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Objective Diabetic foot infection (DFI) represents a major healthcare burden, for which treatment is challenging owing to the pathophysiological alterations intrinsic to diabetes and the alarming increase of antimicrobial resistance. Novel therapies targeting DFI are therefore a pressing research need for which proper models of disease are required. Results Here, we present an optimized diabetic mouse model of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, that resemble key features of DFI, such as pathogen invasion through wound bed and surrounding tissue, necrosis, persistent inflammation and impaired wound healing. Thus, in a time-efficient manner and using simple techniques, this model represents a suitable approach for studying emerging therapies targeting DFI caused by MRSA.

Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)‐based spongy‐like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin‐resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic‐associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA‐infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration.

Ovarian cancer (OC) has a specific type of metastasis, via transcoelomic, and most of the patients are diagnosed at advanced stages with multiple tumors spread within the peritoneal cavity. The role of Malignant Ascites (MA) is to serve as a transporter of tumor cells from the primary location to the peritoneal wall or to the surface of the peritoneal organs. MA comprise cellular components with tumor and non-tumor cells and acellular components, creating a unique microenvironment capable of modifying the tumor behavior. These microenvironment factors influence tumor cell proliferation, progression, chemoresistance, and immune evasion, suggesting that MA play an active role in OC progression. Tumor cells induce a complex immune suppression that neutralizes antitumor immunity, leading to disease progression and treatment failure, provoking a tumor-promoting environment. In this review, we will focus on the High-Grade Serous Carcinoma (HGSC) microenvironment with special attention to the tumor microenvironment immunology.

Convolutional neural networks have been effective in several applications, arising as a promising supporting tool in a relevant Dermatology problem: skin cancer diagnosis. However, generalizing well can be difficult when little training data is available. The fine-tuning transfer learning strategy has been employed to differentiate properly malignant from non-malignant lesions in dermoscopic images. Fine-tuning a pre-trained network allows one to classify data in the target domain, occasionally with few images, using knowledge acquired in another domain. This work proposes eight fine-tuning settings based on convolutional networks previously trained on ImageNet that can be employed mainly in limited data samples to reduce overfitting risk. They differ on the architecture, the learning rate and the number of unfrozen layer blocks. We evaluated the settings in two public datasets with 104 and 200 dermoscopic images. By finding competitive configurations in small datasets, this paper illustrates that deep learning can be effective if one has only a few dozen malignant and non-malignant lesion images to study and differentiate in Dermatology. The proposal is also flexible and potentially useful for other domains. In fact, it performed satisfactorily in an assessment conducted in a larger dataset with 746 computerized tomographic images associated with the coronavirus disease.

Periodontitis is a chronic disease with a high overall prevalence. It involves a complex interplay between the immune-inflammatory pathways and biofilm changes, leading to periodontal attachment loss. The aims of this study were (i) to assess whether the salivary IL-1β, IL-17A, RANK-L and OPG levels have the potential to discriminate between the mild and severe periodontitis conditions; and (ii) to enable diagnostic/prognostic actions to differentiate between distinct levels of the disease. The analysis of the clinical parameters and the evaluation of the salivary immunomediators levels by means of a multiplex flow assay revealed a statistically significantly higher level of IL-1β in the periodontitis III/IV patients, as well as a higher level of RANK-L in the periodontitis III/IV and I/II patients, when compared to the healthy controls. Furthermore, the grade C periodontitis patients presented a significantly higher level of RANK-L compared to the grade B and grade A patients. In the grade C patients, IL-1β had a positive correlation with the PPD and CAL indices and RANK_L had a positive correlation with CAL. The evidence emerging from this study associates the salivary IL-1β and RANK-L levels with an advanced stage of periodontitis, stage III/IV, and with grade C, suggesting the possible cooperative action of both in the inflammatory and bone loss events. In addition to IL-1β, RANK-L could be considered a combined diagnostic biomarker for periodontitis.

A COVID-19, nos últimos dois anos, alterou o modo como vivemos e nos comportamos em sociedade. A forma como se leciona e aprende foi completamente alterar e foi necessária uma adaptação por todos os envolvidos no meio académico. Para além disso, as implicações causadas por esta doença não se aplicam apenas à área da saúde, mas também a outras vertentes como as sociais e económicas. Por este e por outros motivos, é necessário compreender as suas implicações e as suas características.A metodologia utilizada nesta dissertação de mestrado é de carácter qualitativa e a técnica de recolha de informação usada é a realização de entrevistas semiestruturadas. Com um total de sete entrevistas realizadas, a sua análise permitir-me-á estudar o fenómeno com o objetivo de perceber até que ponto a pandemia de Sars-Cov-2 fez alterar as desigualdades sociais no acesso à educação dos alunos da Universidade do Minho.Com este projeto de investigação conseguirei analisar um fenómeno recente e pouco estudo, possibilitando o auxílio no estudo das suas implicações no ensino superior.

O presente relatório de estágio resulta da realização do estágio profissionalizante desenvolvido com vista à conclusão do 2º ciclo de estudos em Gestão Desportiva, tendo como objetivo a obtenção do grau de Mestre em Gestão Desportiva, pela Faculdade de Desporto da Universidade do Porto.O estágio decorreu na Tempo Livre, régie cooperativa da Câmara Municipal de Guimarães, tendo integrado as suas diversas instalações, com objetivo de perceber o seu funcionamento. Este decorreu entre setembro de 2022 e abril de 2023, tendo a duração de 7 meses.O presente relatório compreende uma revisão de literatura referente às áreas relacionadas com as funções desempenhadas pela entidade acolhedora, sendo esta, posteriormente, caraterizada. Após isso, são descritas as atividades realizadas, seguindo-se uma reflexão crítica sobre o estágio, bem como das competências adquiridas resultantes do mesmo, terminando com as conclusões e perspetivas para o meu futuro.A prática profissionalizante permitiu-me solidificar conhecimentos teóricos, aplicados durante o estágio na realização de atividades de coordenação de instalações desportivas, tendo sido bastante vantajosa no desenvolvimento das minhas capacidades e conhecimentos no âmbito da gestão desportiva, uma vez que fiquei mais consciente das funções de um gestor na área do desporto.

Oxytocin (OXT) has multiple functions in the human body, both peripherally, as a hormone, and centrally, as a neuropeptide. OXT plays an important role in social behavior and cognition, which justifies the increasing interest it has been receiving lately. This effect on social cognition appears to be due to the biding of the OXT to specific brain areas that still haven’t been fully explored. We conducted a systematic review, using placebo-controlled studies that used functional magnetic resonance imaging (fMRI) to investigate the influence of intranasal OXT on the human brain, during social cognitive tasks. We identified 16 studies that met our inclusion criteria. The results show that oxytocin had influence in the activity of several brain areas: the amygdala, mainly in the processing of facial emotion and social scenes and in associative learning; the insula, which was implicated in tasks requiring empathy and altruism; cingulate cortex, activated during the anticipation of social reward/punishment; the caudate nucleus and putamen, both very active during cooperation tasks; the temporal and frontal lobes and their different regions, implicated, in a way or another, in every type of task the hippocampus. They also revealed that gender and type of task lead to significant variations in the activity of those brain structures.

O processo de regeneração da pele é bastante complexo e ordenado e, quando não progride adequadamente, leva ao aparecimento de feridas crónicas. As feridas crónicas são referidas como uma \"epidemia silenciosa\", afetando significativamente a qualidade de vida dos pacientes e implicando enormes custos financeiros. Existe, portanto, uma necessidade premente no tratamento eficaz de feridas crónicas, especialmente as infetadas. Embora os antibióticos sejam fundamentais no tratamento de infeção, a sua administração convencional, na maioria sistémica, apresenta sérias limitações como a reduzida difusão na ferida e, por conseguinte, reduzida eficácia, e os efeitos adversos sistémicos. Os sistemas de libertação de fármacos podem ajudar a ultrapassar estas limitações, sendo uma alternativa às terapias convencionais.Neste trabalho, foram desenvolvidas duas formulações de sistemas poliméricos para a libertação tópica e controlada de antibióticos no tratamento de feridas crónicas infetadas de diferente etiologia, nomeadamente a infeção oportunista de feridas diabéticas por Staphylococcus aureus resistente à meticilina (MRSA), e a infeção primária por Mycobacterium ulceransque causa a úlcera de Buruli. No modelo de infeção oportunista, a vancomicina e a clindamicina foram incorporadas em hidrogéis esponjosos de goma gelana (GG), enquanto no modelo de infeção primária, a rifampicina foi encapsulada em partículas de poli(hidroxibutirato-co-valerato), posteriormente incorporadas num hidrogel esponjoso de GG contendo estreptomicina. Ambas as formulações mostraram uma matriz porosa e interligada pela qual os antibióticos difundiram de forma controlada. A libertação controlada não afetou a atividade antibacteriana dos antibióticos, mas reduziu significativamente os efeitos citotóxicos dos antibióticos. Foi ainda otimizado um modelo de ratinho de feridas diabéticas infetadas por MRSA que apresentou características semelhantes à patofisiologia humana, através do qual foi testada a eficácia terapêutica dos hidrogéis esponjosos de GG contendo VAN e CLD. O tratamento com uma dose única destes hidrogéis permitiu reduzir a carga bacteriana das feridas, sem exacerbar a resposta inflamatória do hospedeiro. Embora seja ainda necessário otimizar as doses de antibióticos incorporados nas formulações poliméricas, bem como os modelos animais, as formulações desenvolvidas representam uma abordagem promissora para melhorar o tratamento de feridas crónicas infetadas.

The most frequent genotype associated with Hereditary hemochromatosis is the homozygosity for C282Y, a common HFE mutation. However, other mutations in HFE, transferrin receptor 2 (TFR2), hemojuvelin (HJV) and hepcidin (HAMP) genes, have also been reported in association with this pathology. A mutational analysis of these genes was carried out in 215 Portuguese iron-overloaded individuals previously characterized as non-C282Y or non-H63D homozygous and non-compound heterozygous. The aim was to determine the influence of these genes in the development of iron overload phenotypes in our population. Regarding HFE, some known mutations were found, as S65C and E277K. In addition, three novel missense mutations (L46W, D129N and Y230F) and one nonsense mutation (Y138X) were identified. In TFR2, besides the I238M polymorphism and the rare IVS5 -9T[rightward arrow]A mutation, a novel missense mutation was detected (F280L). Concerning HAMP, the deleterious mutation 5'UTR -25G[rightward arrow]A was found once, associated with Juvenile Hemochromatosis. In HJV, the A310G polymorphism, the novel E275E silent alteration and the novel putative splicing mutation (IVS2 +395C[rightward arrow]G) were identified. In conclusion, only a few number of mutations which can be linked to iron overload was found, revealing their modest contribution for the development of this phenotype in our population, and suggesting that their screening in routine diagnosis is not cost-effective.