Exploring the potential of late permian aggregate resources for utilization in engineering structures through geotechnical, geochemical and petrographic analyses.

The China-Pakistan Economic Corridor (CPEC) is an ongoing mega-construction project in Pakistan that necessitates further exploration of new natural resources of aggregate to facilitate the extensive construction. Therefore, the Late Permian strata of Chhidru and Wargal Limestone for aggregates resources were envisaged to evaluate their optimal way of construction usage through detailed geotechnical, geochemical, and petrographic analyses. Geotechnical analysis was performed under BS and ASTM standards with the help of employing different laboratory tests. A simple regression analysis was employed to ascertain mutual correlations between physical parameters. Based on the petrographic analysis, the Wargal Limestone is classified into mudstones and wackestone, and Chhidru Formation is categorized into wackestone and floatstone microfacies, both containing primary constituents of calcite and bioclasts. The geochemical analysis revealed that the Wargal Limestone and Chhidru Formation encompass calcium oxide (CaO) as the dominant mineral content. These analyses also depicted that the Wargal Limestone aggregates bear no vulnerability to alkali-aggregate reactions (AAR), whereas the Chhidru Formation tends to be susceptible to AAR and deleterious. Moreover, the coefficient of determination and strength characteristics, for instance, unconfined compressive strength and point load test were found inversely associated with bioclast concentrations and directly linked to calcite contents. Based on the geotechnical, petrographic, and geochemical analyses, the Wargal Limestone proved to be a significant potential source for both small and large-scale construction projects, such as CPEC, but the Chhidru Formation aggregates should be used with extra caution due to high silica content.

Therapeutic spectrum of piperine for clinical practice: a scoping review.

Translation of traditional knowledge of herbs into a viable product for clinical use is still an uphill task. Piperine, a pungent alkaloid molecule derived from Piper nigrum and Piper longum possesses diverse pharmacological effects. Traditionally, pepper is used for arthritis, bronchitis, gastritis, diarrhea, snake bite, menstrual pain, fever, and bacterial infections, etc. The anti-inflammatory, antioxidant and immunomodulatory actions of piperine are the possible mechanisms behind its therapeutic potential. Various in-silico and experimental studies have shown piperine as a possible promising molecule in coronavirus disease (COVID-19), ebola, and dengue due to its immunomodulatory and antiviral activities. The other important clinical applications of piperine are due to its bio enhancing effect on drugs, by modulating, absorption in the gastrointestinal tract, altering activities of transporters like p-glycoprotein substrates, and modulating drug metabolism by altering the expression of cytochrome P450 or UDP-glucuronosyltransferase enzymes. Piperine attracted clinicians in treating patients with arthritis, metabolic syndrome, diabetes, skin infections, gastric and liver disorders. This review focused on systematic, evidence-based insight into the use of piperine in clinical settings and mechanistic details behind its therapeutic actions. Also, highlights a number of clinical trials of piperine at various stages exploring its clinical application in cancer, neurological, respiratory, and viral disease, etc.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer, and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69-1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

No Association Between a Genetic Variant of FOXO3 and Risk of Type 2 Diabetes Mellitus in the Elderly Population of North India.

Aging can be considered an evolutionary process that is modulated by various genetic and biochemical processes. Therefore the genetic variants may interplay a role in human longevity as well as age related illness. Forkhead Box O (FOXO) gene is one of the major defensive genes that are known for ameliorating lifespan. FOXO proteins act as nuclear transcription factors that facilitate the action of insulin or insulin-like growth factor (IGF-1) in various physiological processes. The rationale of our study is to find out association between genetic variant rs2253310 of FOXO3 and risk of Type 2 Diabetes Mellitus (T2DM) in elderly population. This case control study involved 172 age sex matched elderly subjects while patients were recruited as per IDF criteria. Clinical, biochemical, ELISA methods were employed for assesement of clinical samples while Taqman method was used for genotyping analysis. Our results revealed that there was no significant difference in genotypic and allelic frequencies for the tested SNP (p > 0.05) between elderly T2DM patients and controls. The SNP rs2253310 was not associated with risk of T2DM in any genetic model. Also no association was found among the studied group between FOXO3 variant and HOMA-IR, HOMA-B index and Fasting plasma glucose. Serum level of inflammatory markers like CRP and TNF-α was significantly higher in patients but its not associated with SNP rs2253310. Our study concluded that, this intronic longevity-associated variant rs2253310 in FOXO3 is not associated with type 2 diabetes in geriatric patients of northern India.

Assessment of drug prescribing pattern using world health organization indicators in a tertiary care teaching hospital.

This cross-sectional study was carried out to assess drug prescribing pattern at a tertiary care teaching medical institute. One thousand prescriptions were randomly collected and analyzed using the world health organization prescribing indicators. The average number of drugs per prescription was 2.91. The percentage of drugs prescribed by generic name, from the essential drug list (National) and as fixed dose combinations (FDCs) was 10.05%, 22.57%, and 49.22%, respectively. The total percentage of encounters with antibiotics, injectables, and FDCs was 19.70%, 2.20%, and 73.60%, respectively. The most common group of drug prescribed was gastrointestinal tract drugs (26.38%) followed by Vitamins and Minerals (23.12%), cardiovascular system drugs (11.56%) and antimicrobials (9.63%). The prescribing practices were not appropriate as they consist of polypharmacy, lesser prescription by generic name, and overprescription of FDCs. There is a need for improvement in the standards of prescribing patterns in many aspects.