sFlt-1/PIGF no Diagnóstico Preditivo de Pré-eclâmpsia: Estudo de Impacto Económico em Portugal

Overview and Aims: The last decade brought relevant insights into the pathophysiology of preeclampsia (PE), namely the role of the circulating levels of placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1). The purpose of this study is to estimate the financial impact of introducing the sFlt-1/PlGF ratio for the evaluation of women with suspicion of PE in the Portuguese National Healthcare System (SNS). Study Design: budget impact study evaluating short-term costs associated with the introduction of the sFlt-1/PlGF ratio from the SNS payer’s perspective. The time horizon for the study is 1 year. Population: The target population consists of women presenting to the healthcare system with signs or symptoms su ggestive of preeclampsia (estimated in 8500 subjects). Methods: A decision-tree model was used to estimate the budget impact of the introduction of the sFlt-1/PlGF ratio in the SNS. The model compares the management costs in the current clinical practice (“no test” scenario) vs. current diagnostic procedures plus the sFlt-1/PlGF ratio (“test” scenario). Clinical inputs have been derived primarily from literature review and, where data was unavailable, expert opinion. Resources and unit costs have been obtained from Portugal-specific sources. Results: In the current standard practice (no test), total costs were estimated to be €9 863 264 (€1160 per patient), with unnecessary admissions representing about €3,5 million. Total costs in the test scenario sum up to €9 781 194 (€1150 per patient), representing a cost saving to the system of €82 070 (€10 per patient), mainly due to a reduction of false positives and related unnecessary hospitalizations of women not developing PE. Conclusions: There is favorable economic evidence about the introduction of the sFlt- 1/PlGF ratio in the SNS. The generated savings appear to offset the costs related to the test.info:eu-repo/semantics/publishedVersio

Meningomyeloradiculitis as an Unusual Presentation of Neuroborreliosis in Childhood

We report a pediatric case of Lyme neuroborreliosis-associated meningomyeloradiculitis with atypical manifestations and negative initial cerebrospinal fluid borrelial antibodies. Transverse myelitis and painful radiculoneuritis have rarely been described in pediatric neuroborreliosis. Clinical manifestations are wide ranging and nonspecific, and the serologic diagnosis is often delayed in the acute phase.info:eu-repo/semantics/publishedVersio

Global environmental changes: setting priorities for Latin American coastal habitats.

The definitive version is available at www.blackwell-synergy.comThe Intergovernmental Panel for Climate Change (IPCC) reports that Global Environmental Changes (GEC) are occurring quicker than at any other time over the last 25 million years and impacting upon marine environments (Bellard et al., 2012). There is overwhelming evidence showing that GEC are affecting both the quality and quantity of the goods and services provided by a wide range of marine ecosystems. In order to discuss regional preparedness for global environmental changes, a workshop was held in Ilhabela, Brazil (22- 26 April 2012) entitled "Evaluating the Sensitivity of Central and South American Benthic Communities to Global Environmental Changes" that drew together scientists from ten Latin American and three European countries. © 2013 Blackwell Publishing Ltd

A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.

BACKGROUND: Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression. CASE PRESENTATION: A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died. CONCLUSIONS: To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome

Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors

BACKGROUND: Circulating tumour cells (CTCs) are detectable in patients with NET and are accurate prognostic markers although the optimum threshold has not been defined. OBJECTIVE: To define optimal prognostic CTC threshold in pancreatic and midgut NET. PATIENTS AND METHODS: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NET (109). Patients were followed for progression free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. RESULTS: AUROC for progression at 12 months in PanNET and midgut NET identified the optimal CTC threshold as ≥1 and ≥2 respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12 month progression with OR of 6.69 (p< 0.01) for PanNET and 5.88 (p<0.003) for midgut. The same thresholds were found to be optimal for predicting death at 36 months with an OR of 2.87 (p< 0.03) and 5.09 (p<0.005) for PanNET and midgut NET respectively. In multivariate Cox hazard regression analysis for PFS in PanNET, ≥ 1 CTC had HR 2.6 (p <0.01) whilst ≥ 2 CTCs had HR 2.25 (p < 0.01) in midgut NET. In multivariate analysis OS in PanNET, ≥ 1 CTC had HR 3.16 (p < 0.01) and in midgut NET, ≥ 2 CTCs had HR of 1.73 (p < 0.06). CONCLUSIONS: The optimal CTC threshold to predict PFS and OS in metastatic PanNET and midgut NET is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials

Mycobacterium bovis: polymerase chain reaction identification in bovine Lymphonode biopsies and genotyping in isolates from Southeast Brazil by spolygotyping and restriction fragment length polymorphism

Diagnosis of the Mycobacterium tuberculosis complex by direct PCR of mediastinal lymphnode DNA and microbiological tests were compared in cattle suspicious of bearing tuberculous-like lesions detected during slaughter. The PCR procedure applied on DNA samples (n=54) obtained by adding alpha -casein into the thiocyanate extraction mix was positive in 70% of the samples. PCR confirmed the identification of 23 samples (100%) that grew in culture, 9 samples (60%) that failed to grow in culture, plus 6 (37.5%) samples that resulted in growth of bacterial contaminants. Genotyping by IS6110-RFLP and DR-spoligotyping analysis of seven samples revealed the presence of several polimorphisms. Seven of the isolates contained multiple copies of IS6110, thus defining the existence of five singular genotypes.ICB Departamento de Bioquímica e Imunologia Laboratório de Biologia Molecular de Produtos NaturaisUniversidade Federal de Minas Gerais ICB Escola de VeterináriaUniversidade Federal de Minas Gerais ICB Departamento de FarmacologiaEscola Paulista de Medicina Departamento de Microbiologia e ParasitologiaLaboratório Central do Estado do Espírito SantoInstituto Biológico de São PauloCentro de Investigación en Ciencias Veterinarias Instituto de BiotecnologiaUNIFESP, EPM, Depto. de Microbiologia e ParasitologiaSciEL

TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a Ph.D. Grant to SM (SFRH/BD/137802/2018). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnolo-gia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT, under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumour immortalization (PDTC/MED-ONC/31438/2017)

Transcriptome changes in newborn goats' skeletal muscle as a result of maternal feed restriction at different stages of gestation

We investigated how feed restriction at 50% of maintenance requirements during different stages of gestation affects the transcriptome of newborn goats' skeletal muscle. Fourteen pregnant dams were randomly assigned into one of the following dietary treatments: animals fed at 50% of maintenance requirement from 8-84 d of gestation and then fed at 100% of maintenance requirement from day 85 of gestation to parturition (RM, n = 6), and animals fed at 100% of maintenance requirement from 8-84 d of gestation and then fed at 50% of maintenance requirement from day 85 of gestation to parturition (MR, n = 8). At birth, samples of offspring's Longissimus muscle were collected for total RNA extraction and sequencing. Our data showed 66 differentially expressed (DE) genes (FDR &lt; 0.05). A total of 6 genes were upregulated and 60 downregulated (FDR &lt; 0.05) in the skeletal muscle of the newborns resulting from treatment RM compared with MR. Our results suggest that the DE genes upregulated in newborn goats' skeletal muscle from the RM group compared to MR, included genes related to satellite cells, and genes that indicates impaired insulin sensitivity and changes in the composition of intramuscular fat. The DE genes upregulated in newborn goats' skeletal muscle from the MR group compared to RM, are also related to impaired insulin sensitivity, as well as a predominantly oxidative metabolism and cellular oxidative stress. However, protective mechanisms against insulin sensitivity and oxidative stress may have been augmented in the skeletal muscle of offspring from MR treatment compared to RM, in order to maintain cellular homeostasis