History-indicated transvaginal cerclage: results from a single-centre

Background: Cervical incompetence occasionally results in mid-trimester pregnancy loss, preterm labour and increased foetal morbimortality. History-indicated cerclage is proposed when obstetric history suggests cervical incompetence. The aim of this study was to evaluate the maternal-foetal outcomes following prophylactic cervical cerclage.Methods: Retrospective study reviewing data of all women undergoing transvaginal history-indicated cerclage from January 1st, 2008 to December 31th, 2017 at Centro Hospitalar Universitário do Algarve - Faro. Primary outcome: gestational age <37weeks at birth. Secondary outcomes: neonatal morbimortality and intensive care unit (NICU) admission and maternal morbidity. Data were analyzed with IBM SPSS Statistics 23.Results: A total of 12 history-indicated cerclages were performed (9 women). At first cerclage, mean maternal age, gestity, parity and live children were 27.6, 2.44, 1.11 and 0.78 (87.7% preterm), respectively. At cerclage placement, mean gestational age and cervical length were 16.1 weeks and 27.5mm. Average hospital admission was 10.7 days. In all cases McDonald technique was performed. Four hospital readmissions occurred for threatened labour. Mean gestational age at cerclage removal was 36.9 weeks (83.3% in ambulatory) and 38.9 at delivery. Average time between cerclage removal and labour was 14.5 days. Spontaneous onset of labour occurred in 75% and vaginal delivery in 83.4%. There were no reports of preterm birth, foetal admission to NICU or maternal complications. Mean number of live children after procedure was 1.58.Conclusions: Prophylactic cervical cerclage seems to improve pregnancy outcome with minimal maternal risks. However, our data suggest over inclusion of women, with unnecessary procedures, emphasizing the importance of re-evaluating inclusion criteria

Gla-rich protein (GRP) as an early and novel marker of vascular calcification and kidney dysfunction in diabetic patients with CKD: a pilot cross-sectional study

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2-4). Spearman's correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.Portuguese Society of Nephrology (SPN) ; Portuguese national funds from FCT-Foundation for Science and Technology through the transitional provision DL57/2016/CP1361/CT0006 UIDB/04326/2020info:eu-repo/semantics/publishedVersio

Predictores del ajuste de los estudiantes durante la transición a la Universidad en España

Adjustment to university is a major life transition that not all emerging adults manage successfully. The Student University Adjustment Questionnaire is the instrument most commonly used to evaluate this multidimensional construct. Research in Spain on the predisposing factors for successful adjustment to university in emerging adults is scarce relative to the large number of studies carried out in North America. The objective of the present study was to analyze the association between students’ gender, family background, pre-university achievement and adjustment to university. Method: Participants were 300 Spanish fi rst-year students (198 women and 102 men) of mean age 18.02 years. Results: Pre-university achievement was the only signifi cant predictor of academic, social and institutional adjustment. Gender directly affected personal-emotional adjustment and indirectly affected academic adjustment mediated by entry grade. Conclusions: Students’ entry characteristics predict adjustment to university in the fi rst year. These fi ndings have important theoretical and practical implications.Antecedentes: la adaptación a la universidad es una de las principales transiciones vitales que no todos los adultos emergentes afrontan con éxito. El Cuestionario de Adaptación del Estudiante a la Universidad es el instrumento más empleado para evaluar este constructo multidimensional. En España no existen investigaciones sobre los factores que predisponen a los adultos emergentes a una adaptación exitosa a la universidad respecto al número de investigaciones llevadas a cabo con muestras norteamericanas. El objetivo de este estudio es analizar la relación entre el género, el background familiar, la nota de acceso y el ajuste a la universidad. Método: participaron 300 estudiantes españoles de primer año (198 mujeres y 102 hombres) con un promedio de edad de 18,02 años. Resultados: la nota de acceso fue el único predictor signifi cativo del ajuste académico, social e institucional. El género infl uye de una manera directa sobre el ajuste personal-emocional e indirecta sobre el ajuste académico, mediado por la nota de acceso. Conclusiones: las características de entrada del estudiante predicen su adaptación en el primer año de universidad. Estos resultados tienen importantes implicaciones teóricas y prácticas.This study is part of a wider project entitled “La Transición a la Universidad en el Contexto del Espacio Europeo de Educación Superior: Infl uencia del Soporte Social y el Nivel de Integración en el Fracaso/Éxito Académico” [Transition to College in European Higher Education: The Influence of Social Support and Integration on Academic Failure/Success], supported by the Spanish Ministry of Science and Innovation (PSI2011-24535). The author Alexandra M. Araújo received funding from the Portuguese Foundation for Science and Technology (FCT) awarded as a Post-Doctoral Grant, under grant agreement number SFRH/BPD/85856/2012

FARMACOGENÉTICA DE DOENÇAS NEUROLÓGICAS

Once a drug has access to the body of an organism, it plays a role in the determination of the specter of effect as well as in its intensity and duration. The extension with the drugs can be absorbed and carried to some target organ influences in its profile of strength and effect. The genetic variation can potentially affect the way an individual reply to the drug in some steps. The absorption of one drugs and its distribution to some organs are processed not only for the physicochemical properties of the drug, but also for endogenous molecules. Many of the susceptibility genes to the illnesses are also target of drugs and can simultaneously predispose the patients to the illness as well as the resistance to the treatment. The identification of new variants for illnesses predisposition can indicate new therapeutical targets and new pathways in the development of drugs and interventions. This systematic characterization of the nature and function of the genetic polymorphisms in enzymes and other advances in the pharmacogenetics has an extensive potential to improve the choice of the appropriate medicine and the correct dose for any patient in particular. In this article, we review the findings in pharmacogenetics of Epilepsy and Alzheimer’s disease.Uma vez que uma droga tenha acesso ao corpo de um organismo, o mesmo desempenha um papel na determinação do espectro de efeitos bem como em sua intensidade e duração. A extensão com que uma droga pode ser absorvida e transportada a vários órgãosalvo influencia no seu perfil de potência e efeito. A variação genética pode potencialm ente afetar a resposta individual à droga em vários passos. A absorção de uma droga e sua distribuição a vários órgãos são processos governados não apenas pelas propriedades físico-químicas da droga, mas também por moléculas endógenas. Muitos dos genes de suscetibilidade a doenças são também alvos de drogas e podem simultaneamente predispor os pacientes à doença bem como à resistência ao tratamento. A identificação de novas variantes para predisposição às doenças pode indicar novos alvos terapêuticos e novas vias no desenvolvimento de drogas e intervenções ambientais. Esta sistemática caracterização da natureza e da função do polimorfismo genético em enzimas metabolizadoras-chave e outros avanços na farmacogenética têm um amplo potencial para melhorar a escolha do medicamento apropriado e a correta dose para qualquer paciente em particular. Nesse artigo, revisamos os achados em farmacogenética na Epilepsia e na Doença de Alzheimer

PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without β-catenin mutations

INTRODUCTION: Activating mutations in exon 3 of the &#946;-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between &#946;-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the &#946;-catenin gene was screened for mutations, and the expression of the &#946;-catenin gene and PROP1 was evaluated. &#946;-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and &#946;-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and &#946;-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the &#946;-catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of &#946;-catenin gene overexpression was found in 71% of the tumors with &#946;-catenin mutations and in 40% of the tumors without mutations, and &#946;-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of &#946;-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear &#946;-catenin staining pattern regardless of the presence of a bcatenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort

Transcriptome analysis of Taenia solium cysticerci using Open reading Frame ESTS (ORESTES)

<p>Abstract</p> <p>Background</p> <p>Human infection by the pork tapeworm <it>Taenia solium </it>affects more than 50 million people worldwide, particularly in underdeveloped and developing countries. Cysticercosis which arises from larval encystation can be life threatening and difficult to treat. Here, we investigate for the first time the transcriptome of the clinically relevant cysticerci larval form.</p> <p>Results</p> <p>Using Expressed Sequence Tags (ESTs) produced by the ORESTES method, a total of 1,520 high quality ESTs were generated from 20 ORESTES cDNA mini-libraries and its analysis revealed fragments of genes with promising applications including 51 ESTs matching antigens previously described in other species, as well as 113 sequences representing proteins with potential extracellular localization, with obvious applications for immune-diagnosis or vaccine development.</p> <p>Conclusion</p> <p>The set of sequences described here will contribute to deciphering the expression profile of this important parasite and will be informative for the genome assembly and annotation, as well as for studies of intra- and inter-specific sequence variability. Genes of interest for developing new diagnostic and therapeutic tools are described and discussed.</p

Development of novel magnetoliposomes containing nickel ferrite nanoparticles covered with gold for applications in thermotherapy

Multifunctional nanosystems combining magnetic and plasmonic properties are a promising approach for cancer therapy, allowing magnetic guidance and a local temperature increase. This capability can provide a triggered drug release and synergistic cytotoxic effect in cancer cells. In this work, nickel ferrite/gold nanoparticles were developed, including nickel ferrite magnetic nanoparticles decorated with plasmonic gold nanoparticles and core/shell nanostructures (with a nickel ferrite core and a gold shell). These nanoparticles were covered with a surfactant/lipid bilayer, originating liposome-like structures with diameters below 160 nm. The heating capacity of these systems, upon excitation with light above 600 nm wavelength, was assessed through the emission quenching of rhodamine B located in the lipid layer. The developed nanosystems show promising results for future applications in thermotherapy.This research was funded by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CF-UM-UP (UID/FIS/04650/2019) and through the research project PTDC/QUI-QFI/28020/2017 (POCI-01-0145-FEDER-028020), financed by European Fund of Regional Development (FEDER), COMPETE2020, and Portugal2020. The magnetic measurements were supported by projects UTAP-EXPL/NTec/0046/2017, NORTE-01-0145-FEDER-028538, and PTDC/FIS-MAC/29454/2017. I.S.R.R. acknowledges FCT for a research grant under CF-UM-UP Strategic Funding (UID/FIS/04650/2019)

Gla-Rich protein, magnesium and phosphate associate with mitral and aortic valves calcification in Didabetic patients with moderate CKD

Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2–4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.info:eu-repo/semantics/publishedVersio

Purification of antileukemic drugs through silica-based supported ionic liquids

L-asparaginase (LA) is an enzyme used as a biopharmaceutical for the treatment of acute lymphoblastic leukemia. LA can be produced via fermentation and its purification usually comprises several steps including precipitation, liquid-liquid extraction and chromatography techniques. Among these, ion exchange chromatography, which is often preceded by precipitation with salts as a first pre-chromatographic step, is the most used. However, theses common strategies for protein purification result in low yields and purity, requiring long processing times, while leading to a consequent increase of the process costs. Therefore, the demand for new cost-effective production/purification processes play now a priority role. This work aims the development of cost-effective technologies to purify LA from the complex fermentation medium from Bacillus Subtillis. Silica-based supported ionic liquids (SILs) are investigated as cost-effective purification materials for the target enzyme. The concentration of the extract from the fermentation, material/ extract from fermentation ratio and contact time effects in the purity and yield of LA were optimized. With this strategy, process costs, energy consumed, and waste generated, may be significantly decreased, which may lead to this biopharmaceutical price decrease and wider application.publishe

Purification of antileukemic drugs through silica-based supported ionic liquids

L-asparaginase (LA) is an enzyme used as a biopharmaceutical for the treatment of acute lymphoblastic leukemia. LA can be produced via fermentation and its purification usually comprises ion exchange chromatography, which is often preceded by precipitation with salts as a first pre-chromatographic step. However, this purification strategy result in low yields and purity, requires long processing times, while leading to a consequent increase of the process costs. Therefore, the demand for new cost-effective purification processes play now a priority role. In this work silica-based supported ionic liquids (SILs) are investigated as an alternative technology to purify LA from the complex fermentation medium from Bacillus subtillis. The concentration of the extract from the fermentation, material/ extract from fermentation ratio and contact time effects in the purity and yield of LA were optimized. With this strategy, process costs, energy consumed, and waste generated, may be significantly decreased, which may lead to this biopharmaceutical price decrease and wider application.publishe