Emerging role of C-peptide as an early biomarker of metabolic syndrome

Background: Metabolic syndrome is a health issue of rising concern as it has a correlation with the occurrence of cardiovascular events. Early identification of this syndrome by evaluating levels of biomarkers such as C peptide can help medical professionals prevent the occurrence of life-threatening cardiovascular diseases.Methods: This cross-sectional study was carried out in 89 subjects who were diagnosed to have metabolic syndrome. General Physical examination was done and fasting C peptide and insulin levels were quantified, followed by statistical analysis and their correlation. The prevalence of defining parameters of Metabolic Syndrome as per IDF 2005 was studied.Results: Out of 89 (100%) subjects, 80 (89.8%) subjects (Mean±SD=6.14±3.47) had C- peptide level >1.89 ng/ml which was statistically highly significant (p<0.001). Also, out of 89 (100%) subjects, 67 (24.71%) subjects had insulin level <25 mIU/L which was statistically significant (p<0.001).Conclusions: It was thereby concluded that serum C peptide levels were raised in patients of Metabolic syndrome and it is superior to serum Insulin levels as an early biomarker of the same

Comparison of Surgical Outcomes of ventriculoperitoneal (VP) Shunt at Choudhary’s Point vs. Keen’s Point

Objectives:&nbsp;&nbsp;The study compared the outcomes of VP shunt at Choudhary’s vs Keen’s point. Material and Methods:&nbsp;&nbsp;A quasi-observational study was conducted on 50 patients who presented to NS-2, PINS, with the complaint of hydrocephalus. The study was conducted for 3 months from 1st November 2021 to 31th Jan 2022. Results:&nbsp;&nbsp;Mean age was 40 years. In 25 (50%) patients, VP shunts were done through Choudhary’s point while in 25 (50%) patients VP shunts were done through Keen’s point. All patients were evaluated on day 3rd POD, 7th POD, 15th POD, and 90th POD. &nbsp;All patients were improved on 3rd POD. On the 7th POD, 15 (30%) patients deteriorated and showed signs of raised ICP. In these patients, the upper end of VP shunts is again revised due to blockage. On 15th POD, the upper end of VP shunts was blocked in 3 (6%) patients and their upper end was revised. On 90th POD, 2 (4%) patients were presented with upper-end blockage, and again shunt revision was done.&nbsp; VP shunts in all these patients were done through keen’s point approach. Blockage of the lower end of VP shunt occurred in 10% of patients in which 8% were operated through Keen’s point approach while resting 2% of patients were operated through Choudhary’s point approach.&nbsp; Conclusion:&nbsp;&nbsp;VP shunts through Choudhary’s point approach yield good results as compared to Keen's point approach. This site is described by professor Muhammad Anwar Choudhary, as more convenient for insertion of VP shunt

4E analysis of a two-stage refrigeration system through surrogate models based on response surface methods and hybrid grey wolf optimizer

Refrigeration systems are complex, non-linear, multi-modal, and multi-dimensional. However, traditional methods are based on a trial and error process to optimize these systems, and a global optimum operating point cannot be guaranteed. Therefore, this work aims to study a two-stage vapor compression refrigeration system (VCRS) through a novel and robust hybrid multi-objective grey wolf optimizer (HMOGWO) algorithm. The system is modeled using response surface methods (RSM) to investigate the impacts of design variables on the set responses. Firstly, the interaction between the system components and their cycle behavior is analyzed by building four surrogate models using RSM. The model fit statistics indicate that they are statistically significant and agree with the design data. Three conflicting scenarios in bi-objective optimization are built focusing on the overall system following the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and Linear Programming Technique for Multidimensional Analysis of Preference (LINMAP) decision-making methods. The optimal solutions indicate that for the first to third scenarios, the exergetic efficiency (EE) and capital expenditure (CAPEX) are optimized by 33.4% and 7.5%, and the EE and operational expenditure (OPEX) are improved by 27.4% and 19.0%. The EE and global warming potential (GWP) are also optimized by 27.2% and 19.1%, where the proposed HMOGWO outperforms the MOGWO and NSGA-II. Finally, the K-means clustering technique is applied for Pareto characterization. Based on the research outcomes, the combined RSM and HMOGWO techniques have proved an excellent solution to simulate and optimize two-stage VCRS

De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function

De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function

Correlation of hemolysis by plasma hemoglobin with biochemical markers during storage of blood under standard conditions in the blood bank of a tertiary health-care center

Background and Objectives: Stored blood undergoes many metabolic, biochemical, and molecular changes known as storage lesions which are responsible for negative posttransfusion effects in recipients. This study aims to detect serial in vitro qualitative changes that occur during processing and blood storage including changes in plasma hemoglobin (Hb), plasma lactate dehydrogenase (LDH), and potassium levels and changes (fall) in pH of packed red blood cell at serial intervals under a standard condition of storage in the blood bank. This is a two year prospective study. Methods: Fifty donors were selected and blood units were collected and stored under blood bank conditions. Mean plasma Hb of stored blood was estimated by measuring the transmittance and absorbance of modified azide-methemoglobin and percentage hemolysis was calculated on days 0, 1, 7, 21, 28, 35, and 42 days. Similarly, plasma LDH and plasma potassium levels were also assessed during storage. Results: It was noted that free Hb level and percentage hemolysis progressively increased with storage along with the level of LDH and potassium. However, the extent of hemolysis did not exceed the permissible limit of up to 42 days of storage. Conclusion: It was concluded that quantitative estimation of Hb is superior to the visual method for the determination of hemolysis. Hemolysis can be further reduced by additive solution saline, adenine, glucose, and mannitol and using di-2-ethyl hexyl pHthalate as s plasticizer in blood bags for storage

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

BACKGROUND: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer). METHODS: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian. RESULTS: The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years. CONCLUSIONS: Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men