Institute of Chartered Accountants of Nigeria

About: Institute of Chartered Accountants of Nigeria is a based out in . It is known for research contribution in the topics: Population & Adipose tissue. The organization has 528 authors who have published 579 publications receiving 18688 citations.

Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

Abstract: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.20, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004). In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234

Inter-Regulation of Kv4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies.

Abstract: Background: Genetic variants in voltage-gated sodium channels (Nav) encoded by SCNXA genes, responsible for INa, and Kv4.3 channels encoded by KCND3, responsible for the transient outward current (Ito), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that Kv4.3 and Nav variants regulate each other’s function, thus modulating INa/Ito balance in cardiomyocytes and INa/I(A) balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Nav1.5 and Kv4.3 channels in HEK293 cells. INa and Ito were recorded. Results: SCN5A variants associated with BrS reduced INa, but increased Ito. Moreover, BrS and SCA19/22 KCND3 variants associated with a gain of function of Ito, significantly reduced INa, whereas the SCA19/22 KCND3 variants associated with a loss of function (LOF) of Ito significantly increased INa. Auxiliary subunits Navβ1, MiRP3 and KChIP2 also modulated INa/Ito balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF SCN5A variants can increase Kv4.3 cell-surface expression. Conclusion: Nav and Kv4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.

Le tissu adipeux - Un nouveau terrain de jeu pour les cellules immunitaires

Abstract: L’existence d’un etat inflammatoire chronique de bas niveau dans l’obesite pouvant intervenir dans la physiopathologie de la maladie et de ses nombreuses complications est bien etablie. Le tissu adipeux lui-meme est un site d’inflammation ou s’accumulent des macrophages. Dans cette synthese, nous decrivons les donnees experimentales et cliniques qui ont permis d’elucider certains des mecanismes cellulaires et moleculaires impliques dans la colonisation du tissu adipeux par les macrophages obtenus a partir de precurseurs monocytaires. Les macrophages sont des cellules dont le phenotype varie suivant l’etat du microenvironnement. Dans l’obesite, ils peuvent exercer des effets deleteres via la production de molecules pro-inflammatoires, mais contribuent egalement a l’homeostasie du tissu adipeux face aux changements de la masse grasse. Une autre consequence de l’inflammation du tissu adipeux est la presence d’une fibrose dont la genese et les consequences sont encore mal connues. L’identification de mecanismes potentiellement protecteurs, tels que la neutralisation immunologique de certains types de lymphocytes ou encore le controle transcriptionnel des genes de l’inflammation, pourrait suggerer de nouvelles perspectives therapeutiques pour limiter l’inflammation dans le tissu adipeux.

Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen

Abstract: Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD (BMP7) or renal biology (COLEC11 and DDR1). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.

The fused lasso penalty for learning interpretable medical scoring systems

Abstract: Score learning aims at taking advantage of supervised learning to estimate interpretable models which facilitate decision making. Ideally, a scoring system is based on simple arithmetic operations, is sparse, and can be easily explained by human experts. In this contribution, we introduce an original methodology to simultaneously learn interpretable binning mapped to a class variable, and the weights associated with these bins contributing to the score. We show by numerical experiments on benchmark data sets that our approach is competitive compared to the state-of-the-art methods. We illustrate by a real medical problem of type 2 diabetes remission prediction that a scoring system learned automatically is comparable to one manually constructed by clinicians.