Síndrome de Williams: proposta de sistema de pontuação para diagnóstico clínico

OBJECTIVE: To develop a scoring system based on clinical findings to assist pediatricians in the diagnosis of William syndrome and to delineate when the fluorescent in-situ hybridization test to detect the microdeletion at 7q11.23 may be needed. METHODS: The fluorescent in-situ hybridization test was performed on 20 patients presenting William syndrome suggestive clinical features. Eleven studies were selected from the literature in which there were 2 groups: patients with positive or negative fluorescent in-situ hybridization tests. Forty-two clinical characteristics were compared to those reported in the literature to determine which ones were associated with the affected patients (ie, bearing deletions) using meta-analysis. The 2-tailed Fisher exact test were used so that the frequency of findings observed in fluorescent in-situ hybridization positive and fluorescent in-situ hybridization negative patients could be compared in the present study together with the patients from the literature. We developed a scoring system based on clinical findings and their significant associations with patients with positive fluorescent in-situ hybridization tests. From themean and standard-deviation values of the data from our patients, we determined the cut-off score that that indicated the need for a fluorescent in-situ hybridization test to confirm diagnosis. RESULTS: Seventeen patients were fluorescent in-situ hybridization positive, and 3 were fluorescent in-situ hybridization negative. The more discriminative findings among fluorescent in-situ hybridization positive patients were the following: typical facies, low birth weight, feeding difficulties, constipation, supravalvar aortic stenosis, mental retardation, and friendly personality. The distribution of the points among the 20 patients ranged from 19 to 28 points with a mean value of 23.3 out of a possible total of 31 points. The cut-off score that indicated the need for a fluorescent in-situ hybridization test was 20. CONCLUSIONS: Our scoring system enables physicians to differentiate between those individuals who can be reliably diagnosed as having Williams syndrome solely from the clinical findings and those who need to undergo fluorescent in-situ hybridization testing for a correct diagnosis.OBJETIVOS: Desenvolver um sistema de pontuação (Score) baseado nos achados clínicos para auxiliar os pediatras no diagnóstico clínico da Síndrome de Williams-Beuren e na indicação do teste de hibridização in situ por fluorescência para detectar a microdeleção em 7q11.23. MÉTODOS: O teste de hibridização in situ por fluorescência foi feito em 20 acometidos pela Síndrome de Williams-Beuren, nos quais 42 achados clínicos foram estudados. Para estabelecer quais desses achados estariam associados ao teste de hibridização in situ por fluorescência positivo, realizou-se uma metanálise com 11 trabalhos da literatura em que havia dois grupos, hibridização in situ por fluorescência positivo e negativo. As freqüências dos achados presentes nos indivíduos fluorescência positivo e fluorescência negativo neste estudo foram comparadas em conjunto com os pacientes da literatura através do teste exato de Fisher. Elaboramos um sistema de pontuação (score) baseado nos achados que mostraram correlação significante (

Natural history of 39 patients with Achondroplasia

OBJECTIVES: To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments. METHODS: Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016. RESULTS: Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. The most prevalent clinical findings were short stature, high forehead, trident hands, genu varum and macrocephaly. The most prevalent radiographic findings were rhizomelic shortening of the long bones and narrowing of the interpediculate distance of the caudal spine. There was motor developmental delay in 18 patients and speech delay in 16 patients. The most common clinical intercurrences were middle ear dysfunction, sleep apnea, limb pain and obesity from 2 to 9 years of age. One patient was large for the gestational age but did not develop obesity. One patient developed hydrocephalus at 10 years old. The current age of the patients varies from 15 months to 36 years. The molecular study performed by Sanger sequencing of the common heterozygous mutation 1138G4A in FGFR3 was positive in all patients. Four cases were inherited, and 35 were sporadic (paternal age from 19 to 66 years). CONCLUSIONS: The diagnoses were made early based on clinical and radiographic findings. All cases were confirmed molecularly. Despite presenting a benign course, it is necessary to establish a systematic protocol for the surveillance of these patients due to the common clinical intercurrences

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

The Two Faces of Anomaly Mediation

Anomaly mediation is a ubiquitous source of supersymmetry (SUSY) breaking which appears in almost every theory of supergravity. In this paper, we show that anomaly mediation really consists of two physically distinct phenomena, which we dub "gravitino mediation" and "Kahler mediation". Gravitino mediation arises from minimally uplifting SUSY anti-de Sitter (AdS) space to Minkowski space, generating soft masses proportional to the gravitino mass. Kahler mediation arises when visible sector fields have linear couplings to SUSY breaking in the Kahler potential, generating soft masses proportional to beta function coefficients. In the literature, these two phenomena are lumped together under the name "anomaly mediation", but here we demonstrate that they can be physically disentangled by measuring associated couplings to the goldstino. In particular, we use the example of gaugino soft masses to show that gravitino mediation generates soft masses without corresponding goldstino couplings. This result naively violates the goldstino equivalence theorem but is in fact necessary for supercurrent conservation in AdS space. Since gravitino mediation persists even when the visible sector is sequestered from SUSY breaking, we can use the absence of goldstino couplings as an unambiguous definition of sequestering.Comment: 21 pages, 1 table; v2, references added, extended discussion in introduction and appendix; v3, JHEP versio

Biology and conservation of freshwater bivalves : past, present and future perspectives

Freshwater bivalves have been highly threatened by human activities, and recently their global decline has been causing conservational and social concern. In this paper, we review the most important research events in freshwater bivalve biology calling attention to the main scientific achievements. A great bias exists in the research effort, with much more information available for bivalve species belonging to the Unionida in comparison to other groups. The same is true for the origin of these studies, since the publishing pattern does not always correspond to the hotspots of biodiversity but is concentrated in the northern hemisphere mainly in North America, Europe and Russia, with regions such as Africa and Southeast Asia being quite understudied. We also summarize information about past, present and future perspectives concerning the most important research topics that include taxonomy, systematics, anatomy, physiology, ecology and conservation of freshwater bivalves. Finally, we introduce the articles published in this Hydrobiologia special issue related with the International Meeting on Biology and Conservation of Freshwater Bivalves held in 2012 in Braganc¸a, Portugal.We would like to express our gratitude to our sponsors and institutions, especially to the Polytechnic Institute of Braganca for all the logistic support. We acknowledge all keynote speakers, authors, session chairpersons and especially to all attendees whose contributions were fundamental for the success of this meeting. We would also like to thank all referees of this special issue and to Koen Martens, Editor-in-Chief of Hydrobiologia, for all the valuable comments and suggestions. The chronogram was built with the help of the expert opinion of fellow colleagues Rafael Araujo, Arthur Bogan, Kevin Cummings, Dan Graf, Wendell Haag, Karl-Otto Nagel and David Strayer to whom we are very grateful. The authors acknowledge the support provided by Portuguese Foundation for Science and Technology (FCT) and COMPETE funds-projects CONBI (Contract: PTDC/AAC-AMB/117688/2010) and ECO-IAS (Contract: PTDC/AAC-AMB/116685/2010), and by the European Regional Development Fund (ERDF) through the COMPETE, under the project "PEst-C/MAR/LA0015/2011"

Cell arrest and cell death in mammalian preimplantation development

The causes, modes, biological role and prospective significance of cell death in preimplantation development in humans and other mammals are still poorly understood. Early bovine embryos represent a very attractive experimental model for the investigation of this fundamental and important issue. To obtain reference data on the temporal and spatial occurrence of cell death in early bovine embryogenesis, three-dimensionally preserved embryos of different ages and stages of development up to hatched blastocysts were examined in toto by confocal laser scanning microscopy. In parallel, transcript abundance profiles for selected apoptosis-related genes were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our study documents that in vitro as well as in vivo, the first four cleavage cycles are prone to a high failure rate including different types of permanent cell cycle arrest and subsequent non-apoptotic blastomere death. In vitro produced and in vivo derived blastocysts showed a significant incidence of cell death in the inner cell mass (ICM), but only in part with morphological features of apoptosis. Importantly, transcripts for CASP3, CASP9, CASP8 and FAS/FASLG were not detectable or found at very low abundances. In vitro and in vivo, errors and failures of the first and the next three cleavage divisions frequently cause immediate embryo death or lead to aberrant subsequent development, and are the main source of developmental heterogeneity. A substantial occurrence of cell death in the ICM even in fast developing blastocysts strongly suggests a regular developmentally controlled elimination of cells, while the nature and mechanisms of ICM cell death are unclear. Morphological findings as well as transcript levels measured for important apoptosis-related genes are in conflict with the view that classical caspase-mediated apoptosis is the major cause of cell death in early bovine development

Williams Syndrome: development of a new scoring system for clinical diagnosis

OBJECTIVE: To develop a scoring system based on clinical findings to assist pediatricians in the diagnosis of William syndrome and to delineate when the fluorescent in-situ hybridization test to detect the microdeletion at 7q11.23 may be needed. METHODS: The fluorescent in-situ hybridization test was performed on 20 patients presenting William syndrome suggestive clinical features. Eleven studies were selected from the literature in which there were 2 groups: patients with positive or negative fluorescent in-situ hybridization tests. Forty-two clinical characteristics were compared to those reported in the literature to determine which ones were associated with the affected patients (ie, bearing deletions) using meta-analysis. The 2-tailed Fisher exact test were used so that the frequency of findings observed in fluorescent in-situ hybridization positive and fluorescent in-situ hybridization negative patients could be compared in the present study together with the patients from the literature. We developed a scoring system based on clinical findings and their significant associations with patients with positive fluorescent in-situ hybridization tests. From themean and standard-deviation values of the data from our patients, we determined the cut-off score that that indicated the need for a fluorescent in-situ hybridization test to confirm diagnosis. RESULTS: Seventeen patients were fluorescent in-situ hybridization positive, and 3 were fluorescent in-situ hybridization negative. The more discriminative findings among fluorescent in-situ hybridization positive patients were the following: typical facies, low birth weight, feeding difficulties, constipation, supravalvar aortic stenosis, mental retardation, and friendly personality. The distribution of the points among the 20 patients ranged from 19 to 28 points with a mean value of 23.3 out of a possible total of 31 points. The cut-off score that indicated the need for a fluorescent in-situ hybridization test was 20. CONCLUSIONS: Our scoring system enables physicians to differentiate between those individuals who can be reliably diagnosed as having Williams syndrome solely from the clinical findings and those who need to undergo fluorescent in-situ hybridization testing for a correct diagnosis.OBJETIVOS: Desenvolver um sistema de pontuação (Score) baseado nos achados clínicos para auxiliar os pediatras no diagnóstico clínico da Síndrome de Williams-Beuren e na indicação do teste de hibridização in situ por fluorescência para detectar a microdeleção em 7q11.23. MÉTODOS: O teste de hibridização in situ por fluorescência foi feito em 20 acometidos pela Síndrome de Williams-Beuren, nos quais 42 achados clínicos foram estudados. Para estabelecer quais desses achados estariam associados ao teste de hibridização in situ por fluorescência positivo, realizou-se uma metanálise com 11 trabalhos da literatura em que havia dois grupos, hibridização in situ por fluorescência positivo e negativo. As freqüências dos achados presentes nos indivíduos fluorescência positivo e fluorescência negativo neste estudo foram comparadas em conjunto com os pacientes da literatura através do teste exato de Fisher. Elaboramos um sistema de pontuação (score) baseado nos achados que mostraram correlação significante (p<0,001) para os pacientes hibridização in situ por fluorescência positivo. Determinamos os valores correspondentes aos percentis baseados na média e desvio-padrão, calculados a partir dos 20 pacientes do presente trabalho. RESULTADOS: Dezessete pacientes foram hibridização in situ por fluorescência positivo e três, negativo. Os achados mais discriminativos nos hibridização in situ por fluorescência positivo (3 pontos no score) foram: fáceis típico, baixo peso ao nascimento, dificuldades alimentares, obstipação, estenose aórtica supravalvar, deficiência mental e personalidade amigável.A distribuição dos valores entre os 20 pacientes variou de 19 a 28 pontos com uma média de 23,3 pontos. CONCLUSÕES: O score elaborado permitiu propor o valor de 20 pontos para a indicação do teste de hibridização in situ por fluorescência nos pacientes com suspeita clínica de Síndrome de Williams-Beuren

Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE.

Introduction  The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods  We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age (<45 years) were stratified into those with PA-VTE ( n  = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n  = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results  Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18-1.98]), recurrent VTE (0.82 [0.34-1.94]), and major bleeding (1.13 [0.33-3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion  VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups