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Background Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet. Methods Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet. Results Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p

11 pages, 5 figures, 3 tables.-- Under a Creative Commons license, The increasing consumption of seafood products raises concerns over their sustainability and the conservation of marine resources. Seafood traceability, enabled by a regulated labelling system, is important to prevent overexploitation of these resources. The regulations (EU) No.1169/2011 and (EU) No 1379/2013 are the European legislative tools that specify the mandatory information that must be present on seafood labels. The present study analysed the labels of seafood products sold in different European countries in order to verify the presence of mandatory information required by EU regulations currently in place. The results show that there is a difference in compliance among groups of products and among countries. The country with the lowest level of compliance was The United Kingdom (still part of EU when the study was carried out), with an overall compliance of 63.7%. The country with the highest level of compliance was Portugal (87.2%). Across all the countries analysed, supermarkets were more compliant than fishmonger’s shops and Processed Prepacked products were more conformed best to the EU labelling legislation when compared to Unprocessed Non-Prepacked products. Differences among different areas of the same country were also observed. Fishing gear, scientific name, fishing/production method and date of freezing were the types of information most frequently missing on the labels examined. The results of this study pose the bases for further actions, that can be taken by relevant institutions, to improve compliance throughout the supply chain., This study was funded by the European Regional Development Fund Interreg Atlantic Area, EAPA_87/2016

The primary genetic risk factor for late onset Alzheimer&rsquo, s disease (LOAD) is the APOE4 allele of Apolipoprotein E (APOE) gene. The three most common variants of APOE are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of APOE variants in an Iberian cohort, thus helping to understand differences in APOE-related LOAD risk observed across populations. We analyzed saliva or buccal swab samples from 229 LOAD patients and 89 healthy elderly controls (&ge, 68 years old) from Northern Portugal and Castile and Le&oacute, n region, Spain. The genotyping was performed by Sanger sequencing, optimized to overcome GC content drawbacks. Results obtained in our Iberian LOAD and control cohorts are in line with previous large meta-analyses on APOE frequencies in Caucasian populations, however, we found differences in allele frequencies between our Portuguese and Spanish subgroups of AD patients. Moreover, when comparing studies from Iberian and other Caucasian cohorts, differences in APOE2 and APOE4 frequencies and subsequent different APOE-related LOAD risks must be clarified. These results show the importance of studying genetic variation at the APOE gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.

Four soil treatments, consisting of two commercial mycorrhizal fungi, one zeolite and an untreated control, were arranged in a factorial design with two foliar fertilization treatments, a foliar spray and a control to study the effects of commercial mycorrhizal fungi and zeolites on the growth of young, rainfed olive trees planted in very acidic soil. The concentrations in the plant tissues of most of essential nutrients, particularly nitrogen (N), phosphorus (P), potassium (K) and boron (B), did not significantly change with the soil treatments, whereas leaf N and B concentrations significantly increased with foliar fertilization. Leaf calcium (Ca) and magnesium (Mg) levels were found to be much lower than their respective sufficiency ranges and increased with soil amendments, also giving positive outcomes for plant water status, photosynthetic activity and assimilation area. Ultimately, the mycorrhizal fungi increased the growth of the young trees, whereas the effect of zeolites was much smaller and not significantly different to the control. Thus, it seems that in this very acidic soil and under rainfed conditions, the major benefits for plants from the application of mycorrhizal fungi and zeolites were the alleviation of drought stress and tissue Ca and Mg disorders. info:eu-repo/semantics/publishedVersion

Background The Zika virus (ZIKV) is a flavivirus and the human disease caused by this virus has been described in the Americas in 2015. ZIKV has been identified as an etiological agent of acute exanthematous disease in Brazil. In the same year, an epidemic of microcephaly with images suggestive of congenital infection raised the suspicion of a relationship between these alterations and ZIKV infection. Epidemiological and histopathological studies point to a strong relationship between prenatal Zika virus infection and microcephaly. Newborns with microcephaly, may also present auditory and visual changes, seizures and severe neurodevelopmental impairment. In 2016, the World Health Organization (WHO) declared Zika virus (ZIKV) infection a public health emergency of international concern. Aims Clinical observation in the ambulatory school of ABRAH (Brazilian Association of Recycling and Homeopathy Assistance) of patients with encephalopathy of various origins, using the medicine Helleborus niger as equalizer of the NS (Nervous System), as described in the Complex Systems of Carillo, shows improvement in motor, cognitive and seizure disorders. Based on this observation, we propose to use this method in patients with ZIKV congenital infection. Methodology To evaluate 15 patients in follow-up at the AFR (Fluminense Rehabilitation Association), through homeopathic anamnesis, clinical, diathesic, biotypological and temperamental classification. The Gross Motor Function Classification System (GMFCS) will be used. All patients will receive Helleborus niger 6 Ch daily for 6 months. Results and discussion This study was forwarded to the research ethics committee and will begin in July 2019. Will be evaluated the use of Helleborus niger in patients with congenital infection by ZIKV, as equalizer of NS. The expected result is overall neurological improvement. Conclusion Helleborus niger, probably stimulating self-regulation through uninjured neurological pathways, will promote autopoiesis and construction of new programs of action, and will enable the improvement of patients with congenital ZIKV infection.

Some practices in Science Education have become obsolete, due to the variety of information disseminated today in social networks. For this reason, ways of teaching centered on debates and knowledge exchange can be a viable path for the participatory construction of scientific knowledge in school spaces. In this context, the Popular Education in Sciences Project (PEPCiências) arises, with the aim of inviting different scientists and professionals to talk about various topics, with the perspective of popularizing Sciences from the recognition and appreciation of another social knowledge. In this text, the impressions of the monitors of this extension project are analyzed and discussed in the light of Popular Education and the volunteering of the invited workshops, with a view to the limits and potential of this action for other schools. Algumas práticas no Ensino de Ciências têm se colocado como obsoletas, dada a variedade de informações disseminadas hoje com as redes sociais. Por isso, formas de ensinar centradas nos debates e na troca de saberes podem ser um caminho viável para a construção participativa do conhecimento científico nos espaços de escolarização. Nesse contexto, surge o Projeto de Educação Popular em Ciências (PEPCiências), com o intuito de convidar diferentes cientistas e profissionais para conversar sobre temas variados, com a perspectiva da popularização das Ciências a partir do reconhecimento e valorização de outros saberes sociais. Neste relato, as impressões dos monitores desse projeto de extensão são analisadas e discutidas à luz da Educação Popular e do voluntariado dos oficineiros convidados, com vistas aos limites e potencialidades dessa ação para outras escolas.

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG data in five frequency bands (&delta, &theta, &alpha, &beta, 1, and &beta, 2) and genome-wide data in a cohort of 105 patients with late onset Alzheimer&rsquo, s disease (LOAD), 41 individuals with mild cognitive impairment and 45 controls from Iberia, correcting for disease status. One novel association was found with an interesting candidate for a role in brain wave biology, CLEC16A (C-type lectin domain family 16), with a variant at this locus passing the adjusted genome-wide significance threshold after Bonferroni correction. This finding reinforces the importance of immune regulation in brain function. Additionally, at a significance cutoff value of 5 &times, 10&minus, 6, 18 independent association signals were detected. These signals comprise brain expression Quantitative Loci (eQTLs) in caudate basal ganglia, spinal cord, anterior cingulate cortex and hypothalamus, as well as chromatin interactions in adult and fetal cortex, neural progenitor cells and hippocampus. Moreover, in the set of genes showing signals of association with brain wave RP in our dataset, there is an overrepresentation of loci previously associated with neurological traits and pathologies, evidencing the pleiotropy of the genetic variation modulating brain function.

RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse. Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.

O estudo tem como objetivo identificar os fatores influenciadores na satisfação e motivação ao trabalho dos servidores públicos de um município do Rio Grande do Sul. A metodologia adotada caracteriza-se como descritiva, bibliográfica, com uma abordagem quantitativa, sendo utilizado como instrumento para coleta de dados um questionário com perguntas padronizadas e de múltipla escolha, aplicado com os servidores públicos efetivos e em exercício do município. Como resultados, os dados permitiram verificar a presença de diversos fatores que motivam os servidores ao trabalho, porém, constatou-se que a remuneração / salário e a valorização e o reconhecimento são fatores que possuem maior influência tanto como motivadores, quanto desmotivadores ao trabalho. Salienta-se que a partir da implantação de estratégias que valorizem as necessidades pessoais e profissionais, será possível obter resultados mais positivos, contribuindo significativamente para aumentar a motivação e satisfação dos servidores ao trabalho no setor público municipal.

Neck circumference (NC) has been proposed as a simple and practical tool, independently associated with cardiometabolic risk factors. However, the association of NC with inter-muscular adipose tissue (IMAT) is still to be determined. We aimed to examine the association of NC with thigh IMAT, and visceral adipose tissue (VAT) measured with computed tomography (CT) in overweight/obese women. 142 premenopausal overweight and obese Caucasian women participated in this cross-sectional study. NC was measured with an inextensible metallic tape above the thyroid cartilage according to International Society for Advancement of Kinanthropometry protocol. Thigh IMAT and VAT volumes were measured with a single cross-sectional CT. Regarding the covariates, fat mass (FM) was assessed with dual-energy x-ray absorptiometry and physical activity was objectively measured with accelerometry. NC was positively associated with thigh IMAT and VAT volumes (standardized β coefficient: β = 0.45, P-value = ≤0.001, β = 0.60, P = ≤ 0.001; respectively), which persisted after adjusting for age, height, overall FM or moderate-to-vigorous physical activity. Our findings show that NC is associated with thigh IMAT volume in overweight and obese premenopausal Caucasian women, regardless of the amount of lower-body fatness. These results suggest underscoring the relevance of NC as a marker of adipose tissue content in thigh skeletal muscle.

The zebrafish is a widely used animal model in biomedical research. Despite this, pathogens continue to be common in laboratory zebrafish. It is important to determine and describe the pathophysiology of cryptic infections on zebrafish to elucidate the impacts on experimental endpoints. Body condition is a basic measurement used experimentally and in health monitoring of animals. We exposed three wild-type zebrafish strains: AB, WIK, and 5D to Pseudoloma neurophilia. After 8 weeks postexposure, we individually imaged and processed fish for histology. Morphometric analysis was performed on images and an index of body condition was calculated based on the ratio of length/width from the dorsal aspect. Histological sections from each fish were examined to establish sex, severity of infection, and tissue distribution. We observed a significant decrease in body condition in female fish that was not observed in males. In addition, we observed a negative correlation between the total gonadal area of P. neurophilia exposed females and unexposed controls. These results illustrate the sex-specific impacts of a common chronic pathogen on zebrafish health and a commonly used experimental endpoint, further supporting the establishment of rigorous health monitoring programs in laboratory zebrafish colonies that include screening for chronic infectious diseases.

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is predominantly caused by mutations in genes that encode sarcomere-associated proteins. Effective gene-based diagnosis is critical for the accurate clinical management of patients and their family members. However, the introduction of high-throughput DNA sequencing approaches for clinical diagnostics has vastly expanded the number of variants of uncertain significance, leading to many inconclusive results that limit the clinical utility of genetic testing. More recently, developments in RNA analysis have been improving diagnostic outcomes by identifying new variants that interfere with splicing. This review summarizes recent discoveries of RNA mis-splicing in HCM and provides an overview of research that aims to apply the concept of RNA therapeutics to HCM.

Supplemental material, Appendix_3_R1_PMJ-19-0343__Thematic_analyse for Nursing competencies across different levels of palliative care provision: A systematic integrative review with thematic synthesis by Minna Hökkä, Sandra Martins Pereira, Tarja Pölkki, Helvi Kyngäs and Pablo Hernández-Marrero in Palliative Medicine

This article aimed to simulate the new method proposed by the Brazilian Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES) for the classification of Qualis 2017-2020 by tracing the path that led to the B3 stratification attributed to the journal Brazilian Archives of Biology and Technology (BABT). Data collection was based on the evaluation of articles published between 2017 and 2018 to obtain the Lattes curricula of the author(s). Other goals were to verify their participation in stricto sensu postgraduate programs recognized by CAPES; to identify the program’s evaluation area according to CAPES; and to establish the association of authors/co-authors with their respective countries. Overall 199 articles were identified, with 897 authors/co-authors, 359 of which are associated with Brazilian institutions. A participation of at least one Brazilian author/co-author could be verified in 69 articles, out of which 60 had at least one professor affiliated to a stricto sensu postgraduate program recognized by CAPES. There was professors linked to 26 of the 49 CAPES evaluation areas, whereby the highest number of publications were Food Science and Agrarian Sciences I, both with 16 occurrences each. It was verified that the criteria established by the CAPES’ guiding document were not adequately followed. It could be concluded that the journal BABT should have been classified in the stratum A2, with a possible oscillation between A1 and A4, so that its classification as a B3 publication is out of the range foreseen in CAPES’ established criteria.

Alzheimer&rsquo, s disease (AD) is the most prevalent cause of dementia, being considered a major health problem, especially in developed countries. Late-onset AD is the most common form of the disease, with symptoms appearing after 65 years old. Genetic determinants of AD risk are vastly unknown, though, &epsilon, 4 allele of the ApoE gene has been reported as the strongest genetic risk factor for AD. The objective of this study was to analyze the relationship between brain complexity and the presence of ApoE &epsilon, 4 alleles along the AD continuum. For this purpose, resting-state electroencephalography (EEG) activity was analyzed by computing Lempel-Ziv complexity (LZC) from 46 healthy control subjects, 49 mild cognitive impairment subjects, 45 mild AD patients, 44 moderate AD patients and 33 severe AD patients, subdivided by ApoE status. Subjects with one or more ApoE &epsilon, 4 alleles were included in the carriers subgroups, whereas the ApoE &epsilon, 4 non-carriers subgroups were formed by subjects without any &epsilon, 4 allele. Our results showed that AD continuum is characterized by a progressive complexity loss. No differences were observed between AD ApoE &epsilon, 4 carriers and non-carriers. However, brain activity from healthy subjects with ApoE &epsilon, 4 allele (carriers subgroup) is more complex than from non-carriers, mainly in left temporal, frontal and posterior regions (p-values &lt, 0.05, FDR-corrected Mann&ndash, Whitney U-test). These results suggest that the presence of ApoE &epsilon, 4 allele could modify the EEG complexity patterns in different brain regions, as the temporal lobes. These alterations might be related to anatomical changes associated to neurodegeneration, increasing the risk of suffering dementia due to AD before its clinical onset. This interesting finding might help to advance in the development of new tools for early AD diagnosis.

Background: Palliative care exists in diverse healthcare settings. Nurses play a crucial role in its provision. Different levels of palliative care provision and education have been recognized in the literature. Therefore, nurses need a set of various competencies to provide high-quality palliative care. Aims: To systematically synthesize the empirical evidence of (1) nursing competencies needed in palliative care and (2) whether these competencies differ across the level of palliative care. Design: Systematic integrative review with thematic synthesis. Prospero: CRD42018114869. Data sources: CINAHL, PubMed, Academic Search Premier, Scopus and Medic databases. Studies on nursing competencies linked to palliative care reported in English, Swedish, Finnish, Spanish, Portuguese or German were considered. Search terms: ‘palliative care or hospice care or end-of-life care’, ‘competency or professional competence or skills’ and ‘nursing’. Articles were independently screened and reviewed by two researchers. Quality appraisal was conducted following Hawker’s criteria. Results: A total of 7454 articles were retrieved, 21 articles were included in the analysis. Six diverse nursing competencies dimensions, namely leadership, communication, collaboration, clinical, ethico-legal and psycho-social and spiritual were identified. The reports rarely defined the level of palliative care and covered a wide array of healthcare settings. Conclusion: Nurses need a wide range of competencies to provide quality palliative care. Few studies focused on which competencies are relevant to a specific level of palliative care. Further research is needed to systematize the nursing competencies and define which nursing competencies are central for different levels of palliative care to enhance palliative care development, education and practice.

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%–100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

Tem havido uma mudança na linguagem da responsabilidade uma vez que a ameaça de litígio por imperícia está incentivando os médicos a assumir um papel mais responsável no cuidado de seus pacientes. Por conseguinte, em vez de prestar atenção à dimensão moral deste princípio, os profissionais algumas vezes estão muito mais preocupados com as repercussões legais. Portanto, este artigo visa analisar a literatura recente sobre responsabilidade nos cuidados intensivos, com foco em sua dimensão ética. Analisando as contribuições de Emmanuel Levinas, Hans Jonas e Paul Ricoeur, que deram ênfase especial sobre o tema da “responsabilidade moral”, vamos tentar lançar alguma luz sobre este princípio ético dentro do contexto específico da medicina de cuidado intensivo. Este artigo sublinha a importância da responsabilidade a fim de chamar a atenção para a necessidade de estabelecer um equilíbrio adequado entre a autonomia e responsabilidades orientadas para si e para o outro. Sugere-se uma abordagem tridimensional para enquadrar a responsabilidade para dentro do contexto de cuidados intensivos., There has been a shift in the language of responsibility because the threat of malpractice litigation is encouraging physicians to assume a more responsible role in caring for their patients. Consequently, instead of paying attention to the moral dimension of this principle, professionals are sometimes much more concerned about legal repercussions. This article aims therefore at analyzing the recent literature on responsibility in intensive care, focusing on its ethical dimension. By analyzing the contributions of Emmanuel Levinas, Hans Jonas and Paul Ricoeur, who placed special emphasis on the theme of “moral responsibility”, we will attempt to shed some light on this ethical principle within the specific context of Intensive Care Medicine. This paper underlines the importance of responsibility in order to draw attention to the need to establish an appropriate balance between autonomy and self/other-oriented responsibilities. A tridimensional approach is suggested to frame responsibility within the context of intensive care.

Introduction The practice and study of pain management pose myriad ethical challenges. There is a consensual opinion that adequate management of pain is a medical obligation rooted in classical Greek practice. However, there is evidence that patients often suffer from uncontrolled and unnecessary pain. This is inconsistent with the leges artis, and its practical implications merit a bioethical analysis. Several factors have been identified as causes of uncontrolled and unnecessary pain, which deprive patients from receiving appropriate treatments that theoretically they have the right to access. Important factors include (with considerable regional, financial, and cultural differences) the following: 1) failure to identify pain as a priority in patient care; 2) failure to establish an adequate physician–patient relationship; 3) insufficient knowledge regarding adequate prescription of analgesics; 4) conflicting notions associated with drug-induced risk of tolerance and fear of addiction; 5) concerns regarding “last-ditch” treatments of severe pain; and 6) failure to be accountable and equitable. Objective The aim of this article was to establish that bioethics can serve as a framework for addressing these challenging issues and, from theoretical to practical approaches, bioethical reflection can contextualize the problem of unrelieved pain. Methods This article is organized into three parts. First, we illustrate that pain management and its undertreatment are indeed ethical issues. The second part describes possible ethical frameworks that can be combined and integrated to better define the ethical issues in pain management. Finally, we discuss possible directions forward to improve ethical decision making in pain management. Discussion We argue that 1) the treatment of pain is an ethical obligation, 2) health science schools, especially medical training institutions, have the duty to teach pain management in a comprehensive fashion, and 3) regulatory measures, which prevent patients from access to opioid treatment as indicated in their cases, are unethical and should be reconsidered. Conclusion Developing an ethical framework for pain management will result in enhanced quality of care, linking the epistemic domains of pain management to their anthropological foundations, thereby making them ethically sound., Video abstract

Background: Communication is present in all encounters in care and of importance to create a caring relation. A good relation between patients, next of kin and health care staff is crucial, not lea ...

Background: Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. Methods: PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. Results: The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. Conclusion: This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS. This work was supported by the Insulin Resistance Study Group of the Endocrinology, Diabetes and Metabolism Portuguese Society. Ana Cristina Santos holds a FCT Investigator contract IF/01060/2015.

AIM: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp).MATERIALS & METHODS: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs.RESULTS: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%.CONCLUSION: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.

Introduction Antimicrobial resistance (AMR) is a challenging global and public health issue, raising bioethical challenges, considerations and strategies. Objectives This research protocol presents a conceptual model leading to formulating an empirically based bioethics framework for antibiotic use, AMR and designing ethically robust strategies to protect human health. Methods Mixed methods research will be used and operationalized into five substudies. The bioethical framework will encompass and integrate two theoretical models: global bioethics and ethical decision-making. Results Being a study protocol, this article reports on planned and ongoing research. Conclusions Based on data collection, future findings and using a comprehensive, integrative, evidence-based approach, a step-by-step bioethical framework will be developed for (i) responsible use of antibiotics in healthcare and (ii) design of strategies to decrease AMR. This will entail the analysis and interpretation of approaches from several bioethical theories, including deontological and consequentialist approaches, and the implications of uncertainty to these approaches.

Resumo: Este estudo visa identificar práticas organizacionais requeridas para gerar inovação em empresa de tecnologia da informação. A pesquisa investigou como ocorre o desenvolvimento de capacidades que são consideradas críticas para o exercício de atividades voltadas à inovação a partir tanto de características organizacionais específicas como da articulação de recursos. Valorizaram-se duas práticas estruturantes para a inovação: o desenvolvimento de tecnologia e a orientação para o mercado. A abordagem de pesquisa foi qualitativa por meio de um estudo de caso exploratório e descritivo. O caso foi desenvolvido na empresa Softplan, uma das maiores empresas de sistemas de gestão do Brasil, com desenvolvimento de softwares para indústria de construção; atividades de infraestrutura, transporte e obras; sistema judiciário e administração pública em geral. Possui mais de 1500 clientes no Brasil e no exterior e mantém alianças com fornecedores mundiais de tecnologia e convênios com diversas universidades, laboratórios e instituições de pesquisa, suportada por atividades de pesquisa e desenvolvimento. Foram conduzidas entrevistas semiestruturadas com gerentes, pesquisa documental, além de observação in loco. A análise da empresa Softplan evidenciou estímulos à criação e manutenção de um comportamento organizacional voltado para inovação como um processo rotineiro. Foram identificadas práticas desenvolvidas em programas organizacionais que visam à criação e seleção de ideias; à aquisição de conhecimento, e ao estímulo à integração entre os profissionais para o surgimento de aprendizagem organizacional. Abstract: This study aims to identify organizational practices required to generate innovation in an information technology company. The research investigated how the development of capabilities considered critical for activities related to innovation take place from both specific organizational characteristics and joint resources. Two structural practices for innovation were valuable: the development of technology and market targeting. The research had qualitative approach and was carried out through an exploratory and descriptive case study. The case was developed in the Softplan company, one of the largest system management companies in Brazil that develops softwares for building industry, infrastructure activities, transportation and construction works, judiciary system and general public administration. The company has over 1.500 customers in Brazil and abroad and maintains alliances with global technology suppliers and agreements with several universities, laboratories and research institutions, supported by research and development activities. Semi-structured interviews were carried out with managers, along with documentary research and on-site observation. The analysis of the Softplan company showed incentives to creating and maintaining an organizational attitude favoring innovation as a routine process. Practices developed in organizational programs were identified aiming at creation and selection of ideas, acquisition of knowledge, and incentive to integration between professionals for emergence of organizational learning.

Objective: The Bioethics Teaching in Secondary Education (Project BEST) aims to promote the teaching of bioethics in secondary schools. This paper describes the development and implementation of the programme in Portugal. Design: Programme development involved two main tasks: (1) using the learning tools previously developed by the US Northwest Association of Biomedical Research and the Council of Europe and (2) applying the project in classrooms, conducting lectures on bioethics for students and teachers, and then using the previously developed learning tools. Setting: 32 schools representing the most densely populated regions of Portugal. Methods: Two surveys, based on previously validated measures, were used to evaluate the project. Results: The surveys were answered by the 179 students and 16 teachers attending a conference held by the project, which concluded the project’s implementation phase. The findings point to the positive impact of this project. Conclusion: Based on evidence collected to date, it is clear that (1) students can develop reflective skills using this kind of an approach, (2) the project is well suited to secondary school syllabuses and to the age range of students from secondary schools, and (3) the teaching of values should start earlier at school, thereby helping young people develop a critical perspective on problems linked to scientific development and its implications on human health.

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10−5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.

To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness.A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection.Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m.Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica.Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção.Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção.A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.