Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P < 0.05; OR 3.2; 95 % CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ 2 = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

Calcitriol-mediated Reversible Hypercalcemia in a Patient with Primary Adrenal Lymphoma.

Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin's lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect.

Role of strengthening exercises in management and prevention of overuse sports injuries of lower extremity: a systematic review.

INTRODUCTION: Overuse injuries are common in sports involving jumping, running, and landing, due to the repetitive nature of these activities and the strain they place on the lower extremity. The objective of the study was to determine the role of strengthening exercises in the management of overuse sports injuries of lower extremity and its effects on prevention of injury recurrence. EVIDENCE ACQUISITION: This study employed a systematic review design. The author extracted and reviewed the papers for this study in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and then used the PEDro scale to rate the articles' quality. For the most recent and well-developed primary data, several electronic databases including Google Scholar, PubMed Central, MEDLINE, Cochrane Library, and PEDro were exhaustively searched. Inclusion criteria were based on PICO (T) model and included study population, intervention nature, outcome measures, time period, methodological quality, and linguistic extent. EVIDENCE SYNTHESIS: The data synthesis involved analyzing randomized control/clinical trials on strengthening exercises for lower extremity overuse sports injuries in athletes, considering outcomes including muscle strength, pain scores, return to sports, and injury prevention. CONCLUSIONS: The methodological quality of the recruited articles ranged from excellent to fair on PEDro scale. Three included studies investigated the effects of strengthening exercises on management of lower extremity injuries of athletes. Four studies evaluated its role on prevention from recurrence of injuries. This study has concluded that strength training plays a fundamental role in management and prevention of overuse injuries. It not only improves the muscle performance, fitness level, speed and agility in sports but also decreases the pain, and aids in early recovery from an injury.

Polymeric membranes for environmental remediation: A product space model perspective.

The development of polymeric membranes from polymers such as polystyrene (PS), polyvinylchloride (PVC), and their associated family has brought great momentum to the environmental remediation universe, mainly due to their surprisingly diverse and multi-purpose nature. Their usage has surged 20 times in the last half-century and is likely to double again in the coming 20 years. As a result, the polymeric materials economy and commercialization of research become increasingly important as a possible option for a country to boost prosperity while decreasing its reliance on limited raw resources and mitigating negative externalities. This transformation demands a systematic strategy, which involves progress beyond improving the existing models and building new avenues for collaboration. In this work, a sophisticated system, i.e., product space model (PSM), has been presented, explicitly appraising the opportunity space for United Kingdom, Italy, Poland, India, Canada, Indonesia, Brazil, Saudi Arabia, Russia and Colombia for their potential future industrialization and commercialization of polymeric membranes for environmental remediation. The results revealed that UK, Italy, Poland and India are at advantageous positions owing to their close proximity of (distance<2) and their placement in Parsimonious policy, which is the most desired quadrant of Policy Map of PSM, Canada and Indonesia have medium level opportunities, while Russia and Saudi Arabia have opportunities with more challenges to fully exploit the unexploited polymers products in terms of membranes for environmental remediation and prove favorable for export diversification, sustainable economic growth, and commercialization.

Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression.

BACKGROUND: Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. METHODS: We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-ß) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). RESULTS: Individual SNP analysis showed highest association of IL-1ß rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ±â€¯1.11) in DN. TNF-α, IL-6 and IL-1ß transcript levels were significantly modulated by promoter region SNPs. CONCLUSIONS: The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1ß gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects.

Gentiana kurroo Royle attenuates the metabolic aberrations in diabetic rats; Swertiamarin, swertisin and lupeol being the possible bioactive principles.

Background Gentiana kuroo Royle is a medicinally important plant of north-western Himalayas used for various ailments. In the present study, the plant extracts were investigated for the antidiabetic effects in streptozotocin-induced diabetic rats. Methods The impact of the extracts on serum glucose levels of diabetic rats was compared with reference drug - glibenclamide-treated diabetic rats. Streptozotocin injection was used to induce diabetes in fasted rats. Various biochemical, physiological and histopathological parameters in diabetic rats were observed for assessing the antidiabetic activity. Results The serum glucose concentrations in diabetic rats were significantly lowered by the extracts (methanolic and hydroethanolic at the doses of 250 and 500 mg/kg body weight). Several related biochemical parameters like creatinine, low-density lipoproteins, triglycerides, cholesterol, alkaline phosphatase, serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase were likewise decreased by the concentrates. The extracts also showed reduction in feed and water consumption of diabetic rats when compared with the diabetic control. The extracts were found to demonstrate regenerative/protective effect on ß-cells of pancreas in diabetic rats. The methanolic and hydroethanolic extracts also exhibited hypoglycaemic effect in normal glucose-fed rats (oral glucose tolerance tests). LC-MS characterization of this extract showed the presence of these compounds - Swertiamarin, swertisin, lupeol, etc. Conclusions The current study demonstrated the counter diabetic capability of G. kuroo Royle being powerful in hyperglycaemia and can viably ensure against other metabolic deviations created by diabetes in rats. The possible bioactive principles responsible for the antidiabetic activity of G. kurroo Royle are Swertiamarin, swertisin and lupeol.

Efficacy and safety of Vitamin D supplementation during pregnancy: A randomized trial of two different levels of dosing on maternal and neonatal Vitamin D outcome.

INTRODUCTION: Pregnant women represent a typical group susceptible to dietary and mineral deficiencies. This study was sought to assess the efficacy and safety of various doses of 25-hydroxyvitamin D (25[OH]D) supplementation during pregnancy and ratify the inadequacy of the recommended daily allowance for Vitamin D in vulnerable groups. MATERIALS AND METHODS: A total of 100 pregnant women were included in this open-label, parallel group, prospective, randomized, and controlled trial. Study subjects were assigned to four treatment groups: Group 1 (n = 26), 1000 IU of Vitamin D daily; Group 2 (n = 21), 30,000 IU of Vitamin D monthly; Group 3 (n = 27), 2000 IU of Vitamin D daily; and Group 4 (n = 26), 60,000 IU Vitamin D monthly. Group 1 and 2 were further analyzed together as Group 1K (1000 IU daily and 30,000 IU monthly), and Group 3 and 4 as Group 2K (2000 IU daily and 60,000 IU monthly). The analysis was done on an intention to treat basis. RESULTS: A total of 87 patients completed the study; 21 in Group 1, 25 in Group 2, 18 in Group 3, and 23 in Group 4. The levels of 25(OH)D at baseline ranged from 1.3 to 58.0 with a mean of 24.2 ± 15.1 ng/ml. Postsupplementation, 25(OH)D levels ranged from 11.5 to 70.3 with a mean of 40.2 ± 12.2 ng/ml. The postsupplementation levels of 25(OH)D were higher in Group 2K (42.86 ± 12.83) than in Group 1K (36.96 ± 10.56) with P value of 0.023. CONCLUSION: We concluded that Vitamin D supplementation with 2000 IU/day or 60,000 IU/month is very effective and safe in achieving Vitamin D sufficiency in pregnant women.

Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition.

Diabetes mellitus is increasing at an alarming rate and has become a global challenge. Insulin resistance in target tissues and a relative deficiency of insulin secretion from pancreatic ß-cells are the major features of type 2 diabetes (T2D). Chronic low-grade inflammation in T2D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and ß-cell dysfunction. Many factors advocate a causal link between metabolic stress and inflammation. Numerous cellular factors trigger inflammatory signalling cascades, and as a result T2D is at the moment considered an inflammatory disorder triggered by disordered metabolism. Cellular mechanisms like activation of Toll-like receptors, Endoplasmic Reticulum stress, and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2D with inflammation. This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2D by capturing relevant evidence from various sources. The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic ß-cells in T2D.

CTTTA Deletion/Insertion polymorphism in 3'-UTR of LEPR gene in type 2 diabetes subjects belonging to Kashmiri population.

BACKGROUND: Type 2 diabetes mellitus is a multi-factorial disease in which both genetic and non-genetic factors interact in order to precipitate the diabetic phenotype. Among various predisposing genetic loci, a pentanucleotide (CTTTA) Del/Ins variant in the 3'-UTR of the LEPR gene is associated with type 2 diabetes and its related traits. This study was done to explicate for the first time the association of this Del/Ins polymorphism of LEPR gene in type 2 diabetes patients belonging to the ethnic population of Kashmir valley. METHODS: 670 unrelated subjects comprising of 320 type 2 diabetes patients and 350 healthy controls were included in the study. Genotyping of the untranslated region of LEPR gene encompassing this Del/Ins variant was done by PCR-RFLP technique and results were validated by direct sequencing. RESULTS: Genotype frequencies for both type 2 diabetes cases and healthy controls were consistent with Hardy-Weinberg equilibrium (χ(2) = 3.09 and 2.37, P = NS). The Del/Del genotype was predominantly found in cases than controls (P = 0.003, OR: 0.62, CI: 0.45-0.85). Carriers of Ins/Ins genotype were relatively protected against the risk factors (P = 0.0004, OR: 0.31, 95% CI: 0.15-0.61). A positive association was observed between the Del allele and the risk factors of type 2 diabetes. CONCLUSION: The results elucidate that the CTTTA Del allele is a genotypic risk factor of type 2 diabetes in the Kashmiri population.

Trp homozygotes at codon 64 of ADRB3 gene are protected against the risk of type 2 diabetes in the Kashmiri population.

The prevalence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Type 2 diabetes is a consequence of complex interactions among multiple genetic variants and environmental risk factors. Polymorphisms in various candidate genes confer susceptibility to diabetes. This study was undertaken to analyse a single nucleotide polymorphism Trp64Arg (C↔T) in the ADRB3 gene and elucidate its effects on type 2 diabetes and its associated risk factors. The study included 200 type 2 diabetes patients and 300 age and gender matched healthy controls belonging to the ethnic Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping and the results were validated by direct sequencing assay. Genotypes for Trp64Arg polymorphism were in Hardy-Weinberg equilibrium (χ(2)=0.48, p=NS). Frequency of the Arg64 allele was 40% and 10.2% in cases and controls, respectively (p<0.05; odds ratio 5.89; 95% CI; 3.69-9.39). The Arg64 allele was directly related to higher body mass index, waist-to-hip ratio, dyslipidemia and uncontrolled disease status. The study signifies that the Arg64 allele of the ADRB3 gene is a genotypic risk factor and confers susceptibility to type 2 diabetes, whereas the homozygous Trp64 genotype exerted a protective effect in our population.

WITHDRAWN: Single nucleotide polymorphisms, haplotype association and tumour expression of the vascular endothelial growth factor (VEGF) gene with lung carcinoma.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.