Gut bacteria and necrotizing enterocolitis: cause or effect?

Development of necrotising enterocolitis (NEC) is considered to be dependent on the bacterial colonisation of the gut. With little concordance between published data and a recent study failing to detect a common strain in infants with NEC, more questions than answers are arising about our understanding of this complex disease

COVID-19 mortality attenuated during widespread Omicron transmission, Denmark, 2020 to 2022

BACKGROUND: It sparked considerable attention from international media when Denmark lifted restrictions against COVID-19 in February 2022 amidst widespread transmission of the new SARS-CoV-2 Omicron variant and a steep rise in reported COVID-19 mortality based on the 30-day COVID-19 death count. AIM: Our aim was to investigate how coincidental infections affected COVID-19 mortality estimates following the introduction of the Omicron variant in late 2021. METHODS: We compared the 30-day COVID-19 death count with the observed mortality using three alternative mortality estimation methods; (i) a mathematical model to correct the 30-day COVID-19 death count for coincidental deaths, (ii) the Causes of Death Registry (CDR) and (iii) all-cause excess mortality. RESULTS: There was a substantial peak in the 30-day COVID-19 death count following the emergence of the Omicron variant in late 2021. However, there was also a substantial change in the proportion of coincidental deaths, increasing from 10–20% to around 40% of the recorded COVID-19 deaths. The high number of 30-day COVID-19 deaths was not reflected in the number of COVID-19 deaths in the CDR and the all-cause excess mortality surveillance. CONCLUSION: Our analysis showed a distinct change in the mortality pattern following the introduction of Omicron in late 2021 with a markedly higher proportion of people estimated to have died with, rather than of, COVID-19 compared with mortality patterns observed earlier in the COVID-19 pandemic. Our findings highlight the importance of incorporating alternative mortality surveillance methods to more correctly estimate the burden of COVID-19 as the pandemic continues to evolve

Airway Inflammation in Chronic Rhinosinusitis with Nasal Polyps and Asthma: The United Airways Concept Further Supported

Background : It has been established that patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have co-existing asthma. Objective : We aimed to test two hypotheses: (i) upper and lower airway inflammation in CRSwNP is uniform in agreement with the united airways concept; and (ii) bronchial inflammation exists in all CRSwNP patients irrespective of clinical asthma status. Methods : We collected biopsies from nasal polyps, inferior turbinates and bronchi of 27 CRSwNP patients and 6 controls. All participants were evaluated for lower airway disease according to international guidelines. Inflammatory cytokines were investigated using a Th1/Th2 assay including 14 chemokines and cytokines; tissue concentrations were normalized according to tissue weight and total protein concentration. Individual cytokines and multivariate inflammatory profiles were compared between biopsy sites and between patients and controls. Results : We found significantly higher concentrations of Th2 cytokines in nasal polyps compared to inferior turbinate and bronchial biopsies. In addition, we showed that the inflammatory profile of nasal polyps and bronchial biopsies correlated significantly (p<0.01). From the Th2 cytokines measured, IL-13 was significantly increased in bronchial biopsies from CRSwNP patients with, but not without asthma. Conclusion : Our findings support the united airways concept; however, we did not find evidence for subclinical bronchial inflammation in CRSwNP patients without asthma. Finally, this study indicates for the first time that nasal polyps potentially play an important role in the airway inflammation rather than being a secondary phenomenon

<em>Enterococcus faecalis</em> Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-kappa B inflammatory response as well as impaired DNA damage response and cell cycle control gene expression

Tools, Techniques and Tightropes: the art of walking and talking private sector management in non-profit organisations

The focus of this paper, first presented at a European Institute for Advanced Studies in Management workshop on challenges of managing in the third sector, is the experiences of small to medium non–profit organisations and their relationship with management tools and techniques. It seeks to raise debate around implications for the creative use of private sector management tools and to contribute to understanding of non–profit management practice. While lessons may be learned from business techniques and processes, the paper contends that execution of business enhancing tools needs to be considered in contexts relevant to the sector's interests and primary aims

Gene expression of the endolymphatic sac

Conclusion: The endolymphatic sac is part of the membranous inner ear and is thought to play a role in the fluid homeostasis and immune defense of the inner ear; however, the exact function of the endolymphatic sac is not fully known. Many of the detected mRNAs in this study suggest that the endolymphatic sac has multiple and diverse functions in the inner ear. Objectives:The objective of this study was to provide a comprehensive review of the genes expressed in the endolymphatic sac in the rat and perform a functional characterization based on measured mRNA abundance. Methods:Microarray technology was used to investigate the gene expression of the endolymphatic sac with the surrounding dura. Characteristic and novel endolymphatic sac genes were determined by comparing with expressions in pure dura. Results: In all, 463 genes were identified specific for the endolymphatic sac. Functional annotation clustering revealed 29 functional clusters

Disability adjusted life years associated with COVID-19 in Denmark in the first year of the pandemic

BACKGROUND: Burden of disease studies measure the public health impact of a disease in a society. The aim of this study was to quantify the direct burden of COVID-19 in the first 12 months of the epidemic in Denmark. METHODS: We collected national surveillance data on positive individuals for SARS-CoV-2 with RT-PCR, hospitalization data, and COVID-19 mortality reported in the period between 26(th) of February, 2020 to 25(th) of February, 2021. We calculated disability adjusted life years (DALYs) based on the European Burden of Disease Network consensus COVID-19 model, which considers mild, severe, critical health states, and premature death. We conducted sensitivity analyses for two different death-registration scenarios, within 30 and 60 days after first positive test, respectively. RESULTS: We estimated that of the 211,823 individuals who tested positive to SARS-CoV-2 by RT-PCR in the one-year period, 124,163 (59%; 95% uncertainty interval (UI) 112,782–133,857) had at least mild symptoms of disease. The total estimated disease burden was 30,180 DALYs (95% UI 30,126; 30,242), corresponding to 520 DALYs/100,000. The disease burden was higher in the age groups above 70 years of age, particularly in men. Years of life lost (YLL) contributed with more than 99% of total DALYs. The results of the scenario analysis showed that defining COVID-19-related fatalities as deaths registered up to 30 days after the first positive test led to a lower YLL estimate than when using a 60-days window. CONCLUSION: COVID-19 led to a substantial public health impact in Denmark in the first full year of the epidemic. Our estimates suggest that it was the the sixth most frequent cause of YLL in Denmark in 2020. This impact will be higher when including the post-acute consequences of COVID-19 and indirect health outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13694-9

Infection stimulated an up-regulation of several transcripts involved in inflammatory and ROS response pathways.

<p>(A) A section of the GSA result. From the portion of gene sets significantly enriched in MKN74 cells infected for 24 hours, a subset of gene sets were manually selected by association with inflammatory response and response to ROS. The numbers in hard brackets indicate effective number of genes in the gene set. The title of each gene set corresponds to the title given on the MSigDB website. Numbers in colored boxes are adjusted p-values (q-values), black indicate statistical significance at 1% Fdr. (B) Characterization by qRT-PCR of transcripts coding for important cytokines and chemokines after <i>E. faecalis</i> infection for 24 hours (MOI50) and 5 days (MOI10). * denotes significantly different from untreated cells p<0.05.</p

<i>E. faecalis</i> infection induced intracellular ROS production.

<p>MKN74 cells infected with <i>E. faecalis</i> for 30 minutes at MOI50. (A) Representative fluorescence microscope image of MKN74 cells stained with ROS detecting probes (green) and superoxide detecting probes (orange) Scale bars  = 50 µm. (B) Quantification of fluorescence intensity using the LSM 510 software. A statistically significant increased intracellular production of ROS (p<0.01) and superoxide (p<0.02) in the infected cells compared to uninfected control cells was observed. * denotes significant difference. (C) Fluorescence image showing MKN74 plasma membrane (red) and <i>E. faecalis</i> (green) after 4 hours of infection. Flanking images show the YZ and XZ plane. (D) Split image of C. No evidence for bacterial invasion of the cells was observed.</p

Proposed model for how chronic infection by pathogenic bacteria affects gastric epithelial cells.

<p>Proposed model for how chronic infection by pathogenic bacteria affects gastric epithelial cells.</p