Social matchUP : a cooperative virtual reality game for people with neurodevelopmental disorders

LAUREA MAGISTRALEI disturbi del neuro-sviluppo (NDD - Neurodevelopmental Disorders) sono un gruppo di patologie che si manifestano nelle prime fasi dello sviluppo di un bambino e che limitano le capacità personali, cognitive e comunicative di un individuo. Le applicazioni che includono ambienti di Realtà Virtuale Condivisi (SVRE – Shared Virtual Reality Environment) consentono alle persone che soffrono di NDD di interagire nello stesso spazio digitale, eliminando il potenziale disagio o timore causato dall'avere una persona reale di fronte a loro. Il framework di design denominato Participatory Design (PD o Codesign) - un metodo di progettazione in cui gli utenti finali sono trattati come partner di progettazione del prodotto durante il processo di design – è stato utilizzato negli ultimi anni proprio nel design di applicazioni digitali per persone con NDD a causa dell’evidente miglioramento nella realizzazione del prodotto finale, ma anche per i benefici sperimentati dai pazienti come individui o come gruppo. Il sistema sviluppato in questa tesi, denominato Social MatchUP, è un gioco in WIVR (Wearable Immersive Virtual Reality) cooperativo per smartphones, ideato per persone con NDD, che migliora la capacità di comunicazione dei giocatori. Social MatchUP trae ispirazione dal gioco del Memory, richiedendo ai giocatori di comunicare per abbinare una serie di immagini. Il gioco permette ai giocatori di interagire in tempo reale all’interno di un ambiente di realtà virtuale condiviso. A partire da un prototipo progettato in collaborazione con degli specialisti di NDD, è stata progettata una seconda versione dell’applicazione applicando il framework di design PD , coinvolgendo otto ragazzi del centro terapeutico che ha collaborato al progetto. Il processo di PD è stato condotto lungo quattro sessioni, coordinate da due a quattro ricercatori con l'aiuto di due educatori e uno psicologo. Tra una sessione e l’altra è stato sviluppato di volta in volta un prototipo migliorato del gioco, includendo modifiche e miglioramenti a seguito dei feedback e delle osservazioni dei pazienti. Sono stati programmati due incontri conclusivi dopo le quattro sessioni iniziali per valutare la qualità del processo, dimostrarne i benefici, e mostrare la versione finale dell'applicazione ai partecipanti. L'efficacia della versione di Social MatchUP progettata con i partecipanti al PD, rispetto al prototipo iniziale, verrà valutata in uno studio a lungo termine. Una serie di funzionalità aggiuntive è in sviluppo per consentire agli utenti di utilizzare l’applicazione a distanza, in contesti differenti rispetto al centro terapeutico.Neurodevelopmental Disorders (NDD) are a group of pathologies that can appear in child’s early developmental process, and that limit personal, cognitive and communicative capabilities. Digital applications including shared virtual reality environments (SVREs) allow NDD people to interact in the same virtual space, but without the possible discomfort or fear caused by having a real person in front of them. The Participatory Design (PD or Codesign) framework - a design method in which end users are treated as equal stakeholders or design partners of the product generated during the design process - has been used in the last years to design digital applications for people with NDD because of the evident improvement on the final product but also the direct benefit for the patients as individuals and as a group. The system developed in this thesis, known as Social MatchUP, is a cooperative WIVR (Wearable Immersive Virtual Reality) game for smartphones, designed for people with NDD, which improves the communication skills between the players. Social MatchUP is inspired by the game of Memory, requiring players to communicate to match a series of images. The game allows players to interact in real time within a shared virtual reality environment. Starting from a prototype designed in collaboration with NDD specialists, a second version of the application was designed by applying the PD framework, involving eight young people from the therapeutic center who collaborated on the project. The PD process was carried out in four sessions with a group of eight participants, coordinated by two to four researchers with the help of two educators and a psychologist. In-between each session an improved prototype of the game, which included some modifications that reflected the participants’ observations from the previous meeting, was developed. Two conclusive meetings have been scheduled after the initial four sessions to evaluate the quality of the process, demonstrate its benefits, and show the final version of the application to the participants. The effectiveness of the codesigned version of Social MatchUP, compared to the initial prototype, will be evaluated in a long-term study. A series of additional features is in development to let users play the game remotely, in contexts different from the therapeutic center

"Delirium Day": a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy

Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling

BACKGROUND: KSRP is a AU-rich element (ARE) binding protein that causes decay of select sets of transcripts in different cell types. We have recently described that phosphatidylinositol 3-kinase/AKT (PI3K-AKT) activation induces stabilization and accumulation of the labile β-catenin mRNA through an impairment of KSRP function. RESULTS: Aim of this study was to identify additional KSRP targets whose stability and steady-state levels are enhanced by PI3K-AKT activation. First, through microarray analyses of the AU-rich transcriptome in pituitary αT3-1 cells, we identified 34 ARE-containing transcripts upregulated in cells expressing a constitutively active form of AKT1. In parallel, by an affinity chromatography-based technique followed by microarray analyses, 12 mRNAs target of KSRP, additional to β-catenin, were identified. Among them, seven mRNAs were upregulated in cells expressing activated AKT1. Both steady-state levels and stability of these new KSRP targets were consistently increased by either KSRP knock-down or PI3K-AKT activation. CONCLUSION: Our study identified a set of transcripts that are targets of KSRP and whose expression is increased by PI3K-AKT activation. These mRNAs encode RNA binding proteins, signaling molecules and a replication-independent histone. The increased expression of these gene products upon PI3K-AKT activation could play a role in the cellular events initiated by this signaling pathway

Proteasome system dysregulation and treatment resistance mechanisms in major depressive disorder

Several studies have demonstrated that allelic variants related to inflammation and the immune system may increase the risk for major depressive disorder (MDD) and reduce patient responsiveness to antidepressant treatment. Proteasomes are fundamental complexes that contribute to the regulation of T-cell function. Only one study has shown a putative role of proteasomal PSMA7, PSMD9 and PSMD13 genes in the susceptibility to an antidepressant response, and sparse data are available regarding the potential alterations in proteasome expression in psychiatric disorders such as MDD. The aim of this study was to clarify the role of these genes in the mechanisms underlying the response/resistance to MDD treatment. We performed a case-control association study on 621 MDD patients, of whom 390 were classified as treatment-resistant depression (TRD), and we collected peripheral blood cells and fibroblasts for mRNA expression analyses. The analyses showed that subjects carrying the homozygous GG genotype of PSMD13 rs3817629 had a twofold greater risk of developing TRD and exhibited a lower PSMD13 mRNA level in fibroblasts than subjects carrying the A allele. In addition, we found a positive association between PSMD9 rs1043307 and the presence of anxiety disorders in comorbidity with MDD, although this result was not significant following correction for multiple comparisons. In conclusion, by confirming the involvement of PSMD13 in the MDD treatment response, our data corroborate the hypothesis that the dysregulation of the complex responsible for the degradation of intracellular proteins and potentially controlling autoimmunity- and immune tolerance–related processes may be involved in several phenotypes, including the TRD

Radiological assessment of dementia: the Italian inter-society consensus for a practical and clinically oriented guide to image acquisition, evaluation, and reporting

Background: Radiological evaluation of dementia is expected to increase more and more in routine practice due to both the primary role of neuroimaging in the diagnostic pathway and the increasing incidence of the disease. Despite this, radiologists often do not follow a disease-oriented approach to image interpretation, for several reasons, leading to reports of limited value to clinicians. In our work, through an intersocietal consensus on the main mandatory knowledge about dementia, we proposed a disease-oriented protocol to optimize and standardize the acquisition/evaluation/interpretation and reporting of radiological images. Our main purpose is to provide a practical guideline for the radiologist to help increase the effectiveness of interdisciplinary dialogue and diagnostic accuracy in daily practice. Results: We defined key clinical and imaging features of the dementias (A), recommended MRI protocol (B), proposed a disease-oriented imaging evaluation and interpretation (C) and report (D) with a glimpse to future avenues (E). The proposed radiological practice is to systematically evaluate and score atrophy, white matter changes, microbleeds, small vessel disease, consider the use of quantitative measures using commercial software tools critically, and adopt a structured disease-oriented report. In the expanding field of cognitive disorders, the only effective assessment approach is the standardized disease-oriented one, which includes a multidisciplinary integration of the clinical picture, MRI, CSF and blood biomarkers and nuclear medicine

The RNA-Binding Protein KSRP Promotes Decay of β-Catenin mRNA and Is Inactivated by PI3K-AKT Signaling

β-catenin plays an essential role in several biological events including cell fate determination, cell proliferation, and transformation. Here we report that β-catenin is encoded by a labile transcript whose half-life is prolonged by Wnt and phosphatidylinositol 3-kinase–AKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRP's ability to promote rapid mRNA decay. Our results uncover an unanticipated level of control of β-catenin expression pointing to KSRP as a required factor to ensure rapid degradation of β-catenin in unstimulated cells. We propose KSRP phosphorylation as a link between phosphatidylinositol 3-kinase–AKT signaling and β-catenin accumulation

A new generation of Parsec-Colibri stellar isochrones including the TP-AGB phase

We introduce a new generation of PARSEC-COLIBRI stellar isochrones that includes a detailed treatment of the thermally pulsing asymptotic giant branch (TP-AGB) phase, covering a wide range of initial metallicities (0.0001. < Z(i) < 0.06). Compared to previous releases, the main novelties and improvements are use of new TP-AGB tracks and related atmosphere models and spectra for M and C-type stars; inclusion of the surface H+He +CNO abundances in the isochrone tables, accounting for the effects of diffusion, dredge-up episodes and hot-bottom burning; inclusion of complete thermal pulse cycles, with a complete description of the in-cycle changes in the stellar parameters; new pulsation models to describe the long-period variability in the fundamental and firstovertone modes; and new dust models that follow the growth of the grains during the AGB evolution, in combination with radiative transfer calculations for the reprocessing of the photospheric emission. Overall, these improvements are expected to lead to a more consistent and detailed description of properties of TP-AGB stars expected in resolved stellar populations, especially in regard to their mean photometric properties from optical to mid-infrared wavelengths. We illustrate the expected numbers of TP-AGB stars of different types in stellar populations covering a wide range of ages and initial metallicities, providing further details on the "C-star island" that appears at intermediate values of age and metallicity, and about the AGB-boosting effect that occurs at ages close to 1.6-Gyr for populations of all metallicities. The isochrones are available through a new dedicated web server

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"

Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys