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eople with substance use disorder only and people with a dual diagnosis.<br /><br />In a large sample of residents of British Columbia (Canada), approximately one in five people had sought care for a substance use disorder or mental illness in the past 5 years. The rate of overdose was elevated in people with a mental illness alone, higher again in people with a substance use disorder alone and highest in people with a dual diagnosis. The adjusted hazard rates were similar for people with substance use disorder only and people with a dual diagnosis.<br /><br /> People with anxiety disorders are more likely to smoke and less likely to succeed when they try to quit. [https://www.selleckchem.com/products/arq531.html BTK inhibitor] Anxiety sensitivity may underlie both phenomena, such that people with high anxiety sensitivity react to interoceptive distress by avoidance. This study aimed to test the efficacy of an exercise program that induced interoceptive distress and thereby created tolerance to this distress in a safe environment.<br /><br /> Randomized clinical trial at four YMCA branches in Austin, Texas, USA. Participants [n=150; 130 (86.7%) white; 101 (67.3%) female; mean<br /><br /> =38.6, standard deviation (SD)<br /><br /> =10.4] were adult, daily smokers with high anxiety sensitivity motivated to quit smoking, who reported no regular moderate-intensity exercise.<br /><br /> Participants were assigned a YMCA personal trainer who guided them through a 15-week intervention aerobic exercise program. Participants assigned to the personalized intervention trained at 60-85% of their heart rate reserve (HRR), whereas participants assigned to the control intervention trained at 20-40% of their HRR. Participants in both groups received standard behavioral support and nicotine replacement therapy.<br /><br /> The primary outcome was biologically verified 7-day point prevalence abstinence (PPA) at 6-month follow-up.<br /><br /> Sixty-one per cent of participants were available at the 6-month follow-up. PPA at 6months was higher in the personalized intervention than the control intervention [27.6 versus 14.8%; odds ratio (OR)=2.20, 95% confidence interval (CI)=1.28, 3.80, P=0.005], assuming missing at random. Anxiety sensitivity declined in both groups with no evidence that this differed between groups.<br /><br /> An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.<br /><br />An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.<br /><br /> To assess differences in the quality of opioid use disorder (OUD) treatment received by Medicare beneficiaries enrolled in health plans that used prior authorization (PA) for buprenorphine-naloxone compared with those enrolled in plans that did not use PA.<br /><br /> Cross-sectional observational study, United States. Continuously enrolled beneficiaries (71 294) with an OUD who filled at least one prescription for buprenorphine-naloxone between March 2012 and July 2017.<br /><br /> Percentage of patients tested for hepatis B, hepatis C, HIV and liver functioning; percentage of patients with urine drug screens and number of urine drug screens; continuous use of buprenorphine-naloxone for at least 180days; co-use of benzodiazepines; number of outpatient visits with and without an OUD diagnosis.<br /><br /> PA was significantly associated with a lower likelihood of testing for hepatitis B [-3.5, 95% confidence interval (CI)=-4.4, -2.7] and C (-5.9, 95% CI=-6.9, -4.9), but the findings were inconclusive as to whether or not there was a difMedicare patients subject to prior authorization for buprenorphine-naloxone are not more likely to receive high-quality treatment for opioid use disorder than patients not subject to prior authorization.Protein kinase B (AKT) hyperactivation and de novo lipogenesis are both common in tumor progression. Sterol regulatory element-binding protein 1 (SREBP1) is the master regulator for tumor lipid metabolism, and protein arginine methyltransferase 5 (PRMT5) is an enzyme that can catalyze symmetric dimethyl arginine (SDMA) modification of the mature form of SREBP1 (mSREBP1) to induce its hyperactivation. Here, we report that SDMA-modified mSREBP1 (mSREBP1-SDMA) was overexpressed and correlated with Ser473-phosphorylated AKT (AKT-473P) expression and poor patient outcomes in human lung adenocarcinomas. Furthermore, patients with AKT-473P and mSREBP1-SDMA coexpression showed the worst prognosis. Mechanistic investigation revealed that AKT activation upregulated SREBP1 at both the transcriptional and post-translational levels, whereas PRMT5 knockdown reversed AKT signaling-mediated mSREBP1 ubiquitin-proteasome pathway stabilization at the post-translational level. Meanwhile, AKT activation promoted nuclear PRMT5 to the cytoplasm without changing total PRMT5 expression, and the transported cytoplasmic PRMT5 (cPRMT5) induced by AKT activation showed a strong mSREBP1-binding ability. Immunohistochemical assay indicated that AKT-473P and mSREBP1-SDMA were positively correlated with cPRMT5 in lung adenocarcinomas, and high cPRMT5 levels in tumors were associated with poor patient outcomes. Additionally, PRMT5 knockdown reversed AKT activation-induced lipid synthesis and growth advantage of lung adenocarcinoma cells both in vitro and in vivo. Finally, we defined an AKT/PRMT5/SREBP1 axis involved in de novo lipogenesis and the growth of lung cancer. Our data also support that cPRMT5 is a potential therapeutic target for hyperactive AKT-driven lung adenocarcinoma.During periods of crisis, cells must compensate to survive. To this end, cells may need to alter the subcellular localization of crucial proteins. Here, we show that during starvation, VCP, the most abundant soluble ATPase, relocalizes and forms aggregate-like structures at perinuclear regions in PC3 prostate cancer cells. This movement is associated with a lowered metabolic state, in which mitochondrial activity and ROS production are reduced. VCP appears to explicitly sense glutamine levels, as removal of glutamine from complete medium triggered VCP relocalization and its addition to starvation media blunted VCP relocalization. Cells cultured in Gln(+) starvation media exhibited uniformly distributed VCP in the cytoplasm (free VCP) and underwent ferroptotic cell death, which was associated with a decrease in GSH levels. Moreover, the addition of a VCP inhibitor, CB-5083, in starvation media prevented VCP relocalization and triggered ferroptotic cell death. Likewise, expression of GFP-fused VCP proteins, irrespective of ATPase activities, displayed free VCP and triggered cell death during starvation.