Butyrate Prevents Induction of CXCL10 and Non-Canonical IRF9 Expression by Activated Human Intestinal Epithelial Cells via HDAC Inhibition

Non-communicable diseases are increasing and have an underlying low-grade inflammation in common, which may affect gut health. To maintain intestinal homeostasis, unwanted epithelial activation needs to be avoided. This study compared the efficacy of butyrate, propionate and acetate to suppress IFN-γ+/−TNF-α induced intestinal epithelial activation in association with their HDAC inhibitory capacity, while studying the canonical and non-canonical STAT1 pathway. HT-29 were activated with IFN-γ+/−TNF-α and treated with short chain fatty acids (SCFAs) or histone deacetylase (HDAC) inhibitors. CXCL10 release and protein and mRNA expression of proteins involved in the STAT1 pathway were determined. All SCFAs dose-dependently inhibited CXCL10 release of the cells after activation with IFN-γ or IFN-γ+TNF-α. Butyrate was the most effective, completely preventing CXCL10 induction. Butyrate did not affect phosphorylated STAT1, nor phosphorylated NFκB p65, but inhibited IRF9 and phosphorylated JAK2 protein expression in activated cells. Additionally, butyrate inhibited CXCL10, SOCS1, JAK2 and IRF9 mRNA in activated cells. The effect of butyrate was mimicked by class I HDAC inhibitors and a general HDAC inhibitor Trichostatin A. Butyrate is the most potent inhibitor of CXCL10 release compared to other SCFAs and acts via HDAC inhibition. This causes downregulation of CXCL10, JAK2 and IRF9 genes, resulting in a decreased IRF9 protein expression which inhibits the non-canonical pathway and CXCL10 transcription

The course of health-related quality of life in the first 2 years after a diagnosis of head and neck cancer:the role of personal, clinical, psychological, physical, social, lifestyle, disease-related, and biological factors

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors. Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment. Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months. Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment.</p

Fusarium: more than a node or a foot-shaped basal cell

Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org)

Awakening from the listeriosis crisis: Food safety challenges, practices and governance in the food retail sector in South Africa

The recent listeriosis outbreak in South Africa brought food safety concerns to the fore in terms of both policy and practice. These concerns encompass both health and nutrition aspects, as well as the economy, because the food system in South Africa contributes significantly to economic growth and food security. However, the food sector is challenged with food safety risks, such as foodborne diseases, food fraud and a general lack of effective enforcement of regulation. The inability of government to effectively regulate the food sector is a contributing factor to increased food safety risks. Focusing on the formal sector, which is subject to regulation, this review provides an overview of the current state of food safety policies and regulations, food safety challenges, and food safety practices in the food system, after the listeriosis crisis of 2017 and 2018

Different Patterns of Kidney Fibrosis Are Indicative of Injury to Distinct Renal Compartments

Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury

A modelling framework for assessment of arterial compliance by fusion of oscillometry and pulse wave velocity information

Background and Objectives: Measurement of arterial compliance is recognized as important for clinical use and for enabling better understanding of circulatory system regulation mechanisms. Estimation of arterial compliance involves either a direct measure of the ratio between arterial volume and pressure changes or an inference from the pulse wave velocity (PWV). In this study we demonstrate an approach to assess arterial compliance by fusion of these two information sources. The approach is based on combining oscillometry as used for blood pressure inference and PWV measurements based on ECG/PPG. Enabling reliable arterial compliance measurements will contribute to the understanding of regulation mechanisms of the arterial tree, possibly establishing arterial compliance as a key measure relevant in hemodynamic monitoring. Methods: A measurement strategy, a physiological model, and a framework based on Bayesian principles are developed for measuring changes in arterial compliance based on combining oscillometry and PWV data. A simulation framework is used to study and validate the algorithm and measurement principle in detail, motivated by previous experimental findings. Results: Simulations demonstrate the possibility of inferring arterial compliance via fusion of simultaneously acquired volume/pressure relationships and PWV data. In addition, the simulation framework demonstrates how Bayesian principles can be used to handle low signal – to – noise ratio and partial information loss. Conclusions: The developed simulation framework shows the feasibility of the proposed approach for assessment of arterial compliance by combining multiple data sources. This represents a first step towards integration of arterial compliance measurements in hemodynamic monitoring using existing clinical technology. The Bayesian approach is of particular relevance for such patient monitoring settings, where measurements are repeated frequently, context is relevant, and data is affected by artefacts. In addition, the simulation framework is necessary for future clinical-study design, in order to determine device specifications and the extent to which noise affects the inference process

Method for measurement of arterial compliance by fusion of oscillometry and pulse wave velocity

Up until now estimation of arterial compliance has been performed either by analysis of arterial pressure changes with respect to volume changes or by inference based on pulse wave velocity (PWV). In this study we demonstrate the possibility of an approach to assess arterial compliance by fusing the two information sources namely the pressure/volume relationship obtained from oscillography and PWV data. The goal is to assess arterial properties easily and robustly, enhancing current hemodynamic monitoring. The approach requires as input signals: an electrocardiogram (ECG), a photo- plethysmogram (PPG) and the arterial oscillation as measured during non-invasive blood pressure measurements based on oscillometry with a cuff. These signals are fused by an algorithm using Bayesian principles underpinned by a physiological model. In our simulations, we demonstrate the feasibility to infer arterial compliance by our proposed strategy. A very first measurement on a healthy volunteer supports our findings from the simulation.Clinical Relevance - Arterial compliance/stiffness is recognized as a key hemodynamic parameter, which is not easily accessible and not a standard parameter currently. The presented method and obtained results are encouraging for future research in this area

Air cuff transducer design for occlusion-based hemodynamic measurements - An experimental and simulation study

In standard clinical practice, cuff devices are widely used for non-invasive blood pressure measurements (NIBP). However, cuff-based NIBP is prone to large errors especially in cases of hypo- and hypertension. In addition to this, the cuff measurement principle allows for estimation of a number of other hemodynamic parameters (e. g. cardiac output, arterial stiffness, augmentation index) by means of analysis of the pulse waveform and/or pulse amplitude recorded in the cuff pressure. However, in standard practice, the cuff is still only used for the measurement of BP.A key reason for the observed measurement errors and the limited set of extracted parameters lies in our poor understanding of the cuff device as a transducer; the cuff pressure response to arm volume pulsations (the cuff transfer function TFcuff) depends on a large number of factors. It is not yet clear to what extent the cuff contributes to the NIBP error, or if the cuff in its current format is reliable for measurement of arterial pulse waveform/amplitude. In this study, we investigate the isolated cuff in order to gain a better understanding of the main sources of measurement errors. By using an experimental setup which measures the cuff response to mechanically simulated arm pulsations, we find that the cuff can explain part of the NIBP errors in cases of hypotension. Also, we find that pulse waveforms can be estimated using a standard cuff; however, measurement of the pulse volume amplitude is unfeasible. We demonstrate that the observed inaccuracies can be eliminated by usage of a calibrator device which obtains real-time information on TFcuff. These findings will enable further investigation of the effects related to the pulse travel along the compressed limb and the interaction between cuff, arm tissue, distal arm hemodynamics and arterial walls for the development of improved occlusion-based measurement strategies

New Hemodynamic Parameters in Peri-Operative and Critical Care: Challenges in Translation

Hemodynamic monitoring technologies are evolving continuously—a large number of bedside monitoring options are becoming available in the clinic. Methods such as echocardiography, electrical bioimpedance, and calibrated/uncalibrated analysis of pulse contours are becoming increasingly common. This is leading to a decline in the use of highly invasive monitoring and allowing for safer, more accurate, and continuous measurements. The new devices mainly aim to monitor the well-known hemodynamic variables (e.g., novel pulse contour, bioreactance methods are aimed at measuring widely-used variables such as blood pressure, cardiac output). Even though hemodynamic monitoring is now safer and more accurate, a number of issues remain due to the limited amount of information available for diagnosis and treatment. Extensive work is being carried out in order to allow for more hemodynamic parameters to be measured in the clinic. In this review, we identify and discuss the main sensing strategies aimed at obtaining a more complete picture of the hemodynamic status of a patient, namely: (i) measurement of the circulatory system response to a defined stimulus; (ii) measurement of the microcirculation; (iii) technologies for assessing dynamic vascular mechanisms; and (iv) machine learning methods. By analyzing these four main research strategies, we aim to convey the key aspects, challenges, and clinical value of measuring novel hemodynamic parameters in critical care