We generated cortical interneurons (cINs) from iPSCs derived from14 healthy controls (HC cINs) and 14 patients with schizophrenia (SCZ cINs). Both HC cINs and SCZ cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons
in vivo
. However, SCZ cINs had dysregulated expression of protocadherin genes, which lie within documented SCZ loci. Mice lacking protocadherin α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. SCZ cINs similarly showed defects in synaptic density and arborization, which were reversed by inhibitors of Protein Kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in SCZ cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development.
Objectives: The majority of patients with head and neck squamous cell carcinoma (HNSCC) do not commence postoperative radiation treatment (PORT) within the recommended 6 weeks. We explore how delayed PORT affects survival outcomes, what factors are associated with delayed PORT initiation, and what interventions exist to reduce delays in PORT initiation. Methods: We conducted a PubMed search to identify articles discussing timely PORT for HNSCC. We performed a narrative review to assess survival outcomes of delayed PORT as well as social determinants of health (SDOH) and clinical factors associated with delayed PORT, using the PROGRESS-Plus health equity framework to guide our analysis. We reviewed interventions designed to reduce delays in PORT. Results: Delayed PORT is associated with reduced overall survival. Delays in PORT disproportionately burden patients of racial/ethnic minority backgrounds, Medicaid or no insurance, low socioeconomic status, limited access to care, more comorbidities, presentation at advanced stages, and those who experience postoperative complications. Delays in PORT initiation tend to occur during transitions in head and neck cancer care. Delays in PORT may be reduced by interventions that identify patients who are most likely to experience delayed PORT, support patients according to their specific needs and barriers to care, and streamline care and referral processes. Conclusions: Both SDOH and clinical factors are associated with delays in timely PORT. Structural change is needed to reduce health disparities and promote equitable access to care for all. When planning care, providers must consider not only biological factors but also SDOH to maximize care outcomes.
We found few examples of comprehensive, patient-centered documents. Work is needed to achieve consensus as to the essential elements of TB treatment literacy and to create additional materials for children, patients with drug-resistant TB, and those with lower literacy levels.
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