Clinical practice guidelines for management of parkinson’s disease : a systematic critical appraisal

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

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

Qualidade de vida dos cuidadores informais de doentes de Huntington

Introdução: A Doença de Huntington (DH) é uma patologia neuro degenerativa hereditária de transmissão autossómica dominante que afeta o movimento e conduz a um défice progressivo das capacidades cognitivas e comportamentais. Cuidar um doente de Huntington é um processo complexo e exigente com um grande impacto na saúde, bem-estar e qualidade de vida do cuidador informal. Objetivo: Avaliar o impacto da DH na Qualidade de Vida do Cuidador Informal, e verificar em que medida as variáveis sociodemográficas, contextuais e clínicas se relacionam com essa Qualidade de Vida. Metodologia: Trata-se de um estudo quantitativo, não experimental, transversal numa lógica de análise descritivo-correlacional com 50 Cuidadores Informais de nacionalidade espanhola, membros da “Asociación de Corea de Huntington Española” - ACHE. Utilizamos a versão espanhola do questionário: Huntington’s Disease Quality of Life Battery for Carers (HDQoLC) como instrumento de colheita de dados especifico para a avaliação da QDV dos Cuidadores de Doentes de Huntington . Resultados: Os participantes são na sua maioria do sexo feminino (68%), com uma media de idades de 50,04 anos, casados (72%) com elevado grau de literacia (52%) e no ativo (72%). São essencialmente cônjuges da pessoa dependente (52%) ou filhos(as) (28%). Os resultados sugerem que os CI possuem uma QDV moderada (53%) na qual os “aspetos práticos do cuidar”, ou seja, o papel de cuidador, tem grande impacto na QDV (43%) a “satisfação com a vida e os “sentimentos sobre a vida com DH” parecem atenuar esta sobrecarga. Os dados obtidos revelam que as variáveis que influenciaram significativamente a Qualidade de Vida total são: as habilitações literárias e o número de horas de cuidados diários. No entanto podemos afirmar que a idade, tempo como CI e os motivos que levaram a assumir o papel de cuidador, tem uma relação expressiva com a dimensão “aspetos práticos do cuidar” da QDV. Conclusões: Os resultados reforçam a multidimensionalidade e variabilidade da qualidade de vida dos cuidadores informais de Doentes de Huntington e evidenciam a necessidade dos profissionais de saúde apostarem em programas de intervenção na comunidade, de forma a implementar estratégias de apoio que minimizem as dificuldades sentidas, aumentem a capacidade para a prestação de cuidados e que promovam a qualidade de vida dos que cuidam. Palavras-chave:; Doença de Huntington; Cuidadores Informais; Qualidade de Vida.

Description and Prediction of Freezing of Gait in Parkinson's Disease from Wearable Inertial Measurements Units

Parkinson's disease (PD) is a neuro-degenerative disorder, the second most common after Alzheimer's disease. After diagnosis, treatments can help to relieve the symptoms, but there is no known cure for PD. PD is characterized by a combination of motor and no-motor dysfunctions. Among the motor symptoms there is the so called Freezing of Gait (FoG). The FoG is a phenomenon in PD patients in which the feet stock to the floor and is difficult for the patient to initiate movement. FoG is a severe problem, since it is associated with falls, anxiety, loss of mobility, accidents, mortality and it has substantial clinical and social consequences decreasing the quality of life in PD patients. Medicine can be very successful in controlling movements disorders and dealing with some of the PD symptoms. However, the relationship between medication and the development of FoG remains unclear. Several studies have demonstrated that visual or auditory rhythmical cuing allows PD patients to improve their motor abilities. Rhythmic auditory stimulation (RAS) was shown to be particularly effective at improving gait, specially with patients that manifest FoG. While RAS allows to reduce the time and the effects of FoGs occurrence in PD patients after the FoG is detected, it can not avoid the episode due to the latency of detection. An improvement of the system would be the prediction of the FoG. This thesis was developed following two main objectives: (1) the finding of specifics properties during pre FoG periods different from normal walking context and other walking events like turns and stops using the information provided by the inertial measurements units (IMUs) and (2) the formulation of a model for automatically detect the pre FoG patterns in order to completely avoid the upcoming freezing event in PD patients. The first part focuses on the analysis of different methods for feature extraction which might lead in the FoG occurrence.

Cortical Abnormalities in Adults and Adolescents with Major Depression based on Brain Scans from 20 Cohorts Worldwide in the ENIGMA Major Depressive Disorder Working Group

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

(Table 2) Trace metal ratios of various benthic foraminifera shells

Benthic foraminiferal d13C and Cd/Ca studies suggest that deep Atlantic circulation during the Last Glacial Maximum was very different from today, with high-nutrient (low d13C, high Cd) deep Southern Ocean Water (SOW) penetrating far into the North Atlantic. However, if some glacial d13C values are biased by productivity artifacts and/or air-sea exchange processes, then the existing d13C data may be consistent with the continual dominance of North Atlantic Deep Water (NADW). Cibicidoides wuellerstorfi Cd/Ca results presented here indicate that the glacial North Atlantic was strongly enriched in dissolved Cd below ~2500 m depth. If NADW formation was still vigorous relative to SOW formation, these data could be explained by either increased preformed nutrient levels in the high-latitude North Atlantic or by increased organic matter remineralization within lower NADW. High glacial Zn/Ca values in the same samples, however, are best explained by a substantially increased mixing with Zn-rich SOW. The cause was most likely a partial replacement of NADW by less dense Glacial North Atlantic Intermediate Water. This reorganization also lowered deep North Atlantic [CO3]2- concentrations by perhaps 10 to 15 µmol/kg.

Age models and stable isotope record of sediment cores from the Atlantic Ocean

The high-resolution delta18O and delta13C records of benthic foraminifera from a 150,000-year long core from the Caribbean Sea indicate that there was generally high delta13C during glaciations and low delta13C during interglaciations. Due to its 1800-m sill depth, the properties of deep water in the Caribbean Sea are similar to those of middepth tropical Atlantic water. During interglaciations, the water filling the deep Caribbean Sea is an admixture of low delta13C Upper Circumpolar Water (UCPW) and high delta13C Upper North Atlantic Deep Water (UNADW). By contrast, only high delta13C UNADW enters during glaciations. Deep ocean circulation changes can influence atmospheric CO2 levels (Broecker and Takahashi, 1985; Boyle, 1988 doi:10.1029/JC093iC12p15701; Keir, 1988 doi:10.1029/PA003i004p00413; Broecker and Peng, 1989 doi:10.1029/GB003i003p00215). By comparing delta13C records of benthic foraminifera from cores lying in Southern Ocean Water, the Caribbean Sea, and at several other Atlantic Ocean sites, the thermohaline state of the Atlantic Ocean (how close it was to a full glacial or full interglacial configuration) is characterized. A continuum of circulation patterns between the glacial and interglacial extremes appears to have existed in the past. Subtracting the deep Pacific (~mean ocean water) delta13C record from the Caribbean delta13C record yields a record which describes large changes in the Atlantic Ocean thermohaline circulation. The delta13C difference varies as the vertical nutrient distribution changes. This new proxy record bears a striking resemblance to the 150,000-year-long atmospheric CO2 record (Barnola et al., 1987 doi:10.1038/329408a0). This favorable comparison between the new proxy record and the atmospheric CO2 record is consistent with Boyle's (1988a) model that vertical nutrient redistribution has driven large atmospheric CO2 changes in the past. Changes in the relative contribution of NADW and Pacific outflow water to the Southern Ocean are also consistent with Broecker and Peng's (1989) recent model for atmospheric CO2 changes.

Sedimentation rates calculated on surface sediment samples from different site of the Atlantic and Pacific Oceans (Table 1)

Radiocarbon ages on CaCO3 from deep-sea cores offer constraints on the nature of the CaCO3 dissolution process. The idea is that the toll taken by dissolution on grains within the core top bioturbation zone should be in proportion to their time of residence in this zone. If so, dissolution would shift the mass distribution in favor of younger grains, thereby reducing the mean radiocarbon age for the grain ensemble. We have searched in vain for evidence supporting the existence of such an age reduction. Instead, we find that for water depths of more than 4 km in the tropical Pacific the radiocarbon age increases with the extent of dissolution. We can find no satisfactory steady state explanation and are forced to conclude that this increase must be the result of chemical erosion. The idea is that during the Holocene the rate of dissolution of CaCO3 has exceeded the rain rate of CaCO3. In this circumstance, bioturbation exhumes CaCO3 from the underlying glacial sediment and mixes it with CaCO3 raining from the sea surface.

Stable carbon and oxygen isotope analyses of Neogloboquadrina pachyderma

Detailed records of the carbon and oxygen isotopic ratios of Neogloboquadrina pachyderma are compared between nine high-latitude sediment cores, from the Northern and Southern Hemispheres, covering the last 140000 yrs. The strong analogies between the delta13C records permit to define a delta13C stratigraphic scale, with three clear cut transitions simultaneous with the oxygen isotopic transitions 6/5 (125 kyrs.), 5/4 (65 kyrs.), and 2/1 (13 kyrs.). The delta13C records of N. pachyderma in the high-latitude cores, which follow the changes in delta13C of the surface water TCO2 near areas of deep water formation present trends similar to the benthic foraminifera delta13C records in cores V19-30 and M12-392, although amplitudes of the isotopic shifts are different. This implies that a large part of the observed variations represents global changes in the carbon distribution between biosphere and ocean. The 13C/12C ratios of N. pachyderma in the North Atlantic cores display larger regional variations at 18 kyrs. B.P. than at present. To explain these differences, we have plotted the 18 kyrs. B.P. delta13C values of N. pachyderma from 17 cores distributed N of 40°N. Comparison with published surface water temperature distribution at 18 kyrs. B.P. indicates that a strong divergent cyclonic cell, centered approximatively 55°N and 15°W, was active during most of the last ice-age maximum. This hydrology, analogous to the present Weddell Sea, explains the published evidences of bottom water formation, if located on the northern flank of the gyre, and the strong polar front on the southern flank, probable location of intermediate water formation.

Stable carbon and oxygen isotope ratios of foraminifera from North Atlantic sediments

Oxygen-18 records of benthic foraminifera from the Atlantic Ocean are significantly different from those of the Pacific and Indian Oceans indicating that the Glacial North Atlantic Deep Water was about 1.3°C cooler than today because different deep water sources appeared in the North Atlantic Ocean during glacial times. The present study seeks to interprete carbon-13 records of planktonic and benthic foraminifera as a tracer of the cycle of the CO2 dissolved in surface and deep water of the ocean during the last climatic cycle. Carbon-13 records of planktonic foraminifera indicate that the delta13C of atmospheric CO2 and total CO2 dissolved in surface water did not vary noticeably (-0.2 +/- 0.3 per mil) during glacial times. Carbon-13 records of benthic foraminifera indicate that the eastern North Atlantic Ocean was an area of deep water formation dying isotopic stage 2, but not during most of stage 3. Moreover, large delta13C differences in the NADW between 20°N and 50°N show that the residence time of the glacial NADW was about 4 times that of today.