Manifestações orais em crianças em tratamento oncológico

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Sintomatologia associada à erupção dentária

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Lupus Eritematoso Sistémico

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes

BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six associations yielded p <10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p = 4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies.

An examination of the construction of meanings for obesity in Ireland

Obesity has been defined as a consequence of energy imbalance, where energy intake exceeds energy expenditure and results in a build-up of adipose tissue. However, this scientific definition masks the complicated social meanings associated with the condition. This research investigated the construction of meaning around obesity at various levels of inquiry to inform how obesity is portrayed and understood in Ireland. A multi-paradigmatic approach was adopted, drawing on theory and methods from psychology and sociology and an analytical framework combining the Common Sense Model and framing theory was employed. In order to examine the exo-level meanings of obesity, content analysis was performed on two media data sets (n=479, n=346) and a thematic analysis was also performed on the multiple newspaper sample (n=346). At the micro-level, obesity discourses were investigated via the thematic analysis of comments sampled from an online message board. Finally, an online survey assessed individual-level beliefs and understandings of obesity. The media analysis revealed that individual blame for obesity was pervasive and the behavioural frame was dominant. A significant increase in attention to obesity over time was observed, manifestations of weight stigma were common, and there was an emotive discourse of blame directed towards the parents of obese children. The micro-level analysis provided insight into the weight-based stigma in society and a clear set of negative ‘default’ judgements accompanied the obese label. The survey analysis confirmed that the behavioural frame was the dominant means of understanding obesity. One of the strengths of this thesis is the link created between framing and the Common Sense Model in the development of an analytical framework for application in the examination of health/illness representations. This approach helped to ascertain the extent of the pervasive biomedical and individual blame discourse on obesity, which establishes the basis for the stigmatisation of obese persons.

Reversal of impairment losses, firm performance and reporting incentives: Evidence from Malaysia

Malaysian Financial Reporting Standard (FRS) No. 136, Impairment of Assets, was issued in 2005. The standard requires public listed companies to report their non-current assets at no more than their recoverable amount. When the value of impaired assets is recovered, or partly recovered, FRS 136 requires the impairment charges to be reversed to its new recoverable amount. This study tests whether the reversal of impairment losses by Malaysian firms is more closely associated with economic reasons or reporting incentives. The sample of this study consists of 182 public companies listed on Bursa Malaysia (formerly known as the Kuala Lumpur Stock Exchange) that reported reversals of their impairment charges during the period 2006-2009. These firms are matched with firms which do not reverse impairment on the basis of industrial classification and size. In the year of reversal, this study finds that the reversal firms are more profitable (before reversals) than their matched firms. On average, the Malaysian stock market values the reversals of impairment losses positively. These results suggest that the reversals generally reflect increases in the value of the previously impaired assets. After partitioning firms that are likely to manage earnings and those that are not, this study finds that there are some Malaysian firms which reverse the impairment charges to manage earnings. Their reversals are not value-relevant, and are negatively associated with future firm performance. On the other hand, the reversals of firms which are deemed not to be earnings managers are positively associated with both future firm performance and current stock price performance, and this is the dominant motivation for the reversal of impairment charges in Malaysia. In further analysis, this study provides evidence that the opportunistic reversals are also associated with other earnings management manifestations, namely abnormal working capital accruals and the motivation to avoid earnings declines. In general, the findings suggest that the fair value measurement in impairment standard provides useful information to the users of financial statements.

Globalization and basketball in China: governance, market and culture

Chinese sports are developing under very complex and unique political, economic, and cultural circumstances in the global age. This study aims to investigate the process of globalization in basketball through an examination of its multidimensional manifestations. The study aligns itself with Ritzer’s (2003, 2007b) conceptualization of dichotomizing the process of globalization into grobalization and glocalization. On that basis, the trajectory of basketball globalization in China is identified as the result of a contextual and competing interplay between the penetration of the NBA and the consequent engagement of Chinese basketball. A qualitative methodological approach was conducted to achieve the research aim. Data were collected from a number of sources, including official documents and semi-structured interviews with relevant basketball participants. The study reveals that globalization and basketball in China, in the political and institutional dimension, is a conflicting process. The universalization of the NBA’s governance model could not be fully assimilated due to the centralization of power in the Chinese government, which is hindering the further professionalization and marketization of basketball. In the economic dimension, the globalization process is seen to interplay with the local basketball market, which is growing thanks to the adaption of the NBA’s marketing strategies. In the cultural dimension, the study demonstrates that the NBA has to some extent cosmopolitanized and consumerized Chinese basketball culture, while resistance from both the state and the Chinese people has risen, creolizing the globalization of basketball culture in China.

Locating the transnational: representations and aesthetics of the city in contemporary European cinemas

This thesis focuses on two Western European cinematic cities, and two unique periods of their respective nations’ histories, in a bid to “locate” the transnational within a contemporary European milieu. I argue that my geo-cinematic case studies are emblematic of broader questions of the problematics of national identity in contemporary Europe in the face of cross-national flows yet, as a result of their representations as cities both “anchored” and “in flux”, they reject a European postnational identity. Through its engagement with cinematic Rome as the “Eternal City” of Europe and cinematic Dublin as the “newly Europeanised” city, my thesis traces how representations and aesthetics of the urban spaces of these two cities correspond with the tensions at the heart of the respective eras in question. Via the figures that inhabit it, navigate it and search for it, the city is utilised to highlight fixity and mobility, centrality and dislocation, in explicit and implicit ways, amid the rapidly changing landscape of its national terrain. It is through my analyses of the filmed places and sociopolitical, socioeconomic and sociocultural spaces of these capital cities under the rubric of the transnational that this research demonstrates the “pluralities” of the construct in its cinematic manifestations. It is also my aim to evaluate the concept of cinematic transnationalism when identifying and accounting for representations of a specific national, historical timeframe, when the momentousness of the changes that occur is not bound by the national, but rather is reflective of the influence of both domestic and external forces. To this end, my thesis draws attention to instances in which the nation is shown to persist and resist dilution, arguing that it is only against the backdrop and continuity of the nation (in its evershifting guises) that the transnational can be conceived in representative and aesthetic terms.

Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

Cutaneous lesions as a clue to severe combined immunodeficiency.

A 2-month-old boy experienced cutaneous lesions that revealed an underlying severe, combined immunodeficiency (SCID). It is important to recognize cutaneous manifestations of primary immunodeficiency disorders, as they may provide the earliest clue to a defect in immune function.

A MEMETIC/PARTICIPATORY APPROACH FOR CHANGING SOCIAL BEHAVIORS AND PROMOTING ENVIRONMENTAL STEWARDSHIP IN JALISCO, MEXICO

This dissertation addressed the issue of sustainable development at the level of individual behaviors. Environmental perceptions were obtained from people living around the biosphere reserve Chamela-Cuixmala in Jalisco, Mexico. Several environmental issues were identified by the people, such as garbage and grey water on the streets, burning plastics, and the lack of usage of recreational areas. All these issues could be addressed with a change in behavior by the villagers. Familiarization activities were conducted to gain people's trust in order to conduct a community forum. These activities included giving talks to school children and organizing workshops. Four different methodologies were generated using memetics and participation to test which would ameliorate those environmental issues identified by the people through a change in behavior. The methodologies were 1) Memes; 2) Participation and Memes; 3) Participation; 4) Neither Participation nor Memes. A meme is an idea expressed within a linguistic structure or architecture that provides it with self-disseminating and self-protecting characteristics within and among the minds of individuals congruent with their values, beliefs and filters. Four villages were chosen as the treatments, and one as the control, for a total of five experimental villages. A different behavior was addressed in each treatment village (garbage, grey-water, burning plastics, recreation.) A nonequivalent control-group design was established. A pretest was conducted in all five villages; the methodologies were tested in the four treatment villages; a posttest was conducted on the five villages. The pretest and posttest consisted in measuring sensory specific indicators which are manifestations of behavior that can either be seen, smelled, touched, heard or tasted. Statistically significant differences in behavior from the control were found for two of the methodologies 1) Memes (p=0.0403) and 2) Participation and Memes (p=0.0064). For the methodologies of 3) Participation alone and 4) Neither, the differences were not significant (p=0.8827, p=0.5627 respectively). When using memes, people's behavior improved when compared to the control. Participation alone did not generate a significant difference. Participation aided in the generation of the memes. Memetics is a tool that can be used to establish a linkage between human behavior and ecological health.

Neuroprotection resulting from insufficiency of RANBP2 is associated with the modulation of protein and lipid homeostasis of functionally diverse but linked pathways in response to oxidative stress.

Oxidative stress is a deleterious stressor associated with a plethora of disease and aging manifestations, including neurodegenerative disorders, yet very few factors and mechanisms promoting the neuroprotection of photoreceptor and other neurons against oxidative stress are known. Insufficiency of RAN-binding protein-2 (RANBP2), a large, mosaic protein with pleiotropic functions, suppresses apoptosis of photoreceptor neurons upon aging and light-elicited oxidative stress, and promotes age-dependent tumorigenesis by mechanisms that are not well understood. Here we show that, by downregulating selective partners of RANBP2, such as RAN GTPase, UBC9 and ErbB-2 (HER2; Neu), and blunting the upregulation of a set of orphan nuclear receptors and the light-dependent accumulation of ubiquitylated substrates, light-elicited oxidative stress and Ranbp2 haploinsufficiency have a selective effect on protein homeostasis in the retina. Among the nuclear orphan receptors affected by insufficiency of RANBP2, we identified an isoform of COUP-TFI (Nr2f1) as the only receptor stably co-associating in vivo with RANBP2 and distinct isoforms of UBC9. Strikingly, most changes in proteostasis caused by insufficiency of RANBP2 in the retina are not observed in the supporting tissue, the retinal pigment epithelium (RPE). Instead, insufficiency of RANBP2 in the RPE prominently suppresses the light-dependent accumulation of lipophilic deposits, and it has divergent effects on the accumulation of free cholesterol and free fatty acids despite the genotype-independent increase of light-elicited oxidative stress in this tissue. Thus, the data indicate that insufficiency of RANBP2 results in the cell-type-dependent downregulation of protein and lipid homeostasis, acting on functionally interconnected pathways in response to oxidative stress. These results provide a rationale for the neuroprotection from light damage of photosensory neurons by RANBP2 insufficiency and for the identification of novel therapeutic targets and approaches promoting neuroprotection.

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

Visual Disobedience: The Geopolitics of Experimental Art in Central America, 1990-Present

This dissertation centers on the relationship between art and politics in postwar Central America as materialized in the specific issues of racial and gendered violence that derive from the region's geopolitical location and history. It argues that the decade of the 1990s marks a moment of change in the region's cultural infrastructure, both institutionally and conceptually, in which artists seek a new visual language of experimental art practices to articulate and conceptualize a critical understanding of place, experience and knowledge. It posits that visual and conceptual manifestations of violence in Central American performance, conceptual art and installation extend beyond a critique of the state, and beyond the scope of political parties in perpetuating violent circumstances in these countries. It argues that instead artists use experimental practices in art to locate manifestations of racial violence in an historical system of domination and as a legacy of colonialism still witnessed, lived, and learned by multiple subjectivities in the region. In this postwar period artists move beyond the cold-war rhetoric of the previous decades and instead root the current social and political injustices in what Aníbal Quijano calls the `coloniality of power.' Through an engagement of decolonial methodologies, this dissertation challenges the label "political art" in Central America and offers what I call "visual disobedience" as a response to the coloniality of seeing. I posit that visual colonization is yet another aspect of the coloniality of power and indispensable to projects of decolonization. It offers an analysis of various works to show how visual disobedience responds specifically to racial and gender violence and the equally violent colonization of visuality in Mesoamerica. Such geopolitical critiques through art unmask themes specific to life and identity in contemporary Central America, from indigenous genocide, femicide, transnational gangs, to mass imprisonments and a new wave of social cleansing. I propose that Central American artists--beyond an anti-colonial stance--are engaging in visual disobedience so as to construct decolonial epistemologies in art, through art, and as art as decolonial gestures for healing.

The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.

G protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D(2) dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO mice). To understand how GRK6 modulates the behavioral manifestations of dopamine deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6-KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian 6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by assessing the phosphorylation of AKT/GSK3β and ERK1/2. GRK6 deficiency reduced cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary movements induced by chronic L-DOPA. These data indicate that approaches to regulate GRK6 activity could be useful in modulating both therapeutic and side-effects of L-DOPA.