Transsulfuration pathway activation attenuates oxidative stress and ferroptosis in sickle primary erythroblasts and transgenic mice.

The transsulfuration (TSS) pathway is an alternative source of cysteine for glutathione synthesis. Little of the TSS pathway in antioxidant capacity in sickle cell disease (SCD) is known. Here, we evaluate the effects of TSS pathway activation through cystathionine beta-synthase (CBS) to attenuate reactive oxygen species (ROS) and ferroptosis stresses in SCD.

Developing an Implementation Model for ADHD Intervention in Community Clinics: Leveraging Artificial Intelligence and Digital Technology.

Implementation of behavior therapy for ADHD faces challenges in community settings. We describe development of a community-based implementation model for adolescent ADHD behavior therapy (Supporting Teens' Autonomy Daily; STAND) blended with Motivational Interviewing (MI). A stakeholder-engaged development approach is used based on the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.

Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease.

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation.

Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.

Infection of lung endothelial cells with pneumococci activates the superoxide-generating enzyme NADPH oxidase 2 (NOX2), involving the pneumococcal virulence factor pneumolysin (PLY). Excessive NOX2 activity disturbs capillary barriers, but its global inhibition can impair bactericidal phagocyte activity during pneumococcal pneumonia. Depletion of the α subunit of the epithelial sodium channel (ENaC) in pulmonary endothelial cells increases expression and PMA-induced activity of NOX2.