Defective transcription/repair factor IN recruitment to specific UV lesions in trichothiodystrophy syndrome

Most trichothiodystrophy (TTD) patients present mutations in the xeroderma pigmentosum D (XPD) gene, coding for a subunit of the transcription/repair factor IIH (TFHH) complex involved in nucleotide excision repair (NER) and transcription. After UV irradiation, most TTD/XPD patients are more severely affected in the NER of cyclobutane pyrimidine dimers (CPD) than of 6-4-photoproducts (6-4PP). The reasons for this differential DNA repair defect are unknown. Here we report the first study of NER in response to CPDs or 6-4PPs separately analyzed in primary fibroblasts. This was done by using heterologous photorepair; recombinant adenovirus vectors carrying photolyases enzymes that repair CPD or 64PP specifically by using the energy of light were introduced in different cell lines. The data presented here reveal that some mutations affect the recruitment of TFHH specifically to CPDs, but not to 6-4PPs. This deficiency is further confirmed by the inability of TTD/XPD cells to recruit, specifically for CPDs, NER factors that arrive in a TFIIH-dependent manner later in the NER pathway. For 6-4PPs, we show that TFHH complexes carrying an NH2-terminal XPD mutated protein are also deficient in recruitment of NER proteins downstream of TFUH. Treatment with the histone deacetylase inhibitor trichostatin A allows the recovery of TFHH recruitment to CPDs in the studied TTD cells and, for COOH-terminal XPD mutations, increases the repair synthesis and survival after UV, suggesting that this defect can be partially related with accessibility of DNA damage in closed chromatin regions.

Some factors associated with dental caries in the primary dentition of children with Down syndrome

Aim It is well reported in the scientific literature that there is a high level of periodontal disease and lower caries prevalence in Down Syndrome (DS) individuals, when compared with age-matched non DS individuals. This study was conducted to investigate the process of dental caries in DS children. Materials and methods In this study the following parameters were considered: oral hygiene habits, levels of Streptococcus mutans (SM) and Lactobacillus spp. (LB), Modified Gingival Index (MGI), and Simplified Oral Hygiene Index (OHI-S). A case group with DS children (n=69) and a control group of non DS children (n=69) were formed to perform this study Dental caries severity was determined using the DMFT index. Samples of non-stimulated saliva were collected to determine the Lactobacillus spp levels. For SM levels, MSB agar plates were used. Results The findings revealed that the case group attended, dental check-ups more frequently brushed their teeth more times per day, flossed less, and also more frequently had SM levels classified as ""high count"". The MGI was higher and the OHI-S was lower than the control group (p<0.001). Conclusion No significant differences were found between the DMFT indexes of children from the two groups (p=0.345). The logistic regression analysis showed that in the case group, age, MGI, and SM count were positively related to dental caries (p<0.05).

Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >= 65 years had 2-year survival rates as follows: 44% (95% Cl, 37% to 52%), 50% (95% Cl, 41% to 59%), 34% (95% Cl, 25% to 43%), and 36% (95% Cl, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% Cl, 35% to 49%), 35% (95% Cl, 27% to 43%), 45% (95% Cl, 36% to 54%), and 38% (95% Cl, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P>.3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

Accumulation of (5 ` S)-8,5 `-cyclo-2 `-deoxyadenosine in organs of Cockayne syndrome complementation group B gene knockout mice

Cockayne syndrome (CS) is a human genetic disorder characterized by sensitivity to UV radiation, neurodegeneration, premature aging among other phenotypes. CS complementation group B (CS-B) gene (csb) encodes the CSB protein (CSB) that is involved in base excision repair of a number of oxidatively induced lesions in genomic DNA in vivo. We hypothesized that CSB may also play a role in cellular repair of the DNA helix-distorting tandem lesion (5`S)-8,5`-cyclo-2`-deoxyadenosine (S-cdA). Among many DNA lesions. S-cdA is unique in that it represents a concomitant damage to both the sugar and base moieties of the same nucleoside. Because of the presence of the C8-C5` covalent bond, S-cdA is repaired by nucleotide excision repair unlike most of other oxidatively induced lesions in DNA, which are subject to base excision repair. To test our hypothesis, we isolated genomic DNA from brain, kidney and liver of wild type and csb knockout (csb(-/-)) mice. Animals were not exposed to any exogenous oxidative stress before the experiment. DNA samples were analysed by liquid chromatography/mass spectrometry with isotope-dilution. Statistically greater background levels of S-cdA were observed in all three organs of csb(-/-) mice than in those of wild type mice. These results suggest the in vivo accumulation of S-cdA in genomic DNA due to lack of its repair in csb(-/-) mice. Thus, this study provides, for the first time, the evidence that CSB plays a role in the repair of the DNA helix-distorting tandem lesion S-cdA. Accumulation of unrepaired S-cdA in vivo may contribute to the pathology associated with CS. Published by Elsevier B.V.

Sdo1p, the yeast orthologue of Shwachman-Bodian-Diamond syndrome protein, binds RNA and interacts with nuclear rRNA-processing factors

The Shwachman-Bodian-Diamond syndrome protein (SBDS) is a member of a highly conserved protein family of not well understood function, with putative orthologues found in different organisms ranging from Archaea, yeast and plants to vertebrate animals. The yeast orthologue of SBDS, Sdo1p, has been previously identified in association with the 60S ribosomal subunit and is proposed to participate in ribosomal recycling. Here we show that Sdo1p interacts with nucleolar rRNA processing factors and ribosomal proteins, indicating that it might bind the pre-60S complex and remain associated with it during processing and transport to the cytoplasm. Corroborating the protein interaction data, Sdo1p localizes to the nucleus and cytoplasm and co-immunoprecipitates precursors of 60S and 40S subunits, as well as the mature rRNAs. Sdo1p binds RNA directly, suggesting that it may associate with the ribosomal subunits also through RNA interaction. Copyright (C) 2009 John Wiley & Sons, Ltd.

Restless legs syndrome - en beskrivning av dess inverkan på individens sömn, livskvalitet samt olika behandlingsformer : En systematisk litteraturstudie

Syftet med denna systematiska litteraturstudie var att beskriva hur restless legs inverkar på individens sömn och livskvalitet. Syftet var även att granska vilka olika former av behandlingar som finns att tillgå vid restless legs. För att finna information om detta ämne har endast vetenskapliga artiklar använts. Datainsamlingen har skett via databaser, internet samt Högskolans bibliotek, och artiklar från år 1995 och framåt har valts ut. Inklusionskriterier för denna studie var att de valda artiklarna skulle vara internationella vetenskapliga artiklar i fulltext. De funna artiklarna granskades med avseende på vetenskaplig kvalitet och poängsattes utifrån för ändamålet avsedda granskningsmallar. Denna bedömning resulterade i 21 artiklar. Resultatet visade att restless legs patienter upplever sömnbristen som det största problemet. För flertalet individer som drabbas av restless legs försämrades livskvaliteten och patienterna drabbades vanligtvis av psykologiska och fysiologiska besvär. Det vanligaste sättet att behandla restless legs var att använda dopaminerga läkemedel samt bensodiazepiner, antiepileptika och opioider. Andra former av behandlingar var järn, homeopatiska läkemedel, hypnos samt fysisk aktivitet. Det förekom även att restless legs patienter på eget initiativ använde hasch eftersom det ansågs lindra symtomen.

Omvårdnadsåtgärder som stärker egenvården hos patienter med Irritable Bowel Syndrome

Syftet med denna systematiska litteraturstudie var att belysa hur sjuksköterskans omvårdnad kan stödja egenvårdsförmågan hos patienter med IBS. Den viktigaste omvårdnadsåtgärden var att tidigt i samband med diagnostiseringen av IBS, ge information och kunskap om sjukdomen, dess prognos samt behandling, vilket visades förbättra upplevd livskvalitet samt ge symtom-lindring. IBS skolor startade av sjuksköterskor förbättrade patienternas hälsobeteende samt minskade symtomen. Genom introduktion av guidebok innehållande råd om kost, motion, stresshantering samt symtomkontroll upplevde patienterna en minskning av symtom, vilket även ledde till en minskning av antalet besök inom sjukvården. När sjuksköterskan använde olika frågeformulär i kontakten med patienter med IBS kunde patienternas problem identifieras och strategier för egenvården planeras samt individuella handlingsplaner skapas. Sjuksköterskans kunskap och förståelse om patientens egen sjukdomsupplevelse samt copingstrategi ledde till att patienten tog en mer aktiv roll i sjukdomshantering. Patienters behandling borde inriktas på livsstilsförändringar, som till exempel psykosocial arbetsmiljö, kost, fysisk aktivitet, samt stresshantering. Genom att patienten förde dagbok över kostintag och sedan gjorde jämförelser med ökade eller minskade symtom kunde faktorer identifieras i matvanor samt kostintag som inverkade på symtomen. Dorotea Orems omvårdnadsmodell har legat till grund för denna studie där tron på människans egna resurser framhålls.

Study of Proteinuria: Isolation of Proteins from the Nephrotic Syndrome

One of the most puzzling phenomena of abnormal renal physiology is the occurrence of the nephrotic syndrome. The syndrome has been defined by a collection of clinical and pathological symptoms, but there is no correlation between the clinical and pathological symptoms nor is the etiology of the syndrome known. Proteinuria is probably the most distinguishing feature in the nephrotic syndrome, and there are two possible explanations for its occurrence: (1) the excessive amounts of protein found in nephrotic urine could be due to an increased basement membrane permeability in the glomerulus of the kidney or (2) dysproteinemia. An attempt has been made to evaluate the theory of dysproteinemia in connection with the syndrome. The albumin fractions of nephrotic urine have been studied for their amino acid composition by separating them from the urine by paper electrophoresis, hydrolyzing them, and identifying the amino acids present by two-dimensional chromatography. There seem to be no variations in the qualitative makeup of nephrotic albumin from that of normal albumin, but the literature shows that there are some slight variations in the quantitative amino acid composition of nephrotic albumin compared with normal albumin. More extensive and highly developed experimentation along the lines of protein structure and composition must be done before it can conclusively be stated that dysproteinemia is of importance in the nephrotic syndrome.

Hyper-Automaton: avaliação interativa de alunos em cursos na WEB baseado em autômatos finitos

O objetivo desta dissertação é a elaboração de uma técnica da aplicação do formalismo de Autômatos Finitos com Saída (Máquina de Mealy e Máquina de Moore) como um modelo estrutural para a organização de hiperdocumentos instrucionais, em destacar especial, Avaliação e Exercício. Esse objetivo é motivado pela organização e agilização do processo de avaliação proporcionado ao professor e ao aluno. Existem diferentes técnicas de ensino utilizadas na Internet, algumas dessas continuam sendo projetadas com o uso de metodologias tradicionais de desenvolvimento, outras têm a capacidade de modelar de forma integrada e consistente alguns aspectos necessários para uma aplicação WEB. Para alcançar o objetivo proposto, foram realizadas pesquisas nas várias áreas abrangidas pelo tema em evidência, tanto relativo ao processo tradicional (aplicação de prova utilizando metodologia tradicional), como o desenvolvimento de software mediado por computador e uso da Internet em si. A modelagem de desenvolvimento para Internet deve integrar características de técnicas de projeto de sistemas de hipermídia devido à natureza hipertextual da Internet. O uso de hiperdocumento como autômatos com saída está na forma básica de representação de hipertexto, em que cada fragmento de informação é associado a um nodo ou a um link (estado/transições) do grafo. Sendo assim, os arcos direcionados representam relacionamentos entre os nodos ou links, ou seja, uma passagem do nodo origem para o nodo destino. As n-uplas dos autômatos apresentam uma correspondência as estruturas de hiperdocumentos na WEB, seu estado/transição inicial corresponde a sua primeira página e suas transições definidas na função programa, funcionam como ligações lógicas, quando selecionadas durante a navegação do hipertexto. Entretanto, faz-se necessário um levantamento dos modelos de hipertextos e das ferramentas de implementação disponíveis para a Internet, a fim de que seja capaz de suportar as peculiaridades do ambiente. Tudo isso deve ser integrado preferencialmente em um paradigma de desenvolvimento amplamente aceito, para que os projetistas não tenham muitas dificuldades em assimilar os conceitos propostos. A proposta apresentada nesta dissertação, batizada de Hyper-Automaton (hipertexto e autômato), consiste na integração de um Curso na WEB, utilizando formalismo de Autômatos Finitos com Saída para a modelagem dos conceitos necessários e definição das fases adequadas para completar a especificação de Sistema Exercício e Avaliação, bem como a especificação da Geração Automática dos Exercícios e Avaliações baseadas em autômatos para a WEB. Os modelos criados abrangem conceitos de Máquina de Mealy, Máquina de Moore e Aplicações de Hiperdocumentos e Ferramentas de Programação para Internet, os mesmos já testados em caso real. Os parâmetros apurados, nos testes, serviram a uma seqüência de etapas importantes para modelar e complementar a especificação do sistema projetado. Com os parâmetros e etapas de modelagem, a metodologia Hyper-Automaton consegue integrar, de forma consistente, as vantagens de várias técnicas específicas de modelagem de documentos e sistemas de hipermídia. Essas vantagens, aliadas ao suporte às ferramentas de desenvolvimento para Internet, garantem que a metodologia fique adequada para a modelagem de Sistemas com aplicação de métodos de autômatos para exercícios e avaliação na WEB.

XHA: eXtensible Hyper-Automation

O objetivo geral desta dissertação é estudar as possibilidades de flexibilização da função de saída do Sistema Hyper-Automaton além das rígidas possibilidades utilizadas atualmente com a utilização direta do HTML, objetivando eliminar as limitações como execução de aplicações proprietárias, caracteres incompatíveis entre browsers, excesso de tráfego na rede, padronizar aplicações, incrementar recursos didáticos, melhorar o suporte a aplicações multimídia atuais e futuras, facilitar a manutenção, implementação e reuso, alterar o layout de saída no browser de maneira dinâmica, explorar outros recursos de links, estabelecer padrões de organização do material instrucional criado pelo professor e muitas outras. Tal sistema anteriormente desenvolvido e funcionando adequadamente, é baseado no formalismo de Autômatos Finitos com Saída como modelo estrutural para organização de hiperdocumentos instrucionais, em especial em cursos na Web, tornando o material hipermídia independente do controle da aplicação. O Sistema Hyper-Automaton, tornou-se portanto, um sistema semi-automatizado para suporte a cursos na Web. Com o desdobramento da pesquisa, esta procurou ir mais além e descreveu possibilidades de não só estudar os aspectos possíveis de formatação de saída do sistema, mas reestruturá-lo totalmente sobre uma linguagem de markup padrão, buscando atualizá-lo tecnologicamente definindo outras possibilidades para que significativos trabalhos futuros possam de maneira mais clara serem alcançados. Dessa maneira, esta dissertação centra-se no estudo da aplicação de formas de flexibilização do Sistema Hyper-Automaton, tanto na parte da estruturação de documentos que são conteúdos instrucionais armazenados, bem como, na forma desse material tornar-se-á disponível através de navegadores WWW compatíveis com as tecnologias propostas, possibilitando o incremento substancial de funcionalidades necessárias para cursos onde a Web é o principal meio. Esta pesquisa dá prosseguimento a dois trabalhos anteriormente concluídos no PPGC e do Curso de Bacharelado em Ciência da Computação da UFRGS no ano de 2000, na seqüência, Hyper-Automaton: Hipertextos e Cursos na Web Utilizando Autômatos Finitos com Saída, dissertação de mestrado de Júlio Henrique de A. P. Machado e Hyper-Automaton: Implementação e Uso, trabalho de diplomação de Leonardo Penczek.

Metabolic syndrome in postmenopausal women: higher prevalence in the Northeastern Region of Brazil than in other Latin American countries and the influence of obesity and socioeconomic factors

SILVEIRA, Inavan Lopes da; MARANHÃO, T. M. O.; AZEVEDO, George Dantas. Metabolic syndrome in postmenopausal women: higher prevalence in the Northeastern Region of Brazil than in other Latin American countries and the influence of obesity and socioeconomic factors. Climacteric (Carnforth), v.10, p.438-439, 2007.

Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome

SOARES, Elvira Maria Mafaldo et al. Prevalence of the metabolic syndrome and its components in Brazilian women with polycystic ovary syndrome. Fertility and Sterility, v.89, n.3, p.649-655, mar. 2008

Ovarian remnant syndrome in small animals

The ovarian remnant syndrome (ORS) is an iatrogenic disorder in bitches and queens, which is characterized by recurrence of estrus following surgical spay, due to the presence of a piece of ovarian tissue within the abdominal cavity. In most cases, the remnant ovary is found in the right ovarian pedicle, due to its topographic position, deeper and more cranial than the left ovary. The main clinical signs of ORS in small animals are the heat behavior and the presence of vaginal swelling/secretion, especially in canines. The diagnosis should be performed by means of vaginal cytology when attraction of males is detected, serum estrogen and progesterone levels and/or by challenging test with GnRH or hCG administration. However, vaginal citology is the most suitable and less expensive diagnostic tool. Nowadays the treatment of choice is a new laparotomy or laparoscopy, followed by removal of the remnant ovarian tissue. The surgical treatment has more chances of success if it is performed in the diestrus (i.e., between 15 and 60 days after the detection of attraction of males). Furthermore, a careful and accurate surgical procedure aided by advanced visualization techniques during ovariohysterectomy or ovariectomy is the best way to prevent ORS in companion animals.

Use of near-infrared Raman spectroscopy to detect IgG and IgM antibodies against Toxoplasma gondii in serum samples of domestic cats

Near-infrared Raman spectroscopy (NIRS) is a particularly promising technique that is being used in recent years for many biomedical applications. Optical spectroscopy has gained increasing prominence as a tool for quantitative analysis of biological samples, clinical diagnostic, concentration measurements of blood metabolites and therapeutic drugs, and analysis of the chemical composition of human tissues. Toxoplasmosis is an important zoonosis in public health, and domestic cats are the most important transmitters of the disease. This disease can be detected by several serological tests, which usually have a high cost and require a long time. The goal of this work was to investigate a new method to diagnosis Toxoplasma gondii infections using NIRS. In order to confirm antibody detection, 24 cat blood scrum samples were analyzed by the Raman spectra, from which 23 presented positive serology to toxoplasmosis and one was a reference negative serum. Characteristic Raman peaks allowed differentiation between negative and positive sera, confirming the possibility of antibody detection by Raman spectroscopy. These results give the first evidence that this technique can be useful to quantify antibodies in cat sera.