Developing Topics.

Background: The β-secretase-1 inhibitors (BACEi), including verubecestat, were extensively studied in prodromal to moderate AD and demonstrated early cognitive decline (negative effect) at doses achieving >50% inhibition of amyloid production. Questions remain as to whether BACEi may still have utility, if used earlier in disease and at lower levels of inhibition. A mechanistic model of the progression of Alzheimer's disease was used to predict effects of alternative BACEi therapeutic approaches on disease progression.

Developing Topics.

Background: BACE inhibitors, while effective in lowering amyloid-beta production, have been associated with mild cognitive worsening in clinical trials. Additional treatment-related adverse events reported in multiple clinical trials were sleep disturbances and insomnia. The purpose of this study is to determine if sleep disturbances occur in mice receiving BACE inhibitor, if sleep disturbances correlate with cognitive impairment, and the mechanism by which this may occur.

Evidence-based Interventions for Youth With Concurrent Mental Health and Substance Use Disorders: A Scoping Review: Interventions fondées sur des données probantes pour les jeunes atteints de troubles concomitants de santé mentale et liés à l'usage de substances psychoactives : une étude de la portée.

Background: Mental health and substance use disorders typically onset during youth and commonly co-occur. Integrated treatment of two or more co-existing mental health and substance use disorders (i.e.

Antibiotic therapy for treating overactive bladder is not supported by clinical evidence.

A number of reports have suggested that the use of prolonged antibiotic treatment could be an effective therapy for patients with overactive bladder (OAB); however, this approach is contrary to existing recommendations regarding the prolonged non-specific use of antibiotics. The existing evidence in this area seems to be circumstantial and anecdotal but, despite this limitation, the use of long-term antibiotic therapy for OAB seems to be increasing. Review and synthesis of the existing evidence for use of antibiotic therapy in patients with OAB identify few studies - just seven papers and four conference proceedings - which are heterogeneous in their design, inclusion and exclusion criteria, treatment regimen employed, approach to the use of antimuscarinic medications, follow-up protocols, and measured outcomes.

Nanopore sequencing as a novel method of characterising anorexia nervosa risk loci.

Background: Anorexia nervosa (AN) is a polygenic, severe metabopsychiatric disorder with poorly understood aetiology. Eight significant loci have been identified by genome-wide association studies (GWAS) and single nucleotide polymorphism (SNP)-based heritability was estimated to be ~ 11-17, yet causal variants remain elusive. It is therefore important to define the full spectrum of genetic variants in the wider regions surrounding these significantly associated loci.