Electromechanical characterization of a tissue-engineered myocardial patch derived from extracellular matrix

ObjectiveExtracellular matrix scaffolds have been successfully used for myocardial wall repair. However, regional functional evaluation (ie, contractility, electrical conductivity) of the extracellular matrix scaffold during the course of remodeling has been limited. In the present study, we evaluated the remodeled scaffold for evidence of electrical activation.MethodsThe extracellular matrix patch was implanted into the porcine right ventricular wall (n = 5) to repair an experimentally produced defect. Electromechanical mapping was performed with the NOGA system (Biosense Webster Inc, Diamond Bar, Calif) 60 days after implantation. Linear local shortening was recorded to assess regional contractility. After sacrifice, detailed histologic examinations were performed.ResultsHistologic examinations showed repopulation of the scaffold with cells, including a monolayer of factor VIII–positive cells in the endocardial surface and multilayered α-smooth muscle actin–positive cells beneath the monolayer cells. The α-smooth muscle actin–positive cells tended to be present at the endocardial aspect of the remodeled scaffold and at the border between the remodeled scaffold and the normal myocardium. Electromechanical mapping demonstrated that the patch had low-level electrical activity (0.56 ± 0.37 mV; P < .0001) in most areas and moderate activity (2.20 ± 0.70 mV; P < .0001) in the margin between the patch and the normal myocardium (7.58 ± 2.23 mV).ConclusionsThe extracellular matrix scaffolds were repopulated by α-smooth muscle actin–positive cells 60 days after implantation into the porcine heart. The presence of the cells corresponded to areas of the remodeling scaffold that showed early signs of electrical conductivity

Impact of endoscopic versus open saphenous vein harvest technique on late coronary artery bypass grafting patient outcomes in the ROOBY (Randomized On/Off Bypass) Trial

ObjectiveIn the Randomized On/Off Bypass (ROOBY) Trial, the efficacy of on-pump versus off-pump coronary artery bypass grafting was evaluated. This ROOBY Trial planned subanalysis compared the effects on postbypass patient clinical outcomes and graft patency of endoscopic vein harvesting and open vein harvesting.MethodsFrom April 2003 to April 2007, the technique used for saphenous vein graft harvesting was recorded in 1471 cases. Of these, 894 patients (341 endoscopic harvest and 553 open harvest) also underwent coronary angiography 1 year after coronary artery bypass grafting. Univariate and multivariable analyses were used to compare patient outcomes in the endoscopic and open groups.ResultsPreoperative patient characteristics were statistically similar between the endoscopic and open groups. Endoscopic vein harvest was used in 38% of the cases. There were no significant differences in both short-term and 1-year composite outcomes between the endoscopic and open groups. For patients with 1-year catheterization follow-up (n = 894), the saphenous vein graft patency rate for the endoscopic group was lower than that in the open harvest group (74.5% vs 85.2%, P < .0001), and the repeat revascularization rate was significantly higher (6.7% vs 3.4%, P < .05). Multivariable regression documented no interaction effect between endoscopic approach and off-pump treatment.ConclusionsIn the ROOBY Trial, endoscopic vein harvest was associated with lower 1-year saphenous vein graft patency and higher 1-year revascularization rates, independent of the use of off-pump or on-pump cardiac surgical approach

LensWatch: I. Resolved HST Observations and Constraints on the Strongly-Lensed Type Ia Supernova 2022qmx ("SN Zwicky")

Supernovae (SNe) that have been multiply-imaged by gravitational lensing are rare and powerful probes for cosmology. Each detection is an opportunity to develop the critical tools and methodologies needed as the sample of lensed SNe increases by orders of magnitude with the upcoming Vera C. Rubin Observatory and Nancy Grace Roman Space Telescope. The latest such discovery is of the quadruply-imaged Type Ia SN 2022qmx (aka, "SN Zwicky"; Goobar et al. 2022) at z = 0.3544. SN Zwicky was discovered by the Zwicky Transient Facility (ZTF) in spatially unresolved data. Here we present follow-up Hubble Space Telescope observations of SN Zwicky, the first from the multi-cycle "LensWatch" program (www.lenswatch.org). We measure photometry for each of the four images of SN Zwicky, which are resolved in three WFC3/UVIS filters (F475W, F625W, F814W) but unresolved with WFC3/IR F160W, and produce an analysis of the lensing system using a variety of independent lens modeling methods. We find consistency between time delays estimated with the single epoch of HST photometry and the lens model predictions constrained through the multiple image positions, with both inferring time delays of <1 day. Our lens models converge to an Einstein radius of (0.168+0.009-0.005)", the smallest yet seen in a lensed SN. The "standard candle" nature of SN Zwicky provides magnification estimates independent of the lens modeling that are brighter by ~1.5 mag and ~0.8 mag for two of the four images, suggesting significant microlensing and/or additional substructure beyond the flexibility of our image-position mass models

Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies

The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives inflammation. We hypothesize that in silico methods would help bridge in vitro hepatocyte data and clinical T/HS, in which the liver is a primary site of inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O 2) or normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex™ technology. Statistical analysis and data-driven modeling were employed to characterize the main components of the cellular response. Statistical analyses, hierarchical and k-means clustering, Principal Component Analysis, and Dynamic Network Analysis suggested MCP-1/CCL2 and IL-1α as central coordinators of hepatocyte-mediated inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer intensive care unit lengths of stay, and prolonged requirement for mechanical ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a main driver of the response of hepatocytes in vitro and as a biomarker for clinical outcomes in T/HS, and suggests an experimental and computational framework for discovery of novel clinical biomarkers in inflammatory diseases. © 2013 Ziraldo et al

SN 2023ixf in Messier 101: Photo-ionization of Dense, Close-in Circumstellar Material in a Nearby Type II Supernova

We present UV/optical observations and models of supernova (SN) 2023ixf, a type II SN located in Messier 101 at 6.9 Mpc. Early-time ("flash") spectroscopy of SN 2023ixf, obtained primarily at Lick Observatory, reveals emission lines of H I, He I/II, C IV, and N III/IV/V with a narrow core and broad, symmetric wings arising from the photo-ionization of dense, close-in circumstellar material (CSM) located around the progenitor star prior to shock breakout. These electron-scattering broadened line profiles persist for $\sim$8 days with respect to first light, at which time Doppler broadened features from the fastest SN ejecta form, suggesting a reduction in CSM density at $r \gtrsim 10^{15}$ cm. The early-time light curve of SN2023ixf shows peak absolute magnitudes (e.g., $M_{u} = -18.6$ mag, $M_{g} = -18.4$ mag) that are $\gtrsim 2$ mag brighter than typical type II supernovae, this photometric boost also being consistent with the shock power supplied from CSM interaction. Comparison of SN 2023ixf to a grid of light curve and multi-epoch spectral models from the non-LTE radiative transfer code CMFGEN and the radiation-hydrodynamics code HERACLES suggests dense, solar-metallicity, CSM confined to $r = (0.5-1) \times 10^{15}$ cm and a progenitor mass-loss rate of $\dot{M} = 10^{-2}$ M$_{\odot}$yr$^{-1}$. For the assumed progenitor wind velocity of $v_w = 50$ km s$^{-1}$, this corresponds to enhanced mass-loss (i.e., ``super-wind'' phase) during the last $\sim$3-6 years before explosion.Comment: 18 pages, 8 figures. Submitted to ApJ

LensWatch. I. Resolved HST Observations and Constraints on the Strongly Lensed Type Ia Supernova 2022qmx (“SN Zwicky”)

Supernovae (SNe) that have been multiply imaged by gravitational lensing are rare and powerful probes for cosmology. Each detection is an opportunity to develop the critical tools and methodologies needed as the sample of lensed SNe increases by orders of magnitude with the upcoming Vera C. Rubin Observatory and Nancy Grace Roman Space Telescope. The latest such discovery is of the quadruply imaged Type Ia SN 2022qmx (aka, “SN Zwicky”) at z = 0.3544. SN Zwicky was discovered by the Zwicky Transient Facility in spatially unresolved data. Here we present follow-up Hubble Space Telescope observations of SN Zwicky, the first from the multicycle “LensWatch (www.lenswatch.org)” program. We measure photometry for each of the four images of SN Zwicky, which are resolved in three WFC3/UVIS filters (F475W, F625W, and F814W) but unresolved with WFC3/IR F160W, and present an analysis of the lensing system using a variety of independent lens modeling methods. We find consistency between lens-model-predicted time delays (≲1 day), and delays estimated with the single epoch of Hubble Space Telescope colors (≲3.5 days), including the uncertainty from chromatic microlensing (∼1-1.5 days). Our lens models converge to an Einstein radius of θ E = ( 0.168 − 0.005 + 0.009 ) ″ , the smallest yet seen in a lensed SN system. The “standard candle” nature of SN Zwicky provides magnification estimates independent of the lens modeling that are brighter than predicted by ∼ 1.7 − 0.6 + 0.8 mag and ∼ 0.9 − 0.6 + 0.8 mag for two of the four images, suggesting significant microlensing and/or additional substructure beyond the flexibility of our image-position mass models

Characterization of NDM-1-and OXA-23-producing Acinetobacter baumannii isolates from inanimate surfaces in a hospital environment in Algeria

International audienceBackground: Investigation of several outbreaks of multidrug-resistant Acinetobacter baumannii infection has demonstrated that contamination of the inanimate hospital environment could be implicated in the spread of these multidrug-resistant strains. Aim: To investigate the occurrence of carbapenem-resistant A. baumannii on inanimate surfaces and possible dissemination in the hospital environment in Algeria as a potential source of infection in humans. Methods: A. baumannii strains were isolated from the hospital environment and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using disc diffusion and E-test methods. Carbapenemase activity was detected using microbiological tests, including modified Hodge test, modified Carba NP test, and EDTA test. Carbapenem resistance determinants were studied by polymerase chain reaction (PCR) and sequencing. Clonal relatedness was determined using multi-locus sequence typing (MLST). Results: A total of 67 A. baumannii isolates were obtained from 868 environmental samples and identified by MALDI-TOF MS. Among them, 61 isolates were resistant to imipenem with minimum inhibitory concentration >32 mu g/mL and positive by the modified Hodge test and modified Carba NP test. In addition, the activity of carbapenemase was inhibited by EDTA in 32 strains. PCR and sequencing showed the presence of bla(OXA-23) gene in 29 strains, and the bla(NDM-1) gene in 32 isolates. MLST demonstrated the presence of five types of ST (ST19, ST2, ST85, ST98, and ST115). Conclusion: Our study demonstrated the dissemination of carbapenemase-producing A. baumannii strains recovered from inanimate surfaces in a hospital environment, surrounding patients, healthcare workers and visitors, in Algeria as a potential source for nosocomial infection. (C) 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved

A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family

International audienceCongenital deafness is certainly one of the most common monogenic diseases in humans, but it is also one of the most genetically heterogeneous, which makes molecular diagnosis challenging in most cases. Whole-exome sequencing in two out of three Algerian siblings affected by recessively-inherited, moderate to severe sensorineural deafness allowed us to identify a novel splice donor site mutation (c.5272+1G>A) in the gene encoding α-tectorin, a major component of the cochlear tectorial membrane. The mutation was present at the homozygous state in the three affected siblings, and at the heterozygous state in their unaffected, consanguineous parents. To our knowledge, this is the first reported TECTA mutation leading to the DFNB21 form of hearing impairment among Maghrebian individuals suffering from congenital hearing impairment, which further illustrates the diversity of the genes involved in congenital deafness in the Maghreb