ABSTRACT
Background. In response to the novel coronavirus disease (COVID-19), the state mandated "Stay At Home" order included closure of schools and public places and physical distancing measures. As a result, social interactions among children were significantly impaired and pediatric outpatient offices and vaccination rates declined. We sought to determine the impact of the COVID-19 pandemic on mental health as well as access to health care in our pediatric population in Wayne County, Michigan. Design/Methods. We conducted a survey through the Wayne County Public School Districts to elicit information regarding subjects' access to pediatric health care as well as experiences pertinent to their child(ren)'s mental health. Results. Approximately 8500 surveys were sent to families and 278 responses were received. Responses revealed that 46% of children spent more time alone during the pandemic, 36.9% had changes in sleep, 25.6% had little pleasure in doing things, and 32.5% were unhappy or sad. 66.2% were able to make new visits during the pandemic, however, 20.1% missed their child's doctors' visits for reasons including clinic cancellations and fear of entering a healthcare setting. Conclusions. The results of this survey demonstrate significant mental health concerns among our pediatric population as approximately 1/3 of families reported changes in behavior or mental health. As school closures persist in response to the ongoing pandemic and social interactions remain limited, it is imperative that pediatricians screen for depression, behavioral problems and other mental health concerns and offer families help to identify appropriate community mental health resources.
ABSTRACT
The inwardly rectifying potassium channel Kir6.2 is the pore-forming subunit of the ATP-sensitive potassium (K(ATP)) channel, which controls insulin secretion by coupling glucose metabolism to membrane potential in beta-cells. Loss of channel function because of mutations in Kir6.2 or its associated regulatory subunit, sulfonylurea receptor 1, causes congenital hyperinsulinism (CHI), a neonatal disease characterized by persistent insulin secretion despite severe hypoglycemia. Here, we report a novel K(ATP) channel gating defect caused by CHI-associated Kir6.2 mutations at arginine 301 (to cysteine, glycine, histidine, or proline). These mutations in addition to reducing channel expression at the cell surface also cause rapid, spontaneous current decay, a gating defect we refer to as inactivation. Based on the crystal structures of Kir3.1 and KirBac1.1, Arg-301 interacts with several residues in the neighboring Kir6.2 subunit. Mutation of a subset of these residues also induces channel inactivation, suggesting that the disease mutations may cause inactivation by disrupting subunit-subunit interactions. To evaluate the effect of channel inactivation on beta-cell function, we expressed an alternative inactivation mutant R301A, which has equivalent surface expression efficiency as wild type channels, in the insulin-secreting cell line INS-1. Mutant expression resulted in more depolarized membrane potential and elevated insulin secretion at basal glucose concentration (3 mm) compared with cells expressing wild type channels, demonstrating that the inactivation gating defect itself is sufficient to cause loss of channel function and hyperinsulinism. Our studies suggest the importance of Kir6.2 subunit-subunit interactions in K(ATP) channel gating and function and reveal a novel gating defect underlying CHI.
