Validation of a method for the determination of the sensible-heat flux with Sodar data in free convection cases

A simple method to determine the value of the ground sensible-heat flux using Sodar data is presented and validated. The measurement of the variance of the wind velocity components gives us an estimate of the intensity of the atmospheric turbulence; the local value of variance of the vertical wind velocity s2w depends on the efficiency of thermal and mechanical turbulence production. The portion of the atmospheric boundary layer, where turbulent kinetic energy is prevalently produced by buoyancy forces, is characterised by profiles of s3w Oz and of (sensible-) heat flux which decrease linearly with height. The extrapolation to the ground of the former profile gives an estimate of the value of sensible-heat flux at the surface. The validation of the results is performed by comparison of the energy involved in the development of convective episodes calculated, over the same time interval, from sensible-heat flux at the surface with that derived from potential temperature profiles relative to two successive radio soundings. When perturbative processes like, for example, rise up of breezes, are absent, the estimates of energies are in excellent agreement, being the angular coefficient of regression line 1.01 and the linear correlation coefficient 0.93

Infarct-like myocarditis with coronary vasculitis and aneurysm formation caused by epstein–barr virus infection

Myocardial infection by Epstein–Barr virus (EBV) may manifest with inflammatory cardiomyopathy, coronary syndrome X, and rarely with infarct-like myocarditis. The aim of the report is to describe a case of myocardial EBV infection causing acute myocarditis with heart failure, necrotizing coronary vasculitis, and multiple left ventricular (LV) aneurysms. A 67-year-old woman presented with fever, chest pain, and heart failure. She underwent non-invasive cardiac studies including electrocardiography, 2D-echocardiography, cardiac magnetic resonance, hematochemical exams with Troponin T determination, and invasive studies including cardiac catheterization, coronary angiography, and LV endomyocardial biopsy. Five endomyocardial samples were processed for histology and immunohistochemistry for inflammatory cells characterization and detection of viral antigens. Two additional frozen samples were evaluated by real-time polymerase chain reaction for the presence of cardiotropic viral genomes. Routine laboratory tests revealed the presence of elevated white blood cells (17 000 103/μL) and increased Troponin T. Electrocardiogram showed sinus tachycardia with ST elevation in V2–V5. Two-dimensional echocardiography showed normal LV dimension with reduced LV contractility (LVEF = 40%) with mild pericardial effusion. Cardiac magnetic resonance revealed the presence of a micro-aneurism in the inferior LV wall, a diffuse oedematous imbibition of LV myocardium suggested by hyper-intensity of T2 mapping, and increased fibrosis as suggested by areas of late gadolinium enhancement signals. Coronary arteries were normal while several micro-aneurysms were observed at LV angiography. At histology, a lymphocytic myocarditis with necrotizing coronary vasculitis sustained by a positive real-time polymerase chain reaction for EBV, detectable in cardiomyocytes and inflamed intramural vessels by positive immunohistochemistry for EBV latent membrane protein 1 antigen, was observed. Myocardial EBV infection is an unusual cause of acute heart failure and cardiac aneurysms, increasing the risk of electrical instability, cardiac perforation, and sudden death

Hypoxia and inflammation as a consequence of β-fibril accumulation. A perspective view for new potential therapeutic targets

Amyloidoses are heterogeneous diseases that result from the deposition of toxic insoluble β-sheet fibrillar protein aggregates in different tissues. The cascade of molecular events leading to amyloidoses and to the related clinical manifestations is not completely understood. Nevertheless, it is known that tissue damage associated to this disease involves alteration of tissue architecture, interaction with cell surface receptors, inflammation elicited by the amyloid protein deposition, oxidative stress, and apoptosis. However, another important aspect to consider is that systemic protein massive deposition not only subverts tissue architecture but also determines a progressive cellular hypertrophy and dilation of the extracellular space enlarging the volume of the organ. Such an alteration increases the distance between cells and vessels with a drop in pO2 that, in turn, causes both necrotic cell death and activation of the hypoxia transcription factor HIF-1α. Herewith, we propose the hypothesis that both cell death and hypoxia represent two important events for the pathogenesis of damage and progression of amyloidoses. In fact, molecules released by necrotic cells activate inflammatory cells from one side while binding to HIF-1α-dependent membrane receptors expressed on hypoxic parenchymal cells on the other side. This latter event generates a signaling cascade triggering NFκB activation and chronic inflammation. Finally, we also suggest that this scenario, once proved and detailed, might suggest important targets for new therapeutic interventions

Myocarditis and intramural coronary vasculitis in polyarteritis nodosa: an unusual treatable form of heart failure

We describe an uncommon cardiac presentation of polyarteritis nodosa. A 68-year-old woman, with a history of fatigue, weight loss, and myalgia of the lower extremities, was admitted for congestive heart failure. Coronary arteries were normal. Endomyocardial biopsy showed active lymphocytic myocarditis with associated intramural small vessels necrotizing vasculitis. The overexpression of TLR-4 and the negativity for myocardial viruses suggested an immune mediated mechanism of cardiac damage. These histologic findings associated to weight loss >4 kg not due to dieting or other factors, myalgias, and polyneuropathy, were consistent with the diagnosis of polyarteritis nodosa. Immunosuppressive treatment, consisting of cyclophosphamide and prednisolone, led to a significant improvement of cardiac function. Polyarteritis nodosa can be the cause of unexplained heart failure due to myocarditis and intramural vessels vasculitis. Its recognition is crucial to obtain a cardiac recovery with a tailored immunosuppressive treatment

Fabry cardiomyopathy: Gb3-induced auto-reactive panmyocarditis requiring heart transplantation

Resistance to enzyme replacement therapy (ERT) is a major therapeutic challenge in Fabry disease (FD). Recent reports attribute to immune-mediated inflammation a main role in promoting disease progression and resistance to ERT. Aim of the study is to report a Gb3-induced auto-reactive panmyocarditis causing inefficacy of ERT and severe electrical instability, which required cardiac transplantation. Examining the explanted heart from a 57-year-old man with FD cardiomyopathy (CM) on 3-year ERT presenting incoming ventricular fibrillation, we documented a severe virus-negative myocarditis extended to cardiomyocytes, intramural coronary vessels, conduction tissue, and subepicardial ganglia. Serology was positive for anti-Gb3, anti-heart, and anti-myosin antibodies. In vitro Gb3 stimulation of patient's peripheral blood mononuclear cells (PBMC) induced high amount production of inflammatory cytokine IL1-\u3b2, IL-6, IL-8, and TNF-\u3b1. PBMC were stained using the monoclonal antibodies CD3-V500, CD4-V450, CD8-APCcy7, CD45RO-PerCPcy5.5 and CD27-FITC from BD Biosciences and CD56-PC7 from Bekman Coulter. The phenotypic analysis of PBMC showed a lower frequency of CD8 (9.2%) vs. 19.3% and NKT cells (1.6% vs. 2.4%) in Fabry patient respect to healthy donor, suggesting a possible homing to peripheral tissues. A Gb3-induced auto-reactive myocarditis is suggested as a possible cause of FDCM progression and ERT resistance. Immune-mediated inflammation of systemic Fabry cells may coexist and be controlled by implemental immunosuppressive therapy

The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology

The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique prognoses and treatment are seldom diagnosed by noninvasive testing.1 Informed clinical decision making that weighs the risks of EMB against the incremental diagnostic, prognostic, and therapeutic value of the procedure is especially challenging for nonspecialists because the relevant published literature is usually cited according to specific cardiac diseases, which are only diagnosed after EM

Physical and chemical mechanisms involved in adhesion of orthodontic bonding composites: in vitro evaluations

BackgroundBond strength of orthodontic composite is strongly influenced by molecular and structural mechanisms. Aim of this in vitro study was to compare bond strength of light-cure orthodontic composites by measuring debonding forces and evaluating locations of bond failure. Investigations on chemical compositions clarified adhesive behaviors and abilities, exploring effects of ageing processes in this junction materials.MethodsTwelve enamel discs, from human premolars, were randomly coupled to one orthodontic adhesive system (Transbond XT (TM) 3 M UNITEK, USA, Light-Cure Orthodontic Paste, LEONE, Italy and Bisco Ortho Bracket Paste LC, BISCO, Illinois) and underwent to Shear Bond Strength test. Metallic brackets were bonded to twenty-seven human premolar, with one of the adhesive systems, to quantify, at FE-SEM magnifications, after debonding, the residual material on enamel and bracket base surfaces. Raman Spectroscopy analysis was performed on eight discs of each composites to investigate on chemical compositions, before and after accelerated aging procedures in human saliva and sugary drink.ResultsOrthodontic adhesive systems showed similar strength of adhesion to enamel. The breakage of adhesive-adherent bond occurs in TXT at enamel-adhesive interface while in Bisco and Leone at adhesive-bracket interface. Accelerated in vitro aging demonstrated good physical-chemical stability for all composites, Bisco only, was weakly contaminated with respect to the other materials.ConclusionA similar, clinically adequate and acceptable bond strength to enamel for debonding maneuvers was recorded in all orthodontic adhesive systems under examination. No significant chemical alterations are recorded, even in highly critical situations, not altering the initial mechanical properties of materials

Prelamin A mediates myocardial inflammation in dilated and HIV-Associated cardiomyopathies

Cardiomyopathies are complex heart muscle diseases that can be inherited or acquired. Dilated cardiomyopathy can result from mutations in LMNA, encoding the nuclear intermediate filament proteins lamin A/C. Some LMNA mutations lead to accumulation of the lamin A precursor, prelamin A, which is disease causing in a number of tissues, yet its impact upon the heart is unknown. Here, we discovered myocardial prelamin A accumulation occurred in a case of dilated cardiomyopathy, and we show that a potentially novel mouse model of cardiac-specific prelamin A accumulation exhibited a phenotype consistent with inflammatory cardiomyopathy, which we observed to be similar to HIV-associated cardiomyopathy, an acquired disease state. Numerous HIV protease therapies are known to inhibit ZMPSTE24, the enzyme responsible for prelamin A processing, and we confirmed that accumulation of prelamin A occurred in HIV' patient cardiac biopsies. These findings (a) confirm a unifying pathological role for prelamin A common to genetic and acquired cardiomyopathies; (b) have implications for the management of HIV patients with cardiac disease, suggesting protease inhibitors should be replaced with alternative therapies (i.e., nonnucleoside reverse transcriptase inhibitors); and (c) suggest that targeting inflammation may be a useful treatment strategy for certain forms of inherited cardiomyopathy

Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation.

ABSTRACT Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients