Evaluation of Neutrophil Elastase Inhibitors as Potential Therapies for Associated Neutropenia.

Neutrophil elastase () mutations are the most common cause of cyclic (CyN) and congenital neutropenia (SCN), two autosomal dominant disorders causing recurrent infections due to impaired neutrophil production. Granulocyte colony-stimulating factor (G-CSF) corrects neutropenia but has adverse effects, including bone pain and in some cases, an increased risk of myelodysplasia (MDS) and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation is an alternative but is limited by its complications and donor availability.

Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.

Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).

Feasibility, validity, and normative data for the remote Uniform Data Set neuropsychological battery at the University of Pennsylvania Alzheimer's Disease Research Center.

Introduction: We investigated the feasibility and validity of the remotely-administered neuropsychological battery from the National Alzheimer's Coordinating Center Uniform Data Set (UDS T-Cog).

Methods: Two hundred twenty Penn Alzheimer's Disease Research Center participants with unimpaired cognition, mild cognitive impairment, and dementia completed the T-Cog during their annual UDS evaluation. We assessed administration feasibility and diagnostic group differences cross-sectionally across telephone versus videoconference modalities, and compared T-Cog to prior in-person UDS scores longitudinally.