Background/Aims: Cardiovascular disease remains a major cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated the association between subclinical carotid atherosclerosis (SCA) and MASLD or MASLD and increased alcohol intake (MetALD) in asymptomatic individuals. Methods: This cross-sectional study included 56,889 adults undergoing health check-ups in South Korea. Hepatic steatosis was diagnosed by ultrasound, and SCA was defined by carotid plaques or increased intima-media thickness. Liver fibrosis was evaluated using the fibrosis-4 index and elastography. Results: SCA was identified in 13.5%. MASLD and MetALD were significantly associated with SCA in models adjusted for demographic and lifestyle factors (adjusted odds ratio [aOR], 1.26;95% confidence interval [CI], 1.19 to 1.33; aOR, 1.43; 95% CI, 1.30 to 1.58; respectively, p<0.001for both). However, these associations attenuated and lost statistical significance when metabolic risk factors were further adjusted. The risk of SCA increased with greater hepatic steatosis and liver fibrosis severity. In patients with MASLD, aORs were 1.70 (hepatic steatosis index >36),1.23 (fibrosis-4 index ≥1.3), and 1.78 (liver stiffness measurement ≥5.6 kPa), compared to indi-viduals without MASLD. Similar trends were observed in the MetALD group. Additionally, hyper-tension and clustering of ≥3 cardiometabolic risk factors were significantly associated with SCA inthe MASLD group, supporting the role of metabolic burden in SCA development. Conclusions MASLD and MetALD were associated with increased SCA risk, particularly in individuals with hepatic steatosis and fibrosis. These findings suggest that metabolic burden and liver disease severity jointly contribute to subclinical atherosclerosis risk.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

PURPOSE: . The purpose of this in vitro study was to compare the accuracy of various 3D printers and a milling machine. MATERIALS AND METHODS: . The die model was designed using CAD (Autodesk Inventor 2018 sp3). The 30 µm cement space was given to the die and the ideal crown of the mandibular left first molar was designed using CAD (ExoCAD). The crowns were produced using the milling machine (Imes-icore 250i) and the 3D printers (Zenith U, Zenith D, W11) and they were divided into four groups. In all groups, the interior of each crown was scanned (Identica blue) and superimposed (Geomagic Control X) with the previously designed die. The difference between the die and the actual crown was measured at specific points. The Kruskal-Wallis test, the Mann-Whitney test, and Bonferroni’s method were performed with a statistical analysis software (P < .008 in inter-group comparison P < .001 in intra-group comparison). RESULTS: . In all groups, the center of the occlusal area and the anti-rotational dimple area showed significantly greater difference and the marginal area showed the smallest difference comparatively. The mean value of the difference in each area and the sum of the differences were higher in order of W11, Imes-icore 250i, Zenith D, and Zenith U. CONCLUSION . The digital light processing (DLP) method shows higher accuracy compared to the sereolithography (SLA) method using the same resin material. [J Adv Prosthodont 2023;15:72-9]

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death.While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation.Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.

Purpose: Mesenchymal-epithelial transition tyrosine kinase receptor (MET) amplification is one of the common acquired resistance mechanisms to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). To evaluate the usefulness of screening methods for MET status, we studied the impact of MET amplification or protein overexpression in EGFR-mutant non-small cell lung cancer patients who were treated with EGFR TKI. Methods: A total of 214 patients treated with EGFR TKI as first-line therapy with available tissue biopsy was analyzed. Paired biopsies were obtained from 111 patients at baseline and at onset of resistance. MET status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: Among 111 patients with paired samples, incidence of MET alteration was increased according to both MET overexpression by IHC (14.4% to 22.5%) and MET amplification by FISH (1.8% to 8.1%) with moderated to strong IHC intensity samples after EGFR TKI treatment. In patients treated with 1st-generation EGFR TKI, MET amplification by FISH was significantly related to shorter progression-free survival (P=0.04) and overall survival (P=0.01). In contrast, there was no difference in clinical outcomes according to MET intensity of IHC. Patients harboring MET amplification by FISH were associated with poor clinical outcomes compared to those with T790M mutation at progression. Conclusion These results suggest that FISH is more informative than IHC for identification of patients with MET amplification as an EGFR TKI resistance mechanism. Given the poor outcome in patients who developed MET amplification, combinational trials with more active MET inhibitor are needed to overcome resistance.