Complex Phenotype of Hypercholesterolemia in a Family with Both ABCG8 and APOB Mutations

Familial hypercholesterolemia is a common genetic hypercholesterolemia caused by mutations in LDLR, APOB and PCSK9 that leads to premature atherosclerosis. Other rare disorders like sitosterolemia can present the same phenotype but have distinct therapeutic interventions. We present a case of severe hypercholesterolemia in a 5-year-old child found to have both familial hypercholesterolemia and sitosterolemia. The proband was diagnosed initially as familial hypercholesterolemia, but the lack of pathogenic variants with Sanger approach questioned this hypothesis. High levels of sitosterol established the diagnosis of sitosterolemia, genetically confirmed by an ABCG8 homozygous variant c.1974C>G/p. (Tyr658*). Next-generation sequencing re sequence for familial hypercholesterolemia genes revealed an APOB heterozygous functional variant (c.11477C>T/p. (Thr3826Met), in a region previously unstudied. The mother presented with the same genotype but a milder phenotype. Control of low-density lipoprotein cholesterol levels was only accomplished with dietary and therapeutic intervention for both sitosterolemia and familial hypercholesterolemia. The correct diagnosis of dyslipidemia is important to establish proper dietary and pharmacological intervention for atherosclerosis prevention.info:eu-repo/semantics/publishedVersio

Pancreatite Aguda Recorrente na Gravidez

Introduction: During pregnancy pancreatitis is a rare and diagnosis is difficult. Cholelithiasis is the most frequent risk factor. Case report: A 26-year-old pregnant woman with abdominal pain, vomiting and low-grade fever. Hyperamylasemia and cholelithiasis was found and pancreatitis diagnosis was made. A second episode of acute pancreatitis was observed and treated with medical therapy. There was no foetal or neonatal complications. In puerperium a third pancreatitis occurred, a laparoscopic cholecystectomy was performed. Discussion: Diagnosis of acute pancreatitis in pregnancy is challenging and it may have serious maternal-fetal implications. Recurrent pattern should be taken into account when choosing the best treatment.info:eu-repo/semantics/publishedVersio

H-Ferritin Is Essential for Macrophages' Capacity to Store or Detoxify Exogenously Added Iron

Macrophages are central cells both in the immune response and in iron homeostasis. Iron is both essential and potentially toxic. Therefore, iron acquisition, transport, storage, and release are tightly regulated, by several important proteins. Cytosolic ferritin is an iron storage protein composed of 24 subunits of either the L- or the H-type chains. H-ferritin differs from L-ferritin in the capacity to oxidize Fe2+ to Fe3+. In this work, we investigated the role played by H-ferritin in the macrophages' ability to respond to immune stimuli and to deal with exogenously added iron. We used mice with a conditional deletion of the H-ferritin gene in the myeloid lineage to obtain bone marrow-derived macrophages. These macrophages had normal viability and gene expression under basal culture conditions. However, when treated with interferon-gamma and lipopolysaccharide they had a lower activation of Nitric Oxide Synthase 2. Furthermore, H-ferritin-deficient macrophages had a higher sensitivity to iron-induced toxicity. This sensitivity was associated with a lower intracellular iron accumulation but a higher production of reactive oxygen species. These data indicate that H-ferritin modulates macrophage response to immune stimuli and that it plays an essential role in protection against iron-induced oxidative stress and cell death.Tis work was fnanced by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/IMI-MIC/1683/2014 (POCI-01-0145-FEDER-016590). PFO and MGA acknowledge FCT for the Investigador FCT 2015. We thank the valuable collaboration of the following i3S Scientifc Platforms: Cell Culture and Genotyping Core Facility (CCGen), [Histology and Electron Microscopy Service (HEMS), and BioSciences Screening], member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)], Animal Facility, and Flow Cytometry Unit (TraCy). We acknowledge Lukas Kuhn (Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland) for kindly providing the frst breeding pairs of Fth1−/− mice. Te authors also acknowledge Marisa Castro, from Departamento de Biologia Molecular from ICBAS, Clara Bento, from i3S, and Edgar Pinto from LAQV – REQUIMTE for technical assistance at diferent stages of the project

The familial hypercholesterolaemia phenotype: Monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes

Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management. This article is protected by copyright. All rights reserved

Combined tools for Surgical Case Packages contents and cost optimization: a preliminary study

This paper presents a solution proposal based on mathematical and statistical tools to optimize Surgical Case Packages of an Operating Room (OR) in a Portuguese public hospital that it is the most complex environment in a hospital. In this particular hospital, more than 27000 surgeries/year are performed, employing, sometimes, misadjusted composition of standard surgical packages and non-optimized grouping of surgical instruments. Problem consequences are, among others, high transport of various surgical cases packages; high number of open cases and delays in surgical times following surgery. These type of problems are waste that do not add value to the service in the context of Lean Healthcare and must be eliminated using the most suitable tools. After the analysis, different tools were used: combinatorial analysis to optimize surgical cases composition and statistical analysis to identify the instruments usage and surgical basic case patterns. An optimization model was developed which produced a sterilizing initial solution of 135.24€. By identifying the most commonly employed instruments, it was concluded that some instruments have never been used and others rarely and some patterns were identified. The results achieved were based on minor sample and in a form of data collection that needs some adjustment

What attributes do patients prefer in a family physician? A cross-sectional study in a northern region of Portugal

Objectives: To determine which modifiable and non-modifiable attributes patients prefer in a family physician, as well as to analyse participants’ characteristics associated with their choices. Design: Cross-sectional study. Setting: Family healthcare units (FHU) in the city of Braga and Barcelos (Northern Portugal). Participants: Adults aged 18 years or more, enrolled in the selected FHU. Main outcome measures: The preferred attributes were assessed with a questionnaire delivered in the FHU. These attributes included gender, age and nationality and the importance of being Portuguese, of greeting with a handshake, of welcoming in the waiting area, of using an identification badge and of wearing a white coat. Results: A total of 556 questionnaires were included in the analysis; 66% and 58% of the participants had no preference for the gender or age of the family physician, respectively. Using a multinomial logistic regression, male participants were 3.8 times more likely to have a preference for a male physician than having no preference, in comparison to female participants (OR 3.864, 95% CI 1.96 to 7.61). More than 69% of the participants considered greeting with a handshake, using an identification badge and wearing a white coat important or very important. There was a statistically significant association between being Portuguese and the major importance given to the use of an identification badge (β=0.68, 95% CI 0.23 to 1.12). Conclusions: Our data show that modifiable attributes of the family physician (greeting, presence of an identification badge and wearing a white coat) are important for patients. Potential changes in family physician attitude in consultation could ultimately affect patient–physician relationship.The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors

Flow cytometry and targeted immune transcriptomics identify distinct profiles in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors with or without interferon-α

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativeco mmons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the dat

Environment of Erbium in a-Si : H and a-SiOx : H

The chemical environment of Er in a-Si:H and a-SiOx:H was determined by extended x-ray absorption fine structure. Only one family of Er sites is found, coordinated on average with two to three O atoms (compared to six in Er2O3). We devised a new model for the incorporation of Er in a-Si:II and a-SiOx:H. According to the model, Er is incorporated in the form of [ErOdelta](+3-2 delta) complexes, with delta less than or equal to 3. The minimum configuration energy is achieved for delta = 3 when the valence requirements of Er are fulfilled. The complexes are low symmetry environments that allow the Er3+ luminescent transition at 1.54 mu m and make Er an acceptor in a-Si:H whereas it is donor in crystalline silicon. [S0031-9007(98)07668-6].81214652465

Rare Primary Dyslipidaemias Associated with Low LDL and HDL Cholesterol Values in Portugal

Background: Dyslipidaemia represents a group of disorders of lipid metabolism, characterized by either an increase or decrease in lipid particles, usually associated with triglycerides, LDL cholesterol (LDL-C) and/or HDL cholesterol (HDL-C). Most hyperlipidaemias and HDL deficiencies confer an increased cardiovascular risk, while hypolipidaemia, such as abeta or hypobetalipoproteinemia, may present different manifestations ranging from poor weight progression to neurological manifestations. The aim of this study is to present 7 cases with rare dyslipidaemias associated with low LDL or low HDL cholesterol values, referred to our laboratory for the genetic identification of the cause of the dyslipidaemia. Methods: Lipid profile was determined for each individual in an automated equipment Integra Cobas (Roche). Molecular analysis was performed by NGS with a target panel of 57 genes involved in lipid metabolism (Sure select QXT, Agilent) and samples were run in a NextSEQ Sequencer (Illumina). Only genes associated to rare forms of low HDL-c or LDL-c were analysed for this work, namely: ABCA1, APOA1, LCAT, SCARB1, APOB, PCSK9, MTTP, SAR1B, and ANGPTL3. All rare variants (MAFA) and the other is a possible compound heterozygous for APOB variants c.2604+1G>A and c.4651C>T/p.(Gln1551*). In two patients only a variant in heterozygosity (c.3365delG/p.(Gly1122Vfs*62) and c.11095A>T/p.(Arg3699*)). In the remaining patient, no variants were identified. NGS proved to be a fundamental key for genetic testing of rare lipid disorders, allowing us to find the genetic cause of disease in 6/7 patients with low HDL-c and LDL-c. Patients with these rare conditions should be identified as early as possible in order to minimize or prevent clinical manifestations. The unsolved case is still under investigation.info:eu-repo/semantics/publishedVersio