Hickeyzhou7824

addictions (U=36,806.5, Z=4.96, P less then .001; U=23,765.5, Z=3.66, P less then .001). Conclusion Although health professional students had similar beliefs and perceptions regarding the opioid crisis, there were notable differences between academic programs. Students with clinical opioid experiences were more likely to plan on working with patients addicted to opioids and be confident in treating these patients. Thus, the inclusion of experiential learning in the medical curricula may be beneficial for both students and their future patients.Adult T cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by Human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in six individuals, 2-10 years before the diagnosis of ATL. Clones of premalignant HTLV-1-infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year pre-diagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high risk, age-matched HTLV-1-carriers who remained ATL-free after a median of 10 years of follow up. These data show that HTLV-1-infected T cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL. Copyright © 2020 American Society of Hematology.Glutaric aciduria type 1 (GA1) is an inborn error of lysine degradation characterized by a specific encephalopathy that is caused by toxic accumulation of lysine degradation intermediates. Substrate reduction through inhibition of DHTKD1, an enzyme upstream of the defective glutaryl-CoA dehydrogenase, has been investigated as a potential therapy, but revealed the existence of an alternative enzymatic source of glutaryl-CoA. Here we show that loss of DHTKD1 in GCDH-deficient HEK-293 cells leads to a 2-fold decrease in the established GA1 clinical biomarker glutarylcarnitine, and demonstrate that OGDH is responsible for this remaining glutarylcarnitine production. We furthermore show that DHTKD1 interacts with OGDH, DLST and DLD to form a hybrid 2-oxoglutaric and 2-oxoadipic acid dehydrogenase complex. In summary, 2-oxoadipic acid is a substrate for DHTKD1, but also for OGDH in a cell model system. The classical 2-oxoglutaric dehydrogenase complex can exist as a previously undiscovered hybrid containing DHTKD1 displaying improved kinetics towards 2-oxoadipic acid. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.PURPOSE To develop and implement an interprofessional framework to increase the capture of health system-generated prescriptions within health system-owned pharmacies. SUMMARY Low prescription capture rates within a health system's internal pharmacies led to an interdisciplinary process improvement effort. A framework was developed to assess the baseline prescription capture rate, select clinics for improvement, understand clinic workflows and key drivers of pharmacy selection, design strategies to increase prescription capture, implement targeted efforts, and measure the effectiveness of the intervention(s). Employing this framework provided revised workflows for nursing and medical assistant staff scripting and for referral of patients to internal pharmacies. These workflows were pilot tested at 3 system clinics. Results indicated that overall prescription capture increased 2.9% to by 2.9 to 4.1 percentage points (range, 10 to 86 prescriptions per month) and specialty prescription capture increased 11.6 to 26.7 percentage points (range, 4 to 26 prescriptions per month) for each clinic within the first 2 months. A total of 99 new patients were referred to internal pharmacies within the first month. CONCLUSION Development and implementation of a framework to increase prescription capture from health system clinics helped increase capture, enhanced clinic engagement and knowledge about pharmacy services, and supported positive clinic-pharmacy relationships. © American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause neurodevelopmental disorders including often severe epilepsy and intellectual disability. The mutational profile is unusual; ~ 50 different missense mutations have been identified but no obvious loss of function mutations, though large heterozygous deletions are known to be compatible with life. A key question is whether the heterozygous missense mutations operate through haploinsufficiency or a gain of function mechanism, an important prerequisite for design of therapeutic strategies. 4Hydroxytamoxifen In order both to address this question and to provide a novel model for neurodevelopmental disorders resulting from mutations in EEF1A2, we created a new mouse model of the D252H mutation. This mutation causes the eEF1A2 protein to be expressed at lower levels in brain but higher in muscle in the mice. We compared both heterozygous and homozygous D252H and null mutant mice using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. Mice that are heterozygous for the missense mutation show no behavioural abnormalities but do have sex-specific deficits in body mass and motor function. The phenotyping of our novel mouse lines, together with analysis of molecular modelling and interacting proteins, suggest that the D252H mutation results in a gain of function. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.