Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration.

Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog, explaining the retarded cell cycle exit and myoblast differentiation. Rescue of Matn2 expression restored differentiation and the expression of p21 and of the myogenic genes. TGF-β1 inhibited myogenic differentiation at least in part by repressing Matn2 expression, which inhibited the onset of a positive-feedback loop whereby Matn2 and Nfix activate the expression of one another and activate myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2(-/-) relative to wild-type mice. The expression levels of Trf3 and myogenic genes were robustly reduced in Matn2(-/-) fetal limbs and in differentiating primary myoblast cultures, establishing Matn2 as a key modulator of the regulatory cascade that initiates terminal myogenic differentiation. Our data thus identify Matn2 as a crucial component of a genetic switch that modulates the onset of tissue repair

Propionic Acid Produced by Propionibacterium acnes Strains Contributes to Their Pathogenicity

Propionibacterium acnes is an important member of the skin microbiome. The bacterium can initiate signalling events and changes in cellular properties in keratinocytes. The aim of this study was to analyse the effect of the bacterium on an immortalized human keratinocyte cell line. The results show that various P. acnes strains affect the cell-growth properties of these cells differentially, inducing cytotoxicity in a strain-specific and dosedependent manner. We propose that bacterially secreted propionic acid may contribute to the cytotoxic effect. This acid has a role in maintaining skin pH and exhibits antimicrobial properties, but may also have deleterious effects when the local concentration rises due to excessive bacterial growth and metabolism. These results, together with available data from the literature, may provide insight into the dual role of P. acnes in healthy skin and during pathogenic conditions, as well as the key molecules involved in these functions. Key words: immortalized keratinocyte cell line (HPV-KER); Propionibacterium acnes; acne vulgaris; short-chain fatty acid; propionic acid

The implementation of quality management systems in hospitals: a comparison between three countries

BACKGROUND: Is the implementation of Quality Management (QM) in health care proceeding satisfactorily and can national health care policies influence the implementation process? Policymakers and researchers in a country need to know the answer to this question. Cross country comparisons can reveal whether sufficient progress is being made and how this can be stimulated. The objective of the study was to investigate agreement and disparities in the implementation of QMS between The Netherlands, Hungary and Finland with respect to the evaluation model used and the national policy strategy of the three countries. METHODS: The study has a cross sectional design, based on measurements in 2000. Empirical data about QM-activities in hospitals were gathered by a self-administered questionnaire. The questionnaires were answered by the directors of the hospitals or the quality coordinators. The analyses are based on data from 101 hospitals in the Netherlands, 116 hospitals in Hungary and 59 hospitals in Finland. Outcome measures are the developmental stage of the Quality Management System (QMS), the development within five focal areas, and distinct QM-activities which were listed in the questionnaire. RESULTS: A mean of 22 QM-activities per hospital was found in the Netherlands and Finland versus 20 QM-activities in Hungarian hospitals. Only a small number of hospitals has already implemented a QMS (4% in The Netherlands,0% in Hungary and 3% in Finland). More hospitals in the Netherlands are concentrating on quality documents, whereas Finnish hospitals are concentrating on training in QM and guidelines. Cyclic quality improvement activities have been developed in the three countries, but in most hospitals the results were not used for improvements. All three countries pay hardly any attention to patient participation. CONCLUSION: The study demonstrates that the implementation of QM-activities can be measured at national level and that differences between countries can be assessed. The hypothesis that governmental legislation or financial reimbursement can stimulate the implementation of QM-activities, more than voluntary recommendations, could not be confirmed. However, the results show that specific obligations can stimulate the implementation of QM-activities more than general, framework legislation

Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease

Background Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. Methods We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Results At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). Conclusions In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .)

Spatial risk assessment of hydrological extremities : Inland excess water hazard, Szabolcs-Szatmár-Bereg Country, Hungary

Inland excess water hazard was regionalized and digitally mapped using auxiliary spatial environmental information for a county in Eastern Hungary. Quantified parameters representing the effect of soil, geology, groundwater, land use and hydrometeorology on the formulation of inland excess water were defined and spatially explicitly derived. The complex role of relief was characterized using multiple derivatives computed from a DEM. Legacy maps displaying inland excess water events were used as a reference dataset. Regression kriging was applied for spatial inference with the correlation between environmental factors and inundation determined using multiple linear regressions. A stochastic factor derived through kriging the residual was added to the regression results,thus producing the final inundation hazard map. This may be of use for numerous landrelated activities

JADES Initial Data Release for the Hubble Ultra Deep Field: Revealing the Faint Infrared Sky with Deep JWST NIRCam Imaging

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/JWST has revolutionized the field of extragalactic astronomy with its sensitive and high-resolution infrared view of the distant Universe. Adding to the new legacy of JWST observations, we present the first NIRCam imaging data release from the JWST Advanced Deep Extragalactic Survey (JADES), providing nine filters of infrared imaging of ∼25 arcmin2 covering the Hubble Ultra Deep Field and portions of Great Observatories Origins Deep Survey South. Utilizing 87 on-sky dual-filter hours of exposure time, these images reveal the deepest ever near-infrared view of this iconic field. We supply carefully constructed nine-band mosaics of the JADES bands, as well as matching reductions of five additional bands from the JWST Extragalactic Medium-band Survey. Combining with existing Hubble Space Telescope imaging, we provide 23-band space-based photometric catalogs and photometric redshifts for ≈47,500 sources. To promote broad engagement with JADES, we have created an interactive FitsMap website to provide an interface for professional researchers and the public to experience these JWST data sets. Combined with the first JADES NIRSpec data release, these public JADES imaging and spectroscopic data sets provide a new foundation for discoveries of the infrared Universe by the worldwide scientific community.Peer reviewe

JADES Imaging of GN-z11: Revealing the Morphology and Environment of a Luminous Galaxy 430 Myr after the Big Bang

We present JWST NIRCam nine-band near-infrared imaging of the luminous z = 10.6 galaxy GN-z11 from the JWST Advanced Deep Extragalactic Survey of the GOODS-N field. We find a spectral energy distribution (SED) entirely consistent with the expected form of a high-redshift galaxy: a clear blue continuum from 1.5 to 4 μm with a complete dropout in F115W. The core of GN-z11 is extremely compact in JWST imaging. We analyze the image with a two-component model, using a point source and a Sérsic profile that fits to a half-light radius of 200 pc and an index n = 0.9. We find a low-surface-brightness haze about 0.″4 to the northeast of the galaxy, which is most likely a foreground object but might be a more extended component of GN-z11. At a spectroscopic redshift of 10.60 (Bunker et al. 2023), the comparison of the NIRCam F410M and F444W images spans the Balmer jump. From population-synthesis modeling, here assuming no light from an active galactic nucleus, we reproduce the SED of GN-z11, finding a stellar mass of ∼109 M ⊙, a star formation rate of ∼20 M ⊙ yr−1, and a young stellar age of ∼20 Myr. Since massive galaxies at high redshift are likely to be highly clustered, we search for faint neighbors of GN-z11, finding nine galaxies out to ∼5 comoving Mpc transverse with photometric redshifts consistent with z = 10.6, and a tenth more tentative dropout only 3″ away. This is consistent with GN-z11 being hosted by a massive dark-matter halo (≈8 × 1010 M ⊙), though lower halo masses cannot be ruled out