Mutação rara do gene NDP em doente pediátrico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Surdez súbita : a marcha diagnóstica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Kernicterus e icterícia neonatal : revisão teórica a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

Children's auditory perception and cognitive processing skills in adverse listening situations

Thesis (Ph.D.)--University of Washington, 2016-06

Defining Atoh1 function and regulation in avian supporting cells during auditory hair cell regeneration

Thesis (Ph.D.)--University of Washington, 2016-06

Successes and failures in assessing acquired language disorders using an Internet-based telerehabilitation system

We have used a telerehabilitation system (eREHAB) to remotely assess acquired language disorders via the Internet. The system was used to establish a 128 kbit/s videoconference between two sites and allowed a remote language assessment to be conducted using the standardized Boston Diagnostic Aphasia Examination (BDAE). The system had the capacity to display text and images, and could play pre-recorded instructions to the participant via various built-in tools. A touch screen allowed tasks involving picture identification to be completed easily. Eighteen participants with a diagnosis of an acquired language disorder were simultaneously assessed using the eREHAB system, and in the traditional face-to-face manner by two speech pathologists. There was very high agreement between the two assessors, with weighted kappa scores of 0.8–1.0 for 88% of the sub-tests of the BDAE. There was also high agreement (80–100%) and high kappa scores (0.67–0.90) between assessors on the six rating scales relating to language characteristics. The agreement between the two assessors for the diagnosis of the type of aphasia was 83%. Limitations of the system related mainly to problems inherent in IP videoconferencing. The inability to maintain the preferred speed of 128 kbit/s for the duration of the videoconference and the resultant increase in video and audio breakup and latency affected the clinician’s ability to administer the BDAE with the same ease and accuracy as in face-to-face administration. These difficulties were exacerbated when participants presented with a moderate to severe language disorder, auditory comprehension deficits or significant hearing loss. Despite these limitations, a valid assessment of language disorder was found to be feasible via this telerehabilitation application.

Ultra high-speed transmission using dispersion managed solitons

This thesis presents the results of numerical modelling of ultra high-speed transmission using DM solitons. The theory of propagation in optical fibres is presented with specific reference to optical communication systems. This theory is then expanded to. incorporate dispersion-managed transmission and the dispersion managed soliton. The first part of this work focuses on ultra high-speed dispersion managed soliton propagation in short period dispersion maps. Initially, the cbaracteristics .of dispersion managed soliton propagation in short period dispersion maps are contrasted to those of the more conventional dispersion managed regime. These properties are then utilised to investigate transmission at single channel data rates of 80 Gbit/s, 160 Gbit/s and 320 Gbit/s. For all three data rates, the tolerable limits for transmission over 1000 km, 3000 km and·transoceanic distances are defined. A major limitation of these higher bjt rate systems arises from the problem of noise-induced interactions, which is where the.accumulation of timing jitter causes neighbouring dispersion-managed solitons to interact. In addition, the systems become more sensitive to initial conditions as the data rate increases, .. The second part of the work focuses on contrasting the performance of a range of propagation regimes, from quasi-linear through to soliton-like propagation at 40 Gbit/s for both single channel and WDM dispersion managed transmission. The results indicated that whilst the optimal single channel performance was achieved for soliton-like propagation, the optimal WDM performance was achieved for propagation regime that lay between quasi-linear and soliton-like.

Foundations of an intervention package to improve communication in residential care settings:a mixed methods study

Background: The prevalence of hearing loss is considerably higher in individuals in residential care than in people within the community-dwelling population, and yet hearing aids and hearing services are relatively underused. Care staff have a key role in supporting access to services. Objectives: This study identifies staff perspectives on hearing loss and their views about potential hearing service improvements. Study design: A four-stage mixed methods study was used, made up of qualitative interviews, observation, a survey and a stakeholder involvement meeting. Results: The qualitative stages indicated that staff were concerned about their levels of interaction with residents. Staff considered maximizing communication as part of their professional role. The quantitative survey indicated that these views were widely held by staff, and the stakeholder stage identified the need for social support and dedicated staff training opportunities. Conclusion: Care home staff regard communication as a shared issue. Future interventions could enhance access to hearing services and provide care home staff with training in hearing loss and hearing aid management. © 2013 Informa Healthcare.

Stochastic anti-resonance in a fibre Raman amplifier

Stochastic anti-resonance, that is resonant enhancement of randomness caused by polarization mode beatings, is analyzed both numerically and analytically on an example of fibre Raman amplifier with randomly varying birefringence. As a result of such anti-resonance, the polarization mode dispersion growth causes an escape of the signal state of polarization from a metastable state corresponding to the pulling of the signal to the pump state of polarization.This phenomenon reveals itself in abrupt growth of gain fluctuations as well as in dropping of Hurst parameter and Kramers length characterizing long memory in a system and noise induced escape from the polarization pulling state. The results based on analytical multiscale averaging technique agree perfectly with the numerical data obtained by direct numerical simulations of underlying stochastic differential equations. This challenging outcome would allow replacing the cumbersome numerical simulations for real-world extra-long high-speed communication systems.

The identification of early factors related to academic achievement among deaf students

The purpose of this research study was to examine specific factors believed to be related to academic achievement in deaf children. More specifically, this research sought to determine whether there was a significant difference in achievement between those students whose parents use oral communication only and those whose parents use some type of sign language. An additional purpose of this research was to determine if there was a significant difference in academic achievement with those deaf students who used amplification devices early in life. This study also sought to determine whether providing early intervention program which emphasizes and enables parents to develop a language rich environment had a significant impact on the academic achievement of deaf children and whether the age at which initial services are received influence deaf student's subsequent academic achievement. This study examined the relationship, if any, between intellectual ability and academic achievement among deaf children. Finally, this study sought to investigate the relationship between the degree of hearing loss and academic achievement. ^ Purposive sampling was used to select subjects for this study. All 228 eligible Deaf/Hard of Hearing (DHH) students enrolled in a Broward County Public School were included in the original sample. Sixty-one students actually participated in this study. A correlational method of statistical analysis as well as a cross classification (crosstabs) was used to analyze the data. ^ The results show that academic achievement in the areas of reading and mathematics was significantly related to parental mode of communication and the mode of communication used in school. Academic achievement, in the area of reading, was also signficantly related to intellectual ability. The reading achievement was also found to be significantly related to degree of hearing loss. Written language was not significantly related to any factors investigated in this study. ^ Additional research should be conducted to further investigate the low academic achievement among deaf children. The diversity among signing systems at school and between home and school should also be analyzed. Finally, future studies should examine curriculum and instruction methods to increase the academic achievement of deaf children. ^

Endothelin receptor B and neural crest derived melanocyte development

Neural Crest cells (NCC) constitute a unique embryonic cell population that arises between the prospective epidermis and the dorsal aspect of the neural tube of vertebrates. NCC migrate ventromedially and dorsolaterally throughout the developing embryo giving rise to the peripheral nervous system constituents and melanocytes that ultimately reside in the skin and hair follicles respectively. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene manifest strikingly similar phenotypes characterized by hypopigmentation, hearing loss and megacolon these are due to absence of melanocytes in the skin and inner ear and lack of enteric ganglia in the distal part of the gut, respectively. Piebald lethal mice and humans with Hirschsprung's disease or Waardenburg syndrome carry different mutations in the Ednrb gene. The major goals of this project were to determine whether the action of Ednrb in NCC is required prior to commitment of these cells to the melanocytic lineage and to investigate its potential participation in the actual process of commitment. In order to achieve these goals transgenic mice that express Ednrb under two different regulatory elements were created. The first, Dct-Ednrb, expresses Ednrb under the control of the DOPAchrome tautomerase (Dct) promoter to direct expression to already committed melanocyte precursors. The second, Nes-Ednrb, expresses Ednrb under the regulation of the human nestin gene second enhancer to direct expression to pre-migratory NCC. Crosses of the Dct-Ednrb mouse with piebald lethal showed that the transgene was capable of rescuing the hypopigmentation phenotype of the later. This result indicates that the action of Ednrb after NCC commit to the melanocytic lineage is sufficient for normal melanocyte development. The Dct-Ednrb was further crossed with two other hypopigmentation mutants that carry mutations in the transcription factors Sox10 and Pax3. The transgene rescued the phenotype of the Sox10 mutant only. This suggests that Ednrb interacts with Sox10 but not with Pax3 during melanocyte development. The Nes-Ednrb mice developed a hypopigmentation phenotype that was augmented when crossed with piebald lethal or lethal spotting (mutation in Edn3, the ligand for Ednrb) mice but was rescued by over expression of Edn3. These results suggest that alterations in Ednrb expression early in development affect melanocyte development. This study provides novel information necessary to better understand the early embryonic development of NCC, clarifies specific interactions between different melanogenic genes and, could eventually help in the implementation of therapies for human pigmentary genetic disorders. ^

Transgenic Expression of Endothelin Receptor-B Rescues the Aganglionosis Phenotype of Piebald Lethal Mice

Neural crest cells (NCC) are a unique population of cells in vertebrates that arise between the presumptive epidermis and the dorsal most region of the neural tube. During neurulation, NCC migrate to many regions of the body to give rise to a wide variety of cell types. NCC that originate from the neural tube at the levels of somite 1-7 colonize the gut and give rise to the enteric ganglia. The endothelin signaling pathway has been shown to be crucial for proper development of some neural crest derivatives. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene exhibit similar phenotypes characterized by hypopigmentation, hearing loss, and megacolon. Thesephenotypes are due to lack of melanocytes in the skin, inner ear and enteric ganglia in the distal portion of the colon, respectively. It is well established that Ednrb is required early during the embryonic development for normal innervation of the gut. However, it is not clear if Ednrb acts on enteric neuron precursor cells or in pre-committed NC precursors. Additionally, it is controversial whether the action of Ednrb is cell autonomous or non- autonomous. We generated transgenic mice that express Ednrb under the control of the Nestin second intron enhancer (Nes) which drives expression to pre-migrating NCC. These mice were crosses to the spontaneous mouse mutant piebald lethal, which carriers a null mutation in Ednrb and exhibits enteric aganglionosis. The Nes-Ednrb was capable of rescuing the aganglianosis phenotype of piebald lethal mutants demonstrating that expression of Ednrb in pre-committed precursors is sufficient for normal enteric ganglia development. This study provides insight in early embryonic development of NCC and could eventually have potential use in cellular therapies for Hirschsprung's disease.

Percepção da equipe de saúde, discentes e usuários sobre a comunicação com indivíduos surdos na atenção primária

The study aimed to identify in the professionals and students of health courses that work in a health Basic Unit in the city of Natal/RN their perceptions of the care of deaf patients, and with the population's needs with hearing loss in relation to health care. This is a cross-sectional, exploratory, descriptive study, conducted between April to July 2014, with a population composed of 21 health professionals, 17 students and 8 deaf users. For data collection, we used a structured questionnaire with open and closed questions applied to groups composed of health professionals (doctors, dentists, nurses and health workers) and students of medical schools, nursing, physical education, nutrition and social service. The professionals/students answered a semi-structured questionnaire with open and closed questions concerning the possible difficulties the care of the deaf and hearing impaired. Data collection with deaf users was conducted through filmed interview for the Brazilian Sign Language (Libras) could be interpreted as to the Portuguese by the researcher. With the latter it was conducted a survey of their reactions when looking for a care in the health service. Regarding the profile of identification of the subjects, it was analyzed by simple descriptive statistics (absolute and relative frequencies). The open questions were analyzed through the content analysis technique which allowed the categorization process preserving all the points raised in the discussion so that the lines were representative of the whole. When asked about the professionals and students attitude used to communicate with deaf patients possible the following categories emerged: the "writing", the "gestures" and the "third party assistance". With regard of the deaf, when asked about their experiences in seeking care in health, the elucidated categories were: "quality of care to the hearing impaired", "communication with the hearing impaired adequacy" and "dependence on third parties." The closed questions were measured and adapted to the 5 degrees of variation Likert Scale, which comprised three of these issues: degree of difficulty in communication to meet a patient with hearing loss (minimum to great difficulty); feeling of comfort while using sign language (minimum to severe discomfort); and knowledge of the Law 10.436, which provides for the Brazilian Sign Language (Libras) (low knowledge to entirely clear). The data collected with professionals and students revealed some misunderstanding and discomfort in health care for deaf patients, reality also evidenced in the opinion of the deaf participants. This study revealed problems in communication, resulting in negative consequences in serving this population. This diagnosis may be relevant to public policy development and curriculum guidelines essential to the training of health professionals, inclusion and improving assistance to deaf.

Prevalência e fatores associados à alteração vocal em idosos institucionalizados com capacidade cognitiva preservada

Voice disorders (VD) in the elderly can interfere negatively in communication, emotional well-being and quality of life, conditions that correspond to greater exposure to illness and social isolation bringing consequent economic impact for the health system. It is assumed that institutionalized confinement, weakness and morbidity associated to nursing home (NH) contribute to transform VD an especially prevalent condition in institutionalized elderly, including those without cognitive impairment. Thus, the aim of this study was to determine the prevalence and associated factors of VD in NH elderly residents without cognitive impairment. There is no epidemiological diagnostic instruments of VD for elderly populations, so the first step of this study was dedicated to prepare and analyze the psychometric properties of a short, inexpensive and easy to use questionnaire named Screening for Voice Disorders in Older Adults (Rastreamento de Alterações Vocais em Idosos—RAVI). The methodological procedures of this step followed the guidelines of the Standards for Educational and Psychological Testing and contemplated validity evidence based on test content, based on response processes, based on internal structure and based on relations with other variables, as well as reliability analysis and clinical consistency. The result of the validation process showed that the RAVI final score generate valid and reliable interpretations for the epidemiological diagnosis of VD in the elderly, which endorsed the use of the questionnaire in the second stage of the study, performed in ten NH located in the city of Natal, Rio Grande do Norte. At this stage, data from socioeconomic and demographic variables, lifestyle, general health conditions and characterization of the institution were collected. It was performed a bivariate analysis and it was calculated the prevalence ratio as a magnitude association measure, with a confidence interval of 95%. The variables with p-value less than 0.20 were included in the multiple logistic regression model that followed the Forward selection method. The odds ratio found in the multivariate model was converted into prevalence ratio and the level of significance was 5%. The sample consisted of 117 subjects with predominance of females and average of 79.68 (± 7.92) years old. The prevalence of VD was 39.3% (95% CI: 30.4-48.1%). The multivariate model showed statistically significant association between VD and depressive symptoms, smoking for a year or more and selfreported hearing loss. In conclusion, VD is a prevalent health condition in NH elderly residents without cognitive impairment and is associated with factors involving psychosocial, lifestyle and communicative disability that require attention of managers and professionals involved with NH environment. Strategies to encourage communication and social integration, actions to combat smoking and minimizing the effects of hearing loss could stimulate the physical well-being, emotional and mental health of institutionalized elderly population, contributing to the vocal and communicative maintenance, a more effective social inclusion and better overall health condition.