Transducers for extracellular signal measurements

Dissertação de mestrado, Engenharia Eletrónica e Telecomunicações, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2017The objective of this thesis is to develop and optimize bioelectronic sensing devices for extracellular signal measurements in vitro. Ultra-sensitive electrodes were fabricated and electrically characterized. A signal detection limit defined by a noise level of 0.3-0.4 μV for a bandwidth of 0.1 - 12.5 Hz was achieved. To obtain this high sensitivity, large area (4 mm2) electrodes were used. The electrode surface is also micro-structured with an array of gold and polymer mushroom-like shapes to further enhance the active area. In comparison with a flat gold surface the micro-structured polymer surface increases the capacitance of the electrode/electrolyte interface by six times. The role of the electrode impedance on the signal quality is discussed in detail. The impedance is modeled by an electrical equivalent circuit and a methodology is presented to extract individual circuit parameters. The electrode low impedance and low noise enable the detection of weak and low frequency quasi-periodic signals produced by astrocytes populations that thus far had remained inaccessible using conventional extracellular electrodes. Signals with 5 μV in amplitude and lasting for 5-10 s were measured with a peak-to-peak signal-to-noise ratio of 10. The microstructured electrodes were also used to stimulate electrical activity in glioma cell cultures and astrocytes populations using a train of voltages pulses. The electrodes and the methodology developed here can be used as an ultrasensitive electrophysiological tool to reveal the synchronization dynamics of ultra-slow ionic signaling between non-electrogenic cells.Esta tese tem o objetivo de desenvolver e otimizar componentes eletrónicos para a deteção de sinais extracelulares in vitro. Elétrodos ultrassensíveis foram fabricados e caracterizados eletricamente. O nível de deteção mínimo alcançado foi definido pelo ruído térmico fundamental gerado pelo sensor. Este ruído é de aproximadamente 0,3-0,4 μV para uma largura de banda de 0,1 - 12,5 Hz. Para obter este nível de deteção utilizaram-se elétrodos de grande área (4 mm2). A superfície do elétrodo também é microestruturada com uma série de formas semelhantes a cogumelos para baixar a impedância do elétrodo. Em comparação com uma superfície plana de ouro, a superfície microestrutura da aumenta em seis vezes a capacidade da interface elétrodo/solução eletrolítica O papel da impedância do elétrodo na qualidade do sinal é discutido em detalhe na tese. A impedância é modelada por um circuito elétrico equivalente. É também apresentada uma metodologia para extrair os parâmetros individuais que caracterizam o sensor. O elétrodo de baixa impedância e baixo nível de ruído possibilita a deteção de sinais fracos e de baixa frequência produzidos por populações de astrócitos. Até agora estes sinais permaneceram inacessíveis usando técnicas de medida mais convencionais. Sinais com 5 μV em amplitude e com duração de 5-10 s foram medidos com uma relação sinal/ruído de pico-apico de 10. Os elétrodos microestruturados também foram utilizados para estimular a atividade elétrica em culturas de células glioma e populações de astrócitos. Esta tese propõe que os elétrodos e a metodologia aqui desenvolvida podem ser usados como uma ferramenta eletrofisiológica ultrassensível para revelar a dinâmica de sincronização da sinalização iónica ultra-lenta (na escala de vários segundos e minutos) entre células não eletrogéneas

Tratamento de auto limpeza de materiais têxteis sintéticos

O presente trabalho tem como objectivo estudar a degradação de matérias orgânicas (e.g. corante têxtil) sobre substratos têxteis sintéticos, tecido de poliéster, tecido de poliéster/policloreto de vinilo (PVC) e filmes de PVC. Para o efeito, os substratos têxteis foram tratados com nanopartículas de dióxido titânio, usando técnicas físicas e químicas. Assim iniciou-se o estudo da actividade fotocatalítica do dióxido de titânio na presença de radiação (UV), verificando-se que o corante Astrazon BN sofre uma decomposição efectiva. A escolha de um corante têxtil como exemplo de uma matéria orgânica prende-se com o facto de facilmente se poder fazer uma avaliação colorimétrica da sua degradação durante o trabalho experimental. Da literatura sabe-se que o dióxido de titânio consegue degradar a generalidade de compostos orgânicos, podendo inferir-se que este agente seja adequado para enfrentar os poluentes do mundo exterior que se possam depositar à sua superfície dos objectos, exibindo assim um comportamento auto-limpante desejado. Ao longo deste trabalho apresentam-se, discutem-se e comentam-se os resultados da degradação efectiva ao longo do tempo de um corante de aplicação têxtil. Os resultados obtidos são bastante promissores, de forma a se pensar que este método é viável em acabamentos de auto-limpeza de materiais e mesmo no tratamento de efluentes orgânicos.The present work aims to study the degradation of organic materials (eg textile dye) on synthetic textile substrates, polyester fabric, polyester/polyvinyl chloride (PVC) fabric and PVC films. For this, the textile substrates were treated with nanoparticles of titanium dioxide, using physical and chemical techniques. Thus the study of the photocatalytic activity of titanium dioxide in the presence of UV radiation was done, thus verifying that the Astrazon BN dye undergoes an effective decomposition. The choice of a textile dye as an example of organic matter relates to the fact that one can easily make a colorimetric evaluation of its degradation during the experimental work. From literature it is known that titanium dioxide can degrade the majority of organic compounds, which can be inferred that this agent is adequate to address the pollutants of the outside world that may be placed on the surface of objects, thus exhibiting a required selfcleaning behaviour. Throughout this paper we present, discuss and comment the results of the actual degradation over time of a textile dye. The results are very promising, so we think that this method is feasible in of self-cleaning finishing of materials and even in the treatment of organic wastewater

Fractional flow reserve-guided strategy in acute coronary syndrome. a systematic review and meta-analysis

Background: There are limited data on the prognosis of deferral of lesion treatment in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR). Objectives: To provide a systematic review of the current evidence on the prognosis of deferred lesions in ACS patients compared with deferred lesions in non-ACS patients, on the basis of FFR. Methods: We searched Medline, EMBASE, and the Cochrane Library for studies published between January 2000 and September 2017 that compared prognosis of deferred revascularization of lesions on the basis of FFR in ACS patients compared with non-ACS patients. We conducted a pooled relative risk meta-analysis of four primary outcomes: mortality, cardiovascular (CV) mortality, myocardial infarction (MI) and target-vessel revascularization (TVR). Results: We identified 7 studies that included a total of 5,107 patients. A pooled meta-analysis showed no significant difference in mortality (relative risk [RR] = 1.44; 95% CI, 0.9–2.4), CV mortality (RR = 1.29; 95% CI = 0.4–4.3) and TVR (RR = 1.46; 95% CI = 0.9–2.3) after deferral of revascularization based on FFR between ACS and non-ACS patients. Such deferral was associated with significant additional risk of MI (RR = 1.83; 95% CI = 1.4–2.4) in ACS patients. Conclusion: The prognostic value of FFR in ACS setting is not as good as in stable patients. The results demonstrate an increased risk of MI but not of mortality, CV mortality, and TVR in ACS patients.publishe

Alteplase for Massive Pulmonary Embolism after Complicated Pericardiocentesis

Background: The occurrence of a high-risk pulmonary embolism (PE) within 48 hours of a complicated pericardiocentesis to remove a haemorrhagic pericardial effusion, is an uncommon clinical challenge. Case summary: The authors report the case of a 75-year-old woman who presented with signs of imminent cardiac tamponade due to recurring idiopathic pericardial effusion. The patient underwent pericardiocentesis that was complicated by the loss of 1.5 litres of blood. Within 48 hours, the patient had collapsed with clear signs of obstructive shock. This was a life-threating situation so alteplase was administered after cardiac tamponade and hypertensive pneumothorax had been excluded. CT chest angiography later confirmed bilateral PE. The patient achieved haemodynamic stability less than an hour after receiving the alteplase. However, due to the high risk of bleeding, the medical team suspended the thrombolysis protocol and switched to unfractionated heparin within the hour. The cause of the PE was not identified despite extensive study, but after 1 year of follow-up the patient remained asymptomatic. Discussion: Despite the presence of a contraindication, the use of thrombolytic therapy in obstructive shock after exclusion of hypertensive pneumothorax can be life-saving, and low-dose thrombolytic therapy may be a valid option in such cases

Caracterização molecular dos doentes portugueses com miocardiopatia dilatada

Introduction: Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by ventricular dilatation and impaired systolic function. Familial forms account for 30-50% of cases. Autosomal dominant inheritance is the predominant pattern of transmission. Causal genetic variants have been identified in several genes and molecular diagnosis has implications for genetic counseling and risk stratification. Objective: We aimed to estimate the frequency of genetic variants and the molecular basis of DCM in Portugal. Methods: We performed a multicenter study of unrelated patients, recruited between 2013 and 2014. Variants in 15 genes were screened using PCR with direct sequencing (next-generation sequencing with at least 30-fold coverage combined with Sanger sequencing). Results: A total of 107 patients were included, 64 (60%) men, mean age at diagnosis 38±13 years, with 48 (45%) familial cases. In total, 31 rare variants in eight genes (mainly in MYBPC3, TNNT2 and LMNA) were identified, in 28 patients (26%). Only four variants had been previously described in association with DCM, 11 with hypertrophic cardiomyopathy, and nine variants were novel. Four variants were likely pathogenic and the remainder were of uncertain significance. We found no major differences in the main clinical and imaging characteristics between patients with or without rare variants and patients with likely pathogenic variants. Conclusions: Our results reflect the complexity and diversity of DCM genetics. For better inter-pretation of the pathogenicity of the variants found and their causative roles in DCM, molecularcascade screening of families is imperative. Further insight into genotype-phenotype correla-tions and risk stratification is desirable.Introdução: A miocardiopatia dilatada (MCD) é uma doença do músculo cardíaco caracterizada por dilatação ventricular e compromisso da função sistólica. As formas familiares são responsáveis por 30 a 50% dos casos. O padrão de hereditariedade predominante é o autossómicodominante. Variantes genéticas causais foram identificadas em vários genes e o diagnósticomolecular tem implicac¸ões para o aconselhamento genético e estratificação de risco.Objetivo: Avaliar a base molecular da MCD em Portugal.Métodos: Estudo multicêntrico de doentes não relacionados, recrutados entre 2013 e 2014.Foram analisados 15 genes, através da técnica de PCR com sequenciac¸ão direta (NGS com pelomenos uma cobertura de 30 vezes combinada com sequenciac¸ão de Sanger).Resultados: Foram incluídos 107 pacientes, 64 (60%) homens, idade média ao diagnóstico de38 ± 13 anos, com 48 (45%) casos familiares. Foram identificadas 31 variantes raras, em oitogenes, (principalmente MYBPC3, TNNT2 e LMNA) em 28 pacientes (26%). Apenas quatro variantestinham sido previamente descritas em associac¸ão com MCD, 11 com miocardiopatia hipertró-fica e nove variantes eram novas. Quatro variantes foram classificadas como provavelmentepatogénicas e as restantes de significado incerto. Não encontrámos diferenc¸as significativas nasprincipais características clínicas e imagiológicas entre doentes com ou sem variantes raras e doentes com variantes provavelmente patogénicas. Conclusões: Estes resultados refletem a complexidade e diversidade genética da MCD. Para uma melhor interpretação da patogenicidade das variantes e potencial causalidade, o rastreio molecular das famílias é imperativo. Uma visão mais aprofundada das correlações genótipo-fenótipo e da estratificação de risco é desejável

A hybrid bi-objective optimization approach for joint determination of safety stock and safety time buffers in multi-item single-stage industrial supply chains

In material requirements planning (MRP) systems, safety stock and safety time are two well-known inventory buffering strategies to protect against supply and demand uncertainties. While the role of safety stocks in coping with uncertainty is well studied, safety time has received only scarce attention in the supply chain management literature. Particularly, most previous operations research models have typically considered the use of such inventory buffers in a separate fashion, but not together. Here, we propose a decision support system (DSS) to address the problem of integrating optimal safety stock and safety time decisions at the component level, in multi-supplier multi-item single-stage industrial supply chains under dynamic demands and stochastic lead times. The DSS is based on a hybrid bi-objective optimization approach that simultaneously optimizes upstream inventory holding costs and β-service levels, suggesting multiple non-dominated Pareto-optimal solutions to decision-makers. We further explore a weighted closed-form analytical expression to select a single Pareto-optimal point from a set of non-dominated solutions, thereby enhancing the practical application of the proposed DSS. We describe the implementation of our approach in a major automotive electronics company operating under a myriad of components with dynamic demand, uncertain supply and requirements plans with different degrees of sparsity. We show the potential of our approach to improve β-service levels while minimizing inventory-related costs. The results suggest that, in certain cases, it appears to be more cost-effective to combine safety stock with safety time compared to considering each inventory buffer independently.This work has been supported by the European Structural and Investment Funds in the FEDER component, through the Operational Competitiveness and Internationalization Pro-gram (COMPETE 2020) [Project No. 39479, Funding reference: POCI-01–0247-FEDER-39479]

Clinical and epidemiological features of hospitalized and ambulatory patients with human monkeypox infection: a retrospective observational study in Portugal

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.The writing of this manuscript received the support of Fundação para a Ciência e a Tecnologia, grant numbers UIDB/04295/2020 and UIDP/04295/2020info:eu-repo/semantics/publishedVersio

A comprehensive assessment of the transcriptome of cork oak (Quercus suber) through EST sequencing

Background: Cork oak (Quercus suber) is one of the rare trees with the ability to produce cork, a material widely used to make wine bottle stoppers, flooring and insulation materials, among many other uses. The molecular mechanisms of cork formation are still poorly understood, in great part due to the difficulty in studying a species with a long life-cycle and for which there is scarce molecular/genomic information. Cork oak forests are of great ecological importance and represent a major economic and social resource in Southern Europe and Northern Africa. However, global warming is threatening the cork oak forests by imposing thermal, hydric and many types of novel biotic stresses. Despite the economic and social value of the Q. suber species, few genomic resources have been developed, useful for biotechnological applications and improved forest management. Results: We generated in excess of 7 million sequence reads, by pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber tissues and organs, developmental stages and physiological conditions. We deployed a stringent sequence processing and assembly pipeline that resulted in the identification of ~159,000 unigenes. These were annotated according to their similarity to known plant genes, to known Interpro domains, GO classes and E.C. numbers. The phylogenetic extent of this ESTs set was investigated, and we found that cork oak revealed a significant new gene space that is not covered by other model species or EST sequencing projects. The raw data, as well as the full annotated assembly, are now available to the community in a dedicated web portal at http://www.corkoakdb.org. Conclusions: This genomic resource represents the first trancriptome study in a cork producing species. It can be explored to develop new tools and approaches to understand stress responses and developmental processes in forest trees, as well as the molecular cascades underlying cork differentiation and disease response.Peer Reviewe

Database Survey of Anti-Inflammatory Plants in South America: A Review

Inflammation is a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. This physiological response is coordinated largely by a variety of chemical mediators that are released from the epithelium, the immunocytes and nerves of the lamina propria. However, if the factor that triggers the inflammation persists, the inflammation can become relentless, leading to an intensification of the lesion. The present work is a literature survey of plant extracts from the South American continent that have been reported to show anti-inflammatory activity. This review refers to 63 bacterial families of which the following stood out: Asteraceae, Fabaceae, Euphorbiaceae, Apocynaceae and Celastraceae, with their countries, parts used, types of extract used, model bioassays, organisms tested and their activity