Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation.

Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.

BECOMING A DEMENTIA CARE PARTNER DURING THE COVID-19 PANDEMIC

Persons with newly diagnosed Alzheimer's disease and related dementias (ADRD) and their care partners confront multiple challenges. These challenges have been even greater during the COVID-19 pandemic, where supportive resources often are limited or even discontinued. We conducted semi-structured interviews with 21 care partners of persons who were recently diagnosed with ADRD (2019-2020) to explore their lived experiences of adjusting to the new role. Directed and conventional content analyses were used and were informed by the life course theory. Care partners perceived difficulty in accessing medical and social services for their loved ones, particularly during the pandemic. Despite experiencing distress, some care partners chose not to seek help for fear of contracting COVID-19. This study provides insights on the unmet needs of care partners during a pandemic and highlights that effective, long-term strategies are needed to continue providing person-centered care to persons with ADRD and their families.

The Research Escape-Hunt: An Escape Room for Resident Education on Research Design and Evidence-Based Medicine

Learning Objectives: We sought to develop a research escape-hunt to teach EM residents: 1) predictive statistics and diagnostic test characteristics, 2) interpretation of data and statistical analysis, 3) study design, 4) informed consent for research, and 8) the ethical principles guiding research. Introduction: Research and evidence-based medicine are important parts of residency training and the ACGME identifies scholarly activity as a core requirement for EM. EM training programs take a variety of approaches to addressing these requirements and there is not a standard, widely accepted curriculum available. Curricular Design: We considered ways to incorporate active, participatory learning experiences that effectively engage adult learners. Within the CORD community, escape- hunts have demonstrated efficacy for other EM content. An escape-hunt was developed with each station focused on one topic and requiring participants to solve a series of puzzles. Prior to the event, participants reviewed materials covering the content including summary sheets and podcast links. The escape-hunt served as an opportunity to further explore and reinforce the asynchronous content. Faculty members were present to help guide teams through the stations and to answer questions about the content. Teams worked to solve each station with the first team to successfully complete all nine stations winning a prize. A subsequent COVID-impacted event was held the following year utilizing Zoom breakout rooms, demonstrating that this innovation can be successfully implemented both in-person and virtually. Impact: Participants reported high levels of satisfaction (100% (21/21)) and engagement (95% (20/21)) with the activity, increased comfort with the content (91% (19/21)), and demonstrated improvements in knowledge across content areas (91% (19/21)). Participants reported using skills relevant to clinical practice such as 'working as a team,' 'task switching,' 'task delegation,' 'brainstorming,' and 'solving complex problems together.' Challenges exist related to props cost and the time for development;however, we now have a materials bank that can be used in the future and we have successfully implemented a COVID-safe virtual event, demonstrating the adaptability of this format.

Playing Out: Exploring How Liverpool’s Live Music Sector Adapted to Survive the Impact of the COVID-19 Pandemic

Drawing on the findings of practitioner group consultations (n=49) and an online survey of music makers (n=37), this article illustrates the devastating impact of 18 months without full-capacity live events on the financial, musical and social wellbeing of the Liverpool City Region’s (LCR) music sector. The analysis shows how uncertainties concerning a return to normal operations, access to funding support, working within socially distanced limitations, and dealing with changing regulations have underlined the live music workers’ experience of the pandemic as well as how a sense of uncertainty persists despite a return to full-capacity events in July 2021. The findings show that digital alternatives partially helped alleviate lockdown’s detrimental effects but, overall, the sector viewed live-streaming as a “stop-gap” incomparable to the conventional concert experience. The research concludes by observing that, despite the numerous practical and economic adaptations and online advances that ensured the sector’s survival, the return to “business as usual” also means a return to pre-pandemic industry economics, which often function to the detriment of the musicians on whom the regional live sector’s operational and financial recovery depend. © Equinox Publishing Ltd 2022, Office 415, The Workstation, 15 Paternoster Row, Sheffield S1 2BX

Excess deaths associated with COVID-19, by age and race and ethnicity - United States, January 26-October 3, 2020

This study aimed to describe excess sodium intake in the context of the CDRR intake goal. This report analyzed National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2016 to yield temporal trends in usual sodium intake >2,300 mg/day and in mean sodium intake, unadjusted and adjusted for total energy intake, among U.S. adults aged 19 years. The percentage of U.S. adults with sodium intake above CDRR intake was 87.0% during 2003-2004 and 86.7% during 2015-2016. Among U.S. adults overall, no significant linear trend was noted from 2003 to 2016 in unadjusted or energy intake-adjusted mean sodium intake. Small, significant declines were observed in mean usual sodium intake among some groups (adults aged 19-50 years, non-Hispanic White adults, adults experiencing obesity, and adults without hypertension). However, after energy adjustment, only adults aged 71 years and Mexican American adults demonstrated significant change in usual sodium intake.

The Silver Linings of COVID-19 and Racism Pandemics?

The coronavirus disease (COVID-19) pandemic has brought health and social disparities to the fore, and intensified bias and racism in the U.S. and globally. In the context of discriminatory rhetoric and anti-Asian sentiments voiced by prominent political figures, Asian Americans have been disproportionately targeted with injustice, scapegoating, and overt racism. Amid heightened sociocultural stress and national divisiveness, the present study explored whether "silver linings" might be found in the form of increased ethnic-racial identity exploration, ethnic-racial socialization, and civic engagement. Survey data from 200 Asian American parents of adolescents (58% mothers;63% foreign born, 37% U.S. born) suggest that awareness of discrimination against Asian Americans post-COVID-19 was associated with greater identity exploration and fewer socialization messages that minimize the importance of race. Awareness of discrimination against other minoritized groups (i.e., Native and Black Americans, Latinxs) was associated with greater post-COVID-19 activism. Additional socialization messages (i.e., promotion of equality, cultural pluralism) were associated with lifetime discrimination experiences and parent gender. Although negative consequences of the pandemic are indisputable, our results offer a small glimmer of hope in terms of building resistance and momentum. What is the public significance of this article? In the face of ethnic-racial bias and racism post-coronavirus disease (COVID-19), Asian American parents of adolescents explore their ethnic-racial identities, communicate positive ethnic-racial socialization messages to their children, and engage in community activism. Although negative consequences of the pandemic are indisputable, there do appear to be "silver linings" that can build resistance and civic engagement.

Reinvigorating the Desire to Teach: Teacher Professional Development for Creativity, Agency, Stress Reduction, and Wellbeing

Research suggests that teachers’ creative development may materialize in more resilience and joy and less stress, but these connections have received little attention. This mixed methods study analyzes the effectiveness of a hybrid professional development model focused on teachers’ creative agency during the COVID-19 pandemic, a period of intensified stress, anxiety, and disconnect. Results indicated the PD experience supported (a) an increase in teachers’ creative agency, empathy, joy, buoyancy, and support in teaching during the pandemic and (b) a reduction in their secondary traumatic stress. Qualitative analyses illustrated a variety of personalized pathways for this development. The evidence suggests teachers’ creative agency and wellbeing can develop through a complementary process, rooted in creativity and the arts. Copyright © 2022 Anderson, Katz-Buonincontro, Livie, Land, Beard, Bousselot and Schuhe.

Piloting of a Toolkit for Delirium Detection and Management at Four Emergency Departments

Study Objectives: Approximately 10-30% of older patients in the emergency department (ED) exhibit delirium, which goes unrecognized by up to 75% of providers. Delirium is linked to increased lengths of stay, in-hospital falls, cognitive decline, and mortality, yet in a recent national survey of ACEP members, only 14% reported having a protocol addressing delirium in the ED. We conducted a feasibility pilot of a delirium toolkit developed to improve screening and management of delirium in the ED. Methods: Supported by a monthly workgroup, four EDs used the toolkit to develop and implement distinct quality improvement (QI) initiatives contextually appropriate to their ED (sites represented a range of ED environments). QI initiatives included delirium screening (using the CAM, bCAM, and/or DTS instruments) as well as delirium management strategies. Toolkit feasibility testing included assessment of implementation speed, protocol adherence, and qualitative feedback. Sites implemented and reported on process metrics for their QI initiatives from July – November 2020. Results: Findings reflect data from three sites (the fourth site did not contribute quantitative data). Over 73% of ED staff received delirium protocol training across sites in the first month of implementation, and staff participation in additional monthly trainings continued at a lower intensity over time. A total of 7,107 delirium screenings were conducted (representing 43% of older adults visiting the three EDs during the study period) and 4.5% of delirium screenings were positive. Over time, the monthly number and proportion of older adults screened for delirium trended slightly downwards, while the proportion of positive delirium screenings trended upwards. The sites provided 1,460 instances of delirium management activities (some patients received more than one). These activities were grouped into over a dozen different categories, with documenting an updated diagnosis or disposition being most common (300 instances), followed by orientation (239 instances) and hydration/nutrition interventions (196 instances). Conclusion: All pilot sites leveraged the ED-Delirium Toolkit to develop QI initiatives, with three of the four sites contributing data demonstrating successful implementation. These delirium QI initiatives were seen as complementary activities to the concurrent pandemic priorities given the recognition of delirium as both a presenting symptom as well as a common complication of COVID-19. ED nurses may have been able to improve targeted screening of patients over time based on the increasing positivity rate and declining proportion and number of screenings conducted. Given the number of staff trained and scale of delirium management activities, use of the toolkit increased awareness of and interventions for addressing delirium in the ED.

Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020-2021.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant has been hypothesized to cause more severe illness than previous variants, especially in children. Successive SARS-CoV-2 IgG serosurveys in the Brazilian Amazon showed that age-specific attack rates and proportions of symptomatic SARS-CoV-2 infections were similar before and after Gamma variant emergence.

The Future of Care Work: Towards a Radical Politics of Care in CSCW Research and Practice

Computer-Supported Cooperative Work (CSCW) and Human- Computer Interaction (HCI) have long studied how technology can support material and relational aspects of care work, typically in clinical healthcare settings. More recently, we see increasing recognition of care work such as informal healthcare provision, child and elderly care, organizing and advocacy, domestic work, and service work. However, the COVID-19 pandemic has underscored long-present tensions between the deep necessity and simultaneous devaluation of our care infrastructures. This highlights the need to attend to the broader social, political, and economic systems that shape care work and the emerging technologies being used in care work. This leads us to ask several critical questions: What counts as care work and why? How is care work (de)valued, (un)supported, or coerced under capitalism and to what end? What narratives drive the push for technology in care work and whom does it benefit? How does care work resist or build resilience against and within oppressive systems? And how can we as researchers advocate for and with care and caregivers? In this one-day workshop, we will bring together researchers from academia, industry, and community-based organizations to reflect on these questions and extend conversations on the future of technology for care work. © 2021 ACM.

The effect of COVID-19 public health restrictions on the health of people with musculoskeletal conditions and symptoms: the CONTAIN study.

OBJECTIVE: To quantify the change in quality of life, disease-specific indicators, health and lifestyle before and during the COVID-19 pandemic among people with musculoskeletal diagnoses and symptoms. METHODS: We undertook an additional follow-up of two existing UK registers involving people with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) and participants in a trial in the UK who had regional pain and were identified at high risk of developing chronic widespread pain. Participants completed the study questionnaire between July and December 2020, throughout which time there were public health restrictions in place. RESULTS: The number of people taking part in the study was 1054 (596 axSpA, 162 PsA, 296 regional pain). In comparison with their previous (pre-pandemic) assessment, there was an age-adjusted significant, small decrease in quality of life measured by EQ-5D [-0.020 (95% CI -0.030, -0.009)] overall and across all population groups examined. This was primarily related to poorer mental health and pain. There was a small increase in fibromyalgia symptoms, but a small decrease in sleep problems. There was a small deterioration in axSpA disease activity, and disease-specific quality of life and anxiety in PsA participants. Predictors of poor quality of life were similar pre- and during the pandemic. The effect of lockdown on activity differed according to age, gender and deprivation. CONCLUSION: Important lessons include focusing on addressing anxiety and providing enhanced support for self-management in the absence of normal health care being available, and awareness that all population groups are likely to be affected.

Gross hematuria is associated with more severe disease and poorer clinical outcomes in covid-19 patients

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic has resulted in 2.5 million deaths globally. Previous studies have suggested the virus may affect the kidneys, resulting in hematuria, proteinuria and acute kidney injury;however, the studies did not differentiate microscopic hematuria (MH) from gross hematuria (GH). In this study, we investigated the clinical outcomes and risk factors associated with GH compared to MH in COVID patients. METHODS: Following IRB approval, 250 consecutive medical records of COVID patients admitted to a tertiary care university hospital from 3/15/20 were analyzed. Patients without a urinalysis during the admission were excluded, the remaining 157 patients were included in the analysis. Patients were divided into three categories based on the presence of hematuria during the admission: none, microscopic hematuria (MH) and gross hematuria (GH). Outcomes including length of hospitalization, ICU admission, intubation, and lab values were compared amongst the categories. Chi-square test was used to compare the categorical variables, while ANOVA and t-test were used for the parametric variables. RESULTS: Of the 157 patients, 66 (42%) did not have hematuria, 36 (22.9%) had MH and 55 (35%) had GH. As seen in Fig.1, GH was associated with worse clinical outcomes such as higher intubation rate at 49.1%, compared to 27.8% in MH (p <0.05). In those with no hematuria, the intubation rate was 7.6%, significantly lower than patients with GH and MH (p <0.05). Mortality rate was also higher in those with GH compared to MH, at 30.9% and 22.2% respectively (p <0.05). Regarding kidney function, patients with GH, MH and no hematuria had acute kidney injury (AKI) at a rate of 67.3%, 58.3% and 39.4%, respectively (p <0.05). Peak C-reactive protein (CRP) values were higher in patients with GH and MH compared to those with no hematuria, at 24.04, 18.07 and 15.36, respectively (p <0.005). CONCLUSIONS: Gross hematuria was associated with poor kidney function, higher intubation rate and mortality compared to those with microscopic or no hematuria. Gross hematuria was linked to elevated biomarkers linked to inflammation and disease severity, such CRP and D-dimer, indicating possible direct effect of the virus on the kidneys. More studies are needed to further delineate the etiology behind hematuria in COVID patients.

Brief review: Cardiac complications and platelet activation in COVID-19 infection.

COVID-19 pneumonia, much like that of bacterial and viral community-acquired pneumonia before it, is accompanied by a high rate of cardio- and cerebrovascular events that are associated with an increased risk of complications and a greater mortality. Although the mechanisms underlying the pathogenesis of these adverse events are not entirely clear and may be multifactorial, platelets appear to have a prominent aetiologic role and this, together with an overview of the clinical evidence, forms the basis of this short review.