"Conventional and innovative replacement treatments in Adrenal iNsufficiency: Identification of new bioMArkers of Glucocorticoid Exposure "AN IMAGE" The interplays between biological clocks, physiological and non-physiological cortisol exposure, metabolic and immune system: impact on morbidity and quality of life of patients with adrenal insufficiency

Livelli "fisiologici" di glucocorticoidi (GC) sono fondamentali nella sincronizzazione dell'orologio biologico di diversi organi e tessuti. L'ipotesi del presente progetto di ricerca è che un ritmo anti-circadiano o una anomala sequenza di picchi e nadir di cortisolo potrebbero innescare processi di de-sincronizzazione, alterando diversi sistemi. Lo scopo è quello di descrivere le interazioni tra orologio biologico, esposizione "fisiologica" e "non fisiologica" al cortisolo nel sistema metabolico ed immune, sia in modelli in vitro che in vivo. Dalla comprensione di queste interazioni, potrebbero essere identificati nuovi "biomarcatori" di esposizione al cortisolo, capaci di fornire una fotografia "istantanea" del "clock status" di un soggetto. I risultati di tale progetto di ricerca potrebbero essere di fondamentale importanza in pazienti affetti da insufficienza surrenalica, una rara endocrinopatia, che necessitano di una terapia ormonale sostitutiva con GC a vita. Gli obiettivi della presente ricerca comprendono: 1. Studi in vitro volti ad indagare gli effetti dell'esposizione fisiologica e non fisiologica al cortisolo su linee cellulari di muscolo C2C12 2. Studi in vivo volti ad esplorare l'impatto dello switch dai GC convenzionali all' idrocortisone a rilascio modificato in una coorte di pazienti affetti da insufficienza surrenalica, in termini di efficacia, sul profilo metabolico, ormonale, cardiovascolare, sulla qualità della vita e sullo status depressivo, ed in termini di sicurezza. 3. Studi ex vivo volti ad indagare gli effetti dell'esposizione fisiologica e non fisiologica al cortisolo su cellule mononucleate circolanti del sangue periferico

Quasi-static and low-velocity impact behavior of intraply hybrid flax/basalt composites

In an attempt to increase the low-velocity impact response of natural fiber composites, a new hybrid intraply woven fabric based on flax and basalt fibers has been used to manufacture laminates with both thermoplastic and thermoset matrices. The matrix type (epoxy or polypropylene (PP) with or without a maleated coupling agent) significantly affected the absorbed energy and the damage mechanisms. The absorbed energy at perforation for PP-based composites was 90% and 50% higher than that of epoxy and compatibilized PP composites, respectively. The hybrid fiber architecture counteracted the influence of low transverse strength of flax fibers on impact response, irrespective of the matrix type. In thermoplastic laminates, the matrix plasticization delayed the onset of major damage during impact and allowed a better balance of quasi-static properties, energy absorption, peak force, and perforation energy compared to epoxy-based composites

Assessment e riabilitazione delle abilità sensomotorie e del linguaggio nell'autismo tramite l'utilizzo di interfacce tangibili e sistemi di analisi computazionale

Il presente lavoro descrive un percorso metodologico che mira ad intrecciare vari approcci e costrutti che avvolgono la sfera clinica dei disturbi dello spettro autistico (ASD) al fine di riuscire ad arricchire, in maniera dinamica ed innovativa, i processi di assessment diagnosi e riabilitazione che la caratterizzano. A partire da due approcci apparentemente lontani, l'Embodied Cognition e l' analisi del comportamento applicata (Applied Behavior Analysis), illustreremo come, avvalendoci delle potenzialità delle nuove tecnologie, possiamo ottenere nuove misure oggettive del disturbo e ridefinire i percorsi di riabilitazione a partire da esse. A partire dai costrutti teorici dell'Embodied Cognition abbiamo immaginato e sviluppato degli strumenti ad hoc per il rilevamento di pattern di movimento specifici. Servendoci dei principi metodologici dell'Applied Behavior Analysis, il lavoro illustra nuovi modi di affrontare la riabilitazione nell'ambito dell'autismo. Dividendo il lavoro in tre sessioni sperimentali il lavoro illustra tre aspetti distinti ma consequenziali dell'approccio all'autismo secondo questa nuova ottica: La prima sessione sperimentale è dedicata all'implementazione e alla verifica dell'efficacia di un nuovo strumento di comunicazione aumentativa alternativa (CAA) LI-AR, studiato ad hoc per riabilitare il comportamento comunicativo nell'autismo. La seconda sessione sperimentale descrive le potenzialità di un nuovo strumento per il rilevamento di pattern tipici di movimento nell'autismo. La terza sessione unisce gli approcci e propone l'utilizzo, in ambito riabilitativo, di un nuovo strumento che sfruttando una metodologia basata sul condizionamento classico e quindi di natura comportamentista, mira a riabilitare un aspetto trasparente del comportamento, ovvero, la propriocezione e i rapporti di causalità tra corpo e mondo esterno, tipicamente alterati in ASD. Lo studio spinge a ripensare ai modi di affrontare l'autismo senza perdere di vista la storia che ha caratterizzato la clinica del disturbo, ma anzi, a partire da essa, con l'obiettivo di potenziare i costrutti comportamentisti, ad oggi di elezione per il trattamento della sindrome, intrecciandoli ad approcci cognitivisti e cercando di sfruttare al massimo i vantaggi che oggi la tecnologia e i sistemi di intelligenza artificiale possono fornirci

Metastatic tumors to the stomach: clinical and endoscopic features.

AIM: To evaluate the clinical and endoscopic patterns in a large series of patients with metastatic tumors in the stomach. METHODS: A total of 64 patients with gastric metastases from solid malignant tumors were retrospectively examined between 1990 and 2005. The clinicopathological findings were reviewed along with tumor characteristics such as endoscopic pattern, location, size and origin of the primary sites. RESULTS: Common indications for endoscopy were anemia, bleeding and epigastric pain. Metastases presented as solitary (62.5%) or multiple (37.5%) tumors were mainly located in the middle or upper third of stomach. The main primary metastatic tumors were from breast and lung cancer and malignant melanoma. CONCLUSION: As the prognosis of cancer patients has been improving gradually, gastrointestinal (GI) metastases will be encountered more often. Endoscopic examinations should be conducted carefully in patients with malignancies, and endoscopic biopsies and information on the patient's clinical history are useful for correct diagnosis of gastric metastases

Visualization of Thermal Effects in Polypropylene-based Composites under Cyclic Bending Tests☆

Abstract The attention of this paper is focused on surface temperature changes which are experienced by thermoplastic composite materials under cyclic bending tests. Such changes are visualized and measured with an infrared imaging device and later analyzed to gain information which, coupled with other mechanical and/or chemical properties, may be exploited for the material characterization. In particular, thermoplastic composites based on a polypropylene matrix, which may be neat, or modified by the addition of a relatively low amount of a specific compatibilizing agent, and reinforced with glass or jute woven fibres are investigated

Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?

OBJECTIVE: Diabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients. DESIGN: Cross-sectional study on 140 patients with CS. METHODS: A total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1±20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups. RESULTS: Seventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes (P<0.001), metabolic syndrome (P<0.001), age (P<0.001) and waist circumference (P=0.043) and decreasing trends in HOMA-β (P<0.001) and oral disposition index (DIo) (P<0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUCINS), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected. CONCLUSIONS: Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications

Polypoid vascular malformation of the small intestine.

A 56-year-old man underwent capsule endoscopy because of obscure GI bleeding. Capsule endoscopy showed a pink and somewhat nodular polypoid lesion of the small bowel partially obstructing the intestinal lumen (A). The patient underwent an ileal resection and the operative specimen showed loss of mucosal folds and the presence of an erythematous area with a polypoid formation of 3.5 × 3 cm (B). Histologic examination revealed the presence of numerous ectatic thin-walled blood vessels and a small number of thick-walled vessels in the submucosa (C and D, arrows; H&E, orig. mag. ×4), surrounded by hypertrophic muscularis mucosae and a chronic inflammatory infiltrate that infiltrated the muscularis propria; the diagnosis of polypoid angiodysplasia was suggested. There has been no recurrence of GI bleeding 14 months after the ileal resection

An educational game-based approach to learning Geometry in Elementary School: A preliminary study

El aprendizaje de la geometría es primordial en matemáticas para identificar las figuras geométricas y aprender sus propiedades. El empleo de juegos educativos en el aula, ofrece nuevas oportunidades para motivar a los estudiantes y aprender matemáticas en la vida diaria desde una perspectiva socio-constructivista dentro de las posturas falibilistas y cuasi- -empiristas. El objetivo de este trabajo es diseñar y evaluar una secuencia didáctica sobre geometría para primaria, donde la base del aprendizaje se articule a través de diferentes juegos educativos integrados de manera conjunta en la secuencia, permitiendo comparar el aprendizaje adquirido con los resultados de tareas más tradicionales. El estudio preliminar se desarrolló con 13 estudiantes de 7 años de un colegio de Málaga (España). Para cada contenido, se incluyeron en la secuencia tareas tradicionales (con fichas de trabajo con escasas oportunidades en el contexto social) y juegos (games y task involving play – TIP o tareas que promueven escenarios entre play y game–). El análisis cualitativo y cuantitativo de cada tarea mediante categorías y el test de Wilcoxon mostraron que los juegos educativos resultan más favorables para el aprendizaje de la geometría que los contenidos planteados con una tarea tradicional, en particular, aquellas relacionadas con la identificación de polígonos. Los resultados apuntan a que el tipo de juego educativo que resulta más efectivo en el aprendizaje de la geometría son los TIPs, ya que sólo en éstos se obtuvieron diferencias estadísticamente significativas al compararlos con tareas tradicionales.Learning geometry is paramount in mathematics to identify geometric shapes and learn their properties. The use of educational games in the classroom offers new opportunities to motivate students and to learn mathematics in daily-life contexts from a socioconstructivist perspective within the fallibilist and quasi-empiricist positions. The aim of this paper is to design and evaluate a teaching unit on geometry for elementary school, where the basis of learning is articulated through different educational games integrated together in the sequence, allowing us to compare the acquired learning with the results of more traditional tasks. The preliminary study was developed with 13 seven-year-old students from a school in Malaga (Spain). For each content, traditional tasks (worksheets with scarce opportunities in the social context) and games (together with task involving play - TIP or tasks promoting scenarios between play and game) were included in the teaching unit. The qualitative and quantitative analysis of each task using categories and the Wilcoxon test showed that educational games are more favorable to the learning of geometry than the contents proposed with a traditional task, in particular, those related to the identification of polygons. The results suggest that the type of educational game that is most effective in learning geometry is TIP, since only in these games statistically significant differences were obtained when compared to traditional tasks

Therapeutic Drug Monitoring of Quinidine in Pediatric Patients with KCNT1 Genetic Variants

Quinidine (QND) is an old antimalarial drug that was used in the early 20th century as an antiarrhythmic agent. Currently, QND is receiving attention for its use in epilepsy of infancy with migrating focal seizures (EIMFS) due to potassium sodium-activated channel subfamily T member 1 (KCNT1) genetic variants. Here, we report the application of Therapeutic Drug Monitoring (TDM) in pediatric patients carrying KCNT1 genetic variants and orally treated with QND for developmental and epileptic encephalopathies (DEE). We measured plasma levels of QND and its metabolite hydroquinidine (H-QND) by using a validated method based on liquid chromatography coupled with mass spectrometry (LC-MS/MS). Three pediatric patients (median age 4.125 years, IQR 2.375-4.125) received increasing doses of QND. Cardiac toxicity was monitored at every dose change. Reduction in seizure frequency ranged from 50 to 90%. Our results show that QND is a promising drug for pediatric patients with DEE due to KCNT1 genetic variants. Although QND blood levels were significantly lower than the therapeutic range as an anti-arrhythmic drug, patients showed a significant improvement in seizure burden. These data underlie the utility of TDM for QND not only to monitor its toxic effects but also to evaluate possible drug-drug interactions