On the size of apical foramen in anterior teeth, bicuspids and molars

The present authors have used a replica method to obtain area size measurements for the apical foramen in 4,613 human permanent teeth, and have obtained the following results:1. The morphology of the apical foramen is rich in variety which make it difficult to express its accurate size using foramen diameter measurement. It is therefore more appropriate to determine its size as an area measurement.2. Much variation was observed in the size of the apical foramen even for teeth of the same type. It was, however, also observed that the foramen is smaller in smaller types of teeth and larger in larger types of teeth. It was also observed that, in teeth of the same type, those with a greater number of roots have smaller foramen than those with a smaller number of roots.Les auteurs ont utilisé la méthode des répliques pour mesurer la surface des foramen apicaux de 4.613 dents humaines définitives. Les résultats obtenus ont été les suivants:1. La morphologie du foramen apical est à ce point variée qu’il est difficile d’exprimer sa taille précise en mesurant le diamètre du foramen. De ce fait il est préférable de déterminer sa dimension par une mesure de surface.2. Un grand nombre de variations ont même été observées dans la dimension du foramen apical pour les dents du même type. Cependant, il a été aussi observé que le foramen est plus petit dans les dents de type petit et plus larges dans les dents de grand type. Il a été constaté également que dans les dents de même type, celles comptant un plus grand nombre de racines possèdent des foramen plus petits que ceux des dents dont les racines sont moins nombreuses

Pits and fissures: etch resistance in prismless enamel walls

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: In a previous study to examine the nature of etching on the walls of fissures, there was a consistent result of resistance to deep etching on parts of the walls and a zone of lesser etching on part of the walls as evidenced by the uptake of stain. The staining had been used to examine the nature of the etch pattern. The aims of this study were to define the nature of this etch resistant area. Methods: A sample of 55 teeth, both molars and premolars, were divided into three groups. In the first group the wetting of fissures by the etchant was examined; the second group tested for the effects of pellicle-cuticle-debris or air entrapment on the etching process. The final group looked at alternative mechanical treatments of the fissure prior to etching. Results: The specimens split along the fissures showed clearly that the etch resistant zone was not due to lack of contact with the etchant or the presence of a pellicle-cuticle-debris covering, but to the presence of a prismless enamel structure. This study showed that this zone inhibited tag development on the fissure walls. Conclusions: The mechanical removal of this prismless layer of enamel within the fissure system should result in an improved bonding of a fissure sealant through better tag development, in turn leading to a reduction in the failure rate of a sealant used to prevent caries.MF Burrow, JF Burrow and OF Makinso

Decrease of miR-146b-5p in Monocytes during Obesity Is Associated with Loss of the Anti-Inflammatory but Not Insulin Signaling Action of Adiponectin

Background: Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK)/NFkB pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR)-146b-5p inhibits NFkB-mediated inflammation by targeted repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6). Therefore, we measured the expression of miR-146b-5p in monocytes of obese subjects. Because it was low we determined the involvement of this miR in the anti-inflammatory, antioxidative and insulin signaling action of globular adiponectin. Methods: miR-146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative stress and insulin signaling and the association with globular adiponectin was assessed in human THP-1 monocytes. Results: miR-146b-5p was downregulated in monocytes of obese persons. Low globular adiponectin decreased miR-146b-5p and IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen species (ROS). Intracellular ROS and insulin receptor substrate-1 (IRS1) protein were unchanged. Silencing of miR-146b-5p with an antisense inhibitor resulted in increased expression of IRAK1 and TRAF6 leading to more NFkB p65 DNA binding activity and TNFa. As

Exendin-4 Improves Steatohepatitis by Increasing Sirt1 Expression in High-Fat Diet-Induced Obese C57BL/6J Mice

The effects of exendin-4 on Sirt1 expression as a mechanism of reducing fatty liver have not been previously reported. Therefore, we investigated whether the beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1 in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture models. Exendin-4 treatment decreased body weight, serum free fatty acid (FA), and triglyceride levels in HF-induced obese C57BL/6J mice. Histological analysis showed that exendin-4 reversed HF-induced hepatic accumulation of lipids and inflammation. Exendin-4 treatment increased mRNA and protein expression of Sirt1 and its downstream factor, AMPK, in vivo and also induced genes associated with FA oxidation and glucose metabolism. In addition, a significant increase in the hepatic expression of Lkb1 and Nampt mRNA was observed in exendin-4-treated groups. We also observed increased expression of phospho-Foxo1 and GLUT2, which are involved in hepatic glucose metabolism. In HepG2 and Huh7 cells, mRNA and protein expressions of GLP-1R were increased by exendin-4 treatment in a dose-dependent manner. Exendin-4 enhanced protein expression of Sirt1 and phospho-AMPKα in HepG2 cells treated with 0.4 mM palmitic acid. We also found that Sirt1 was an upstream regulator of AMPK in hepatocytes. A novel finding of this study was the observation that expression of GLP-1R is proportional to exendin-4 concentration and exendin-4 could attenuate fatty liver through activation of Sirt1

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

2020_Nov_ASIrs2_WB

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2020_Nov_ASIrs2_WB

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2021_Aug An Antisense Transcript Transcribed from Irs2 Locus Contributes to the Pathogenesis of Hepatic Steatosis in Insulin Resistance

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2021_Aug An Antisense Transcript Transcribed from Irs2 Locus Contributes to the Pathogenesis of Hepatic Steatosis in Insulin Resistance

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