Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism With Intellectual Disability: An Observational Study.

Catatonia is a highly morbid psychomotor and affective disorder, which can affect autistic individuals with and without intellectual disability. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments in autistic individuals has not been described. We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024.

Lip Augmentation in Patients with Fitzpatrick Skin Type V and VI: Use of a Validated Lip Fullness Scale and Determining Preinjection Lip Size Preference and Postinjection Patient Satisfaction.

There is limited literature assessing cosmetic lip size preferences in darker-skinned individuals. To measure preinjection lip augmentation preferences and postinjection satisfaction using the revised Lip Fullness Scale (LFS) in female participants with Fitzpatrick Skin Type V and VI. Females, aged 21 and over, with Fitzpatrick Skin Type V and VI desiring lip augmentation were recruited from a high-volume outpatient facial plastic surgery clinic.

The safety and efficacy of cannabinoids for the treatment of mental health and substance use disorders: protocol for a systematic review and meta-analysis.

There has been a global increase in the use of cannabinoids as a treatment for mental health (MH) and substance use disorders (SUD). In 2016, an Australian government-funded review found that although medicinal cannabinoids accounted for a small reduction in MH symptoms, the results varied according to study design. There has since been a rise in randomised controlled trials (RCTs) aiming to examine the efficacy of cannabinoids for the treatment of MH and SUD.