BACKGROUND OLZ/SAM is a combination of olanzapine, an atypical antipsychotic, and samidorphan, an opioid antagonist, and is in development for the treatment of schizophrenia and bipolar I disorder. OLZ/SAM is under development with the intent to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. This thorough QT study assessed the effects of therapeutic and supratherapeutic doses of OLZ/SAM on cardiac repolarization in patients with schizophrenia. METHODS In this randomized, double-blind, placebo- and positive (moxifloxacin)-controlled, parallel-group study, 100 patients aged 18 to 60 years with stable schizophrenia were randomized 32 to the active arm and control arm. Subjects in the active arm received a therapeutic dose of 10/10 mg (10 mg olanzapine/10 mg samidorphan) on days 2-4, 20/20 mg on days 5-8, and a supratherapeutic dose of 30/30 mg (1.5 times and 3 times the maximum recommended daily dose of olanzapine and samidorphan, respectively) on QT/QTc prolongation. BACKGROUND Endovascular treatment of Trans-Atlantic Inter-Society Consensus (TASC) II D aortoiliac lesions is now an accepted form of revascularization. We sought to demonstrate that native microchannel recanalization and orbital atherectomy is a successful recanalization method of TASC II D aortoiliac lesions refractory to standard recanalization techniques. METHODS Four consecutive patients from 2016 to 2018 with symptomatic TASC II D aortoiliac occlusive disease prohibitive for open bypass and failed traditional prodding guidewire or device recanalization technique were identified and underwent advanced native microchannel selection and subsequent orbital atherectomy (Cardiovascular Systems, Inc, St Paul, MN). Native microchannels of the calcified lesions were probed and traversed with a 0.014″ wire. The atherectomy crown was tracked over the wire, and orbital atherectomy was initiated with a 1.25 mm crown starting at the lowest revolution and continued until the microchannel is sufficiently large to trackor reconstruction of the aortic bifurcation. At 30 days, all patients had improvement in pain and primary patency of 100%. Long-term follow-up at 21.6 months noted continued improvement in symptoms and primary patency of 75%. The fourth patient died at 4 months from lung cancer with occluded iliac stents by imaging at that time. CONCLUSIONS Native microchannel recanalization with subsequent orbital atherectomy is an option in high-risk patients with TASC II D aortoiliac disease who have failed traditional recanalization techniques. Further work in proper patient selection and safe utilization of atherectomy devices in the CIA is needed. Published by Elsevier Inc.BACKGROUND This paper aims to identify the health-related predictors of survival in centenarians. METHODS A population-based study conducted in North Portugal (PT100) followed 140 individuals from the age of 100+ years. A detailed questionnaire at baseline was completed including information on sociodemographic characteristics, physical health, functional, cognitive, and nutritional status and life-style. Survival of study participants was checked every six months over the period of December 2013 until June 2019. RESULTS In the univariate Cox proportional hazards model, longer survival was associated with the absence of acute disease, better functional status, absence of physical fatigue and better cognition. Multivariate analysis revealed that acute disease, functional status and physical fatigue remained significant. CONCLUSIONS Acute disease, functional status and physical fatigue are predictors of survival in the PT100 centenarians. Mitochondrial dysfunction plays an important role in acute kidney injury (AKI). Thus, the agents improving the mitochondrial function could be beneficial for treating AKI. Ursodeoxycholic acid (UDCA) has been demonstrated to prevent mitochondrial dysfunction under pathology, however, its role in AKI and the underlying mechanism remain unknown. This study aimed to evaluate the effect of UDCA on cisplatin-induced AKI. In vivo, C57BL/6 J mice were treated with cisplatin (25 mg/kg) for 72 h to induce AKI through a single intraperitoneal (i.p.) injection with or without UDCA (60 mg/kg/day) administration by gavage. Renal function, mitochondrial function and oxidative stress were analyzed to evaluate kidney injury. In vitro, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cells (HK2) were treated with cisplatin with or without UDCA treatment for 24 h. Transcriptomic RNA-seq was preformed to analyze possible targets of UDCA. Our results showed that cisplatin-induced increments of serum creaKI. ETHNOPHARMACOLOGICAL RELEVANCE Hyperthyroidism is closely associated with liver injury. The preliminary clinical observation suggests that Yinning Tablet, a hospitalized preparation of traditional Chinese formula for hyperthyroidism, improves not only hyperthyroidism, but also hyperthyroidism-associated liver injury. AIM To evaluate the effect and underlying mechanisms of Yinning Tablet on thyroid hormone-induced liver injury. MATERIALS AND METHODS Female rats were orally administered L-thyroxine (1 mg/kg) once daily for 60 days, and co-treated with the carefully identified Yinning Tablet extract (0.6-2.4 g/kg) during the last 30 days. Blood and liver variables were determined enzymatically, histologically, by ELISA, radioimmunoassay, Real-Time PCR or Western blot, respectively. RESULTS Co-treatment with the extract attenuated L-thyroxine-induced increases in serum alanine transaminase and aspartate transaminase activities, the ratio of liver weight to body weight, cytoplasmic vacuolization in hepatocytes, infiltrated inflammatory cells and confused structures in liver tissue, accompanied by attenuation of increased serum triiodo-l-thyronine concentration and hepatic deiodinase type I overexpression in rats. Importantly, Yinning Tablet suppressed L-thyroxine-triggered hepatic Bax, cleaved caspases-3, -8 and -9 protein overexpression, and Bcl-2 protein downregulation. Furthermore, the increases in cytochrome c protein expression, Ca2+-ATPase activity and malondialdehyde content, and decreases in activities of Na+/K+-ATPase, catalase, superoxide dismutase and glutathione peroxidase, and total antioxidant capacity in liver tissue were attenuated. CONCLUSION The present results suggest that Yinning Tablet ameliorates thyroid hormone-induced liver injury in rats by regulating mitochondria-mediated apoptotic signals.  https://www.selleckchem.com/products/fluoxetine.html  Our findings go insight into the pharmacological basis of the hospitalized preparation for treatment of hyperthyroidism-associated liver injury.