Bilateral giant retinal tears in Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant condition in which the connective tissues of bones, ligaments and sclerae do not form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the defective formation or quantity of type I collagen, the principle matrix in these tissues. Molecular genetic studies have now elucidated multiple genetic subtypes of the disorder but little literature exists on the risk of retinal tears and detachments in OI. CASE PRESENTATION: We report the first case of a child with a rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as LEPRE1) gene mutation presenting with bilateral giant retinal tears and the surgical challenges encountered in performing retinal detachment repair due to scleral thinning. The P3H1 gene encodes for prolyl 3-hydroxylase 1 which is involved in the post-translational modification of not only collagen type I but also types II and V which when mutated may result in pathological posterior vitreous detachment (PVD) and giant retinal tear detachments. CONCLUSIONS: Genetic analyses are increasingly important in such cases and may guide patient monitoring and potential prophylactic treatment, known to significantly reduce the probability of giant retinal tear detachments in other high-risk collagenopathies such as Stickler Syndrome Type I

A follow-up study of the outcome of children post-craniopharyngioma surgery

The management of craniopharyngiomas in childhood remains both complex and controversial. Although histologically benign, this tumour often follows a more malignant course, not only in terms of local disease progression but also in terms of visual, neurological, neuropsychological and endocrine outcome. Seventy-five children diagnosed as having a craniopharyngioma between the ages of 1.0 and 16.4 years and treated from 1973 to early 1994 were studied to investigate the associated morbidity and mortality of this tumour and its treatment and to demonstrate which pre- and intra-operative factors were indicative of a poor outcome as defined by a quantitive assessment of morbidity. All patients had tumour surgery which entailed attempted total excision in 59 cases and subtotal resection or cyst aspiration in 16 cases. Thirty-seven children received radiotherapy, 21 following tumour recurrence. The study involved a review of clinical details and cranial imaging of all patients and a follow-up study assessment of 66 survivors - which included ophthalmological, neurological, psychological and growth and endocrine evaluation. Sixty-three patients underwent magnetic resonance imaging with a 3-dimensional volume acquisition sequence. Predictors of high morbidity included severe hydrocephalus, intra-operative adverse events and young age at presentation. Predictors of increased hypothalamic morbidity included symptoms of hypothalamic disturbance already established at diagnosis, greater height of the tumour in the mid-line, and attempts to remove adherent tumour from the region of the hypothalamus at operation. Large tumour size, young age, and severe hydrocephalus were predictors of tumour recurrence, whereas complete tumour resection (as determined by post-operative neuroimaging) and radiotherapy given electively after subtotal excision were significantly less likely to be associated with recurrent disease. Risk factors for poor cognitive outcome included complications at the time of operation and multiple surgical procedures. Treatment with radiotherapy did not significantly influence intellectual outcome. At follow-up assessment, 15% of all patients were blind, 24% had severe neurological sequelae, 56% had evidence of hypothalamic dysfunction, excluding the endocrinopathies which were almost universal, and 75% of patients had evidence of behavioural or educational difficulties. Although severe hypothalamic syndromes were uncommon (16%), they contributed significantly to morbidity and mortality and the clinical manifestations - particularly post-operative weight gain - correlated well with the extent of hypothalamic damage seen on magnetic resonance imaging. Based on these findings, it is clear that close liaison with a multidisciplinary team is essential, so that the spectra of possible sequelae can be identified early and appropriate support instituted promptly. An individualised, more flexible treatment approach is proposed whereby surgical strategies may be modified in an attempt to provide long-term tumour control with the lowest morbidity

The ‘why’ and ‘what for’ of participation in tourism activities: travel motivations of people with disabilities

The aim of this study is to identify the motivations that lead people with disabilities (PwD) to make the decision to participate in tourism and to ascertain whether there are differences in these motivations between PwD with and without tourism experiences. To achieve this goal, a guiding research model was created based on the mechanism of selfdetermination theory (SDT). A mixed methodology approach was used. First, semi-structured interviews were conducted with a sample of PwD living in Portugal (N = 28). Second, a questionnaire was administered to a sample of Portuguese with disabilities (N = 348). The results obtained highlight that PwD are motivated to participate in tourism activities, mainly because of the benefits they expect to gain from these experiences. However, a great number have never had the possibility of participating in tourism activities. Intrinsic or self-determined motivations such as pleasure, increased knowledge, well-being and personal development, stand out. Moreover, PwD who have never had the opportunity to participate in tourism activities perceive more benefits than those who have already participated. The paper ends with the theoretical and practical implications, the limitations and future research to increase knowledge in an area that has been little explored in the literature.info:eu-repo/semantics/publishedVersio

Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. REPORT: Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G>A p.(Arg1914His); c.3010C>T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G>A p.(Arg1914His); c.2032C>T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. DISCUSSION: Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from 'Classical' OI. CONCLUSIONS: Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients

Rapid prenatal diagnosis using targeted exome sequencing: a cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management.

Purpose Unexpected fetal abnormalities occur in 2-5% of pregnancies. While traditional cytogenetic and microarray approaches achieve diagnosis in around 40% of cases, lack of diagnosis in others impedes parental counseling, informed decision making, and pregnancy management. Postnatally exome sequencing yields high diagnostic rates, but relies on careful phenotyping to interpret genotype results. Here we used a multidisciplinary approach to explore the utility of rapid fetal exome sequencing for prenatal diagnosis using skeletal dysplasias as an exemplar. Methods Parents in pregnancies undergoing invasive testing because of sonographic fetal abnormalities, where multidisciplinary review considered skeletal dysplasia a likely etiology, were consented for exome trio sequencing (both parents and fetus). Variant interpretation focused on a virtual panel of 240 genes known to cause skeletal dysplasias. Results Definitive molecular diagnosis was made in 13/16 (81%) cases. In some cases, fetal ultrasound findings alone were of sufficient severity for parents to opt for termination. In others, molecular diagnosis informed accurate prediction of outcome, improved parental counseling, and enabled parents to terminate or continue the pregnancy with certainty. Conclusion Trio sequencing with expert multidisciplinary review for case selection and data interpretation yields timely, high diagnostic rates in fetuses presenting with unexpected skeletal abnormalities. This improves parental counseling and pregnancy management.Genetics in Medicine advance online publication, 29 March 2018; doi:10.1038/gim.2018.30

A acessibilidade da oferta turística para pessoas portadoras de deficiências: o caso do município da Lousã como exemplo de boas práticas

O conceito de Turismo Acessível ou de Turismo para Todos prevê o acesso às instalações e serviços turísticos e à oferta de serviços e atividades orientada aos gostos e preferências de pessoas portadoras de deficiência ou com necessidades e exigências diferentes dos outros segmentos da procura. Ou seja, qualquer cidadão com mobilidade reduzida deve poder aceder ao que está à disposição de qualquer outro turista, em segurança, sem ter que recorrer a serviços específicos. Grande parte dos obstáculos que se colocam às pessoas portadoras de deficiência nas suas atividades turísticas resulta da falta de conhecimento das suas necessidades específicas e também da desvalorização do seu potencial, enquanto segmento de procura turística. Neste artigo, pretende-se analisar os principais aspetos da acessibilidade dos serviços turísticos para pessoas com mobilidade reduzida e o papel dos diferentes atores na remoção das barreiras existentes, utilizando como caso de estudo o município da Lousã

Is physiological glucocorticoid replacement important in children?

Cortisol has a distinct circadian rhythm with low concentrations at night, rising in the early hours of the morning, peaking on waking and declining over the day to low concentrations in the evening. Loss of this circadian rhythm, as seen in jetlag and shift work, is associated with fatigue in the short term and diabetes and obesity in the medium to long term. Patients with adrenal insufficiency on current glucocorticoid replacement with hydrocortisone have unphysiological cortisol concentrations being low on waking and high after each dose of hydrocortisone. Patients with adrenal insufficiency complain of fatigue, a poor quality of life and there is evidence of poor health outcomes including obesity potentially related to glucocorticoid replacement. New technologies are being developed that deliver more physiological glucocorticoid replacement including hydrocortisone by subcutaneous pump, Plenadren, a once-daily modified-release hydrocortisone and Chronocort, a delayed and sustained absorption hydrocortisone formulation that replicates the overnight profile of cortisol. In this review, we summarise the evidence regarding physiological glucocorticoid replacement with a focus on relevance to paediatrics

A dimensão turística dos eventos: estudo de caso Festival do Norte

In different formats and for various reasons events have always made part of our life. The many factors involved in the creation of an event led to the existence of a huge variety of event categories, making it a complex phenomenon that has been getting more and more importance in the tourism industry. Its rapid growth as an important tourism product was not followed by an intense investigation on this topic. Therefore the connection between events and tourism in not completely clear, causing some difficulties when it comes to classify if an event is a tourism product. Based on an extensive analysis of the existing investigation, this study has the goal to contribute to this discussion by trying to establish the existing relation between tourism and the event industry, while trying to define a set of quantitative and qualitative metrics that allow to measure an event tourism dimension. In order to show the applicability of these metrics they were tested trough the analyses of the North Festival, which also had the goal to conclude if the festival was in fact a tourism event.Desde sempre que os eventos, em diferentes formatos e por variados motivos, integram a vida de todos os indivíduos. A suas inúmeras tipologias, contextos e fatores que influenciam a sua classificação tornam o estudo dos eventos um fenómeno complexo. Fenómeno esse, que tem vindo a adquirir, cada vez mais, um lugar de destaque no âmbito do turismo. Contudo, o seu rápido crescimento enquanto potencial fator de motivação de viagem e de transformação de destinos não tem sido acompanhado pelo estudo da indústria e da sua ligação ao turismo, traduzindo-se em alguma indefinição relativamente aos indicadores que permitem aferir se um evento é um produto turístico. Este artigo, através de uma extensa revisão da literatura, pretende aprofundar o conhecimento da ligação entre os eventos e o turismo, procurando identificar um conjunto de indicadores, quantitativos e qualitativos, suscetíveis de avaliar a dimensão turística de um evento. A aplicação destes indicadores ao Festival do Norte permitiu testá-los e concluir sobre a dimensão turística deste evento

As experiências de viagem das pessoas com incapacidade: estratégias de negociação e dinâmicas de envolvimento

No abstract available.Sem resumo disponível

Dinâmicas de envolvimento das pessoas com incapacidade nas atividades turísticas

Doutoramento em TurismoA promoção de uma sociedade mais inclusiva tem vindo a refletir-se numa progressiva tomada de consciência das dimensões associadas ao turismo acessível para todos. Ao mesmo tempo, no plano discursivo, assume-se cada vez mais o turismo como um bem social de primeira necessidade, essencial na qualidade de vida. No entanto, também é igualmente reconhecido que o acesso às práticas turísticas, por parte de pessoas com incapacidade, continua a ser moldado por dificuldades de vária ordem, às quais o sector do turismo não tem sabido responder, ou, pelo menos, a perceção consciente deste facto social tem sido muito débil e incipiente. Partindo destes pressupostos, a nossa investigação centrou-se, particularmente, na compreensão das dinâmicas de envolvimento e de participação das pessoas com incapacidade nas atividades turísticas. Concretamente, pretendemos analisar os aspetos associados à experiência das pessoas com incapacidade visual ou incapacidade física, identificando os fatores que restringem (inibidores) e os fatores que afetam a decisão de viajar de forma positiva (os facilitadores), procurando compreender como é que as pessoas se adaptam e se tornam viajantes ativos. Para a concretização deste objetivo utilizou-se um estudo qualitativo, baseado em entrevistas longas, que procurou dar voz aos atores com incapacidade visual e física. O tratamento da informação recolhida foi efetuado com base na análise de conteúdo de tipo temático-categorial. Os resultados assim obtidos permitem extrair as seguintes conclusões principais: a participação em atividades turísticas por parte das pessoas com incapacidade física e visual resulta de um processo dinâmico e interativo, no qual intervêm múltiplos fatores, com influência positiva ou negativa, na confluência do seu contexto pessoal, da sua condição de incapacidade e do seu ambiental social, com um impacto variável nas diferentes etapas do processo.The need for a more inclusive society has been reflected in a gradual awareness of the dimensions associated with tourism for all. At the same time, it is assumed that tourism is a basic necessity, essential to quality of life and should therefore be accessible to all people, regardless of their physical, economic, or social conditions. However, it is acknowledged that access to tourism by persons with disabilities continues to be shaped by a variety of constraints that are not being clearly or consistently addressed by those in charge of tourism planning and management. Based on these assumptions, our research focused primarily on the understanding of the engagement and participation in tourist activities of people with disabilities. Specifically, we intend to analyze aspects related to the experience of people with visual and physical impairments, identifying the factors that constrain (constraints) and the factors that facilitate the decision to travel (facilitators), seeking to understand how people adapt and become active travelers. To accomplish this objective the empirical work was based on a qualitative methodology using in-depth interviews, which sought to give voice to people with visual and physical disabilities. The treatment of information gathered was based on content analysis of thematic-categorical type whose results allow us to take the following main conclusions: The participation in tourist activities by people with physical and visual disabilities results from an ongoing and interactive process, which is shaped by multiple factors, with positive or negative influence, at the conflux of their personal context, their impairment condition and social environment, with a variable impact on different stages of the process. Although there are some similarities in the two groups of interviewees, it is possible to identify differences in the influence of factors analyzed (inhibitors and facilitators) as well as the negotiation strategies used for continued participation in tourism. Each type of impairment presents distinct limitations that influence the perception of the factors that restrict (structural, interpersonal and intrapersonal constraints) or facilitate (structural, interpersonal and intrapersonal facilitators) participation in tourism as well as distinct types of interaction between these factors