Abstract
Background
The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated ...infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis.
Methods
We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention’s Emerging Infections Program during April–August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher’s exact tests.
Results
Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit–level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%).
Conclusions
One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.
We used surveillance data to assess differences in candidemia patients with and without a prior COVID-19 diagnosis. Patients with COVID-19 and candidemia lacked established underlying conditions associated with candidemia but had twice the mortality rate versus candidemia patients without COVID-19.
The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor ...in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transcriptomic analyses have identified tens of thousands of intergenic, intronic, and cis-antisense long noncoding RNAs (lncRNAs) that are expressed from mammalian genomes. Despite progress in ...functional characterization, little is known about the post-transcriptional regulation of lncRNAs and their half-lives. Although many are easily detectable by a variety of techniques, it has been assumed that lncRNAs are generally unstable, but this has not been examined genome-wide. Utilizing a custom noncoding RNA array, we determined the half-lives of ∼800 lncRNAs and ∼12,000 mRNAs in the mouse Neuro-2a cell line. We find only a minority of lncRNAs are unstable. LncRNA half-lives vary over a wide range, comparable to, although on average less than, that of mRNAs, suggestive of complex metabolism and widespread functionality. Combining half-lives with comprehensive lncRNA annotations identified hundreds of unstable (half-life < 2 h) intergenic, cis-antisense, and intronic lncRNAs, as well as lncRNAs showing extreme stability (half-life > 16 h). Analysis of lncRNA features revealed that intergenic and cis-antisense RNAs are more stable than those derived from introns, as are spliced lncRNAs compared to unspliced (single exon) transcripts. Subcellular localization of lncRNAs indicated widespread trafficking to different cellular locations, with nuclear-localized lncRNAs more likely to be unstable. Surprisingly, one of the least stable lncRNAs is the well-characterized paraspeckle RNA Neat1, suggesting Neat1 instability contributes to the dynamic nature of this subnuclear domain. We have created an online interactive resource (http://stability.matticklab.com) that allows easy navigation of lncRNA and mRNA stability profiles and provides a comprehensive annotation of ~7200 mouse lncRNAs.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and ...immunosuppression carry a high morbidity and mortality, and polymorphisms in genes related to epithelial integrity and host defense predispose to IPF.
To investigate the role of bacteria in the pathogenesis and progression of IPF.
We prospectively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, nonsmokers, and subjects with moderate chronic obstructive pulmonary disease as control subjects. Subjects underwent bronchoalveolar lavage (BAL), from which genomic DNA was isolated. The V3-V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA quantitative polymerase chain reaction and pyrosequencing.
Sixty-five patients with IPF had double the burden of bacteria in BAL fluid compared with 44 control subjects. Baseline bacterial burden predicted the rate of decline in lung volume and risk of death and associated independently with the rs35705950 polymorphism of the MUC5B mucin gene, a proven host susceptibility factor for IPF. Sequencing yielded 912,883 high-quality reads from all subjects. We identified Haemophilus, Streptococcus, Neisseria, and Veillonella spp. to be more abundant in cases than control subjects. Regression analyses indicated that these specific operational taxonomic units as well as bacterial burden associated independently with IPF.
IPF is characterized by an increased bacterial burden in BAL that predicts decline in lung function and death. Trials of antimicrobial therapy are needed to determine if microbial burden is pathogenic in the disease.
To study macular hole (MH) surgery in terms of baseline demographics, intraoperative complications, post-vitrectomy cataract, reoperation, and visual outcome.
National Ophthalmology Database study.
A ...total of 1078 eyes from 1045 patients undergoing primary MH surgery.
Participating centers prospectively collected clinical data using a single electronic medical record (EMR) system, with automatic extraction of anonymized data to a national database, over 8 years. The following data were extracted for eyes undergoing MH surgery: demographics, procedure elements, intraoperative complications, visual acuity (VA), and further surgery.
Description of the primary procedures performed, intraoperative complication rate, change in VA, proportion of eyes undergoing subsequent surgery for persisting MH, cataract, or retinal detachment.
The median age was 70.3 years, with a 2.2:1 female preponderance. All operations included a pars plana vitrectomy (PPV)-41.1% with hexafluoroethane (C2F6), 25.6% with perfluoropropane (C3F8), 24.5% with sulfahexafluoride (SF6), 2.2% with air, and 0.4% with silicone oil. A PPV was combined with internal limiting membrane (ILM) peel in 94.1% and cataract surgery in 40.5%. One or more intraoperative complications occurred in 12.4%. The median presenting logarithm of the minimum angle of resolution (logMAR) VA improved from 0.80 to 0.50 after a median follow-up of 0.6 years; 57.8% of eyes improved ≥0.30 logMAR units (∼2 Snellen lines). The choice of gas tamponade did not significantly influence the visual outcome, but eyes undergoing ILM peel were significantly more likely to gain ≥0.30 logMAR units, as were eyes with poor presenting VA. Subsequently, 4.2% of eyes underwent repeat surgery for MH and 2.4% for retinal detachment, and, excluding pseudophakic eyes, 64.6% underwent cataract surgery within 1 year.
This study provides pooled, anonymized data on the demographics, complications, and visual outcome of MH surgery. This may enable vitreoretinal surgeons to benchmark their case-mix and outcomes, and facilitate risk-benefit and cost-benefit analyses.
Developing tissues that contain mutant or compromised cells present risks to animal health. Accordingly, the appearance of a population of suboptimal cells in a tissue elicits cellular interactions ...that prevent their contribution to the adult. Here we report that this quality control process, cell competition, uses specific components of the evolutionarily ancient and conserved innate immune system to eliminate Drosophila cells perceived as unfit. We find that Toll-related receptors (TRRs) and the cytokine Spätzle (Spz) lead to NFκB-dependent apoptosis. Diverse "loser" cells require different TRRs and NFκB factors and activate distinct pro-death genes, implying that the particular response is stipulated by the competitive context. Our findings demonstrate a functional repurposing of components of TRRs and NFκB signaling modules in the surveillance of cell fitness during development.
An unambiguous determination of the three-dimensional structure of nanoparticles is challenging. Electron tomography requires a series of images taken for many different specimen orientations. This ...approach is ideal for stable and stationary structures. But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam, constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy, coupled with simple imaging simulation, to determine with atomic resolution the size, three-dimensional shape, orientation and atomic arrangement of size-selected gold nanoclusters that are preformed in the gas phase and soft-landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 309±6 atoms can be identified with either Ino-decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years. We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions. We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
In this study, 454 pyrosequencing of the 16S rRNA gene was used to investigate sediment bacterial community response to contaminant disturbance across six estuaries with differing levels of ...‘modification’. We observed a significant influence of metal and polycyclic aromatic hydrocarbon contaminants in shaping bacterial community composition, structure and diversity, with metals being the more influential contaminant. An abundant and pervasive ‘core’ set of bacteria found in every sample were largely responsible for mediating community response to contamination. These 13 core operational taxonomic units were mostly comprised of Gamma‐, Delta‐, Alphaproteobacteria and Acidobacteria. Sediment silt and metals together explained the most variation in bacterial community composition (19.7%). Following this strong contaminant signature, salinity and temperature represented important environmental variables predicting 10.9% of community variation. While overall network connectivity measures supported the idea of an inherently diverse soil microbiome with some degree of functional redundancy, lower values observed in contaminated sediments indicate potential structural perturbations in the community from fracturing or loss of bacterial associations. The large number of unclassified sequences obtained in this study contribute to improving our understanding of environmentally relevant strains in relation to anthropogenic contamination, which have been overlooked in laboratory studies.
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