The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumour development. High MAGOH/MAGOHB expression was observed in 14 tumour types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM

A protocol for a randomised controlled trial of prefabricated versus customised foot orthoses for people with rheumatoid arthritis: the FOCOS RA trial [Foot Orthoses – Customised v Off-the-Shelf in Rheumatoid Arthritis]

Background Foot pain is common in rheumatoid arthritis and appears to persist despite modern day medical management. Several clinical practice guidelines currently recommend the use of foot orthoses for the treatment of foot pain in people with rheumatoid arthritis. However, an evidence gap currently exists concerning the comparative clinical- and cost-effectiveness of prefabricated and customised foot orthoses in people with early rheumatoid arthritis. Early intervention with orthotics may offer the best opportunity for positive therapeutic outcomes. The primary aim of this study is to evaluate the comparative clinical- and cost-effectiveness of prefabricated versus customised orthoses for reducing foot pain over 12 months. Methods/design This is a multi-centre two-arm parallel randomised controlled trial comparing prefabricated versus customised orthoses in participants with early rheumatoid arthritis (< 2 years disease duration). A total of 160 (a minimum of 80 randomised to each arm) eligible participants will be recruited from United Kingdom National Health Service Rheumatology Outpatient Clinics. The primary outcome will be foot pain measured via the Foot Function Index pain subscale at 12 months. Secondary outcomes will include foot related impairments and disability via the Foot Impact Scale for rheumatoid arthritis, global functional status via the Stanford Health Assessment Questionnaire, foot disease activity via the Rheumatoid Arthritis Foot Disease Activity Index, and health-related quality of life at baseline, 6 and 12 months. Process outcomes will include recruitment/retention rates, data completion rates, intervention adherence rates, and participant intervention and trial participation satisfaction. Cost-utility and cost-effectiveness analyses will be undertaken. Discussion Outcome measures collected at baseline, 6 and 12 months will be used to evaluate the comparative clinical- and cost- effectiveness of customised versus prefabricated orthoses for this treatment of early rheumatoid arthritis foot conditions. This trial will help to guide orthotic prescription recommendations for the management of foot pain for people with early rheumatoid arthritis in future. Trial registration ISRCTN13654421. Registered 09 February 2016

Numerical study of different ceiling-mounted air distribution systems for a virtual classroom environment

This paper presents a comparative numerical study of different ceiling-mounted-localized air distribution systems placed above students in a virtual classroom in summer conditions. The influence of four different ceiling-mounted-localized air distribution systems, using vertical descendent jets, on the thermal comfort, local thermal discomfort, and air quality levels was numerically evaluated. The air distribution index, developed previously, was used for non-uniform environment. This index considers the thermal comfort level, air quality level, effectiveness for heat removal, and effectiveness for contaminant removal. Numerical simulations were conducted for a virtual classroom equipped with one of four different ceiling-mounted-localized air distribution systems and with 6 desks, 6 or 12 students, and 2 upper airflow outlets. Inlet air supply temperature of 20 and 24? and an outdoor air temperature of 28? were used. The simulation results show that the air supply system having a vertical air jet placed at 1.8m above the floor level (Case III), and with an inlet area of 0.01m(2) and a supply air velocity of 3m/s would represent the best option in comparison with other air supply methods. In general, the air distribution index value decreases with an increase in inlet air temperature and the number of occupants. The air distribution index values are highest for Case III representing a classroom with 6 or 12 occupants with an inlet air temperature of 20 or 24?.info:eu-repo/semantics/publishedVersio

Ocorrência de dessonorização no desvio fonológico: relação com fonemas mais acometidos, gravidade do desvio e idade Occurrence of devoicing in phonological disorders: relationship with most affected phonemes, severity of the disorder and age

OBJETIVO: Verificar a ocorrência do processo fonológico de dessonorização de fonemas plosivos e fricativos em crianças com desvio fonológico, envolvendo as seguintes variáveis: fonemas mais acometidos, gravidade de desvio fonológico e idade. MÉTODOS: A amostra constituiu-se de 50 crianças, com média de idade de 6 anos e 5 meses. Os dados de fala foram coletados por meio da Avaliação Fonológica da Criança e submetidos à análise contrastiva, sendo a gravidade do desvio fonológico determinada conforme o Percentual de Consoantes Corretas-Revisado. Então, analisou-se quais fonemas plosivos e fricativos sonoros eram acometidos pelo processo de dessonorização, com percentual de ocorrência maior que 40%. Posteriormente, realizou-se análise estatística. RESULTADOS: Verificou-se que ao comparar os seis fonemas, simultaneamente, não houve diferença quanto ao emprego da dessonorização. Obteve-se diferença somente para /g/ x /v/, e /b/ x /v/. Quanto à faixa etária, não houve diferença. Quanto à gravidade do desvio, foi possível constatar que houve diferença apenas para a variável dessonorização de /d/ e /&#658;/. CONCLUSÃO: O processo fonológico de dessonorização possui alta ocorrência em crianças com desvio fonológico, sendo mais prevalente para consoantes plosivas. A idade não influencia a ocorrência deste processo e a gravidade do desvio é um fator relevante para seu emprego, sendo mais prevalente nos graus mais graves.<br>PURPOSE: To verify the occurrence of the phonological process of plosives and fricatives devoicing in children with phonological disorders. The following variables were involved: most affected phonemes, severity of phonological disorder, and age. METHODS: Participants were 50 children, with an average age of 6 years and 5 months. Speech data were collected by means of the Avaliação Fonológica da Criança (Phonological Assessment of Children) and submitted to contrastive analysis. The severity of the phonological disorder was determined by the Percentage of Consonants Correct - Revised. Then, it was analyzed which plosive and fricative phonemes were affected by the devoicing strategy, with occurrence greater than 40%. Afterwards, statistical analysis was performed. RESULTS: The simultaneous comparison the six phonemes showed no difference regarding the use of devoicing. Difference was found only for /g/ x /v/, and for /b/ x /v/. Regarding age, no significant difference was found. As for the severity of phonological disorder, difference was found only for the variable devoicing of /d/ and /&#658;/. CONCLUSION: The phonological process of devoicing have high occurrence in children with phonological disorder, with higher prevalence for stops consonants. Age does not influence the occurrence of this process, and the severity of the phonological disorder is a relevant factor to its use, with higher prevalence in the most severe degrees