Biological age is increased by stress and restored upon recovery.

Aging is classically conceptualized as an ever-increasing trajectory of damage accumulation and loss of function, leading to increases in morbidity and mortality. However, recent in vitro studies have raised the possibility of age reversal. Here, we report that biological age is fluid and exhibits rapid changes in both directions. At epigenetic, transcriptomic, and metabolomic levels, we find that the biological age of young mice is increased by heterochronic parabiosis and restored following surgical detachment. We also identify transient changes in biological age during major surgery, pregnancy, and severe COVID-19 in humans and/or mice. Together, these data show that biological age undergoes a rapid increase in response to diverse forms of stress, which is reversed following recovery from stress. Our study uncovers a new layer of aging dynamics that should be considered in future studies. The elevation of biological age by stress may be a quantifiable and actionable target for future interventions.

User Experience of COVID-19 Chatbots: Scoping Review.

BACKGROUND: The COVID-19 pandemic has had global impacts and caused some health systems to experience substantial pressure. The need for accurate health information has been felt widely. Chatbots have great potential to reach people with authoritative information, and a number of chatbots have been quickly developed to disseminate information about COVID-19. However, little is known about user experiences of and perspectives on these tools. OBJECTIVE: This study aimed to describe what is known about the user experience and user uptake of COVID-19 chatbots. METHODS: A scoping review was carried out in June 2021 using keywords to cover the literature concerning chatbots, user engagement, and COVID-19. The search strategy included databases covering health, communication, marketing, and the COVID-19 pandemic specifically, including MEDLINE Ovid, Embase, CINAHL, ACM Digital Library, Emerald, and EBSCO. Studies that assessed the design, marketing, and user features of COVID-19 chatbots or those that explored user perspectives and experience were included. We excluded papers that were not related to COVID-19; did not include any reporting on user perspectives, experience, or the general use of chatbot features or marketing; or where a version was not available in English. The authors independently screened results for inclusion, using both backward and forward citation checking of the included papers. A thematic analysis was carried out with the included papers. RESULTS: A total of 517 papers were sourced from the literature, and 10 were included in the final review. Our scoping review identified a number of factors impacting adoption and engagement including content, trust, digital ability, and acceptability. The papers included discussions about chatbots developed for COVID-19 screening and general COVID-19 information, as well as studies investigating user perceptions and opinions on COVID-19 chatbots. CONCLUSIONS: The COVID-19 pandemic presented a unique and specific challenge for digital health interventions. Design and implementation were required at a rapid speed as digital health service adoption accelerated globally. Chatbots for COVID-19 have been developed quickly as the pandemic has challenged health systems. There is a need for more comprehensive and routine reporting of factors impacting adoption and engagement. This paper has shown both the potential of chatbots to reach users in an emergency and the need to better understand how users engage and what they want.

Changing tenant covenant perceptions and flexibility in the lease model in UK city centres

The retailing industry in the UK is experiencing unprecedented structural change. The impact on retailers has often dominated headlines, along with the impacts on local services and economies, but with little attention given to the implications for property owners and practitioners. Exploring and understanding the responsiveness of landlords, and their behaviours, is essential to understanding the adaptiveness of a retailing system. This study employs semi-structured interviews to examine the short- and long-term changes in the retail market and the actions of landlords in response. The findings span the period prior to and during the first year of the Covid-19 pandemic in 2020, and reveal that fundamental changes have occurred to establish tenant covenant norms and the traditional retail leasing model. The paper explores these changes, including a shift in tenant risk, reposition of the leasing model in favour of tenants, generally, and greater application of turnover rents. The pressing challenge for current valuation practitioners, therefore, is to incorporate these fundamental changes within the market into the pricing of retail assets. Significant progress in this area to date, as explored in the paper, has been limited although greater application of discounted cashflow techniques is set to be encouraged by the RICS.

The experience economy in UK city centres: A multidimensional and interconnected response to the ‘death of the high street'?

Since the 1990s the UK's city centre high streets have been losing market share to out-of-town shopping and e-retailing. The shocks of the Global Financial Crisis and COVID-19 have hastened this and precipitated widespread store closures. The experience economy is increasingly promoted as a means to avert the ‘death of the high street', and this prompts our study of its evolution. An exploration of the literature reveals the experience economy to be an interconnected phenomenon focused on the creation of a memorable event that elicits a sensory response via multi-dimensional innovation and design. Using this to guide our empirical work, we undertake a comparative mixed method longitudinal case study of five UK city centres. We initially chart the changing manifestations of experience uses before analysing supporting interviews and observations that reveal three interconnected layers of the experience economy: in-store commercial experiences;leisure and entertainment-orientated adaptations to shopping centres and department stores;and the wider regeneration of the public realm. Implications for city centre management are discussed. (English) [ FROM AUTHOR]

Changing tenant covenant perceptions and flexibility in the lease model in UK city centres

The retailing industry in the UK is experiencing unprecedented structural change. The impact on retailers has often dominated headlines, along with the impacts on local services and economies, but with little attention given to the implications for property owners and practitioners. Exploring and understanding the responsiveness of landlords, and their behaviours, is essential to understanding the adaptiveness of a retailing system. This study employs semistructured interviews to examine the short- and long-term changes in the retail market and the actions of landlords in response. The findings span the period prior to and during the first year of the Covid-19 pandemic in 2020, and reveal that fundamental changes have occurred to establish tenant covenant norms and the traditional retail leasing model. The paper explores these changes, including a shift in tenant risk, reposition of the leasing model in favour of tenants, generally, and greater application of turnover rents. The pressing challenge for current valuation practitioners, therefore, is to incorporate these fundamental changes within the market into the pricing of retail assets. Significant progress in this area to date, as explored in the paper, has been limited although greater application of discounted cashflow techniques is set to be encouraged by the RICS.

Natural History of Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis.

BACKGROUND: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication. METHODS: Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured. RESULTS: Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes. CONCLUSIONS: COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

The SWIS trial: Protocol of a pragmatic cluster randomised controlled trial of school based social work.

BACKGROUND: Child and family social workers in the UK work closely with other agencies including schools and the police, and typically they are based in local authority offices. This study will evaluate the effectiveness of placing social workers in schools (SWIS) on the need for social care interventions. SWIS was piloted in three local authorities in 2018-2020, and findings from a feasibility study of the pilots suggests SWIS may operate through three key pathways: (1) by enhancing schools' response to safeguarding issues, (2) through increased collaboration between social workers, school staff, and parents, and (3) by improving relationships between social workers and young people. METHODS: The study is a two-arm pragmatic cluster randomised controlled trial building on three feasibility studies which found SWIS to be promising. Social workers will work within secondary schools across local authorities in England. 280 mainstream secondary schools will be randomly allocated with a 1:1 ratio to SWIS or a comparison arm, which will be schools that continue as normal, without a social worker. The primary outcome will be the rate of Child Protection (Section 47) enquiries. Secondary outcomes will comprise rate of referrals to children's social care, rate of Child in Need (Section 17) assessments, days spent in care, and educational attendance and attainment. The study also includes an economic evaluation, and an implementation and process evaluation. Social care outcomes will be measured in July 2022, and educational outcomes will be measured in July 2023. Days in care will be measured at both time points. DISCUSSION: Findings will explore the effectiveness and cost-effectiveness of SWIS on the need for social care interventions. A final report will be published in January 2024. TRIAL REGISTRATION: The study was registered retrospectively with the International Standard Randomised Controlled Trial Number registry on 13.11.2020 (ISRCTN90922032).

Gamification and older adults: Opportunities for gamification to support health promotion initiatives for older adults in the context of COVID-19.

The COVID-19 pandemic has increased reliance on digital service delivery, including the delivery of health promotion initiatives. Health promotion interventions need to carefully consider user engagement. Gamification is a strategy used to engage and motivate people, and evidence shows overall cautious positive results in the use of gamification for older people across a range of health areas although more evidence is needed. Gamification has been used as a strategy in COVID-19 related initiatives and there is potential to build on the evidence to further develop gamification initiatives for those living in the Western Pacific region to impact positively on healthy behaviours and health outcomes.

Feasibility & Preliminary Efficacy of Structured Programming and a Parent Intervention to Mitigate Accelerated Summer BMI Gain: A pilot study.

BackgroundThis study assessed initial feasibility and preliminary efficacy of providing children a free summer day camp and a parent intervention to improve self-regulation and mitigate accelerated summer BMI gain.MethodsThis pilot 2x2 factorial randomized control trial used a mixed methods design to evaluate providing children a free summer day camp (SCV), a parent intervention (PI), and the combination of these two strategies (SCV + PI) to mitigate accelerated summer body mass index (BMI) gain. Feasibility (i.e., recruitment capability, retention, compliance, treatment fidelity, acceptability) was examined using means, standard deviations, and percentages for relevant variables. Changes in BMI were estimated using intent-to-treat and post-hoc dose response analyses via multilevel mixed effects regressions.ResultsA total of 89 families participated, with 24 participants randomized to the PI group, 21 randomized to the SCV group, 23 randomized to the SCV + PI group, and 21 randomized to the control. Parents and children found the summer program acceptable but attendance at the summer program and engagement in the PI were low due to COVID-19 and lack of transportation. Intent-to-treat analyses showed no statistically significant difference between groups in summer BMI gain. Post-hoc dose response analyses showed that for each day (0 to 29) of summer programming children attended they gained - 0.009 (95CI= -0.018, -0.001) less in BMI z-score.ConclusionsEngagement in both the SCV and PI was not ideal and was likely due to COVID-19 and lack of transportation. Providing children with structured summer programming to mitigate accelerated summer BMI gain may be an effective strategy. Thus, a larger trial may be warranted, but more work is needed to ensure children attend the programming.Trial registration: The trial reported herein was prospectively registered at clinicaltrials.gov. Trial #:NCT04608188.

The Effects of Using the Sun Safe App on Sun Health Knowledge and Behaviors of Young Teenagers: Results of Pilot Intervention Studies

Background: A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app—Sun Safe—through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). Objective: The aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. Methods: Young teenagers (aged 12-13 years;N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. Results: Of the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (>50%) reporting that they used a smartphone to access their designated app either “once a fortnight” or “once/twice in total.” Improved sun health knowledge—particularly about the UV Index—was observed in participants who were given access to Sun Safe compared with those who used the placebo (−6.2 [percentage correct] difference in predicted means, 95% CI –12.4 to –0.03;P=.049;2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8;P=.02;Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic–related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by >100 minutes per day (–105 minutes per day difference in predicted means, 95% CI –150 to –59 minutes per day;P=.002;paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). Conclusions: Access to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger sample sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.

Moving on trial: protocol for a pilot randomised controlled trial of models of housing and support to reduce risks of COVID-19 infection and homelessness.

BACKGROUND: It is estimated that around 160,000 households in Britain experience homelessness each year, although no definitive statistics exist. Between March and September 2020, as part of the initial 'Everyone In' government response to COVID-19 in England, 10,566 people were living in emergency accommodation and nearly 18,911 people had been moved into settled accommodation. However, some forms of temporary accommodation may not be suitable as shared facilities make it impossible for people to adhere to government guidelines to reduce the spread of COVID-19. METHODS: This is parallel group, pilot randomised controlled trial. The target is to recruit three local authorities, each of which will recruit 50 participants (thus a total of approximately 150 participants). Individuals are eligible if they are aged 18 and over, in a single-person homeless household, temporarily accommodated by the LA with recourse to public funds. Participants will be randomised to receive settled accommodation (intervention group) or temporary accommodation (control group). The intervention group includes settled housing such as Private Rented Sector (low and medium support), Social Housing (low and medium support), and Housing First (High support). The control group will maintain treatment as usual. The follow-up period will last 6 months. The primary outcome is to assess the feasibility of recruitment, retention, and acceptability of trial processes against progression criteria laid out in a traffic light system (green: all criteria are met, the trial should progress as designed in this pilot; amber: the majority of criteria are met and with adaptations to methods all criteria could be met; red: the minority of criteria are met and the pilot RCT should not proceed). Secondary outcomes include assessment of completeness of data collection at 3 and 6 months and percentage of participants consenting to data linkage, as well as a process evaluation and economic evaluation. DISCUSSION: This trial will address feasibility questions associated with progression to a fully powered effectiveness trial of models of housing to reduce risk of COVID-19 infection and homelessness. TRIAL REGISTRATION: ISRCTN69564614 . Registered on December 16, 2020.

Association of Antineoplastic Therapy With Decreased SARS-CoV-2 Infection Rates in Patients With Cancer.

Importance: Novel therapies for SARS-CoV-2 infection are urgently needed. Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity. Objectives: To determine whether patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates. Design, Setting, and Participants: We used the Library of Integrated Network-Based Cellular Signatures database to identify antineoplastic compounds associated with decreased ACE2 gene expression across cell lines. We then evaluated a retrospective cohort of 1701 patients who were undergoing antineoplastic therapy at Memorial Sloan Kettering Cancer Center in New York, New York, during the COVID-19 pandemic to determine if treatment with an ACE2-lowering antineoplastic was associated with a decreased odds ratio (OR) of SARS-CoV-2 infection. Patients included in the analysis underwent active treatment for cancer and received a SARS-CoV-2 test between March 10 and May 28, 2020. Main Outcome and Measure: The association between potential ACE2-lowering antineoplastic treatment and a positive SARS-CoV-2 test. Results: In the cohort of 1701 patients, SARS-CoV-2 infection rates were determined for 949 (55.8%) female and 752 (44.2%) male patients (mean [SD] age, 63.1 [13.1] years) with diverse cancers receiving antineoplastic therapy. In silico analysis of gene expression signatures after drug treatment identified 91 compounds associated with downregulation of ACE2 across cell lines. Of the total cohort, 215 (12.6%) patients were treated with 8 of these compounds, including 3 mTOR/PI3K inhibitors and 2 antimetabolites. In a multivariable analysis of patients who received an ACE2-lowering antineoplastic adjusting for confounders, 15 of 215 (7.0%) patients had a positive SARS-CoV-2 test compared with 191 of 1486 (12.9%) patients who received other antineoplastic therapies (OR, 0.53; 95% CI, 0.29-0.88). Findings were confirmed in additional sensitivity analyses including cancer type, steroid use, and a propensity-matched subcohort. Gemcitabine treatment was associated with reduced SARS-CoV-2 infection (OR, 0.42; 95% CI, 0.17-0.87). Conclusions and Relevance: In this cohort study, in silico analysis of drug-associated gene expression signatures identified potential ACE2-lowering antineoplastic compounds, including mTOR/PI3K inhibitors and antimetabolites. Patients who received these compounds exhibited statistically significantly lower rates of SARS-CoV-2 infection compared with patients given other antineoplastics. Further evaluation of the biological and clinical anti-SARS-CoV-2 properties of identified antineoplastic compounds is warranted.

Rapid Response to Cytokine Storm Inhibition Using Anakinra in a Patient With COVID-19 Myocarditis.

A 62-year-old woman with coronavirus disease 2019 developed acute respiratory failure and cardiogenic shock in the setting of a systemic hyperinflammatory state and apparent ST-elevation myocardial infarction. Cardiac magnetic resonance imaging showed fulminant acute myocarditis with severe left ventricular dysfunction. Treatment with the recombinant interleukin-1 receptor antagonist anakinra and dexamethasone resulted in rapid clinical improvement, reduction in serum inflammatory markers, and a marked recovery in cardiac magnetic resonance--based markers of inflammation and contractile dysfunction. The patient was subsequently discharged from the hospital. Emerging evidence supports use of anti-inflammatory therapies, including anakinra and dexamethasone, in severe cases of coronavirus disease 2019.

Une femme de 62 ans atteinte de la COVID-19 a développé une insuffisance respiratoire aiguë et un choc cardiogène dans le contexte d'un état hyperinflammatoire général et d'un infarctus du myocarde avec élévation du segment ST apparent. L'imagerie par résonance magnétique cardiaque a révélé une myocardite aiguë fulminante accompagnée d'une dysfonction ventriculaire gauche sévère. Le traitement par l'anakinra, un antagoniste des récepteurs de l'interleukine 1 recombinant, et la dexaméthasone, a entraîné une amélioration clinique rapide, une diminution des marqueurs inflammatoires sériques et un rétablissement marqué selon les marqueurs de l'inflammation et de la dysfonction contractile à la résonance magnétique cardiaque. La patiente a par la suite reçu son congé de l'hôpital. De nouvelles données probantes militent en faveur de l'emploi de traitements anti-inflammatoires, comme l'anakinra et la dexaméthasone, dans les cas sévères de COVID-19.