Vecchie e nuove Immunodeficienze Primitive: strategie per il sospetto e la diagnosi.

Viene analizzata l'epidemiologia delle immunodeficienze in Slovenia e Friuli venezia Giulia. Vengono valutati i sintomi di presentazione di immunodeficienza in base all'età di esordio e di diagnosi e gli esami di laboratorio più utili nell'iter diagnostico.L'identificazione di nuovi tipi di immunodeficienza richiede una rivalutazione delle strategie di sospetto e diagnosi. Sulla base delle nuove conoscenze e di un'analisi della casistica osservata presso l'Istituto Burlo Garofolo e presso la Clinica Pediatrica di Lubiana, vengono formulati alcuni consigli per migliorare il sospetto e la diagnosi delle diverse immunodeficienze.IRCCS Burlo Garofolo, progetto RC 03/0

Magnitude modelling of HRTF using principal component analysis applied to complex values

Principal components analysis (PCA) is frequently used for modelling the magnitude of the head related transfer functions (HRTFs). Assuming that the HRTFs are minimum phase systems, the phase is obtained from the Hilbert transform of the log-magnitude. In recent years, the PCA applied to HRTFs is also used to model individual HRTFs relating the PCA weights with anthropometric measurements of the head, torso and pinnae. The HRTF log-magnitude is the most used format of input data to the PCA, but it has been shown that if the input data is HRTF linear magnitude, the cumulative variance converges faster, and the mean square error (MSE) is smaller. This study demonstrates that PCA applied directly on HRTF complex values is even better than the two formats mentioned above, that is, the MSE is the smallest and the cumulative variance converges faster after the 8th principal component. Different objective experiments around all the median plane put in evidence the differences which, although small, seem to be perceptually detectable. To elucidate this point, psychoacoustic discrimination tests are done between measured and reconstructed HRTFs from the three types of input data mentioned, in the median plane between −45◦ and +90◦.http://acoustics.ippt.pan.pl/index.php/aa/article/view/294publishedVersionFil: Ramos, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Transferencia en Acústica; Argentina.Fil: Ramos, Oscar Alberto. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación y Transferencia en Acústica; Argentina.Fil: Ramos, Oscar Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Tommasini, Fabián Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Transferencia en Acústica; Argentina.Fil: Tommasini, Fabián Carlos. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación y Transferencia en Acústica; Argentina.Fil: Tommasini, Fabián Carlos. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Tommasini, Fabián Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Otras Ingenierías y Tecnología

Druggable monogenic immune defects hidden in diverse medical specialties: Focus on overlap syndromes

In the last two decades two new paradigms changed our way of perceiving primary immunodeficiencies: An increasing number of immune defects are more associated with inflammatory or autoimmune features rather than with infections. Some primary immune defects are due to hyperactive pathways that can be targeted by specific inhibitors, providing innovative precision treatments that can change the natural history of diseases. In this article we review some of these "druggable" inborn errors of immunity and describe how they can be suspected and diagnosed in diverse pediatric and adult medicine specialties. Since the availability of precision treatments can dramatically impact the course of these diseases, preventing the development of organ damage, it is crucial to widen the awareness of these conditions and to provide practical hints for a prompt detection and cure

Vasculitis, Autoimmunity, and Cytokines: How the Immune System Can Harm the Brain

More and more findings suggest that neurological disorders could have an immunopathological cause. Thus, immune-targeted therapies are increasingly proposed in neurology (even if often controversial), as anakinra, inhibiting IL-1 for febrile inflammatory illnesses, and JAK inhibitors for anti-interferons treatment. Precision medicine in neurology could be fostered by a better understanding of the disease machinery, to develop a rational use of immuno-modulators in clinical trials. In this review, we focus on monogenic disorders with neurological hyper-inflammation/autoimmunity as simplified "models" to correlate immune pathology and targeted treatments. The study of monogenic models yields great advantages for the elucidation of the pathogenic mechanisms that can be reproduced in cellular/animal models, overcoming the limitations of biological samples to study. Moreover, monogenic disorders provide a unique tool to study the mechanisms of neuroinflammatory and autoimmune brain damage, in all their manifestations. The insight of clinical, pathological, and therapeutic aspects of the considered monogenic models can impact knowledge about brain inflammation and can provide useful hints to better understand and cure some neurologic multifactorial disorders

Ultrasonographic Assessment for Tenosynovitis in Juvenile Idiopathic Arthritis with Ankle Involvement: Diagnostic and Therapeutic Significance

Background: The role of musculoskeletal ultrasound in JIA is still controversial, although there is growing evidence on its utility, especially in the diagnosis of tenosynovitis. Methods: We presented a retrospective cross-sectional study of a group of patients with JIA with ankle swelling followed in a Pediatric Rheumatology Service of a tertiary-level pediatric hospital in Northern Italy during the follow-up period between January 1st 2003 and December 31st 2019. Preliminary results have been presented at the EULAR Congress 2021. We enrolled only patients who underwent msk-US, and we identified those with a clinical and sonographic diagnosis of tenosynovitis. For each patient, we collected data on demographics, clinical characteristics, and therapeutic strategies during the follow-up. Results: On December 31st 2019, 56 swollen ankles of 48 patients were assessed with msk-US. Twenty-two ankles showed sonographic signs of joint synovitis, sixteen ankles presented signs of both joint synovitis and tenosynovitis, and fourteen ankles presented sonographic signs of tenosynovitis only. Overall, tenosynovitis was detected on 27 (56%) out of 48 children with at least a swollen ankle. In 13 patients out of 27 with tenosynovitis (48%), there was no joint synovitis of ankle or foot. Twenty-five patients with tenosynovitis (92%) achieved clinical and radiological remission: seven patients achieved remission of tenosynovitis with methotrexate only, and fifteen patients with biological drugs alone or in combination therapy. Conclusions: We observed that more than half of the patients with ankle swelling presented a tenosynovitis, and about 50% of them did not show sonographic signs of an active joint synovitis. Among patients with tenosynovitis, biological therapy alone or in association with DMARDs showed effectiveness in inducing disease remission

Fever tree revisited: From malaria to autoinflammatory diseases

Over the centuries the idea of recurrent fevers has mainly been associated with malaria, but many other fevers, such as typhoid and diphtheria were cause for concern. It is only in recent times, with the more severe forms of fever from infectious origin becoming less frequent or a cause for worry that we started noticing recurrent fevers without any clear infectious cause, being described as having a pathogenesis of autoinflammatory nature. The use of molecular examinations in many cases can allow a diagnosis where the cause is monogenic. In other cases, however the pathogenesis is likely to be multifactorial and the diagnostic-therapeutic approach is strictly clinical. The old fever tree paradigm developed to describe fevers caused by malaria has been revisited here to describe today's periodic fevers from the periodic fever adenitis pharyngitis aphthae syndrome to the more rare autoinflammatory diseases. This model may allow us to place cases that are yet to be identified which are likely to be of multifactorial origin

An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Gouti\ue8res syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences

Usage of Spectral Distortion for Objective Evaluation of Personalized HRTF in the Median Plane

Measuring the head-related transfer functions (HRTFs) for each subject is a complex process. Therefore, it is necessary to develop procedures that allow the estimation of personalized HRTFs. It is common to estimate the weights of the principal component analysis (PCA) of a group of subjects based on some anthropometric parameters using multivariable regression modelling. Moreover, to objectively evaluate the goodness of fit} between the original HRTFs and the personalized ones, the spectral distortion (SD) is usually used too. However, its suitability in the median plane, in which the spectral profiles are crucial to localize a sound source, has not yet been demonstrated. This paper analyses the validity of the SD as a measure of the quality of the HRTF personalization in the median plane, from the localization point of view. The HRTFs were modelled from the weights estimated by multiple linear regression and artificial neural networks (ANNs). The SD was used to compare the HRTFs measured with those estimated. Likewise, the level of fitting accuracy of characteristic resonance and notches in the median plane was also compared. Despite the fact that the SD scores of ANNs are lower than those of the multiple linear regression and are similar to those reported by other studies, the errors obtained from analysing both central frequencies and levels for resonance and notches could be discriminated.Fil: Tommasini, Fabián Carlos. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Centro de Investigación y Transferencia en Acústica; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ramos, Oscar Alberto. Centro de Investigación y Transferencia en Acústica; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Hug, Mercedes Ximena. Centro de Investigación y Transferencia en Acústica; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Bermejo, Fernando Raul. Centro de Investigación y Transferencia en Acústica; Argentina. Universidad Tecnológica Nacional. Facultad Regional Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin