We designed the Korean Radiation Oncology Group 09-03 phase III clinical trial to compare accelerated hypofractionated radiation therapy (RT) using a concomitant boost to the gross tumor volume (GTV) ...with conventionally fractionated 60-Gy RT in patients with stage III unresectable non-small cell lung cancer (NSCLC).
A conventionally fractionated RT group (arm 1; 124 patients) received a 2-Gy daily dose to a total cumulative dose of 44 Gy to the planning target volume (PTV) in 22 fractions and 60 Gy to the GTV in 30 fractions over 6 weeks. A hypofractionated RT group (arm 2; 142 patients) received a 1.8-Gy daily dose to the PTV with a synchronous boost of 0.6 Gy to the GTV, for total cumulative doses of 45 Gy to the PTV and 60 Gy to the GTV in 25 fractions over 5 weeks. All patients received concurrent weekly chemotherapy consisting of paclitaxel and cisplatin.
The objective response rate of all patients was 86.5% (arm 1, 84.6%; arm 2, 88.1%; P = .612). The median overall survival was 26 months (arm 1, 26 months; arm 2, 27 months; P = .508). The median progression-free survival was 11 months (arm 1, 10 months; arm 2, 13 months; P = .295). The local tumor control rates at 2 and 5 years were 58.3% and 50.7%, respectively (arm 1, 62.4% and 51.0%, respectively; arm 2, 54.0% and 48.6%, respectively; P = .615). There were no significant between-group differences in the cumulative incidence of grade ≥3 radiation pneumonitis (P = .134) or radiation esophagitis (P = .539).
This clinical trial did not confirm the superiority of accelerated 2.4-Gy hypofractionated RT compared with conventional 2-Gy fractionation in patients with unresectable stage III NSCLC undergoing concurrent chemoradiation therapy.
Objective
This study aimed to investigate the association between low muscle mass or sarcopenic obesity and the risk of incident chronic kidney disease (CKD) in patients with type 2 diabetes mellitus ...(T2DM).
Methods
A total of 3123 patients with T2DM with preserved renal function were followed up for incident CKD. Skeletal muscle mass was estimated from bioelectrical impedance analysis. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2. Sarcopenic obesity was defined as the coexistence of sarcopenia and abdominal obesity.
Results
During 8.9 years of follow‐up, 530 (17.0%) patients developed incident CKD. When patients were divided into three groups based on sex‐specific tertiles, lower muscle mass was not associated with an increased risk of incident CKD after adjustment for risk factors. However, when patients were divided into four groups according to the presence of sarcopenia and obesity, sarcopenic obesity was associated with an increased risk of incident CKD (adjusted hazard ratio 1.77; 95% CI: 1.24‐2.51; p = 0.001) compared with the other groups.
Conclusions
Sarcopenic obesity, but not low muscle mass alone, may increase the risk of CKD in patients with T2DM.
Background and Aim
Non‐alcoholic fatty liver disease (NAFLD) is getting an increasing attention for its clinical implications on cardiovascular disease (CVD). However, epidemiologic data are not so ...evident to sustain the causative association between NAFLD and hypertension, the major cause of CVD. Accordingly, we designed this study to investigate the clinical association between NAFLD and the development of hypertension.
Methods
To assess the natural course of blood pressure according to degree of NAFLD (normal, mild, and moderate to severe), we conducted a prospective cohort study on the 22 090 Korean men without hypertension for 5 years. We serially checked the various metabolic factors including systolic and diastolic blood pressure in order to monitor the development of hypertension.
Results
The incidence rate of hypertension increased according to the degree of NAFLD (normal: 14.4%, mild: 21.8%, moderate to severe: 30.1%, P < 0.001). Even after adjusting for other multiple covariates, the hazard ratios (95% confidence intervals) for hypertension were higher in the mild group (1.07; 1.00–1.15) and moderate to severe group (1.14; 1.00–1.30), compared with normal group, respectively (P for trend < 0.001).
Conclusion
Development of hypertension is more potentially associated with the more progressive NAFLD than normal or milder state. In addition, NAFLD was an independent risk factor for hypertension.
Minipigs have remarkably similar physiology to humans, therefore, they it can be a good animal model for inflammation study. Thus, the conventional (serum chemistry, histopathology) and novel ...analytic tools immune cell identification in tissue, cytokine level in peripheral blood mononuclear cells (PBMC) and serum, NF-kB target gene analysis in tissue were applied to determine inflammation in Chicago Miniature Swine (CMS) minipig. Lipopolysaccharide (LPS)-induced acute systemic inflammation caused liver and kidney damage in serum chemistry and histopathology. Immunohistochemistry (IHC) also showed an increase of immune cell distribution in spleen and lung during inflammation. Moreover, NF-kB-target gene expression was upregulated in lung and kidney in acute inflammation and in heart, liver, and intestine in chronic inflammation. Cytokine mRNA was elevated in PBMC under acute inflammation along with elevated absolute cytokine levels in serum. Overall, LPS-mediated systemic inflammation affects the various organs, and can be detected by IHC of immune cells, gene analysis in PBMC, and measuring the absolute cytokine in serum along with conventional inflammation analytic tools.
In the present study, we explore the protective effects of Citrus aurantium L. extract (CAE) against acute and chronic CCl4-induced hepatotoxicity. The quantitative analysis of CAE was performed ...using HPLC-UV to determine the nobiletin content was approximately 27%. For the acute model, the male ICR mice were orally treated with water, silymarin (positive control, 200 mg/kg) and CAE (50 and 200 mg/kg) for 3 days prior to CCl4 (1 mL/kg, 50% v/v in olive oil) IP injection. For the chronic model (n = 6/group), the mice were treated with each treatment for 28 consecutive days and CCl4 (1 mL/kg, 20%) was injected twice a week. In both the acute and chronic models, the CCl4 alone treated group showed histopathologic alterations with a significantly increase in serum hepatic enzyme levels together with a disrupted anti-oxidative status. In contrast, the CAE treatments restored pathologic alterations and recovered the oxidative status by enhancing antioxidant enzymes and reducing lipid peroxidation levels. Furthermore, CAE enhanced nuclear factor E2-related factor 2 (Nrf2) and its related cytoprotective signals, including NAD(P)H quinone oxidoreductase 1, UDP-glucuronosyltransferase, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrates that CAE exerts a protective effect against CCl4-induced hepatotoxicity with its anti-oxidant, anti-inflammatory, and anti-apoptotic activity.
•The hepato-protective effects of Citrus aurantium peel extract (CAE), which contains >50% PMFs using the both acute and chronic CCl4 intoxication models.•The antioxidant status and Nrf2-related protein expression in the liver were explored to understand the mechanistic pathway of the hepato-protective effects of CAE.•In conclusion, the nobiletin rich extract, CAE, protects the liver against acute and chronic CCl4-induced hepatotoxicity by decreasing inflammation and apoptosis.
Y2O3 coatings during atmospheric plasma spray (APS) processes are used to suppress the corrosion of internal process chamber parts for semiconductor plasma etching. Highly corrosive fluorine-based ...plasma corrodes the surface, causing contamination particle and process drift, which are the main causes of yield reduction. In this paper, defluorination is proposed to reduce the amount of contamination particle generation by removing the YOxFy layer on the surface of APS-Y2O3 material after plasma etching. After exposure to CF4/Ar/O2 plasma, chemical–mechanical polishing occurred using KOH, surfactant, and piranha solutions, respectively. The highest and lowest defluorination efficiencies were obtained with the piranha and surfactant solutions, respectively. The results were validated by field-emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. In particular, the piranha solution generated the lowest amount of contamination particles and lowest amount of etching. In contrast, the thickness reduction due to the defluorination process resulted in the highest breakdown voltage among the surfactant solutions, thereby prompting optimization studies. Finally, the mechanisms of the plasma etching and defluorination processes were derived, and a new method for controlling the amount of contamination particle generation was presented.
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•APS-Y2O3 was exposed to CF4/Ar/O2 plasma to confirm the amount of contamination particle generation and surface changes.•Defluorination was performed to reduce the amount of contamination particle generation during the plasma etching process.•Piranha solution showed the highest defluorination efficiency and the surfactant the lowest among all the results obtained.•However, the breakdown voltage characteristics show the opposite, suggesting a trade-off relationship.
The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes ...distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.
Sarcopenia leads to metabolic and vascular abnormalities. However, little is known regarding the independent relationship between skeletal muscle mass and atherosclerosis in patients with type 2 ...diabetes mellitus (T2DM). This study aimed to evaluate the association between skeletal muscle mass and carotid atherosclerosis in men and women with T2DM.
In this cross-sectional study, a total of 8202 patients with T2DM were recruited from the Seoul Metabolic Syndrome cohort. Skeletal muscle mass was estimated using bioimpedance analysis, while skeletal muscle mass index (SMI, %) was defined as total skeletal muscle mass (kg)/body weight (kg) × 100. Both carotid arteries were examined by B-mode ultrasound. Carotid atherosclerosis was defined by having a carotid plaque or mean carotid intima-media thickness (IMT) ≥1.1 mm.
Among the entire population, 4299 (52.4%) subjects had carotid atherosclerosis. The prevalence of carotid atherosclerosis increased with decreasing SMI quartiles for both sexes. The odds ratios for carotid atherosclerosis were 2.33 (95% confidence interval CI, 1.17–4.63) and 2.24 (95% CI, 1.06–4.741) in the lowest versus highest SMI quartile in men and women, respectively, after the adjustment for clinical risk factors. In men, the risk of atherosclerosis increased linearly with decreasing SMI quartiles (p for trend = 0.036).
Low skeletal muscle mass was independently associated with the presence of carotid atherosclerosis in men and women with T2DM.
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•Patients with type 2 diabetes mellitus (T2DM) and carotid atherosclerosis had lower skeletal muscle mass.•Low skeletal muscle mass was associated with increased risk of carotid atherosclerosis in both men and women with T2DM.•The risk of atherosclerosis may be modified by skeletal muscle mass maintenance in patients with T2DM.
Nonalcoholic fatty liver disease (NAFLD) is increasing in worldwide prevalence, closely tracking the obesity epidemic, but specific pharmaceutical treatments for NAFLD are lacking. Defining the key ...molecular pathways underlying the pathogenesis of NAFLD is essential for developing new drugs. Here we demonstrate that inhibition of gut-derived serotonin synthesis ameliorates hepatic steatosis through a reduction in liver serotonin receptor 2A (HTR2A) signaling. Local serotonin concentrations in the portal blood, which can directly travel to and affect the liver, are selectively increased by high-fat diet (HFD) feeding in mice. Both gut-specific Tph1 knockout mice and liver-specific Htr2a knockout mice are resistant to HFD-induced hepatic steatosis, without affecting systemic energy homeostasis. Moreover, selective HTR2A antagonist treatment prevents HFD-induced hepatic steatosis. Thus, the gut TPH1-liver HTR2A axis shows promise as a drug target to ameliorate NAFLD with minimal systemic metabolic effects.
Because minipig skin is similar to human skin in anatomy and physiology, establishing an atopic dermatitis (AD) minipig model seems meaningful.
We applied 1-fluoro-2,4-dinitrobenzene (DNFB) or ...ovalbumin onto the back skin of five Yucatan minipigs aged 8-10 months and 19 kg in median weight. Two minipigs with the same parameters served as controls.
Both DNFB and ovalbumin mediated epithelial hyperplasia, spongiosis, and immune cell infiltration in the dermis, which is a typical histopathological feature of AD. Moreover, AD upregulated the Th1- and Th2-related cytokine expressions in DNFB- or in ovalbumin-treated skin. Notably, AD-induced minipigs exhibited greater cytokine serum concentrations.
Histopathological finding and cytokine analysis revealed that DNFB or ovalbumin mediates AD. However, ovalbumin-treated minipig is a more reliable and precise AD model owing to the DNFB-induced severe skin damage. In summary, ovalbumin-treated skin shows similar AD as human in histopathological and molecular analysis.
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