Induction of microsatellite instability by oxidative DNA damage

Instability of repetitive sequences, both in intronic sequences and within coding regions, has been demonstrated to be a hallmark of genomic instability in human cancer. Understanding how these mutational events arise may provide an opportunity for prevention or early intervention in cancer development. To study the source of this instability, we have identified a region of the β-lactamase gene that is tolerant to the insertion of fragments of exogenous DNA as large as 1,614 bp with minimal loss of enzyme activity, as determined by antibiotic resistance. Fragments inserted out-of-frame render Escherichia coli sensitive to antibiotic, and compensatory frameshift mutations that restore the reading frame of β-lactamase can be selected on the basis of antibiotic resistance. We have utilized this site to insert a synthetic microsatellite sequence within the β-lactamase gene and selected for mutations yielding frameshifts. This assay provides for detection of one frameshift mutation in a background of 106 wild-type sequences. Mismatch repair deficiency increased the observed frameshift frequency ≈300-fold. Exposure of plasmid containing microsatellite sequences to hydrogen peroxide resulted in frameshift mutations that were localized exclusively to the microsatellite sequences, whereas DNA damage by UV or N-methyl-N′-nitro-N-nitrosoguanidine did not result in enhanced mutagenesis. We postulate that in tumor cells, endogenous production of oxygen free radicals may be a major factor in promoting instability of microsatellite sequences. This β-lactamase assay may provide a sensitive methodology for the detection and quantitation of mutations associated with the development of cancer.

O crescimento no primeiro ano de vida e o excesso de peso no início da idade escolar

INTRODUÇÃO - A obesidade é uma preocupação de saúde pública cada vez mais importante, em todo o mundo. A obesidade infantil, por sua vez, vem sendo associada a um alto risco de agravos infantis e de obesidade e doenças crônicas não transmissíveis na fase adulta. Admite-se que o início da vida seja um momento crítico e determinante para o risco do indivíduo desenvolver sobrepeso ou obesidade. Entretanto, não está definido se existe algum período de maior vulnerabilidade na fase pós-natal e qual seria o melhor marcador do crescimento da criança para indicar uma possível intervenção precoce que possa minimizar o risco de desenvolver excesso de peso ou obesidade. OBJETIVO - Analisar as relações existentes entre indicadores antropométricos de crescimento no primeiro ano de vida e o desenvolvimento de excesso de peso no início da idade escolar. MÉTODOS - Estudo de uma coorte histórica de uma unidade básica de saúde em São Paulo, Brasil. Os momentos analisados foram aos três, seis e doze meses e aos sete anos de idade. Avaliou-se a velocidade de crescimento e o crescimento alcançado durante o primeiro ano de vida frente aos desfechos: excesso de peso e obesidade aos sete anos de idade. As variáveis foram analisadas estatisticamente através do Coeficiente de Correlação de Pearson e das curvas ROC, além de terem sido estimadas a sensibilidade, a especificidade e o risco relativo. RESULTADOS - Os Coeficientes de Correlação de Pearson do ganho de peso por ganho de comprimento nos períodos de 0 a 3 meses, 0 a 6 meses e 0 a 12 meses foram, respectivamente, 0,23 (IC 95 por cento : 0,13 a 0,33), 0,29 (IC 95 por cento : 0,19 a 0,39) e 0,34 (IC 95 por cento : 0,24 a 0,43), todos significantes estatisticamente. Os Coeficientes de Correlação de Pearson do escore z do Índice de Massa Corpórea (IMC) para 3, 6 e 12 meses foram, respectivamente, 0,39 (IC 95 por cento : 0,29 a 0,48), 0,41 (IC 95 por cento : 0,32 a 0,50) e 0,42 (IC 95 por cento : 0,33 a 0,51). Para excesso de peso na idade escolar, a utilização do marcador escore z do IMC aos 12 meses maior que 0,49 apresentou sensibilidade de 68,29 por cento (IC 95 por cento : 59,3 por cento a 76,4 por cento ), especificidade de 63,51 por cento (IC 95 por cento : 56,6 por cento a 70,0 por cento ) e risco relativo estimado de 2,31 (IC 95 por cento : 1,69 a 3,17). Para obesidade, o mesmo marcador apresentou sensibilidade de 76,47 por cento (IC 95 por cento : 62,5 por cento a 87,2 por cento ), especificidade de 56,89 por cento (IC 95 por cento : 50,9 por cento a 62,7 por cento ) e risco relativo estimado de 3,49 (IC 95 por cento : 1,90 a 6,43). CONCLUSÕES - O primeiro trimestre de vida se revelou como sendo o período mais crítico, entre os estudados, para o desenvolvimento de sobrepeso ou obesidade no início da idade escolar. No entanto, o escore z do IMC acima de 0,49 aos 12 meses de vida se mostrou como o melhor marcador para esses dois desfechos.

Habilidades de processamento fonológico e de escrita em crianças com distúrbio específico de linguagem: um estudo comparativo com a normalidade

Introdução: Crianças com distúrbio específico de linguagem (DEL) são propensas a apresentar dificuldade no processo de alfabetização devido às múltiplas alterações de linguagem que possuem. Este estudo comparou e caracterizou o desempenho de crianças com DEL e em desenvolvimento típico de linguagem em atividades de aliteração, rima, memória de curto prazo fonológica, ditado de palavras e de pseudopalavras. A principal hipótese do estudo era de que o grupo DEL apresentaria desempenho inferior do que o grupo em desenvolvimento típico em todas as habilidades estudadas. Método: Participaram do estudo 12 crianças com DEL (GP) e 48 em desenvolvimento típico (GC) com idade entre 7 anos e 9 anos e 11 meses. Todos os sujeitos cursavam o 2º ou 3º ano do ensino fundamental I e apresentavam audição e rendimento intelectual não-verbal preservados. Para a seleção dos grupos foram utilizadas medidas de vocabulário receptivo, fonologia e nível socioeconômico. Já as medidas experimentais avaliadas foram testes padronizados de aliteração, rima, memória de curto prazo fonológica e a aplicação de um ditado de palavras e de pseudopalavras elaborados para esta pesquisa. Resultados: ambos os grupos apresentaram pior desempenho em tarefas de rima do que de aliteração e o GP apresentou desempenho inferior em ambas as tarefas quando comparado ao GC. A análise dos distratores nas atividades de aliteração e rima apontou que em tarefas de aliteração, o GP cometeu mais erros de tipologia semântico enquanto na prova de rima foram mais erros de tipologia fonológico. O GP obteve desempenho inferior ao GC nas avaliações da memória de curto prazo fonológica, ditado de palavras e de pseudopalavras. O GP evidenciou maior dificuldade no ditado de pseudopalavras no que no de palavras e o GC não apresentou diferença significativa no desempenho dos ditados. No ditado de palavras, o GP cometeu mais erros na palavra toda enquanto no ditado de pseudopalavras ocorreram mais erros na palavra toda e na sílaba final. Na comparação do desempenho dos grupos de acordo com a escolaridade, notou-se que os sujeitos do GC do 2º e 3º ano não evidenciaram diferença significativa em seu desempenho nas tarefas, enquanto os sujeitos do GP do 3º ano apresentaram melhor desempenho do que os do 2º ano em todas as medidas experimentais, com exceção da memória de curto prazo fonológica. Conclusões: o GP apresentou dificuldade em tarefas de processamento fonológico e de escrita que foram realizadas com relativa facilidade pelo GC. Os sujeitos com DEL evidenciaram uma análise mais global dos estímulos apresentados nas tarefas de consciência fonológica, o que os fez desprezar aspectos segmentais importantes. A dificuldade em abordar as informações de modo analítico, somado a alterações linguísticas e do processamento fonológico, levou o GP a apresentar maior taxa de erros nas tarefas de ditado. Apesar das alterações apontadas, os sujeitos do GP do 3º ano obtiveram melhor desempenho do que os do 2º ano em todas as habilidades com exceção da memória de curto prazo fonológica, que é sua marca clínica. Estes dados reforçam a necessidade do diagnóstico e intervenção precoces para esta população, onde as habilidades abordadas neste estudo devem ser incluídas no processo terapêutico

Endolymphatic sac tumor : A report of 2 cases with long term follow-up

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

Quando a oftalmologia diagnostica uma patologia sistémica : a propósito de um caso clínico

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

Fatores de risco para a progressão da gamapatia monoclonal de significado indeterminado para mieloma múltiplo

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

The Great Financial Plumbing: From Northern Rock to Banking Union. CEPS Paperback, 19 October 2015

The financial and economic crises have led to an enormous plumbing exercise, involving a fundamental re-design of the global and European regulatory and supervisory system. This book systematically assesses the big items on the G-20 and EU agendas and the effectiveness with which they have been implemented in the EU. Its publication coincides with the demand by European Commissioner Jonathan Hill, in the context of the Capital Markets Union, for a 'comprehensive review' of the impact and coherence of EU legislation in the area of financial services. Karel Lannoo argues in the book that much has been done by European policy-makers to make the financial system safer and to prevent banking crises of the magnitude that erupted in 2008 and 2011, but that the new framework puts an enormous burden on banks and supervisors to implement and enforce it correctly. With the huge amount of secondary or 'level-2' legislation in place, this process has spiralled out of control, and as member states always find new ways of ‘gold-plating’ EU rules, the EU always finds further reasons to achieve a 'single rulebook'. This process has to be brought to a halt, and mutual recognition, a basic single-market principle, reinforced. The new framework also brings huge advantages, which should offer benefits to all parties. Banking Union is a huge step forward, which introduces 'one-stop shopping' for banks in the eurozone, another basic single market principle, and a true single supervisor. The clarity of the new resolution framework should, if correctly applied, trigger early intervention and bring an end to forbearance, thereby enforcing market discipline in the banking sector. It should also avoid reliance on taxpayers' money to bail-out banks in trouble, which totalled 14% of EU GDP during the crisis.

Papel do educador na avaliação e intervenção de crianças com necessidades educativas especiais

Relátorio de estágio apresentado para obtenção do grau de Mestre na especialidade de Educação Pré-escolar

Final legislative report : 97th General Assembly House Joint Resolution 50 /

House Joint Resolution (HJR) 50 created the Early Intervention Taskforce to partner with the Department of Human Services to undertake a comprehensive and thorough review of the Early Intervention system and develop recommendations and an action plan to address issues related to workforce, financing, monitoring and evaluation, service delivery and transitions. The Early Intervention Taskforce was chaired by the Department of Human Services, with membership defined in HJR 50 to include representation from state agencies, advocacy organizations, professional groups, Early intervention training and consultation groups, the Illinois Interagency Council on Early Intervention, Child and Family Connections managers/staff, and parents of children in the Early Intervention Program.

Sociodemographic and clinical correlates of immune activation in postpartum HIV-1/HSV-2 co-infected Kenyan women

Thesis (Master's)--University of Washington, 2016-06

The use of non-verbal repair strategies by children with autism

This study examined possible links between the occurrence of prosodic changes to vocalizations and gestures and the use of problem behaviors by children with autism when attempting to repair communication breakdowns. The repair strategies of six children with autism aged 2-5 years and with fewer than 10 words or signs were analyzed. Mother-child dyads were videotaped at home interacting in naturally occurring contexts. Videotapes were analyzed and coded for communication breakdowns and repair attempts made by the child. Repairs were further analyzed according to the type of repair strategy used, changes in prosidy, and whether the repair mode involved problematic or non-problematic behavior. In most situations, this group of children attempted to repair breakdowns in communication that occurred while interacting with their mothers. Most children used both nonproblematic and problematic behaviors and were less likely to use augmentations as a repair strategy than repetitions and substitutions. Some repetitions and some augmentations involved the use of gestures or vocalizations with increased emphasis or prosidy. Possible links between repair strategies involving increased prosidy and the use of problem behaviors are discussed together with the implications and significance of these finding in relation to early intervention for children with significant communication impairments. (C) 2004 Elsevier Ltd. All rights reserved.

Aggressive behaviour in the high-secure forensic setting: the perceptions of patients

Twenty-seven patients undergoing treatment in a high-secure forensic facility participated in focus group interviews to elicit their perceptions of (1) the factors leading to aggressive behaviour; and (2) strategies to reduce the risk of such behaviour. The focus group interviews were audiotaped, transcribed and analysed using content analysis. The participants identified that a combination of patient, staff and environmental factors contributed to violence in the study wards. The cause of aggressive behaviour centred around five major themes: the environment; empty days; staff interactions; medication issues; and patient-centred factors. Potential strategies identified by patients to reduce aggressive behaviour included: early intervention; the provision of meaningful activities to reduce boredom; separation of acutely disturbed patients; improved staff attitudes; implementation of effective justice procedures; and a patient advocate to mediate during times of conflict. Findings suggested that social and organizational factors need to be addressed to change the punitive subculture inherent in forensic psychiatric facilities, and to ensure a balance between security and effective therapy.

Influence of gender on mental health literacy in young Australians

Objectives: To determine the effects of gender on mental health literacy in young people between 12 and 25 years of age. Design: Computer-Assisted Telephone Interviewing was employed to conduct a cross-sectional structured interview focusing on young people's awareness of depression and psychosis. Participants: The sample comprised 1207 young Australians (539 males and 668 females) between the ages of 12-25 recruited from two metropolitan and two regional areas within Victoria. Six hundred and six respondents were presented a depression vignette and 601 were presented a psychosis vignette. Results: Female respondents (60.7%) were significantly more likely to correctly identify depression in the vignette as compared to male respondents (34.5%). No significant gender differences were noted for the psychosis vignette. Males were less significantly likely to endorse seeing a doctor or psychologist/counsellor for the treatment of psychosis. Males were also significantly more likely than females to endorse alcohol as a way of dealing with depression and antibiotics as useful for dealing with psychosis. Conclusion: Gender differences in mental health literacy are striking. Males showed significantly lower recognition of symptoms associated with mental illness and were more likely endorse the use alcohol to deal with mental health problems. Such factors may contribute to the delays in help seeking seen in young males. Further research is needed to delineate how these gender differences in young people may obstruct help seeking, early intervention and other aspects of mental health service delivery.

Psychotic symptom and cannabis relapse in recent-onset psychosis - Prospective study

Background: Cannabis use appears to exacerbate psychotic symptoms and increase risk of psychotic relapse. However, the relative contribution of cannabis use compared with other risk factors is unclear. The influence of psychotic symptoms on cannabis use has received little attention. Aims: To examine the influence of cannabis use on psychotic symptom relapse and the influence of psychotic symptom severity on relapse in cannabis use in the 6 months following hospital admission. Method: At baseline, 84 participants with recent-onset psychosis were assessed and 81 were followed up weekly for 6 months, using telephone and face-to-face interviews. Results: A higher frequency of cannabis use was predictive of psychotic relapse, after controlling for medication adherence, other substance use and duration of untreated psychosis. An increase in psychotic symptoms was predictive of relapse to cannabis use, and medication adherence reduced cannabis relapse risk. Conclusions: The relationship between cannabis use and psychosis may be bidirectional, highlighting the need for early intervention programmes to target cannabis use and psychotic symptom severity in this population. Declaration of interest: None. Funding detailed in Acknowledgements.

Idiopathic sclerosing orbital inflammation

Objective: To perform a multicenter review of the clinical features and treatment of 31 patients with idiopathic sclerosing orbital inflammation. Methods: We included all patients with histologically confirmed idiopathic sclerosing orbital inflammation from 5 regional orbital centers. We reviewed the case notes to determine the clinical presentation, diagnostic features, and response to treatment. The main outcome measures were duration and nature of symptoms, anatomical location of disease, histopathological findings, treatment modalities, treatment efficacy and adverse effects, and final clinical status. Results: We included 13 male and 18 female patients ranging in age from 7 to 83 years. The average duration of symptoms at presentation was 13.4 months. There was a predilection for the lateral and superior quadrants. Thirteen patients had apical disease, and 4 had extraorbital involvement. Histopathological findings invariably showed sclerosis associated with a sparse mixed cellular infiltrate. Twenty- seven patients were treated with oral prednisolone, response to which was good in 9 patients, partial in 11, and poor in 7. Six patients were treated with a second- line immunosuppressive agent, and 6 received radiotherapy. The response to radiotherapy was generally poor. Conclusions: Idiopathic sclerosing orbital inflammation is a rare condition that can be difficult to diagnose and manage. Early intervention with immunosuppression in the form of corticosteroids combinedwith secondline agents can result in control and even regression of the disease.