Análise das parcerias público-privadas: o caso do sector da saúde em Portugal

Dissertação submetida como requisito parcial para obtenção do grau de: Mestre em Ciências Empresariais – Ramo em PME´SO presente trabalho pretende realizar uma análise das Parcerias Público-Privadas em Portugal na área social, económica e política, tal como descrever e explorar quais os fatores concretos que conduziram e conduzem o Estado a realizar este tipo de contratos.The present project intends to carry out an analysis of Public-Private Partnerships in Portugal in the social, economic and political area, as well as to describe and explain the concrete factors that led the State to carry out this type of contract

Uncover the mechanism behind miRNA function on cell survival

Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaAs doenças cardiovasculares (DCV) são a principal causa de morte mundial e é esperado que a prevalência destas doenças aumente nos próximos anos. De entre as DCV, o enfarte do miocárdio é causado por uma obstrução das artérias coronárias e resulta numa vasta morte de cardiomiócitos. A reparação do miocárdio é devido a uma extensa resposta inflamatória e à proliferação de células não contráteis, o que resulta na formação de um tecido cicatrizado sem contratilidade. Por fim, as propriedades não contráteis do tecido cicatrizado induzem disfunção cardíaca a longo prazo, o que poderá culminar em insuficiência cardíaca e morte. Intervenções cirúrgicas e terapias farmacológicas são as estratégias adotadas para minimizar os danos e a ocorrências de eventos futuros. No entanto, estas terapias não são capazes de restaurar o tecido danificado por miocárdio funcional. Terapias regenerativas variam desde a estimulação de uma resposta endógena a uma administração exógena de células para remuscularizar e/ou revascularizar o coração. Estas estratégias têm vindo a ser avaliadas em estudos clínicos, no entanto, os resultados apenas demonstram uma ligeira melhoria da função cardíaca. Parte dos resultados observados são devidos ao ambiente inflamatório e hipóxico que é estabelecido após um enfarte e que previne a sobrevivência das células após transplantação. Entretanto, o endotélio surgiu como um órgão dinâmico capaz de controlar cardiomiócitos e melhorar o ambiente adverso do coração.Previamente, o nosso grupo realizou um “high-throughput screening” onde identificou o miRNA-425-5p como um miRNA de pro-sobrevivência, capaz de aumentar a sobrevivência de células endoteliais após hipoxia (0.1%O2). Apesar do miRNA-425-5p estar descrito na literatura como tendo funções anti-apoptóticas e proliferativas, o mecanismo pelo qual o miRNA-425-5p exerce o efeito de pro-sobrevivência em células endoteliais é pouco entendido. Neste trabalho, propomos investigar os alvos do miRNA-425-5p usando técnicas de qPCR e silenciamento de genes. Os resultados demonstram que o miRNA-425-5p é capaz de reprimir os genes RGS5, DACH1 e/ou VASH1, o que se correlaciona com o aumento da sobrevivência de células endoteliais. Adicionalmente, propomos utilizar EVs para entregar o miRNA-425-5p a células endoteliais e os nossos resultados sugerem que os EVs são capazes de entregar o miRNA-425-5p e aumentar a sobrevivência endotelial.Concluindo, o presente trabalho demonstra que o miRNA-425-5p é um agente capaz de aumentar a sobrevivência endotelial após isquemia pela redução da expressão dos genes RGS5, DACH1 e/ou VASH1. Além disso, demonstramos que os EVs são capazes de entregar o miRNA-425-5p nas células e consequentemente promover a sobrevivência endotelial.Cardiovascular diseases (CVD) are the leading cause of death worldwide and is expected that the prevalence will increase in the next years. Among the CVD, myocardial infarction (MI) is caused by an obstruction of coronary arteries and results in a massive cardiomyocytes death. Regeneration of the myocardium is due to an extensive inflammatory response and the proliferation of non-contractile cells which results in the formation of non-contractile scar tissue. Ultimately, the non-contractile properties of the scar tissue induce a long-term cardiac dysfunction that could culminate in heart failure and death. Surgical interventions and pharmacologic therapies are the strategies adopted to minimize the damaged and prevent further events to happen. Nevertheless, those therapies cannot restore the damaged tissue for functional myocardium. Cardiac regenerative therapies range from the stimulation of endogenous response to an administration of exogenous stem cells to re-muscularized and/or re-vascularized the heart. Those strategies have been evaluated in several clinical trials, however, the outcomes showed only a mild improvement in cardiac function. Part of the results observed are due to the inflammatory and hypoxic environment established after MI, which prevents the survival of transplanted cells. Meanwhile, the endothelium emerges as a dynamic organ that can control cardiomyocytes and ameliorate the harsh environment.Previously, our group performed a high-throughput screening where identified miRNA-425-5p as pro-survival miRNA, able to increase the survival of endothelial cells after a hypoxic injury (0.1% O2). Although miRNA-425-5p is described in the literature by having anti-apoptotic and proliferative functions, the mechanism behind the miRNA-425-5p pro-survival function in endothelial cells is poorly understood. Here we propose to investigate the miRNA-425-5p targets by qPCR technique and genes knockdown. Our results demonstrated that miRNA-425-5p is able to repress the expression of RGS5, DACH1 and VASH1 genes, which correlates with an increased in endothelial cell survival. Furthermore, we propose to use EVs for the delivery of miRNA-425-5p into cells and our data suggest that EVs could transfect miRNA-425-5p and enhance endothelial survival.Concluding, the present work demonstrated that miRNA-425-5p is a suitable agent to enhance the endothelial survival after ischemia, by reducing the expression of RGS5, DACH1 and/or VASH1 genes. Additionally, we showed that exosomes are able to deliver miRNA-425-5p in endothelial cells and by that promote survival of endothelial cells.Outro - Project “Exo-Heart”: POCI-01-0145-FEDER-02991

Translating the determinant aspects on the study design in the dental implant field

AbstractObjective In this article, we analyzed the important categories capable of interfering with the determinants of scientific advancement in the type of study, considering seven leading journals over a 20-year.Methodology A bibliometric review was performed at the website of well-established implant dentistry journals in five-time points defined to represent a 20-year period of observation. The measures associated with the type of study design were: the country of origin of the article, country income, continent of the corresponding author, inter-institutional collaboration, interdisciplinary collaboration, type of funding, and topic of research. Logistic regression was used in the multiple models to identify the exploratory factors associated with the type of study.Results From a total of 1,944 articles, 50.6% comprised clinical studies. High-income countries and continents stood out for developing more clinical research than others. Since research funders request more collaborative research, overall clinical studies depended upon more inter-institutional collaboration than the others. Most clinical studies were partly supported by research institutes or universities and by industry. About the research topic, the majority of the clinical and animal studies disclosed surgical procedures.Conclusions High-income countries and continents are more likely to develop clinical studies in the surgical procedures field. The highest collaborations in terms of the number of institutions and funding sources are more prevalent in clinical research designs. Indeed, most in vivo studies in dental implant fields are performed to evaluate new materials or even new surgical procedures

MicroRNA-124-3p-enriched small extracellular vesicles as a therapeutic approach for Parkinson's disease

Parkinson's disease is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra with no effective cure available. MicroRNA-124 has been regarded as a promising therapeutic entity for Parkinson's disease due to its pro-neurogenic and neuroprotective roles. However, its efficient delivery to the brain remains challenging. Here, we used umbilical cord blood mononuclear cell-derived extracellular vesicles as a biological vehicle to deliver microRNA (miR)-124-3p and evaluate its therapeutic effects in a mouse model of Parkinson's disease. In vitro, miR-124-3p-loaded small extracellular vesicles induced neuronal differentiation in subventricular zone neural stem cell cultures and protected N27 dopaminergic cells against 6-hydroxydopamine-induced toxicity. In vivo, intracerebroventricularly administered small extracellular vesicles were detected in the subventricular zone lining the lateral ventricles and in the striatum and substantia nigra, the brain regions most affected by the disease. Most importantly, although miR-124-3p-loaded small extracellular vesicles did not increase the number of new neurons in the 6-hydroxydopamine-lesioned striatum, the formulation protected dopaminergic neurons in the substantia nigra and striatal fibers, which fully counteracted motor behavior symptoms. Our findings reveal a novel promising therapeutic application of small extracellular vesicles as delivery agents for miR-124-3p in the context of Parkinson's disease

The Potential Role of a Surface-Modified Additive-Manufactured Healing Abutment on the Expression of Integrins α2, β1, αv, and β6 in the Peri-Implant Mucosa: A Preliminary Human Study

The stability of peri-implant soft tissues is essential for long-term success. Integrins play a vital role in biological processes through developing and maintaining cell interactions; however, few studies have evaluated the effects of modifications to abutment surfaces on cell adhesion across integrin expression. Therefore, this pilot study assessed the influence of different surface topographies of titanium healing abutments prepared by additive manufacturing (AM) on the gene expression levels of the integrin subunits α2, β1, αv, and β6 in the human peri-implant mucosa. Thirteen healthy adults were included. Depending on the number of required implants, the subjects were distributed in different groups as a function of healing abutment topography: group 1 (fully rough surface); group 2 (upper machined + lower rough); group 3 (rough upper surface + lower machined); group 4 (fully machined). A total of 40 samples (n = 10/group) of the peri-implant mucosa around the abutments were collected 30 days after implant placement, and subsequently, the gene expression levels were evaluated using real-time PCR. The levels of gene expression of β1-subunit integrin were upregulated for individuals receiving fully rough surface abutments compared with the other surface topographies (p < 0.05). However, the healing abutment topography did not affect the gene expression levels of the α2, αv, and β6 integrin subunits in the human peri-implant mucosa (p > 0.05). This preliminary study suggested that controlled modifications of the surface topography of titanium healing abutments produced by AM may influence the quality of the peri-implant mucosa in the early stages of the soft tissue healing process

Design and development of a web-based prospective nationwide registry for ocular inflammatory diseases: UVEITE.PT - The Portuguese Ocular Inflammation Registry

© 2023 Taylor & Francis Group, LLCUveitis is a heterogeneous collection of infrequent diseases, which poses significant challenges to cost-effective research in the field. Medical registries are being increasingly recognized as crucial tools to provide high-quality data, thus enabling prospective clinical research. This paper describes the design and technical structure development of an innovative countrywide electronic medical record for uveitis, Uveite.pt, and gives an overview of the cohort registered since its foundation, March 2020.Uveite.pt is an electronic medical record platform developed by the Portuguese Ocular Inflammation Group (POIG), a scientific committee of the Portuguese Ophthalmology Society. This is a nationwide customized web-based platform for uveitis patients useful for both clinical practice and real-world-based research, working as a central repository and reporting tool for uveitis. This paper describes the technical principles, the design and the development of a web-based interoperable registry for uveitis in Portugal and provides an overview of more than 400 patients registered in the first 18 months since inception.In infrequent diseases, the existence of registries enables to gather evidence and increase research possibilities to clinicians. The adoption of this platform enables standardization and improvement of clinical practice in uveitis. It is useful to apprehend the repercussion of medical and surgical treatments in uveitis and scleritis, supporting clinicians in the strict monitoring of drug adverse reactions and surgical outcomes.info:eu-repo/semantics/publishedVersio

Extracellular vesicles enriched with an endothelial cell pro-survival microRNA affects skin tissue regeneration

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro, we showed that miR-425-5p, one of the hits, was able to enhance EC survival and migration. In vivo, using a mouse Matrigel plug assay, we showed that ECs transfected with miR-425-5p displayed enhanced survival compared with scramble-transfected ECs. Mechanistically, we showed that miR-425-5p modulated the PTEN/PI3K/AKT pathway and inhibition of miR-425-5p target genes (DACH1, PTEN, RGS5, and VASH1) phenocopied the pro-survival. For the in vivo delivery of miR-425-5p, we modulated small extracellular vesicles (sEVs) with miR-425-5p and showed, in vitro, that miR-425-5p-modulated sEVs were (1) capable of enhancing the survival of ECs exposed to ischemia-mimic conditions, and (2) efficiently internalized by skin cells. Finally, using a streptozotocin-induced diabetic wound healing mouse model, we showed that, compared with miR-scrambled-modulated sEVs, topical administration of miR-425-5p-modulated sEVs significantly enhanced wound healing, a process mediated by enhanced vascularization and skin re-epithelialization. © 2022 The Author