Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise.

SummaryExercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise.

Traditional influenza surveillance informs control strategies but can lag behind outbreak onset and undercount cases. Wastewater surveillance is effective for monitoring near real-time dynamics of outbreaks but has not been attempted for influenza. We quantified influenza A virus (IAV) RNA in wastewater during two active outbreaks on university campuses in different parts of the United States and during different times of year using case data from an outbreak investigation and high-quality surveillance data from student athletes. In both cases, the IAV RNA concentrations were strongly associated with reported IAV incidence rates (Kendall's τ values of 0.58 and 0.67 for the University of Michigan and Stanford University, respectively). Furthermore, the RNA concentrations reflected outbreak patterns and magnitudes. For the University of Michigan outbreak, evidence from sequencing IAV RNA from wastewater indicated the same circulating strain identified in cases during the outbreak. The results demonstrate that wastewater surveillance can effectively detect influenza outbreaks and will therefore be a valuable supplement to traditional forms of influenza surveillance.

Background: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease (CVD), and recent studies have also identified BAT as an endocrine organ. While BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function. Methods: To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation. We then performed lipidomics and identified an increase in the lipokine, 12,13-diHOME. We utilized a mouse model with sustained overexpression of 12,13-diHOME and investigated the role of 12,13-diHOME in a NOS1 -/- mouse and in isolated cardiomyocytes to determine effects on function and respiration. We also investigated 12,13-diHOME in a cohort of human patients with heart disease. Results: Here, we determined that transplantation of BAT (+BAT) improves cardiac function via the release of the lipokine 12,13-diHOME. Sustained overexpression of 12,13-diHOME using tissue nanotransfection negated the deleterious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13-diHOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13-diHOME increased mitochondrial respiration. The effects of 12,13-diHOME were absent in NOS1 -/- mice and cardiomyocytes. We also provide the first evidence that 12,13-diHOME is decreased in human patients with heart disease. Conclusions: Our results identify an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13-diHOME and NOS1.

Importance: Filtering facepiece respirators, including N95 masks, are a critical component of infection prevention in hospitals. Due to unprecedented shortages in N95 respirators, many healthcare systems have explored reprocessing of N95 respirators. Data supporting these approaches are lacking in real hospital settings. In particular, published studies have not yet reported an evaluation of multiple viruses, bacteria, and fungi along with respirator filtration and fit in a single, full-scale study. Objective: We initiated a full-scale study to evaluate different N95 FFR decontamination strategies and their impact on respirator integrity and inactivating multiple microorganisms, with experimental conditions informed by the needs and constraints of the hospital. Methods: We explored several reprocessing methods using new 3MTM 1860 N95 respirators, including dry (<10% relative humidity) and moist (62-66% relative humidity) heat (80-82 oC) in the drying cycle of industrial instrument washers, ethylene oxide (EtO), pulsed xenon UV (UV-PX), hydrogen peroxide gas plasma (HPGP), and vaporous hydrogen peroxide (VHP). Respirator samples were treated and analyzed for biological indicator inactivation using four viruses (MS2, phi6, influenza A virus, murine hepatitis virus), three bacteria (Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus), and the fungus Aspergillus niger. The impact of different application media was also evaluated. In parallel, decontaminated respirators were evaluated for filtration integrity and fit. Results: VHP resulted in >2 log10 inactivation of all tested biological indicators. The combination of UV-PX + moist heat resulted in >2 log10 inactivation of all biological indicators except G. stearothermohphilus. Greater than 95% filtration efficiency was maintained following 2 (UV-PX + <10% relative humidity heat) or 10 (VHP) cycles of treatment, and proper fit was also preserved. UV-PX + dry heat was insufficient to inactivate all biological indicators. Although very effective at virus decontamination, HPGP resulted in decreased filtration efficiency after 3 cycles, and EtO treatment raised potential toxicity concerns. The observed inactivation of viruses with UV-PX, heat, and hydrogen peroxide treatments varied as a function of which culture media (PBS buffer or DMEM) they were deposited in. Conclusions and Relevance: High levels of biological indicator inactivation were achieved following treatment with either moist heat or VHP. These same treatments did not significantly impact mask filtration or fit. Hospitals have a variety of scalable options to safely reprocess N95 masks. Beyond value in the current Covid-19 pandemic, the broad group of microorganisms and conditions tested make these results relevant in potential future pandemic scenarios.

Diego); they were not purchased from the Jackson Laboratory. Both of these changes have now been made online and do not affect the results or conclusions of the study. The authors would like to apologize for any inconvenience this may have caused.

No abstract

Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated.