Desafios éticos e legais da medicina personalizada: exemplos paradigmáticos de investigação, prevenção, diagnóstico e tratamento

A B S T R A C T - This article overviews the important ethical and legal challenges of different steps of thepersonalized medicine journey such as research, prevention, diagnosis and treatment bydiscussing paradigmatic examples including biobanks, genetic tests and gene therapy. Sci-entific progress in the area of genetics, the completion of the Human Genome Project and theability to sequence genomes for competitive prices have offered the promise of revolution-izing healthcare and raised important challenges to classical paradigms in the biomedicallaw and ethics fields. Issues such as informed consent, privacy and confidentiality, anddiscrimination require particular analysis in this context. In the last years the concept ofpersonalized medicine has been a source of considerable hype and hope. Law and ethicsshould be important allies to limit the former and potentiate the later.R E S U M O - Este artigo sumariza alguns dos desafios ético-legais mais importantes das diferentes etapas da medicina personalizada, partindo da investigação, passando pela prevenção e pelo diagnóstico, e terminando no tratamento. Esta análise é realizada através da discussão de exemplos paradigmáticos de cada etapa, como os biobancos, os testes genéticos e a terapia génica. O progresso científico na área da genómica, a finalização do Projeto do Genoma Humano e a capacidade de sequenciar genomas inteiros a preços cada vez mais competitivos originaram a promessa de revolucionar a área da saúde e colocaram desafios importantes a alguns conceitos tradicionais nas áreas da ética e do direito biomédico. Consequentemente, temas como o consentimento informado, a privacidade e a confidencialidade e a discriminação exigem uma análise atenta e particular neste contexto. Nos últimos anos, o conceito de medicina personalizada tem sido, simultaneamente, uma fonte de expetativas exageradas e de grande esperança. O direito e a ética devem ser aliados fundamentais para limitar as primeiras e potenciar a última.info:eu-repo/semantics/publishedVersio

Counterexample Guided Inductive Optimization Applied to Mobile Robots Path Planning (Extended Version)

We describe and evaluate a novel optimization-based off-line path planning algorithm for mobile robots based on the Counterexample-Guided Inductive Optimization (CEGIO) technique. CEGIO iteratively employs counterexamples generated from Boolean Satisfiability (SAT) and Satisfiability Modulo Theories (SMT) solvers, in order to guide the optimization process and to ensure global optimization. This paper marks the first application of CEGIO for planning mobile robot path. In particular, CEGIO has been successfully applied to obtain optimal two-dimensional paths for autonomous mobile robots using off-the-shelf SAT and SMT solvers.Comment: 7 pages, 14rd Latin American Robotics Symposium (LARS'2017

systematic review

Publisher Copyright: ©Ana Soraia Cunha, Ana Rita Pedro, João V Cordeiro. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.07.2023.BACKGROUND: The COVID-19 pandemic accelerated the digital transition in health care, which required a rapid adaptation for stakeholders. Telemedicine has emerged as an ideal tool to ensure continuity of care by allowing remote access to specialized medical services. However, its rapid implementation has exacerbated disparities in health care access, especially for the most susceptible populations. OBJECTIVE: We aimed to characterize the determinant factors (facilitators and barriers) of access to hospital medical specialty telemedicine consultations during the COVID-19 pandemic and to identify the main opportunities and challenges (technological, ethical, legal, and social) generated by the use of telemedicine in the context of the COVID-19 pandemic. METHODS: We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 4 databases (Scopus, Web of Science, PubMed, and Cochrane COVID-19 Study Register) were searched for empirical studies published between January 3, 2020, and December 31, 2021, using established criteria. The protocol of this review was registered and published in PROSPERO (CRD42022302825). A methodological quality assessment was performed, and the results were integrated into a thematic synthesis. The identification of the main opportunities and challenges was done by interpreting and aggregating the thematic synthesis results. RESULTS: Of the 106 studies identified, 9 met the inclusion criteria and the intended quality characteristics. All studies were originally from the United States. The following facilitating factors of telemedicine use were identified: health insurance coverage; prevention of SARS-CoV-2 infection; access to internet services; access to technological devices; better management of work-life balance; and savings in travel costs. We identified the following barriers to telemedicine use: lack of access to internet services; lack of access to technological devices; racial and ethnic disparities; low digital literacy; low income; age; language barriers; health insurance coverage; concerns about data privacy and confidentiality; geographic disparities; and the need for complementary diagnostic tests or the delivery of test results. CONCLUSIONS: The facilitating factors and barriers identified in this systematic review present different opportunities and challenges, including those of a technological nature (access to technological devices and internet services and level of digital literacy), a sociocultural and demographic nature (ethnic and racial disparities, geographic disparities, language barriers, and age), a socioeconomic nature (income level and health insurance coverage), and an ethical and legal nature (data privacy and confidentiality). To expand telemedicine access to hospital-based specialty medical consultations and provide high-quality care to all, including the most susceptible communities, the challenges identified must be thoroughly researched and addressed with informed and dedicated responses.publishersversionpublishe

The Release of Vaccinia Virus from Infected Cells Requires RhoA-mDia Modulation of Cortical Actin

SummaryPrior to being released from the infected cell, intracellular enveloped vaccinia virus particles are transported from their perinuclear assembly site to the plasma membrane along microtubules by the motor kinesin-1. After fusion with the plasma membrane, stimulation of actin tails beneath extracellular virus particles acts to enhance cell-to-cell virus spread. However, we lack molecular understanding of events that occur at the cell periphery just before and during the liberation of virus particles. Using live cell imaging, we show that virus particles move in the cell cortex, independently of actin tail formation. These cortical movements and the subsequent release of virus particles, which are both actin dependent, require F11L-mediated inhibition of RhoA-mDia signaling. We suggest that the exit of vaccinia virus from infected cells has strong parallels to exocytosis, as it is dependent on the assembly and organization of actin in the cell cortex

Surface modification of banana-based lignocellulose fibres

Lignocellulosic raw materials were isolated from rachis of Musa acuminata Colla var. cavendish and characterised before and after chemical modification. The rachis was submitted to different mechanical treatments, milling and defibration, resulting in rachis powder and rachis fi bers, respectively. The chemical composition of these two samples was established and it was shown that rachis fibres exhibited higher polysaccharide and lignin contents and lower amounts of ash and extractives components, as compared with the rachis powder. The effects of solvent extrac tion, alkali treatment and chemical modification using phenyl isocyanate, maleic anhydride, alkenyl succinic anhydride and alkyl ketone dimer as grafting agents were studied. The materials were characterized in terms of chemical structure by ATR–FT-IR and 13C-CP-MAS-NMR spectroscopy, morphology by scanning electron microscopy and surface energies by inverse gas chromatography and contact angle measurements. The surface energy of these materials was found to be very close to other similar lignocellulosic materials. Finally, the water absorption of these materials before and after treatment was ascertained. The modified fibres showed considerable changes in ATR–FT-IR and 13C-CP-MAS-NMR spectra and surface properties, providing very convincing evidence that chemical grafting had occurred.info:eu-repo/semantics/publishedVersio

a comprehensive survey of medical doctor's perspectives in Portugal

Publisher Copyright: Copyright: © 2023 Pedro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Artificial Intelligence (AI) is increasingly influential across various sectors, including healthcare, with the potential to revolutionize clinical practice. However, risks associated with AI adoption in medicine have also been identified. Despite the general understanding that AI will impact healthcare, studies that assess the perceptions of medical doctors about AI use in medicine are still scarce. We set out to survey the medical doctors licensed to practice medicine in Portugal about the impact, advantages, and disadvantages of AI adoption in clinical practice. We designed an observational, descriptive, cross-sectional study with a quantitative approach and developed an online survey which addressed the following aspects: impact on healthcare quality of the extraction and processing of health data via AI; delegation of clinical procedures on AI tools; perception of the impact of AI in clinical practice; perceived advantages of using AI in clinical practice; perceived disadvantages of using AI in clinical practice and predisposition to adopt AI in professional activity. Our sample was also subject to demographic, professional and digital use and proficiency characterization. We obtained 1013 valid, fully answered questionnaires (sample representativeness of 99%, confidence level (p< 0.01), for the total universe of medical doctors licensed to practice in Portugal). Our results reveal that, in general terms, the medical community surveyed is optimistic about AI use in medicine and are predisposed to adopt it while still aware of some disadvantages and challenges to AI use in healthcare. Most medical doctors surveyed are also convinced that AI should be part of medical formation. These findings contribute to facilitating the professional integration of AI in medical practice in Portugal, aiding the seamless integration of AI into clinical workflows by leveraging its perceived strengths according to healthcare professionals. This study identifies challenges such as gaps in medical curricula, which hinder the adoption of AI applications due to inadequate digital health training. Due to high professional integration in the healthcare sector, particularly within the European Union, our results are also relevant for other jurisdictions and across diverse healthcare systems.publishersversionpublishe

Computational Modelling and Sustainable Synthesis of a Highly Selective Electrochemical MIP-Based Sensor for Citalopram Detection

A novel molecularly imprinted polymer (MIP) has been developed based on a simple and sustainable strategy for the selective determination of citalopram (CTL) using screen-printed carbon electrodes (SPCEs). The MIP layer was prepared by electrochemical in situ polymerization of the 3-amino-4 hydroxybenzoic acid (AHBA) functional monomer and CTL as a template molecule. To simulate the polymerization mixture and predict the most suitable ratio between the template and functional monomer, computational studies, namely molecular dynamics (MD) simulations, were carried out. During the experimental preparation process, essential parameters controlling the performance of the MIP sensor, including CTL:AHBA concentration, number of polymerization cycles, and square wave voltammetry (SWV) frequency were investigated and optimized. The electrochemical characteristics of the prepared MIP sensor were evaluated by both cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Based on the optimal conditions, a linear electrochemical response of the sensor was obtained by SWV measurements from 0.1 to 1.25 µmol L−1 with a limit of detection (LOD) of 0.162 µmol L−1 (S/N = 3). Moreover, the MIP sensor revealed excellent CTL selectivity against very close analogues, as well as high imprinting factor of 22. Its applicability in spiked river water samples demonstrated its potential for adequate monitoring of CTL. This sensor offers a facile strategy to achieve portability while expressing a willingness to care for the environmentPatrícia Rebelo (SFRH/BD/132384/2017) and João Pacheco (SFRH/BPD/101419/2014) are grateful to Fundação para a Ciência e a Tecnologia (FCT) and European Union (EU) for their grants, financed by POPH-QREN-Tipologia 4.1-Formação Avançada, funded by Fundo Social Europeu (FSE) and Ministério da Ciência, Tecnologia e Ensino Superior (MCTES). Isabel Seguro is grateful to the project Farmasense (39957) that was funded by Sistema de Incentivos à Investigação e Desenvolvimento Tecnológico de Portugal 2020, through the Programa Operacional do Norte (NORTE 2020) and the Fundo Europeu de Desenvolvimento Regional (FEDER). This work was further supported by UID/QUI/50006/2020 (LAQV-REQUIMTE) and the project PTDC/QUI-QAN/3899/2021 with funding from FCT/MCTES through national funds. The research was funded also by FCT and BiodivRestore Joint Call 2020–2021-European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003777-BiodivRestore-406/DivRestore/0002/2020-BioReset-“Biodiversity restoration and conservation of inland water ecosystems for environmental and human well-being”info:eu-repo/semantics/publishedVersio

perceptions and choices among rheumatology outpatients

OBJECTIVE: Biobanks for research (BBR) have enormous value for research, including those specifically oriented to chronic diseases. Knowing public attitudes and perceptions is key to design and implement patient-centered BBR. We assessed patient awareness, perception and choices among rheumatology outpatients regarding aging biobanking activities. METHODS: We conducted a cross-sectional survey of patients, aged 50 or older, attending an outpatient rheumatology tertiary department. Demographic data and perceptions about biobanking were collected and statistical analysis was performed. RESULTS: 132 valid questionnaires were obtained (mean age: 63,4; 68,2% female; mean education years: 8,35). 61,7% of respondents did not know the specific term "biobank", 57,7% knew they could donate biological material for BBR, 89,9% agreed with these infrastructures and 88,3% would consider participation Those participants with more years of education were more knowledgeable and prone to biobank participation. Willingness to participate in BBR was mainly related (86,4%) to the advancement of scientific knowledge and not individual gain. Scientific research institutes were indicated as the most adequate institutions to manage BBR. Informed consent, anonymity and confidentiality ranked as top requisites for biobank participation. 61,3% of respondents expressed their agreement with aging biobanks, considering these as a sign of respect for specific problems of people of older ages such as higher disease burdens. CONCLUSION: Knowledge of biobanks was found to be limited. Participants were positive toward the setting up of biobanks in general and patient-centered aging biobanks in particular. Knowledge about biobanks and acceptance were higher among participants with higher education years.publishersversionpublishe

X-linked Adrenal Hypoplasia Congenita: report of two families and a new NR0B1 mutation

Background: X-linked Adrenal Hypoplasia Congenita (X-linked AHC) tipically manifests as adrenal insufficiency in a bimodal clinical presentation (5–60 days and 2–13 years) and, at pubertal age, hypogonadotropic hypogonadism (HH) in males. It is caused by mutations in NR0B1 (present in Xp21.2), a gene with a critical role in the development of adrenals and hypothalamic-pituitary-gonadal (HPG) axis. It represents ~1% of all causes of primary adrenal insufficiency under age 18. We present two kindreds with NR0B1 mutations, one with a previously unreported mutation. Clinical case - family A: The proband presented with adrenal crisis at day 18 of life. Family history was relevant for an uncle death as a newborn. Hormonal assays revealed elevated ACTH (34,5 pmol/L, reference: T, leading to a premature stop codon, p.Lys362*, in exon 1. His mother and sister were both asymptomatic carriers for this mutation. This mutation, not described previously, leads probably to a non-functional truncated protein. Clinical case - family B: Kindred B had two males who presented with adrenal crisis at the newborn age (proband: 14 days; brother: 16 days). At 6 months of age, the proband had elevated ACTH (193.2 pmol/L, reference: G; p.Tyr81*, in exon 1, present in the two affected males. His mother and one sister were also asymptomatic carriers. Conclusion: Our kindreds highlights the clinical aspects of the rare X-linked AHC and its challenging differential diagnosis. The diagnosis was based on …. Completar … and an apparently X-linked mode of inheritance. Molecular analysis of the NR0B1 gene allowed the identification of the molecular defect in both families. Two different nonsense mutation in exon 1 were identified, giving rise most probably to truncated non-functional proteins, confirming the disease severity or the clinical phenotype of the affected boys. Mutation identification was relevant for genetic counseling of the parents, as well as for the patient’s sisters