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lo studio ha confrontato le funzioni esecutive di pazienti con disturbi psicotici coinvolti in programmi riabilitativi in Strutture Residenziali di Palermo. Metodi: sono stati reclutati 16 utenti di Comunità Alloggio (CA) e 14 utenti di Comunità Terapeutiche Assistite (CTA), tra 18 e 65 anni, valutati tramite somministrazione di Trail Making Test(TMT), Wisconsin Card Sorting Test (WCST), Frontal Assessment Battery (FAB), Stroop Test, 4 subtest della WAIS-R e Brief Psychiatric Rating Scale (BPRS). Risultati: i due campioni presentano caratteristiche sociodemografiche omogenee. Gli utenti delle CTA fanno rilevare maggiore uso di neurolettici (73,3% vs. 18.8% p 0,004) e un trend non significativo di minore espressività sintomatologica (BPRS: 2,39 vs. 2,58); essi, inoltre, sono maggiormente coinvolti in interventi riabilitativi avanzati con uso di tecniche cognitive (40,0% vs. 6,3% p 0,037) ed espressive (83,3% vs. 16,7% p 0,000) e presentavano migliori prestazioni cognitive al FAB(p 0,048), agli Errori Perseverativi del WCST(p 0,000) e allo Stroop Test(p 0,027). Conclusioni: l’analisi dei risultati suggerisce che gli utenti delle CA presentano deficit in differenti domini cognitivi, maggiore difficoltà a distribuire l’attenzione tra più compiti simultanei e scarsa flessibilità cognitiva, riconducibile a storia clinica e durata di trattamento antipsicotico più datati. Pertanto, la maggiore partecipazione degli utenti delle CTA in training riabilitativi intensivi,cognitivi ed espressivi, potrebbe spiegare il più efficace recupero delle funzioni esecutive studiate. Bibliografia Addington J, Girard TA, Christensen BK, et al. Social cognition mediates illness-related and cognitive influences on social function in patients with schizophrenia-spectrum disorders. J Psychiatry Neurosci 2010;35:49-54. McGurk SR, Mueser KT. Cognitive functioning,symptoms, and work in supported employment: an review and heuristic model. Schizophr Res 2004;70:147-73. Krabbendam L, Aleman A. Cognitive rehabilitation in schizophrenia: a quantitative analysis of controlled

In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes.Aim of the study is to examine the reliability and validity of Besta Scale, an instrument used to measure in hemiplegic children from 18 months to 12 years of age both grasp on request (capacity) and spontaneous use of upper limb (performance) in bimanual play activities and in ADL.Psychometric analysis of reliability and of validity of the Besta scale was performed.Outpatient study sampleReliability study: A sample of 39 patients was enrolled. The administration of Besta scale was video-recorded in a standardized manner. All videos were scored by 20 independent raters on subsequent viewing. 3 raters randomly selected from the 20-raters group rescored the same video two years later for intra-rater reliability. Intra and inter-rater reliability were calculated using Intraclass Correlation Coefficient (ICC) and Kendall's coefficient (K), respectively. Internal consistency reliability was assessed using Alpha's Chronbach coefficient. Validity study: a sample of 105 children was assessed 5 times (at t0 and 2, 3, 6 and 12 months later) by 20 independent raters. Each patient underwent at the same time to QUEST and Besta scale administration and assessment. Criterion validity was calculated using rho-Pearson coefficient.Reliability study: The inter-rater reliability calculated with Kendall's coefficient resulted moderate K=0.47. The intra-rater (or test-retest) reliability for 3 raters was excellent (ICC=0.927). The Cronbach's alpha for internal consistency was 0.972. Validity study: Besta scale showed a good criterion validity compared to QUEST increasing by age and severity of impairment. Rho Pearson's correlation coefficient r was 0.81 (P0.0001). Limitations. Besta scales in infants finds hard to distinguish between mild to moderately impaired hand function.Besta scale scoring system is a valid and reliable tool, utilizable in a clinical setting to monitor evolution of unimanual and bimanual manipulation and to distinguish hand's capacity from performance.

Summary Constitutive NF-κB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-κB-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45β/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-κB pathway is possible and, at least for myeloma patients, promises a profound benefit., Highlights • GADD45β is a critical mediator of the NF-κB antiapoptotic function in MM • GADD45β binds to MKK7 and promotes MM cell survival by blocking MKK7/JNK signaling • GADD45β/MKK7 inhibitors display potent activity against MM, in vitro and in vivo • GADD45β/MKK7 inhibitors are far more cancer selective than IKK/NF-κB inhibitors, NF-κB is implicated in MM and other malignancies, but it is challenging to block NF-κB only in diseased cells. Tornatore et al. identify an interaction between MKK7 and NF-κB-regulated GADD45β as a therapeutic target and develop a peptide that disrupts the complex and selectively kills MM cells.

Constitutive NF-B-K signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-B-K-targeting strategies lack cancer cell specificity. Here, we identify the interaction between the NF-B-K-regulated antiapoptotic factor GADD45 beta and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45 beta/ MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates rnyeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-KB pathway is possible and, at least for myeloma patients, promises a profound benefit.