Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol

BACKGROUND: Experimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD). In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ. In the hypothesis that chronic inflammation and increased collagen metabolism are reflected also in the systemic circulation, we aimed this study to evaluate the effects on left ventricular wall structure by assessing splancnic and systemic collagen metabolism (procollagen III assay), deposition (ultrasonic tissue characterization), and cardiac function (echocardiography) in patients with different long standing history of IBD, before and after surgery. METHODS: Thirty patients affected by active IBD, 15 with Crohn and 15 with Ulcerative Colitis, submitted to surgery will be enrolled in the study in a double blind fashion. They will be studied before the surgical operation and 6, 12 months after surgery. A control group of 15 healthy age and gender-matched subjects will also be studied. At each interval blood samples will be collected in order to assess the collagen metabolism; a transthoracic echocardiogram will be recorded for the subsequent determination of cardiac function and collagen deposition. DISCUSSION: From this study protocol we expect additional information about the association between IBD and cardiovascular disorders; in particular to address the question if chronic inflammation, through the altered collagen metabolism, could affect left ventricular structure and function in a manner directly related to the estimated duration of the disease

Pre-supernova feedback mechanisms drive the destruction of molecular clouds in nearby star-forming disc galaxies

It is a major open question which physical processes stop gas accretion on to giant molecular clouds (GMCs) and limit the efficiency at which gas is converted into stars. While feedback from supernova explosions has been the popular feedback mechanism included in simulations of galaxy formation and evolution, ‘early’ feedback mechanisms such as stellar winds, photoionization, and radiation pressure are expected to play an important role in dispersing the gas after the onset of star formation. These feedback processes typically take place on small scales (∼10–100 pc) and their effects have therefore been difficult to constrain in environments other than the Milky Way. We apply a novel statistical method to ∼1 arcsec resolution maps of CO and H α across a sample of nine nearby galaxies, to measure the time over which GMCs are dispersed by feedback from young, high-mass stars, as a function of the galactic environment. We find that GMCs are typically dispersed within ∼3 Myr on average after the emergence of unembedded high-mass stars, with variations within galaxies associated with morphological features rather than radial trends. Comparison with analytical predictions demonstrates that, independently of the environment, early feedback mechanisms (particularly photoionization and stellar winds) play a crucial role in dispersing GMCs and limiting their star formation efficiency in nearby galaxies. Finally, we show that the efficiency at which the energy injected by these early feedback mechanisms couples with the parent GMC is relatively low (a few tens of per cent), such that the vast majority of momentum and energy emitted by the young stellar populations escapes the parent GMC

The lifecycle of molecular clouds in nearby star-forming disc galaxies

It remains a major challenge to derive a theory of cloud-scale ($\lesssim100$ pc) star formation and feedback, describing how galaxies convert gas into stars as a function of the galactic environment. Progress has been hampered by a lack of robust empirical constraints on the giant molecular cloud (GMC) lifecycle. We address this problem by systematically applying a new statistical method for measuring the evolutionary timeline of the GMC lifecycle, star formation, and feedback to a sample of nine nearby disc galaxies, observed as part of the PHANGS-ALMA survey. We measure the spatially-resolved ($\sim100$ pc) CO-to-H$\alpha$ flux ratio and find a universal de-correlation between molecular gas and young stars on GMC scales, allowing us to quantify the underlying evolutionary timeline. GMC lifetimes are short, typically 10-30 Myr, and exhibit environmental variation, between and within galaxies. At kpc-scale molecular gas surface densities $\Sigma_{\rm H_2}\geqslant8$M$_{\odot}$pc$^{-2}$, the GMC lifetime correlates with time-scales for galactic dynamical processes, whereas at $\Sigma_{\rm H_2}\leqslant8$M$_{\odot}$pc$^{-2}$ GMCs decouple from galactic dynamics and live for an internal dynamical time-scale. After a long inert phase without massive star formation traced by H$\alpha$ (75-90% of the cloud lifetime), GMCs disperse within just 1-5 Myr once massive stars emerge. The dispersal is most likely due to early stellar feedback, causing GMCs to achieve integrated star formation efficiencies of 4-10% These results show that galactic star formation is governed by cloud-scale, environmentally-dependent, dynamical processes driving rapid evolutionary cycling. GMCs and HII regions are the fundamental units undergoing these lifecycles, with mean separations of 100-300 pc in star-forming discs. Future work should characterise the multi-scale physics and mass flows driving these lifecycles

PHANGS-JWST First Results: Duration of the early phase of massive star formation in NGC628

The earliest stages of star formation, when young stars are still deeply embedded in their natal clouds, represent a critical phase in the matter cycle between gas clouds and young stellar regions. Until now, the high-resolution infrared observations required for characterizing this heavily obscured phase (during which massive stars have formed, but optical emission is not detected) could only be obtained for a handful of the most nearby galaxies. One of the main hurdles has been the limited angular resolution of the Spitzer Space Telescope. With the revolutionary capabilities of the JWST, it is now possible to investigate the matter cycle during the earliest phases of star formation as a function of the galactic environment. In this Letter, we demonstrate this by measuring the duration of the embedded phase of star formation and the implied time over which molecular clouds remain inert in the galaxy NGC 628 at a distance of 9.8 Mpc, demonstrating that the cosmic volume where this measurement can be made has increased by a factor of > 100 compared to Spitzer. We show that young massive stars remain embedded for 5.1 +2.7 −1.4 Myr (2.3 +2.7 −1.4 Myr of which being heavily obscured), representing ∼ 20% of the total cloud lifetime. These values are in broad agreement with previous measurements in five nearby (D < 3.5 Mpc) galaxies and constitute a proof of concept for the systematic characterization of the early phase of star formation across the nearby galaxy population with the PHANGS–JWST survey

PHANGS-JWST First Results: The Dust Filament Network of NGC 628 and Its Relation to Star Formation Activity

PHANGS-JWST mid-infrared (MIR) imaging of nearby spiral galaxies has revealed ubiquitous filaments of dust emission in intricate detail. We present a pilot study to systematically map the dust filament network (DFN) at multiple scales between 25 and 400 pc in NGC 628. MIRI images at 7.7, 10, 11.3, and 21 μm of NGC 628 are used to generate maps of the filaments in emission, while PHANGS-HST B-band imaging yields maps of dust attenuation features. We quantify the correspondence between filaments traced by MIR thermal continuum/polycyclic aromatic hydrocarbon (PAH) emission and filaments detected via extinction/scattering of visible light; the fraction of MIR flux contained in the DFN; and the fraction of H ii regions, young star clusters, and associations within the DFN. We examine the dependence of these quantities on the physical scale at which the DFN is extracted. With our highest-resolution DFN maps (25 pc filament width), we find that filaments in emission and attenuation are cospatial in 40% of sight lines, often exhibiting detailed morphological agreement; that ∼30% of the MIR flux is associated with the DFN; and that 75%-80% of the star formation in H ii regions and 60% of the mass in star clusters younger than 5 Myr are contained within the DFN. However, the DFN at this scale is anticorrelated with looser associations of stars younger than 5 Myr identified using PHANGS-HST near-UV imaging. We discuss the impact of these findings on studies of star formation and the interstellar medium, and the broad range of new investigations enabled by multiscale maps of the DFN

PHANGS-JWST First Results: Multiwavelength View of Feedback-driven Bubbles (the Phantom Voids) across NGC 628

We present a high-resolution view of bubbles within the Phantom Galaxy (NGC 628), a nearby (∼10 Mpc), star-forming (∼2 M ⊙ yr−1), face-on (i ∼ 9°) grand-design spiral galaxy. With new data obtained as part of the Physics at High Angular resolution in Nearby GalaxieS (PHANGS)-JWST treasury program, we perform a detailed case study of two regions of interest, one of which contains the largest and most prominent bubble in the galaxy (the Phantom Void, over 1 kpc in diameter), and the other being a smaller region that may be the precursor to such a large bubble (the Precursor Phantom Void). When comparing to matched-resolution Hα observations from the Hubble Space Telescope, we see that the ionized gas is brightest in the shells of both bubbles, and is coincident with the youngest (∼1 Myr) and most massive (∼105 M ⊙) stellar associations. We also find an older generation (∼20 Myr) of stellar associations is present within the bubble of the Phantom Void. From our kinematic analysis of the H I, H2 (CO), and H ii gas across the Phantom Void, we infer a high expansion speed of around 15 to 50 km s−1. The large size and high expansion speed of the Phantom Void suggest that the driving mechanism is sustained stellar feedback due to multiple mechanisms, where early feedback first cleared a bubble (as we observe now in the Precursor Phantom Void), and since then supernovae have been exploding within the cavity and have accelerated the shell. Finally, comparison to simulations shows a striking resemblance to our JWST observations, and suggests that such large-scale, stellar-feedback-driven bubbles should be common within other galaxies

Clinical Significance of Markers of Collagen Metabolism in Rheumatic Mitral Valve Disease

Rheumatic Heart Disease (RHD), a chronic acquired heart disorder results from Acute Rheumatic Fever. It is a major public health concern in developing countries. In RHD, mostly the valves get affected. The present study investigated whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression. This is a case control study comprising 118 subjects. It included 77 cases and 41 healthy controls. Cases were classified into two groups- Mitral Stenosis (MS) and Mitral Regurgitation (MR). Carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), total Matrix Metalloproteinase-1(MMP-1) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) were assessed. Histopathology studies were performed on excised mitral valve leaflets. A p value ,0.05 was considered statistically significant. Plasma PICP and PIIINP concentrations increased significantly (p,0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p,0.05). In MS, PICP level and MMP- 1/TIMP-1 ratio strongly correlated with mitral valve area (r =20.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r =20.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r =20.48 respectively) and systolic diameters (r = 0.65; r =20.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.9120.99; p,0.0001). A cut-off .459 ng/mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathology analysis revealed inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. Conclusions: Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis