An integrated youth mental health service in a densely populated metropolitan area in Japan: Clinical case management bridges the gap between mental health and illness services.

AIMS: A global movement, including in Asia, is seeking to establish integrated youth mental health services that provide early intervention in the continuum from mental health to mental illness. Clinical case management (CCM), in which a case manager becomes not only a coordinator of services but also a provider of psychosocial support, can establish a 'one-stop network' that supports youth in densely populated areas with various social resources. In 2019, we opened a community-based centre called 'SODA' in front of a metropolitan railway station, which was designed to be highly accessible, stigma-free and youth-friendly to provide CCM. We aimed to clarify its services and effectiveness of CCM. METHODS: Data from 105 youths were investigated in a case-controlled study, dividing them into two groups: those who had received CCM for 6 months, and those whose needs were met in fewer sessions. RESULTS: Twenty-one subjects who received CCM for 6 months had difficulties in more domains than the others. The mean of the total service minutes for the subjects who received CCM for 6 months was 491.3 min: psychological support (accounted for 24.8% of the time), support for community living (31.2%), work support (13.8%), family support (10.5%) and support for cooperation with other organizations (19.8%). Global Assessment of Functioning (GAF) score improved significantly, from 46.6 at baseline to 59.3 at 6 months. CONCLUSION: Even in metropolitan areas with numerous medical facilities, young people can face high barriers to access. CCM can be effective as an early intervention for subjects developing mental illness.

Broadly Applicable and Comprehensive Synthetic Method for N-Alkyl-Rich Drug-like Cyclic Peptides.

We report a versatile and durable method for synthesizing highly N-alkylated drug-like cyclic peptides. This is the first reported method for synthesizing such peptides in parallel with a high success rate and acceptable purity that does not require optimizations for a particular sequence. We set up each reaction condition by overcoming the following issues: (1) diketopiperazine (DKP) formation, (2) insufficient peptide bond formation due to the steric hindrance of the N-alkylated amino acid, and (3) instability of highly N-alkylated peptides under acidic conditions. Using this newly established method, we successfully synthesized thousands of cyclic peptides to explore the scope of this modality in drug discovery. We here demonstrate the syntheses of a hundred representative examples, including our first clinical N-alkyl-rich cyclic peptide (LUNA18) that inhibits an intracellular tough target (RAS), in 31% total yield and 97% purity on average after 23 or 24 reaction steps.