A Potential Association between Ribonuclease 1 Dynamics in the Blood and the Outcome in COVID-19 Patients.

The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus is the most recent and well-known outbreak of a coronavirus. RNase 1 is a small endogenous antimicrobial polypeptide that possesses antiviral activity against viral diseases. In this study, we investigated a potential association between ribonuclease 1 and the outcome in COVID-19 patients and the impact of increased and decreased RNase 1 levels serum during the course of the disease. Therefore, two patient populations, Cohort A (n = 35) and B (n = 80), were subclassified into two groups, in which the RNase 1 concentration increased or decreased from time point one to time point two. We show that the RNase 1 serum levels significantly increased in the increasing group of both cohorts (p = 0.0171; p < 0.0001). We detect that patients in the increasing group who died had significantly higher RNase 1 serum levels at both time points in Cohort A (p = 0.0170; p = 0.0393) and Cohort B (p = 0.0253; p = 0.0034) than patients who survived. Additionally, we measured a significant correlation of RNase 1 serum levels with serum creatinine as well as creatinine clearance in the increasing and decreasing group at both time points of Cohort A. Based on these results, there is now good evidence that RNase 1 may play a role in renal dysfunction associated with ICU COVID-19 patients and that increasing RNase 1 serum level may be a potential biomarker to predict outcome in COVID-19 patients.

The association of psychological protective factors with caregiver mental health outcomes.

The primary objectives were to investigate the association of resilience, purpose-in-life, and social connections in additive combinations with mental health outcomes of caregivers: 1) reduced levels of loneliness and/or depression; and 2) higher levels of positive perception of aging and quality of life. The study sample was identified from adults age ≥65, who had completed a survey during May-June 2018 or May-June 2019, and self-identified as caregivers (N=1,015; 15.4%). Resilience, purpose-in-life, and social connections were dichotomized as high/low; then counted with equal weighting 0 to 3. Among caregiver respondents, 24%, 29%, 32%, and 15% had 0, 1, 2, or 3 of these protective factors, respectively. As the number of protective factors increased, loneliness and depression decreased and positive perception of aging and quality of life increased. Caregiver interventions that include a focus on psychological protective factors may help to buffer caregiving-related stress thereby improving mental health and quality of life.

DAMPs Released from Proinflammatory Macrophages Induce Inflammation in Cardiomyocytes via Activation of TLR4 and TNFR.

Cardiac dysfunction is a life-threatening complication in sepsis. Upon infection and cardiac stress, the cardiac macrophage population expands. Recruited macrophages exhibit a predominantly proinflammatory phenotype and release danger-associated molecular patterns (DAMPs) that contribute to cardiac dysfunction. However, the underlying pathomechanisms are highly complex and not fully understood. Here, we utilized an indirect macrophage-cardiomyocyte co-culture model to study the effects of proinflammatory macrophages on the activation of different cardiac receptors (TLR3, TLR4, and TNFR) and their role in cardiac inflammation and caspase-3/7 activation. The stimulation of cardiomyocytes with conditioned medium of LPS-stimulated macrophages resulted in elevated IL-6 protein concentrations and relative IL-6 and TNFα mRNA levels. Conditioned medium from LPS-stimulated macrophages also induced NFκB translocation and increased caspase-3/7 activation in cardiomyocytes. Analyzing the role of different cardiac receptors, we found that TLR4 and TNFR inhibition reduces cardiac inflammation and that the inhibition of TNFR prevents NFκB translocation into the nuclei of cardiomyocytes, induced by exposure to conditioned medium of proinflammatory macrophages. Moreover, we demonstrated that TLR3 inhibition reduces macrophage-mediated caspase-3/7 activation. Our results suggest that the immune response of macrophages under inflammatory conditions leads to the release of DAMPs, such as eRNA and cytokines, which in turn induce cardiomyocyte dysfunction. Thus, the data obtained in this study contribute to a better understanding of the pathophysiological mechanisms of cardiac dysfunction.

The association of increasing resilience with positive health outcomes among older adults.

Our objective was to investigate three levels of resilience (low, medium, and high), identify associated characteristics, and measure the impact of increasing resilience on quality of life (QOL), healthcare utilization and expenditures, and preventive services compliance. The study sample was identified from adults age ≥65 who completed surveys during May-June 2019 (N=3,573). Other protective factors, including purpose-in-life, optimism, locus of control, and social connections, were dichotomized as high/low and counted with equal weighting (0 to 4). Among survey respondents, the prevalence of low, medium, and high resilience levels was 27%, 29%, and 44%, respectively. The strongest predictors of medium and high resilience included increasing number of other protective factors, lower stress, and no depression. Individuals with medium and high resilience had significantly higher QOL and lower healthcare utilization and expenditures. Resilience strategies integrated into healthy aging programming could be associated with improvements in QOL and/or healthcare utilization and expenditure outcomes.

The association of resilience, social connections, and internal locus of control with pain outcomes among older adults.

Our objective was to investigate the hypothesis that psychological resources, including resilience, social connections, and internal locus of control, separately and in additive combinations, would be associated with selected pain outcomes: 1) days of opioid use and 2) medical/drug expenditures over 2 years. A mailed survey was sent to a stratified sample of older adults age≥65 with diagnosed back pain, osteoarthritis, and/or rheumatoid arthritis. Each of the resources was dichotomized as high/low and/or counted with equal weighting. Among respondents (N=3,131), the prevalence of mild/no and moderate/severe pain severity was 59% and 41%, respectively. As hypothesized, each resource was associated with lower levels of pain; additively, reported pain severity decreased as the number of resources increased. For moderate/severe pain, there was reduced opioid use among those with more resources; and, for mild/no pain, decreased medical/drug expenditures among those with ≥2 resources. Interventions that integrate psychological resources may enhance their effectiveness.

The association of physical activity with loneliness, social isolation, and selected psychological protective factors among older adults.

The primary objectives were to investigate the association of physical activity levels with 1) loneliness and social isolation; 2) protective factors: resilience, purpose-in-life, and perception of aging; and 3) the impact of these factors on healthcare expenditure patterns across physical activity levels. The study sample was identified from adults age ≥65 who completed a health survey in 2018 or 2019 (N=6,652). Among survey respondents, the prevalence of low, moderate, and high physical activity levels was 29%, 31%, and 41%, respectively. Moderate and high physical activity were associated with 15%-30% lower likelihoods of loneliness and social isolation; and with 27% to 150% higher protective factors. In addition, physical activity was associated with the mitigation of increased healthcare expenditures associated with loneliness, social isolation, and low levels of protective factors. Thus, physical activity could serve as an intervention to reduce loneliness and social isolation, augment protective factors, and mitigate excess healthcare expenditures.

The impact of COVID-19 on older adults: Results from an annual survey.

OBJECTIVES: Assess well-being among older adults through secondary analysis measured during an annual survey in 2018, 2019, and 2020, to determine trends from before and during the COVID-19 pandemic. METHODS: Mailed surveys sent annually included measures related to various psychosocial factors. MAIN FINDINGS: Response rates were 29% in 2018, 25% in 2019, and 24% in 2020. Most respondents reported average or high resilience (89% 2018-2020), high purpose (64% in 2018 and 2019, 63% in 2020), moderate optimism (46% in 2019, 44% in 2020) and low stress (88% in 2019 and 2020). Reported loneliness increased 13% from 2018 to 2020. In 2020, only 45% reported high comfort with technology, decreasing with age (>75). PRINCIPAL CONCLUSION: Psychosocial well-being of respondents were doing well despite changes related to COVID-19. However, increased loneliness may negatively impact long-term health outcomes; thus, a focus on technology options to stay socially connected and access healthcare are needed.

Repetitive Treatment with Volatile Anesthetics Does Not Affect the In Vivo Plasma Concentration and Composition of Extracellular Vesicles in Rats.

BACKGROUND: Anesthetic-induced preconditioning (AIP) with volatile anesthetics is a well-known experimental technique to protect tissues from ischemic injury or oxidative stress. Additionally, plasmatic extracellular vesicle (EV) populations and their cargo are known to be affected by AIP in vitro, and to provide organ protective properties via their cargo. We investigated whether AIP would affect the generation of EVs in an in vivo rat model. METHODS: Twenty male Sprague Dawley rats received a repetitive treatment with either isoflurane or with sevoflurane for a duration of 4 or 8 weeks. EVs from blood plasma were characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM) and Western blot. A scratch assay (H9C2 cardiomyoblast cell line) was performed to investigate the protective capabilities of the isolated EVs. RESULTS: TEM images as well as Western blot analysis indicated that EVs were successfully isolated. The AIP changed the flotillin and CD63 expression on the EV surface, but not the EV concentration. The scratch assay did not show increased cell migration and/or proliferation after EV treatment. CONCLUSION: AIP in rats changed the cargo of EVs but had no effect on EV concentration or cell migration/proliferation. Future studies are needed to investigate the cargo on a miRNA level and to investigate the properties of these EVs in additional functional experiments.

The additive impact of multiple psychosocial protective factors on selected health outcomes among older adults.

Our objective was to investigate the additive properties of five psychosocial protective factors: purpose-in-life, resilience, optimism, internal locus of control and social connections. Self-reported psychological (depression, stress) and physical (health status, functionality) health outcomes and measured healthcare utilization and expenditures were included. The study sample was identified from adults age ≥65 who completed a health survey during May-June 2019 (N = 3,577). Each of the five protective factors was dichotomized as high/low (1/0) and counted with equal weighting. The protective factors were additive such that significant improvements in psychological and physical health outcomes were evident across factor subgroups: as the number of factors increased, health outcomes improved. The magnitude of the improvements was greatest between 0 and 1 factor. In addition, a significant linear trend for reduced healthcare expenditures ($1,356 reduction per factor added) was evident. Interventions promoting at least one protective factor would be beneficial for older adult populations.

EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research.

We argue that the field of extracellular vesicle (EV) biology needs more transparent reporting to facilitate interpretation and replication of experiments. To achieve this, we describe EV-TRACK, a crowdsourcing knowledgebase (http://evtrack.org) that centralizes EV biology and methodology with the goal of stimulating authors, reviewers, editors and funders to put experimental guidelines into practice.

The association of pain locus of control with pain outcomes among older adults.

Our primary objective was to 1) determine the prevalence of pain locus of control (LOC) subscales in a population of older adults with pain conditions, and 2) estimate their associated protective effects on pain outcomes. A mailed survey was sent to a stratified sample of older adults age≥65 with diagnosed back pain, osteoarthritis and/or rheumatoid arthritis. Multivariate logistic regression modeling was used to determine the relative protective associations of positive resources, including LOC, resilience and social networks, on pain outcomes. Among respondents (N = 3,824), 31% were identified as internal; 34% as powerful others; and 35% as chance. In adjusted models, internal was associated with outcomes of lower pain severity, reduced chronic opioid use and increased physical functionality. Powerful others was partially protective; chance was associated with the poorest outcomes. Multidimensional pain programs should incorporate the enhancement of positive resources, including LOC, to maximize the effectiveness of pain management strategies.

The impact of internal locus of control on healthcare utilization, expenditures, and health status across older adult income levels.

Our objectives were to 1) determine the prevalence of locus of control (LOC) dimensions stratified by older adult income levels; 2) characterize internal LOC attributes within income subgroups; and 3) investigate LOC associations with healthcare utilization and expenditures; self-rated health and functionality. The survey sample was identified from adults age ≥65 years with diagnosed pain conditions. Internal LOC characteristics were determined from logistic regressions; outcomes regression-adjusted. Among respondents, internal prevalence for low (N = 554), medium (N = 1,394) and high income (N = 2040) was 27%, 30% and 30%, respectively. Internal was associated with high resilience, less stress, exercise and less opioid use across income levels. Lower-income internal was additionally associated with diverse social networks, physical therapy and less drug use. Those with high internal generally had lower healthcare utilization and expenditures; better self-rated health and functionality. Internal LOC is a powerful positive resource associated with better health outcomes, especially influential for lower income.

Characteristics associated with transition from opioid initiation to chronic opioid use among opioid-naïve older adults.

Our primary objective was to determine the prevalence and characteristics of opioid-naïve older adults who initiated opioids and transitioned to chronic use. Study populations included older adults ≥ 65years with continuous medical and drug plan enrollment one-year prior to opioid initiation (pre-period) through one-year after initiation (post-period). Characteristics were determined using multivariate logistic regression. Among eligible insureds (N = 180,498), 70% used only the initial opioid prescription; 30% continued to use opioids requiring ≥ 2 prescriptions with ≥ 15 days' supply. Overall, 6% transitioned to chronic use > 90days. Characteristics associated with chronic use included: (1) Low income, older, females, in poor health, with new/chronic back pain; (2) opioid initiation with long-acting opioids or tramadol; (3) prescriptions for other pain, sleep or antipsychotic medications; and (4) indications of pre and/or post mental health issues. Careful screening, monitoring and/or alternative non-opioid pain management strategies may be warranted for those at risk for chronic opioid use.

Prevalence and characteristics associated with high dose opioid users among older adults.

Our primary objective was to determine the prevalence and characteristics of high dose opioid users among older adults. Study populations included adults ≥65 years with: 1) 12-month continuous medical plan enrollment; and 2) at least 2 opioid prescriptions with a cumulative day supply ≥15 days. Opioid users were categorized as high dose >120 milligram morphine equivalents (MME) per day or lower dose ≤120 MMEs per day. Among eligible insureds, 3% (N = 7616) were identified as high dose opioid users. Compared to lower dose users, high dose opioid users were male, younger, depressed, in poorer health, had back pain, used benzodiazepines and/or sleep medications, and used 4 or more pharmacies. The prevalence of high dose opioid users was relatively small but users were characterized by a complex mix of physical and mental health issues. Interventions to reduce reliance on opioids may need mental health management to promote more effective pain management.

Remote Ischemic Preconditioning Does Not Affect the Release of Humoral Factors in Propofol-Anesthetized Cardiac Surgery Patients: A Secondary Analysis of the RIPHeart Study.

In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3ß), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3ß, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.

Practical non-pharmacological intervention approaches for sleep problems among older adults.

Poor sleep is common among older adults, often caused by multiple underlying factors such as chronic stress. Poor sleep is subsequently associated with negative health outcomes including higher morbidity and mortality. Our primary purpose is to explore practical non-pharmacological intervention approaches integrating stress management to improve sleep quality among older adults. In doing so, we highlight approaches that appear to hold promise in real-world settings with older individuals. We conducted a tailored literature review specifically on approaches to improve sleep quality among older adults, with emphasis on those integrating stress management. Online search engines were reviewed to identify research in these areas. Various non-pharmacological intervention approaches, such as mindfulness and cognitive behavioral therapy, have shown promise in improving sleep quality and health outcomes within this population. Those integrating chronic stress management appear to be particularly successful. Thus further development of multidimensional sleep interventions integrating stress management with seniors is warranted.

Caregivers for older adults: Prevalence, characteristics, and health care utilization and expenditures.

The purpose of this study was to provide an overview of caregiver prevalence and characteristics and to estimate the impact of caregiving on health care utilization and expenditures among AARP® Medicare Supplement insureds to inform caregiver intervention strategies. A subgroup with live-in partners was used to investigate the additional effect of live-in health status on caregiver health. Multivariate regression models were utilized to determine caregivers' characteristics and associated impacts on their health care utilization and expenditures. Among respondents (n = 18,928), 14.9% self-identified as caregivers. The strongest characteristics included being younger, healthier, but reporting depression or loneliness. Caregivers of sicker live-ins were female, older and indicated moderate loneliness; caregivers of healthier live-ins were younger, healthier, but reported severe loneliness. Caregivers had significantly lower inpatient admissions and medical and prescription drug expenditures. These results indicated an adverse impact on psychological health associated with caregiving but no evidence of a negative impact on physical health.

A qualitative study to examine older adults' perceptions of health: Keys to aging successfully.

Older adult health is often defined in clinical terms. Research has demonstrated that many older adults self-report aging successfully regardless of clinical health status. This qualitative study used claims data to identify older adults on three levels of health status: healthy and active, managing diseases, or very sick, to better understand how health is defined and maintained. In total, 32 participants from two cities were interviewed. Interviews were audio- and video-recorded and then transcribed. Thematic analysis identified five themes: disconnectedness between objective and subjective health; health defined to include psychological and social components; resilience and coping mechanisms indicative of successful aging; social support systems integral to health; and the goal of maintaining functioning. These results indicate the importance of individual perceptions of health rather than just counts of chronic diseases. Health management programs should provide holistic approaches to maximize health outcomes and to promote successful aging.

Argon Induces Protective Effects in Cardiomyocytes during the Second Window of Preconditioning.

Increasing evidence indicates that argon has organoprotective properties. So far, the underlying mechanisms remain poorly understood. Therefore, we investigated the effect of argon preconditioning in cardiomyocytes within the first and second window of preconditioning. Primary isolated cardiomyocytes from neonatal rats were subjected to 50% argon for 1 h, and subsequently exposed to a sublethal dosage of hypoxia (<1% O2) for 5 h either within the first (0-3 h) or second window (24-48 h) of preconditioning. Subsequently, the cell viability and proliferation was measured. The argon-induced effects were assessed by evaluation of mRNA and protein expression after preconditioning. Argon preconditioning did not show any cardioprotective effects in the early window of preconditioning, whereas it leads to a significant increase of cell viability 24 h after preconditioning compared to untreated cells (p = 0.015) independent of proliferation. Argon-preconditioning significantly increased the mRNA expression of heat shock protein (HSP) B1 (HSP27) (p = 0.048), superoxide dismutase 2 (SOD2) (p = 0.001), vascular endothelial growth factor (VEGF) (p < 0.001) and inducible nitric oxide synthase (iNOS) (p = 0.001). No difference was found with respect to activation of pro-survival kinases in the early and late window of preconditioning. The findings provide the first evidence of argon-induced effects on the survival of cardiomyocytes during the second window of preconditioning, which may be mediated through the induction of HSP27, SOD2, VEGF and iNOS.

Determination of direct oral anticoagulants from human serum samples.

Dabigatran, rivaroxaban, and apixaban are direct oral anticoagulants (DOAC) inhibiting thrombin or factor Xa and effectively preventing thromboembolic complications using fixed doses without need for laboratory-guided dose adjustment. Plasma samples are needed to determine the actual concentration or activity of DOACs, which may be required for special patient populations such as those with acute deterioration of renal function due to any disease, before surgical interventions, during bleeding or thrombotic episodes while on therapy with DOACs, the elderly and youngest populations, unexpected pregnancy, suspicion of overdose and toxication, and to control adherence to therapy. Serum samples have several advantages over plasma samples such as no need of sampling with a specific coagulation tube, reduced pre-analytical errors, and longer storage stability. Determination of rivaroxaban and apixaban from serum samples of patients on treatment performed well and better than samples of patients treated with dabigatran compared with plasma samples. Specific adaption to automated coagulation platforms may improve the performance of the assays from serum samples.