Dissertations / Theses on the topic 'Left brain'

The purpose of this quantitative, single-subject research was to examine the effects of hemisphere integration on maladaptive behaviors as measured by the BASC-III assessment. Morgan and Sideridis report that problem behavior rates in United Schools range from 10-30% and 92% of teacher respondents identified that problem behaviors have worsened over their careers (2013). Research has been done on the importance of neuroscience in the field of education, but there is a gap between the research and application. Baseline data on the targeted behaviors was collected by administering the BASC-III Teacher Rating Scale (TRS) on the participant to two special education teachers and a general education teacher, as well as, having the participant independently fill out the Self-Report of Personality (SRP). The student then engaged in two daily integrated hemisphere activities in the form of a Tell Me Activity. Data was collected on the frequency of errors and the duration of that activity. The intervention was administered for 30 trials. After the 30 trials, all participants were then given the BASC-III assessment again. Pre and Post BASC-III T Scores were compared to determine student growth. The participant showed growth in 20 out of 45 BASC-III categories over three TRS reports (15 categories each report). The participant also showed growth in 8 out of 15 BASC-III categories on the SRP. While although the participant showed growth, the participant showed minimum growth in functional levels. Overall, this research remains inconclusive due to the researcher’s inability to determine the functional relation between the intervention and maladaptive behaviors.

The aim of this dissertation was to provide a translation from English to Italian of an extract from a review article about cerebral asymmetries titled “Left Brain, Right Brain: Facts and Fantasies”, published by Michael C. Corballis in 2014. A corpus was built to ensure that the translation had the appropriate terminology. A program called AntConc was employed for corpus analysis. After a brief introduction to the aim and structure of the work, the dissertation is divided into four chapters. Chapter one provides an overview of two theoretical concepts in order to gradually introduce the subject: the language used in specialized contexts and the genre analysis. Chapter two focuses on the textual analysis of the source text: this stage is crucial for a good comprehension of the text and for the detection of the main difficulties it raises. Chapter three consists of the translated text, while Chapter four provides a commentary of the translation, in which I describe the main problems encountered during the translation process and the strategies adopted to solve them.

The nature of the human brain has preoccupied philosophers and scientists for centuries. As early as the 4th Century BCE, Greek philosophers speculated that the anatomically distinct hemispheres of the brain implied specialisation of function. It was not until the "splitbrain" operations of the 1950s, however, that the precise specialisation of each hemisphere could be demonstrated. The right hemisphere apparently assumed responsibility for spacial, holistic processes, while the left hemisphere processed analytical, sequential tasks. During that same decade, educational psychologists observed two markedly different ways in which individuals perceive and relate to the world. It was later observed that these "cognitive styles" seemed directly related to the bi-polar functions of the right and left hemispheres of the brain. This implied a genetic basis for cognitive style. Subsequent research suggested that cognitive style is to a considerable extent a result of the environment of socialisation, and therefore, different cultures would demonstrate different cognitive styles. Such cultural differences in learning expectations might have serious implications for both teachers and learners in the field of export education. The literature review in this study identified physical, environmental, and experiential factors which appear to influence cognitive style. This information formed the basis of the biographical section of a questionnaire which elicited the learning style preferences of pre-tertiary students from Australia (native speakers), Indonesia and Japan. The study posed the negative hypothesis: There are no significant differences in patterns of cognitive styles between cultures. The results of the field study contradicted the negative hypothesis, identifying significant differences in patterns of cognitive styles between the three cultural groups.

The Problem of this study was to determine if the cognitive style of elementary school principals affects the principal's evaluation of a teacher when there is a match or mismatch between the principal's and teacher's cognitive style. Using the Productivity Environmental Preference Survey, the dimensions of right brain/left brain hemispheric dimensions of cognitive style were measured for the sample population. The sample population included 40 elementary school principals and 120 elementary school teachers. The 120 teachers were made up of teachers selected by each of the 40 principals as the most effective teachers in the school. The statistical analysis of the data indicated there was not a significant correlation between the principal's right brain/left brain dimensions of cognitive style and the right brain/left brain dimensions of cognitive style of the teachers selected as the three most effective teachers in the school (r =.10, p =.281).

The left hemisphere interpreter refers to a function in the left hemisphere of the brain that search for and produce causal explanations for events, behaviours and feelings, even though no such apparent pattern exists between them. Confabulation is said to occur when a person presents or acts on obviously false information, despite being aware that they are false. People who confabulate also tend to defend their confabulations even when they are presented with counterevidence. Research related to these two areas seems to deal with the same phenomenon, namely the human tendency to infer explanations for events, even if the explanations have no actual bearing in reality. Despite this, research on the left hemisphere interpreter has progressed relatively independently from research related to the concept of confabulation. This thesis has therefore aimed at reviewing each area and comparing them in a search for common relations. What has been found as a common theme is the emphasis they both place on the potentially underlying function of the interpreter and confabulation. Many researchers across the two fields stress the adaptive and vital function of keeping the brain free from both contradiction and unpredictability, and propose that this function is served by confabulations and the left hemisphere interpreter. This finding may provide a possible opening for collaboration across the fields, and for the continued understanding of these exciting and perplexing phenomena.

Thesis (Ph. D.)--University of California, San Diego, 2009.
Title from first page of PDF file (viewed September 16, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

Stroke, or cerebrovascular accident (CVA), is a prominent cause of long term disability in the United States. It has been evidenced that the outcome of a CVA patient differs as a function of the cerebral hemisphere that is damaged by the stroke, especially in terms of emotional changes. The Right Hemisphere Model of Emotion posits that the right hemisphere is specialized for processing emotional content, regardless of valence. In contrast, the Bi-Hemispheric Model of Emotion posits that each hemisphere has its own emotional specialization. The current experiment tested the competing predictions of the two theoretical perspectives in a mixed sample of left cerebrovascular accident (LCVA) patients and right cerebrovascular accident (RCVA) patients using a Dichotic Listening task and the Affective Auditory Verbal Learning Test (AAVLT). Heart Rate (HR) and Pulse Oxygen Saturation (SpO2) were also recorded as sympathetic measures. It was expected that the predictions of the Bi-Hemispheric Model would be supported. A series of mixed design ANOVAs were used to analyze the data. Results revealed that both groups may have exhibited decreased auditory detection abilities in the ear contralateral to CVA location. Additionally, CVA patients recalled significantly more positive words, than negative or neutral words, and exhibited a significant learning curve. LCVA patients exhibited a recency effect, while RCVA patients exhibited a heightened primacy effect. Findings from HR and SPO2 measures suggested a parasympathetic response to neutral information as well as an impaired sympathetic response to negative information in RCVA patients. Taken together these results lend partial support to the hypotheses drawn from the Bi-Hemispheric Model of Emotion, as evidenced by the diametrically opposite effects in these groups, which appears to reflect opposing cerebral processes.
Ph. D.

The present study investigated hemispheric lateralization and the use of serial versus global processing of facial stimuli in a recognition task. The subjects were 19 male and 29 female undergraduate students. Identi-Kit faces which varied on four features (hair, eyes, mouth, and chin) were tachistoscopically presented. The accuracy of the subjects' responses were recorded. Analyses of variance suggested that subjects did not differ in use of inner or outer details, but did differ in use of upper and lower details. The data suggested a top-to-bottom order of processing for stimuli presented in both visual fields, with the most accurate recognition based on the hair, eyes, mouth, and chin, in that order.

Functional reorganization may explain why. despite a large tumour in eloquent cortex. the patient has no neurological impairment. The aims of the present study were to 1. Investigate the effect of tumour growth on neural circuits for speech production and visual processing and 2. Determine the effect of tumour removal on speech production and visual processing. Three patients with large, left-hemisphere brain tumours had pre- surgery and post-surgery functional neuroimaging (fMRI) and language testing (CAT). In addition, these patients underwent surgery for tumour resection. Pre-operative fMRI demonstrated functional reorganization in the patients. All three patients showed regions of overactivation and underactivation in local and remote regions relative to tumour location. Of particular interest, two patients showed increased activity in the right hemisphere homologue of their left parietal tumour whereas one patient illustrated a decreased activation in the right hemisphere homologue region to her left postcentral tumour. A comparison of pre and post-surgery fMRI results demonstrated that functional reorganization primarily occurs prior to surgery although some changes in activation occur after surgery. This study provides evidence that the right hemisphere homologue region is differentially activated (over and under) across patients. Furthermore, our study suggests that the effect of brain tumour growth is more prominent than tumour resection.

The present experiment was conducted to explore the time-course of lexical ambiguity resolution in normal control (NC) subjects and the nature of right hemisphere-damaged (RHD) and left hemisphere-damaged (LHD) patients' impairments in this process. NC, RHD and LHD subjects performed a cross-modal lexical decision task, in which they heard sentence contexts that were biased toward the dominant or subordinate meanings of ambiguous words occurring before the end of the sentence. Written target words related to the dominant or subordinate meaning of the ambiguous words were introduced either at the onset of the ambiguous word (immediate condition), or 1000 ms later (delayed condition). Results revealed that both dominant and subordinate meanings were primed in the immediate condition, irrespective of context type or group. In the delayed condition, only the contextually-appropriate dominant meanings were primed in normal control subjects, whereas both patient groups showed significant priming only for the contextually-inappropriate dominant meanings. Findings for the NC subjects are interpreted in support of a modular model of lexical ambiguity resolution, and more specifically of an exhaustive access view. Patients' results are discussed with reference to a delayed suppression mechanism of inappropriate meanings, which is thought to be involved in these patients' language comprehension deficits.

Apraxia, a high-level movement disorder, is associated with performance errors during gesture imitation, demonstrating the use of familiar objects that are present (actual object-use) or absent (pantomime), or all three scenarios. Focusing on objects, apraxia has an isolated effect on manipulation judgements regarding skilled object-use. These manipulation deficits are potentially attributed to damage to a purported ventro-dorsal stream resulting in impaired internal representations of movement (i.e. motor imagery). Instead, patients over-rely on visual affordances during object-directed motor behaviour. The cortical regions associated with the ventro-dorsal stream correspond to those damaged in apraxia, in particular the left inferior parietal lobe (IPL), adding weight to this proposal. Using a perceptual matching task with familiar objects and an action execution grasping task with novel objects, behavioural work with left hemisphere stroke patients assessed whether apraxic deficits are specific to object manipulation and whether these patients over-rely on object affordances during skilled object-manipulation. In parallel, the effect of neuromodulation technique transcranial direct current stimulation (tDCS) on motor imagery was explored with healthy populations. Performance changes during left IPL stimulation was assessed during classic motor mental rotation and the same perceptual matching task used with patients. Apraxic patients showed a selective impairment during object manipulation judgements of the perceptual matching task, which increased with apraxia severity. Despite tDCS over the left or right IPL equally affecting motor mental rotation performance in healthy populations, during the perceptual matching task only modulation of the left IPL slowed reaction times when making manipulation judgements but not functional semantic judgements regarding object-use. These results suggest that disruption of ventro-dorsal processing specifically disturbs motor representations of object-use. When repeatedly grasping novel objects of differing weight distribution, most apraxic patients consistently selected a structurally afforded grasp-point, indicating that apraxic patients over-rely on visual affordances after ventro-dorsal disruption. These results confirm that the ventro-dorsal stream, in particular the left IPL, is critical in integrating perceptual internal representations of skilled movement into context-dependent action plans based on visual information. Over-reliance on visual affordances caused by disruption to this pathway not only affects perceptual manipulation judgements of familiar objects but also experience-based learning when grasping novel objects.

Thesis: S.M. in Science Writing, Massachusetts Institute of Technology, Department of Comparative Media Studies/Writing, 2018.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 15-16).
Traumatic brain injuries are one of the most common injuries in domestic violence, with studies finding that approximately 75 percent of women tested report at least one TBI. These injuries leave invisible scars in the form of memory problems. But despite the large prevalence of TBIs in the population, there is a lack of research, stunted by both funding and a lack of subjects. The trouble with research extends to chronic traumatic encephalopathy, a degenerative disease caused by repetitive hits to the head. Although domestic violence researchers suggest that the population will develop CTE, which is only diagnosed post-mortem, a lack of donated brains means the disease has yet to be found among domestic violence victims.
by Heather Mongilio.
S.M. in Science Writing

Since the face forms over the brain in the course of embryonic development, facial anthropometry may reflect brain structure. The motor functions of each side are controlled by the side of the brain opposite the body side. The purpose of this study was to establish whether a correlation exists between handedness and the location of the external auditory meatuses, as a possible consequence of brain asymmetry. Facial photographs were taken of 78 volunteers. Straws, placed in the external ear canals, were used to mark the external auditory meatuses. The level of the top of each meatus was measured from each volunteer's visual plane, as established by connecting the center of a point of reflected light in each pupil. Each volunteer was also given the Edinburgh Laterality Inventory (Durden-Smith and DeSimone, 1984:53) to determine "true" handedness (50 right-handers and 28 left-handers). Right-handers, as determined by either writing hand or laterality inventory, were found to exhibit a greater tendency for the left auditory meatus to be lower. Specifically, 68% of the right-handers, as opposed to 39% of the left-handers, exhibited a left external auditory meatus located at a lower position on the skull than the right meatus. This was significant at the 0.05 level. The differences in external auditory meatal distances from the visual plane were greater on the left in right-handers 68% of the time, equal 10%, and greater on the right 22% of the time. A reverse correlation for the right asymmetry for left-handers was not found. Instead, for the left-handed sample a nearly even distribution for meatal location was found: 39% left asymmetry, 29% symmetry, and 32% right asymmetry.The study strongly supported the hypothesis that right-handers have a significant tendency for left asymmetry in location of the external auditory meatuses. The study did not support the hypothesis that the meatal asymmetry correlates to the side opposite the handedness of the individual. Of-perhaps greater significance is the finding that the percentages of left asymmetry of both groups match the brain asymmetry percentages found by Galaburda (1984:15) for the planum temporale, an extension on the upper surface of the temporal lobe of the brain. The level of the external auditory meatuses, as a reflection of brain asymmetry, may serve as an external measurement of the location of Wernicke's area which is located near the planum temporale and has a major role in speaking and comprehension of the spoken word and in reading and writing. Simple techniques for locating the language centers of the brain would be an advantage in developing education plans and teaching strategies for students with each of the possible hemispheric dominance patterns.
Department of Anthropology

Thesis (M.S.)--Kutztown University of Pennsylvania, 1992.
Source: Masters Abstracts International, Volume: 45-06, page: 2717. Abstract precedes thesis as 2 preliminary leaves. Typescript. Includes bibliographical references (leaves 53-54).

Recent research has argued that the intact functioning of both the left (LH) and right cerebral hemispheres (RE) is integral for comprehending lexically ambiguous words (Chiarello, 1998; Faust & Chiarello, 1998; Faust & Gemsbacher, 1996). While studies of neurologically intact individuals have attributed specific functions to the LH and RH, studies of brain-damaged patients have failed to provide complementary evidence for these hemispheric abilities. In addition, the majority of studies have focused on ambiguity resolution in single-sentence (local) contexts, and, as such, do not address whether each hemisphere is sensitive to different types of context, a factor which could potentially serve to modulate brain-damaged patients' ability to resolve ambiguity. To illuminate the role of the cerebral hemispheres in ambiguity resolution and to explore the sensitivity of each hemisphere to different types of context, three studies were undertaken in this thesis. The first study examined left-hemisphere-damaged (LHD) nonfluent aphasic, right-hemisphere-damaged (RHD) and non-brain-damaged (NBD) control subjects' ability to use a single-sentence local context to resolve lexically ambiguous words. Results indicated that both patient groups were unable to use this type of context. While LHD patients activated both meanings regardless of context at a short (0 ms) ISI and no meanings at a longer (750 ms) ISI, RHD patients only activated more frequent first meanings at both ISIs. The second study explored these same groups' ability to use a two-sentence global context. Results of this experiment in part paralleled those of the previous one, showing that LHD patients were unable to activate any meanings at either ISI, whereas RHD patients, at both ISIs, again activated more frequent meanings regardless of context. The final study investigated these individuals' ability to use a four-sentence discourse context. Findings of this study, across all groups,

The ability of the brain to change and form new neuropathways after brain injury is remarkable. The current study investigates the brains ability to form new pathways for language processing following traumatic brain injury (TBI), specifically a left temporal lobectomy. Two subjects participated in this study; one participant with TBI and one age-matched control. Sentence stimuli consisted of four types: semantically correct, semantically incorrect, syntactically correct, and syntactically incorrect. Participants underwent a fMRI scan while the auditory stimuli were presented in four blocks. Participants were asked to record if the sentence was correct or incorrect by pressing the corresponding button. It was found that reaction times for both the participant with TBI and the control were longer for the incorrect conditions. The participant with TBI generally had longer reaction times compared to the control participant and had more errors. During the fMRI scans, patient movement occurred. The block design was not set up to account for movement. Due to this factor, imaging results are questionable. While there were differences between the participant with TBI and the control participant, these differences are expected to be much larger in someone with this degree of brain injury. It is recommended for further studies to be conducted in this area with a revised block design to account for patient movement.

Though the current understanding of language processing is incomplete, it has been established that the left hemisphere is dominant for language in the majority of the population. Damage to language centers of the brain and to white matter tracts connecting these language centers results in a language deficit known as aphasia. Neuroplasticity in the brain can often compensate for these language deficits by strengthening neuronal connections between the right and left hemisphere, or by enhancing the neuronal connectivity of undamaged areas in the left hemisphere. Thus the brain can compensate for damaged language centers by using alternative cortical areas. These compensatory language areas may be homologous areas of the right hemisphere, or other undamaged portions of the left hemisphere. Various imaging techniques have been used to demonstrate this phenomenon. The current neuroimaging technique known as quantitative electroencephalographic brain imaging allows investigators to evaluate the functional anatomical location of language processing. When this mapping is overlaid on a magnetic resonance image, investigators are able to locate areas in the brain of the participant that are electrically activated during elicited speech tasks. This method was used in a single case study to examine the brain of an individual with a unique traumatic brain injury in which the anterior portion of the individual's left temporal lobe was surgically removed and considerable recovery of language subsequently occurred. The stimulus for the quantitative electroencephalography included identifying syntactically incorrect sentences. Imaging results from the participant with traumatic brain injury were compared to imaging results obtained from an age-matched control. Differences in quantitative electroencephalography between the two participants included a delayed P1-N1-P2 response and an absent P600 in the participant with traumatic brain injury. Behavioral results include an increased number of incorrect responses from the participant with traumatic brain injury as compared to the control participant. These results imply an interesting cortical distribution of language processing that could be further assessed by functional magnetic resonance imaging.

It is widely accepted that the left hemisphere of the brain is specialised and dominant for language comprehension and production and that those with left hemisphere damage often display profound language disruption (Geschwind, 1965). The importance of the left hemisphere is shown by communication problems or extreme difficulty in producing speech following damage to this brain region. In contrast, following right hemisphere damage, disruption to language is less perceptible to the casual observer. The evidence base currently available acknowledges a critical role for the right hemisphere in processing inferred or implied information by maintaining relevant facts and/or suppressing irrelevant ones but the exact role of the right hemisphere and its coordination with the left is open for debate (Johns, Tooley and Traxler, 2008). Two theories have been proposed to explain communication/language difficulties in individuals with right hemisphere damage: (i) the “coarse semantic coding” hypothesis and (ii) the “suppression deficit” hypothesis. The “coarse semantic coding” hypothesis proposes that damage to the right hemisphere causes an over reliance on fine coding assumed to be undertaken by the left hemisphere in the comprehension of language, implying the recall of most literal interpretations. The “suppression deficit” hypothesis proposes that damage in the right hemisphere means multiple activations of meanings of words are not attenuated leading to ineffective suppression of inappropriate interpretations. This project investigated competing evidence for each of these hypotheses by studying the processing abilities of individuals with depressed unilateral brain function caused by stroke or innovatively produced by transcranial DC stimulation (tDCS), on semantic judgement tasks using metaphorical language. The results demonstrated the strongest of evidence for the coarse semantic coding hypothesis when the data from participants with damage to the right hemisphere, both caused by stroke and simulated by tDCS was considered. Overall, the study has furthered the understanding of the role of the right hemisphere in language comprehension and demonstrated the contribution of the tDCS methodology in the field.

The purpose of this study was to examine whether or not the method of reading (either aloud or silently) would affect the reading comprehension performance of left hemispheredamaged (LHD) and non-brain-damaged (NBD) subjects across inference levels using the Nelson Reading Skills Test (NRST) (Hanna, Schell, & Schreiner, 1977). The experimental group was comprised of fifteen subjects who had suffered a cerebrovascular accident (CVA) to the left hemisphere of the brain. Subjects were selected after they had demonstrated an adequate level of function on the Short Porch Index of Conununicative Ability (SPICA) (DiSimoni, Keith, & Darley, 1980), to perform the tasks required in this study. Subjects were then randomly assigned to either "left hemispheredamaged aloud reading" or "left hemisphere-damaged silent reading" subgroups. The non-brain-damaged (NBD) control group consisted of fifteen individuals with no known history of neurological impairment. Control group subjects were also randomly assigned to either the "non-brain damaged aloud reading" subgroup or the "non-brain damaged silent reading" subgroup. All subjects were administered the revised version of the Nelson Reading Skills Test (NRST) (1977), Form 4 of Level B. NRST test questions can be grouped into three categories representing literal, translational, and high levels of inference. Subjects were required to read five paragraphs and answer thirty-three questions pertaining to the reading material by pointing to the correct answer from a list of four choices. Subjects were allowed to refer back to the paragraph when attempting to answer test questions. Results revealed total NRST performance to be significantly better for NBD subjects. Within both experimental and control groups, no significant difference was found to exist between the test scores of the oral and silent reading subgroups. The research data did not reflect the expected error pattern of most errors occurring on high inference level questions and fewest errors on literal inferences for either group of subjects.

This investigation was an attempt to replicate and expand previous research which suggested that laterality of electromyographic biofeedback input had a significant effect in lowering frontalis muscle activity. In 1984 Ginn and Harrell conducted a study in which they reported that subjects receiving left ear only audio biofeedback had significantly greater reductions in frontalis muscle activity than those receiving right ear only or both ear feedback. This study was limited to one biofeedback session and subjects were selected based on demonstration of right hand/ear dominance. The purpose of the present study was to determine whether the left ear effect reported by Ginn and Harrell could be replicated. Furthermore, the current investigation sought to extend the previous finding to left handed subjects and explore the stability of the effect, if found, by adding a second biofeedback session. Subjects were 96 students recruited from undergraduate psychology classes. They were screened for handedness by the Edinburgh Handedness Inventory which resulted in identification of 48 right handers and 48 left handers. Subjects were randomly assigned to one of four groups consisting of left ear feedback, right ear feedback, both ears feedback, and controls. This resulted in eight conditions. Analysis of variance of microvolt changes from baseline found no statistically significant differences between groups. An examination of the rank order of the data reveal a left ear group performance in the same direction as those reported by Ginn and Harrell (1984).

Savant syndrome is a rare condition in which some people have extraordinary talents despite some serious mental or physical disability. It is a syndrome with remarkable features, standing in stark contrast to a person’s overall character. The term savant, or idiot savant, describes a person who, in spite of low intelligence, has a skill in some specific narrow area. Savants can have a specific talent in, for instance, music, art, calendar calculation or foreign language but whatever the specific talent is, it is always connected to extraordinary memory. Savant syndrome seems to be also connected to autism or autistic characteristics. In this paper I aim to give a clear description of the savant syndrome and explain its connection to autism. Further, I present how specific theories try to describe the causes of savant syndrome, and connect the theories to results of empirical research in order to give an overall view of the syndrome’s appearance. I will also compare the theories and evaluate their strengths and weaknesses with respect to the discoveries and progress that has been made within the area of savant syndrome research.

Submitted by JULIANE ROSA POIATI null (jpoiati@yahoo.com.br) on 2017-07-26T13:28:20Z No. of bitstreams: 1 Tese Pronta recente.docx: 323161 bytes, checksum: 961cdd07383986392eeebc8675ed5302 (MD5)
Rejected by Luiz Galeffi (luizgaleffi@gmail.com), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: A versão final da dissertação/tese deve ser submetida no formato PDF (Portable Document Format). O arquivo PDF não deve estar protegido e a dissertação/tese deve estar em um único arquivo, inclusive os apêndices e anexos, se houver. Por favor, corrija o formato do arquivo e realize uma nova submissão. Agradecemos a compreensão. on 2017-07-26T19:10:07Z (GMT)
Submitted by JULIANE ROSA POIATI null (jpoiati@yahoo.com.br) on 2017-07-27T00:19:47Z No. of bitstreams: 1 Tese Pronta recente.pdf: 1203025 bytes, checksum: 3f33e46e228494eaa8c4c9ba0d1246d1 (MD5)
Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-07-31T14:34:20Z (GMT) No. of bitstreams: 1 poiati_jr_dr_bot.pdf: 1203025 bytes, checksum: 3f33e46e228494eaa8c4c9ba0d1246d1 (MD5)
Made available in DSpace on 2017-07-31T14:34:20Z (GMT). No. of bitstreams: 1 poiati_jr_dr_bot.pdf: 1203025 bytes, checksum: 3f33e46e228494eaa8c4c9ba0d1246d1 (MD5) Previous issue date: 2017-05-26
Objetivo: Determinar o valor da concentração do BNP que se associa à presença de hipertrofia do ventrículo esquerdo (VE) em mulheres com pré-eclâmpsia (PE). Métodos: Realizou-se estudo observacional, descritivo e transversal em gestantes com diagnóstico de pré-eclâmpsia, que receberam assistência obstétrica no Hospital das Clínicas da Faculdade de Medicina de Botucatu - Unesp. Foram excluídas do estudo gestantes portadoras de patologia clínica ou gestacional associada a alterações cardiovasculares (diabetes, hipertensão arterial crônica, cardiopatias, colagenoses, nefropatias). Considerando a prevalência de hipertrofia concêntrica do VE nessa população de 27% e assumindo a margem de erro de 10% e confiabilidade de 95%, o tamanho amostral calculado foi de 76 gestantes. No momento do diagnóstico de PE as gestantes selecionadas foram submetidas à coleta de sangue venoso para determinação da concentração sérica de BNP e ao exame de ecocardiograma para identificação de hipertrofia concêntrica do VE. As correlações entre o índice de massa do VE (iMVE) e entre a espessura relativa da parede (ER) e o BNP foram realizadas pelo teste de Spearman. O ponto de corte da concentração do BNP, que identifica hipertrofia concêntrica do VE, foi estabelecido pela curva ROC, utilizando-se o programa estatístico SPSS for Windows. Resultados: A hipertrofia concêntrica do ventrículo esquerdo foi diagnosticada em 48,7% das gestantes. O ponto de corte do valor da concentração do BNP, que identifica a hipertrofia concêntrica do VE, foi 203pg/mL (sensibilidade de 88%, especificidade de 80%, valor preditivo positivo de 69%, valor preditivo negativo de 93% e acurácia de 83%). A área sob a curva foi 0,87 (IC 95%= 0,79 – 0,95). A correlação entre o iMVE e a ER com a concentração do BNP foi significativa (iMVE: r=0,49; p<0,0001; ER: r=0,50; p<0,0001). Conclusões: O presente estudo encontrou correlação positiva entre os valores de BNP e hipertrofia do VE, além de determinar o ponto de corte (203 pg/ml) para o diagnóstico dessa condição. Utilizar o BNP como rastreamento de hipertrofia do VE pode ajudar na racionalização da indicação do ecocardiograma para confirmação diagnóstica.
Objective: To determine BNP concentration value associated with the presence of left ventricular hypertrophy (LV) in women with pre-eclampsia (PE). Methods: An observational, descriptive and cross-sectional study was performed in pregnant women diagnosed with preeclampsia, who have received obstetric care at Botucatu Medical School Clinical Hospital - Unesp. Pregnant women with clinical or gestational pathology associated with cardiovascular alterations such as diabetes, chronic hypertension, heart diseases, collagenosis, nephropathies were excluded from the study. Considering the prevalence of LV concentric hypertrophy in this population of 27% and assuming the margin of error of 10%, as well as reliability of 95%, the calculated sample size was of 76 pregnant women. At the moment of PE diagnosis the selected pregnant women were submitted to both venous blood collection (in order to determine BNP serum concentration) and to echocardiogram examination (to identify LV concentric hypertrophy). Correlations between LV mass index (iMVL), relative wall thickness (WT) and BNP were performed with Spearman test. The cut off of BNP concentration, which identifies LV concentric hypertrophy, was established with ROC curve, using the statistical program SPSS for Windows. Results: Left ventricular concentric hypertrophy was diagnosed in 48.7% of the pregnant women. The cut off value of BNP concentration, which identifies LV concentric hypertrophy, was 203pg / mL (sensitivity 88%, specificity 80%, positive predictive value 69%, negative predictive value 93%, and accuracy 83%). The area under the curve was 0.87 (95% CI = 0.79-0.95). The correlation between iMVL and WT with BNP concentration was significant (iMVE: r=0,49; p<0,0001; ER: r=0,50; p<0,0001). Conclusions: The present study found a positive correlation between BNP values and LV hypertrophy. Moreover, it determined the cut off (203 pg / ml) for the diagnosis of this condition. Therefore, using BNP as a screening method for LV hypertrophy may help to rationalize echocardiographic indication for diagnosis confirmation.

Heart failure is common, has a poor prognosis and can be treated. The incidence is increasing, partly because of improved survival after myocardial infarction and partly because the population is aging and heart failure is a disease of the elderly. Despite advances in our understanding of the pathophysiology of heart failure, the diagnosis of heart failure remains enigmatic and requires the skills of the physician. Those skills have not yet been superseded by technology. The natriuretic peptide family of hormones have been used extensively to study a range of cardiovascular disorders. Plasma levels of brain natriuretic peptide (BNP-32), are elevated following myocardial infarction and in patients with heart failure with well documented associations of BNP-32 with indices of left ventricular function and prognosis in patients suffering these conditions. Amino-terminal pro brain natriuretic peptide (NT-proBNP) is a recently identified processing fragment of preproBNP (y-BNP) which circulates in plasma in higher concentrations than BNP-32 itself and may represent a more competent marker of underlying left ventricular function. Measurement of plasma NT-proBNP may serve an objective and cost- effective method for investigating ventricular dysfunction in clinical practice. Another candidate peptide for assessing left ventricular systolic dysfunction is Cardiotrophin -1 (CT-1), a member of the growing family lnterleukin-6 (IL-6) related cytokines that function via the glycoprotein 130 signalling pathway. CT-1 was originally identified as a cytokine capable of inducing cardiac hypertrophy. More recent indications from animal work suggest a role for CT-1 in the pathogenesis of left ventricular dysfunction following myocardial infarction and in models of heart failure. There is a clear need to take a broader view of heart failure management and seek to apply improvements in diagnostic methods and treatment more widely in the community for the benefit of all eligible patients. Increased emphasis on the early detection of left ventricular systolic dysfunction and intervention to delay progression and improve long term outcome should be our main priority.

Les nouvelles techniques d’imagerie cérébrales, notamment les différentes modalités de l’imagerie par résonance magnétique (IRM), permettent pour la première fois dans l’histoire des neurosciences, d’étudier le cerveau humain in vivo. Ces technologies rendent désormais possible l’étude des symptômes provoquées par des lésions cérébrales chez les patients vivants. Mais ceci requiert le développement de nouvelles analyses, adaptées à ces données encore inaccessibles quelques décennies plus tôt. La plupart des méthodes actuelles pour relier des déficits neuropsychologiques aux dommages cérébraux se concentrent sur la région lésée elle même, négligeant les connexions structurelles et fonctionnelles affectées. Dans cette thèse, nous présentons tout d’abord un ensemble de méthodes, implémentées dans notre logiciel, le BCBtoolkit, permettant l’étude des déconnexions à la fois structurelles et fonctionnelles, ainsi que leur impact sur le comportement. Nous avons utilisé ces analyses pour cartographier les effets de lésions focales frontales sur la performance dans la tâche de fluence catégorielle. Nous présentons ensuite deux études dans lesquelles nous avons utilisé ces approches pour étudier les mécanismes cérébraux de plusieurs fonctions associées à la créativité. Et nous terminons cette thèse par une discussion sur les interactions entre les différentes structures du cerveau, qui permettent de générer les comportements humains. Nos études dévoilent la participation de nombreux réseaux, aussi bien structurels que fonctionnels, dans les différentes fonctions cognitives de haut niveau. Nous tentons, ultimement, de modéliser théoriquement leurs interactions
The new brain imaging techniques, notably the different magnetic resonance imaging (MRI) modalities, allow the study of the human brain in vivo for the first time in neuroscience's history. These technologies now make possible to study the symptoms caused by brain lesions in living patients. However, it requires the development of new analyses adapted for this new kind of data which was not available a few decades ago. Most of the classical lesion--symptom analyses are focused on the lesioned area, often neglecting the affected structural and functional connections. In this thesis, we begin by presenting a set of methods, implemented in our software the BCBtoolkit, enabling the study of both structural and functional disconnections and their effect on the behaviour. We applied these analyses to map the impact of focal brain lesions on the performance in category fluency. We then present two studies using this approach to investigate the underlying mechanisms of several cognitive functions associated with creativity. We finally discuss the possible interaction between the different brain structures, which generate human behaviours. Our studies unveil numerous networks, both structural or functional, participating in the different high-level cognitive functions. Ultimately, we propose a theoretical model for these interactions

FUNDAMENTOS: Na cardiomiopatia hipertrófica (CMH) a disfunção diastólica do ventrículo esquerdo (VE) é causada por hipertrofia dos miócitos e fibrose intersticial. A Angiotensina II (Ang II) pode promover hipertrofia, fibrose e alteração de relaxamento miocárdico. Na hipertrofia secundária a hipertensão o bloqueio dos receptores tipo 1 (AT1) da Ang II diminui a hipertrofia e a fibrose e, em animais com CMH losartan causou reversão da fibrose miocárdica. Os efeitos do antagonismo da Ang II na CMH humana não são conhecidos. OBJETIVOS: Avaliar os efeitos do losartan, um bloqueador dos receptores AT1 da Ang II, sobre a hipertrofia e a função diastólica do VE em pacientes com CMH não obstrutiva. CASUÍSTICA E MÉTODO: Foram estudados 27 pacientes consecutivos portadores de CMH na forma não obstrutiva, com média de idade de 34,4 anos, sendo 14 homens, que receberam losartan 100 mg/dia durante 6 meses. Antes do tratamento e ao final do mesmo foram avaliadas: a classe funcional (CF), a hipertrofia e a função diastólica do VE esquerdo pela ecocardiografia (modo-M, Doppler mitral, venoso pulmonar e Doppler tecidual do anel mitral) e a concentração plasmática do fragmento amino-terminal do pro-peptídeo natriurético tipo B (NT-proBNP). Valores bi-caudais de p<0,05 em testes pareados foram considerados estatisticamente significantes. v RESULTADOS: CF - dos 19 pacientes sintomáticos antes do tratamento, 8 (42%) tornaram-se assintomáticos (p=0,008). A CF média passou de 2,04±0,81 para 1,48±0,64 (p=0,0001). Doppler ecocardiografia - redução do diâmetro atrial esquerdo de 43,3±6,2 mm para 40,5±6,1 mm (p<0,0001), diminuição da velocidade da onda atrial reversa do fluxo venoso pulmonar de 36,4±9,7 cm/s para 32,2±6,2 cm/s (p=0,008), aumento da velocidade diastólica inicial (Ea) do anel mitral de 10,7±3,2 cm/s para 11,95±3,01 cm/s (p=0,004), aumento da razão Ea/Aa de 1,11±0,36 para 1,33±0,48 (p=0,009), e diminuição da razão E/Ea de 8,37±5,4 para 6,46±3,2 (p=0,004). Não ocorreram modificações nas espessuras parietais nem nos diâmetros do VE. NT-proBNP - diminuição do valor mediano de 652 pg/ml para 349 pg/ml, assim como dos quartis e dos valores máximo e mínimo (p=0,003). CONCLUSÃO: Em pacientes com CMH não obstrutiva o antagonismo da angiotensina II com losartan 100 mg/dia durante 6 meses resultou em melhora bioquímica e da função diastólica do VE, sem evidente regressão de hipertrofia ao ecocardiograma. Esses resultados são promissores e indicam possíveis benefícios que podem ser obtidos com medicamentos que atuam inibindo o sistema renina-angiotensina em pacientes com CMH.
BACKGROUND: In hypertrophic cardiomyopathy (HCM) diastolic dysfunction of the left ventricle (LV) is caused by myocite hypertrophy and interstitial fibrosis. Angiotensin II (Ang II) has trophic and profibrotic effects on the heart, and may impair myocardial relaxation. In hypertensive LV hypertrophy Ang II type 1 (AT1) receptors blockade can reverse hypertrophy and fibrosis, and in animals with HCM, losartan reversed myocardial fibrosis. The effects of Ang II antagonism in humans with HCM are unknown. OBJECTIVES: To evaluate the effects of losartan, an AT1 blocker, in patients with non-obstructive HCM, with emphasis on LV diastolic function. PATIENTS AND METHODS: 27 consecutive patients, mean age 34.4 years, 14 males, were treated with losartan 100 mg/day during 6 months. Evaluations were performed at baseline and at 6 months, as follows: functional class (FC), left atrium diameter (LAD), LV hypertrophy and LV diastolic function (M-mode echocardiography, mitral flow and pulmonary venous flow Doppler, mitral annulus tissue Doppler), and plasma concentrations of the amino-terminal fragment of proBNP (NT-proBNP). RESULTADOS: FC - of the 19 symptomatic patients before the treatment, 8 (42%) were free of symptoms at 6 months (p=0.008). There were no changes in LV wall and cavity measures. LAD decreased from 43.3±6.2 mm to 40.5±6.1 mm (p<0.0001), and pulmonary venous atrial reverse velocity decreased from 36.4±9.7 cm/s to 32.2±6.2 cm/s (p=0.008). Tissue Doppler: mitral annulus early diastolic velocity (Ea) increased from 10.7±3.2 cm/s to 11.95±3.01 cm/s (p=0.004), Ea/Aa ratio increased from 1.11±0.36 to 1.33±0.48 (p=0.009), and E/Ea ratio decreased from 8.37±5.4 to 6.46±3.2 (p=0.004). NT-proBNP - there was a decrease in the median value from 652 pg/ml to 349 pg/ml, as well as a decrease in quartiles, maximum and minimum values (p=0.003). CONCLUSION: In patients with non-obstructive HCM, treatment with losartan 100 mg/day during 6 months resulted in Doppler echocardiographic and biochemical changes indicative of LV diastolic function amelioration, in the absence of evident LV hypertrophy regression. These preliminary results are promising and suggest that inhibition of the renin-angiotensin system may be benefic in human HCM

Emotions and its effect on the individual’s general functioning are a key concept of humanity. The modern child is confronted with all kinds of emotional developmental tasks with direct influence on his ultimate figuration to adulthood. Emotion is an internal experience in contrast to the fact that various reactions are displayed externally as a result thereof. Children’s behavior demonstrates that which are experienced internally. It might also be a way to conceal especially those emotions. Emotional awareness manifests through demonstration or concealing of inner feelings. The child’s external reactions to inner feelings must be based on knowledge of what is being experienced. Behavior is mostly a reaction to ignorance of the inner experience which might manifest in anxiety attacks, anger and emotional episodes. Empowerment of the child to recognize and experience emotions enables him to gain insight of emotions as a natural part of human nature. This causes him to develop the ability to express emotion in a socially acceptable manner. The process of emotional awareness alerts the child to the fact those specific emotions results in specific bodily experiences. Emotional awareness is an indication of the child’s knowledge of emotions and its impact in emotional, physical and psychological reactions. It provides an explanation for anxieties and fears which enables the child to own these feelings and take control of it. The middle childhood phase is the period that follows the achievement of a mass of developmental skills like the mastery of language, control over bodily functions and cognitive abilities. These abilities are refined in this phase. Emotional awareness and especially concepts of self and the purpose of individuals in the systems that surrounds him evolves. Considerable part of the child’s day during this phase, is spent at school. Emotional wellbeing can thus efficiently be recognized and addressed by the educational system. The educator’s knowledge of emotional awareness will ensure meaningful emotional development of learners. Results obtained from questionaires completed by educators in primary education indicates a need for understanding of problem behavior in children. The need for education on emotional awareness and techniques for development of emotional awareness in learners is also expressed. The focus of this study is thus on the concept of educators regarding the emotional awareness of learners; the role of emotional awareness in the child’s development and the educators knowledge regarding development of emotional skills and promotion of emotional awareness.
Dissertation (MSD (Play Therapy))--University of Pretoria, 2006.
Social Work and Criminology
MSD
unrestricted

Kardijalni biomarkeri u predviđanju operativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore Evaluacija rezultata u kardiohirurgiji podrazumeva praćenje ishoda operativnog lečenja u određenom vremenskom periodu. Najčešće je to interval od 30 dana od datuma intervencije. Najčešći kriterijumi za praćenje su stopa mortaliteta i morbiditeta, dužina boravka u jedinici intenzivnog lečenja, ukupna dužina hospitalizacije i troškovi lečenja. Stratifikacija rizika podrazumeva da se bolesnici mogu podeliti u grupe u zavisnosti od broja i važnosti preoperativno utvrđenih faktora rizika, odnosno da se pre operacije može predvideti ishod hirurške intervencije kod svakog od njih pojedinačno. U Evropi je, u periodu između 1995. i 1999. godine, na osnovu multicentrične studije u 8 evropskih zemalja i 128 kardiohirurških centara u kojima je operisano 19.030 odraslih bolesnika, kreiran EvroSKOR - EuroSCORE (European System for Cardiac Operative Risk Evaluation) model za stratifikaciju rizika u kardiohirurgiji. Međutim, neminovne promene i napredak u operativnom lečenju doveli su do toga da je neophodno ažurirati postojeći sistem stratifikacije. Tako je 2012. godine u rutinsku upotrebu uveden novi sistem Euroscore II. Na Klinici za kardiohirurgiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV), EuroSCORE model uveden je u rutinsku upotrebu od početka 2001. godine. Analizom rezultata, posle dvogodišnje primene, pokazalo se da je model bio precizan, odnosno da nije postojala značajna razlika između očekivanog (3,7%) i stvarnog mortaliteta (3,47%). U poslednjih nekoliko godina, kod bolesnika kojima sledi kardiohirurška intervencija, u smislu razmatranja njihove prediktivne vrednosti, sve više pažnje se poklanja kardijalnim biomarkerima. Najznačajniji biomarkeri u kardiovaskularnoj medicini su: Troponin, Kreatin kinaza MB izoenzim (CKMB), N-terminalni pro B-tip natriuretski peptid (NT-proBNP), C-reaktivni protein (CRP), Laktat dehidrogenaza (LDH), Mokraćna kiselina (Acidum uricum). Ciljevi ovog rada su bili da se kreira model za predviđanje preoperativnog rizika kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore na osnovu preoperativnih vrednosti određenih biomarkera i da se kreira novi model sa kombinacijom prethodnog modela i već postojećeg modela EuroSCORE II. Ispitana su 704 bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcione frakcije manje ili jednake 50%. Bolesnici su operisani na Institutu za kardiovaskularne bolesti Vojvodine, od 20. januara 2014. do 20. aprila 2016. Kod bolesnika su urađene tri vrste operacija: revaskularizacija miokarda-koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije. Od biohemijskih analiza, 24 sata pre operacije, urađene su sledeće analize: troponin I, kreatin kinaza, kreatin kinaza MB izoenzim, masena kreatin kinaza, laktat dehidrogenaza, C-reaktivni protein, NT-proBNP i mokraćna kiselina. Praćen je postoperativni mortalitet, postoperativni infarkt miokarda i postoperativni cerebrovaskularni incident i njihova povezanost sa preoperativnim vrednostima nabrojanih biomarkera. U studiju su bili uključeni svi bolesnici sa stečenim bolestima srca, stariji od 18 godina, kod kojih je ejekciona frakcija leve komore bila manja ili jednaka 50% i kod kojih su izvršene sledeće vrste operacija: revaskularizacija miokarda - koronarna hirurgija, hirurgija stečenih srčanih mana - valvularna hirurgija i kombinovane operacije - koronarna i valvularna hirurgija. Rezultati su pokazali da je postoperativni mortalitet bio 3,13%, da je postoperativni infarkt miokarda imalo 7,95% a postoperativni cerebrovaskularni incident 9,23% od ukupnog broja ispitanika. 1. Povezanost vrednosti biomarkera sa postoperativnim infarktom miokarda kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I su bile povezane sa postoperativnim infarktom miokarda. Povezanost preoperativnih vrednosti biomarkera sa postoperativnim cerebrovaskularnim incidentom kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore: povišene preoperativne vrednosti troponina I i CRP-a su bile povezane sa postoperativnim cerebrovaskularnim incidentom. 2. Analiziran je uticaj preoperativnog nivoa svih biomarkera, pojedinačno, na značajne neželjene kardijalne i cerebrovaskularne događaje - Major Adverse Cardiac and Cerebrovascular Events (MACCE) kao ishod posle operacije na srcu, kod bolesnika sa oslabljenom ejekcionom frakcijom leve komore. Dobijeni su sledeći rezultati: Preoperativna vrednost nivoa troponina I veća od 0,01μg/L i MACCE bili su povezani. Povećane preoperativne vrednosti nivoa C-reaktivnog proteina (CRP) i postoperativni MACCE bili su povezani. Povećane preoperativne vrednosti nivoa laktat dehidrogenaze (LDH) i MACCE bili su povezani. Zaključci ove teze su: 1. Nezavisni prediktor postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, jeste povišena preoperativna vrednost troponina I. 2.Vrednost preoperativnog troponina I je slab marker za predviđanje postoperativnog infarkta miokarda i značajnih neželjenih kardijalnih i cerebrovaskularnih događaja, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 3. Na pojavu postoperativnog cerebrovaskularnog incidenta, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, ne utiče nijedna od ispitivanih varijabli. 4. Nezavisni prediktori postoperativnog mortaliteta kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%, na osnovu kojih je moguće kreirati prediktivni Model su godine starosti i povišene preoperativne vrednosti NT-proBNP. 5. Kreirani Model je dobar marker za predikciju ishoda posle operacije na srcu, kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 6. Povišena preoperativna vrednost NT- proBNP može da bude dobar marker u predikciji smrtnog ishoda posle operacije na srcu kod bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 7. Model EuroSCORE II se pokazao kao slabiji marker za predikciju ishoda posle operacije na srcu kod kardiohirurških bolesnika sa oslabljenom sistolnom funkcijom leve komore, ejekcionom frakcijom manjom ili jednakom 50%. 8. Testiranjem kreiranog modela, podelom na manje rizične i više rizične bolesnike, u odnosu na visinu ejekcione frakcije leve komore, pokazalo se da je model dobar marker za predviđanje smrtnog ishoda posle operacije na srcu, u obe grupe.
Cardiac surgery operative risk assessment in patients with imapired systolic left ventricular function using cardial biomarkers Evaluation of results in cardiac surgery involves monitoring the outcomes of operative treatment in a given time period. Typically, this interval includes 30 days from the date of operation. The most common criteria used for monitoring are the rate of mortality and morbidity, length of stay in the intensive care unit, the total length of hospitalization and medical costs. Risk stratification means that patients can be divided into groups depending on the number and importance of preoperatively identified risk factors, and that the outcome of surgery for each of the patients can be predicted preoperatively. In Europe, in the period of 1995-1999 on the basis of a multi-center study in 8 European countries and 128 cardiac centers in which 19,030 adult patients were operated on, EuroSCORE (European System for Cardiac Operative Risk Evaluation) model for risk stratification in cardiac surgery was developed. However, the inevitable changes and progress in the surgical treatment rendered the EuroSCORE model obsolete warranting updated system. It was in 2012 when a new system EuroSCORE II was introduced into practice At the Clinic for Cardiac Surgery of the Institute of Cardiovascular Diseases, EuroSCORE model was introduced in routine clinical use since the beginning of 2001. By analyzing the results, two years after application, it was shown that the model was accurate, and that there was no significant difference between the expected (3.7%) and the actual mortality (3.47%) In recent years, in patients who are candidates for cardiac surgery, more attention is paid to cardiac biomarkers in terms of evaluating their predictive power. The most significant biomarkers in cardiovascular medicine are: Troponin, creatine kinase MB isoenzyme (CKMB), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), Lactate dehydrogenase (LDH), and uric acid (Uric uricum). The objectives of this study were to create a model to predict preoperative risk for cardiac surgery patients with impaired systolic left ventricular function on the basis of preoperative levels of certain biomarkers and to create a new model with a combination of the previous model and already existing EuroSCORE II model. The study included 704 patients with impaired systolic left ventricular function, ejection fraction less than or equal to 50%. All patients underwent cardiac surgery at the Institute of Cardiovascular Diseases, from January 20th 2014 until 20th April 2016. Patients were submitted to three types of operations: revascularization - coronary surgery, surgery of acquired heart defects - valvular surgery and combined operations. Following biochemical analyses were performed 24 hours prior to surgery: troponin I, creatine kinase, creatine kinase MB isoenzyme, mass creatine kinase, lactate dehydrogenase, C-reactive protein, NT-proBNP and uric acid. Postoperative mortality, postoperative onset of myocardial infarction and occurence of cerebrovascular accident and their correlation with preoperative values of listed biomarkers were registered. The study included all patients with acquired heart disease, older than 18 years, with the left ventricular ejection fraction less than or equal to 50% who were submitted to the following types of operations: revascularization - coronary surgery, surgery of acquired heart diseases - valvular surgery and combined operations - coronary and valvular surgery. The results showed that the postoperative mortality was 3.13%, new onset of postoperative myocardial infarction was detected in 7.95% of the patients and postoperative cerebrovascular accident developed in 9.23% of patients. Correlation of preoperative biomarkers values with postoperative myocardial infarction in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I were associated with postoperative myocardial infarction. Correlation of preoperative biomarkers values with postoperative cerebrovascular incident occurence in patients with impaired left ventricular ejection fraction - elevated preoperative troponin I and CRP were associated with postoperative cerebrovascular incident. The influence of preoperative levels of all biomarkers, separetly, on the rate of significant adverse cardiac and cerebrovascular events - Major Adverse Cardiac and Cerebrovascular Events (MACCE) as the heart surgery outcome, in patients with impaired left ventricular ejection fraction. The following results were obtained: Increased preoperative levels of C-reactive protein (CRP) and postoperative MACCE were related. Increased preoperative levels of lactate dehydrogenase (LDH) and MACCE were related. The conclusions of this thesis are: 1. Independent predictor of postoperative myocardial infarction onset and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%) is elevated preoperative value of troponin I. 2. Preoperative Troponin I value was poor marker for predicting postoperative myocardial infarction and significant adverse cardiac and cerebrovascular events in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 3. None of the studied variables showed influence on the postoperative cerebrovascular accident occurence, in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 4. Independent predictors of postoperative mortality in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%), that could be used to create a predictive model are: age and elevated preoperative value of NT-proBNP. 5. Developed model showed satisfactory results for predicting outcome after heart surgery in cardiac surgery patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 6. Elevated preoperative value of NT-proBNP may be a good marker for mortality prediction after the cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 7. EuroSCORE II model showed poor performance when predicting outcomes after cardiac surgery in patients with impaired systolic left ventricular function (ejection fraction less than or equal to 50%). 8. Validation of the newly-created model, considering low and medium risk patients, based on the value of left ventricular ejection fraction, showed that the model is a good marker for the mortality prediction in both groups.

Plusieurs modèles compartimentaux ont déjà été développés pour représenter le métabolisme desneurones et astrocytes. De tels modèles impliquent un trop grand nombre de variables pour êtreaccessibles à l’analyse mathématique et jusqu’à maintenant ils n’ont été discutés que par le biais desimulations numériques. Le point de vue adopté ici est de réduire la contribution de plusieurscompartiments en un terme de forçage, ne conservant que quelques variables dynamiques, et decaractériser ces termes de forçage qui sont compatibles avec les observations expérimentales. Nousdiscutons d’abord un système forcé à deux dimensions puis nous passons à un système à quatredimensions, qui permet alors de faire la distinction entre neurones et astrocytes. Nous nousconcentrons dans ces deux cas sur la compréhension de deux phénomènes important observésexpérimentalement. Le premier est la déflexion initiale ou dip initial de la concentration de lactateextracellulaire rapportée pour la première fois par Hu et Wilson, visualisée in vivo après unestimulation électrique de l’hippocampe d’un rat. L’autre est l’accrochage des fréquences en réponse àl’application d’une séquence périodique de stimulus, observé par Hu et Wilson, et discuté plus tard parl’équipe Aubert-Costalat-Magistretti-Pellerin, sur la base de simulations numériques du systèmeAubert-Costalat. Plus précisément, le dip initial peut être parfaitement expliqué dans le cadre d’unedynamique lente-rapide, par le théorème de l’existence d’une variété lente quand la variété critique estattractive. L’accrochage des fréquences est discutée à la fois au travers de simulations numériques deMatlab et d’une analyse mathématique des systèmes forcés lents-rapides
Several compartmental models have been developed to represent the metabolism of neurons andastrocytes. Such models involve too many variables to be accessible to mathematical analysis and untilnow they were only discussed via numerical simulations. The viewpoint adopted here is to reduceseveral compartments contributions into a forcing term, keeping very few dynamical variables, andcharacterize these forcing terms which are compatible with the observations. We first discuss a twodimensionalforced system and then move to a four-dimensional system which allows to distinguishbetween neurons and astrocytes. We focus on these two cases in the understanding of two importantphenomena observed in experiments. One is the initial dip in the extracellular lactacte concentration,first reported in vivo by Hu and Wilson on rat brain hippocampus after an electrical stimulation. Theother is a frequency locking response to the application of a periodic sequence of stimuli, alsoobserved by Hu and Wilson, and further discussed by Aubert-Costalat-Magistretti-Pellerin, on thebasis of numerical simulations of the Aubert-Costalat system. More precisely, the initial dip can bewell explained, in the setting of fast-slow dynamics, by the theorem of existence of slow manifoldwhen the critical manifold is transversally attractive. The frequency locking is discussed both viaMatlab numerical simulations and mathematical analysis of forced fast-slow systems

Tout ce qui vit, naît, se nourrit, se reproduit et meurt. Pour le cerveau, la question se complexifie car à la survie des neurones s'ajoute le coût de l'activité cérébrale. La question de la gestion énergétique pour les neurones est particulière car les cellules de notre cerveau évoluent de manière concertée et non par compétition. On sait avec l'imagerie médicale que l'usine neuronale ne fonctionne pas uniquement grâce au glucose ; elle utilise d'autres apports énergétiques tels que le lactate ou le glutamate pour soutenir sa production. Lorsqu'une tumeur apparaît, elle change le métabolisme énergétique pour survivre et soutenir sa propre croissance. En particulier, les cellules cancéreuses se fournissent en lactate et choisissent leur substrat préféré en fonction de l'oxygène disponible. La modélisation mathématique des substrats énergétiques est un outil de choix pour décrire et prédire de tels flux. Coupler ces modèles à des données issues de l'IRM et de la SRM permet d'améliorer la prise en charge du patient présentant un gliome.Cette thèse propose l'approche de plusieurs dynamiques en substrat dans le cerveau sain et gliomateux en se basant sur des systèmes d'équations : échanges locaux en lactate (EDO, système lent-rapide), échanges globaux en substrats (EDO), cycle glutamate/glutamine (EDR) et échanges en lactate en dimensions supérieures (EDP). Ces modèles sont expliqués, décrits grâce aux mathématiques et permettent l'élaboration de simulations ajustées selon des données patient ou issues de la littérature.L'énergie est nécessaire au maintien de la vie. Mais si votre voisin consomme une partie de vos ressources, pouvez-vous encore espérer survivre ?
Everything that lives is born, eats, reproduces and dies. For the brain, the question is more complex because neurons have to survive and to support brain activity. Energy management is also particular because brain cells evolve together with no competition. Thanks to medical imaging, we know that neurons do not consume only glucose. They can use others energetic substrates such as lactate and glutamate as a power source.When a tumor appears, it changes the energetic metabolism to survive and support its own growth. In particular, cancer cells like to consume lactate. They also choose their favorite substrate based on the available oxygen. Modeling of energy substrates is useful to describe and predict energetic kinetics and changes. Mathematical models could get with clinical and medical results to describe, explain or predict low grade glioma dynamics. They can help to characterize and quantify a tumor evolution, then leading to improve their therapeutical management. Exchanges between mathematics and MRI (and MRS) enable to get accurate data and to build suitable mathematical models.This thesis deals with several approaches of substrates dynamics in healthy and gliomatous brains. These researches are based on systems of equations. We model local lactate exchanges (ODE, fast-slow systems), global substrates exchanges (ODE), glutamate/glutamine cycle (RDE) and local lactate exchanges in higher dimensions (PDE). We describe, analyze and give simulations of these models. Simulations are fitted on patient MRI data or literature data. Energy is necessary to live. But if your neighbor consumes a part of your resources, can you still survive ?
Tutto ciò che vive nasce, si nutre, si riproduce e muore. Per il cervello, la questione è più complessa perché i neuroni devono sopravvivere e sostenere l'attività cerebrale. La gestione energetica cerebrale è particolare anche perché le cellule cerebrali evolvono insieme, senza concorrenza. Inoltre, grazie alle immagini mediche, sappiamo che i neuroni non consumano solo del glucosio ma usano altri substrati energetici come il lattato o il glutammato.Quando un tumore si stabilisce, cambia il metabolismo energetico del cervello per sopravvivere e sostenere la propria crescita. In particolare, cellule tumorali consumano del lattato e scelgono il loro substrato preferito basandosi all'ossigeno disponibile.La matematica, e in particolare l'elaborazione di modelli matematici può aiutarci a ottimizzare i dati disponibili, che possono essere, di volta in volta, delle proprietà cellulare o delle lastre MRI o MRS. La modellizzazione dei substrati energetici potrebbe descrivere, spiegare o prevedere le dinamiche energetiche nel cervello.Questa tesi tratta di diversi approcci della dinamica dei substrati nei cervelli sani e gliomatosi. Queste ricerche si basano su sistemi di equazioni. Modellizziamo scambi locali di lattato (ODE, sistemi fast-slow), scambi globali di substrati (ODE), ciclo glutammato/glutammina (RDE) e scambi locali di lattato in dimensioni superiori (PDE). Descriviamo, analizziamo e diamo simulazioni di questi modelli. Le simulazioni sono adeguate su dati MRI paziente o dati di letteratura.Per vivere, l’energia è una necessità. Ma se i Suoi vicini consumassero le Sue risorse, riuscirebbe ancora a sopravvivere ?

碩士
長庚大學
職能治療學系
99
Background : Apraxia is a common symptom in patients with left brain damage (LBD) or right brain damage (RBD). Current studies and clinical uses in the area of praxis usually focus more on imitating and pretending tool-use, the real tool-use is less discussed. This study aimed to discuss tool-using performance in patients with left and right brain injury. Methods: Fifteen pairs of LBD and RBD stroke patients matched by age and education participated in the study. All patients were right handed. In the experiment, each patient had to pretend, imitate and really use 10 different tools under two sequential conditions (single step and multiple step) with the ipsilesional limb. The method used to evaluate praxis was applied to analyze the error types of performance during each condition. Besides, the sensori-motor, cognitive, and speech function were also evaluated and treated as the controlled variables. Results: The results reveal (1) The LBD group made significantly more qualitative errors than RBD group in condition of pretending, imitating and really using tools. (2) The LBD group made significantly more qualitative errors than RBD group in single and multiple step conditions. Discussions and conclusions: The LBD group produced a wide range of spatiotemporal and conceptual errors in all conditions, while the RBD group made specific temporal errors - occurrence in all conditions. The findings of this study support the postulate that the left hemisphere stores the spatiotemporal and conceptual representations of learned skilled movement, while the sequential program is represented by left hemisphere, too. Finally, a more complete model than those used in the literature review based on findings of this present study is proposed.

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2013
During neonatal life, elevation of unconjugated bilirubin (UCB) levels may lead to minor neurological dysfunction or even to bilirubin encephalopathy (kernicterus). The pathogenesis of this condition involves UCB passage across the blood-brain barrier (BBB), but it is still unknown the role of this barrier in the consequent brain injury. Thus, this thesis intended to investigate the response of human brain microvascular endothelial cells (HBMEC), a simplified in vitro model of the BBB, to UCB, to evaluate the modulation of these effects by therapeutic molecules, and to dissect the neuro-glialvascular alterations in brain parenchyma of neonatal kernicterus cases.First, we observed that HBMEC incubation with UCB induced cell death,cytokine release and oxidative stress. As some of the molecules that the HBMEC produced are known modulators of permeability and angiogenesis, we continued our studies with the evaluation of barrier integrity. Our second study showed that prolonged exposure to high concentrations of UCB caused monolayer fragility and compromised barrier integrity. To complement these studies, we investigated the action of the neuroprotective bile acids, ursodeoxycholic acid (UDCA) and glycoursodeoxycholic acid (GUDCA) against UCB toxicity. The bile acids showed optimal protective abilities in distinct parameters: GUDCA was effective in preventing cell death, while UDCA reduced the production of angiogenic-related molecules and prevented the elevation of permeability. Importantly, the bile acids efficiency was demonstrated in a broad window of opportunity, with both protective and recovery properties. Next, we continued our work by analysing brain regions with great susceptibility to bilirubin, as the cerebellum, hippocampus and basal ganglia, which showed marked neuronal loss. Additionally, the results revealed new players in the neuropathology of kernicterus, including increased vascularization and dysfunction in several BBB components, as astrocytes, pericytes and basement membrane.In conclusion, high levels of UCB compromise endothelial integrity, mainly after prolonged exposure, ultimately leading to BBB breakdown and enhanced UCB passage into the brain. Additionally, our data shows the potential of UDCA and GUDCA as preventive, but also restorative therapeutic molecules against UCB-injury. Moreover, evaluation of kernicterus cases suggests a link between region-specific susceptibility and marked vascular dysfunction. These findings contribute to a better understanding of the neurotoxic steps involved in the irreversible brain damage cause by severe jaundice.
Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/61646/2009, projetos PEst-OE/SAU/UI4013/2011 e PTDC/SAU-FCF/68819/2006)

Tese de mestrado. Biologia (Biologia Evolutiva e do Desenvolvimento). Universidade de Lisboa, Faculdade de Ciências, 2013
The vertebrate brain is functionally and anatomically left-right (L-R) asymmetric, yet how these asymmetries arise and are maintained during development is still poorly understood. ln zebrafish, the epithalamus comprises some of the most conspicuous asymmetries found in vertebrates, making it a valuable model to study their development. In it left and right dorsal habenulae (dHb) develop differently in size, cytoarquitecture and axonal connectivity. Additionally, the parapineal organ migrates to the left side and exclusively projects to the left habenula (lRb), being required for the development of its molecular and subsequent cytoarchitectural left-sided identity. Several studies have shown that Nodal Wnt and Notch signalling pathways have an important role in dHb asymmetric specification. However, how they interact with each other to achieve this is still largely unknown. Through a forward genetic screen our lab has identified the narcissus mutation which induces defects in the asymmetric specification of dRb neurons. Here, we show that in narcissus mutants, both habenulae display symmetric expression of some, but not all, 1Hb markers, and that the asymmetric afferent projections to the interpeduncular nucleus (IPN) and efferent innervation from the olfactory bulb and parapineal are disrupted. Additionally, both habenulae display significantly less BrdU incorporation in two tested timepoints, but asymmetric early neurogenesis still occurs. Together, our findings demonstrate that narcissus is required for the correct specification of L-R asymmetries in the zebrafish brain and provide a valuable background for future studies to decipher its role in the establishment and maintenance of these asymmetries during embryonic development.
O cérebro é essencialmente assimétrico em termos anatómicos e funcionais, estando descritas assimetrias entre a esquerda e a direita no sistema nervoso de espécies representativas de praticamente todas as classes de vertebrados. De facto, há muito se sabe que várias funcionalidades se encontram extremamente lateralizadas no cérebro humano, como é o exemplo do processamento da linguagem, dominante no hemisfério esquerdo, e certas capacidades visuoespaciais no hemisfério direito. Mais recentemente, vários estudos mostraram haver uma relação positiva entre cérebros pouco lateralizados e deficiências congénitas de linguagem, como no caso da dislexia, levando à hipótese de que estas poderão estar ligadas a problemas no estabelecimento de assimetrias durante o processo ontogénico. Apesar disto, pouco se sabe atualmente sobre como as assimetrias de esquerda-direita (E-D) aparecem e como são mantidas durante o desenvolvimento embrionário do sistema nervoso. Há vários anos que o peixe-zebra tem provado ser um modelo valioso na área da biologia do desenvolvimento de vertebrados, muito devido ao seu bem caracterizado sistema genético, à facilidade de manipulação genética e celular e às suas propriedades óticas que facilitam técnicas de microscopia in vivo. No estudo do estabelecimento de assimetrias E-D, o peixe-zebra apresenta-se como particularmente útil. Neste organismo, a região cerebral do epitálamo, composta pelas habénulas e pelo complexo pineal, apresenta várias assimetrias entre a esquerda e a direita a nível citoarquitectónico, de expressão de genes e connectividade neuronal. A habénula dorsal do lado esquerdo é ligeiramente maior que a do lado direito, possuindo também uma maior concentração de neuropilo e expressão diferencial de genes. Esta diferença de expressão é na verdade tão acentuada, que permite a divisão dos núcleos da habénula nos subnúcleos lateral, demarcado pela expressão de kctd12.1, e medial, que expressa kctd12.2, e cujo tamanho é também proporcionalmente maior na esquerda e direita, respetivamente. Adicionalmente, o órgão parapineal, que origina de um subconjunto de células anteriores da glândula pineal, migra para o lado esquerdo e estabelece projeções axonais exclusivamente com a habénula esquerda, sendo inclusivamente necessário para a correta especificação dos neurónios do sub-núcleo lateral nesse lado. Cada habénula projeta também diferencialmente para o núcleo interpeduncular, situado no mesencéfalo, onde a região dorsal e ventral é inervada preferencialmente pelas habénulas esquerda e direita, respetivamente. Como se estabelecem estas assimetrias é ainda um tópico de grande debate. Sabe-se que a sinalização de Nodal, um dos primeiros eventos a quebrar a assimetria no embrião e necessária para o correto estabelecimento das assimetrias viscerais, possui também um papel crucial no estabelecimento das assimetrias epitamâmicas. Nodal é normalmente expresso no lado esquerdo do diencéfalo durante as primeiras fases do desenvolvimento, atuando como um bias no estabelecimento da lateralidade das assimetrias. De facto, vários estudos apontam para uma troca de informação entre a assimetria visceral e epitalâmica, sendo a primeira necessária para o estabelecimento da última através de uma interação mediada pela via de sinalização Wnt. Vários estudos apontam na verdade para o requerimento de algumas das maiores vias de sinalização para o correto estabelecimento e manutenção de assimetrias no epitálamo. Para além de necessária para a quebra de assimetria inicial, a sinalização Wnt tem também um papel crucial na correta especificação dos sub-núcleos habenulares, pois a sua inibição através de tratamentos farmacológicos ou por mutações genéticas induz a diferenciação de um maior rácio de neurónios do sub-tipo dorsal lateral em ambas as habénulas, assumindo estas uma especificação característica de esquerda. Adicionalmente, a via de sinalização Notch parece estar envolvida na manutenção da cronologia do programa de neurogénese diferente entre esquerda e direita, mostrando-se essencial para a especificação diferencial dos neurónios dos dois lados. De facto, a maior parte dos neurónios do sub-núcleo lateral nasce por volta das 32 horas-pós-fertilização (hpf) enquanto que neurónios do sub-núcleo medial nascem mais tarde às 48 hpf. Apesar de várias hipóteses serem apontadas para esta assimetria, a mais plausível assenta na ideia de que na direita, uma ativação assimétrica da sinalização Notch leva a uma mais longa manutenção da população de células estaminais, inibindo assim a neurogénese nesse lado. Apesar deste conhecimento, pouco se sabe em relação a como interagem estas vias de sinalização para o estabelecimento de assimetrias no epitálamo. Para melhor compreender isto, o nosso laboratório realizou um screening genético para identificar mutações que resultem em problemas de assimetria epitalâmica. Um destes mutantes, narcissus (nss), é caracterizado pela bilateralidade de marcadores característicos da habénula esquerda, como kctd12.1, e sub-expressão de marcadores da habénula direita, como kctd8. Neste estudo, procurei caracterizar em maior detalhe o mutante narcissus e tentei identificar os mecanismos através dos quais este gera as perturbações de assimetria observadas. Nos mutantes narcissus, todas as projeções aferentes e eferentes assimétricas para e das habénulas estão afetadas. Apesar da parapineal migrar corretamente para a esquerda, as suas projeções para a habénula esquerda possuem uma distribuição mais extensa do que em embriões controlo, cujas projeções tendem a acumularem-se em regiões mais próximas da habénula. Adicionalmente, a projeção assimétrica para a habénula direita, proveniente de células mitrais no bolbo olfactório e marcadas pela expressão do transgénico Tg(lhx2a:gap-YFP) estão completamente ausentes nos mutantes narcissus. Este defeito não será no entanto a provável causa da expressão simétrica de kctd12.1, pois a ablação seletiva destas projeções em embriões controlo antes da formação da enervação no epitálamo não revelou qualquer alteração de expressão de kctd12.1 e do marcador da habenula direita kctd8. Inesperadamente, ambas as habénulas projetam também preferencialmente para a região ventral do núcleo interpeduncular, um fenótipo provavelmente causado por uma deficiência da sinalização de orientação axonial mediada por Nrpla/Sema3D, intimamente responsável por esta conexão. Ao contrário de outros mutantes onde marcadores da habénula esquerda são bilateralmente expressos, nos mutantes de narcissus, a expressão de Pku558b, que marca maioritariamente uma sub-população de neurónios na habénula do sub-tipo dorsal lateral, continua assimétrica aos 4 dias pós-fertilização (dpf). Por outro lado, a expressão de kctd12.1 começa por ser assimétrica até 2 dpf, apenas adquirindo bilateralidade aos 3 dpf. Através da análise da data do nascimento dos neurónios dos diferentes sub-núdeos habenulares, identificámos que nos mutantes narcissus ocorre significativamente menos proliferação nas habénulas às 32 e às 50 hpf, dois estádios do desenvolvimento em que a maioria dos neurónios dos dois sub-núcleos nascem. Este resultado sugere um mecanismo em mutantes onde uma diminuição da população de progenitores habenulares pode ser responsável pelos fenótipos observados. Apesar disto, a neurogénese assimétrica inicial mantém-se intacta nos mutantes narcissus. Em conclusão, neste trabalho demonstrámos que narcissus é crucial para o desenvolvimento das assimetrias no epitálamo do peixe-zebra, providenciando um valioso conhecimento para o decifrar do seu papel no estabelecimento e manutenção destas assimetrias em estudos futuros.

博士
國立臺灣大學
生化科學研究所
105
Left-right asymmetric patterning is important for proper development of visceral organs and neurogenesis that is dependent on the appropriate activity of Nodal signaling. In zebrafish, after breaking the left-right symmetry by nodal flow inside Kupffer''s vesicle (KV), ndr3 (Nodal-related 3) is asymmetrically expressed in the left lateral plate mesoderm (LPM) and turns on downstream genes encoding the Nodal ligands (ndr2 and ndr3 itself), the antagonists of Nodal ligands (lft1 and lft2), and the downstream effector of Nodal signaling (pitx2). This Self-Enhancement and Laterality Inhibition system of Nodal signaling are considered as a conserved molecular cascade across species to control their temporal and spatial expression precisely. Zebrafish caudal-related homeobox 1b (cdx1b) belongs to the caudal type homeobox (cdx) gene family, which has been implicated in anterior-posterior axial patterning and intestinal development across diverse bilaterians. Previous studies have shown that zebrafish Cdx1b regulates early endoderm formation and differentiation of various intestinal cell lineages. In this thesis, a new role of Cdx1b in left-right asymmetrical patterning was discovered. Knockdown of cdx1b by specific antisense morpholino oligonucleotides (MOs) caused the loss of left-laterality in the epithalamus, the failure of heart looping, and isomerism or situs inversus of visceral organs. In the cdx1b-knockdown embryos (cdx1b morphants), left-sided expression of Nodal signaling genes (ndr3, lft1, lft2, and pitx2c)were altered in the LPM, and expressions of ndr2, lft1 and pitx2c were not detected in the left dorsal diencephalon during the late somite and early pharygula stages (18-26 hpf). During the early- somite stages (4-6 somite stages), the cilia of KV were shortened and the Nodal flow was weakened in the cdx1b morphants. The symmetric right-sided expression of charon (the antagonist of Nodal around KV) was also altered in the cdx1b morphants. Knockdown of cdx1b reduced the expression of ndr2, lft1, and pitx2c in the prechordal plate and the anterior ventral neuroectoderm at the bud stage. In addition, decreased expression of gsc, a downstream target of Nodal signaling in the prechordal plate and ventral neuroectoderm, and shh, a structure marker of these tissues, were observed in the cdx1b morphants. These results indicate that Cdx1b is important for patterning of the Nodal-induced anterior mesendoderm and the anterior ventral neuroectoderm. Based on motif predictions by the JASPAR and UCSC websites, chromatin immunoprecipitation results showed that Cdx1b can bind on the conserved promotor/enhancer region of ndr2 (chr12:49,427,858-49,428,038) and lft1 (chr20:35,102,628-35,102,818). Together, these results suggest that Cdx1b may regulate transcription of ndr2 and lft1 to maintain proper activity of Nodal signaling that is essential for the mesendoderm induction, the anterior neurulation and subsequent establishment of laterality of epithalamus in the zebrafish embryo.

BACKGROUND: Social cognitive ability is a significant determinant of functional outcome and deficits in social cognition are a disabling symptom of psychotic disorders. The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits. Using ‘resting-state’ fMRI (functional magnetic resonance imaging) and a trans-diagnostic, data-driven analytic strategy, we sought to identify the brain network basis of emotional intelligence, a key domain of social cognition. METHODS: Subjects included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 46 healthy comparison participants from three different sites: Beth Israel Deaconess Medical Center, Boston, MA, McLean Hospital, Belmont, MA, and University of Pittsburgh, Pittsburgh, PA. All participants underwent a structural T1/MPRAGE and resting-state fMRI scan. Emotional Intelligence was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). A connectome-wide analysis of brain connectivity examined how each individual brain voxel’s connectivity correlated with emotional intelligence using multivariate distance matrix regression (MDMR). RESULTS: We identified a region in the left superior parietal lobule (SPL) where individual network topology predicted emotional intelligence. Specifically, the association of this region with the Default Mode Network (DMN) predicted higher emotional intelligence (r = 0.424, p < 0.001) and association with the Dorsal Attention Network (DAN) predicted lower emotional intelligence (r = -0.504, p < 0.001). This correlation was observed in both schizophrenia and healthy comparison participants. These results held true despite corrections for sex, age, race, medication dosage (chlorpromazine equivalents), and full scale IQ (FSIQ), and was replicable per site. Post-hoc analyses showed that membership of the left SPL was entirely within the DMN in high scorers and within the DAN in low scorers. This relationship was also shown to be specific to the identified left SPL region when compared to adjacent regions. Sulcal depth analysis of the left SPL revealed a correlation to emotional intelligence (r = 0.269, p = 0.0075). CONCLUSIONS: Previous studies have demonstrated individual variance in brain network topology but the cognitive or behavioral relevance of these differences was undetermined. We observe that the left SPL, a region of high individual variance at the cytoarchitectonic level, also demonstrates individual variance in its association with large scale brain networks and that network topology predicts emotional intelligence. This is the first demonstration of a clinical phenotype in individual brain network topology.
2019-07-03T00:00:00Z

碩士
國立雲林科技大學
電子與資訊工程研究所
96
This paper presents the evident effects of acupunctural point stimulation, using electroencephalography(EEG) measurements. With acupuncture stimulation and the EEG measurement on the same meridian, EEG is able to accurately detect the effects of acupoint stimulation on brain waves. In our study, 24 subjects without heart or nervous diseases were randomly separated into two groups of 12. In the first group, the subjects laid on a bed with eyes closed for 10 minutes. They then received acupuncture at their waiguan points（TE5）on their left hands for 20 minutes. After plucked the fine point, they were observed after a five-minute pause. The other 12 subjects belonged to the sham group. They followed the same procedures as the acupuncture group, but the needle was instead inserted at non-acupoints in their left hands. The electrode located on EEG waves were presented as: T3, T4, 01, 02. The study did not adopt needle twirling to develop our experiments. According to our adopted continuous wavelet transform analysis, the brain waves are identified as: δ(0.5~4HZ), θ(4~8HZ), α(8~13HZ) and β(13~30HZ). During acupuncture stimulation, the θ wave’s energy increased more at all statistical points than before. Upon removing the needle, T3 and T4 points slowly declined and revealed the obvious differences in energy levels between rest and exposure to acupuncture. During acupuncture, only T3 on the α wave showed small statistical energy variations, but levels began decreasing after the first five minutes. Using EEG readouts gathered during our research, we prove that acupuncture affects brain waves and that the stimulation changes based on the potential of the cranium and scalp tissue.