No abstract

Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one‐step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.

There are inconsistent findings about depression in Asians. This study examined risk factors for depression in Asian and Caucasian adolescents. Stratified bivariate secondary analyses of risk indicators and depressed mood were performed in this cross-sectional study of high school survey data (9th to 12th grades) from 2,542 students (198 Asian). Asians had a higher prevalence of depressed symptoms, but similar risk factors as Caucasians. Smoking and injury at work were major risk factors for depressed mood among Asians. Asian-specific risk factors for depression were being foreign-born and having a work-related injury. Asian and Caucasian teens have similar risk factors for depressed mood, though being foreign born and having a work-related injury are risk factors specific to Asian youth, possibly related to social-economic status. Providers of care in school, such as school nurses, can be important primary screeners of depression for Asian students in particular.

We report the development of a catalytic method for the enantioselective addition of indoles to pyrone-derived electrophiles. Arylpyrrolidino-derived thioureas catalyze the addition with high stereoselectivity in the presence of catalytic quantities of an achiral Brønsted acid. The indole–pyrone adducts feature a quaternary stereocenter and represent an unusual class of indolines bearing structural resemblance to the hybrid natural product pleiocarpamine.

Psychosocial problems in adolescents with epilepsy have been of concern for many years, but have been difficult to assess. This article presents the multicenter development of the Adolescent Psychosocial Seizure Inventory (APSI), an empirically based self-report test patterned after the Washington Psychosocial Seizure Inventory, which is used to evaluate psychosocial problems in adults. After pilot work, 120 adolescents with epilepsy from five centers in North America took the APSI and were interviewed by professionals with respect to adequacy of adjustment in eight psychosocial areas. At least one parent or guardian was also interviewed. Interrater reliability of professional ratings in each area was established. Using an item-by-item, empirically based technique, eight psychosocial scales were developed as well as three validity scales. Reliability of the scales was established by both internal consistency and test-retest procedures. Results for each adolescent are presented in profile form. These results give a visual display of the types and extent of problems that likely would be identified in a detailed professional assessment. It is anticipated that the APSI will be of value in a variety of treatment and research contexts.