Relationship of Left Ventricular Global Longitudinal Strain with Cardiac Autonomic Denervation As Assessed by 123I-mIBG Scintigraphy in Patients with Heart Failure with Reduced Ejection Fraction Submitted to Cardiac Resynchronization Therapy: Assessment of Cardiac Autonomic Denervation by GLS in Patients with Heart Failure with Reduced Ejection Fraction Submitted to CRT

BACKGROUND: Heart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF. METHODS/RESULTS: BETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of - 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). CONCLUSION: Myocardial contractility as assessed by GLS is moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.info:eu-repo/semantics/publishedVersio

Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors

Post Eclosion Age Predicts the Prevalence of Midgut Trypanosome Infections in Glossina

The teneral phenomenon, as observed in Glossina sp., refers to the increased susceptibility of the fly to trypanosome infection when the first bloodmeal taken is trypanosome-infected. In recent years, the term teneral has gradually become synonymous with unfed, and thus fails to consider the age of the newly emerged fly at the time the first bloodmeal is taken. Furthermore, conflicting evidence exists of the effect of the age of the teneral fly post eclosion when it is given the infected first bloodmeal in determining the infection prevalence. This study demonstrates that it is not the feeding history of the fly but rather the age (hours after eclosion of the fly from the puparium) of the fly when it takes the first (infective) bloodmeal that determines the level of fly susceptibility to trypanosome infection. We examine this phenomenon in male and female flies from two distinct tsetse clades (Glossina morsitans morsitans and Glossina palpalis palpalis) infected with two salivarian trypanosome species, Trypanosoma (Trypanozoon) brucei brucei and Trypanosoma (Nannomonas) congolense using Fisher's exact test to examine differences in infection rates. Teneral tsetse aged less than 24 hours post-eclosion (h.p.e.) are twice as susceptible to trypanosome infection as flies aged 48 h.p.e. This trend is conserved across sex, vector clade and parasite species. The life cycle stage of the parasite fed to the fly (mammalian versus insect form trypanosomes) does not alter this age-related bias in infection. Reducing the numbers of parasites fed to 48 h.p.e., but not to 24 h.p.e. flies, increases teneral refractoriness. The importance of this phenomenon in disease biology in the field as well as the necessity of employing flies of consistent age in laboratory-based infection studies is discussed

A genome-wide association study of asthma symptoms in Latin American children

Abstract\ud \ud Background\ud Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.\ud \ud \ud Methods\ud 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples.\ud \ud \ud Results\ud Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45–2.18, p-value 2.83 × 10−8) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02–4.49, p-value 6.68 × 10−8 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10−7). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.\ud \ud \ud Conclusions\ud We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.This work was supported by the Department of Science and Technology\ud (DECIT, Ministry of Health), National Fund for Scientific and Technological\ud Development (FNDCT, Ministry of Science and Technology), Funding of\ud Studies and Projects (FINEP, Ministry of Science and Technology, Brazil), the\ud Brazilian National Research Council (CNPq) and the Wellcome Trust UK, Ref\ud 072405/Z/03/Z.\ud E.G.B. was funded by grants from National Institutes of Health (HL088133,\ud HL078885, HL004464, HL104608, HL117004, ES015794 and MD006902) and\ud by the American Asthma Foundation, the Sandler Foundation and the RWJF\ud Amos Medical Faculty Development Award.\ud Supported in part by the Intramural Research Program of the NIH, National\ud Institute of Environmental Health Sciences, USA

Status and performance of the underground muon detector of the Pierre Auger Observatory

The Auger Muons and Infill for the Ground Array (AMIGA) is an enhancement of the Pierre Auger Observatory, whose purpose is to lower the energy threshold of the observatory down to 1016.5 eV, and to measure the muonic content of air showers directly. These measurements will significantly contribute to the determination of primary particle masses in the range between the second knee and the ankle, to the study of hadronic interaction models with air showers, and, in turn, to the understanding of the muon puzzle. The underground muon detector of AMIGA is concomitant to two triangular grids of water-Cherenkov stations with spacings of 433 and 750 m; each grid position is equipped with a 30 m2 plastic scintillator buried at 2.3 m depth. After the engineering array completion in early 2018 and general improvements to the design, the production phase commenced. In this work, we report on the status of the underground muon detector, the progress of its deployment, and the performance achieved after two years of operation. The detector construction is foreseen to finish by mid-2022

A combined fit of energy spectrum, shower depth distribution and arrival directions to constrain astrophysical models of UHECR sources

The combined fit of the measured energy spectrum and distribution of depths of shower maximum of ultra-high-energy cosmic rays is known to constrain the parameters of astrophysical scenarios with homogeneous source distributions. Further measurements show that the cosmic-ray arrival directions agree better with the directions and fluxes of catalogs of starburst galaxies and active galactic nuclei than with isotropy. Here, we present a novel combination of both analyses. For that, a three-dimensional universe model containing a nearby source population and a homogeneous background source distribution is built, and its parameters are adapted using a combined fit of the energy spectrum, depth of shower maximum distribution and energy-dependent arrival directions. The model takes into account a symmetric magnetic field blurring, source evolution and interactions during propagation. We use simulated data, which resemble measurements of the Pierre Auger Observatory, to evaluate the method’s sensitivity. With this, we are able to verify that the source parameters as well as the fraction of events from the nearby source population and the size of the magnetic field blurring are determined correctly, and that the data is described by the fitted model including the catalog sources with their respective fluxes and three-dimensional positions. We demonstrate that by combining all three measurements we reach the sensitivity necessary to discriminate between the catalogs of starburst galaxies and active galactic nuclei

Update of the Offline Framework for AugerPrime

Work on the Offline Framework for the Pierre Auger Observatory was started in 2003 to create a universal framework for event reconstruction and simulation. The development and installation of the AugerPrime upgrade of the Pierre Auger Observatory require an update of the Offline Framework to handle the additional detector components and the upgraded Surface Detector Electronics. The design of the Offline Framework proved to be sufficiently flexible to accommodate the changes needed to be able to handle the AugerPrime detector. This flexibility has been a goal since the development of the code started. The framework separates data structures from processing modules. The detector components map directly onto data structures. It was straightforward to update or add processing modules to handle the additional information from the new detectors. We will discuss the general structure of the Offline Framework, explaining the design decisions that provided its flexibility and point out the few of the features of the original design that required deeper changes, which could have been avoided in hindsight. Given the disruptive nature of the AugerPrime upgrade, the developers decided that the update for AugerPrime was the moment to change also the language standard for the implementation and move to the latest version of C++, to break strict backward compatibility eliminating deprecated interfaces, and to modernize the development infrastructure. We will discuss the changes that were made to the structure in general and the modules that were added to the framework to handle the new detector components

Constraining Lorentz Invariance Violation using the muon content of extensive air showers measured at the Pierre Auger Observatory

Lorentz Invariance (LI) implies that the space-time structure is the same for all observers. On the other hand, various quantum gravity theories suggest that it may be violated when approaching the Planck scale. At extreme energies, like those available in the collision of Ultra-High Energy Cosmic Rays (UHECRs) with atmosphere nuclei, one should also expect a change in the interactions due to Lorentz Invariance Violation (LIV). In this work, the effects of LIV on the development of Extensive Air Showers (EAS) have been considered. After having introduced LIV as a perturbation term in the single-particle dispersion relation, a library of simulated showers with different energies, primary particles and LIV strengths has been produced. Possible LIV has been studied using the muon content of air showers measured at the Pierre Auger Observatory. Limits on LIV parameters have been derived from a comparison between the Monte Carlo expectations and muon fluctuation measurements from the Pierre Auger Observatory

A search for ultra-high-energy photons at the Pierre Auger Observatory exploiting air-shower Universality

The Pierre Auger Observatory is the most sensitive detector to primary photons with energies above ∼ 0.2 EeV. It measures extensive air showers using a hybrid technique that combines a fluorescence detector (FD) with a ground array of particle detectors (SD). The signatures of a photon-induced air shower are a larger atmospheric depth at the shower maximum (Xmax) and a steeper lateral distribution function, along with a lower number of muons with respect to the bulk of hadron-induced background. Using observables measured by the FD and SD, three photon searches in different energy bands are performed. In particular, between threshold energies of 1–10 EeV, a new analysis technique has been developed by combining the FD-based measurement of Xmax with the SD signal through a parameter related to its muon content, derived from the universality of the air showers. This technique has led to a better photon/hadron separation and, consequently, to a higher search sensitivity, resulting in a tighter upper limit than before. The outcome of this new analysis is presented here, along with previous results in the energy ranges below 1 EeV and above 10 EeV. From the data collected by the Pierre Auger Observatory in about 15 years of operation, the most stringent constraints on the fraction of photons in the cosmic flux are set over almost three decades in energy