848 research outputs found
Multifunctional Nanoparticles for Targeted Drug Delivery and Imaging for Ischemic Myocardial Injury
Currently, there is no major discovery of an effective cure to restore the function of an injured heart, despite the existing and developing therapies. While existing options ameliorate the care of myocardial infarction (MI) and heart failure patients, cardiac stem cell therapy has only recently shown positive results in clinical trials, and thus there is an urgent medical need to develop advanced therapeutic entities to reverse this disease burden. The employment of biomaterials as potential therapeutics for MI is at the pre-clinical stage. Particulate systems are arising as a promising tool to provide minimally invasive treatment, an important aspect to take into account for clinical translation and patient compliance.
Porous silicon (PSi) and spermine-acetalated dextran (AcDXSp) are emerging biomaterials for applications in varying biomedical fields. Drug delivery is one of these fields benefiting from the materials’ properties, such as biocompatibility, biodegradability, customized particle preparation, surface functionalization, simple yet efficient drug loading, and tunable release of the therapeutic cargos. Therefore, the aim of this thesis was to develop multifunctional PSi and AcDXSp platforms for targeted drug delivery to and imaging of the ischemic heart. Initially, the biocompatibility of PSi-based carriers of different sizes and surface chemistries was evaluated.
Secondly, three different PSi-based nanosystems were developed, functionalized with a metal chelator for radiolabeling and three different peptides (atrial natriuretic peptide (ANP) and two other heart-homing peptides), with the aim to screen the targetability of the nanoparticles to the ischemic heart. All the nanosystems showed no toxicity up to 50 µg/mL concentration, and cell–nanoparticle interaction studies in cardiomyocytes and non-myocytes revealed a preferential cellular interaction with ANP-functionalized nanoparticles in both the cell types, through the natriuretic peptide receptors (NPRs) present at the cell surface.
Thirdly, the ANP-PSi functionalized nanoparticles were PEGylated in order to improve the colloidal stability and enhance the circulation time. Upon labeling with radioisotope Indium-111, the ANP-PSi nanoparticles displayed a preferential accumulation and selectivity towards the endocardial layer of the ischemic heart. In vivo delivery of a cardioprotective small drug molecule from the ANP-PSi showed attenuation of the extracellular signal-regulated kinase pathway that is involved in the hypertrophic signaling of the injured heart. Lastly, and in parallel, the development of functionalized and dual-loaded AcDXSp nanoparticles for potential application in cellular reprogramming was proven successful, by utilizing acidic pH-triggered drug delivery of the two poorly water-soluble cargos. The incubation of non-myocytes with ANP-functionalized AcDXSp nanoparticles showed therapeutic modulation of key signaling pathways involved in the direct fibroblast reprogramming into cardiomyocytes.
Overall, PSi and AcDXSp-based (nano)particulate systems were developed, bringing new insights about potential therapeutic advances in the applicability of imaging and targeted delivery of relevant pharmacological molecules to the ischemic heart with a minimally invasive therapeutic approach.Jo olemassa olevista ja kehitteillä olevista hoidoista huolimatta vaurioituneen sydämen toimintakyvyn palauttamiseen ei ole tehokasta hoitoa. Vaikka nykyiset vaihtoehdot parantavat sydäninfarktista (MI) ja sydämen vajaatoiminnasta kärsivien potilaiden hoitoa, ja vaikka sydämen kantasoluhoito on hiljattain saanut aikaan positiivisia tuloksia sydänlihaskantasoluhoidoissa, on silti suuri tarve kehittää lääketieteellisiä terapioita sydänperäisiin tauteihin. Biomateriaalien soveltaminen sydäninfarktin hoitoon on prekliinisessä vaiheessa. Nanohiukkasiin perustuvat hoitomuodot ovat lupaavia, sillä ne mahdollistavat ei-invasiivisen hoidon, mikä on tärkeä näkökulma ottaen huomioon kliinisen käytettävyyden ja potilaiden hoitomyöntyvyyden.
Huokoinen pii (PSi) ja spermiini-asetyloitu dekstraani (AcDXSp) ovat lupaavia biomateriaaleja, jotka soveltuvat useille biolääketieteen osa-alueille. Lääkeaineen kuljetus on yksi näistä alueista, joka hyötyy AcDXSp:n seuraavista ominaisuuksista: bioyhteensopivuus, biohajoavuus, asiakaskohtaiset hiukkasten valmistustekniikat, mahdollisuus hiukkasten pinnan funktionalisointiin, yksinkertainen ja tehokas lääkkeen kuormaaminen sekä terapeuttisten aineiden säädeltävissä oleva vapautuminen. Tämän väitöstyön tarkoituksena oli kehittää monitoimisia PSi- ja AcDXSp sovelluksia sepelvaltimotautiin kohdennettua lääkkeenkuljetusta ja kuvantamista varten. Aluksi tutkittiin erikokoisten ja erilailla pintakäsiteltyjen PSi-pohjaisten lääkkeenkuljettimien bioyhteensopivuutta.
Seuraavaksi kehitettiin kolme erilaista PSi-pohjaista nanolääkkeenkuljetinta, jotka funktionalisoitiin metallikompleksilla isotooppileimausta varten ja kolmella erilaisella peptidillä (A-tyypin natriureettinen peptidi (ANP) ja kaksi muuta sydämeen kuljettavaa peptidiä), tarkoituksena tutkia nanohiukkasten kohdennettavuutta sepelvaltimotautiin. Kehitetyillä nanolääkekuljettimilla ei havaittu sytotoksisuutta 50 µg/mL pienemmillä pitoisuuksilla. Solu-nanohiukkas-vuorovaikutustutkimukset sydänlihassoluilla (kardiomyosyytit) ja sidekudossoluilla (fibroblastit) osoittivat ANP-funktionalisoitujen nanohiukkasten vuorovaikuttavan molempien solutyyppien kanssa niiden pinnalla esiintyvien natriureettisten peptidireseptorien kautta.
ANP-funktionalisoidut nanohiukkaset PEGyloitiin kolloidisen stabiilisuuden ja verenkiertoajan parantamiseksi. Kun nanohiukkaset isotooppileimattiin Indium-111:llä, ANP-PSi nanohiukkaset osoittautuivat kerääntyvän iskeemisen sydämen sisäkalvoon (endokardium). In vivo-kokeissa ANP-PSi-hiukkasista vapautuvan sydäntä suojaavan lääkkeen huomattiin estävän solun ulkopuolista kinaasitietä (EKR), joka liittyy sydäninfarkitissa vaurioituneen sydämen hypertrofiseen viestintään. Lopuksi osoitettiin funktionalisoitujen ja kahdella huonosti liukenevalla lääkeaineella kapseloitujen AcDXSp-nanohiukkasten soveltuvuus solujen uudelleenohjelmointiin happamassa pH:ssa käynnistyvän lääkkeenvapautumisen avulla. Fibroblastien inkubointi ANP-funktionalisoitujen AcDXSp-nanohiukkasten kanssa osoitti, että nanohiukkaset kykenivät vaikuttamaan terapeuttisesti tärkeimpiin signaaliteihin, jotka liittyvät fibroblastien uudelleenohjelmointiin kardiomyosyyteiksi.
Väitöstyössä onnistuttiin kehittämään uudenlaisia PSi- ja AcDXSp-nanohiukkasjärjestelmiä, jotka tuovat uutta tietämystä sovellettaessa ei-invasiivista kuvantamista ja kohdennettua lääkkeenaineen kuljetusta sepelvaltimotaudin hoidossa
NETPAPER : win buyers in a new, online and business to business company
NETPAPER is a Portuguese Startup that was born in October 2014. The main goal of the company is: promote and generate traffic on the brands websites; and create a stronger relationship and knowledge between the brands and the consumers.
NETPAPER is a B2B company in the digital marketing area. This area and the internet has been evolving a lot in the last years. The biggest advantages of NETPAPER are: companies win traffic and knowledge about their websites; and consumers win prizes.
One year after NETPAPER creation, the company already should have more buyers that had in the reality, so something was going wrong. The company partners decided they had to do something in order to solve the situation, they needed to win buyers faster. And the paths they could follow were: improve the ways to attract buyers, online or simplify the NETPAPER concept.A NETPAPER é uma Startup Portuguesa que nasceu em Outubro de 2014. Os principais objetivos da empresa são: divulgar e gerar tráfego nos sites das marcas; dar aos utilizadores mais conhecimento sobre as marcas; e criar uma relação mais forte entre as marcas e os consumidores.
A NETPAPER Ă© uma empresa que disponibiliza um serviço na área do marketing digital. Esta área e a internet tĂŞm evoluĂdo muito nos Ăşltimos anos. As maiores vantagens da NETPAPER sĂŁo: as empresas ganham tráfego e conhecimento sobre os seus sites e os consumidores ganham prĂ©mios.
Um ano depois da criação da NETPAPER, a empresa já deveria ter mais clientes do que tinha na realidade, por isso alguma coisa não estava a correr bem. As sócias da empresa decidiram que tinham de fazer algo para resolver esta situação, a empresa precisava de ganhar clientes mais rapidamente. E os caminhos que a empresa podia seguir eram: melhorar a forma de atrair os clientes, Online ou simplificar o conceito de NETPAPER
Os efeitos da fisioterapia em doentes com Esclerose Múltipla: revisão bibliográfica
Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciada em FisioterapiaIntrodução: A esclerose múltipla (EM), doença que destrói a mielina dos axónios da
substância branca do sistema nervoso central, vai atingir especificamente a parte motora do
indivĂduo, no entanto tambĂ©m afeta a parte cognitiva e a visual, pelo que esta revisĂŁo
bibliográfica tem como objetivo analisar a influência da fisioterapia nas pessoas com EM.
Metodologia: A base de dados utilizada para a pesquisa foi a Pubmed. Os critérios de
inclusão abrangeram artigos randomizados controlados que descrevessem a intervenção da
fisioterapia em doentes com EM, publicados nos Ăşltimos 5 anos e disponĂveis em texto
integral. Como critérios de exclusão foram considerados artigos com estudos que tivessem
mais do que um tipo de tratamento em simultâneo. Resultados: Os artigos incluĂdos no
estudo foram 8, com uma média de 5,5 em 10 na escala de PEDro. Os parâmetros avaliados
foram: estabilidade postural, suporte social, barreiras percebidas, estratégias adotadas,
frequĂŞncia cardĂaca, esforço percebido, funcionalidade e qualidade de vida. ConclusĂŁo: Na
revisĂŁo, foi possĂvel constatar que na maioria dos estudos, a Fisioterapia mostrou benefĂcios
no tratamento dos indivĂduos com EM.Introduction: Multiple sclerosis (MS), a disease that destroys the myelin of the white matter
of the central nervous system, will specifically affect the motor part of the individual, but it
also affects the cognitive and visual aspects to analyze the influence of physical therapy in
people with MS. Methodology: Inclusion criteria were randomised controlled articles
describing the intervention of physiotherapy, in patients with Multiple Sclerosis, published in
the last 5 years and available in full text. Exclusion criteria were considered articles with
studies that had more than one type of treatment simultaneously. Results: 8 studies were
included in the study, with an average of 5.5 in 10 on the PEDro scale. The parameters
evaluated were postural stability, social support, perceived barriers, adopted strategy, heart
rate, perceived effort, functionality and quality of life. Conclusion: In the review, it was
possible to verify that in the majority of the studies, Physical therapy showed benefits in the
treatment of individuals with MS.N/
A Semiparametric Estimation of Liquidity Effects on Option Pricing
This paper proposes a semiparametric option pricing model with liquidity, as proxied by the relative bid-ask spread. The nonparametric volatility function with liquidity as an explanatory variable is estimated using the Symmetrized Nearest Neighbors (SNN) estimator rather than the traditional kernel estimator. Moreover, special care is taken in obtaining the smoothing parameter. The in-sample performance of the model turns out to be statistically favorable relative to a competing model without liquidity. However, the out-of-sample performance of both models is quite disappointing despite the fact that we are not to reject the stability of risk-neutral densities estimated over different quarters during our sample period.multivariate kernel regression, bandwidth selection, symmetrized nearest neighbors, volatility smile, option pricing
Impacto das disfunções musculoesqueléticas no estado funcional de pessoas consideradas saudáveis
Musculoskeletal impairments represent a huge burden on the health of people around the world, as they affect the structure and function of muscles, bones and joints, which triggers changes in movement patterns. These changes will lead to a decline in functional status, with consequent repercussions on quality of life.
The aim of this study was to determine the impact that musculoskeletal impairments have on functional status through four functional tests. This cross-sectional study was carried out in community institutions, senior schools, sports centers and day care centers, participants aged 40 years or older were included. Sociodemographic and anthropometric characteristics were collected, musculoskeletal disorders were self-reported, and then, functional status was assessed. The functional status of the upper limbs was assessed with handgrip strength with a dynamometer and lower limbs was assessed with isometric quadriceps muscle strength with a handheld dynamometer, the 1-minute stand to stand test (1min.STS) and the 5 times sit to stand test (5STS).
545 participants were included in the study, of which, 56 (10.6%) had musculoskeletal impairment. The main factors associated with decreased functional status were being a woman, older age, high BMI and medication consumption.
In conclusion, this study shows a relationship between people who had musculoskeletal dysfunction and a lower performance in functional status compared to those without impairment. It also demonstrates that age, BMI, medication, and sex differences influence the outcome of functional tests that lead to a decline in functional status. Physiotherapy can help raise awareness of this issue and the implementation of health programs, namely through exercise to improve people's function and quality of life over time.As disfunções musculoesquelĂ©ticas representam uma enorme sobrecarga para a saĂşde das pessoas em todo o mundo, uma vez que afetam a estrutura e função de mĂşsculos, ossos e articulações, o que desencadeia alterações nos padrões de movimento. Estas alterações vĂŁo originar um declĂnio no estado funcional, com repercussões consequentes na qualidade de vida.
O objetivo deste estudo foi determinar o impacto que as disfunções musculosquelĂ©ticas apresentam no estado funcional atravĂ©s de quatro testes funcionais. Este estudo transversal foi realizado em instituições comunitárias, escolas de terceira idade, centros desportivos e centros de dia, foram incluĂdos participantes com idade superior ou igual a 40 anos. As caracterĂsticas sociodemográficas e antropomĂ©tricas foram recolhidas, as disfunções musculosquelĂ©ticas foram autorreferidas e, em seguida, o estado funcional foi avaliado. O estado funcional dos membros superiores foi avaliado com a força de preensĂŁo manual com um dinamĂłmetro e dos membros inferiores foi avaliado com a força muscular isomĂ©trica do quadrĂceps com o dinamĂłmetro de mĂŁo, o teste de levantar e sentar 1 minuto (1min.STS) e o teste de sentar e levantar 5 vezes (5STS).
545 participantes foram incluĂdos no estudo, destes, 56 (10.6%) apresentavam disfunção musculosquelĂ©tica. Os principais fatores associados ao estado funcional diminuĂdo foram ser mulher, idade superior, alto IMC e o consumo de medicação.
Em conclusĂŁo, este estudo mostra uma relação entre pessoas que apresentavam disfunção musculoesquelĂ©tica e um menor desempenho no estado funcional em comparação com aquelas sem comprometimento. TambĂ©m demonstra que a idade, o IMC, a medicação e diferenças de sexo influenciam o resultado dos testes funcionais que levam a um declĂnio do estado funcional. A fisioterapia pode ajudar na consciencialização para esta temática e na implementação de programas de saĂşde, nomeadamente, atravĂ©s do exercĂcio para melhoria da função e qualidade de vida das pessoas ao longo do tempo.Mestrado em Fisioterapi
Indicadores de maus-tratos a pessoas idosas na cidade de Braga : estudo preliminar
Objectivo: Recolher em condições seguras alguns indicadores de maus-tratos fĂsicos, psicolĂłgicos, financeiros e de negligĂŞncia, numa amostra sectorial da população idosa da cidade de Braga
Participantes: 82 pessoas, 18 das quais do sexo masculino e 64 do sexo masculino, com idades entre os 63 e os 88 anos que frequentam um de trĂŞs centros de dia que seleccionamos na cidade de Braga
Instrumentos: Questions to Elicit Elder Abuse (Carney, Kahan & Paris, 2003), traduzido pelos autores deste estudo.
Resultados: Os resultados indicam a presença de indicadores de maus-tratos num número muito significativo de participantes, sobretudo indicadores de negligência e de abuso emocional; a variável estudada mais associada à presença de indicadores de maus-tratos foi a percepção do estado de saúde. Contudo o género e a idade também aparecem significativamente associados ao fenómeno.
DiscussĂŁo: Os dados obtidos sugerem a importância de se estender a outros locais nacionais e de se usar outras metodologias para investigar o abuso a pessoas idosas. Dos dados obtidos, parecem estar em maior risco de abuso as pessoas com mais idade, o gĂ©nero feminino e pessoas com percepção de má saĂşde. Obviamente que importará conhecer mais sobre as condições de ocorrĂŞncia do abuso, substanciando-o, recolhendo e explorando episĂłdios de maus-tratos, para que o estudo neste domĂnio seja nĂŁo sĂł um conjunto de descrições de ocorrĂŞncias onde se cruzam necessariamente certas variáveis mas, tambĂ©m, uma tarefa de compreensĂŁo do comportamento humano
Carcinoma gástrico: Há razões que justifiquem um comportamento biolĂłgico diferente nos dois gĂ©neros? Â
Atlantica : contemporary art from Mozambique and its diaspora
info:eu-repo/semantics/publishedVersio
Human-artificial intelligence engagement exploring the perspectives of users and tourism managers
The progress and sophistication of technological systems promise to accelerate the tourism sector, influencing business management at the commercial, human resources, and planning levels.
The main objective of this thesis is to analyse the evolution of the literature on artificial intelligence and how it can be integrated with the constructs of engagement, intimate knowledge, authenticity, attachment, and psychological ownership. Several analyses were carried out to achieve the intended results.
First, a comprehensive literature review was done, through the analysis of scientific articles, to understand the development of scientific research on artificial intelligence and user engagement.
Secondly, a qualitative study was conducted to evaluate the impact of virtual assistants in the tourism industry, both at the organization and customer levels, using the thematic analysis method in structured interviews with top managers of the tourism sector. The results show that the benefits of using artificial intelligence outweigh the negative ones and will impact firm management.
Finally, two quantitative studies were performed to analyse which factors influence customer engagement. The first study analyses the constructs of authenticity and attachment as motivators of engagement between tourists and virtual assistants, proving that these factors significantly influence the interaction between both. The second study investigates the communication between the virtual assistant and the user, emphasizing the importance of intimate knowledge, authenticity, and connection as psychological motivators. The results show that all three constructs significantly impact customer engagement with the virtual assistant
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