Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes

Background and aimsIncreased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2^EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.Methods and resultsMales with recent-onset type 2 diabetes with (TM6SF2^EK: n = 16) or without (TM6SF2^EE: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-²H₂]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with ¹H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2^EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2^EE. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2^EE only.ConclusionsThe TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.     

Use of calcium-containing bioactive desensitizers in dental bleaching: A systematic review and meta-analysis

BackgroundTopical application of calcium-containing bioactive desensitizers (CBs) has been used to minimize bleaching-induced tooth sensitivity (TS). This study answered the research question “Is the risk of TS lower when CBs are used with dental bleaching in adults compared with bleaching without desensitizers?”Types of Studies ReviewedThe authors included randomized clinical trials comparing topical CB application with a placebo or no intervention during bleaching. Searches for eligible articles were performed in MEDLINE via PubMed, Cochrane Library, Brazilian Library in Dentistry, Latin American and Caribbean Health Sciences Literature, Scopus, Web of Science, Embase, and gray literature without language and date restrictions and updated in September 2022. The risk of bias was evaluated using Risk of Bias Version 2.0. The authors conducted meta-analyses with the random-effects model. The authors assessed heterogeneity with the Cochrane Q test, I² statistics, and prediction interval. The authors used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence.ResultsAfter database screening, 22 studies remained, with most at high risk of bias. No difference in the risk of TS was detected (risk ratio, 0.95; 95% CI, 0.90 to 1.01; P = .08, low certainty). In a visual analog scale, the intensity of TS (mean difference, ?0.98; 95% CI, ?1.36 to ?0.60; P < .0001, very low certainty) was lower for the CB group. The color change was unaffected (P > .08).Practical ImplicationsAlthough topical CB dental bleaching did not reduce the risk of TS and color change, these agents slightly reduced the TS intensity, but the certainty of the evidence is very low.     

Optical properties of esthetic temporary cements and final restoration color

BackgroundOpaque cements can be esthetically unfavorable and alternative translucent materials have been developed. The aim of this study was to evaluate the color interference of a new translucent cement compared with conventional materials, in association with interim restoration with different thickness and shades.MethodsBis-acryl composite disks were prepared in 2 thicknesses (1.2 mm, 0.6 mm) and 3 shades (A3.5, A2, bleached) to simulate the restorations. Cementation over dentin disks was performed with 1 translucent cement (Provicol QM Aesthetic; VOCO), 2 conventional cements (Provicol; VOCO, Temp-Bond NE; Kerr Dental), and 1 transparent liquid (polyethylene glycol 400). The difference between the color of the specimens cemented with the transparent liquid and that of the specimens cemented with each cement was calculated (ΔEab). The data were analyzed using 3-way analysis of variance and Tukey tests (5%).ResultsSignificant differences were observed for all factors and some interactions (P < .05). For Provicol QM Aesthetic, the shade and thickness did not influence the ΔEab. For Provicol and Temp-Bond NE, the lighter and thinner the specimen, the higher the ΔEab. Only Provicol QM Aesthetic had smaller means than the perceptibility threshold. Temp-Bond NE and Provicol had higher values than the acceptability threshold for some combinations.ConclusionsThe highly translucent cement had less color interference than the conventional materials. The thickness and resin shade only affected the results for the opaque cements. The thinner specimens and the lighter shades had higher color interference.Practical ImplicationsThe use of a more translucent cement can produce a smaller color interference on the esthetic outcome of interim restorations.     

Subendocardial and Transmural Myocardial Ischemia: Clinical Characteristics,Prevalence, and Outcomes With and Without Revascularization

BackgroundSubendocardial ischemia is commonly diagnosed but not quantified by imaging.ObjectivesThis study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.MethodsRegional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.ResultsOf 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90).ConclusionsReduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.