Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Sindrome di Poirier-Bienvenu da mutazione del gene CSNK2B: studio multicentrico retrospettivo di correlazione genotipo-fenotipo

La sindrome di Poirier–Bienvenu (POBINDS) è una malattia rara, correlate alla mutazione del gene CSNK2B. Tale gene codifica per la subunità beta della proteina CK2, implicata in molti processi biologici, tra cui lo sviluppo neuronale e la trasmissione sinaptica. La sindrome POBINDS è caratterizzata dalla presenza di epilessia ad esordio precoce e disabilità intellettiva. Vista la scarsità attuale di casi riscontrati, è difficile stabilire un’accurata definizione nella correlazione genotipo-fenotipo; è certo, però, che i sintomi neurologici non sono gli unici ad essere presenti in questi pazienti. Il nostro studio multicentrico, retrospettivo ha reclutato 12 pazienti affetti da mutazione di CSNK2B, rilevata tramite l’utilizzo di metodiche di Next Generation Sequencing. Di tali pazienti sono state raccolte informazioni cliniche, laboratoristiche e strumentali, al fine di determinarne la gravità del fenotipo ed un’eventuale correlazione con particolari genotipi. I 12 pazienti presentano mutazioni de novo in eterozigosi del gene CSNK2B. La quasi totalità dei pazienti ha presentato epilessia, e la maggior parte di essi ha presentato disabilità intellettiva di variabile gravità. Sono stati inoltre rilevate anomalie vascolari, dismorfismi faciali e disturbi endocrinologici. Le analisi genetiche hanno rivelato 6 nuove varianti di CSNK2B non precedentemente riportate. Anche se non è possibile stabilire una correlazione genotipo-fenotipo nei nostri pazienti, la nostra ricerca va ad espandere lo spettro fenotipico dei pazienti affetti da POBINDS, identificando nuove mutazioni a carico del gene CSNK2B

Development of QSAR models for predicting hepatocarcinogenic toxicity of chemicals

A dataset comprising 55 chemicals with hepatocarcinogenic potency indices was collected from the Carcinogenic Potency Database with the aim of developing QSAR models enabling prediction of the above unwanted property for New Chemical Entities. The dataset was rationally split into training and test sets by means of a sphere-exclusion type algorithm. Among the many algorithms explored to search regression models, only a Support Vector Machine (SVM) method led to a QSAR model, which was proved to pass rigorous validation criteria, in accordance with the OECD guidelines. The proposed model is capable to explain the hepatocarcinogenic toxicity and could be exploited for predicting this property for chemicals at the early stage of their development, so optimizing resources and reducing animal testing

QSAR models for predicting biological properties, developed by combining structure- and ligand-based approaches: an application to the hERG potassium channel inhibition

A strategy for developing accurate quantitative structure-activity relationship models enabling predictions of biological properties, when suitable knowledge concerning both ligands and biological target is available, was tested on a data set where molecules are characterized by high structural diversity. Such a strategy was applied to human ether-a-go-go-related gene K(+) channel inhibition and consists of a combination of ligand- and structure-based approaches, which can be carried out whenever the three-dimensional structure of the target macromolecule is known or may be modeled with good accuracy. Molecular conformations of ligands were obtained by means of molecular docking, performed in a previously built theoretical model of the channel pore, so that descriptors depending upon the three-dimensional molecular structure were properly computed. A modification of the directed sphere-exclusion algorithm was developed and exploited to properly splitting the whole dataset into Training/Test set pairs. Molecular descriptors, computed by means of the codessa program, were used for the search of reliable quantitative structure-activity relationship models that were subsequently identified through a rigorous validation analysis. Finally, pIC(50) values of a prediction set, external to the initial dataset, were predicted and the results confirmed the high predictive power of the model within a quite wide chemical space

The role of imaging in the evaluation of joint involvement in 102 consecutive patients with systemic lupus erythematosus

Objective: To assess the prevalence of joint involvement in consecutive patients with systemic lupus erythematosus (SLE) by means of clinical assessment, joint US and MRI and to evaluate the sensitivity and specificity of physician evaluation of joint involvement. Methods: At enrolment, patients underwent a complete physical examination including a 44-joint count, and hand deformities were scored. On the day of enrolment, each patient underwent a non-dominant hand-wrist ultrasound (US) examination and a non-dominant hand-wrist MRI study without contrast injection. Results: One hundred and two patients (F 95, M 7) were enrolled. By physician examination hand or wrist involvement was diagnosed in 23.5%. At least one pathological finding was revealed by US examination at wrist and/or hand joints in 55%. We found a low sensitivity (46.5%) with high specificity (93.2%) of the physician assessment for the evaluation of joint involvement.The MRI imaging showed at least one erosion in 47.3% patients at the hand and in 98.9% at the wrist; in healthy subjects erosions were found in 19.6% and 97.8% at the hand and wrist, respectively. Conclusions: In conclusion, (i) physicians tend to underestimate the severity of joint involvement in SLE; (ii) US assessment shows a high prevalence of joint and tendon involvement; and (iii) the MRI evaluation shows a high prevalence of damage, suggesting that joint involvement in SLE could be more severe than expected