Diagnóstico Pré-Natal de Uropatia: Importância do Desenvolvimento Embriológico Renal

As uropatias malformativas constituem a principalcausa de anomalia neonatal nao letal. Estas anomalias do desenvolvimento devem ser interpretadas com base no conhecimento da morbilidade e, em alguns casos, a mortalidade associada a este tipo de patologia 1,2. As malformações congénitas devem ser pensadas com base no conhecimento da dinâmica do normal desenvolvimento embrionário e dos múltiplos factores reguladores intervenientes, so assim será possivel estabelecer estratégias eficazes de investigação e terapêutica

Prenatally Diagnosed Uropathies: Ten Years of Follow-Up

Introdução: As anomalias do tracto urinário são detectadas com uma frequência cada vez maior devido à sistematização da vigilância ecográfica durante a gravidez aliada à sofisticação técnica e à experiência dos ecografistas. Objectivo: Analisar os principais diagnósticos pós-natais investigados na sequência do estudo evolutivo prolongado das uropatias fetais seguidas no ambulatório da nefrologia pediátrica do Hospital de Dona Estefânia. Doentes e Métodos: Estudo retrospectivo dos 392 casos de uropatia fetal observados num período de dez anos e submetidos ao protocolo de investigação em uso na unidade. Resultados: O estudo inclui 362 casos; excluímos 30 processos que não completaram a investigação. A relação sexo masculino: feminino foi de 2: 1. O diagnóstico pré-natal foi realizado em média às 28.9 semanas e a idade média de admissão foi de 68 dias. No estudo evolutivo pós-natal verificou-se a formulação de um diagnóstico definitivo em 349 (96.4%) das crianças. Em 109 crianças (30%) a anomalia fetal foi transitória. Em 75 (20.7%) a dilatação era funcional. Confirmou-se a existência de uropatia em 165/362 crianças: refluxo vesico-ureteral 70/165 (42.4%), displasia multiquística 21%, síndroma da junção pielo-ureteral 16.4%, entre os principais. Nenhum caso evoluiu para insuficiência renal e há a registar, apenas, um caso de hipertensão arterial por poliquistose renal. Conclusão: A planificação da investigação pós-natal reveste-se ainda de alguma controvérsia e continua a evoluir principalmente no grupo das anomalias unilaterais e assintomáticas

Prenatal Diagnosis of Urinary Tract Anomalies and Value of Voiding Cystography for Postnatal Outcome

A utilização sistemática da cistouretrografia miccional, no âmbito da investigação pós-natal das anomalias fetais do aparelho urinário, é controversa. A possibilidade de diagnosticar refluxo vesico-ureteral (RVU) antes de surgir infecção urinária é aliciante pela influência que pode ter na história natural da nefropatia do refluxo. Neste artigo, partindo de uma série de 116 casos de anomalia fetal do aparelho urinário num período de 5 anos, apresentam-se as características e evolução de 19 casos de RVU. A cistouretrografia miccional (CUM) efectuada em 109 casos (94%) identificou RVU em 19 (17.4%). Predominou o sexo masculino (5:1). Em 13 casos (19 unidades renais refluentes) o RVU era a única anomalia urinária detectada (grupo I); em 6 casos (8 unidades refluentes) o RVU estava associado a outras anomalias do tracto urinário (grupo II). Em 10 unidades refluentes do grupo I (55%) a avaliação ecográfica pós-natal foi considerada normal. Uma ecografia pós-natal normal não exclui a existência de RVU e, de acordo com os nossos resultados, todos os casos de dilatação da pélvis renal fetal beneficiam, no período pós-natal, de controlos ecográficos seriados e da realização de CUM. A confirmação precoce de RVU e a consequente instituição de quimioprofilaxia podem contribuir para a redução da morbilidade associada à infecção urinária e à nefropatia de refluxo

Understanding the formation of deep eutectic solvents: betaine as a universal hydrogen bond acceptor

© 2020 Wiley-VCH GmbH The mechanism of formation of betaine-based deep eutectic solvents (DES) is presented for the first time. Due to its polarity unbalance, it was found that betaine displays strong negative deviations from ideality when mixed with a variety of different organic substances. These results pave the way for a comprehensive design of novel deep eutectic solvents. A connection to biologically relevant systems was made using betaine (osmolyte) and urea (protein denaturant), showing that these two compounds formed a DES, the molecular interactions of which were greatly enhanced in the presence of water.This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES, and CIMO-Mountain Research Center, UIDB/00690/2020, financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement.info:eu-repo/semantics/publishedVersio

O Problema de Sócrates em Leo Strauss: Filosofia e Poesia

Sócrates (469-399 a. C.) é ainda hoje um mistério. Por um lado é um daqueles poucos filósofos de que se diz que mudou para sempre o panorama da filosofia. Por outro lado, como nunca escreveu nada, tudo o que sabemos dele chega-nos em segunda mão e todas as descrições da sua vida e pensamento são intensamente polémicas. A versão de Sócrates mais conhecida é a da Apologia de Platão, sobre o seu julgamento e condenação na democrática Atenas, por corromper a juventude e por irreverência para com os deuses da cidade. Mas como lembra Leo Strauss, qualquer estudante do secundário sabe que o Sócrates dos diálogos é o porta voz das ideias de Platão. E acrescenta, com o seu habitual humor, nós não desejamos saber menos que qualquer estudante do secundário. E, se muito se discute sobre o que Sócrates realmente disse, todos o consideram admirável não só como pensador, mas como um modelo da vida filosófica. Tão difícil é distinguir o Sócrates histórico do Sócrates dos seus intérpretes, que o conjunto dessas disputas é o que costuma designar-se como "o problema de Sócrates", expressão cunhada inicialmente por Nietzsche com outro sentido, pois acusava Sócrates do declínio do Ocidente.info:eu-repo/semantics/publishedVersio

Hypophosphatemic Rickets: A New Mutation

Introduction: Phosphopenic rickets is characterized by hypophosphatemia with hyperphosphaturia, normal calcemia and normal or mildly elevated PTH. This pathology may be caused by mutations in PHEX gene (phosphate regulating endopeptidase homolog X-linked). We present a clinical report of a girl with phosphopenic rickets, as consequence of a new mutation of PHEX gene. Clinical Case: We present a 4-year-old female, with unremarkable family history, who presented with failure to thrive since the first year of life (height at the 5th centile, and with the age of four below 5th centile). Blood tests showed hypophosphatemia (2.4 mg/dL), elevated alkaline phosphatase (495 U/L), normal calcemia, mildly elevated PTH (97.2 pg/mL; RR <68.3) and normal levels of 25(OH)D and 1.25(OH)D vitamins. The radiological study showed bone deformity of the radius and femur. Diagnosis of hypophosphatemic rickets was made and she was medicated with phosphorus and calcitriol. Currently, the patient has no clinical or radiographic signs of rickets, osseous age is according to real age and there was a considerable increase in growth rate (between 25th and 50th centiles). Renal ultrasound shows incipient signs of nephrocalcinosis since she was 9-year-old. The genetic study detected a heterozigous mutation of the PHEX gene: variant c.767_768del (p.Thr256Serfs*7). This variant is not described in the literature or databases. However, since it introduces a premature stop codon that can produce a truncated protein, this is very likely a pathogenic variant. The parent’s genetic study is still in progress. Conclusions: Presently more than 200 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. We describe a new mutation of this gene. Knowledge about new mutations can improve patient’s outcome.info:eu-repo/semantics/publishedVersio

Greener terpene-terpene eutectic mixtures as hydrophobic solvents

Natural products can be the basis for the development of green solvents, relevant for the advancement of new, more sustainable processes and products. In this work, 10 binary mixtures constituted by terpenes are prepared and characterized. Their solid−liquid phase diagrams show that room-temperature solvents can be prepared from solid terpenes in a wide composition range. These diagrams are accurately described by the conductor-like screening model for real solvents, showing it to be a useful predictive tool for the design of novel natural solvents. At the eutectic point, these mixtures possess low viscosities, densities lower than water, and high boiling temperatures. The low water solubility in the eutectic solvents together with its negligible impact on the properties measured is a strong indicator of the hydrophobic character of these mixtures. The tunable character of these mixtures is demonstrated by studying the solvatochromic parameters in the entire concentration region, the properties of the final solvents being tuned by simply varying the mole fraction of the terpenes. The high potential of this tunable character is shown in the selective extraction of dyes from their aqueous solutions. This work is expected to devise new insights concerning these solvents as well as to boost their application in green industrial processes.This work was developed in the scope of the project CICECO-Aveiro Institute of Materials POCI-01-0145-FEDER-007679 (UID/CTM/50011/2019) and Associate Laboratory LSRE-LCM (UID/EQU/50020/2019), funded by national funds through FCT/MCTES (PIDDAC). FCT is also acknowledged for funding the project DeepBiorefinery (PTDC/AGRTEC/1191/2014). M.A.R.M. acknowledges the financial support from NORTE-01-0145-FEDER-000006 funded by NORTE2020 through PT2020 and ERDF. L.P.S. acknowledges FCT for her Ph.D. grant SFRH/BD/135976/ 2018. G.J.M. acknowledges the national funding agencies CNPq (305870/2014-9, 309780/2014-4, 140702/2017-2, 406918/2016-3, 406963/2016-9), FAPESP (2014/21252-0, 2016/08566-1), and FAEPEX/UNICAMP (0125/16).info:eu-repo/semantics/publishedVersio

Heterologous expression of Streptococcus mutans cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOIn S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors.In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors811829FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2014/07231-0; 2013/25080-7308644/2011-

Nephrolithiasis in a Portuguese Pediatric Population

Introduction and Aims: Nephrolithiasis incidence in children has increased considerably. It is associated with substantial morbidity, recurrence and increased adulthood cardiovascular risk and chronic kidney disease. A thorough investigation is essential, as rare forms of urolithiasis have increased risk of renal failure. We aim to determine the epidemiology and outcomes of a pediatric population with nephrolithiasis presented in a nephrology unit of a tertiary centre. Methods: Retrospective study of the records of all children (<18 years) with nephrolithiasis diagnosis between 2008‑17. Clinical features, etiology, recurrence, treatment, and outcomes were evaluated and compared throughout the study period through two equal periods (2008‑12 versus 2013‑17). Results: We identified 80 cases: isolated nephrolithiasis (86%) and associated with nephrocalcinosis (14%). Mean follow‑up was 36 months (14–120). Median age at presentation was 8.6 years [3 months – 17 years]: 21% < 2 years‑old and 46% ≥ 10 years. The annual ratio of referrals for nephrolithiasis increased on average 1.2% per year [0.3‑11.8%]. Multiple etiological factors were present in 34%. A metabolic abnormality was identified in 54%: hypocitraturia (34%), hypercalcuria (24%), hyperoxaluria (15%), hyperuricosuria (15%) and cystinuria (1%), without age predominance (p=0.2). Urinary tract infection (24%) was the next most significant etiology and was more frequent below 2 years of age (p=0.001) and associated with struvite calculi (p=0.033). Median age at diagnosis was significantly lower in the study’s first half (5 vs 10 years; p=0.019) and an infectious etiology was more frequent (p=0.043). In a logistic‑regression analysis, a family history of nephrolithiasis was associated with a metabolic cause (p<0.01). Sixty‑three percent became stone free and 24% had recurrence. Discussion: Nephrolithiasis new referrals gradually increased throughout the study period. The most common etiology was metabolic, which is usually responsible for nephrolithiasis appearance and its recurrence, emphasizing the need for a complete evaluation.info:eu-repo/semantics/publishedVersio