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Long COVID impacts people's physical health and cognition which immensely affects their psychosocial well-being. A larger study was conducted that explored the psychosocial impacts of Long COVID on individuals and caregivers. This paper focuses on the impact of these stressful disruptions on one's health and psychosocial well-being, and how individuals cope with them. Utilizing a qualitative descriptive approach, we conducted interviews with 67 participants (52 people with Long COVID (mean age: 50.4) and 15 caregivers (mean age: 50.0)). People with Long COVID and caregivers were recruited from healthcare institutions through care team referrals, patient partners, and health organizations and via social media platforms. A thematic codebook developed through inter-coder agreement processes was used to analyze the data. Three key themes were identified: (1) Disruptions in people with Long COVID and caregivers' lives are characterized by a deviation from their perceived 'normalcy', (2) Disruptions lead to substantial stress, loss and grief (independence, agency, meaning, and purpose), and (3) People with Long COVID and caregivers cope with stressful disruptions by adapting their daily activities. Our findings make the case for supportive rehabilitation strategies that address the psychosocial repercussions of Long COVID to help mitigate feelings of loss and grief, thereby increasing individuals' overall quality of life and well-being.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

BackgroundFalls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls.MethodsEstimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records.ResultsGlobally, the age-standardised incidence of falls was 2238 (1990–2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622–5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5–9.8) per 100 000 which equated to 695 771 (644 927–741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897–17 636 830) YLLs, 19 252 699 (13 725 429–26 140 433) YLDs and 35 940 787 (30 185 695–42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age.ConclusionsThis study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.

The majority of emerging zoonoses originate in wildlife, and many are caused by viruses. However, there are no rigorous estimates of total viral diversity (here termed “virodiversity”) for any wildlife species, despite the utility of this to future surveillance and control of emerging zoonoses. In this case study, we repeatedly sampled a mammalian wildlife host known to harbor emerging zoonotic pathogens (the Indian Flying Fox, Pteropus giganteus ) and used PCR with degenerate viral family-level primers to discover and analyze the occurrence patterns of 55 viruses from nine viral families. We then adapted statistical techniques used to estimate biodiversity in vertebrates and plants and estimated the total viral richness of these nine families in P. giganteus to be 58 viruses. Our analyses demonstrate proof-of-concept of a strategy for estimating viral richness and provide the first statistically supported estimate of the number of undiscovered viruses in a mammalian host. We used a simple extrapolation to estimate that there are a minimum of 320,000 mammalian viruses awaiting discovery within these nine families, assuming all species harbor a similar number of viruses, with minimal turnover between host species. We estimate the cost of discovering these viruses to be ~ $6.3 billion (or ~$ 1.4 billion for 85% of the total diversity), which if annualized over a 10-year study time frame would represent a small fraction of the cost of many pandemic zoonoses. IMPORTANCE Recent years have seen a dramatic increase in viral discovery efforts. However, most lack rigorous systematic design, which limits our ability to understand viral diversity and its ecological drivers and reduces their value to public health intervention. Here, we present a new framework for the discovery of novel viruses in wildlife and use it to make the first-ever estimate of the number of viruses that exist in a mammalian host. As pathogens continue to emerge from wildlife, this estimate allows us to put preliminary bounds around the potential size of the total zoonotic pool and facilitates a better understanding of where best to allocate resources for the subsequent discovery of global viral diversity. Recent years have seen a dramatic increase in viral discovery efforts. However, most lack rigorous systematic design, which limits our ability to understand viral diversity and its ecological drivers and reduces their value to public health intervention. Here, we present a new framework for the discovery of novel viruses in wildlife and use it to make the first-ever estimate of the number of viruses that exist in a mammalian host. As pathogens continue to emerge from wildlife, this estimate allows us to put preliminary bounds around the potential size of the total zoonotic pool and facilitates a better understanding of where best to allocate resources for the subsequent discovery of global viral diversity.

Macroclimate warming is often assumed to occur within forests despite the potential for tree cover to modify microclimates. Here, using paired measurements, we compared the temperatures under the canopy versus in the open at 98 sites across 5 continents. We show that forests function as a thermal insulator, cooling the understory when ambient temperatures are hot and warming the understory when ambient temperatures are cold. The understory versus open temperature offset is magnified as temperatures become more extreme and is of greater magnitude than the warming of land temperatures over the past century. Tree canopies may thus reduce the severity of warming impacts on forest biodiversity and functioning. Comparing temperatures in the forest understory versus open habitat across boreal, temperate and tropical biomes, the authors show that tree canopies act as thermal insulators that buffer the understory against temperature extremes.

Congenital CMV infection (cCMVi) affects 0.5–1% of all live births worldwide, making it the leading cause of sensorineural hearing loss (SNHL) in childhood. The majority of infants with cCMVi have normal hearing at birth, but are at risk of developing late-onset SNHL. Currently, we lack reliable biomarkers to predict the development of SNHL in these infants. Here, we evaluate blood transcriptional profiles in 80 infants with cCMVi (49 symptomatic, 31 asymptomatic), enrolled in the first 3 weeks of life, and followed for 3 years to assess emergence of late-onset SNHL. The biosignatures of symptomatic and asymptomatic cCMVi are indistinguishable, suggesting that immune responses of infants with asymptomatic and symptomatic cCMVi are not different. Random forest analyses of initial samples in infants with cCMVi, irrespective of their clinical classification, identify a 16-gene classifier signature associated with the development of SNHL with 92% accuracy, suggesting its potential value as a biomarker. Congenital CMV infection can result in sensorineural hearing loss, but predicting this outcome is not yet possible. Here, the authors show that while blood gene expression profiles are not substantially different between symptomatic and asymptomatic infants with congenital CMV infection, a 16-gene signature is identified and able to predict late-onset hearing loss in these children.

1. Macroclimatic variation along latitudinal gradients provides an excellent natural laboratory to investigate the role of temperature and the potential impacts of climate warming on terrestrial organisms. 2. Here, we review the use of latitudinal gradients for ecological climate change research, in comparison with altitudinal gradients and experimental warming, and illustrate their use and caveats with a meta-analysis of latitudinal intraspecific variation in important life-history traits of vascular plants. 3. We first provide an overview of latitudinal patterns in temperature and other abiotic and biotic environmental variables in terrestrial ecosystems. We then assess the latitudinal intraspecific variation present in five key life-history traits [plant height, specific leaf area (SLA), foliar nitrogen: phosphorus (N:P) stoichiometry, seed mass and root: shoot (R:S) ratio] in natural populations or common garden experiments across a total of 98 plant species. 4. Intraspecific leaf N:P ratio and seed mass significantly decreased with latitude in natural populations. Conversely, the plant height decreased and SLA increased significantly with latitude of population origin in common garden experiments. However, less than a third of the investigated latitudinal transect studies also formally disentangled the effects of temperature from other environmental drivers which potentially hampers the translation from latitudinal effects into a temperature signal. 5. Synthesis. Latitudinal gradients provide a methodological set-up to overcome the drawbacks of other observational and experimental warming methods. Our synthesis indicates that many lifehistory traits of plants vary with latitude but the translation of latitudinal clines into responses to temperature is a crucial step. Therefore, especially adaptive differentiation of populations and confounding environmental factors other than temperature need to be considered. More generally, integrated approaches of observational studies along temperature gradients, experimental methods and common garden experiments increasingly emerge as the way forward to further our understanding of species and community responses to climate warming.

The relationship between Body Mass Index (BMI) and work productivity, including absenteeism and presenteeism remains unclear. The objective of this study was to examine work productivity among adults with varied BMI using population-based data. Data source was the 2009–2010 Canadian Community Health Survey. The outcomes reflected work absence (absenteeism) and reduced activities at work (presenteeism). The key explanatory variable was BMI in six categories. Logistic regressions were used to measure the association between outcome and explanatory variables adjusting for potential confounders. The sample consisted of 56,971 respondents ranging in age from 20 to 69years. Relative to normal BMI, the odds of absenteeism were higher for those in the obesity class III (OR=1.60, 95% CI: 1.39; 1.83). Presenteeism was weakly associated with all obesity categories (OR=1.49, 95% CI: 1.38; 1.61, for obesity class I). Overweight was marginally associated with absenteeism and presenteeism. Underweight was inversely associated with absenteeism. This study found that obesity is an independent risk factor for reduced work productivity. Both absenteeism and presenteeism were associated with obesity. However, being overweight was weakly associated with work productivity.

Background Prior studies of clinical prognostication in idiopathic pulmonary fibrosis (IPF) using computed tomography (CT) have often used subjective analyses or have evaluated quantitative measures in isolation. This study examined associations between both densitometric and local histogram based quantitative CT measurements with pulmonary function test (PFT) parameters and mortality. In addition, this study sought to compare risk prediction scores that incorporate quantitative CT measures with previously described systems. Methods Forty six patients with biopsy proven IPF were identified from a registry of patients with interstitial lung disease at Brigham and Women’s Hospital in Boston, MA. CT scans for each subject were visually scored using a previously published method. After a semi-automated method was used to segment the lungs from the surrounding tissue, densitometric measurements including the percent high attenuating area, mean lung density, skewness and kurtosis were made for the entirety of each patient’s lungs. A separate, automated tool was used to detect and quantify the percent of lung occupied by interstitial lung features. These analyses were used to create clinical and quantitative CT based risk prediction scores, and the performance of these was compared to the performance of clinical and visual analysis based methods. Results All of the densitometric measures were correlated with forced vital capacity and diffusing capacity, as were the total amount of interstitial change and the percentage of interstitial change that was honeycombing measured using the local histogram method. Higher percent high attenuating area, higher mean lung density, lower skewness, lower kurtosis and a higher percentage of honeycombing were associated with worse transplant free survival. The quantitative CT based risk prediction scores performed similarly to the clinical and visual analysis based methods. Conclusions Both densitometric and feature based quantitative CT measures correlate with pulmonary function test measures and are associated with transplant free survival. These objective measures may be useful for identifying high risk patients and monitoring disease progression. Further work will be needed to validate these measures and the quantitative imaging based risk prediction scores in other cohorts.