Mindy R. Waite

Pitx2, a paired-like homeodomain transcription factor, is expressed in post-mitotic neurons within highly restricted domains of the embryonic mouse brain. Previous reports identified critical roles for PITX2 in histogenesis of the hypothalamus and midbrain, but the cellular identities of PITX2-positive neurons in these regions were not fully explored. This study characterizes Pitx2 expression with respect to midbrain transcription factor and neurotransmitter phenotypes in mid-to-late mouse gestation. In the dorsal midbrain, we identified Pitx2-positive neurons in the stratum griseum intermedium (SGI) as GABAergic and observed a requirement for PITX2 in GABAergic differentiation. We also identified two Pitx2-positive neuronal populations in the ventral midbrain, the red nucleus, and a ventromedial population, both of which contain glutamatergic precursors. Our data suggest that PITX2 is present in regionally restricted subpopulations of midbrain neurons and may have unique functions that promote GABAergic and glutamatergic differentiation.

The hypothalamic mammillary region is critical for spatial memory and vestibular processing. Pitx2 encodes a paired-like transcription factor that is highly expressed in the developing mammillary region and is required for subthalamic nucleus formation. Here we analyzed a loss of function Pitx2-TaulacZ knock-in allele to study the effects of Pitx2 deficiency on neuronal projections in the embryonic mammillary region. Pitx2-expressing neurons contribute axons to principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are improperly bundled and disorganized, yet project caudally toward the tectum and tegmentum. Embryos with Nestin-Cre mediated conditional Pitx2 deficiency exhibit truncated mammillothalamic tracts (mtt) that fail to elongate, and reduced Pax6-positive cells at the branching point of the principal mammillary and mtt. These data suggest that Pitx2 mediates cell-autonomous and nonautonomous guidance cues necessary for mammillary collaterals destined to project to the anterior thalamus.

Purpose: The COVID-19 pandemic continues to have major and long-lasting impacts on health care delivery and mental health. As health care shifted to telehealth, legislation was adjusted to expand telehealth allowances, creating a unique opportunity to elucidate outcomes. The aim of this study was to assess long-term patient and clinician satisfaction and outcomes with virtual behavioral health. Methods: Data were obtained over 16 months from surveys to patients and clinicians receiving/providing virtual treatment. Outcomes data also were collected from medical records of adults receiving in-person and virtual behavioral health treatment. Data were summarized using descriptive statistics. Groups were compared using various chi-squared tests for categorical variables, Likert response trends over time, and conditional independence, with Wilcoxon rank-sum or Jonckheere trend test used to assess continuous variables. P-values of ≤0.05 were considered statistically significant. Results: Patients gave high ratings to virtual treatment and indicated a preference for virtual formats. Both patient and clinician preference for virtual visits increased significantly with time, and many clinicians perceived virtual services to be equally effective to in-person. Virtual programs had higher completion rates, attendance rates, and number of treatment visits, suggesting that virtual behavioral health had equivalent or better outcomes to in-person treatment and that attitudes toward telehealth changed over time. Conclusions: If trends found in this study continue, telehealth may emerge as a preferred option long term This is important considering the increase in mental health needs associated with the COVID-19 pandemic and the eventuality that in-person restrictions ease as the pandemic subsides.