Psychosocial work environment stressors for school staff during the COVID-19 pandemic: Barriers and facilitators for supporting wellbeing.

Introduction: After periods of remote and/or hybrid learning as a result of the COVID-19 global pandemic, the return to in-person learning has been beneficial for both students and teachers, but it has not been without challenges. This study was designed to assess the impact of the return to in-person learning on the school experience, and efforts made to ease the transition in furthering a positive in-person learning environment. Materials and methods: We conducted a series of listening sessions with 4 stakeholder groups: students (n = 39), parents (n = 28), teachers/school staff (n = 41), and a combination of listening sessions and semi-structured interviews with building level and district administrators (n = 12), focusing on in-school experiences during the 2021-2022 school year amidst the COVID-19 pandemic. A primarily deductive qualitative analysis approach was employed to code the data followed by a primarily inductive thematic analysis, followed by thematic aggregation, thus providing depth and identification of nuances in the data. Results: Three main themes emerged around school staff experiences: (1) increased levels of stress and anxiety manifested in key ways, including students' challenges with personal behavior management contributing to increased aggression and staff shortages; (2) school staff described key contributors to stress and anxiety, including feeling excluded from decision making and challenges with clear and consistent communication; and (3) school staff described key facilitators that supported their management of anxiety and stress, including adaptability, heightened attention and resources to wellbeing, and leveraging interpersonal relationships. Discussion: School staff and students faced significant stress and anxiety during the 2021-2022 school year. Further exploration and identification of approaches to mitigate key contributors to increased stress and anxiety for school staff, along with increased opportunities for implementing key facilitators that were identified as important in managing and navigating the increased stress and anxiety offer valuable opportunities for helping to create a supportive work environment for school staff in the future.

Alagille Syndrome and Repeat Oxygenator Failure during Cardiopulmonary Bypass: A Word of Caution.

Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but may not be limited to the liver, heart, musculoskeletal, skin, and the eyes. The most common congenital heart defect associated with Alagille syndrome is multilevel right ventricular outflow tract obstruction with multiple central and peripheral branch pulmonary arterial stenoses occurring in up to two-thirds of these patients. We report two cases of Alagille syndrome who underwent extensive pulmonary arterial branch rehabilitation and experienced unusual oxygenator failure during cardiopulmonary bypass (CPB). We present lessons learned from these two cases and the changes that we implemented in our practice that facilitated smooth conduct of CPB in other cases that we performed subsequently.

Analysis of human ITPase nucleobase specificity by site-directed mutagenesis.

Inosine triphosphate (ITP) pyrophosphohydrolase, or ITPase, is an intracellular enzyme that is responsible for the hydrolysis of the acidic anhydride bond between the alpha and beta phosphates in ITP, and other noncanonical nucleoside triphosphates, producing the corresponding nucleoside monophosphate and pyrophosphate. This activity protects the cell by preventing noncanonical nucleoside triphosphates from accumulating in (deoxy) nucleoside triphosphate ((d)NTP) pools and/or being integrated into nucleic acids. This enzyme is encoded by the ITPA gene in mammals. It has been reported that Itpa homozygous-null knock-out mice die before weaning and have gross cardiac abnormalities. Additionally, certain variations in the human ITPA gene have been linked to adverse reactions to the immunosuppressive prodrugs azathioprine and 6-mercaptopurine and protection against ribavirin-induced hemolytic anemia. These drugs are bioactivated to form noncanonical nucleoside triphosphates. Human ITPase enzymes engineered to modulate nucleobase specificity may be valuable tools for studying the role of ITPase in heart development and drug metabolism or developing gain-of-function mutants or inhibitory molecules. Based on x-ray crystallography and amino acid sequence data, a panel of putative human ITPase nucleobase specificity mutants has been generated. We targeted eight highly conserved amino acid positions within the ITPase sequence that correspond to amino acids predicted to directly interact with the nucleobase or help organize the nucleobase binding pocket. The ability of the mutants to protect against exogenous and endogenous noncanonical purines was tested with two Escherichia coli complementation assays. Nucleobase specificity of the mutants was investigated with an in vitro biochemical assay using ITP, GTP and ATP as substrates. This methodology allowed us to identify gain-of-function mutants and categorize the eight amino acid positions according to their ability to protect against noncanonical purines as follows: Glu-22, Trp-151 and Arg-178, essential for protection; Phe-149, Asp-152, Lys-172 and Ser-176, intermediate protection; His-177, dispensable for protection against noncanonical purines.