Língua Brasileira de Sinais na formação de servidores públicos municipais de uma cidade do interior paulista

This article aimed to analyze the effects of a training course in Libras on a group of civil servants from different municipal sectors in a city in the interior of São Paulo, with a view to providing them with basic know ledge to offer a more qualified service to the deaf and mitigate the communicative barriers between them. It had as participants 37 public servants, in a work load of 30 hours counting on the presence of hearing professionals specialized in the are a and two deaf fluent in Libras. An initial questionnaire was applied to meet the demands of the employees and a final one on the self-assessment of their learning’s and expectations. The results showed that the majority considered the course of great importance and felt more prepared to offer the deaf a better quality of care, but there were also those who answered that they still felt a certain in security, requiring more time of practice and study to establish greater communication for mutual understanding. Regarding the training received, it was considered defective and in accordance with the importance of learning that language, at least basically, not only for in-service communication, but for social inclusion, high lighting the relationship established between theory and practice, at all times. , which provided a more critical and reflective training on the acquired knowledge. In the face of social inclusion, it is necessary to carry out training courses in Libras, since the linguistic condition of the deaf is carried out in the form of visual-spatial transmission instead of oral-auditory as in other people.Resumo: O presente artigo teve por objetivo analisar os efeitos de um curso de formação em Libras a um grupo de servidores públicos de diferentes setores municipais de uma cidade do interior paulista, com vistas a dotá-los de conhecimentosbásicos para oferecer um atendimento mais qualificado aos surdos e atenuar as barreiras comunicativas entre ambos. Teve como participantes 37 servidores públicos, numa carga horária de 30 horascontando com a presença de profissionais ouvintes especializados na área e dois surdos fluentes em Libras. Aplicou-se um questionário inicial para atender às demandas dos servidores e um final sobre a autoavaliação de seus aprendizados e expectativas. Os resultados mostraram que a maioriaconsiderou o curso de grande importância e se sentiu mais preparada para oferecer aos surdos um atendimento de melhor qualidade, mas, também, houve aqueles que responderam ainda sentir certa insegurança, requerendo um maior tempo de prática e estudo para estabelecer uma comunicação de maior alcance para compreensão mútua. Em relação à formação recebida, esta foi considerada eficaz e em conformidade à importância de aprender essa língua, ao menos basicamente, não só para a comunicação em serviço, mas para a inclusão social destacando a relação estabelecida entre teoria e prática, em todos os instantes, o que proporcionou uma formação mais crítica e reflexiva sobre os conhecimentos adquiridos. Frente à inclusão social, faz-se necessário a realização de cursos de formação em Libras, uma vez que a condição linguística do surdo se realiza na modalidade de transmissão visual-espacial em vez de oral-auditiva como nas demais pessoas

The economic impact of moderate stage Alzheimer's disease in Italy: Evidence from the UP-TECH randomized trial

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. Results: The societal burden of AD, composed of public, patient, and informal care costs, was about �20,000/yr. Out of this, the cost borne by the public sector was �4,534/yr. The main driver of public cost was the national cash-for-care allowance (�2,324/yr), followed by drug prescriptions (�1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at �13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (Trial Registration number: NCT01700556). Copyright � International Psychogeriatric Association 2015

Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian Families Assisting Older Alzheimer's Disease Patients: Evidence from the Up-Tech Study

Background: The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs. Method: We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables - education, social class, and the availability of a care allowance - and three outcomes - employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers). Results: The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW. Discussion: Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems. � 2015 The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved

Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?

Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases

Identification and characterization of signaling and axonal migration defects in the MPS II zebrafish model

La Mucopolisaccaridosi di tipo II (MPS II), conosciuta anche come Sindrome di Hunter, è una malattia da accumulo lisosomiale con ereditarietà legata al cromosoma X. Questa patologia è causata da mutazioni a livello del gene codificante per l’iduronato-2-sulfatasi, un enzima lisosomiale coinvolto nel primo step di degradazione di eparan e dermatan solfato. Lo spettro di sintomi che ne deriva è estremamente ampio con manifestazioni sia somatiche che legate al sistema nervoso centrale. Mentre l’approccio di terapia enzimatica sostitutiva risulta efficace nell’alleviare i sintomi di natura somatica, il trattamento del sistema nervoso centrale rimane tutt’ora di grande difficoltà. La patogenesi delle mucopolisaccaridosi è stata storicamente attribuita al progressivo accumulo di glicosamminoglicani e al conseguente instaurarsi di una condizione infiammatoria; tuttavia, è ormai chiaro che più complessi meccanismi, tra cui deregolazione della via autofagica e alterazione di vie di segnale durante lo sviluppo, contribuiscano all’insorgenza della patologia. In questo contesto, mi sono servita del modello zebrafish per l’MPS II per studiare i meccanismi patologici precoci relativi allo sviluppo cerebrale. In particolare, la mia ricerca si è focalizzata sull’analisi di Netrin/Dcc (Deleted in colorectal cancer), una delle più importanti vie di segnale coinvolte nel processo noto come axon guidance. Sebbene sia Netrin che Dcc mostrassero un alterato profilo di espressione, solo Dcc si è rilevato consistentemente deregolato a livello proteico, sia nell’intera testa che nel cervello isolato di larve ids mutanti. L’ottimizzazione di un protocollo per colture primarie di zebrafish ha inoltre consentito di attribuire questa alterazione specificamente al comparto neuronale. Tale modello in vitro ha evidenziato difetti nella via di segnale regolata da Dcc, nell’acidificazione lisosomiale (Lysotracker) e nei livelli proteici di Rab7 nei neuroni derivati da ids mutanti. In aggiunta, con l’intento di valutare la morfologia assonale, ho applicato le colture di neuroni primari ad un supporto di microfluidica: nello specifico, ho osservato una riduzione nella lunghezza assonale dei neuroni mutanti rispetto ai controlli. Poiché la regolazione del recettore Dcc è strettamente dipendente dal traffico vescicolare, ho successivamente analizzato la sua localizzazione intracellulare nella testa delle larve MPS II. A tal proposito, sono stata impegnata nella messa a punto di un nuovo protocollo di precipitazione frazionata applicabile ad estratti proteici di zebrafish. Questo mi ha permesso di osservare una alterata localizzazione di Dcc a livello intracellulare nelle larve ids mutanti. In aggiunta, l’alterazione dei livelli di Dcc si è dimostrata un fenomeno non solo relativo ai primi stadi di sviluppo, ma anche a fasi più tardive della vita dello zebrafish. Questo aspetto è accompagnato da anomalie nei livelli proteici della proteina acida fibrillare gliale (Gfap), rintracciabili già a partire da 1 mese di età nei cervelli di zebrafish MPS II, suggerendo un'attivazione precoce delle cellule gliali. Per quanto riguarda l'analisi dei livelli di eparan solfato, non sono state rilevate significative differenze tra controlli sani e larve ids mutanti nelle prime fasi di sviluppo. Tuttavia, la valutazione tramite l'immunofluorescenza ha evidenziato, nelle larve MPS II, un'architettura anomala del plesso coroideo struttura rivelatasi arricchita di eparan solfato. Infine, analisi retinotopiche del tetto ottico e test basati su stimolazioni visive hanno suggerito alterazioni lievi ma non significative nei pesci mutanti a stadi larvali.Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare X-linked lysosomal storage disorder caused by the lack or deficiency of iduronate 2-sulfatase (IDS), a lysosomal enzyme involved in the first step of heparan and dermatan sulfate degradative pathway. This results in a plethora of somatic and central nervous system (CNS)-related symptoms with high clinical variability and different age of onset. While enzyme replacement therapy can alleviate somatic manifestations, the CNS remains untreatable. Historically, the pathogenesis of MPSs has been attributed to the progressive intracellular accumulation of undegraded glycosaminoglycans (GAGs) and inflammation; however, it is now clear that more complex pathogenic mechanisms may contribute to the pathological manifestations, including impaired autophagy and altered developmental cell signalling. In this context, I exploited the MPS II zebrafish model to deepen the understanding of early pathological mechanisms during brain development. In particular, I focused my research on the investigation of Netrin and Deleted in colorectal cancer (Dcc), one of the most important pair of ligand and receptors, involved in axon guidance-mediated chemoattraction. While both Netrin and Dcc showed altered expression pattern in a in situ-based screening, only Dcc was consistently found altered at protein levels. To this purpose, I performed western blot analysis on dissected heads and isolated brains at early developmental stages. Moreover, to scale up the resolution of my investigation, I set up an optimized protocol for zebrafish primary neuronal-enriched cell culture. This tool allowed me to narrow down Dcc dysregulation specifically to the neuronal compartment. The in vitro neuronal model allowed to detect alterations in Dcc downstream cascade activation, lysosomal acidification and Ras-associated binding 7 (Rab7) protein levels in mutant cells. In addition, I applied zebrafish primary neurons to a microfluidic system to dissect axonal morphology. Indeed, mutant-derived neurons showed shorter axons when compared to control cells. Since Dcc regulation relies on vesicular trafficking, I analysed Dcc intracellular localization in the head of MPS II larvae. Toward this aim, I set up a novel protocol of fractional precipitation applied to zebrafish protein extracts that allowed me to find an altered Dcc localization in ids mutant conditions. Moreover, Dcc analysis at later time points highlighted a consistent dysregulation of this receptor beyond the developmental phase. In addition, a Glial fibrillary acidic protein (Gfap) protein levels analysis revealed that pathological abnormalities are traceable since 1 month of age in MPS II zebrafish brains, suggesting early glial cell activation. Western blot analysis of heparan sulfates (HS) showed no significant differences between wild type and ids mutant larvae at early developmental stages. On the other hand, whole mount brain HS immunofluorescence pointed out abnormal choroid plexus architecture in MPS II larvae. Finally, retinotopic mapping and multiple behavioural tests based on visual stimulation suggested subtle but not significant alterations in mutant fish at larval stages

Lysosomal Function and Axon Guidance: Is There a Meaningful Liaison?

Axonal trajectories and neural circuit activities strongly rely on a complex system of molecular cues that finely orchestrate the patterning of neural commissures. Several of these axon guidance molecules undergo continuous recycling during brain development, according to incompletely understood intracellular mechanisms, that in part rely on endocytic and autophagic cascades. Based on their pivotal role in both pathways, lysosomes are emerging as a key hub in the sophisticated regulation of axonal guidance cue delivery, localization, and function. In this review, we will attempt to collect some of the most relevant research on the tight connection between lysosomal function and axon guidance regulation, providing some proof of concepts that may be helpful to understanding the relation between lysosomal storage disorders and neurodegenerative diseases

Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System

Among multiple cytoprotective mechanisms, eukaryotic cells exhibit a complex transcriptional program relying on the Nrf2 transcription factor, which is generally recruited upon biological stressors including oxidative-stress-based cellular insults. The relevance of this master regulator has remarkably emerged in recent years in several research fields such as cancer, inflammatory disorders and age-related neurological diseases. Here, we document the generation and characterization of a novel Nrf2/ARE pathway biosensor fish which exhibits a dynamic spatiotemporal expression profile during the early developmental stages. The transgenic line is responsive to known Nrf2 pathway modulators but also to Edaravone, which direct activity on the Nrf2 pathway has never been documented in a live transgenic fish model. We also show that the reporter is faithfully activated during fin regeneration, and its degree of expression is slightly affected in a glucocerebrosidase (Gba1) morphant zebrafish model. Therefore, this novel transgenic fish may represent a valuable tool to be exploited for the characterization of zebrafish models of human diseases, as well as for primary high-throughput drug screening

Migrant care workers as protective factor against caregiver burden: results from a longitudinal analysis of the EUROFAMCARE study in Italy

Objective. The aim of the analysis is to assess the impact of privately employed Migrant Care Workers (MCWs) on the burden of Italian family members who are caring for a disabled older person. Methods. EUROFAMCARE is a one-year prospective survey carried out to provide evidence on the availability and use of support services by family carers of older people in Europe. In Italy, 990 family caregivers were enrolled and successful follow-ups were completed for 863 subjects. The survey assessed also the level of caregiver burden using the COPE index, which has three sub-sections: “Positive Value”(-PV), “Quality of Support”(-QS) and “Negative Impact”(-NI). We used the one-year change of the COPE-NI as dependent variable and we realised multilevel regression models to estimate the longitudinal predictors of caregivers’ burden increase. Results. At cross-sectional level, the most burdened caregivers are those caring for a demented relative (COPE-NI=13.6), with no educational title (14.5) and looking after their own spouses (15.1). Longitudinally those employing a MCW are significantly protected against burden increase (regression coefficient:-1.52;p<0.01) while those who cannot rely on the support of other family members are exposed to the risk of burden increase (0.991;p<0.05).Other formal services do not have any protective effect. Conclusion. Our study suggests that employing a MCW, rather than using formal services, is associated with a reduction of caregiving burden. Further research should assess whether the shift in care responsibilities to MCWs implies also a transfer of care burden, and understand how these workers can be better supported by existing formal services

A novel CRISPR/Cas9-based iduronate-2-sulfatase (IDS) knockout human neuronal cell line reveals earliest pathological changes

Abstract Multiple complex intracellular cascades contributing to Hunter syndrome (mucopolysaccharidosis type II) pathogenesis have been recognized and documented in the past years. However, the hierarchy of early cellular abnormalities leading to irreversible neuronal damage is far from being completely understood. To tackle this issue, we have generated two novel iduronate-2-sulfatase (IDS) loss of function human neuronal cell lines by means of genome editing. We show that both neuronal cell lines exhibit no enzymatic activity and increased GAG storage despite a completely different genotype. At a cellular level, they display reduced differentiation, significantly decreased LAMP1 and RAB7 protein levels, impaired lysosomal acidification and increased lipid storage. Moreover, one of the two clones is characterized by a marked decrease of the autophagic marker p62, while none of the two mutants exhibit marked oxidative stress and mitochondrial morphological changes. Based on our preliminary findings, we hypothesize that neuronal differentiation might be significantly affected by IDS functional impairment