolic complications.

Immunomodulation: An immune regulatory mechanism in carcinoma therapeutics.

Cancer has been generally related to the possession of numerous mutations which interrupt important signaling pathways. Nevertheless, deregulated immunological signaling is considered as one of the key factors associated with the development and progression of cancer. The signaling pathways operate as modular network with different components interacting in a switch-like fashion with two proteins interplaying between each other leading to direct or indirect inhibition or stimulation of down-stream factors. Genetic, epigenetic, and transcriptomic alterations maintain the pathological conduit of different signaling pathways via affecting diverse mechanisms including cell destiny. At present, immunotherapy is one of the best therapies opted for cancer treatment. The cancer immunotherapy strategy includes harnessing the specificity and killing mechanisms of the immunological system to target and eradicate malignant cells. Targeted therapies utilizing several little molecules including Galunisertib, Astragaloside-IV, Melatonin, and Jervine capable of regulating key signaling pathways can effectively help in the management of different carcinomas.

Association between T2DM and the lowering of testosterone levels among Kashmiri males.

OBJECTIVE: The objective of this study is to study association between testosterone and diabetes in Kashmiri males. METHODS: A total of 300 males with Type 2 diabetes visited an outpatient and inpatient clinic at Shri Maharaja Hari Singh (SMHS) hospital, Srinagar, J&K India. The blood sugar and HbA1c, which are the markers of diabetes, and sérum testosterone levels were measured. The blood samples from both the cases and controls were collected. RESULTS: Out of 300 subjects, 42% had a testosterone deficiency. A relationship between type 2 diabetic males and healthy males was observed, and testosterone levels were determined to be significantly lower among diabetic males (p < 0.001) when compared to healthy males. Then, we compared diabetic markers among testosterone deficient and normal testosterone level groups; the mean fasting plasma glucose (p = 0.0019) and glycated haemoglobin (HbA1c; p = 0.0449) levels were significantly higher in the testosterone deficient group than in the control group. To elucidate the relationship between the serum total testosterone level and fasting plasma glucose and HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r = -0.252, p = 0.001) and HbA1c values (r = -0.697, p = 0.001) showed a significant negative correlation with serum testosterone levels among diabetic males. CONCLUSION: This study shows that diabetes causes low testosterone levels among males, and lower testosterone levels can act as a marker for diabetes. Thus, with timely intervention, mortality and co-morbidity associated with diabetes can be prevented.