Implementação da Marcação CE para estruturas metálicas: estudo de caso na serralharia da Carpincasais

Dissertação de mestrado em Engenharia Industrial

Registro de ocorrência de Panstrongylus lignarius (Walker, 1837) (Hemiptera: Reduviidae: Triatominae) no Estado de Mato Grosso, Brasil

Neste trabalho, relata-se pela primeira vez a ocorrência de Panstrongylus lignarius no Estado de Mato Grosso. Entre 2001 e 2009, cinco espécimes foram capturados pelos moradores dos municípios de Paranaíta, Alta Floresta, Lucas do Rio Verde, Sorriso e Guarantã do Norte e enviados ao Laboratório de Entomologia da Secretaria de Estado de Saúde de Mato Grosso, onde foram identificados como Panstrongylus lignarius (Walker, 1837). O encontro dessa espécie no estado do Mato Grosso, Brasil, amplia a sua distribuição geográfica.

Morfometria e análise populacional de colônias de Apoica flavissima (Hymenoptera, Vespidae) coletadas na Amazônia brasileira

Duas colônias da vespa social Apoica flavissima foram coletadas e analisadas quanto aos parâmetros morfométricos e a população residente no ninho. Estas estavam fundadas a cerca de 700 mm do chão, nidificadas em plantas herbáceas, nas proximidades de igarapés. Ambas se encontravam no inicio do seu ciclo biológico e apresentavam um pequeno número de indivíduos, quando comparado com outros trabalhos com este gênero. Os adultos foram mensurados com médias de 21,62 mm de comprimento do corpo; 3,8 mm de largura máxima do tórax e 3,5 mm de largura da cabeça. As pupas apresentaram 20,05 mm de comprimento corpóreo; 3,75 mm de largura máxima do tórax e 3,51 mm de largura da cabeça. Ambientes naturais devem favorecer o crescimento dos indivíduos assim como manter os seus padrões de nidificação. Assim, uma discrepante taxa de crescimento e diferentes hábitos de nidificação, podem indicar a influência do ambiente sobre a biologia deste grupo.

Metabolic profiling and classification of propolis samples from Southern Brazil: an NMR-based platform coupled with machine learning

The chemical composition of propolis is affected by environmental factors and harvest season, making it difficult to standardize its extracts for medicinal usage. By detecting a typical chemical profile associated with propolis from a specific production region or season, certain types of propolis may be used to obtain a specific pharmacological activity. In this study, propolis from three agroecological regions (plain, plateau, and highlands) from southern Brazil, collected over the four seasons of 2010, were investigated through a novel NMR-based metabolomics data analysis workflow. Chemometrics and machine learning algorithms (PLS-DA and RF), including methods to estimate variable importance in classification, were used in this study. The machine learning and feature selection methods permitted construction of models for propolis sample classification with high accuracy (>75%, reaching 90% in the best case), better discriminating samples regarding their collection seasons comparatively to the harvest regions. PLS-DA and RF allowed the identification of biomarkers for sample discrimination, expanding the set of discriminating features and adding relevant information for the identification of the class-determining metabolites. The NMR-based metabolomics analytical platform, coupled to bioinformatic tools, allowed characterization and classification of Brazilian propolis samples regarding the metabolite signature of important compounds, i.e., chemical fingerprint, harvest seasons, and production regions.

Prevalência e fatores associados à sintomatologia depressiva em idosos residentes no Nordeste do Brasil

OBJETIVO: Analisar a influência de fatores sociodemográficos, de saúde física, capacidade funcional e função cognitiva sobre a sintomatologia depressiva de idosos do município de Santa Cruz, no Rio Grande do Norte. MÉTODOS: Estudo com delineamento transversal de base populacional, incluindo 310 idosos, acima de 60 anos, residentes na zona urbana da cidade, nos quais se aplicou a Escala de Depressão Geriátrica (GDS-15).Aanálise estatística foi realizada com nível de significância p = 0,05, com cálculo da respectiva odds ratio (OR) na regressão logística binária. RESULTADOS: Encontrou-se uma prevalência de 25,5% de sujeitos considerados casos de depressão, nos quais, a partir de análise multivariada, verificou-se associação significativa com idade acima de 75 anos (p = 0,046), analfabetismo (p = 0,037), má percepção de saúde (p < 0,001) e dependência para atividades instrumentais da vida diária (AIVD) (p = 0,001). CONCLUSÕES: As variáveis idade acima de 75 anos, analfabetismo, má percepção de saúde e dependência para AIVD estiveram associadas de forma independente à presença de sintomatologia depressiva nos idosos da nossa população. Os autores discutem que a identificação de fatores que influenciam o surgimento de sintomas depressivos em idosos constitui passo fundamental para o planejamento das ações que visem reduzir os efeitos dessa enfermidade na qualidade de vida dessas pessoas.

Redefining the MED13L syndrome

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.

Searching for therapeutic strategies in a mouse modelo of Machado-Joseph disease: targeting proteostases

Tese de Doutoramento em Ciências da Saúde

The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis

DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.

Defeito total do septo atrioventricular. Correlação anatomofuncional entre pacientes com e sem síndrome de Down

OBJETIVO: Comparar o grau de repercussão, fatores responsáveis e época de aparecimento dos sintomas do defeito do septo atrioventricular (DSAV), em pacientes com e sem síndrome de Down. MÉTODOS: Foram estudados 80 pacientes com idade <2 anos, sendo 55 (69%) com síndrome de Down - grupo I (GI) e 25 (31%) sem síndrome de Down - grupo II (GII). Avaliaram-se a idade de manifestação dos sintomas, sua intensidade, classe funcional (CF), repercussão clínica, tipo anatômico e grau de malformação da valva atrioventricular (VAV). RESULTADOS: A idade média de manifestação dos sintomas foi de 50 (±75) dias nos dois grupos. A CF II (NYHA) predominou no GI (31 casos - 56,5%) e a CF III-IV no GII (19 - 76%) p<0,005. O quadro de insuficiência cardíaca esteve presente em 34 (62%) pacientes do GI e em 21 (84%) do GII e, o de hipertensão pulmonar em 21 (38%) do GI e em 4 (16%) do GII, p<0,04. Pressão média da artéria pulmonar >50mmHg ocorreu em 56% dos casos do GI em relação a 28% do GII p<0,019. A evolução até a cirurgia foi instável (agravamentos da insuficiência cardíaca) em 33 (60%) do GI e em 21 (84%) do GII p<0,03. O tipo A de Rastelli foi o mais encontrado nos dois grupos, 35 (67%) pacientes no GI e nos 25 (100%) do GII. A alteração anatômica da VAV foi importante em 8% no GI e em 38% no GII. CONCLUSÃO: Há sugestão de predominância de hiper-reatividade vascular pulmonar nas crianças com síndrome de Down e de manifestações de insuficiência cardíaca nas geneticamente normais.

Cardiomiopatia hipertrófica tratada por técnica intervencionista de redução septal

Mulher de 75 anos com cardiomiopatia hipertrófica obstrutiva, com dispnéia classe IV, refratária ao tratamento clínico, apresentava contra-indicações relativas para abordagens cirúrgica e de implante de marcapasso. Realizou-se procedimento intervencionista para injeção seletiva de álcool absoluto no 1º ramo septal da artéria interventricular anterior. O infarto septal provocado acompanhou-se de liberação enzimática, elevação de ST e bloqueio de ramo direito do feixe de His. Não houve complicações inesperadas, e o gradiente da via ejetiva de ventrículo esquerdo, de 66mmHg, foi imediatamente abolido. Controle ecocardiográfico evidencia manutenção desse resultado, até o momento, dois meses após o procedimento, em correspondência a marcante alívio sintomático.

Avaliação hemodinâmica e evolução clínica de crianças portadoras de cardiomiopatia dilatada grave candidatas a transplante cardíaco

OBJETIVO: Estudar o perfil dos parâmetros hemodinâmicos e a evolução clínica de crianças candidatas a transplante cardíaco, portadoras de cardiomiopatia grave. MÉTODOS: Foram 24 crianças, com idade entre 4 meses e 10 anos e 8 meses (média de 3,7±2,5 anos), no período de fevereiro/92 a maio/96, submetidas a estudo hemodinâmico e medidos os seguintes parâmetros: débito cardíaco, pressão média de artéria pulmonar (PMAP) e pressão capilar pulmonar. Foram calculados o índice de resistência vascular pulmonar (IRVP) e gradiente de pressão transpulmonar (GPT). RESULTADOS: Do ponto de vista evolutivo, 10 (41,6%) crianças foram transplantadas (grupo A), 5 (20,8%) aguardam o transplante (grupo B) e 9 (37,6%) faleceram (grupo C). Observou-se que a média das idades dos pacientes do grupo B foi significativamente menor que do grupo C. Dos dados hemodinâmicos, a PMAP, GTP e IRVP apresentaram médias significativamente menores no grupo A em relação ao grupo C. CONCLUSÃO: O perfil hemodinâmico de crianças candidatas ao transplante cardíaco mostrou-se compatível ao quadro clínico de insuficiência cardíaca grave. A idade foi o único fator que diferenciou o grupo B e C (p= 0,036). O IRVP, PMAP e o GTP foram fatores que diferenciaram de modo significativo o grupo A e o grupo C (p=0,010; p=0,044 e p=0,023, respectivamente). Quanto maior a idade no momento da indicação do transplante na criança, pior foi seu prognóstico.

Aortopulmonary window. Clinical and surgical assessment of 18 cases

OBJECTIVE: Aortopulmonary window (APW) is an uncommon congenital malformation. Its clinical presentation is dependent on the size of the defect and on the associated lesions. We evaluated our experience with this anomaly and compared it with 296 cases reported in the literature. METHODS: Retrospective study of 18 patients diagnosed as having APW (age range from 13 days to 31 years, 13 (72.2%) females), divided into two groups: Group A (GA): 10 patients with isolated APW, and Group B (GB): 8 patients with associated lesions. RESULTS: Heart failure occurred in 14 patients, and cyanosis in 3: 2 from GB (tetralogy of Fallot - TF, and double outlet right ventricle - DORV), and one from GA with pulmonary hypertension. In 5 patients from GA the diagnosis of mitral regurgitation was made based on a systolic murmur and LV hypertrophy on the EKG. In GB, clinical findings were determined by the associated defect. Diagnosis was established by echocardiography in 11 (61.2%) of the patients. In 3 patients, a wrong diagnosis of mitral regurgitation was made, in 1 a patent ductus arteriosus was diagnosed and in 3 others, the diagnosis of APW was masked by other important associated defects (2 cases of DORV and 1 case of TF). The diagnosis was made by catheterization in 3 (16.6%) patients, by surgery in 3 (16.6%) and by necropsy in 1 (5.5%). Corrective surgery was performed in 14 (77.7%) patients, with one immediate death and good long-term follow-up in the remaining patients. CONCLUSION: APW can be confused with other defects. Clinical findings, associated with an adequate echocardiogram can provide the information for the correct diagnosis.

Anomalous origin of the left coronary artery from the right pulmonary artery with intramural aortic trajectory. Clinicosurgical diagnostic implications

OBJECTIVE: Anomalous origin of the left coronary artery from the right pulmonary artery (AOLCARPA), is a rare entity that is usually associated with other defects. Of the 20 cases of AOLCARPA reported in the literature, 14 (70%) had associations. We describe four patients with AOLCARPA without associated defects, but with a peculiar intramural aortic trajectory. METHODS: Fifty-five patients with anomalous origin of the left coronary artery were operated upon at INCOR-FMUSP. Four of the patients had the anomalous origin from the right pulmonary artery (RPA) without associated defects but with intramural aortic trajectory. Clinical and laboratory examinations were analyzed, as well as surgical findings. RESULTS: All patients had congestive heart failure (CHF) and 3 also had angina pectoris. Two patients had a murmur of mitral regurgitation, signs of myocardial infarction on the ECG and cardiomegaly. The shortening fraction varied from 9% to 23%. The hemodynamic study confirmed the diagnosis of anomalous origin of the coronary artery, but the intramural trajectory and the origin from the RPA were established only at surgery. In 3 patients, the technique of side-to-side anastomosis was performed with a good outcome. One patient, who underwent end-to-side anastomosis, died 6 months after the surgery. CONCLUSION: Association with other defects usually occurs in the AOLCARPA, and the intramural aortic trajectory is difficult to clinically diagnose but easy to surgically correct.

Ebstein's anomaly with coarctation of the aorta. An unusual association

Ebstein's anomaly with coarctation of the aorta is an extremely unusual condition. In this report, the clinical and surgical features of 3 male patients, aged 7 months, 4 years and 14 years, are discussed. All patients were in situs solitus. The first 2 patients had atrioventricular and ventriculoarterial discordance and progressed to heart failure in the neonatal period. The third had atrioventricular and ventriculoarterial concordance, as well as Wolf-Parkinson-White syndrome, with frequent episodes of paroxysmal tachycardia. The 3 patients underwent surgery for correction of the coarctation of the aorta. The patient with atrioventricular and ventriculoarterial concordance underwent tricuspid valvuloplasty using a DeVega-like technique. In addition, ablation of 2 anomalous pathways (Kent bundle), which were detected by the electrophysiologic study, was also subsequently performed. The 3 patients showed a good postoperative outcome for 2 years, although, in those with discordance, the surgical procedure did not influence the dysplasia of the tricuspid valve, because this valve showed light to moderate dysfunction.