Synthesis of the Antimicrobial Peptide Murepavadin Using Novel Coupling Agents.

The problem of antimicrobial resistance is becoming a daunting challenge for human society and healthcare systems around the world. Hence, there is a constant need to develop new antibiotics to fight resistant bacteria, among other important social and economic measures. In this regard, murepavadin is a cyclic antibacterial peptide in development. The synthesis of murepavadin was undertaken in order to optimize the preparative protocol and scale-up, in particular, the use of new activation reagents. In our hands, classical approaches using carbodiimide/hydroxybenzotriazole rendered low yields. The use of novel carbodiimide and reagents based on OxymaPure® and Oxy-B is discussed together with the proper use of chromatographic conditions for the adequate characterization of peptide crudes. Higher yields and purities were obtained. Finally, the antimicrobial activity of different synthetic batches was tested in three Pseudomonas aeruginosa strains, including highly resistant ones. All murepavadin batches yielded the same highly active MIC values and proved that the chiral integrity of the molecule was preserved throughout the whole synthetic procedure.

Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders.

INTRODUCTION: Clinical High Risk for Psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population. METHOD: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis. RESULTS: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c = 0.51). Retraining resulted in moderate discrimination (Harrel's c = 0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0% - 23.1%) over two years. CONCLUSION: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention.

Improving Pathways to Care for Patients at High Psychosis Risk in Switzerland: PsyYoung Study Protocol.

AIMS: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments. It investigates the effects of service changes on the referrals and outcomes of young people with ARMS or a FEP. METHODS: Six psychiatric outpatient clinics in three cantons (Basel-Stadt, Vaud, and Geneva) participated in the project. They passed through an implementation phase including service changes and the adaptation of a standardized stepped care model for diagnosis and assessment, in addition to measures for increasing the awareness, networking and training of local professionals. PRELIMINARY RESULTS: All participating cantons had entered the implementation phase. By March 2023, there were 619 referrals to participating sites. A total of 163 patients (37% FEP and 31% ARMS) and 15 close relatives had participated in individual longitudinal assessments, and 26 patients participated in qualitative interviews. CONCLUSION: This national collaborative project addresses the issue of early intervention for emerging psychoses, and creates spaces for fruitful reflections and collaboration in Switzerland. The ultimate aim of PsyYoung is to harmonize clinical practices in early intervention of psychosis on a national level.

Immigrant Patients Adapt to the Culture of Admission and Experience Less Safety in Forensic Psychiatric Care.

Patients with an immigrant background are overrepresented in forensic psychiatric hospitals. As a result, daily work is impeded by language barriers and cultural differences. Furthermore, general therapy processes have not yet been adapted to this special patient population, and little reliable knowledge is available. All immigrants go through an acculturation process, which is related to their mental well-being. Four acculturation strategies exist: integration, separation, assimilation, and marginalization. The strategy chosen depends on the extent of someone's orientation toward their country of origin and the country of admission. The current study aimed to expand knowledge of forensic patients with a migration background in Germany by evaluating their self-reported acculturation processes and associated individual and social factors, e.g., the ward climate. Therefore, we studied forensic patients with a migration background from 11 forensic hospitals in Bavaria, Germany. Besides completing the Frankfurter Acculturation Scale (FRACC) and Essen Climate Evaluation Schema (EssenCES), the participants provided information on their clinical and biographical history. We recruited 235 patients with a migration background and found that the participants oriented themselves more toward the culture of admission and less toward the country of origin than the reference sample did. Moreover, the patients experienced significantly less safety on the ward than the forensic reference sample did. A possible explanation for the patients' orientation is the lack of possibilities to adhere to their cultural traditions. Patients may feel less safe because of their limited knowledge of German and cultural misunderstandings.