Harmonizing government responses to the COVID-19 pandemic.

Public health and safety measures (PHSM) made in response to the COVID-19 pandemic have been singular, rapid, and profuse compared to the content, speed, and volume of normal policy-making. Not only can they have a profound effect on the spread of the disease, but they may also have multitudinous secondary effects, in both the social and natural worlds. Unfortunately, despite the best efforts by numerous research groups, existing data on COVID-19 PHSM only partially captures their full geographical scale and policy scope for any significant duration of time. This paper introduces our effort to harmonize data from the eight largest such efforts for policies made before September 21, 2021 into the taxonomy developed by the CoronaNet Research Project in order to respond to the need for comprehensive, high quality COVID-19 data. In doing so, we present a comprehensive comparative analysis of existing data from different COVID-19 PHSM datasets, introduce our novel methodology for harmonizing COVID-19 PHSM data, and provide a clear-eyed assessment of the pros and cons of our efforts.

Transcriptional signatures of early-life stress and antidepressant treatment efficacy.

Individuals with a history of early-life stress (ELS) tend to have an altered course of depression and lower treatment response rates. Research suggests that ELS alters brain development, but the molecular changes in the brain following ELS that may mediate altered antidepressant response have not been systematically studied. Sex and gender also impact the risk of depression and treatment response. Here, we leveraged existing RNA sequencing datasets from 1) blood samples from depressed female- and male-identifying patients treated with escitalopram or desvenlafaxine and assessed for treatment response or failure; 2) the nucleus accumbens (NAc) of female and male mice exposed to ELS and/or adult stress; and 3) the NAc of mice after adult stress, antidepressant treatment with imipramine or ketamine, and assessed for treatment response or failure. We find that transcriptomic signatures of adult stress after a history of ELS correspond with transcriptomic signatures of treatment nonresponse, across species and multiple classes of antidepressants. Transcriptomic correspondence with treatment outcome was stronger among females and weaker among males. We next pharmacologically tested these predictions in our mouse model of early-life and adult social defeat stress and treatment with either chronic escitalopram or acute ketamine. Among female mice, the strongest predictor of behavior was an interaction between ELS and ketamine treatment. Among males, however, early experience and treatment were poor predictors of behavior, mirroring our bioinformatic predictions. These studies provide neurobiological evidence for molecular adaptations in the brain related to sex and ELS that contribute to antidepressant treatment response.

A comparative analysis of the effects of containment policies on the epidemiological manifestation of the COVID-19 pandemic across nine European countries.

The COVID-19 pandemic has been a catastrophic event that has seriously endangered the world's population. Governments have largely been unprepared to deal with such an unprecedented calamity, partially due to the lack of sufficient or adequately fine-grained data necessary for forecasting the pandemic's evolution. To fill this gap, researchers worldwide have been collecting data about different aspects of COVID-19's evolution and government responses to them so as to provide the foundation for informative models and tools that can be used to mitigate the current pandemic and possibly prevent future ones. Indeed, since the early stages of the pandemic, a number of research initiatives were launched with this goal, including the PERISCOPE (Pan-European Response to the ImpactS of COVID-19 and future Pandemics and Epidemics) Project, funded by the European Commission. PERISCOPE aims to investigate the broad socio-economic and behavioral impacts of the COVID-19 pandemic, with the goal of making Europe more resilient and prepared for future large-scale risks. The purpose of this study, carried out as part of the PERISCOPE project, is to provide a first European-level analysis of the effect of government policies on the spread of the virus. To do so, we assessed the relationship between a novel index, the Policy Intensity Index, and four epidemiological variables collected by the European Centre for Disease Control and Prevention, and then applied a comprehensive Pan-European population model based on Multilevel Vector Autoregression. This model aims at identifying effects that are common to some European countries while treating country-specific policies as covariates, explaining the different evolution of the pandemic in nine selected countries due to data availability: Spain, France, Netherlands, Latvia, Slovenia, Greece, Ireland, Cyprus, Estonia. Results show that specific policies' effectiveness tend to vary consistently within the different countries, although in general policies related to Health Monitoring and Health Resources are the most effective for all countries.

Predictors of Adherence to Continuous Positive Airway Pressure in Older Adults With Apnea and Amnestic Mild Cognitive Impairment.

BACKGROUND: Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer's disease. METHODS: The data are from Memories 2, "Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea." Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors. RESULTS: The 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors. CONCLUSIONS: Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

A New Interactive Tool to Visualize and Analyze COVID-19 Data: The PERISCOPE Atlas.

Since the start of the 21st century, the world has not confronted a more serious threat to global public health than the COVID-19 pandemic. While governments initially took radical actions in response to the pandemic to avoid catastrophic collapse of their health care systems, government policies have also had numerous knock-on socioeconomic, political, behavioral and economic effects. Researchers, thus, have a unique opportunity to forward our collective understanding of the modern world and to respond to the emergency situation in a way that optimizes resources and maximizes results. The PERISCOPE project, funded by the European Commission, brings together a large number of research institutions to collect data and carry out research to understand all the impacts of the pandemic, and create predictive models that can be used to optimize intervention strategies and better face possible future health emergencies. One of the main tangible outcomes of this project is the PERISCOPE Atlas: an interactive tool that allows to visualize and analyze COVID-19-related health, economic and sociopolitical data, featuring a WebGIS and several dashboards. This paper describes the first release of the Atlas, listing the data sources used, the main functionalities and the future development.

COVID-19 Government Response Event Dataset (CoronaNet v.1.0).

Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.

Architect i2000 SR has improved turnaround time for infectious disease serology testing over Vitros ECiQ.

BACKGROUND: Vitros ECiQ and Architect i2000 SR are two automated instruments used to detect serology biomarkers of hepatitis A, B and C viruses, and HIV infections. We compared performance of the Architect to the Vitro EciQ after implementation at our institution. METHODS: A retrospective review was performed to compare patient samples tested on the Vitros ECiQ or Architect for hepatitis and HIV serological assays. The positivity rate, frequency of equivocal results, turnaround times (TAT), and hands-on time (HOT) were analyzed. RESULTS: There was no statistical difference in the positivity rate between the two instruments, with the exception of two assays. An increase in equivocal results was observed for the Architect (0.2% vs 0.5%). Notably, the TAT for the Architect i2000 was shorter for all except one assay (31.6 vs 33.7 hours) and demonstrated improved workflow. CONCLUSIONS: Overall, both instruments performed comparably. Architect had shorter TAT over Vitros.

Human, Tissue-Engineered, Skeletal Muscle Myobundles to Measure Oxygen Uptake and Assess Mitochondrial Toxicity.

Mitochondrial dysfunction is responsible for the toxicity of a number of drugs. Current isolated mitochondria or cellular monoculture mitochondrial respiration measurement systems lack physiological relevance. Using a tissue engineering rather than cell- or mitochondria-based approach enables a more physiologically relevant detection of drug-induced mitochondrial impairment. To probe oxygen consumption and mitochondrial health, we assayed the bioenergetic profile of engineered three-dimensional human skeletal muscle myobundles derived from primary myoblasts. Through experimental and computational techniques, we did not find external or internal oxygen transport limiting the engineered myobundles in the commercial O2k system to measure oxygen consumption. In response to the complex I inhibitor rotenone, myobundle basal respiration decreased dose dependently with an IC50 of 9.24 ± 0.03 nM. At a 20 nM concentration of rotenone, myobundle maximal respiration decreased by 44.4% ± 9.8%. Respiratory depression by rotenone suggests that cultured myobundles rely heavily on the complex I pathway for ATP synthesis during times of both basal and increased energy demand. To address whether these decrements in mitochondrial function corresponded to alterations in physiological muscle function, we determined fatigue susceptibility that revealed a 46.0% ± 7.4% depression at 20 nM rotenone. The bioenergetic health index, which is a measure of normal oxidative mitochondrial function, was inversely correlated with the extent of fatigue. The human myobundles reproduce normal muscle metabolism under both basal and maximal energy demand conditions enabling the detection of drug-induced mitochondrial toxicity.

Are organisational factors affecting the emotional withdrawal of community nurses?

Objective The aim of the present study was to investigate the effects of work organisation on the emotional labour withdrawal behaviour of Australian community nurses. Methods Using a paper-based survey, a sample of 312 Australian community nurses reported on their emotional dissonance, withdrawal behaviours (i.e. job neglect, job dissatisfaction, stress-related presenteeism) and work organisation. A model to determine the partial mediation effect of work organisation was developed based on a literature review. The fit of the proposed model was assessed via structural equation modelling using Analysis of Moment Structures (AMOS; IMB). Results Community nurses with higher levels of emotional dissonance were less likely to be satisfied with their job and work organisation and had a higher tendency to exhibit withdrawal behaviours. Work organisational factors mediated this relationship. Conclusion Emotional dissonance can be a potential stressor for community nurses that can trigger withdrawal behaviours. Improving work organisational factors may help reduce emotional conflict and its effect on withdrawal behaviours. What is known about the topic? Although emotional labour has been broadly investigated in the literature, very few studies have addressed the effect of the quality of work organisation on nurses' withdrawal behaviours in a nursing setting. What does this paper add? This paper provides evidence that work organisation affects levels of emotional dissonance and has an effect on job neglect through stress-related presenteeism. What are the implications for practitioners? In order to minimise stress-related presenteeism and job neglect, healthcare organisations need to establish a positive working environment, designed to improve the quality of relationships with management, provide appropriate rewards, recognition and effective workload management and support high-quality relationships with colleagues.

Cell Density and Joint microRNA-133a and microRNA-696 Inhibition Enhance Differentiation and Contractile Function of Engineered Human Skeletal Muscle Tissues.

To utilize three-dimensional (3D) engineered human skeletal muscle tissue for translational studies and in vitro studies of drug toxicity, there is a need to promote differentiation and functional behavior. In this study, we identified conditions to promote contraction of engineered human skeletal muscle bundles and examined the effects of transient inhibition of microRNAs (miRs) on myogenic differentiation and function of two-dimensional (2D) and 3D cultures of human myotubes. In 2D cultures, simultaneously inhibiting both miR-133a, which promotes myoblast proliferation, and miR-696, which represses oxidative metabolism, resulted in an increase in sarcomeric α-actinin protein and the metabolic coactivator PGC-1α protein compared to transfection with a scrambled miR sequence (negative control). Although PGC-1α was elevated following joint inhibition of miRs 133a and 696, there was no difference in myosin heavy chain (MHC) protein isoforms. 3D engineered human skeletal muscle myobundles seeded with 5 × 10(6) human skeletal myoblasts (HSkM)/mL and cultured for 2 weeks after onset of differentiation consistently did not contract when stimulated electrically, whereas those seeded with myoblasts at 10 × 10(6) HSkM/mL or higher did contract. When HSkM were transfected with both anti-miRs and seeded into fibrin hydrogels and cultured for 2 weeks under static conditions, twitch and tetanic specific forces after electrical stimulation were greater than for myobundles prepared with HSkM transfected with scrambled sequences. Immunofluorescence and Western blots of 3D myobundles indicate that anti-miR-133a or anti-miR-696 treatment led to modest increases in slow MHC, but no consistent increase in fast MHC. Similar to results in 2D, only myobundles prepared with myoblasts treated with anti-miR-133a and anti-miR-696 produced an increase in PGC-1α mRNA. PGC-1α targets were differentially affected by the treatment. HIF-2α mRNA showed an expression pattern similar to that of PGC-1α mRNA, but COXII mRNA levels were not affected by the anti-miRs. Overall, joint inhibition of miR-133a and miR-696 accelerated differentiation, elevated the metabolic coactivator PGC-1α, and increased the contractile force in 3D engineered human skeletal muscle bundles.

Monitoring of cytomegalovirus viral loads by two molecular assays in whole-blood and plasma samples from hematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) viral loads in hematopoietic stem cell transplant (HSCT) recipients are typically monitored using quantitative molecular assays. The Roche Cobas AmpliPrep/Cobas TaqMan CMV test (Cobas CMV) has recently been cleared by the FDA for the monitoring of CMV viral loads in plasma samples from transplant patients. In this study, we compare and correlate the viral loads obtained by a laboratory-developed test (LC CMV) (using Roche analyte-specific reagents [ASR] on the LightCycler 2.0) on whole-blood specimens with those obtained on corresponding plasma and whole-blood specimens by the Cobas CMV assay. Testing was performed on 773 archived patient specimens. The strength of the agreement was good for the two assays performed on whole blood (κ=0.6; 95% confidence interval [CI], 0.51 to 0.7) and moderate when the tests were performed on different sample types (κ=0.54; 95% CI, 0.47 to 0.62 for the LC CMV whole blood [WB] assay versus Cobas plasma [PL], and κ=0.57; 95% CI, 0.5 to 0.65 for the Cobas WB assay versus Cobas PL), although the difference was not statistically significant. Using a combination gold standard (i.e., a true positive was a specimen that was positive by two or more methods), the sensitivity and specificity of the assays were 78.8% and 99.3% for the LC CMV assay, 85.2% and 98.1% for the Cobas CMV WB assay, and 100% and 90.5% for Cobas CMV PL assay, respectively. A comparison of the CMV viral load trends in both plasma and whole blood from a few patients with multiple positive successive samples showed similar slopes, with differences in the slope ranging from 0.01 to 0.22. However, the absolute value for individual viral load differed markedly with whole-blood viral loads, being on average 0.5- to 1.22-log higher than those in plasma. The Cobas CMV assay provides a valid option for the monitoring of viral loads in transplant patients. Due to its increased sensitivity, the detection of CMV DNA in patients with low viral loads (i.e., those below limit of quantification [LOQ]) is increased with the Cobas CMV assay in plasma specimens. Longitudinal prospective studies will be needed to examine the clinical significance of these low-level viral loads.

Physiology and metabolism of tissue-engineered skeletal muscle.

Skeletal muscle is a major target for tissue engineering, given its relative size in the body, fraction of cardiac output that passes through muscle beds, as well as its key role in energy metabolism and diabetes, and the need for therapies for muscle diseases such as muscular dystrophy and sarcopenia. To date, most studies with tissue-engineered skeletal muscle have utilized murine and rat cell sources. On the other hand, successful engineering of functional human muscle would enable different applications including improved methods for preclinical testing of drugs and therapies. Some of the requirements for engineering functional skeletal muscle include expression of adult forms of muscle proteins, comparable contractile forces to those produced by native muscle, and physiological force-length and force-frequency relations. This review discusses the various strategies and challenges associated with these requirements, specific applications with cultured human myoblasts, and future directions.

Conditions that promote primary human skeletal myoblast culture and muscle differentiation in vitro.

Conditions under which skeletal myoblasts are cultured in vitro are critical to growth and differentiation of these cells into mature skeletal myofibers. We examined several culture conditions that promoted human skeletal myoblast (HSkM) culture and examined the effect of microRNAs and mechanical stimulation on differentiation. Culture conditions for HSkM are different from those that enable rapid C2C12 myoblast differentiation. Culture on a growth factor-reduced Matrigel (GFR-MG)-coated surface in 2% equine serum-supplemented differentiation medium to promote HSkM differentiation under static conditions was compared with culture conditions used for C2C12 cell differentiation. Such conditions led to a >20-fold increase in myogenic miR-1, miR-133a, and miR-206 expression, a >2-fold increase in myogenic transcription factor Mef-2C expression, and an increase in sarcomeric α-actinin protein. Imposing ±10% cyclic stretch at 0.5 Hz for 1 h followed by 5 h of rest over 2 wk produced a >20% increase in miR-1, miR-133a, and miR-206 expression in 8% equine serum and a >35% decrease in 2% equine serum relative to static conditions. HSkM differentiation was accelerated in vitro by inhibition of proliferation-promoting miR-133a: immunofluorescence for sarcomeric α-actinin exhibited accelerated development of striations compared with the corresponding negative control, and Western blotting showed 30% more α-actinin at day 6 postdifferentiation. This study showed that 100 µg/ml GFR-MG coating and 2% equine serum-supplemented differentiation medium enhanced HSkM differentiation and myogenic miR expression and that addition of antisense miR-133a alone can accelerate primary human skeletal muscle differentiation in vitro.

The role of team climate in the management of emotional labour: implications for nurse retention.

AIMS: This article examines the relationships among emotional labour, team climate, burnout, perceived quality of care and turnover intention among nurses in Australia, with the aim of addressing nurse retention and burnout. BACKGROUND: Emotional labour refers to the regulation of emotion during interpersonal transactions. It may involve faking unfelt emotions, hiding genuine emotions and deep acting whereby the individuals attempt to influence their inner feelings to induce the appropriate outward countenance. Currently, there is a dearth of literature that investigates the link between emotional labour and perceived quality of care and ultimately turnover intention. The contribution of team climate in the relationship between emotional labour and burnout is still uncertain. DESIGN: A cross-sectional quantitative study conducted with self-completed questionnaires. METHODS: The study was conducted in 2011 with 201 registered nurses. Validated measures were used to measure the aforementioned constructs. Confirmatory factor analyses were used to examine the factor structure of the measured variables and hypotheses were tested using structural equation modelling. RESULTS: The final model demonstrates that faking has a significant negative influence on perceived quality of care. Hiding predicts burnout, leading to an increase in turnover intention. Team climate moderates the relationship between hiding and burnout, which may subsequently influence turnover intention. CONCLUSION: The establishment of a strong team climate may help nurses to manage the emotional demands of their role, promote their well-being and retention.

Design considerations for an integrated microphysiological muscle tissue for drug and tissue toxicity testing.

Microphysiological systems provide a tool to simulate normal and pathological function of organs for prolonged periods. These systems must incorporate the key functions of the individual organs and enable interactions among the corresponding microphysiological units. The relative size of different microphysiological organs and their flow rates are scaled in proportion to in vivo values. We have developed a microphysiological three-dimensional engineered human skeletal muscle system connected to a circulatory system that consists of a tissue-engineered blood vessel as part of a high-pressure arterial system. The engineered human skeletal muscle tissue reproduces key mechanical behaviors of skeletal muscle in vivo. Pulsatile flow is produced using a novel computer-controlled magnetically activated ferrogel. The system is versatile and the muscle unit can be integrated with other organ systems. Periodic monitoring of biomechanical function provides a non-invasive assessment of the health of the tissue and a way to measure the response to drugs and toxins.

Deletion of HIF-1α partially rescues the abnormal hyaloid vascular system in Cited2 conditional knockout mouse eyes.

PURPOSE: Cited2 (CBP/p300-interacting transactivators with glutamic acid (E) and aspartic acid (D)-rich tail 2) is a member of a new family of transcriptional modulators. Cited2 null embryos exhibit hyaloid hypercellularity consisting of aberrant vasculature in the eye. The purpose of the study is to address whether abnormal lenticular development is a primary defect of Cited2 deletion and whether deletion of hypoxia inducible factor (HIF)-1α or an HIF-1α target gene, vascular endothelial growth factor (VEGF), could rescue abnormal hyaloid vascular system (HVS) in Cited2 deficient adult eyes. METHODS: Le-Cre specific Cited2 knockout (Cited2(CKO)) mice with or without deletion of HIF-1α or VEGF were generated by standard Cre-Lox methods. Eyes collected from six-eight weeks old mice were characterized by Real Time PCR and immunohistological staining. RESULTS: Cited2(CKO) mice had smaller lenses, abnormal lens stalk formation, and failed regression of the HVS in the adult eye. The eye phenotype had features similar to persistent hyperplastic primary vitreous (PHPV), a human congenital eye disorder leading to abnormal lenticular development. Deletion of HIF-1α or VEGF in Cited2 knockout eyes partially rescued the abnormal HVS but had no effect on the smaller lens and abnormal lens stalk differentiation. Intravitreal injection of Topotecan (TPT), a compound that inhibits HIF-1α expression, partially eliminated HVS defects in Cited2(CKO) lenses. CONCLUSIONS: Abnormal HVS is a primary defect in Cited2 knockout mice, resulting in part from dysregulated functions of HIF-1 and VEGF. The Cited2(CKO) mouse line could be used as a novel disease model for PHPV and as an in vivo model for testing potential HIF-1 inhibitors.

HIF-1α deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency.

Cited2 is a transcriptional modulator involved in various biologic processes including fetal liver hematopoiesis. In the present study, the function of Cited2 in adult hematopoiesis was investigated in conditional knockout mice. Deletion of Cited2 using Mx1-Cre resulted in increased hematopoietic stem cell (HSC) apoptosis, loss of quiescence, and increased cycling, leading to a severely impaired reconstitution capacity as assessed by 5-fluorouracil treatment and long-term transplantation. Transcriptional profiling revealed that multiple HSC quiescence- and hypoxia-related genes such as Egr1, p57, and Hes1 were affected in Cited2-deficient HSCs. Because Cited2 is a negative regulator of HIF-1, which is essential for maintaining HSC quiescence, and because we demonstrated previously that decreased HIF-1α gene dosage partially rescues both cardiac and lens defects caused by Cited2 deficiency, we generated Cited2 and HIF-1α double-knockout mice. Additional deletion of HIF-1α in Cited2-knockout BM partially rescued impaired HSC quiescence and reconstitution capacity. At the transcriptional level, deletion of HIF-1α restored expression of p57 and Hes1 but not Egr1 to normal levels. Our results suggest that Cited2 regulates HSC quiescence through both HIF-1-dependent and HIF-1-independent pathways.

Effect of microRNA modulation on bioartificial muscle function.

Cellular therapies have recently employed the use of small RNA molecules, particularly microRNAs (miRNAs), to regulate various cellular processes that may be altered in disease states. In this study, we examined the effect of transient muscle-specific miRNA inhibition on the function of three-dimensional skeletal muscle cultures, or bioartificial muscles (BAMs). Skeletal myoblast differentiation in vitro is enhanced by inhibiting a proliferation-promoting miRNA (miR-133) expressed in muscle tissues. As assessed by functional force measurements in response to electrical stimulation at frequencies ranging from 0 to 20 Hz, peak forces exhibited by BAMs with miR-133 inhibition (anti-miR-133) were on average 20% higher than the corresponding negative control, although dynamic responses to electrical stimulation in miRNA-transfected BAMs and negative controls were similar to nontransfected controls. Immunostaining for alpha-actinin and myosin also showed more distinct striations and myofiber organization in anti-miR-133 BAMs, and fiber diameters were significantly larger in these BAMs over both the nontransfected and negative controls. Compared to the negative control, anti-miR-133 BAMs exhibited more intense nuclear staining for Mef2, a key myogenic differentiation marker. To our knowledge, this study is the first to demonstrate that miRNA mediation has functional effects on tissue-engineered constructs.