A Long-term Psychological Observation in an Adolescent affected with Gardner Diamond Syndrome

Gardner-Diamond syndrome (GDS) is an uncommon disease clinically characterized by a wide spectrum of psycho-emotive symptoms associated with painful ecchymoses/purpuric lesions and positivity of auto-erythrocyte sensitization skin test. Herein, a perspective clinical and psychological observation of an adolescent GDS is firstly reported focusing on her psychological features long-term monitored for a 1-year period. The administration of a standardized tools battery allowed us to define psychological features of the young patient over time and to monitored clinical course and response to treatment

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/-) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/- mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers

La cura del trauma

Il Corso propone una formazione teorico-pratica sull’impatto del trauma psicologico sull’individuo e sulla società, integrando i principi evidence-based della diagnosi e dell’intervento clinico alle discipline sociali che intervengono nella comprensione della complessità traumatica e delle sue conseguenze. Sarà proposto un inquadramento della natura degli eventi traumatici partendo dalle traiettorie di vulnerabilità individuali e contestuali, con un’attenzione alle ripercussioni neurofisiologiche e psicopatologiche. I partecipanti acquisiranno una conoscenza approfondita sulle modalità di valutazione delle sindromi trauma-correlate – secondo l’approccio del DSM 5 e dell’ICD-11 di prossima pubblicazione - e le loro comorbidità ed effetti indiretti (i.e. disturbi del linguaggio, apprendimento, iperattività, disregolazione degli impulsi) secondo una prospettiva lifespan. Il Corso propone una formazione teorico-pratica sull’impatto del trauma psicologico sull’individuo e sulla società, integrando i principi evidence-based della diagnosi e dell’intervento clinico alle discipline sociali che intervengono nella comprensione della complessità traumatica e delle sue conseguenze. Sarà proposto un inquadramento della natura degli eventi traumatici partendo dalle traiettorie di vulnerabilità individuali e contestuali, con un’attenzione alle ripercussioni neurofisiologiche e psicopatologiche. I partecipanti acquisiranno una conoscenza approfondita sulle modalità di valutazione delle sindromi trauma-correlate – secondo l’approccio del DSM 5 e dell’ICD-11 di prossima pubblicazione - e le loro comorbidità ed effetti indiretti (i.e. disturbi del linguaggio, apprendimento, iperattività, disregolazione degli impulsi) secondo una prospettiva lifespan. Per quanto riguarda l’intervento clinico, il corso ha l’obiettivo di presentare strumenti terapeutici sostenibili e brevi, basati sull’evidenza scientifica. In particolare, saranno presentati due modelli terapeutici: la Narrative Exposure Therapy (NET) e la Brief Eclectic Psychotherapy for PTSD (BEPP). Entrambi i modelli sono costruiti per moduli e manualizzati, tali da rendere l’implementazione nei servizi più agevole e adatta al monitoraggio di follow-up rispetto alla eventuale remissione dei sintomi post-traumatici. Nel passaggio dall’assessment alla terapia, i partecipanti familiarizzeranno anche con le tecniche di psicoeducazione, elemento fondamentale per la normalizzazione, collaborazione al trattamento ed empowerment del paziente. Il Corso offre, inoltre, l’integrazione della clinica alla prospettiva transculturale, utile per rispondere ai bisogni e interpretazione del trauma nei contesti migratori, di guerra e dei richiedenti asilo. Nella seconda parte del corso, la riflessione si sposterà sulle ricadute del trauma sulla società e sulla necessità, dunque, di costruire modelli di servizi trauma-informed e di implementare strategie politico-sanitarie multidisciplinari e integrate. In questa cornice, i partecipanti acquisiranno competenze anche sul ruolo del trauma nelle organizzazioni e relative ricadute sui professionisti della salute mentale

Mutations in GMPPB Presenting with Pseudometabolic Myopathy

Mutations in the guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) gene encoding a key enzyme of the glycosylation pathway have been described in families with congenital (CMD) and limb girdle (LGMD) muscular dystrophy with reduced alpha-dystroglycan (\u3b1-DG) at muscle biopsy.Patients typically display a combined phenotype of muscular dystrophy, brain malformations, and generalized epilepsy. However, a wide spectrum of clinical severity has been described ranging from classical CMD presentation to children with mild, yet progressive LGMD with or without intellectual disability. Cardiac involvement, including a long QT interval and left ventricular dilatation, has also been described in four cases.Two missense mutations in GMPPB gene, one novel and one already reported, have been identified in a 21-year-old man presenting with elevated CK (38,650 UI/L; normal values <150 UI/L) without overt muscle weakness. Major complaints included limb myalgia, exercise intolerance, and several episodes of myoglobinuria consistent with a form of metabolic myopathy. Muscle biopsy showed only minimal alterations, whereas a marked reduction of glycosylated \u3b1-DG was evident.This case further expands the phenotypic spectrum of GMPPB mutations and highlights the importance of exhaustive molecular characterization of patients with reduced glycosylation of \u3b1-DG at muscle biopsy

Consumption of healthy foods at different content of antioxidant vitamins and phytochemicals and metabolic risk factors for cardiovascular disease in men and women of the Moli-sani study.

BACKGROUND/OBJECTIVES:To categorize healthy food groups into categories of low-antioxidant (LAC) or high-antioxidant vitamins and phytochemicals content (HAC) and comparatively associate them with metabolic risk factors for cardiovascular disease (CVD). SUBJECTS/METHODS: A total of 6879 women (55±12 years) and 6892 men (56 ± 12 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The antioxidant content of each food group was evaluated using Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione and United States Department of Agriculture (USDA) food composition tables. Healthy foods, according to a Mediterranean dietary pattern, were categorized into HAC or LAC; total food antioxidant content (FAC) score was constructed for a comparative evaluation of the consumption of these two groups. RESULTS: In men, an increase in FAC score, which represents an increased consumption of HAC with respect to LAC foods, was associated with a decrease in systolic blood pressure, diastolic blood pressure and C-reactive protein (CRP) (β=-0.5, P=0.02, β=-0.3, P=0.02 and β=-0.03, P=0.03, respectively). Logistic regression analyses showed that in men 15% (30 units) increase in FAC score was associated with 6% decrease in the likelihood of having hypertension (odds ratio (OR)=0.94, 95% confidence interval (CI) 0.91-0.98) and 3% decrease in the likelihood of having a high CRP risk level (OR=0.97, 95% CI 0.94-0.99). No significant associations were observed in women. CONCLUSIONS: A possible greater protective role of healthy HAC as compared with healthy LAC foods on hypertension and inflammation was detected in men. These results stress the importance of studying healthy foods according to their content in antioxidant vitamins and phytochemicals, in primary prevention of CVD

Typical breakfast food consumption and risk factors for cardiovascular disease in a large sample of Italian adults.

BACKGROUND AND AIMS: The overall consumption of foods most frequently consumed in a typical Italian breakfast might be associated with a better cardiovascular risk profile in Italian adults. METHOD SAND RESULTS: 18,177 subjects (53,2% women), aged ≥ 35 yrs, randomly selected from the Moli-sani Project population were studied. The European Prospective Investigation into Cancer and Nutrition (EPIC) FFQ was used for dietary assessment. To derive breakfast pattern, an "a priori" approach was used: firstly, foods typical of the Italian breakfast were selected: milk, coffee, tea, yogurt, crispbread/rusks, breakfast cereals, brioche, biscuits, honey, sugar and jam. The breakfast score was obtained adding the amounts of all selected foods, expressed in grams/day, previously standardized to mean zero and standard deviation 1. Subjects showing a higher breakfast score appeared to be younger, more frequently women or smokers, with higher social status but less likely practicing physical activity. After multivariable analyses, subjects with a higher breakfast food consumption had a lower risk to have high body mass index, abdominal obesity, systolic and diastolic blood pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all) and C Reactive Protein (P =0.022). The associations were unrelated to age, sex, smoking, obesity, physical activity and social status. Subjects with a higher food breakfast score also showed a better physical healthy status score, a lower risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P < 0.0001 for both women and men). CONCLUSION: Consumption of typical Italian breakfast foods positively affects CVD risk profile in an adult Italian population

Typical breakfast food consumption and risk factors for cardiovascular disease in a large sample of Italian adults.

16nonenonedi Giuseppe R; Di Castelnuovo A; Melegari C; De Lucia F; Santimone I; Sciarretta A; Barisciano P; Persichillo M; De Curtis A; Zito F; Krogh V; Donati MB; de Gaetano G; Iacoviello ; D.Assanelli; Moli-sani Project Investigators.di Giuseppe, R; Di Castelnuovo, A; Melegari, C; De Lucia, F; Santimone, I; Sciarretta, A; Barisciano, P; Persichillo, M; De Curtis, A; Zito, F; Krogh, V; Donati, Mb; de Gaetano, G; Iacoviello, ; Assanelli, Deodato; Moli sani Project, Investigator