Transforming the Workforce to Provide Better Chronic Care: The Role of Nurse Care Managers in Rhode Island

This series explores the evolution of primary care systems to better meet the needs of consumers with complex health conditions. It demonstrates that changes in the workforce are required to empower consumers to better manage their health.The series is a collaboration of the National Academy for State Health Policy and the AARP Public Policy Institute. We recognize that it takes a team of skilled professionals to deliver improved chronic care. In this series, we focus on how registered nurses -- who make up the largest segment of the health care workforce -- are being deployed in ambulatory delivery systems to take on new roles. Future series will focus on other members of the health care team.We selected six initiatives that offer replicable policy strategies to develop, implement, and sustain patient-centered approaches to care. Each case study highlights one of these initiatives and provides policy recommendations and an "on-the-ground" look at the work of its nurses

Maximizing the Efficacy of CRISPR/Cas Homology-Directed Repair Gene Targeting

Clustered regularly interspaced short palindromic repeats/CRISPR-associated system (CRISPR/Cas) is a powerful gene editing tool that can introduce double-strand breaks (DSBs) at precise target sites in genomic DNA. In mammalian cells, the CRISPR/Cas-generated DSBs can be repaired by either template-free error-prone end joining (e.g., non-homologous end joining/microhomology-mediated end joining [NHEJ]/[MMEJ]) or templated error-free homology-directed repair (HDR) pathways. CRISPR/Cas with NHEJ/MMEJ DNA repair results in various length insertions/deletion mutations (indels), which can cause frameshift mutations leading to a stop codon and subsequent gene-specific knockout (i.e., loss of function). In contrast, CRISPR/Cas with HDR DNA repair, utilizing an exogenous repair template harboring specific nucleotide (nt) changes, can be employed to intentionally edit out or introduce mutations or insertions at specific genomic sites (i.e., targeted gene knock-in). This review provides an overview of HDR-based gene-targeting strategies to facilitate the knock-in process, including improving gRNA cleavage efficiency, optimizing HDR efficacy, decreasing off-target effects, suppressing NHEJ/MMEJ activity, and thus expediting the screening of CRISPR/Cas-edited clonal cells

Myeloperoxidase-dependent oxidation of etoposide in human myeloid progenitor CD34+ cells

ABSTRACT Etoposide is a widely used anticancer drug successfully utilized for treatment of many types of cancer in children and adults. Its use, however, is associated with an increased risk of development of secondary acute myelogenous leukemia (t-AML) involving MLL gene MOL #68718