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Purpose We investigated the impact of surgical masks (SM) during oxygen therapy using oxygen masks in volunteer- and simulation-based studies. Methods Fifteen volunteers wore the Hudson RCI.sup.® or Open-Face Mask.sup.® with/without an SM. The fraction of inspired oxygen concentration (FIO.sub.2), end-tidal CO.sub.2 (EtCO.sub.2), partial pressure of inspired CO.sub.2 (PICO.sub.2), and respiratory rate (RR) were measured. The oxygen flow rate increased from 0 to 10 L/min. In the simulation-based study, FIO.sub.2 was measured using a simulator that reproduced spontaneous breathing. RR was 12 or 24 bpm, and the tidal volume (Tv) was 300, 500, or 700 mL. The effect of oxygen mask fitting conditions was also examined. The primary outcome measure was FIO.sub.2 at 6 L/min. Results In the volunteer-based study, FIO.sub.2 was reduced when the SM was used with the Hudson RCI.sup.® or Open-Face Mask.sup.®. The FIO.sub.2 drop was larger with the Open-Face Mask.sup.® than with the Hudson RCI.sup.®. The RR, EtCO.sub.2, and PICO.sub.2 significantly changed with the SM, but the differences were not clinically meaningful. In the simulation-based study, the SM with the Hudson RCI.sup.® did not reduce FIO.sub.2, but the SM with the Open-Face Mask.sup.® significantly decreased FIO.sub.2 under several conditions. However, the SM with the Hudson Mask.sup.® reduced FIO.sub.2 when the fit of the mask was inadequate. With the Open-Face Mask.sup.®, lower RR and Tv resulted in larger differences in FIO.sub.2. Conclusions The SM decreased FIO.sub.2 during oxygen therapy with oxygen masks. The impact of SM depended on the type of the oxygen mask, mask fitting, and respiratory condition., Author(s): Michiko Kinoshita [sup.1], Yuki Ishikawa [sup.1], Ryo Sekiguchi [sup.1], Miyuki Matsuda [sup.1], Katsuya Tanaka [sup.1] Author Affiliations: (1) grid.412772.5, 0000 0004 0378 2191, Department of Anesthesiology, Tokushima University Hospital, [...]

Anti-aminoacyl-tRNA synthetase (ARS) antibodies are myositis-specific antibodies associated with anti-synthetase syndrome (ASSD). Some patients are positive for anti-ARS antibodies on enzyme-linked immunosorbent assay (ELISA) but negative on RNA-immunoprecipitation (RNA-IP) (the gold standard method). Whether these patients should be considered truly positive for anti-ARS antibodies remains unclear. Therefore, we investigated the clinical characteristics of these patients and verified the authenticity of their anti-ARS positivity. Patients who were positive for anti-ARS antibodies on ELISA were divided into the non-discrepant (positive on RNA-IP, n = 52) and discrepant (negative on RNA-IP, n = 8) groups. Patient clinical characteristics were compared between the groups. For each positive individual, the authenticity of anti-ARS antibody positivity on ELISA was cross-examined using protein-IP and western blotting. All patients in the discrepant group had lung involvement, including five (63%) with interstitial lung disease. The overall survival time was significantly lower in the discrepant group than in the non-discrepant group (p < 0.05). Validation tests confirmed the presence of anti-ARS antibodies in the sera of the discrepant group but indicated different reactivity from typical anti-ARS antibodies. In conclusion, some anti-ARS antibodies are detected by ELISA but not RNA-IP. Such anti-ARS antibody discrepancies need further elucidation to attain validation of the diagnostic process in ASSD. [ABSTRACT FROM AUTHOR]

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

Natural selection signatures across Japanese subpopulations are under-explored. Here we conducted genome-wide selection scans with 622,926 single nucleotide polymorphisms for 20,366 Japanese individuals, who were recruited from the main-islands of Japanese Archipelago (Hondo) and the Ryukyu Archipelago (Ryukyu), representing two major Japanese subpopulations. The integrated haplotype score (iHS) analysis identified several signals in one or both subpopulations. We found a novel candidate locus at IKZF2, especially in Ryukyu. Significant signals were observed in the major histocompatibility complex region in both subpopulations. The lead variants differed and demonstrated substantial allele frequency differences between Hondo and Ryukyu. The lead variant in Hondo tags HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 , a haplotype specific to Japanese and Korean. While in Ryukyu, the lead variant tags DRB1*15:01-DQB1*06:02 , which had been recognized as a genetic risk factor for narcolepsy. In contrast, it is reported to confer protective effects against type 1 diabetes and human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. The FastSMC analysis identified 8 loci potentially affected by selection within the past 20–150 generations, including 2 novel candidate loci. The analysis also showed differences in selection patterns of ALDH2 between Hondo and Ryukyu, a gene recognized to be specifically targeted by selection in East Asian. In summary, our study provided insights into the selection signatures within the Japanese and nominated potential sources of selection pressure. [ABSTRACT FROM AUTHOR]