Computer-Aided Designing and Manufacturing of Lingual Fixed Orthodontic Appliance Using 2D/3D Registration Software and Rapid Prototyping

The availability of 3D dental model scanning technology, combined with the ability to register CBCT data with digital models, has enabled the fabrication of orthognathic surgical CAD/CAM designed splints, customized brackets, and indirect bonding systems. In this study, custom lingual orthodontic appliances were virtually designed by merging 3D model images with lateral and posterior-anterior cephalograms. By exporting design information to 3D CAD software, we have produced a stereolithographic prototype and converted it into a cobalt-chrome alloy appliance as a way of combining traditional prosthetic investment and cast techniques. While the bonding procedure of the appliance could be reinforced, CAD technology simplified the fabrication process by eliminating the soldering phase. This report describes CAD/CAM fabrication of the complex anteroposterior lingual bonded retraction appliance for intrusive retraction of the maxillary anterior dentition. Furthermore, the CAD/CAM method eliminates the extra step of determining the lever arm on the lateral cephalograms and subsequent design modifications on the study model

Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects

<p>Abstract</p> <p>Background</p> <p>Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.</p> <p>Methods</p> <p>Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.</p> <p>Results</p> <p>SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.</p> <p>Conclusions</p> <p>Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.</p

Association between blood pressure and the risk of chronic kidney disease in treatment-naïve hypertensive patients

Background Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals. Methods This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or the development of proteinuria. The secondary outcome was incident cardiovascular disease (CVD). Results In the time-varying Cox models, the hazard ratios (95% confidence interval [CI]) for CKD were 1.39 (1.10–1.77) with SBP 130–139 mmHg, 1.79 (1.40–2.28) with SBP 140–159 mmHg, and 3.22 (2.35–4.40) with SBP ≥ 160 mmHg, compared with SBP 100–119 mmHg. In addition, the hazard ratios (95% CI) for CKD were 1.88 (1.48–2.37) with DBP 90–99 mmHg and 4.30 (3.20–5.76) with DBP ≥ 100 mmHg, compared with DBP 70–79 mmHg. A significantly increased CVD risk was also observed in subjects with SBP ≥ 130 mmHg or DBP ≥ 90 mmHg. Conclusion Our findings indicate that SBP ≥ 130 mmHg and DBP ≥ 90 mmHg are associated with an increased risk of CKD. Therefore, BP-lowering strategies should be considered starting at those thresholds to prevent CKD development

Pericoronary fat attenuation index in computed tomography angiography is associated with mortality in end-stage renal disease

Background An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. Methods In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. Results Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of all-cause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94–3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11–4.61). Conclusion The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients

Trib2 regulates the pluripotency of embryonic stem cells and enhances reprogramming efficiency

Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process

The occurrence of coronary artery lesions in Kawasaki disease based on C-reactive protein levels: a retrospective cohort study

Background This study aimed to assess the occurrence of coronary artery lesions (CAL) in patients with Kawasaki disease (KD) according to serum C-reactive protein (CRP) levels. Methods This retrospective analysis was based on the nationwide survey of KD conducted in the Republic of Korea between 2015 and 2017. We enrolled 9131 patients and defined low (< 3 mg/dL) and high (≥3 mg/dL) CRP groups. Demographic data, clinical characteristics, z-scores, and scores based on the Japanese criteria for CAL were compared between the two groups. Logistic regression analysis was used to identify CAL risk factors. Results The low CRP group accounted for 23% of patients. The mean age at diagnosis was higher in high CRP group compared to the low CRP group (34.4 ± 24.9 vs 31.7 ± 24.8 months, p < 0.001). Fever duration before treatment was not significantly different between the two groups (5.1 ± 1.7 days vs. 5.2 ± 2.1 days; p = 0.206). A non-response to intravenous immunoglobulin treatment was found in 1377 patients (20.1%) and 225 patients (11.7%) in the high and low CRP groups, respectively (p < 0.001). CAL were found in 12.9 and 18.3% of the high and low CRP patients, respectively (p < 0.001), based on z-scores; and in 9.9 and 12.5%, respectively (p = 0.001), based on the Japanese criteria in the acute phase. The giant coronary artery aneurysm occurrence ratio was similar between groups (p = 1.0). Conclusions CAL occurred in patients with both high and low CRP. Therefore, patients with KD should be carefully monitored regardless of their CRP levels

Metformin use and cardiovascular outcomes in patients with diabetes and chronic kidney disease: a nationwide cohort study

Background Metformin has recently been shown not to increase the risk of lactic acidosis in patients with chronic kidney disease (CKD). Thus, the criteria for metformin use in this population has expanded. However, the relationship between metformin use and clinical outcomes in CKD remains controversial. Methods This study considered data from 97,713 diabetes patients with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcomes were all-cause mortality and incident end-stage renal disease (ESRD). Results Metformin users had a significantly higher risk of MACCE than non-users (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.14–1.26; p < 0.001). However, metformin users had a lower risk of all-cause mortality (HR, 0.78; 95% CI, 0.74–0.81; p < 0.001) and ESRD (HR, 0.44; 95% CI, 0.42–0.47; p < 0.001) during follow-up than non-users did. The relationships between metformin use and clinical outcomes remained consistent in propensity score matching analyses and subgroup analyses of patients with adequate adherence to anti-diabetes medication. Conclusion Treatment with metformin was associated with an increased risk of MACCE in patients with diabetes and CKD. However, metformin users had a lower risk of all-cause mortality and ESRD during follow-up than non-users did. Therefore, metformin needs to be carefully used in patients with CKD

Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension

BACKGROUND: Renovascular hypertension (RVH) impairs cardiac structure and left ventricular (LV) function, but whether mitochondrial injury is implicated in RVH-induced myocardial damage and dysfunction has not been defined. We hypothesized that cardiac remodeling in swine RVH is partly attributable to cardiac mitochondrial injury. METHODS AND RESULTS: After 12 weeks of hypercholesterolemic (HC)-RVH or control (n=14 each), pigs were treated for another 4 weeks with vehicle or with the mitochondrial-targeted peptide (MTP), Bendavia (0.1 mg/kg subcutaneously, 5 days/week), which stabilizes mitochondrial inner-membrane cardiolipin (n=7 each). Cardiac function was subsequently assessed by multidetector-computed tomography and oxygenation by blood-oxygen-level-dependent magnetic resonance imaging. Cardiolipin content, mitochondrial biogenesis, as well as sarcoplasmic-reticulum calcium cycling, myocardial tissue injury, and coronary endothelial function were assessed ex vivo. Additionally, mitochondrial cardiolipin content, oxidative stress, and bioenergetics were assessed in rat cardiomyocytes incubated with tert-butyl hydroperoxide (tBHP) untreated or treated with MTP. Chronic mitoprotection in vivo restored cardiolipin content and mitochondrial biogenesis. Thapsigargin-sensitive sarcoplasmic reticulum Ca(2+)-ATPase activity that declined in HC-RVH normalized in MTP-treated pigs. Mitoprotection also improved LV relaxation (E/A ratio) and ameliorated cardiac hypertrophy, without affecting blood pressure or systolic function. Myocardial remodeling and coronary endothelial function improved only in MTP-treated pigs. In tBHP-treated cardiomyocytes, mitochondrial targeting attenuated a fall in cardiolipin content and bioenergetics. CONCLUSIONS: Chronic mitoprotection blunted myocardial hypertrophy, improved LV relaxation, and attenuated myocardial cellular and microvascular remodeling, despite sustained HC-RVH, suggesting that mitochondrial injury partly contributes to hypertensive cardiomyopathy