In eukaryotic cells, variations in the levels of cytosolic free calcium regulate processes as important and disparate as chemotaxis, chromosome segregation, fertilization, ion transport, muscle contraction, passage through cell cycle transition points, proteolysis, secretion, and substrate uptake (7). Cytosolic free calcium concentration is tightly controlled by the action of specific pumps and channels in the plasma membrane and subcellular organelles (8,83). Response to increased cytosolic free calcium concentration is mediated by either direct binding to calcium-sensitive enzymes, such as protein kinase C (49) and calpain (72), or activation of a protein transducer, such as calmodulin (15).In prokaryotic cells, an equivalent important role for calcium has been harder to demonstrate but is now becoming evident (53,59,69). Research on a variety of bacterial processes has passed from the phase of demonstrating a likely involvement of calcium to clarifying the nature of this involvement. In this minireview, recent evidence on the existence of bacterial components (both proteinaceous and nonproteinaceous) concerned with calcium regulation is evaluated, since investigation of these components is one of the surest routes to confirming the involvement of calcium in a process. These components include voltage-gated calcium channels responsible for influx that can be formed from poly-3-hydroxybutyratepolyphosphate complexes, primary and secondary transporters responsible for efflux, and calmodulin-like proteins responsible for mediating responses to calcium. Such calcium-dependent regulation may be exerted directly by changes in nucleoid structure or indirectly by phosphorylation or proteolysis of target proteins. Despite the problems sometimes associated with studies of calcium, this ion is increasingly implicated in a number of bacterial functions, including heat shock, pathogenicity, chemotaxis, differentiation, and the cell cycle. INTRACELLULAR CALCIUM LEVELSEstimates of the intracellular free calcium concentration of 0.1 and 1 M in the model organism Escherichia coli have been obtained with Fura-2 {1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran -5 -oxy] -2-(2Ј -amino -5Ј -methylphenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid} (24, 77) and aequorin (85), respectively. Such levels are similar to those in eukaryotic cells and are a 1,000 times less than those typically found outside the cell. Three factors are considered responsible for this low level: the low permeability of the envelope with tightly controlled influx mechanisms, a high buffering capacity, and effective export systems. CALCIUM INFLUXIn eukaryotic cells, a number of mechanisms for gated entry of calcium have been characterized. Families of calcium channels have been identified, which can be classified broadly by the stimulus for channel opening into voltage-operated, receptoroperated, mechanically operated or tonically active calcium channels (83). In particular, eukaryotic L-type, voltage-operated calcium channels (VOCCs) are activated by membrane depolari...

Objective Clinical implications of asymptomatic cases of the novel coronavirus disease 2019 (COVID-19) in nursing homes remain poorly understood. We assessed the association of symptom status and medical comorbidities on mortality and hospitalization risk associated with COVID-19 in residents of a large nursing home system. Design Retrospective cohort study. Setting and Participants 1,970 residents from 15 nursing home facilities with universal COVID-19 testing in Maryland. Methods We used descriptive statistics to compare baseline characteristics, logistic regression to assess the association of comorbidities with COVID-19, and Cox regression to assess the association of asymptomatic and symptomatic COVID-19 with mortality and hospitalization. We assessed the association of comorbidities with mortality and hospitalization risk. Symptom status was assessed at the time of the first test. Maximum follow-up was 94 days. Results Among the 1,970 residents (mean age 73.8, 57% female, 68% Black), 752 (38.2%) were positive on their first test. Residents who were positive for COVID-19 and had multiple symptoms at the time of testing had the highest risk of mortality (HR 4.44; 95% CI: 2.97, 6.65) and hospitalization (SHR 2.38; 95% CI: 1.70, 3.33), even after accounting for comorbidity burden. Cases who were asymptomatic at testing had a higher risk of mortality (HR 2.92; 95% CI: 1.95, 4.35), but not hospitalization (HR 1.06; 95% CI: 0.82, 1.38) compared to those who were negative for COVID-19. Of 52 SARS-CoV-2 positive residents who were asymptomatic at the time of testing and were closely monitored for 14 days at one facility, only 6 (11.6%) developed symptoms. Conclusions and Implications Asymptomatic infection with SARS-CoV-2 in the nursing home setting was associated with increased risk of death suggesting a need for closer monitoring of these residents, particularly those with underlying cardiovascular and respiratory comorbidities.

On August 11, 2020, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in nursing homes once it is introduced (1,2). To prevent outbreaks, more data are needed to identify sources of introduction and means of transmission within nursing homes. Nursing home residents who receive hemodialysis (dialysis) might be at higher risk for SARS-CoV-2 infections because of their frequent exposures outside the nursing home to both community dialysis patients and staff members at dialysis centers (3). Investigation of a COVID-19 outbreak in a Maryland nursing home (facility A) identified a higher prevalence of infection among residents undergoing dialysis (47%; 15 of 32) than among those not receiving dialysis (16%; 22 of 138) (p<0.001). Among residents with COVID-19, the 30-day hospitalization rate among those receiving dialysis (53%) was higher than that among residents not receiving dialysis (18%) (p = 0.03); the proportion of dialysis patients who died was 40% compared with those who did not receive dialysis (27%) (p = 0.42). Careful consideration of infection control practices throughout the dialysis process (e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting), clear communication between nursing homes and dialysis centers, and coordination of testing practices between these sites are critical to preventing COVID-19 outbreaks in this medically vulnerable population. In April 2020, a COVID-19 outbreak occurred at a Maryland nursing home (facility A), a 200-bed skilled nursing facility specializing in postacute and long-term care, with an independently operated dialysis center co-located on site. In Maryland, during the month of April, approximately 25% of all SARS-CoV-2 tests had positive results when considering the rolling 7-day average, and approximately half of nursing homes in the state had active outbreaks. † The Maryland Department of Health conducted SARS-CoV-2 testing for symptomatic nursing home residents with a 3-5-day turnaround time for results. Because of the evolving outbreak and limited testing capacity at the health department, a Johns Hopkins response team provided SARS-CoV-2 testing with a 24-hour turnaround * These authors contributed equally to this work. † https://coronavirus.maryland.gov/.

An innovative approach, Integrated Care Transitions Approach (ICTA), is proposed that incorporates the best practices of the four models discussed in this article and factors identified as essential for an effective care transition while addressing limitations of existing transitional care models. ICTA's four key characteristics and seven key elements are unique and stem from factors that help achieve effective care transitions.

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