ABSTRACT
Home dialysis modalities are used in a minority of patients with kidney failure in the United States. During the 2018 National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) Home Dialysis Conference, numerous ideas were suggested to help minimize barriers for the uptake and retention of home dialysis therapies. First, educational tools are needed to increase knowledge about home dialysis modalities (eg, continuous ambulatory peritoneal dialysis, continuous cycling peritoneal dialysis, and home hemodialysis). Implementation of a hub and spoke model, pairing smaller and/or newer home dialysis programs with larger more sophisticated programs that offer education and mentoring, may help dialysis programs to grow and prosper. This pairing can be facilitated by traditional conferences and newer modalities such as telemedicine and training applications. Peer support to patients, such as that offered through the NKF Peers Program, and support and respite to care partners can have beneficial effects toward both increasing the number of patients who choose home dialysis as a modality and improving retention in home dialysis programs. Anticipating and understanding both patient and care partner burden is important for the development and implementation of patient- and care partner-centered support programs that can be deployed before a patient ceases home therapy. Finally, aligning Medicare reimbursement to support appropriate increased home dialysis uptake to prioritize both transplantation and home dialysis as the first-line treatments for kidney failure.
Subject(s)
Health Knowledge, Attitudes, Practice , Hemodialysis, Home , Patient Education as Topic/organization & administration , Peritoneal Dialysis, Continuous Ambulatory/methods , Peritoneal Dialysis/methods , Renal Insufficiency/therapy , Communication Barriers , Health Services Needs and Demand , Hemodialysis, Home/education , Hemodialysis, Home/methods , Home Care Services/organization & administration , Home Care Services/standards , Humans , Medicare , Program Development , Quality Improvement/organization & administration , Stakeholder Participation , United StatesABSTRACT
Sleeping Beauty (SB) is a prominent Tc1/mariner superfamily DNA transposon that provides a popular genome engineering tool in a broad range of organisms. It is mobilized by a transposase enzyme that catalyses DNA cleavage and integration at short specific sequences at the transposon ends. To facilitate SB's applications, here we determine the crystal structure of the transposase catalytic domain and use it to model the SB transposase/transposon end/target DNA complex. Together with biochemical and cell-based transposition assays, our structure reveals mechanistic insights into SB transposition and rationalizes previous hyperactive transposase mutations. Moreover, our data enables us to design two additional hyperactive transposase variants. Our work provides a useful resource and proof-of-concept for structure-based engineering of tailored SB transposases.
