Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines

BACKGROUND: Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes. RESULTS: We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC) and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L), GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files. CONCLUSION: This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases

Physiological and autonomic stress responses after prolonged sleep restriction and subsequent recovery sleep in healthy young men

Purpose Sleep restriction is increasingly common and associated with the development of health problems. We investigated how the neuroendocrine stress systems respond to prolonged sleep restriction and subsequent recovery sleep in healthy young men. Methods After two baseline (BL) nights of 8 h time in bed (TIB), TIB was restricted to 4 h per night for five nights (sleep restriction, SR, n = 15), followed by three recovery nights (REC) of 8 h TIB, representing a busy workweek and a recovery weekend. The control group (n = 8) had 8 h TIB throughout the experiment. A variety of autonomic cardiovascular parameters, together with salivary neuropeptide Y (NPY) and cortisol levels, were assessed. Results In the control group, none of the parameters changed. In the experimental group, heart rate increased from 60 +/- 1.8 beats per minute (bpm) at BL, to 63 +/- 1.1 bpm after SR and further to 65 +/- 1.8 bpm after REC. In addition, whole day low-frequency to-high frequency (LF/HF) power ratio of heart rate variability increased from 4.6 +/- 0.4 at BL to 6.0 +/- 0.6 after SR. Other parameters, including salivary NPY and cortisol levels, remained unaffected. Conclusions Increased heart rate and LF/HF power ratio are early signs of an increased sympathetic activity after prolonged sleep restriction. To reliably interpret the clinical significance of these early signs of physiological stress, a follow-up study would be needed to evaluate if the stress responses escalate and lead to more unfavourable reactions, such as elevated blood pressure and a subsequent elevated risk for cardiovascular health problems.Peer reviewe

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Technologies for fall risk assessment and conceptual design in personal health record system

Abstract Falls among older people are a major economic and public health problem. Due to the demographic change and aging of populations, there is an urgent need for accurate screening tools to identify those at risk to target effective falls prevention strategies. Clinical fall risk assessments are costly and time-consuming and thus cannot be performed frequently. Technologies provide means for assessing fall risk during daily living, making self-evaluations and fast methods for fall risk assessment for professional use. This study collects and evaluates existing technological solutions for fall risk assessment including various different sensor technologies. The study also presents one easy to use solution for assessing fall risk and suggests a concept-design for integrating sensor-based solutions into the Finnish national Kanta Personal Health Record. The optimal solution for technological fall risk assessment is still unclear. A wide implementation still requires extensive validation studies, adoption to health care processes and novel IoT -solutions for collecting large amounts of sensor data. Thorough methods should be utilised in designing the privacy and security aspects of fall risk assessment solutions, as well as different user profiles, to allow suitable interfaces and visualisations to users. It should always be clear what kind of data are collected from users and how the data are utilised. The consent of the users should also always be collected

Euclid preparation : XXV. The Euclid Morphology Challenge: Towards model-fitting photometry for billions of galaxies

The European Space Agency's Euclid mission will provide high-quality imaging for about 1.5 billion galaxies. A software pipeline to automatically process and analyse such a huge amount of data in real time is being developed by the Science Ground Segment of the Euclid Consortium; this pipeline will include a model-fitting algorithm, which will provide photometric and morphological estimates of paramount importance for the core science goals of the mission and for legacy science. The Euclid Morphology Challenge is a comparative investigation of the performance of five model-fitting software packages on simulated Euclid data, aimed at providing the baseline to identify the best-suited algorithm to be implemented in the pipeline. In this paper we describe the simulated dataset, and we discuss the photometry results. A companion paper is focussed on the structural and morphological estimates. We created mock Euclid images simulating five fields of view of 0.48 deg(2) each in the I-E band of the VIS instrument, containing a total of about one and a half million galaxies (of which 350 000 have a nominal signal-to-noise ratio above 5), each with three realisations of galaxy profiles (single and double Sersic, and 'realistic' profiles obtained with a neural network); for one of the fields in the double Sersic realisation, we also simulated images for the three near-infrared Y-E, J(E), and H-E bands of the NISP-P instrument, and five Rubin/LSST optical complementary bands (u, g, r, i, and z), which together form a typical dataset for an Euclid observation. The images were simulated at the expected Euclid Wide Survey depths. To analyse the results, we created diagnostic plots and defined metrics to take into account the completeness of the provided catalogues, as well as the median biases, dispersions, and outlier fractions of their measured flux distributions. Five model-fitting software packages (DeepLeGATo, Galapagos-2, Morfometryka, ProFit, and SourceXtractor++) were compared, all typically providing good results. Of the differences among them, some were at least partly due to the distinct strategies adopted to perform the measurements. In the best-case scenario, the median bias of the measured fluxes in the analytical profile realisations is below 1% at a signal-to-noise ratio above 5 in I-E, and above 10 in all the other bands; the dispersion of the distribution is typically comparable to the theoretically expected one, with a small fraction of catastrophic outliers. However, we can expect that real observations will prove to be more demanding, since the results were found to be less accurate for the most realistic realisation. We conclude that existing model-fitting software can provide accurate photometric measurements on Euclid datasets. The results of the challenge are fully available and reproducible through an online plotting tool.Peer reviewe

Activator protein-1 in carotid plaques is related to cerebrovascular symptoms and cholesteryl ester content.

INTRODUCTION: Transcription factor activator protein-1 regulates genes involved in inflammation and repair. The aim of this study was to determine whether transcription factor activator protein-1 activity in carotid plaques is related to symptoms, lipid accumulation, or extracellular matrix composition. METHODS: Twenty-eight atherosclerotic carotid plaques were removed by endarterectomy and divided into two groups based on the presence or absence of ipsilateral symptoms (<1 month ago). Activator protein-1 DNA binding activity was assessed, and subunit (c-Jun, JunD, JunB, c-Fos, FosB, Fra-1, Fra-2) protein levels analyzed by immunoblotting. Distribution of c-Jun in plaques was analyzed by immunohistochemistry. RESULTS: Plaques associated with symptoms had increased activator protein-1 activity and increased expression of c-Jun and JunD, as compared to asymptomatic plaques. Fra-1 and Fra-2 were present in equal amounts in both groups, whereas JunB, FosB, and c-Fos were undetectable. Activator protein-1 activity correlated with cholesteryl ester and elastin in plaques and decreased with age. Activator protein-1 activity did not correlate with collagen, calcified tissue, or proteoglycan content. CONCLUSIONS: Activator protein-1 is increased in plaques associated with symptoms. The correlation between activator protein-1 and cholesteryl esters suggests that high activator protein-1 is a marker of plaque vulnerability. Activator protein-1 expression can also reflect the activation of repair processes