Comorbidita' ADHD-Epilessia: analisi delle caratteristiche cliniche ed EEG

L’associazione tra ADHD ed Epilessia e/o anomalie EEG è documentata in letteratura sia in termini di comparsa di deficit di attenzione ed iperattività in bambini prescolari e scolari con epilessia, che viceversa di comparsa di crisi epilettiche in bambini con ADHD. L’Epilessia è una condizione clinica caratterizzata dal ripetersi di crisi epilettiche definite come “manifestazioni cliniche parossistiche, motorie, sensitive, sensoriali o psichiche, accompagnate o meno da perdita di coscienza, e legate ad una scarica ipersincrona di una popolazione più o meno estesa di neuroni della corteccia cerebrale”. La prevalenza dell’Epilessia nella popolazione generale è dello 0,5-1% e presenta 2 picchi di incidenza: nel primo anno di vita e dopo i 75 anni. L’ADHD di tipo combinato è caratterizzato secondo i criteri diagnostici del DSM-V da: iperattività/impulsività e inattenzione, insorti prima dei 12 anni, presenti in più di 2 contesti (scuola, famiglia, sport …) e che comportano compromissione della vita di relazione e scolastica del bambino. La prevalenza dell’ADHD nella popolazione scolare varia dal 3 al 7% con un rapporto maschio:femmina di 4:1. L’incidenza dell’epilessia in pazienti con ADHD è del 2%, mentre l’incidenza dell’ADHD in pazienti con epilessia è del 30-40%. Per quanto riguarda le anomalie EEG nei soggetti con ADHD hanno un’incidenza che varia dal 23 al 56%, a seconda della modalità di registrazione dell’EEG, in più della metà dei casi sono anomalie focali localizzate principalmente nelle aree anteriori. Le forme di epilessia più frequentemente riportate in letteratura, in associazione all’ADHD, sono: l’Epilessia del Lobo Frontale, l’Epilessia Assenza dell’Infanzia, l’Epilessia a Parossismi Rolandici (Centro-Temporali) e l’Epilessia a Punte-Onde lente Continue nel Sonno (POCS). Le caratteristiche neuropsicologiche dei pazienti con ADHD ed epilessia e/o anomalie EEG sono caratterizzate da un quoziente intellettivo (QIT) mediamente più basso, indipendentemente dalla presenza di epilessia e/o anomalie EEG, un’incidenza maggiore di comorbidità psichiatriche (disturbo d’ansia, disturbo della condotta, disturbo oppositivo-provocatorio, disturbo di somatizzazione e disturbo ossessivo-compulsivo), difficoltà di apprendimento (lettura, scrittura, comprensione). Obiettivi Gli obiettivi del nostro studio sono stati: •descrivere le caratteristiche cliniche ed EEG della comorbidità ADHD-Epilessia •analizzare le differenze nel fenotipo neuropsicologico e comportamentale tra pazienti con ADHD con e senza crisi/anomalie EEG al fine di identificare eventuali fattori di rischio •identificare eventuali associazioni tra le anomalie EEG e le caratteristiche fenotipiche dell’ADHD. Il campione è costituito da 50 soggetti con ADHD di tipo combinato ed almeno un EEG nella loro valutazione clinico-diagnostica, di cui 43 maschi (86%) e 7 femmine (14%). All’ultimo follow-up i soggetti dello studio avevano un’età compresa tra un minimo di 5,4 anni e un massimo di 19,0 anni, con una media di 10,6 e deviazione standard (DS) 2,9. Il campione clinico è stato suddiviso in 2 gruppi sperimentali: 1. ADHD ed epilessia e/o anomalie EEG (ADHDE) 2. ADHD senza anomalie o crisi (ADHD-Simplex) Tramite revisione delle cartelle cliniche e compilazione di un database sono state analizzate come variabili: la familiarità per patologie neuropsichiatriche, le comorbidità neuropsichiatriche, la presenza, il tipo e la localizzazione di anomalie EEG, e nei pazienti con epilessia le caratteristiche di quest’ultima. Risultati: Il 52% (26/50) del nostro campione non presenta anomalie EEG, il 20% presenta anomalie solo in sonno e il 28% presenta anomalie sia in sonno che in veglia. Del gruppo di pazienti con anomalie EEG il 59% ha anomalie focali sulle aree anteriori, il 25% multifocali e/o diffuse e il 16% focali sulle regioni posteriori. Il gruppo con epilessia (13/50) ha nel 77% dei casi crisi di tipo focale, mentre il restante 23% crisi generalizzate. L’analisi del sottotipo di crisi ha evidenziato che il 38,5% dei soggetti ha crisi focali complesse, il 38,5% ha crisi focali secondariamente generalizzate, il 15,3% ha crisi generalizzate tonico-cloniche e il 7,7% ha crisi miocloniche. Per quanto riguarda invece il livello di sviluppo cognitivo del campione totale, questo risultava nella norma in 25/50 soggetti (50%), mentre 11/50 (22%) avevano un livello cognitivo in area limite, 8/50 (16%) un ritardo mentale lieve, e 6/50 (12%) un ritardo mentale di grado medio. Dal confronto dei due gruppi sperimentali (ADHD-Simplex e ADHDE) è emersa un’associazione significativa con la familiarità per epilessia nel gruppo ADHDE, mentre per il gruppo ADHD-Simplex si sono ritrovate associazioni significative con punteggi patologici di alcune sottoscale delle CBCL 6-12 (problemi di attenzione, comportamento aggressivo, trasgressione regole e problemi esternalizzanti). Un’ulteriore analisi è stata effettuata suddividendo i pazienti con anomalie EEG focali in due gruppi in base alla localizzazione delle anomalie: ADHD con anomalie EEG anteriori e ADHD con anomalie EEG posteriori. Quest’analisi ha rivelato che i soggetti con anomalie nelle aree posteriori hanno un’associazione statisticamente significativa con: ritardo mentale medio, disturbo pervasivo dello sviluppo, anamnesi positiva per sofferenza peri-natale, disturbo d’ansia e presenza di familiarità per disturbo dell’umore. Discussione/Conclusioni Questo studio conferma l’associazione tra ADHD ed epilessia e/o anomalie EEG già descritta in letteratura. Per quanto riguarda le caratteristiche delle anomalie EEG si conferma la prevalenza di anomalie di tipo focale, a prevalente localizzazione anteriore, possibilmente associate ad alterazioni morfologiche e neurotrasmettitoriali caratteristiche della corteccia frontale e prefrontale dei soggetti con ADHD. Il confronto tra il gruppo ADHDE e ADHD-Simplex ha fatto emergere, tramite l’utilizzo delle CBCL, più marcati comportamenti disfunzionali e maggiori difficoltà attentive nel gruppo senza crisi/anomalie EEG. Per quanto riguarda invece il livello cognitivo, il 50% dei soggetti del campione presenta difficoltà cognitive o un chiaro ritardo mentale, che non sembra tuttavia essere influenzato dalla presenza o meno di epilessia e/o anomalie EEG. L’analisi in base alla localizzazione delle anomalie EEG ha mostrato che i soggetti con ADHD e anomalie EEG focali posteriori presentano un fenotipo clinico più grave rispetto a quelli con anomalie anteriori, per una maggiore frequenza di ritardo mentale lieve/medio ed un rischio maggiore di presentare altre patologie psichiatriche in comorbidità come ad esempio un disturbo d’ansia e/o un disturbo pervasivo dello sviluppo. Questo risultato appare importante nell’ambito della pratica clinica in quanto la precoce identificazione di anomalie EEG posteriori in pazienti con ADHD e il conseguente monitoraggio clinico di questi soggetti potrebbe consentire la diagnosi precoce di disabilità neurocomportamentali e l’avvio di opportune misure terapeutiche. Appare utile infine un futuro ampliamento del campione per poter validare ulteriormente questi risultati e aprire la strada ad ulteriori ricerche quali ad esempio l’effetto di terapie farmacologiche specifiche per l’ADHD sull’epilessia

Efficacy of Supra-HFR in Removing FGF23 and Cytokines: A Single Session Analysis

Background/Aim: Supra hemodiafiltration with reinfusion of the endogenous ultrafiltrate (Supra-HFR) is a dialysis technique used to improve uremic toxin removal in the range of the middle molecular weight molecules. Supra-HFR does not require the preparation and online infusion of high purity dialysis water because it allows the production of an endogenous ultrafiltrate that undergoes detoxification through an adsorbing resin. Patients and Methods: We investigated the ability of Supra-HFR to remove fibroblast growth factor 23 (FGF23), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), interleukin 8 (IL-8), and transforming growth factor alpha (TGF-alpha) after a single session dialysis in nine patients affected by end stage renal disease (ESRD). The same patients underwent a single session of online hemodiafiltration (OLHDF) to evaluate possible differences in FGF23 and IL-6 levels. Results: A significant reduction in FGF23 was observed with both Supra-HFR (p=0.001) and OL-HDF. As for TNF-alpha and TGF-alpha, which were measured using Supra-HFR only, their percentage values were significantly lower at the end of dialysi

A flexible sensor technology for the distributed measurement of interaction pressure

We present a sensor technology for the measure of the physical human-robot interaction pressure developed in the last years at Scuola Superiore Sant'Anna. The system is composed of flexible matrices of opto-electronic sensors covered by a soft silicone cover. This sensory system is completely modular and scalable, allowing one to cover areas of any sizes and shapes, and to measure different pressure ranges. In this work we present the main application areas for this technology. A first generation of the system was used to monitor human-robot interaction in upper- (NEUROExos; Scuola Superiore Sant'Anna) and lower-limb (LOPES; University of Twente) exoskeletons for rehabilitation. A second generation, with increased resolution and wireless connection, was used to develop a pressure-sensitive foot insole and an improved human-robot interaction measurement systems. The experimental characterization of the latter system along with its validation on three healthy subjects is presented here for the first time. A perspective on future uses and development of the technology is finally drafted

An Active Form of Sphingosine Kinase-1 Is Released in the Extracellular Medium as Component of Membrane Vesicles Shed by Two Human Tumor Cell Lines

Expression of sphingosine kinase-1 (SphK-1) correlates with a poor survival rate of tumor patients. This effect is probably due to the ability of SphK-1 to be released into the extracellular medium where it catalyzes the biosynthesis of sphingosine-1-phosphate (S1P), a signaling molecule endowed with profound proangiogenic effects. SphK-1 is a leaderless protein which is secreted by an unconventional mechanism. In this paper, we will show that in human hepatocarcinoma Sk-Hep1 cells, extracellular signaling is followed by targeting the enzyme to the cell surface and parallels targeting of FGF-2 to the budding vesicles. We will also show that SphK-1 is present in a catalitycally active form in vesicles shed by SK-Hep1 and human breast carcinoma 8701-BC cells. The enzyme substrate sphingosine is present in shed vesicles where it is produced by neutral ceramidase. Shed vesicles are therefore a site for S1P production in the extracellular medium and conceivably also within host cell following vesicle endocytosis

The night of randomized clinical trials where all patients are black: a need to estimate variability in treatment effects

In the Sixties, the few anti-thrombotic drugs available were administered following several criteria including tradition of the "School", preference of the doctor in charge, pressure of pharmaceutical companies [...

Ultra-processed food consumption and its correlates among Italian children, adolescents and adults from the Italian Nutrition & Health Survey (INHES) cohort study.

AbstractObjective:To assess ultra-processed food (UPF) consumption and its socio-demographic, psychosocial and behavioural correlates in a general population of Italian children, adolescents and adults.Design:Cross-sectional telephone-based surveySetting:Italy, 2010–2013.Participants:In total, 9078 participants (5–97 years) from the Italian Nutrition & Health Survey. Dietary intakes were collected by a 1-d 24-h dietary recall. UPF was defined by the NOVA classification and expressed as percentage of total energies.Results:Average energy intake from UPF (95 % CI) was 17·3 % (17·1 %, 17·6 %) among adults and 25·9 % (24·8 %, 27·0 %) in children/adolescents. Top sources of UPF were processed meats (32·5 %) and bread substitutes (16·7 %). Among adults, age (β = −3·10; 95 % CI (−4·40, −1·80) for >65 years v. 20–40 years; βs are dimensionless) and residing in Southern Italy (β = −0·73; 95 % CI (−1·32, −0·14) v. Northern) inversely associated with UPF. Screen view during meals was directly linked to UPF, as well as poor self-rated health (β = 5·32; 95 % CI (2·66, 7·99)), adverse life events (β = 2·33; 95 % CI (1·48, 3·18)) and low sleep quality (β = 2·34; 95 % CI (1·45, 3·23)). Boys consumed two-point percent more UPF of the total energy than girls (β = 2·01; 95 % CI (0·20, 3·82)). For all ages, a Mediterranean diet was inversely associated with UPF (β = −4·86; 95 % CI (−5·53, −4·20) for good v. poor adherence in adults and (β = −5·08; 95 % CI (−8·38, −1·77) for kids).Conclusions:UPF contributes a modest proportion of energy to the diets of Italian adults while being one-quarter of the total energies in children/adolescents. UPF was associated with several psychosocial factors and eating behaviours. Increased adherence to Mediterranean diet would possibly result in lower UPF consumption

Impact of Single Hemodialysis Treatment on immune Cell Subpopulations

: Hemodialysis (HD) is known to trigger a chronic inflammatory status, affecting the innate and acquired immune response. This study was aimed at a comparative analysis of immune cell subsets, proliferation, and apoptosis in subjects receiving chronic HD treatment with respect to a healthy control. Regardless of the dialysis filter used, we observed a reshaping of the acquired immune component both with respect to healthy patients and between the various sessions of dialysis treatment, with an impairment of CD3 cells, along with an increase in CD4 and CD8 cell populations producing pro-inflammatory factors such as IL-17 and IFN-gamma. The population of B cells, monocytes and NK cells were not impaired by the dialysis procedure. These results confirmed the high impact of the HD treatment on the patient's immune system, underlying the imbalance of T cell counterparts

Ozone and procaine increase secretion of platelet-derived factors in platelet-rich plasma

Platelet-rich plasma (PRP) is gaining more and more attention in regenerative medicine as an innovative and efficient therapeutic approach. The regenerative properties of PRP rely on the numerous bioactive molecules released by the platelets: growth factors are involved in proliferation and differentiation of endothelial cells and fibroblasts, angiogenesis and extracellular matrix formation, while cytokines are mainly involved in immune cell recruitment and inflammation modulation. Attempts are ongoing to improve the therapeutic potential of PRP by combining it with agents able to promote regenerative processes. Two interesting candidates are ozone, administered at low doses as gaseous oxygen-ozone mixtures, and procaine. In the present study, we investigated the effects induced on platelets by the in vitro treatment of PRP with ozone or procaine, or both. We combined transmission electron microscopy to obtain information on platelet modifications and bioanalytical assays to quantify the secreted factors. The results demonstrate that, although platelets were already activated by the procedure to prepare PRP, both ozone and procaine induced differential morpho-functional modifications in platelets resulting in an increased release of factors. In detail, ozone induced an increase in surface protrusions and open canalicular system dilation suggestive of a marked α-granule release, while procaine caused a decrease in surface protrusions and open canalicular system dilation but a remarkable increase in microvesicle release suggestive of high secretory activity. Consistently, nine of the thirteen platelet-derived factors analysed in the PRP serum significantly increased after treatment with ozone and/or procaine. Therefore, ozone and procaine proved to have a remarkable stimulating potential without causing any damage to platelets, probably because they act through physiological, although different, secretory pathways

Machine-learning prediction model for acute skin toxicity after breast radiation therapy using spectrophotometry

PurposeRadiation-induced skin toxicity is a common and distressing side effect of breast radiation therapy (RT). We investigated the use of quantitative spectrophotometric markers as input parameters in supervised machine learning models to develop a predictive model for acute radiation toxicity. Methods and materialsOne hundred twenty-nine patients treated for adjuvant whole-breast radiotherapy were evaluated. Two spectrophotometer variables, i.e. the melanin (I-M) and erythema (I-E) indices, were used to quantitatively assess the skin physical changes. Measurements were performed at 4-time intervals: before RT, at the end of RT and 1 and 6 months after the end of RT. Together with clinical covariates, melanin and erythema indices were correlated with skin toxicity, evaluated using the Radiation Therapy Oncology Group (RTOG) guidelines. Binary group classes were labeled according to a RTOG cut-off score of >= 2. The patient's dataset was randomly split into a training and testing set used for model development/validation and testing (75%/25% split). A 5-times repeated holdout cross-validation was performed. Three supervised machine learning models, including support vector machine (SVM), classification and regression tree analysis (CART) and logistic regression (LR), were employed for modeling and skin toxicity prediction purposes. ResultsThirty-four (26.4%) patients presented with adverse skin effects (RTOG >= 2) at the end of treatment. The two spectrophotometric variables at the beginning of RT (I-M,I-T0 and I-E,I-T0), together with the volumes of breast (PTV2) and boost surgical cavity (PTV1), the body mass index (BMI) and the dose fractionation scheme (FRAC) were found significantly associated with the RTOG score groups (p<0.05) in univariate analysis. The diagnostic performances measured by the area-under-curve (AUC) were 0.816, 0.734, 0.714, 0.691 and 0.664 for IM, IE, PTV2, PTV1 and BMI, respectively. Classification performances reported precision, recall and F1-values greater than 0.8 for all models. The SVM classifier using the RBF kernel had the best performance, with accuracy, precision, recall and F-score equal to 89.8%, 88.7%, 98.6% and 93.3%, respectively. CART analysis classified patients with I-M,I-T0 >= 99 to be associated with RTOG >= 2 toxicity; subsequently, PTV1 and PTV2 played a significant role in increasing the classification rate. The CART model provided a very high diagnostic performance of AUC=0.959. ConclusionsSpectrophotometry is an objective and reliable tool able to assess radiation induced skin tissue injury. Using a machine learning approach, we were able to predict grade RTOG >= 2 skin toxicity in patients undergoing breast RT. This approach may prove useful for treatment management aiming to improve patient quality of life