An Evaluation of a Multisite, Health Systems-Based Direct Care Worker Retention Program: Key Findings and Recommendations.

The U.S. direct care workforce employs nearly 4.6 million people and represents one of the fastest growing occupations in the United States. Direct care workers, or "caregivers," include nursing assistants, home care workers, and residential care aides, all of whom provide basic care to older adults and individuals with disabilities in various health care settings. Despite a growing need for caregivers, supply has not kept up with demand due to high turnover and low wages. In addition, caregivers often face high levels of workplace stress, limited training and growth opportunities, and personal stressors. Ranging from 35 to 90 percent, depending on the health care setting, the turnover rates of direct care workers pose a major challenge for health systems, as well as care recipients and workers themselves. In 2019, the Ralph C. Wilson Jr. Foundation funded three health systems to support the implementation of a new program: Transformational Healthcare Readiness through Innovative Vocational Education (THRIVE). This 12-month program was designed to help address barriers that entry-level caregivers experience and reduce turnover through a comprehensive risk assessment, training, and one-on-one coaching. Researchers from RAND conducted a process and outcome evaluation to determine whether THRIVE was meeting its goals of improving retention and achieving a positive return on investment (ROI). They also examined potential areas for program improvement.

Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids.

BACKGROUND: Human immunodeficiency virus type-1 (HIV-1) and opiates cause long-term inflammatory insult to the central nervous system (CNS) and worsen disease progression and HIV-1-related neuropathology. The combination of these proinflammatory factors reflects a devastating problem as opioids have high abuse liability and continue to be prescribed for certain patients experiencing HIV-1-related pain. METHODS: Here, we examined the impact of chronic (3-month) HIV-1 transactivator of transcription (Tat) exposure to short-term (8-day), escalating morphine in HIV-1 Tat transgenic mice that express the HIV-1 Tat protein in a GFAP promoter-regulated, doxycycline (DOX)-inducible manner. In addition to assessing morphine-induced tolerance in nociceptive responses organized at spinal (i.e., tail-flick) and supraspinal (i.e., hot-plate) levels, we evaluated neuroinflammation via positron emission tomography (PET) imaging using the [18F]-PBR111 ligand, immunohistochemistry, and cytokine analyses. Further, we examined endocannabinoid (eCB) levels, related non-eCB lipids, and amino acids via mass spectrometry.  RESULTS: Tat-expressing [Tat(+)] transgenic mice displayed antinociceptive tolerance in the tail withdrawal and hot-plate assays compared to control mice lacking Tat [Tat(-)]. This tolerance was accompanied by morphine-dependent increases in Iba-1 ± 3-nitrotryosine immunoreactive microglia, and alterations in pro- and anti-inflammatory cytokines, and chemokines in the spinal cord and striatum, while increases in neuroinflammation were absent by PET imaging of [18F]-PBR111 uptake. Tat and morphine exposure differentially affected eCB levels, non-eCB lipids, and specific amino acids in a region-dependent manner. In the striatum, non-eCB lipids were significantly increased by short-term, escalating morphine exposure, including peroxisome proliferator activator receptor alpha (PPAR-α) ligands N-oleoyl ethanolamide (OEA) and N-palmitoyl ethanolamide (PEA), as well as the amino acids phenylalanine and proline. In the spinal cord, Tat exposure increased amino acids leucine and valine, while morphine decreased levels of tyrosine and valine but did not affect eCBs or non-eCB lipids. CONCLUSION: Overall results demonstrate that 3 months of Tat exposure increased morphine tolerance and potentially innate immune tolerance evidenced by reductions in specific cytokines (e.g., IL-1α, IL-12p40) and microglial reactivity. In contrast, short-term, escalating morphine exposure acted as a secondary stressor revealing an allostatic shift in CNS baseline inflammatory responsiveness from sustained Tat exposure.

Galectin-1 Protein Therapy Prevents Pathology and Improves Muscle Function in the mdx Mouse Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by mutations in the dystrophin gene, leading to the loss of a critical component of the sarcolemmal dystrophin glycoprotein complex. Galectin-1 is a small 14 kDa protein normally found in skeletal muscle and has been shown to be a modifier of immune response, muscle repair, and apoptosis. Galectin-1 levels are elevated in the muscle of mouse and dog models of DMD. Together, these findings led us to hypothesize that Galectin-1 may serve as a modifier of disease progression in DMD. To test this hypothesis, recombinant mouse Galectin-1 was produced and used to treat myogenic cells and the mdx mouse model of DMD. Here we show that intramuscular and intraperitoneal injections of Galectin-1 into mdx mice prevented pathology and improved muscle function in skeletal muscle. These improvements were a result of enhanced sarcolemmal stability mediated by elevated utrophin and α7ß1 integrin protein levels. Together our results demonstrate for the first time that Galectin-1 may serve as an exciting new protein therapeutic for the treatment of DMD.

Characterization of RERG: an estrogen-regulated tumor suppressor gene.

RERG (Ras-related and estrogen-regulated growth inhibitor), a gene that encodes a small GTP binding and hydrolyzing protein (GTPase) of the Ras superfamily, was originally identified in gene microarray analysis as a gene of which expression is down-regulated in estrogen receptor (ER)-negative breast tumors. Subsequently, RERG mRNA was detected in ER-positive breast tumor-derived cell lines, but not in any of the ER-negative cell lines examined. Furthermore, a comparison of matched tumor and normal tissue samples suggests that RERG expression is lost in kidney, breast, ovary, and colon tumors. The lack of RERG expression in many highly aggressive breast carcinomas suggests that RERG plays an inhibitory role in cell growth and division. In fact, growth of breast tumor cells was inhibited by overexpression of RERG both in vitro and in vivo. In this chapter, we summarize the reagents and approaches used to characterize RERG gene expression, to demonstrate that RERG functions as a GTP/GDP molecular switch, and to characterize the growth inhibitory activity of RERG.