G protein-coupled receptor kinase 5 (GRK5) contributes to impaired cardiac function and immune cell recruitment in post-ischemic heart failure.

AIMS: Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown. In this study, we evaluated whether myocardial GRK5 plays a critical role post-MI in mice and included the examination of specific cardiac immune and inflammatory responses. METHODS AND RESULTS: Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) were subjected to MI and, functional as well as structural changes together with outcomes were studied. TgGRK5 post-MI mice showed decreased cardiac function, augmented left ventricular dimension and decreased survival rate compared to NLC post-MI mice. Cardiac hypertrophy and fibrosis as well as fetal gene expression were increased post-MI in TgGRK5 compared to NLC mice. In TgGRK5 mice, GRK5 elevation produced immuno-regulators that contributed to the elevated and long-lasting leukocyte recruitment into the injured heart and ultimately to chronic cardiac inflammation. We found an increased presence of pro-inflammatory neutrophils and macrophages as well as neutrophils, macrophages and T-lymphocytes at 4-days and 8-weeks respectively post-MI in TgGRK5 hearts. Conversely, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (predominantly monocytes) to the heart, improved contractility and reduced mortality compared to WT post-MI mice. Interestingly, cardiomyocyte-specific GRK2 transgenic mice did not share the same phenotype of TgGRK5 mice and did not have increased cardiac leukocyte migration and cytokine or chemokine production post-MI. CONCLUSIONS: Our study shows that myocyte GRK5 has a crucial and GRK-selective role on the regulation of leucocyte infiltration into the heart, cardiac function and survival in a murine model of post-ischemic HF, supporting GRK5 inhibition as a therapeutic target for HF.

Rapid Creation of a Multiagency Alternate Care Site for COVID-19- Positive Individuals Experiencing Homelessness.

Cook County Health partnered with the Chicago Departments of Public Health and Family & Support Services and several dozen community-based organizations to rapidly establish a temporary medical respite shelter during the spring 2020 COVID-19 peak for individuals experiencing homelessness in Chicago and Cook County, Illinois. This program provided low-barrier isolation housing to medically complex adults until their safe return to congregate settings. We describe strategies used by the health care agency, which is not a Health Resource and Services Administration Health Care for the Homeless grantee, to provide medical services and care coordination.

An examination of mediators of the transfer of cognitive speed of processing training to everyday functional performance.

The purpose of these analyses was to examine mediators of the transfer of cognitive speed of processing training to improved everyday functional performance (J. D. Edwards, V. G. Wadley,, D. E. Vance, D. L. Roenker, & K. K. Ball, 2005, The impact of speed of processing training on cognitive and everyday performance. Aging & Mental Health, 9, 262-271). Cognitive speed of processing and visual attention (as measured by the Useful Field of View Test; UFOV) were examined as mediators of training transfer. Secondary data analyses were conducted from the Staying Keen in Later Life (SKILL) study, a randomized cohort study including 126 community dwelling adults 63 to 87 years of age. In the SKILL study, participants were randomized to an active control group or cognitive speed of processing training (SOPT), a nonverbal, computerized intervention involving perceptual practice of visual tasks. Prior analyses found significant effects of training as measured by the UFOV and Timed Instrumental Activities of Daily Living (TIADL) Tests. Results from the present analyses indicate that speed of processing for a divided attention task significantly mediated the effect of SOPT on everyday performance (e.g., TIADL) in a multiple mediation model accounting for 91% of the variance. These findings suggest that everyday functional improvements found from SOPT are directly attributable to improved UFOV performance, speed of processing for divided attention in particular. Targeting divided attention in cognitive interventions may be important to positively affect everyday functioning among older adults.

Everyday reasoning abilities in persons with Parkinson's disease.

Parkinson's disease (PD) patients develop progressive cognitive decline. The degree to which such decline impacts instrumental activities of daily living (IADL) among individuals in the early stages of PD without dementia is not well documented. The Everyday Cognitive Battery Reasoning subtest (ECB) was used to assess ability to solve everyday reasoning tasks for IADL among 19 non-demented older adults with PD in comparison to 20 older adults without PD. The two groups were similar in age, education, race and gender. Individuals with PD had significantly lower scores (M = 61.98, SD = 12.03) than the comparison group (M = 69.80, SD = 9.48). Individuals with PD, who do not have dementia, may be more likely to experience difficulties in IADL requiring reasoning including medication use, finances, and nutrition. Even more serious implications lie in the capacity to make treatment choices.

Mycoplasma hominis lipid-associated membrane protein antigens for effective detection of M. hominis-specific antibodies in humans.

Lipid-associated membrane proteins (LAMPs) from 14 Mycoplasma hominis isolates or strains share similar protein and antigenicity profiles. Of 31 human immunodeficiency virus-infected patients from whose samples M. hominis was cultured, 28 tested strongly positive for serum antibodies to M. hominis LAMPs. The remaining 3 serum samples showed low antibody titer to LAMPs from all of the 14 M. hominis isolates or strains, which was likely the result of the compromised immune systems of the patients. Thus, M. hominis LAMPs as a whole are homogenous in antigenicity within the species, despite having many different serotypes. Serological study involving 564 healthy blood donors and 211 patients attending sexually transmitted disease clinics by LAMPs showed that general populations were widely exposed to M. hominis. Women were infected with M. hominis at a younger age than were men. The prevalence of infection increased markedly among sexually active persons.