Loneliness Among US Adults During the Early Phase of the COVID-19 Pandemic: Findings From the COVID-19 Coping Study

We aimed to estimate the prevalence of loneliness and identify the key sociodemographic, employment, living, and health-related risk factors for loneliness among middle-aged and older adults during the early COVID-19 pandemic in the US, when shelter-in-place and social distancing restrictions were in place for much of the country. Data were collected from online questionnaires in the COVID-19 Coping Study, a national study of 6,938 US adults aged 55-110 years, from April 2nd through May 31st, 2020. We estimated the population-weighted prevalence of loneliness (scores of ≥6/9 on the 3-item UCLA Loneliness Scale), overall and according to sociodemographic, employment, living, and health-related factors. We used population-weighted modified Poisson regression models to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the associations between these factors and loneliness, adjusted for age, sex, race, ethnicity, and education. Overall, 29.5% (95% CI: 27.9%, 31.3%) of US adults aged 55-110 were considered high in loneliness in April and May, 2020. In population-weighted, adjusted models, loneliness was most frequent among those with depression, those who were divorced or separated, those who lived alone, those diagnosed with multiple comorbid conditions, and individuals who were unemployed prior to the pandemic. In conclusion, we identified subpopulations of middle-aged and older US adults that were highly affected by loneliness during a period when COVID-19 shelter-in-place orders were in place across most of the country. These insights may inform the allocation of recourses to mitigate loneliness during times of restricted activity.

Engineered osteoclasts as living treatment materials for heterotopic ossification therapy

Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as “living treatment agents” for cell therapy.

Restricted activity and negative self-assessment of health as risk indicators for latent disability analysis performed on population groups different as per sex and age

A necessity to detect and assess probable latent disability makes the present research vital; it can be done using available parameters that characterize population health. Our research object was adult population living in the Russian Federation. Our research goal was to reveal a relation between self-assessment of health and health-related restrictions among respondents form different sex and age groups in order to determine latent disability among overall RF population. Previously Russian researchers revealed certain relations between disability and low self-assessment of one’s health. However, there was no profound study on an issue related to using such criteria as «negative self-assessment of health» and «restricted activities» used to reveal latent dis-ability. This aspect has not been examined in great detail in domestic research and it makes the present work truly vital. We took data collected via the Russian sociologic study performed within the European sociological study (ESS) in 2018–2019 as well as data from sampling studies on pop-ulation in the RF performed by the Federal Statistics Service in 2018 and 2019. To analyze a relation between self-assessment of health and existing restricted activity, we calculated Kramer’s coefficients for different sex and age groups of respondents who took part in the Russian sociologic study. Calculated Kramer’s coefficient values indicate there is an average relation between such parameters as «self-assessment of health» and «existing restricted activity». We established that 7% of respondents who were not disabled still had health characteristics implying there was a disability risk. It was shown that use of such criteria as «self-assessment of health» and «existing restricted activities» allowed more authentic assessment of latent disability among males aged 50–59 and women aged 20–29, 30–39, and 40–49. In future we plan to obtain more accurate results using data from other representative sociologic studies on population including regional ones.

Restricted activity and negative self-assessment of health as risk indicators for latent disability analysis performed on population groups different as per sex and age

A necessity to detect and assess probable latent disability makes the present research vital; it can be done using available parameters that characterize population health. Our research object was adult population living in the Russian Federation. Our research goal was to reveal a relation between self-assessment of health and health-related restrictions among respondents form different sex and age groups in order to determine latent disability among overall RF population. Previously Russian researchers revealed certain relations between disability and low self-assessment of one’s health. However, there was no profound study on an issue related to using such criteria as «negative self-assessment of health» and «restricted activities» used to reveal latent dis-ability. This aspect has not been examined in great detail in domestic research and it makes the present work truly vital. We took data collected via the Russian sociologic study performed within the European sociological study (ESS) in 2018–2019 as well as data from sampling studies on pop-ulation in the RF performed by the Federal Statistics Service in 2018 and 2019. To analyze a relation between self-assessment of health and existing restricted activity, we calculated Kramer’s coefficients for different sex and age groups of respondents who took part in the Russian sociologic study. Calculated Kramer’s coefficient values indicate there is an average relation between such parameters as «self-assessment of health» and «existing restricted activity». We established that 7% of respondents who were not disabled still had health characteristics implying there was a disability risk. It was shown that use of such criteria as «self-assessment of health» and «existing restricted activities» allowed more authentic assessment of latent disability among males aged 50–59 and women aged 20–29, 30–39, and 40–49. In future we plan to obtain more accurate results using data from other representative sociologic studies on population including regional ones.

SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2alow NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Such NK cell differentiation was lacking in SIVmac-infected macaques. Adaptive NK cells displayed no increased NKG2C expression. This study reveals a previously unknown profile of NK cell adaptation to a viral infection, thus accelerating strategies toward NK-cell directed therapies and viral control in tissues.

Divergent Evolution of Eukaryotic CC- and A-Adding Enzymes

Synthesis of the CCA end of essential tRNAs is performed either by CCA-adding enzymes or as a collaboration between enzymes restricted to CC- and A-incorporation. While the occurrence of such tRNA nucleotidyltransferases with partial activities seemed to be restricted to Bacteria, the first example of such split CCA-adding activities was reported in Schizosaccharomyces pombe. Here, we demonstrate that the choanoflagellate Salpingoeca rosetta also carries CC- and A-adding enzymes. However, these enzymes have distinct evolutionary origins. Furthermore, the restricted activity of the eukaryotic CC-adding enzymes has evolved in a different way compared to their bacterial counterparts. Yet, the molecular basis is very similar, as highly conserved positions within a catalytically important flexible loop region are missing in the CC-adding enzymes. For both the CC-adding enzymes from S. rosetta as well as S. pombe, introduction of the loop elements from closely related enzymes with full activity was able to restore CCA-addition, corroborating the significance of this loop in the evolution of bacterial as well as eukaryotic tRNA nucleotidyltransferases. Our data demonstrate that partial CC- and A-adding activities in Bacteria and Eukaryotes are based on the same mechanistic principles but, surprisingly, originate from different evolutionary events.

Factors Associated With Insidious and Noninsidious Disability

Background Although disability is often precipitated by an illness/injury, it may arise insidiously. Our objectives were to identify the factors associated with the development of insidious and noninsidious disability and to determine whether these risk factors differ between the two types of disability. Methods We prospectively evaluated 754 community-living persons, 70+ years, from 1998 to 2016. The unit of analysis was an 18-month person-interval, with risk factors assessed at the start of each interval. Disability in four activities of daily living and exposure to intervening events, defined as illnesses/injuries leading to hospitalization, emergency department visits, or restricted activity, were assessed each month. Insidious and noninsidious disability were defined based on the absence and presence of an intervening event. Results The rate of noninsidious disability (21.7%) was twice that of insidious disability (10.8%). In multivariable recurrent-event Cox analyses, six factors were associated with both disability outcomes: non-Hispanic white race, lower extremity muscle weakness, poor manual dexterity, and (most strongly) frailty, cognitive impairment, and low functional self-efficacy. Three factors were associated with only noninsidious disability (older age, number of chronic conditions, and depressive symptoms), whereas four were associated with only insidious disability (female sex, lives with others, low SPPB score, and upper extremity weakness). The modest differences in risk factors identified for the two outcomes in multivariable analyses were less apparent in the bivariate analyses. Conclusions Although arising from different mechanisms, insidious and noninsidious disability share a similar set of risk factors. Interventions to prevent disability should prioritize this shared set of risk factors.

CHRONIC PAIN, FEAR OF FALLING, AND RESTRICTED ACTIVITY DAYS IN AN OLDER POPULATION

Both chronic pain and fear of falling can lead to activity restriction and increased fall risk among vulnerable elders. Little is known about pain characteristics that may be associated with fear of falling, contributing to restricted activity. We studied 765 adults aged ≥65y (mean=78.9y) in the MOBILIZE Boston Study, to evaluate the cross-sectional relationship between pain characteristics and fear of falling measured using the Falls Efficacy Scale (FES). In addition, we examined the impact of pain and fear of falling on restricted activity. We measured 3 domains of global pain: pain distribution (none, single site or multisite pain), and Brief Pain Inventory subscales of pain severity and pain interference. Restricted activity days (RADs) refer to the count of self-reported days of reduced activity due to illness or injury in the previous 12 months. We performed multivariable logistic regressions predicting fear of falling (FES<90/100) adjusted for sociodemographics, fall history and fall risk factors. Participants with multisite pain or moderate-to-high pain interference ratings were more likely to have fear of falling (adj.OR 1.97, 95%CI 1.05-3.67; adj.OR 4.02, 95%CI 2.0-8.06, respectively). Pain severity was not associated with FES. Older adults with multisite pain and fear of falling reported significantly more RADs than those with multisite pain without fear of falling (79±135 and 26±74 RADs, respectively; test for pain x FES interaction, p=0.01). Older adults with chronic pain have greater fear of falling which may contribute to restricted activity. Efforts are needed to increase activity and falls efficacy among older adults with chronic pain.