Advances and challenges in geroscience research: An update

Aging remains the most pervasive risk factor for a wide range of chronic diseases that afflict modern societies. In the United States alone, incidence of age-related diseases (e.g., cardiovascular disease, stroke, Alzheimer’s disease, vascular cognitive impairment and dementia, cancer, hypertension, type-2 diabetes, chronic obstructive pulmonary disease, and osteoarthritis) is on the rise, posing an unsustainable socioeconomic burden even for the most developed countries. Tackling each and every age-related disease alone is proving to be costly and ineffective. The emerging field of geroscience has posed itself as an interdisciplinary approach that aims to understand the relationship between the biology of aging and the pathophysiology of chronic age-related diseases. According to the geroscience concept, aging is the single major risk factor that underlies several age-related chronic diseases, and manipulation of cellular and systemic aging processes can delay the manifestation and/or severity of these age-related chronic pathologies. The goal of this endeavor is to achieve health improvements by preventing/delaying the pathogenesis of several age-related diseases simultaneously in the elderly population by targeting key cellular and molecular processes of aging instead of managing diseases of aging as they arise individually. In this review, we discuss recent advances in the field of geroscience, highlighting their implications for potential future therapeutic targets and the associated scientific challenges and opportunities that lay ahead

In vitro haemodynamic testing of Amplatzer plugs for paravalvular leak occlusion after Transcather Aortic Valve Implantation

Objective: We aimed to in-vitro test Amplatzer devices (Amplatzer Vascular Plug II and Amplatzer Vascular Plug III, SJM St. Paul, MN) in closing PVL generated by transcatheter balloon expandable aortic valve prosthesis in order to quantify the effective treatment of PVL. Background: Transcatheter aortic valve replacement (TAVI) procedures represent the treatment of choice for high risk patients. Despite evolving technologies paravalvular leak (PVL) is still a major unaddressed issue. This severe complication significantly impair long-term survival. Percutaneous treatment of this complication is usually performed with the implantation of not specifically designed and not approved vascular devices. Methods: A 23mm Sapien XT (Edwards Lifesciences, Irvine, CA) was implanted in a rubber aortic root and a semi-elliptical shape PVL was created. The vascular occluder devices were implanted in the PVL and hemodynamic performance was tested in a pulse duplicator according to international standard ISO 5840-3:2013. Different type of comparison tests together with high speed camera recording allowed us to define the global efficiency of the occluders and their interaction with the transcatheter prosthesis. Results: The results revealed that the use of vascular plugs was not per se sufficient to produce an effective or substantial reduction of PVL with a maximum efficiency inferior of 50%. Recorded video showed clearly that the vascular plug always interfered with the leaflet of the prosthetic valve. Conclusions: Current used devices do not guarantee effective treatment of PVL and may otherwise compromise the structural integrity of the prosthetic valve implanted. Specific designed devices are required

Effects of inhalable particulate matter on blood coagulation.

BACKGROUND: Particulate matter (PM) exposure has been linked to increased risk of cardiovascular disease, possibly resulting from hypercoagulability and thrombosis. Lung and systemic inflammation resulting from PM inhalation may activate blood coagulation, but mechanisms for PM-related hypercoagulability are still largely unknown. OBJECTIVES: To identify coagulation mechanisms activated by PM in a population with well-characterized exposure. METHODS: We measured prothrombin time (PT), activated partial thromboplastin time, endogenous thrombin potentials (ETPs) with/without exogenous triggers and with/without soluble thrombomodulin, tissue-type plasminogen activator (t-PA) antigen, D-dimer and C-reactive protein (CRP) in 37 workers in a steel production plant with well-characterized exposure to PM with aerodynamic diameter of < 1 mum (PM(1)) and coarse PM (PM(10) - PM(1)). Blood samples were collected from each subject on the first (baseline) and last (postexposure) day of a 4-day work week. We analyzed differences between baseline and postexposure levels using a paired Student's t-test. We fitted multivariate mixed-regression models to estimate the associations of interquartile range PM(1) and coarse PM exposure with parameter levels. RESULTS: None of the parameters showed any significant changes from baseline in postexposure samples. However, exposure levels were associated with shorter PT (beta[PM(1)] = -0.33 s, P = 0.08; beta[PM(coarse)] = - 0.33 s, P = 0.01), and higher ETP without exogenous triggers and with thrombomodulin (beta[PM(1)] = + 99 nm min, P = 0.02; beta[PM(coarse)] = + 66 nm min, P = 0.05), t-PA (beta[PM(1)] = + 0.72 ng mL(-1), P = 0.01; beta[PM(coarse)] = + 0.88 ng mL(-1), P = 0.04), and CRP (beta[PM(1)] = + 0.59 mg L(-1), P = 0.03; beta[PM(coarse)] = + 0.48 mg L(-1), P = 0.01). CONCLUSIONS: PM exposure did not show any short-term effect within the week of the study. The association of PM exposure with PT, ETP and CRP provides some evidence of long-term effects on inflammation and coagulation

Enhanced flux pinning in neutron irradiated MgB2

We study the effect of neutron irradiation on the critical current density Jc of isotopically pure polycrystalline Mg11B2 samples. For fluences in the range 1017-1018 cm-2, Jc is enhanced and its dependence on magnetic field is significantly improved: we demonstrate that, in this regime, point-like pinning centers are effectively introduced in the system proportionally to the neutron fluence. Instead, for larger fluences, a strong suppression of the critical temperature accompanied by a decrease of both the upper critical field Bc2 and Jc is found.Comment: 13 pages, 3 igure

The behavior of grain boundaries in the Fe-based superconductors

The Fe-based superconductors (FBS) are an important new class of superconducting materials. As with any new superconductor with a high transition temperature and upper critical field, there is a need to establish what their applications potential might be. Applications require high critical current densities, so the usefulness of any new superconductor is determined both by the capability to develop strong vortex pinning and by the absence or ability to overcome any strong current-limiting mechanisms of which grain boundaries in the cuprates are a cautionary example. In this review we first consider the positive role that grain boundary properties play in the metallic, low temperature superconductors and then review the theoretical background and current experimental data relating to the properties of grain boundaries in FBS polycrystals, bi-crystal thin films, and wires. Based on this evidence, we conclude that grain boundaries in FBS are weak linked in a qualitatively similar way to grain boundaries in the cuprate superconductors, but also that the effects are a little less marked. Initial experiments with the textured substrates used for cuprate coated conductors show similar benefit for the critical current density of FBS thin films too. We also note that the particular richness of the pairing symmetry and the multiband parent state in FBS may provide opportunities for grain boundary modification as a better understanding of their pairing state and grain boundary properties are developed.Comment: To appear in Reports on Progress in Physic

Neutron Irradiation of Mg11B2 : From the Enhancement to the Suppression of Superconducting Properties

In this letter we present the effect of neutron irradiation up to fluences of 3.9 1019 n/cm2 on the superconducting properties of MgB2. In order to obtain a disorder structure homogeneously distributed, the experiment was carried out on bulk samples prepared with the 11B isotope. Up to fluences of 1018 n/cm2 the critical temperature is slightly diminished (36 K) and the superconducting properties are significantly improved; the upper critical field is increased from 13.5 T to 20.3 T at 12 K and the irreversibility field is doubled at 5 K. For larger neutron fluences the critical temperature is suppressed down to 12 K and the superconducting properties come out strongly degraded.Comment: 13 pages, 4 figures. Submitted to Appl.Phys.Let