Quality of Life Associated with Physical Activity but not Sedentary Time in Youth

Purpose: It has been reported that youth who engaged in more screen time had lower quality of life scores compared to those that were more physically active. Furthermore, increased sedentary behavior increases health risks particularly the risk for obesity. A cross-sectional analysis was completed to examine the relationship between healthrelated quality-of-life (HRQOL) and accelerometer-measured sedentary time (ST) and physical activity (PA) in 9-10-yearold youth who were recruited for the family-based, childhood obesity intervention, iCook 4-H. It was hypothesized that objectively measured ST would be negatively correlated and PA would be positively correlated with HRQOL.Methods: A subset of participants (n=118) wore Actigraph GT3X+ accelerometers for 7 days and completed the Pediatric Quality of Life survey (PedsQLTM, version 4.0) to assess HRQOL. Mean daily minutes of accelerometermeasured ST (547 ± 60) and PA including light-intensity (LPA=240 ± 49), moderate-intensity (MPA=35 ± 11), vigorous-intensity (VPA=17 ± 9), and moderate-to vigorousintensity (MVPA=52 ± 19) were evaluated during waking hours. Multiple linear regressions were used to assess relationship between ST and PA intensities with HRQOL. Statistical significance was set at p ≤ 0.05.Results: There were no significant associations between ST or LPA with HRQOL. MPA, VPA and MVPA were positively associated with multiple HRQOL domains.Conclusion: The lack of relationship between objectively measured ST and LPA with the total HRQOL score and subscales merits further investigation. The findings of the current study support the need for lifestyle interventions that engage families in behavior that increases MVPA

Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model.

The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta VOCs and Omicron in the hamster COVID-19 model. Omicron replication and associated lung disease in vehicle treated hamsters was reduced compared to the earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of Alpha, Beta and Delta VOC infected hamsters. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious titers compared to viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants

Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice

The multimammate mouse (Mastomys natalensis; M. natalensis) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), Leishmania spp., Yersinia spp., and Borrelia spp. Although M. natalensis are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of M. natalensis. As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with M. natalensis. Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by M. natalensis lymphocytes. In contrast to C57BL/6J mice, lymphocytes from M. natalensis were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in M. natalensis to commonly used mitogens differ from a laboratory-bred mouse strain.</jats:p

SARS-CoV-2 reinfection prevents acute respiratory disease in Syrian hamsters but not replication in the upper respiratory tract

Human cases of SARS-CoV-2 reinfection have been documented throughout the pandemic, but are likely under-reported. In the current study, we use the Syrian hamster SARS-CoV-2 model to assess reinfection with homologous WA1 and heterologous B.1.1.7 (Alpha) and B.1.351 (Beta) SARS-CoV-2 variants over time. Upon primary infection with SARS-CoV-2 WA1, hamsters rapidly develop a strong and long-lasting humoral immune response. After reinfection with homologous and heterologous SARS-CoV-2 variants, this immune response protects hamsters from clinical disease, virus replication in the lower respiratory tract, and acute lung pathology. However, reinfection leads to SARS-CoV-2 replication in the upper respiratory tract with the potential for virus shedding. Our findings indicate that reinfection results in restricted SARS-CoV-2 replication despite substantial levels of humoral immunity, denoting the potential for transmission through reinfected asymptomatic individuals

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

Distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. Transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. In the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. We show for the first time detection of infectivity in white and brown fat. Since high amounts of ruminant fat are consumed by humans and also incorporated into animal feed, fat-containing tissues may pose a previously unappreciated hazard for spread of prion infection

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

AbstractThe COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.</jats:p

Republicanism and the political economy of democracy

Europe is experiencing rapidly accelerating poverty and social exclusion, following half a decade of financial crisis and austerity politics. The key problem behind Europe's malaise, in our view, is the economic disenfranchisement of large parts of its population in the winner-takes-all-society. This article proposes that we examine the contribution of republican political theory as a distinctive approach that provides us with the conceptual and normative resources to reclaim what we call the political economy of democracy, the constellation of political and economic institutions aimed at promoting broad economic sovereignty and individuals' capacities to govern their own lives. This article identifies three key ideas that together constitute a distinctively republican approach to political economy: (1) establish an economic floor; (2) impose an economic ceiling to counter excess economic inequality; and (3) democratize the governance and regulation of the main economic institutions

Portfolio optimization and index tracking for the shipping stock and freight markets using evolutionary algorithms

This paper reproduces the performance of an international market capitalization shipping stock index and two physical shipping indexes by investing only in US stock portfolios. The index-tracking problem is addressed using the differential evolution algorithm and the genetic algorithm. Portfolios are constructed by a subset of stocks picked from the shipping or the Dow Jones Composite Average indexes. To test the performance of the heuristics, three different trading scenarios are examined: annually, quarterly and monthly rebalancing, accounting for transaction costs where necessary. Competing portfolios are also assessed through predictive ability tests. Overall, the proposed investment strategies carry less risk compared to the tracked benchmark indexes while providing investors the opportunity to efficiently replic ate the performance of both the stock and physical shipping indexes in the most cost-effective way