Echocardiographic evaluation of left ventricular outflow tract obstruction in complete transposition of the great arteries

Subpulmonic stenosis in complete d-transposition of the great arteries (d-TGA) is a frequently associated malformation, the precise diagnosis of which is essential for optimal medical and surgical treatment. Sixteen patients with d-TGA and subpulmonic stenosis have been studied by M-mode and two-dimensional (2DE) echocardiography and cardiac catheterization. Dynamic obstruction was found in six patients and fixed stenosis in 10. Systolic anterior motion of the mitral valve without fixed obstruction of the left ventricular outflow tract (LVOT) was present in patients with dynamic stenosis. Measurements of left ventricular end-diastolic posterior wall thickness to minor semiaxis ratio correlated well (p < 0.001) with the pressure gradient across the LVOT. Various types of anatomic fixed obstruction are described. M-mode echocardiography provides assessment of dynamic obstruction but does not allow quantitative evaluation of the length of the narrowed segment. The latter can be achieved by 2DE, which offers improved definition of different anatomic types

OSAS severity is associated to decreased heart rate turbulence slope

Obstructive sleep apnea syndrome (OSAS) has been associated to impaired baroreflex sensitivity (BRS) which has recently been shown to be non-invasively assessed by heart rate turbulence (HRT) analysis. Although HRT seems to be better suited than traditional heart rate variability indexes for autonomic assessment in presence of respiratory and arrhythmic disorders, very few papers addressed its evaluation in OSAS. Aim of the study is to find out whether and to which extend HRT is associated to OSAS severity. We studied HRT in polysomnographic recordings of 221 mild to severe OSAS pts. Results showed that, while HRT onset values did not significantly differ between mild (-0,78±1,50), moderate (-0,89±1,78) and severe (-0,70±1,28) pts., HRT slope significantly decreases (Kruskal-Wallis P value <0.05) from mild (3,27±2,7) to moderate (2,6±2,6) and severe (1,98±2,5) pts., with a significant Dunn's multiple comparisons post test only between mild vs. severe OSAS pts. Data indicate that the main BRS alterations do not appear in the early HRT phase triggered by transient vagal inhibition, but during the slow one, due to the sympathetic hyperactivity affecting the heart rate recovery. These findings support the conclusion that HRT assessment could have a prognostic value related to the development of cardiovascular disease in OSAS

Statistical Analysis and Kinematic Assessment of Upper Limb Reaching Task in Parkinson’s Disease

The impact of neurodegenerative disorders is twofold; they affect both quality of life and healthcare expenditure. In the case of Parkinson’s disease, several strategies have been attempted to support the pharmacological treatment with rehabilitation protocols aimed at restoring motor function. In this scenario, the study of upper limb control mechanisms is particularly relevant due to the complexity of the joints involved in the movement of the arm. For these reasons, it is difficult to define proper indicators of the rehabilitation outcome. In this work, we propose a methodology to analyze and extract an ensemble of kinematic parameters from signals acquired during a complex upper limb reaching task. The methodology is tested in both healthy subjects and Parkinson’s disease patients (N = 12), and a statistical analysis is carried out to establish the value of the extracted kinematic features in distinguishing between the two groups under study. The parameters with the greatest number of significances across the submovements are duration, mean velocity, maximum velocity, maximum acceleration, and smoothness. Results allowed the identification of a subset of significant kinematic parameters that could serve as a proof-of-concept for a future definition of potential indicators of the rehabilitation outcome in Parkinson’s disease

Hematological and serum biochemistry values in free-ranging crested porcupine

The crested porcupine is a widespread naturalized Italian rodent of African origin; nevertheless, very little information on the population abundance and its health status is available. In this study, the hematological and serum chemistry profile of 10 free-ranging captured crested porcupines was established for the first time. The mean hematological values resulted: 5.7 SD 0.4 M/μL for red blood cells; 13.6 SD 0.8 g/dL for hemoglobin; 77.3 SD 5.7 fL for mean corpuscular volume and 30.1 SD 4.7 g/dL for mean corpuscular hemoglobin concentration; 14.4 SD 7.2 K/μL for white blood cells; and 557.0 SD 469.9 K/μL for platelets. The mean urea and creatinine values resulted with 19.8 SD 8.3 mg/dL and 1.6 SD 3.0 mg/dL, respectively. The mean value of total protein was 6.7 SD 1.0 g/dL, with values of albumin higher than globulins. The mean activity of creatine kinase, aspartate transaminase, gamma-glutamyl transpeptidase, and alkaline phosphatase was 927.3 SD 607.6 U/L, 199.2 SD 70.8 U/L, 16.9 SD 13.7 U/L, and 256 SD 75.8 U/L, respectively. Highest values of alkaline phosphatase were recorded in two porcupines presenting severe injuries with clear signs of infection. These preliminary results may be a helpful tool in order to assess porcupine health status

A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy

T-bet plays a crucial role in Th1 development. We investigated the role of T-bet in the development of allograft rejection in an established MHC class II–mismatched (bm12 into B6) model of chronic allograft vasculopathy (CAV). Intriguingly, and in contrast to IFN-γ−/− mice that are protected from CAV, T-bet−/− recipients develop markedly accelerated allograft rejection accompanied by early severe vascular inflammation and vasculopathy, and infiltration by predominantly IL-17–producing CD4 T cells. Concurrently, T-bet−/− mice exhibit a T helper type 1 (Th1)–deficient environment characterized by profound IFN-γ deficiency, a Th2 switch characterized by increased production of interleukin (IL) 4, IL-5, IL-10, and IL-13 cytokines, as well as increased production of the proinflammatory cytokines IL-6, IL-12p40, and IL-17. Neutralization of IL-17 inhibits accelerated allograft rejection and vasculopathy in T-bet−/− mice. Interestingly, CD4 but not CD8 T cell deficiency in T-bet−/− mice affords dramatic protection from vasculopathy and facilitates long-term graft acceptance. This is the first study establishing that in the absence of Th1-mediated alloimmune responses, CD4 Th17 cells mediate an aggressive proinflammatory response culminating in severe accelerated allograft rejection and vasculopathy. These results have important implications for the development of novel therapies to target this intractable problem in clinical solid organ transplantation

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

OBJECTIVE - To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent alloand autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS - Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS - BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS - The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis