Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes

<p>Abstract</p> <p>Background</p> <p>To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set).</p> <p>Methods</p> <p>Type 2 diabetes subjects with CRI (serum creatinine ≥3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of ≥ 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely- <it>ADPRT1</it>, <it>AKR1B1, RAGE, GFPT2 </it>and <it>PAI-1 </it>with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes.</p> <p>Results</p> <p>Single nucleotide polymorphisms -429 T>C in <it>RAGE </it>and rs7725 C>T SNP in 3' UTR in <it>GFPT2 </it>gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in <it>GFPT2 </it>was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor <it>TGF-β1 </it>(investigated using the same sample set and reported elsewhere) and <it>GFPT2 </it>genotype was observed.</p> <p>Conclusions</p> <p>Association of SNPs in <it>RAGE </it>and <it>GFPT2 </it>suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-β1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-β1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in <it>GFPT2 </it>implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests <it>GFPT2 </it>could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations.</p

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

http://deepblue.lib.umich.edu/bitstream/2027.42/51490/1/Virtanen JK, Serum Homocysteine, Folate and Risk of Stroke, 2005.pd

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.Peer reviewe

Rigorous science – Artistic freedom. The challenge of thesis supervision in an art university

No Abstract. South African Journal of Higher Education Vol. 21 (8) 2007: pp. 1091-110

Emerging adulthood in the time of pandemic:the COVID-19 crisis in the lives of rural young adults in Finland

Abstract This article discusses changes introduced into the everyday life and lifecourse dispositions of young adults in two sparsely populated regions in Finland during the COVID-19 lockdown period of spring 2020. By the age of 20, many of them had already spent some years living independently during their school years. Due to the pandemic, many had to move back to their rural home regions. This article shows that the sudden advent of the pandemic as a global risk and the restriction measures that followed affected these young, emerging adults in many ways, even though there were no infections in their immediate environments. Special attention is paid to their relationships with their remote home regions, which suddenly gained new, positive meanings in comparison to the global and national COVID-19 hotspots. The analysis is based on interviews conducted with 30 young adults in May 2020 and pre-existing longitudinal data from the same participants

Behavioral deficits and recovery following transient focal cerebral ischemia in rats : glutamatergic and GABAergic receptor densities

The neurobiologic mechanisms underlying the recovery process following stroke are poorly understood. The present study investigated glutamatergic and gamma-amino butyric acid (GABA)-ergic receptor densities following experimental stroke in rats exposed to different environmental housing or pharmacologic interventions. About 2 days after transient (120 min) middle cerebral artery (MCA) occlusion, the rats were singly housed in standard cages or were moved to an enriched environment and treated for 10 days with either 0.9% NaCl or with the alpha(2)-adrenoceptor antagonist, atipamezole (1.0 mg/kg, s.c.). The limb-placing, foot-slip, and watermaze tests were used to assess behavioral deficits and recovery following ischemia. The rats were decapitated on day 25 after the operation and their brains were processed for [H-3]MK-801, [H-3]D,L,-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), [H-3]kainate, and [H-3]muscimol autoradiography. Receptor binding site densities were different between sham-operated rats and ischemic rats only in the lesion core and lateral ventroposterior thalamic nucleus. Ischemic rats housed in an enriched environment and treated with atipamezole had better performance in the limb-placing test. The deficit in the water-maze test was most pronounced in ischemic rats housed in standard cages. There were a number of correlations between the behavioral data and receptor binding densities in ischemic rats. For example, recovery in the limb-placing test correlated with [H-3]AMPA receptor binding sites in the contralateral frontal cortex (r = 0.616, P < 0.05), hindlimb cortex (r = 0.649, P < 0.05), and parietal cortex (r = 0.674, P < 0.05) in ischemic rats housed in an enriched environment. There were similar correlations between limb-placing recovery and [H-3]kainate binding sites in the contralateral cortices in ischemic rats housed in standard cages. In addition, there were particularly strong clustered correlations between swimming speed in the water-maze test and [H-3]AMPA receptor binding sites in the hippocampal subregions in the ischemic rats housed in an enriched environment. The present results suggest that transient focal cerebral ischemia does not induce significant long-term changes in glutamatergic and GABAergic receptors in areas remote from the infarct area. The correlational data, however, suggest an important role for the contralateral cortex in the behavioral outcome and maintenance of the recovered state of ischemic rats, depending on housing conditions. In addition, attenuation of spatial learning deficits observed in ischemic rats housed in an enriched environment might be due to an increase in the swimming speed through hippocampal AMPA receptor-mediated mechanisms. (C) 2002 Elsevier Science B.V. All rights reserved