54 research outputs found
The “History” of Desmosines: Forty Years of Debate on the Hypothesis That These Two Unnatural Amino Acids May Be Potential Biomarkers of Chronic Obstructive Pulmonary Disease
Desmosine and isodesmosine (collectively known as desmosines), two unnatural amino acids unique to mature elastin in humans, have been widely discussed as being potential biomarkers of disorders, which involve connective tissue and whose clinical manifestations result in elastin degradation. In particular, experimental data accumulated over the last 40 years have demonstrated that patients with chronic obstructive pulmonary disease (COPD) excrete higher amounts of urinary desmosines than healthy controls. Based on this evidence, it has been speculated by several authors that these cross-links may be potential biomarkers of COPD with clinical significance. Nevertheless, a strict correlation between the amount of these amino acids and the severity of the disease still has to be demonstrated. For this reason, the debate on the opportunity to consider desmosines as biomarkers of COPD is still open, and the development of sophisticated methods aimed at obtaining very precise measurement of their concentration is still considered technically challenging. The aim of this chapter is to trace the history of this debate through the presentation and discussion of a large number of articles dealing with the detection and quantification of desmosines in different biological fluids, from early years until the present
Elastodontic Therapy of Hyperdivergent Class II Patients Using AMCOP® Devices: A Retrospective Study
Background: The management of a hyperdivergent growth pattern is one of the most challenging in orthodontics and different treatments are advocated. The present study analyses the effectiveness of elastodontic therapy with AMCOP® devices in treating children with hyperdivergent class II malocclusion and the effect on the upper airway patency. Methods: The study group included 21 patients (10 males and 11 females, mean age 8.22 ± 1.17 years) with a hyperdivergent growth and a class II malocclusion treated with AMCOP® devices. Cephalometric analysis was performed before treatment (T0) and after treatment (T1). Results: After treatment, the cephalometric analysis revealed a correction of the class II malocclusion and a modification of the growth pattern with a divergence reduction. The improvement of the upper airway space was also observed. Conclusion: The elastodontic therapy effectively corrected hyperdivergent class II malocclusion in growing patients over a short period
Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine : results from a randomized, controlled, observer-blind study in adolescents and young adult
A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.GlaxoSmithKline Biologicals SAhttps://www.tandfonline.com/journals/KHVIMedical Microbiolog
The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars
We present 294 pulsars found in GeV data from the Large Area Telescope (LAT)
on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs)
discovered in deep radio searches of LAT sources will likely reveal pulsations
once phase-connected rotation ephemerides are achieved. A further dozen optical
and/or X-ray binary systems co-located with LAT sources also likely harbor
gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and
candidates, 10% of all known pulsars, compared to known before Fermi.
Half of the gamma-ray pulsars are young. Of these, the half that are undetected
in radio have a broader Galactic latitude distribution than the young
radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall,
>235 are bright enough above 50 MeV to fit the pulse profile, the energy
spectrum, or both. For the common two-peaked profiles, the gamma-ray peak
closest to the magnetic pole crossing generally has a softer spectrum. The
spectral energy distributions tend to narrow as the spindown power
decreases to its observed minimum near erg s, approaching the
shape for synchrotron radiation from monoenergetic electrons. We calculate
gamma-ray luminosities when distances are available. Our all-sky gamma-ray
sensitivity map is useful for population syntheses. The electronic catalog
version provides gamma-ray pulsar ephemerides, properties and fit results to
guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen
All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe
The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class
mission concept that will provide essential contributions to multimessenger
astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in
the 200 keV to 10 GeV energy range with a wide field of view, good spectral
resolution, and polarization sensitivity. Therefore, AMEGO is key in the study
of multimessenger astrophysical objects that have unique signatures in the
gamma-ray regime, such as neutron star mergers, supernovae, and flaring active
galactic nuclei. The order-of-magnitude improvement compared to previous MeV
missions also enables discoveries of a wide range of phenomena whose energy
output peaks in the relatively unexplored medium-energy gamma-ray band
Molecular Landscape and Therapeutic Strategies in Cholangiocarcinoma: An Integrated Translational Approach towards Precision Medicine
Cholangiocarcinomas (CCAs) are heterogeneous biliary tract malignancies with dismal prognosis, mainly due to tumor aggressiveness, late diagnosis, and poor response to current therapeutic options. High-throughput technologies have been used as a fundamental tool in unveiling CCA molecular landscape, and several molecular classifications have been proposed, leading to various targeted therapy trials. In this review, we aim to analyze the critical issues concerning the status of precision medicine in CCA, discussing molecular signatures and clusters, related to both anatomical classification and different etiopathogenesis, and the latest therapeutic strategies. Furthermore, we propose an integrated approach comprising the CCA molecular mechanism, pathobiology, clinical and histological findings, and treatment perspectives for the ultimate purpose of improving the methods of patient allocations in clinical trials and the response to personalized therapies
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