A Case of Amyloid Goitre in Heavy Chain Amyloidosis: Diagnostic Challenges and Clinical Implications.

Immunoglobulin heavy chain amyloidosis (AH amyloidosis) is an extremely rare subtype of immunoglobulin-derived amyloidosis and there is limited literature on how to diagnose and manage this disorder. We describe a rare case of AH amyloidosis with amyloid goitre and the importance of mass spectrometry in the identification of the different types of amyloids. While additional studies are needed, several observations suggest important practical implications, including differences in clinical picture, prognosis, and pathologic diagnosis. LEARNING POINTS: Immunoglobulin heavy chain amyloidosis is an extremely rare subtype of immunoglobulin-derived amyloidosis and amyloid goitre is even rarer.There is limited literature on how to diagnose and manage this disorder.This case portrays one of these cases - one of the few existing in the literature - and reinforces the diagnostic complexity of this entity.

[Multiple Myeloma Treatment Guidelines by the Portuguese Group of Multiple Myeloma]. / Recomendações do Grupo Português do Mieloma Múltiplo para Tratamento do Mieloma Múltiplo.

The treatment of multiple myeloma has profoundly changed with the introduction of several innovative therapies. The optimization of therapeutic sequencing through the combined use of the various drugs developed in recent years and the attention given to the characteristics of patients have allowed the reduction of toxicities and increased survival and quality of life of patients with multiple myeloma. These treatment recommendations from the Portuguese Multiple Myeloma Group offer guidance for first-line treatment and progression/relapse situations. These recommendations are given highlighting the data that justify each choice and referring to the respective levels of evidence that support these options. Whenever possible, the respective national regulatory framework is presented. These recommendations constitute an advance towards the best treatment of multiple myeloma in Portugal.

O tratamento do mieloma múltiplo tem sido amplamente alterado com introdução de várias terapêuticas inovadoras. A otimização da sequenciação terapêutica através do uso combinado dos vários fármacos desenvolvidos nos últimos anos e a atenção dada às características dos doentes têm permitido diminuir toxicidades e aumentar a sobrevivência dos doentes, bem como aumentar a sua qualidade de vida. As presentes recomendações terapêuticas do Grupo Português do Mieloma Múltiplo oferecem orientações para o tratamento de primeira linha e progressão/recaída. As recomendações são fundamentadas evidenciando os dados que justificam cada escolha e referindo os respetivos níveis de evidência que suportam essas opções. Sempre que possível é apresentado o respetivo enquadramento regulamentar nacional. Estas recomendações constituem um avanço para o melhor tratamento do mieloma múltiplo em Portugal.

Screening a Targeted Panel of Genes by Next-Generation Sequencing Improves Risk Stratification in Real World Patients with Acute Myeloid Leukemia.

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria.

CANCROX: a cross-species cancer therapy database.

Cancer comprises a set of more than 200 diseases resulting from the uncontrolled growth of cells that invade tissues and organs, which can spread to other regions of the body. The types of cancer found in humans are also described in animal models, a fact that has raised the interest of the scientific community in comparative oncology studies. In this study, bioinformatics tools were used to implement a computational model that uses text mining and natural language processing to construct a reference database that relates human and canine genes potentially associated with cancer, defining genetic pathways and information about cancer and cancer therapies. The CANCROX reference database was constructed by processing the scientific literature and lists more than 1300 drugs and therapies used to treat cancer, in addition to over 10 000 combinations of these drugs, including 40 types of cancer. A user-friendly interface was developed that enables researchers to search for different types of information about therapies, drug combinations, genes and types of cancer. In addition, data visualization tools allow to explore and relate different drugs and therapies for the treatment of cancer, providing information for groups studying animal models, in this case the dog, as well as groups studying cancer in humans.

Effects of habitat fragmentation on the persistence of medium and large mammal species in the Brazilian Savanna of Goiás State / Efeitos da fragmentação de habitat na persistência de espécies de mamíferos de médio e grande porte no Cerrado em Goiás

Abstract: Habitat loss and fragmentation are the main threats to the conservation of Cerrado biodiversity. The objective of this study was to evaluate the implications of habitat loss on the persistence of medium and large mammal species, considering the spatial and temporal changes (years 1985, 2000 and 2014) to the evaluated fragments. The study was carried out in 14 fragments (10.5 - 618 ha), located in Southeastern Goiás, Brazil. Records for 24 mammal species were obtained and revealed the two sites with the largest habitat amount in the landscape contained higher species richness than the remaining sites. The three mammal groups based on body mass (weight < 5 kg; weight between 5 and 20 kg; and weight > 20 kg) analyzed in this study showed different responses regarding landscape changes. For larger mammals (between 5 - 20 kg and > 20 kg), there was significant association between current species richness and the amount of habitat in 2014, while the species richness of smaller mammals did not significantly correlate with any of the variables assessed for any of the years. Therefore, the amount of habitat present within the current landscape was the most important variable regarding mammal species richness, especially for the larger species. The time lag was not evident at the time scale evaluated, and this delay in response may have occurred in a relatively short time (< 15 years). For the remaining fragments in the studied landscapes, most are too small to support populations of some larger mammal species and may also leave individuals more vulnerable to anthropogenic actions (e.g. hunting), whose effects may accelerate local extinctions.

Resumo: A perda e a fragmentação de habitats são as principais ameaças à conservação da biodiversidade no bioma Cerrado. O presente estudo objetivou avaliar as implicações da perda de habitat na persistência de espécies de mamíferos de médio e grande porte, levando em consideração as alterações espaciais e temporais dos fragmentos avaliados. O estudo foi realizado em 14 fragmentos (10,5 - 618 ha), localizados na região sudeste de Goiás, Brasil. Foram obtidos registros de 24 espécies de mamíferos, sendo que os dois locais com as maiores quantidades de habitat na paisagem apresentaram maior riqueza de espécies que as demais áreas. Os três grupos de mamíferos baseados na massa corporal criados neste estudo (peso < 5 kg; peso entre 5 e 20 kg; e peso > 20 kg) apresentaram respostas diferentes em relação às mudanças na paisagem. Para os mamíferos de maior porte, houve significativa associação entre a riqueza atual de espécies e a quantidade de habitat na paisagem de 2014, mas a riqueza de espécies de mamíferos de menor porte não apresentou relação significativa com nenhuma das variáveis das paisagens analisadas. Portanto, a quantidade de habitat presente na paisagem atual foi a variável mais importante para a riqueza de espécies de mamíferos, principalmente para as espécies de maior porte. O tempo de latência não ficou evidente na escala temporal avaliada, sendo que esse atraso na resposta pode ter ocorrido em tempo relativamente curto (< 15 anos), pois os fragmentos remanescentes nas paisagens estudadas em sua maioria são pequenos para suportar populações de mamíferos de maior porte e também podem deixar os indivíduos mais vulneráveis às ações antrópicas (e.g. caça), cujos efeitos podem acelerar as extinções locais.

Bisfenol A: o uso em embalagens para alimentos, exposição e toxicidade – Uma Revisão / Bisphenol A: Review on its use in the food packaging, exposure and toxicity

O bisfenol A é um composto industrial produzido em larga escala em todo o mundo, sendo utilizado para produzir polímeros sintéticos, inclusive as resinas epóxi, que são empregadas no envernizamento interno e externo de latas de alimentos, e na produção de policarbonato com aplicações em mamadeiras e garrafões de água. Outras aplicações menos significativas são a produção de policloreto de vinila (PVC), manufatura de papel térmico, poliuretano, poliamida e de produto para retardamento de chama, bem como na preparação de “selantes” e resinas dentárias. O bisfenol A é considerado como disruptor endócrino que interfere na produção, liberação, transporte, metabolismo, ligação ou eliminação dos hormônios naturais, responsáveis pela manutenção do equilíbrio e regulação dos processos de desenvolvimento. Dentre as várias vias de exposição humana ao bisfenol A, a exposição alimentar é a mais preocupante por atingir potencialmente um maior número de pessoas, em diversas faixas etárias, e que pode ocorrer durante longos períodos em pequenas doses e sem serem detectadas. Na presente revisão foram abordadas as vias de exposição ao bisfenol A, sua toxicidade e as legislações quanto aos limites para garantir a saúde humana...

Assemblage of medium and large size mammals in an urban Semideciduous Seasonal Forest fragment in Cerrado biome

Nowadays, the processes of deforestation and loss of habitats represent a major threat to many species of mammals. These processes cause changes in natural landscapes by decreasing area, connectivity, and fragment size, and increasing edge effects and number of fragments. Understanding which and how many species persist in disturbed fragments may indicate the species' minimum requirements and might contribute to their conservation. Here we show how the mammalian fauna of medium and large size (higher than 1 kg) are structured in a semideciduous seasonal forest fragment of 36.5 ha in the urban area of Jataí, Goiás. We performed the sampling with 30 sand track plots (1 x 1 m). We analyzed the relative record frequency and built a collector's curve to demonstrate the sampling effort. With a total effort of 600 track plots × days, we recorded twelve species of mammals with our tracks sampling method, from which only the wild mammals were included in the analyzes (11 species). The estimated species richness reached 13 species (SD (Standard Deviation) = ±1, CI (Confidence Interval) = ±2 (11 – 15 species). The species with the highest relative record frequency was Didelphis albiventris and the species with the lowest was Tamandua tetradactyla. The fragment size must be a limiting factor to the richness and to the occurrence of species, as it may not be sufficient to allow the persistence of a population or an individual. Disturbances that originated from houses, like domestic animals and movement of people, also contributed to the removal and extinction of species. To conserve the species in the fragment, we suggest the prevention of entrance of people and of domestic animals. We also recommend increased connectivity of the fragment with the landscape external to the urban area in order to allow the movement of the currently present species.

Atualmente, os processos de perda e fragmentação de habitats representam uma das maiores ameaças às espécies de mamíferos, provocando mudanças nas paisagens diminuindo a área natural, a conectividade e o tamanho dos fragmentos e aumentando o número dos fragmentos e o efeito de borda. Entender quais e quantas espécies habitam fragmentos perturbados pode indicar seus requerimentos mínimos contribuindo para sua conservação. Neste trabalho é mostrado como está estruturada a mastofauna de médio e grande porte (>1 kg) em um fragmento de Floresta Estacional Semidecidual de 36,5 ha na área urbana do município de Jataí, Goiás. A coleta foi realizada com o uso de 30 parcelas de areia (1 x 1 m), foi também analisada a frequência de registro e construída uma curva do coletor para demonstrar o esforço de coleta. Com um esforço total de 600 parcelas/dias foram registradas doze espécies de mamíferos, mas somente não domésticas foram inclusas nas análises (onze espécies). A riqueza estimada foi de 13 espécies (DP (Desvio Padrão) = ± 1, IC (Intervalo de Confiança) ± 2 (11 – 15 espécies). A espécie com a maior frequência relativa de registros foi Didelphis albiventris e a com menor frequência relativa foi Tamandua tetradactyla. O tamanho do fragmento deve ser um limitante para a riqueza e permanência das espécies, pois pode não ser suficiente para a persistência de uma população ou mesmo de um individuo. Perturbações advindas das moradias como animais domésticos e o trânsito de pessoas também devem contribuir para o afastamento e extinção das espécies. Para conservação das espécies no fragmento, sugerimos a proibição da entrada de pessoas e animais domésticos, bem como aumentar a conectividade do fragmento com a paisagem exterior à área urbana, a fim de permitir a movimentação das espécies presentes.

Immunolocalization of IFN-gamma in the lesions of resistant and susceptible mice to Paracoccidioides brasiliensis infection.

The important role of interferon-gamma (IFN-γ) in protective immunity in mycosis is well established, except for its participation in fungal granulomas. Herein, we employ immunohistochemical reactions to describe the in situ localization of IFN-γ in granulomas of susceptible (B10.A) and resistant (A/J) mice to infection with Paracoccidioides brasiliensis (Pb). After infection with the highly virulent Pb18, IFN-γ-positive lymphomononuclear cells were localized mainly at the periphery of granulomas in both mouse strains. The numbers of positive cells found in compact granulomas of A/J mice increased significantly from 15 to 120 days postinfection. At this time, significantly more positive cells were detected in the compact granulomas of resistant mice than in the loose, multifocal lesions of the susceptible ones. In infection with the slightly virulent Pb265, the same pattern of IFN-γ localization was found as in Pb18 infection, but there was decreased staining at 120 days due to the presence of only residual lesions in both mouse strains. The marked IFN-γ staining observed in the granulomas of resistant mice at the later stage of Pb infection confirms its importance in fungal dissemination control, and suggests a contribution to the development of paracoccidioidal granuloma.

Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection.

Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination.

Nitric oxide participation in granulomatous response induced by Paracoccidioides brasiliensis infection in mice.

The role of nitric oxide (NO) in granulomas of Paracoccidioides brasiliensis-infected inducible NO synthase-deficient C57BL/6 mice (iNOS KO) and their wild-type counterparts and its association with osteopontin (OPN) and matrix metalloproteinases (MMPs) was studied. At 15 days after infection (DAI), iNOS KO mice showed compact and necrotic granulomas with OPN+ macrophages and multinucleated giant cells, whereas wild-type mice developed loose granulomas with many fungi and OPN+ cells distributed throughout the tissue. In addition, high OPN levels and fungal load were observed in iNOS KO mice. Both experimental groups had MMP-9 activity. At 120 DAI, iNOS KO had smaller granulomas with OPN+ cells, lower OPN levels, lower fungal load and decreased MMP-9 activity compared with wild-type mice. These findings suggest that NO has an important role in granuloma modulation, by controlling OPN and MMP production, as well as by inducing loose granulomas formation and fungal dissemination, resulting, at later phases, in progression of paracoccidioidomycosis.

Osteopontin involvement in granuloma formation and in the severity of Paracoccidioides brasiliensis infection.

The participation of osteopontin (OPN) in Paracoccidioides brasiliensis infected mice, its association to granulomatogenesis, severity of infection, pattern of lesions, nitric oxide (NO) levels and fungal load were evaluated in this investigation. Immunohistochemistry analysis showed marked OPN staining in extracellular matrix and in macrophages and multinucleated giant cells at the center of lesions, suggesting a possible role of OPN in the distribution of these cells within the granulomas. At 15 days post-infection with a virulent P. brasiliensis isolate, OPN+ cells were more numerous and intensely immunostained in the loose granulomas of susceptible mice than in those of resistant mice. In addition, high fungal loads and low NO levels were observed in susceptible mice. At 120 days after infection, resistant mice had increased total OPN levels (ELISA) and OPN positivity in compact granulomas, higher NO levels and lower fungal loads than susceptible mice. Residual lesions associated with low OPN levels, high NO and control of fungal dissemination were observed in both mouse strains at 120 days post-infection with the slightly virulent fungal isolate. Therefore, OPN could be associated with higher severity of the disease in an early phase of infection and with a degree of control of the progressive infection.

Ressecção Transuretral da Próstata (RTUP): Complicações / Transurethral Resection of the Prostate (TURP): Postoperative and Transoperative complications in a Teaching Hospital

Objetivo: Avaliar o impacto da ressecção transuretral da próstata (RTUP) aplicada em pacientes com hiperplasia prostática benigna e a prevalência das complicações intra-operatórias e pós-operatórias em um centro médico de referência. Metodologia: Analisamos 172 prontuários de pacientes submetidos a RTUP para HPB no Hospital de Base de 2000 a 2002. Segundo um protocolo elaborado, Observamos no pré-operatório dados demográficos, antecedentes mórbidos e indicação cirúrgica. A condição clínica foi medida, no pré e pósoperatórios, pelo IPSS (international prostatic symptoms score), prevalência dos sintomas prostáticos (LUTS), dosagem de PSA (prostatic specific antigen), ultra-sonografia (US) e antomopatológico. Em relação à RTUP, investigamos o tipo de anestesia, o tempo operatório, e as complicações intra-operatórias e pós-operatórias. Resultados: Obtivemos idade média de 68.68 anos, união estável em 81%, e 87% de caucasóides. A prevalência dos sintomas do trato urinário baixo, conhecidos pela sigla LUTS da língua inglesa que significa lower urinary tract symptoms após a RTUP abaixou significativamente (p<0.05), exceto para dor suprapúbica e disúria. No pré-operatório, os valores médios do PSA total e do volume prostático foram 9.87ng/ml e 51.71g, respectivamente. A duração média da RTUP foi de 61.3 min, com ocorrência de intoxicação hídrica em 9.9% e hemorragia em 5.8%. O tempo de internação foi de 3.42 dias, encontrando complicações pós-operatórias em 62.1% dos casos, com altas incidências de infecção urinária, hemorragia, falha da micção e incontinência urinária. Conclusão: Na avaliação do tratamento cirúrgico da HPB, reconhecido como padrão-ouro, houve redução significativa dos LUTS apesar da elevada morbidade relacionada à RTUP neste estudo