Abstract
Background
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium- to large-sized ...respiratory droplets, although airborne transmission may be possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19.
Methods
We used a well-established golden Syrian hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index hamsters and naive hamsters into closed system units each comprising 2 different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed between the cages was investigated. Besides clinical scoring, hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression.
Results
Noncontact transmission was found in 66.7% (10/15) of exposed naive hamsters. Surgical mask partition for challenged index or naive hamsters significantly reduced transmission to 25% (6/24, P = .018). Surgical mask partition for challenged index hamsters significantly reduced transmission to only 16.7% (2/12, P = .019) of exposed naive hamsters. Unlike the severe manifestations of challenged hamsters, infected naive hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues.
Conclusions
SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei which could be reduced by surgical mask partition in the hamster model. This is the first in vivo experimental evidence to support the possible benefit of surgical mask in prevention of COVID-19 transmission, especially when masks were worn by infected individuals.
Noncontact transmission of SARS-CoV-2 was demonstrated in a Syrian hamster model. Surgical mask partition significantly reduced the transmission of SARS-CoV-2 from challenged index hamsters to the exposed naive hamsters via respiratory droplets and/or airborne droplet nuclei.
Localization is an important research topic that has been applied in many different applications. Different wireless technologies have been applied in localization but each has its own limitations. ...LoRa wireless technology has recently been proposed to support M2M (Machine-to-Machine) and IoT (Internet of Things) applications. Its key features (long range, low power and low cost) show that LoRa technology can be an appropriate alternative for localization in both large-scale indoor and outdoor environments. To the best of our knowledge, we are among the first (1) working on localization using LoRa technology, (2) to develop RSSI-based (Receiver Signal Strength Indicator based) localization algorithms in LoRa networks, and (3) to reduce the effect of Gaussian and non-Gaussian noise during localization in LoRa networks. This paper proposes different RSSI-based localization algorithms to reduce the effect of Gaussian and non-Gaussian noise in LoRa networks. The performance investigation in our simulation models and real experiments show that the proposed localization algorithms work properly in both outdoor and large-scale indoor environments. In outdoor environments, their performance is comparable to GPS (Global Positioning System), the most popular satellite-based localization system.
Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have ...better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO).
We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded.
A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 95% CI 1.214-4.314, p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 95% CI 1.018-1.104, p = 0.005) or MP referenced to PBW (HR 1.004 95% CI 1.002-1.007, p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H
O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H
O) (63.6% vs. 29.7%, p < 0.001).
MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.
Stomach and intestinal stem cells are located in discrete niches called the isthmus and crypt, respectively. Recent studies have demonstrated a surprisingly conserved role for Wnt signaling in ...gastrointestinal development. Although intestinal stromal cells secrete Wnt ligands to promote stem cell renewal, the source of stomach Wnt ligands is still unclear. Here, by performing single cell analysis, we identify gastrointestinal stromal cell populations with transcriptome signatures that are conserved between the stomach and intestine. In close proximity to epithelial cells, these perictye-like cells highly express telocyte and pericyte markers as well as Wnt ligands, and they are enriched for Hh signaling. By analyzing mice activated for Hh signaling, we show a conserved mechanism of GLI2 activation of Wnt ligands. Moreover, genetic inhibition of Wnt secretion in perictye-like stromal cells or stromal cells more broadly demonstrates their essential roles in gastrointestinal regeneration and development, respectively, highlighting a redundancy in gastrointestinal stem cell niches.
Abstract
Background
Waning immunity occurs in patients who have recovered from Coronavirus Disease 2019 (COVID-19). However, it remains unclear whether true re-infection occurs.
Methods
Whole genome ...sequencing was performed directly on respiratory specimens collected during 2 episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG, were analyzed.
Results
The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was evidence of acute infection including elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. The virus genome from the first episode contained a a stop codon at position 64 of ORF8, leading to a truncation of 58 amino acids. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. Compared to viral genomes in GISAID, the first virus genome was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020.
Conclusions
Epidemiological, clinical, serological, and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among humans despite herd immunity due to natural infection. Further studies of patients with re-infection will shed light on protective immunological correlates for guiding vaccine design.
Our results suggest SARS-CoV-2 may continue to circulate among the human populations despite herd immunity due to natural infection or vaccination. Further studies of patients with re-infection will shed light on protective correlates important for vaccine design.
Biological nitrogen fixation is catalyzed by the enzyme nitrogenase, which facilitates the cleavage of the relatively inert triple bond of N2. Nitrogenase is most commonly associated with the ...molybdenum–iron cofactor called FeMoco or the M-cluster, and it has been the subject of extensive structural and spectroscopic characterization over the past 60 years. In the late 1980s and early 1990s, two “alternative nitrogenase” systems were discovered, isolated, and found to incorporate V or Fe in place of Mo. These systems are regulated by separate gene clusters; however, there is a high degree of structural and functional similarity between each nitrogenase. Limited studies with the V- and Fe-nitrogenases initially demonstrated that these enzymes were analogously active as the Mo-nitrogenase, but more recent investigations have found capabilities that are unique to the alternative systems. In this review, we will discuss the reactivity, biosynthetic, and mechanistic proposals for the alternative nitrogenases as well as their electronic and structural properties in comparison to the well-characterized Mo-dependent system. Studies over the past 10 years have been particularly fruitful, though key aspects about V- and Fe-nitrogenases remain unexplored.
The active site of nitrogenase, the M-cluster, is a metal-sulfur cluster containing a carbide at its core. Using radiolabeling experiments, we show that this carbide originates from the methyl group ...of S-adenosylmethionine (SAM) and that it is inserted into the M-cluster by the assembly protein NifB. Our SAM cleavage and deuterium substitution analyses suggest a similarity between the mechanism of carbon insertion by NifB and the proposed mechanism of RNA methylation by the radical SAM enzymes RlmN and Cfr, which involves methyl transfer from one SAM equivalent, followed by hydrogen atom abstraction from the methyl group by a 5'-deoxyadenosyl radical generated from a second SAM equivalent. This work is an initial step toward unraveling the importance of the interstitial carbide and providing insights into the nitrogenase mechanism.
The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It ...remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity‐modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five‐year progression‐free survival (PFS), overall survival (OS) and cancer‐specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA‐I (T1–T4 N0–N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA‐II (T1–T4 N0–N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA‐III (T1–T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA‐IVA (T3–T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1–T2 N0–N2; II: T3–T4 N0–N2 or T1–T2 N3 and III: T3–T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA‐based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.
What's new?
The AJCC/UICC TNM stage classification is the most widely accepted common language to describe the magnitude and spread of cancer. However, a new pretreatment staging system comprising both anatomic and non‐anatomic factors is warranted to improve survival prediction. Here, the authors propose new stage groups incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA for non‐metastatic nasopharyngeal carcinoma (NPC). Their prospective study measuring pretreatment plasma EBV DNA in 518 completely staged non‐metastatic NPC patients who were later treated with intensity‐modulated radiation therapy with/without adjunct chemotherapy demonstrates significantly better survival prediction with the newly proposed stages as compared to the current edition TNM.
The objective of this study was to compare virulence among different Aeromonas species causing bloodstream infections.
Nine of four species of Aeromonas blood isolates, including A. dhakensis, A. ...hydrophila, A. veronii and A. caviae were randomly selected for analysis. The species was identified by the DNA sequence matching of rpoD. Clinically, the patients with A. dhakensis bacteremia had a higher sepsis-related mortality rate than those with other species (37.5% vs. 0%, P = 0.028). Virulence of different Aeromonas species were tested in C. elegans, mouse fibroblast C2C12 cell line and BALB/c mice models. C. elegans fed with A. dhakensis and A. caviae had the lowest and highest survival rates compared with other species, respectively (all P values <0.0001). A. dhakensis isolates also exhibited more cytotoxicity in C2C12 cell line (all P values <0.0001). Fourteen-day survival rate of mice intramuscularly inoculated with A. dhakensis was lower than that of other species (all P values <0.0001). Hemolytic activity and several virulence factor genes were rarely detected in the A. caviae isolates.
Clinical data, ex vivo experiments, and animal studies suggest there is virulence variation among clinically important Aeromonas species.
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