Synapses are crucial for communication among neurons in the central nervous system. Contactin-associated protein- like 2 (Caspr2) is a neuronal protein that is a member of the neurexin superfamily and is found in the juxtaparanodal regions of myelinated axons. Caspr2 has also been found in synapses and therefore is also thought to function as a cell adhesion molecule. As such, it should also induce synaptogenesis in vitro similar to the interaction between neurexins (located presynaptically) and neuroligins (located postsynaptically). Neurexins and neuroligins are calcium-dependent cell adhesion proteins that mediate the signaling across synapses and have the ability to affect the neuronal network by promoting the formation of excitatory or inhibitory synapses. Mutations in neurexins and neuroligins have been implicated with autism and autism spectrum disorders, among other neurodevelopmental disorders. As a member of the neurexin superfamily, Caspr2 shares the same increased risk for autism. Here I describe a co-culture experiment with rat hippocampal neurons and Caspr2-expressing HEK293 cells to test for synapse formation and its location in particular synapse sub-types

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are challenging conditions to treat due to complex pathophysiology and associated comorbidities. However, recent trials have demonstrated improved outcomes with guideline-directed medical therapy (GDMT) for each subtype of heart failure. OBJECTIVE: We investigated the relationship of determinants of health and risk factors with GDMT use for HFrEF and HFpEF in a large, diverse US cohort. METHODS: Using the NIH-sponsored All of Us Program, we compared demographics, risk factors (e.g., hypertension, diabetes, smoking), and SDOH measures between HFrEF and HFpEF in US adults aged 18 years and older. We examined the proportions of HFrEF patients receiving fewer than four or all four GDMTs. HFpEF patients receiving two medications were compared with those receiving less than two recommended medications. Multiple logistic regression was used for data analysis. RESULT: Of 6049 HFrEF patients, 5838 (97 %) received fewer than four GDMTs, and 210 (3 %) received quadruple therapy. Of 3774 HFpEF patients, 162 (4 %) were on 2/3 GDMT, and only 38 (1 %) were on all three recommended medications. Patients with ASCVD and diabetes had higher odds of being on more than half of the recommended GDMT for both HFrEF and HFpEF. Additionally, females had higher odds of being on 2/3 GDMT for HFpEF (1.46 [1.08, 2.00]). Race, income, education, and health insurance types did not predict GDMT optimization. CONCLUSION: HFrEF and HFpEF GDMT remain underutilized. Future efforts to address comorbidities and system-wide healthcare interventions may improve heart failure GDMT.