Dysregulation of circulating collagen turnover markers in very early systemic sclerosis.

Objective: Clinical observation suggests that vascular activation and autoimmunity precede remodelling of the extracellular matrix (ECM) in systemic sclerosis (SSc). We challenge this paradigm by hypothesising that ECM biomarkers are already disturbed in patients with very early SSc (veSSc) when fibrosis is not yet clinically detectable.

Methods: 42 patients with veSSc, defined as the presence of Raynaud's phenomenon and at least one of puffy fingers, positive antinuclear antibodies or pathological nailfold capillaroscopy, not meeting the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for SSc, were compared with healthy controls (HCs, n=29).

Fibroblasts are not just fibroblasts: clear differences between dermal and pulmonary fibroblasts' response to fibrotic growth factors.

Systemic Sclerosis (SSc) hallmark is skin fibrosis, but up to 80% of the patients have fibrotic involvement in the pulmonary system. Antifibrotic drugs which have failed in a general SSc population have now been approved in patients with SSc-associated interstitial lung disease (ILD). This indicates that the fibrotic progression and regulation of fibroblasts likely depend on local factors specific to the tissue type.

Binge drinking induces an acute burst of markers of hepatic fibrogenesis (PRO-C3).

Background & Aims: Binge drinking is associated with an increased risk of liver disease. Morbidity and mortality of alcohol-related liver disease (ALD) is associated with collagen deposition in the hepatic extracellular matrix (ECM). However, the acute effects of binge drinking on ECM turnover are unknown.

Circulating collagen neo-epitopes and their role in the prediction of fibrosis in patients with systemic sclerosis: a multicentre cohort study.

Background: Extracellular matrix remodelling is a hallmark of systemic sclerosis. We evaluated extracellular matrix neo-epitopes as potential serum biomarkers for progression of fibrosis in systemic sclerosis.

Methods: We included patients meeting the 2013 American College of Rheumatology and European League Against Rheumatism criteria and healthy controls from a derivation and validation cohort.

Dermal fibroblasts have different extracellular matrix profiles induced by TGF-β, PDGF and IL-6 in a model for skin fibrosis.

Different stimulants might induce different extracellular matrix profiles. It is essential to gain an understanding and quantification of these changes to allow for focused anti-fibrotic drug development. This study investigated the expression of extracellular matrix by dermal fibroblast mimicking fibrotic skin diseases as SSc using clinically validated biomarkers.

Type III, IV, and VI Collagens Turnover in Systemic Sclerosis - a Longitudinal Study.

Tissue turnover, especially in the skin, is altered in systemic sclerosis (SSc), leading to tissue accumulation. The objective was to examine type III, IV, and VI collagens turnovers in SSc and investigate longitudinal alterations in relation to modified Rodnan Skin Score (mRSS). We included patients fulfilling the 2013 ACR/EULAR criteria for SSc (limited cutaneous [lcSSc, n = 20], diffuse cutaneous SSc [dcSSc, n = 23]) and healthy controls (HC, n = 10).

Correlation between serological biomarkers of extracellular matrix turnover and lung fibrosis and pulmonary artery hypertension in patients with systemic sclerosis.

Objective: To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).

Methods: Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover, excluding type II collagen, were evaluated using nine serological biomarkers.

Association of metabolites reflecting type III and VI collagen formation with modified Rodnan skin score in systemic sclerosis - a cross-sectional study.

The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS). Limited (lSSc,  = 76) and diffuse SSc (dSSc,  = 41) fulfilling the ACR/EULAR 1980 and 2013 classification criteria for SSc and asymptomatic controls ( = 9) were included. PRO-C1, PRO-C3 and PRO-C6 were measured in serum.

Serum biomarkers of collagen turnover as potential diagnostic tools in diffuse systemic sclerosis: A cross-sectional study.

Background: Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and the diagnostic power of these.

Citrullinated vimentin and biglycan protein fingerprints as candidate serological biomarkers for disease activity in systemic sclerosis: a pilot study.

Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin) could identify diffuse SSc (dSSc) subjects from controls and the biomarkers discriminative power. DSSc subjects ( = 40) fulfilling the 2013 EULAR/ACR classification criteria were divided in early (<2years of symptoms) and late (≥10 years of symptoms).

Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis.

Objectives: The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular matrix of the synovial lining layer. We aimed to investigate the association of type IV collagen turnover with RA disease activity, response to IL-6 inhibition and radiographic progression.

Type V Collagen is Persistently Altered After Inguinal Hernia Repair.

Background And Aims: Hernia formation is associated with alterations of collagen metabolism. Collagen synthesis and degradation cause a systemic release of products, which are measurable in serum. Recently, we reported changes in type V and IV collagen metabolisms in patients with inguinal and incisional hernia.

Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders.

Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients with systemic sclerosis (SSc), whereas reduced levels in the airways have been related to asthma.

IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE study.

Objectives: The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders.

Methods: RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase III trial. RA patients with previous inadequate response to anti-TNFα therapy (n=299) were randomly assigned to tocilizumab 4 or 8 mg/kg with methotrexate (10-25 mg weekly) or placebo with methotrexate.

Reproducibility of Dual-Microphone Voice Range Profile Equipment.

Purpose: The aim of this study was to add further knowledge about the usefulness of the Voice Range Profile (VRP) assessment in clinical settings and research by analyzing VRP dual-microphone equipment precision, reliability, and room effect.

Method: Test-retest studies were conducted in an anechoic chamber and an office: (a) comparing sound pressure levels (SPLs) from a dual-microphone VRP device, the Voice Profiler, when given the same input repeatedly (test-retest reliability); (b) comparing SPLs from 3 devices when given the same input repeatedly (intervariation); and (c) assessing the room effect.

Results: (a) The mean standard deviation across 17 measurement points was 0.

Simulated Critical Differences for Speech Reception Thresholds.

Purpose: Critical differences state by how much 2 test results have to differ in order to be significantly different. Critical differences for discrimination scores have been available for several decades, but they do not exist for speech reception thresholds (SRTs). This study presents and discusses how critical differences for SRTs can be estimated by Monte Carlo simulations.

Speech perception in medico-legal assessment of hearing disabilities.

Objective: Examination of Danish data for medico-legal compensations regarding hearing disabilities. The study purposes are: (1) to investigate whether discrimination scores (DSs) relate to patients' subjective experience of their hearing and communication ability (the latter referring to audio-visual perception), (2) to compare DSs from different discrimination tests (auditory/audio-visual perception and without/with noise), and (3) to relate different handicap measures in the scaling used for compensation purposes in Denmark.

Design: Data from a 15 year period (1999-2014) were collected and analysed.

User-operated speech in noise test: implementation and comparison with a traditional test.

Objective: The purpose of this study was to implement and evaluate a user-operated speech in noise test.

Design: The test is based on the Danish speech material Dantale II, which consists of five words sentences ( Wagener et al, 2003 ). For each word presented the subject selected a response from ten alternative words.

An axisymmetric boundary element formulation of sound wave propagation in fluids including viscous and thermal losses.

The formulation presented in this paper is based on the boundary element method (BEM) and implements Kirchhoff's decomposition into viscous, thermal, and acoustic components, which can be treated independently everywhere in the domain except on the boundaries. The acoustic variables with losses are solved using extended boundary conditions that assume (i) negligible temperature fluctuations at the boundary and (ii) normal and tangential matching of the boundary's particle velocity. The proposed model does not require constructing a special mesh for the viscous and thermal boundary layers as is the case with the existing finite element method (FEM) implementations with losses.

The triterpene cyclase protein family: a systematic analysis.

Triterpene cyclases catalyze a broad range of cyclization reactions to form polycyclic triterpenes. Triterpene cyclases that convert squalene to hopene are named squalene-hopene cyclases (SHC) and triterpene cyclases that convert oxidosqualene are named oxidosqualene cyclases (OSC). Many sequences have been published, but there is only one structure available for each of SHCs and OSCs.

Sound exposure of symphony orchestra musicians.

Background: Assessment of sound exposure by noise dosimetry can be challenging especially when measuring the exposure of classical orchestra musicians where sound originate from many different instruments. A new measurement method of bilateral sound exposure of classical musicians was developed and used to characterize sound exposure of the left and right ear simultaneously in two different symphony orchestras.

Objectives: To measure binaural sound exposure of professional classical musicians and to identify possible exposure risk factors of specific musicians.

Engineering of Candida antarctica lipase B for hydrolysis of bulky carboxylic acid esters.

Candida antarctica lipase B (CALB) is a widely used biocatalyst with high activity and specificity for a wide range of primary and secondary alcohols. However, the range of converted carboxylic acids is more narrow and mainly limited to unbranched fatty acids. To further broaden the biotechnological applications of CALB it is of interest to expand the range of converted carboxylic acid and extend it to carboxylic acids that are branched or substituted in close proximity of the carboxyl group.

Structural classification by the Lipase Engineering Database: a case study of Candida antarctica lipase A.

Background: The Lipase Engineering Database (LED) integrates information on sequence, structure and function of lipases, esterases and related proteins with the alpha/beta hydrolase fold. A new superfamily for Candida antarctica lipase A (CALA) was introduced including the recently published crystal structure of CALA. Since CALA has a highly divergent sequence in comparison to other alpha/beta hydrolases, the Lipase Engineering Database was used to classify CALA in the frame of the already established classification system.

Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking.

Background: Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate.