The D1 dopamine receptor (D1R) is widely expressed in the kidney and plays a crucial role in blood pressure regulation. Although much is known about D1R desensitization, especially through G-protein-coupled receptor kinase 4 (GRK4), comparatively little is known about other aspects of D1R trafficking and the proteins involved in the process. We now report the discovery of a dynamic interaction between sorting nexin 5 (SNX5), a component of the mammalian retromer, and D1R in human renal epithelial cells. We show that internalization of agonist-activated D1R is regulated by both SNX5 and GRK4, and that SNX5 is critical to the recycling of the receptor to the plasma membrane. SNX5 depletion increases agonist-activated D1R phosphorylation (>50% at basal condition), prevents D1R internalization and cAMP response, and delays receptor recycling compared to mock siRNA-transfected controls. Moreover, renal restricted subcapsular infusion of Snx5-specific siRNA (vs. mock siRNA) decreases sodium excretion (Δ=-0.2±0.005 mEq/mg creatinine) and further elevates the systolic blood pressure (Δ=48±5 mm Hg) in spontaneously hypertensive rats, indicating that SNX5 depletion impairs renal D1R function. These studies demonstrate an essential role for SNX5 in regulating D1R function, which may have important diagnostic, prognostic, and therapeutic implications in the management of essential hypertension.
A multifaceted intervention led to improved utilization of acute inpatient rehabilitation consultation while increasing the frequency of rehabilitation treatment for patients with highest functional impairment.
Background and Objectives: Health professionals may face sexual harassment from patients, faculty, and colleagues. Medicine’s hierarchy deters response to sexual harassment. Current evidence consists largely of quantitative data regarding the frequency and types of sexual harassment. More information is needed about the nature of the experience and how or why professionals choose to report or respond.
Methods: We developed and administered a semistructured interview guide to elicit family medicine faculty and residents’ experiences with sexual harassment and gender bias. Facilitators led a series of focus groups divided by faculty (N=28) and residents (N=24). We ensured voluntary consent and groups were audiotaped, transcribed and deidentified. We coded the transcripts using immersion-crystallization theory to identify emergent themes.
Results: Sexual harassment from patients and colleagues was described as witnessed or personally experienced by faculty and resident participants in 100% of the focus groups. Respondents identified the presence of mentors, clear reporting process and follow-up, history of good organizational response to reporting, and education and training as facilitators to reporting sexual harassment. Barriers to reporting included fear of retaliation, lack of trust of the system to respond, lack of clarity about “what counts,” and confusion with the reporting process.
Conclusions: It is important to capitalize on facilitators to reporting sexual harassment, starting with acknowledging the frequency of sexual harassment and gender discrimination. Addressing barriers to responding through education and training for our learners and faculty is critical. Clarifying the reporting process, having clear expectations for behavior, and a continuum of responses may help increase the frequency of reporting.
Recognizing a need for more guidance on the SARS-CoV-2 (COVID-19) pandemic, members of the Archives of Physical Medicine and Rehabilitation Editorial Board invited several clinicians with early experience managing the disease to collaborate on a document to help guide rehabilitation clinicians in the community. This consensus document is written in a “question and answer” format and contains information on the following items: common manifestations of the disease; rehabilitation recommendations in the acute hospital setting, recommendations for inpatient rehabilitation and special considerations. These suggestions are intended for use by rehabilitation clinicians in the inpatient setting caring for patients with confirmed or suspected COVID-19. The text represents the authors’ best judgment at the time it was written. However, our knowledge of COVID-19 is growing rapidly. The reader should take advantage of the most up to date information when making clinical decisions.
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