uBibliorum
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Recent Submissions
From Hypoxia to Healing: Optimizing Stem Cell Therapy for Neonatal Hypoxic-Ischemic Brain Injury
Publication . Serrenho, Inês Isabel Pires; Baltazar, Graça Maria Fernandes; Manadas, Bruno José Fernandes Oliveira; Grãos, Mário Martins Rodrigues
Neonatal hypoxic-ischemic encephalopathy (HIE), caused by oxygen and blood flow deprivation to the neonatal brain, is a leading cause of mortality and long-term neurological disabilities in children under five. Its complex pathophysiology— comprising excitotoxicity, inflammation, oxidative stress, and delayed cell death—poses significant therapeutic challenges. Moreover, current management with therapeutic hypothermia (TH) shows limited efficacy, particularly in severe cases, and excludes many neonates due to strict enrollment criteria. To overcome these limitations, preclinical research has explored stem cell therapies (SCT), particularly using stem cells from umbilical cord blood (UCB) and tissue (UC). These therapies show promise in reducing brain injury and improving outcomes, but challenges remain in optimizing doses, delivery methods, and scalability. Building on previous work, this thesis evaluated several approaches to optimize SCT for neonatal HIE. First, administration of UCBCs alone and in combination with TH in a rat model of HIE, reduced brain lesion size and improved functional outcomes more effectively than TH alone, while also reducing glial reactivity—an effect not observed with TH alone. These findings establish UCBCs as a potential therapy, particularly when TH is unavailable or insufficient. Nonetheless, the use of these cells can present disadvantages: autologous use, limited culture and expansion, thus not being possible to manipulate with preconditioning strategies. Thus, we focused on the use of UC-derived MSCs that overcome some of the limitations previously mentioned. Also, since preconditioning strategies are being explored as ways to potentiate MSCs therapeutic effects, we hypothesized that hypoxic preconditioning could enhance UC-MSC efficacy and what explored the potential mechanisms behind neurological recovery. Proteomic analysis revealed that HIE rats treated with hypoxiapreconditioned MSCs had an enrichment of pathways related to synapse function, brain connectivity, and energy metabolism. Moreover, administration of UC-MSCs preconditioned with short hypoxia induced a greater functional recovery in HIE rats than administration of UC-MSCs preconditioned mild hypoxia. Stem cell therapy requires high doses of stem cells, which limits its clinical translatability. To optimize SCT and significantly reduce effective doses of MSCs, we evaluated the impact of two delivery methods and the combination of different strategies on the efficacy of UC-MSCs. Intranasal administration of UC-MSCs was more effective in reducing the infarct volume enhancing motor and cognitive recovery than intravenous administration, restoring myelination in the corpus callosum, and mitigating glial reactivity. Intranasal administration of half the dose of hypoxia-preconditioned UCMSCs reduced neurological deficits associated with neonatal HIE. Strikingly, intranasal administration of secretome from hypoxia-preconditioned MSCs demonstrated similar therapeutic efficacy, offering a promising cell-free alternative. Finally, to address the limitations associated with the expansion of UC-MSCs and donor variability on the therapeutic potency of these cells, we aimed to determine if induced pluripotent stem cell-derived MSCs (iMSCs) could hold the same potential in the neonatal HIE model. Intranasal administration of iMSCs or their secretome improved motor and cognitive recovery, reduced brain lesion size, modulated glial reactivity, and enhanced neurogenesis in the hippocampus of HIE rats. The comparable outcomes between iMSCs and their secretome underscore the critical role of secreted factors, presenting a scalable, cell-free option for clinical application. In summary, this thesis advances the field of regenerative medicine for neonatal HIE by identifying innovative strategies to optimize stem cell therapies. The findings demonstrate the potential of intranasal delivery and hypoxic preconditioning to reduce the required cell doses while maintaining efficacy, making these therapies more feasible for clinical use. Furthermore, secretome-based approaches offer a scalable alternative that addresses logistical challenges. Beyond neonatal HIE, these strategies may have broader implications for other neurodevelopmental and neurological disorders, as well as for veterinary medicine. While significant progress has been made, future research should aim to elucidate the mechanisms underlying MSC and secretome efficacy and advance these approaches toward clinical trials, paving the way for innovations in regenerative medicine.
Use of Unmanned Aerial Vehicles (UAVs) for Transport Pavement Inspection
Publication . Santos, Bertha; Gavinhos, Pedro; Almeida, Pedro G.; Nery, Dayane; Rujikiatkamjorn, C.; Xue, J.; Indraratna, B.
Technological evolution has allowed the use of unmanned aerial vehicles
(UAVs) in an easier and more diversified way, creating opportunities for its
application in various fields of engineering, namely in the inspection of transport
infrastructures. The present study begins with the analysis of the main practices that
resort to the use of UAVs, in order to frame its application in the field of transport
pavement inspection. A review of studies and other available literature served as a
starting point to define the methodology adopted for the development of the case
study presented. The methodology includes the collection of images of a flexible
road pavement section, its processing, and the creation of an orthoimage and a 3D
model from which it was possible to identify and characterize the distresses present
on the pavement surface. The main results obtained point to planimetric and altimetric
deviations of less than 2 and 10 mm, respectively, for the images collected by
theMavic 2 Pro drone at 3 and 20mhigh.With the collected data, itwas also possible
to calculate the global quality index PCI for the inspected pavement section. Under
these conditions, it is possible to conclude that the accuracy is very good and suitable
for the intended purpose, allowing fast data collection at low cost. This new technological
approach supports infrastructure managers in the design of maintenance
programs and in the scheduling of interventions, thus contributing to the increase of
the durability and safety levels of the inspected pavements.
Automated Geographic Information System Multi-Criteria Decision Tool to Assess Urban Road Suitability for ActiveMobility
Publication . Santos, Bertha; Ferreira, Sandro Alfaro ; Lucena, Pollyana;
The planning of greener, more accessible, and safer cities is the focus of several strategies that aim to improve the population’s quality of life. This concern for the environment and the population’s quality of life has led to the implementation of active mobility policies. The effectiveness of the mobility solutions that are sought heavily depends on the identification of the main factors that favor their use, as well as how adequate urban spaces are in minimizing existing difficulties. This study presents an automated geographic information system (GIS) decision support tool that allows the identification of the level of suitability of urban transportation networks for the use of active modes. The tool is based on the determination of a set of mobility indices: walkability, bikeability, e-bikeability, and active mobility (a combination of walking and cycling suitability). The indices are obtained through a spatial multi-criteria analysis that considers the geometric features of roads, population density, and the location and attractiveness of the city’s main trip-generation points. The treatment, representation, and study of the variables considered in the analysis are carried out with the aid of geoprocessing, using the spatial and network analysis tools available in the GIS. The Model Builder functionality available in ArcGIS® was used to automate the various processes required to calculate walking, cycling, and e-biking travel times, as well as the mobility indices. The developed tool was tested and validated through its application to a case study involving the road network of the urban perimeter of the medium-sized city of Covilhã, Portugal. However, the tool is designed to be applied with minimal adaptation to different scenarios and levels of known input information, providing average or typical values when specific information is not available. As a result, a flexible and automated GIS-based tool was obtained to support urban space and mobility managers in the implementation of efficient measures compatible with each city’s scenario.
Desenvolvimento de Soluções Sustentáveis para Resíduos Têxteis Hospitalares
Publication . Mendes, Carla Manuela Fonseca; Belino, Nuno José Ramos; Barata, Teresa Raquel Aurélio da Silva Nunes
Atualmente, as preocupações relacionadas com o consumo excessivo de recursos e com os danos causados ao meio ambiente têm aumentado significativamente, o que contrasta, de maneira marcante, com os padrões observados há alguns anos. Discutir esses fatores implica abordar conceitos como sustentabilidade, economia circular e controlo de resíduos. As instituições públicas não são exceção a essa dinâmica. O desperdício de qualquer material deve ser evitado por uma série de razões, tanto económicas, quanto ambientais.
Embora os hospitais sejam unidades operacionais distintas de outras instituições, a prestação de cuidados de saúde não pode ser utilizada como justificativa para o desinteresse na adoção de políticas de controlo de resíduos e recursos. Embora já existam diversas iniciativas voltadas para a contenção e controlo de recursos nas instituições de saúde, é cada vez mais imperativo promover a implementação dessas medidas e incentivar ações de melhoria contínua nesse contexto. Hospitais são produtores de toneladas de resíduos, incluindo resíduos têxteis que, por se classificarem como hospitalares, são eliminados sem qualquer valorização.
Foi nesse enquadramento que foram desenvolvidos têxteis que poderão ser usados em ambiente hospitalar e geriátrico, aproveitando resíduos têxteis provenientes de unidades de saúde, nomeadamente, fardamentos e têxteis provenientes das unidades dos doentes, cujo destino seria o aterro ou incineração. A investigação procurou aplicar os princípios da economia circular, criando várias estruturas têxteis a partir de resíduos de têxteis reutilizáveis e descartáveis, por meio da reciclagem mecânica e termomecânica, originando artigos que poderão ser utilizados em ambiente de prestação de cuidados, com características semelhantes aos produtos originais.
A possibilidade de reciclagem deste tipo de resíduo apresenta uma mais valia, não só para as unidades de saúde, que deixam de ter que pagar para eliminar os resíduos têxteis, mas também representa um ganho para o ambiente, transformando um material tido como um resíduo, numa matéria prima.
Reverse Logistics: A Mixed-Methods Analysis of Barriers, Strategies, and Key Determinants
Publication . Soares, Miguel Norberto Mendes; Paço, Arminda Maria Finisterra do; Braga, Alexandra Maria Silva
Growing concern about the environmental impacts of supply chain activities have
stimulated the adoption of more sustainable models, highlighting the transition from a
linear paradigm to a circular model. In this context, Reverse Logistics (RL) emerges as
a fundamental strategic tool, allowing the recovery, re-use and recycling of products
and material at the end of their life-cycle, and contributing to environmental, social and
economic sustainability. Despite the recognised importance of RL as a strategic tool to
promote the sustainability of supply chains, many companies, especially Small and
Medium-Sized Enterprises (SMEs) in the textile and footwear sectors in Portugal, find
effective implementation difficult. Therefore, this study aimed to identify and analyse
the main barriers hindering adoption of RL in these industries, as well as exploring
strategies to implement viable and effective RL networks.
To do so, and to increase knowledge about the implementation of RL in textile and
footwear SMEs, a mixed methodological approach was adopted, including quantitative
and qualitative methods in the five studies making up this thesis.
The study began with a Systematic Literature Review (SLR) (first study), following the
Denyer and Tranfield (2009) protocol, to map existing scientific knowledge about RL
and sustainability. The search carried out in May 2023 on the Web of Science and
Scopus databases used the key-words “Reverse Logistics” and “Sustainability.
The second study applied the Fuzzy Delphi method to validate and categorize in terms
of relevance the barriers to implementing RL. This method allowed validation of a
number of barriers with a negative impact on implementation of an efficient reverse
flow network.
The third study combined Interpretive Structural Modeling (ISM) and Matrices
d’Impacts Cross-Multiplication Appliqúe a Classmate (MICMAC) analysis to map
hierarchical relations among the barriers. A focus group with eight RL specialists,
carried out via Zoom, developed a graphic model of interdependences. The MICMAC
analysis classified the barriers in four quadrants (autonomous, dependent, linking and
independent), identifying those with the biggest impact.
The fourth study focused on SMEs in the textile and footwear sectors, using semistructured interviews with supply chain managers. The intentional sample was formed
of participants with practical experience of RL, meaning the themes addressed could be dealt with in depth. The interviews lasted 30 minutes on average and explored specific
barriers in the SME context and strategies to overcome them.
Finally, the fifth study included the Fuzzy Analytic Hierarchy Process (FAHP) and
Fuzzy F-MARCOS to prioritize RL implementation strategies. FAHP attributed weights
and criteria based on specialists’ linguistic evaluations, while Fuzzy Measurement of
Alternatives and Ranking according to Compromise Solution (F-MARCOS) ordered the
strategic alternatives, handling uncertainties inherent to multi-criteria decisions.
The main research trends in this area were identified, namely, the development of
optimization models, performance assessment, outsourcing activities and the
challenges of implementation. The most significant barriers to implementation of RL
were found to be categorized in seven groups, highlighting the uncertainty in returning
products, high costs and the lack of management commitment as the main factors
preventing effective implementation. Analysis of the inter-relations among barriers,
using ISM and MICMAC methods, showed that the "lack of an appropriate
organisational structure" has the greatest influence, with a direct effect on social
responsibility.
In the textile and footwear sector, the reasons for adopting RL include environmental
sustainability, economic benefits and social responsibility. Nevertheless, companies
face challenges such as high operational costs and a lack of collaboration. To overcome
these obstacles, this study proposes strategies such as the outsourcing of RL activities
and developing strategic partnerships.