The Role of Lymphadenectomy in the Management of Renal Tumor

Objetivos: Avaliar os benefícios e morbilidade da linfadenectomia (LND) como componente integral da nefrectomia radical. Material e Métodos: Efetuámos uma pesquisa bibliográfica exaustiva com recurso a vários motores de busca informática, incluindo MEDLINE, PUBMED, GOOGLE SEARCH e AUA MEDSEARCH, correspondendo o período de análise aos últimos 30 anos, entre 1980 e 2010, e utilizando como palavras-chave, exclusivamente em terminologia anglosaxónica, as seguintes: lymph node dissection, lymphadenectomy, renal cell carcinoma, renal tumor, kidneyneoplasms, radical nephrectomy, staging e prognosis. Para uma validação rigorosa das publicações relevantes, utilizámos a Tabela de Níveis de Evidência e Graus de Recomendação de Oxford publicada em Março de 2009. Com base nestas informações, tentámos analisar em detalhe o papel da linfadenectomia no tratamento do carcinoma de células renais e o seu impacto em termos prognósticos. Resultados: Em mais de 150 artigos, considerados pelos autores como relevantes e bem estruturados, apenas 1 era um estudo prospetivo e aleatorizado (Nível de Evidência 1/Grau de Recomendação A). Neste estudo de 772 doentes N0 M0, a taxa de LND positiva foi de 4,0% em status ganglionar clinicamente negativo, não tendo havido qualquer vantagem na sobrevivência e, por isso, não foi recomendada por rotina. Embora a informação obtida da maioria dos estudos seja contraditória, vários estudos retrospetivos recomendam a LND como potencialmente benéfica em casos selecionados de tumor agressivo e em contexto de nefrectomia citorredutora seguida de terapêutica adjuvante,realçando alguns autores a remoção total, sempre que possível, de quaisquer adenopatias palpáveis. Conclusão: A LND não está recomendada, por rotina, em tumores renais com gânglios linfáticos clinicamente negativos. Terá algum benefício potencial em casos selecionados de tumor agressivo e em contexto de cirurgia citorredutora seguida de terapêutica adjuvante, incentivando-se nestas situações a remoção total, se possível, das adenopatias palpáveis. Consequentemente, o tipo de LND deverá ser individualizada e dependente do estadio/extensão da doença neoplásica. Será, provavelmente, útil em futuros protocolos de terapêutica adjuvante desde que associados a inquestionável melhoria da sobrevivência

Male Uro-Rectal Iatrogenic Fistula Treatment in Pelvic Tumours: A National Multi-Institutional Study

Introdução: As fístulas uro-rectais (FUR) constituem uma complicação devastadora do tratamento de tumores pélvicos e um desafio cirúrgico para o cirurgião reconstrutivo. Contudo, apesar da sua crescente incidência associada a uma utilização cada vez mais frequente das diferentes modalidades não-cirúrgicas, especialmente de radioterapia, com ou sem cirurgia, para o tratamento de tumores pélvicos, a fístula urorectal permanece relativamente rara. Dada a elevada improbabilidade do encerramento espontâneo da fístula uro-rectal, a correcção cirúrgica torna-se necessária na quase totalidade dos casos. Apesar da existência de várias técnicas cirúrgicas, as taxas de falência/recorrência são habitualmente elevadas, particularmente em fístulas rádicas. Descrevemos neste estudo a nossa experiência limitada no tratamento de fístulas urorectais resultantes de tratamentos de tumores pélvicos (aparelho urinário inferior e recto). Métodos: Entre Outubro de 2008 e Fevereiro de 2015, foram identificados 12 pacientes do sexo masculino com fístula urorectal e tratados nas nossas instituições. Foi efectuada revisão dos processos clínicos dos pacientes, incluindo a idade, sintomas, presença de comorbilidades, marcha diagnóstica, tipo e etiologia da fístula, tipo de reconstrução cirúrgica, follow-up e resultados. Foram excluídos do estudo todos os pacientes com fístula não-neoplásica/inflamatória. Resultados: Foram identificados e tratados 12 pacientes nas nossas instituições. Um dos pacientes, após ressecção anterior do recto, desenvolveu metástases ganglionares e hepáticas 4 meses após o diagnóstico da fístula urorectal, durante tratamento médico/antibiótico de abcesso pélvico e sua resolução após drenagem e, consequentemente, foi excluído do tratamento cirúrgico e do estudo. A idade média dos doentes era de 68 anos (53 – 78). Nove pacientes desenvolveram fístula uro-rectal após terapêutica de carcinoma da próstata): Dois após braquiterapia de baixa dosagem combinada com radioterapia externa; cinco após prostatectomia radical retropúbica (PRR), com radioterapia externa adjuvante em um; um após braquiterapia de baixa dosagem seguida de ressecção transuretral por obstrução prostática; e um após ultra-som focalizado de alta intensidade e radioterapia externa. Em dois pacientes, a fístula resultou de tratamento cirúrgico de carcinoma rectal, associado a radioterapia externa em um deles. Foi efectuada em todos os pacientes derivação fecal com colostomia e derivação urinária, ou com cateterização suprapúbica, ou com cateterização uretral durante o período de espera para a reconstrução cirúrgica. Não houve encerramento espontâneo de fístula urorectal em nenhum paciente. Onze pacientes foram submetidos a reconstrução cirúrgica. Foi utilizada abordagem exclusivamente perineal em sete doentes e abdominoperineal em quatro. Obteve-se encerramento eficaz da fístula em seis pacientes à primeira tentativa cirúrgica, dois doentes necessitaram uma segunda tentativa, enquanto que em um doente foram necessárias três tentativas cirúrgicas (duas delas em outras instituições) de forma a atingir um resultado com sucesso. Ocorreu falência cirúrgica em dois doentes, os quais, actualmente, não desejam qualquer tentativa reconstrutiva adicional. Estes dois doentes e um doente, em quem a reconstrução foi eficaz, permanecem ainda com colostomia. O tempo médio de follow- -up foi de 25,5 meses (3-75). Conclusão: As fístulas uro-rectais são uma complicação pouco frequente, mas devastadora, do tratamento dos tumores pélvicos, habitualmente associada com morbilidade debilitante e degradação da qualidade de vida. Embora a sua reconstrução cirúrgica possa ser extremamente difícil, ela é possível com sucesso na maioria dos casos através de uma abordagem perineal ou abdominoperineal agressiva e interposição de tecidos, quando indicada.info:eu-repo/semantics/publishedVersio

Imaging Coulomb Islands in a Quantum Hall Interferometer

In the Quantum Hall regime, near integer filling factors, electrons should only be transmitted through spatially-separated edge states. However, in mesoscopic systems, electronic transmission turns out to be more complex, giving rise to a large spectrum of magnetoresistance oscillations. To explain these observations, recent models put forward that, as edge states come close to each other, electrons can hop between counterpropagating edge channels, or tunnel through Coulomb islands. Here, we use scanning gate microscopy to demonstrate the presence of quantum Hall Coulomb islands, and reveal the spatial structure of transport inside a quantum Hall interferometer. Electron islands locations are found by modulating the tunneling between edge states and confined electron orbits. Tuning the magnetic field, we unveil a continuous evolution of active electron islands. This allows to decrypt the complexity of high magnetic field magnetoresistance oscillations, and opens the way to further local scale manipulations of quantum Hall localized states

Dissecting the Relation between a Nuclear Receptor and GATA: Binding Affinity Studies of Thyroid Hormone Receptor and GATA2 on TSHβ Promoter

Background: Much is known about how genes regulated by nuclear receptors (NRs) are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up-or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 (GATA2-Zf) has an important role in down-regulation of the thyrotropin gene (TSH beta) by liganded thyroid hormone receptor (TR). Methodology/Principal Findings: In an effort to better understand the mechanism that drives TSH beta down-regulation by a liganded TR and GATA2, we have carried out equilibrium binding assays using fluorescence anisotropy to study the interaction of recombinant TR and GATA2-Zf with regulatory elements present in the TSH beta promoter. Surprisingly, we observed that ligand (T3) weakens TR binding to a negative regulatory element (NRE) present in the TSH beta promoter. We also show that TR may interact with GATA2-Zf in the absence of ligand, but T3 is crucial for increasing the affinity of this complex for different GATA response elements (GATA-REs). Importantly, these results indicate that TR complex formation enhances DNA binding of the TR-GATA2 in a ligand-dependent manner. Conclusions: Our findings extend previous results obtained in vivo, further improving our understanding of how liganded nuclear receptors down-regulate gene transcription, with the cooperative binding of transcription factors to DNA forming the core of this process.Medical Research Council (MRC), UKConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazi

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Stroke Correlates in Chagasic and Non-Chagasic Cardiomyopathies

BACKGROUND: Aging and migration have brought changes to the epidemiology and stroke has been shown to be independently associated with Chagas disease. We studied stroke correlates in cardiomyopathy patients with focus on the chagasic etiology. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional review of medical records of 790 patients with a cardiomyopathy. Patients with chagasic (329) and non-chagasic (461) cardiomyopathies were compared. There were 108 stroke cases, significantly more frequent in the Chagas group (17.3% versus 11.1%; p<0.01). Chagasic etiology (odds ratio [OR], 1.79), pacemaker (OR, 2.49), atrial fibrillation (OR, 3.03) and coronary artery disease (OR, 1.92) were stroke predictors in a multivariable analysis of the entire cohort. In a second step, the population was split into those with or without a Chagas-related cardiomyopathy. Univariable post-stratification stroke predictors in the Chagas cohort were pacemaker (OR, 2.73), and coronary artery disease (CAD) (OR, 2.58); while atrial fibrillation (OR, 2.98), age over 55 (OR, 2.92), hypertension (OR, 2.62) and coronary artery disease (OR, 1.94) did so in the non-Chagas cohort. Chagasic stroke patients presented a very high frequency of individuals without any vascular risk factors (40.4%; OR, 4.8). In a post-stratification logistic regression model, stroke remained associated with pacemaker (OR, 2.72) and coronary artery disease (OR, 2.60) in 322 chagasic patients, and with age over 55 (OR, 2.38), atrial fibrillation (OR 3.25) and hypertension (OR 2.12; p = 0.052) in 444 non-chagasic patients. CONCLUSIONS/SIGNIFICANCE: Chagas cardiomyopathy presented both a higher frequency of stroke and an independent association with it. There was a high frequency of strokes without any vascular risk factors in the Chagas as opposed to the non-Chagas cohort. Pacemaker rhythm and CAD were independently associated with stroke in the Chagas group while age over 55 years, hypertension and atrial fibrillation did so in the non-Chagas cardiomyopathies

Long-Term Weekly Iron-Folic Acid and De-Worming Is Associated with Stabilised Haemoglobin and Increasing Iron Stores in Non-Pregnant Women in Vietnam

BACKGROUND: The prevalence of anaemia and iron deficiency in women remains high worldwide. WHO recommends weekly iron-folic acid supplementation where anaemia rates in non-pregnant women of reproductive age are higher than 20%. In 2006, a demonstration project consisting of weekly iron-folic acid supplementation and regular de-worming was set up in two districts in a northern province in Vietnam where anaemia and hookworm rates were 38% and 76% respectively. In 2008 the project was expanded to all districts in the province, targeting some 250,000 women. The objectives of this study were to: 1) examine changes in haemoglobin, iron stores and soil transmitted helminth infection prevalence over three years and 2) assess women's access to and compliance with the intervention. METHODS AND FINDINGS: The study was a semi-cross-sectional, semi-longitudinal panel design with a baseline survey, three impact surveys at three-, twelve- and thirty months after commencement of the intervention, and three compliance surveys after ten weeks, eighteen and thirty six months. RESULTS: After thirty months, mean haemoglobin stabilised at 130.3 g/L, an increase of 8.2 g/L from baseline, and mean serum ferritin rose from 23.9 µg/L to 52 µg/L. Hookworm prevalence fell from 76% to 22% over the same period. After thirty six months, 81% of the target population were receiving supplements and 87% were taking 75% or more of the supplements they received. CONCLUSIONS: Weekly iron-folic acid supplementation and regular de-worming was effective in significantly and sustainably reducing the prevalence of anaemia and soil transmitted helminth infections and high compliance rates were maintained over three years

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production