Explore the vast range of titles available.

\"This book provides an approach to peace through tourism by presenting a theoretical framework of tourism dynamics in international relations, as well as a set of peacebuilding case studies that illustrate the role of tourism in violent or critical scenarios of conflict\"-- Provided by publisher.

Triple negative breast cancer (TNBC) is an aggressive, heterogeneous cancer with lack of targeted therapies. The cancer-associated sialyl-Tn (STn) antigen has a significant role in cancer, yet its involvement in TNBC remains unexplored. This study investigates STn’s role in TNBC, analysing its expression in the primary tumour tissues of 126 TNBC patients alongside other biomarkers and clinical features. STn was detected in 23.8% of cases, exhibiting significantly reduced survival and lower c-Myc expression. Additionally, data from The Cancer Genome Atlas (TCGA) TNBC cohort confirmed this association, showing that high levels of ST6GALNAC1 , gene encoding the enzyme responsible for the STn synthesis, were inversely correlated with MYC expression and positively associated with TGF-β signalling genes and immunosuppressive cell infiltrates, such as macrophages M2 and regulatory T cells. Accordingly, STn-positive TNBC cell lines exhibited increased proliferation and lower c-Myc protein expression, while co-culture with macrophages enhanced M2 polarization. This study discloses, for the first time, a subgroup of TNBC patients expressing the STn antigen, pointing to an immunosuppressive environment that may lead to the observed negative correlation between STn and c-Myc. These results introduce STn as a potential prognostic biomarker and therapeutic target, laying the groundwork for more effective, personalized treatments for TNBC.

Sialic acids at the cell surface of dendritic cells (DCs) play an important immunomodulatory role, and their manipulation enhances DC maturation, leading to heightened T cell activation. Particularly, at the molecular level, the increased stability of surface MHC-I molecules in monocyte-derived DCs (MoDCs) underpins an improved DC: T cell interaction. In this study, we focused on the impact of sialic acid remodelling by treatment with Clostridium perfringens sialidase on MoDCs' phenotypic and functional characteristics. Our investigation juxtaposes this novel approach with the conventional cytokine-based maturation regimen commonly employed in clinical settings.Notably, C. perfringens sialidase remarkably increased MHC-I levels compared to other sialidases having different specificities, supporting the idea that higher MHC-I is due to the cleavage of specific sialoglycans on cell surface proteins. Sialidase treatment induced rapid elevated surface expression of MHC-I, MHC-II and CD40 within an hour, a response not fully replicated by 48 h cytokine cocktail treatment. These increases were also observable 48 h post sialidase treatment. While CD86 and PD-L1 showed significant increases after 48 h of cytokine maturation, 48 h post sialidase treatment showed a higher increase in CD86 and shorter increase in PD-L1. CCR-7 expression was significantly increased 48 h after sialidase treatment but not significantly affected by cytokine maturation. Both treatments promoted higher secretion of the IL-12 cytokine. However, the cytokine cocktail induced a more pronounced IL-12 production. SNA lectin staining analysis demonstrated that the sialic acid profile is significantly altered by sialidase treatment, but not by the cytokine cocktail, which causes only slight sialic acid upregulation. Notably, the lipid-presenting molecules CD1a, CD1b and CD1c remained unaffected by sialidase treatment in MoDCs, a finding also further supported by experiments performed on C1R cells. Inhibition of endogenous sialidases Neu1 and Neu3 during MoDC differentiation did not affect surface MHC-I expression and cytokine secretion. Yet, sialidase activity in MoDCs was minimal, suggesting that sialidase inhibition does not significantly alter MHC-I-related functions. Our study highlights the unique maturation profile induced by sialic acid manipulation in MoDCs. These findings provide insights into the potential of sialic acid manipulation as a rapid immunomodulatory strategy, offering promising avenues for targeted interventions in inflammatory contexts.

Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP) is a vitamin K dependent protein (VKDP) shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP) are synthesized and gamma-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA) up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein gamma-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNF alpha, IL-1 beta and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel molecular mediator linking inflammation and calcification events, with potential therapeutic application.

Although the prognostic effect of obesity has been studied in critically ill patients its impact on outcomes of septic patients and its role as a risk factor for acute kidney injury (AKI) is not consensual. We aimed to analyze the impact of obesity on the occurrence of AKI and on in-hospital mortality in a cohort of critically ill septic patients. This study is retrospective including 456 adult patients with sepsis admitted to the Division of Intensive Medicine of the Centro Hospitalar Lisboa Norte (Lisbon, Portugal) between January 2008 and December 2014. Obesity was defined as a body mass index of 30 kg/m 2 or higher. The Kidney Disease Improving Global Outcomes classification was used to diagnose and classify patients developing AKI. AKI occurred in 87.5% of patients (19.5% with stage 1, 22.6% with stage 2 and 45.4% with stage 3). Obese patients developed AKI more frequently than non-obese patients (92.8% versus 85.5%, p = .035; unadjusted OR 2.2 (95% CI: 1.04-4.6), p = .039; adjusted OR 2.31 (95% CI: 1.07-5.02), p = .034). The percentage of obese patients, however, did not differ between AKI stages (stage 1, 25.1%; stage 2, 28.6%; stage 3, 15.4%; p = .145). There was no association between obesity and mortality (p = .739). Of note, when comparing AKI patients with or without obesity in terms of in-hospital mortality there were also no significant differences between those groups (38.4% versus 38.4%, p = .998). Obesity was associated with the occurrence of AKI in critically ill patients with sepsis; however, it was not associated with in-hospital mortality.

ABSTRACT Objectives: to understand the values attributed by nurses and physicians working in obstetric care for abortion. Methods: this is a phenomenological study based on Max Scheler’s theory of values, with 19 semi-structured online interviews with healthcare professionals working in legal abortion, using the snowball sampling recruitment technique. The collected data were transcribed in full and submitted to content analysis. Results: it was evident from healthcare professionals’ statements that abortion has a vital, moral and ethical professional value. Furthermore, the lack of value given to abortion by physicians and nurses was demonstrated as well as the vital value attributed to women’s lives by public health. Final Considerations: in order to understand the values attributed by nurses and physicians, there was the need to advance the values of health, rights, dignity and respect for women in the face of abortion. RESUMEN Objetivos: comprender los valores atribuidos por enfermeras y médicos que actúan en la atención del aborto obstétrico. Métodos: se trata de un estudio fenomenológico basado en la teoría de valores de Max Scheler, con 19 entrevistas semiestructuradas en línea a profesionales de la salud que trabajan en el aborto legal, utilizando la técnica de reclutamiento por muestreo de bola de nieve. Los datos recopilados fueron transcritos en su totalidad y sometidos a análisis de contenido. Resultados: se evidenció, a partir de las declaraciones de los profesionales de la salud, que el aborto tiene un valor ético vital, moral y profesional. Además, quedó demostrada la infravaloración del aborto por parte de médicos y enfermeras, así como el valor vital que la salud pública atribuye a la vida de las mujeres. Consideraciones Finales: para comprender los valores atribuidos por enfermeras y médicos, se mostró la necesidad de avanzar en los valores de salud, derechos, dignidad y respeto a las mujeres frente al aborto. RESUMO Objetivos: compreender os valores atribuídos pelos enfermeiros e médicos atuantes na assistência obstétrica ao abortamento. Métodos: trata-se de estudo fenomenológico fundamentado no referencial da teoria dos valores de Max Scheler, com 19 entrevistas semiestruturadas online com profissionais de saúde atuantes no abortamento legal, por meio da técnica de recrutamento snowball sampling. Os dados coletados foram transcritos na íntegra e submetidos à análise de conteúdo. Resultados: evidenciou-se, pelos depoimentos dos profissionais de saúde, que o abortamento possui um valor vital, moral e ético profissional. Além disso, mostrou-se o desvalor do abortamento por parte de médicos e enfermeiros, e ainda o valor vital para a vida das mulheres atribuído pela saúde pública. Considerações Finais: com a finalidade da compreensão dos valores atribuídos por enfermeiros e médicos, mostrou-se a necessidade do avanço para os valores à saúde, ao direito, à dignidade e ao respeito das mulheres diante do abortamento.

This article studies the relationship between company size and performance for small and medium-sized Portuguese companies. Using dynamic panel estimators, we conclude that performance is related positively to size. This relationship suggests the greater relevance of scale effects, diversification and the greater ability of larger companies to cope with market changes. Furthermore, our empirical results show that performance is persistent, not showing discontinuity, suggesting that small and medium-sized Portuguese companies are relatively successful in coping with possible scenarios of aggressive competition. Debt and level of fixed assets influence performance negatively, and separation of management and ownership influence performance positively. Liquidity, risk and ownership control are not relevant in explaining the performance of small and medium-sized Portuguese companies.

PurposeUsing the Risk, Injury, Failure, Loss of kidney function, End-stage kidney disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) systems, the incidence of acute kidney injury (AKI) and their ability to predict in-hospital mortality in severe sepsis or septic shock was compared.Materials and methodsWe performed a retrospective analysis of 457 critically ill patients with severe sepsis or septic shock hospitalized between January 2008 and December 2014. Multivariate logistic regression was employed to evaluate the association between the RIFLE, AKIN and KDIGO systems with in-hospital mortality. Model fit was assessed by the goodness-of-fit test and discrimination by the area under the receiver operating characteristic (AUROC) curve. Statistical significance was defined as P < 0.05.ResultsRIFLE (84.2%) and KDIGO (87.5%) identified more patients with AKI than AKIN (72.8%) (P < 0.001). AKI defined by AKIN and KDIGO was associated with in-hospital mortality {AKIN: adjusted odds ratio [OR] 2.3[95% confidence interval (CI) 1.3–4], P = 0.006; KDIGO: adjusted OR 2.7[95% CI 1.2–6.2], P = 0.021} while AKI defined by RIFLE was not [adjusted OR 2.0 (95% CI 1–4), P = 0.063]. The AUROC curve for in-hospital mortality was similar between the three classifications (RIFLE 0.652, P < 0.001; AKIN 0.686, P < 0.001; KDIGO 0.658, P < 0.001).ConclusionsRIFLE and KDIGO diagnosed more patients with AKI than AKIN, but the prediction ability for in-hospital mortality was similar between the three systems.

The formation of distant metastasis resulting from vascular dissemination is one of the leading causes of mortality in non-small cell lung cancer (NSCLC). This metastatic dissemination initiates with the adhesion of circulating cancer cells to the endothelium. The minimal requirement for the binding of leukocytes to endothelial E-selectins and subsequent transmigration is the epitope of the fucosylated glycan, sialyl Lewis x (sLex), attached to specific cell surface glycoproteins. sLex and its isomer sialyl Lewis a (sLea) have been described in NSCLC, but their functional role in cancer cell adhesion to endothelium is still poorly understood. In this study, it was hypothesised that, similarly to leukocytes, sLe glycans play a role in NSCLC cell adhesion to E-selectins. To assess this, paired tumour and normal lung tissue samples from 18 NSCLC patients were analyzed. Immunoblotting and immunohisto-chemistry assays demonstrated that tumour tissues exhibited significantly stronger reactivity with anti-sLex/sLea antibody and E-selectin chimera than normal tissues (2.2- and 1.8-fold higher, respectively), as well as a higher immunoreactive score. High sLex/sLea expression was associated with bone metastasis. The overall α1,3-fucosyltransferase (FUT) activity was increased in tumour tissues, along with the mRNA levels of FUT3, FUT6 and FUT7, whereas FUT4 mRNA expression was decreased. The expression of E-selectin ligands exhibited a weak but significant correlation with the FUT3/FUT4 and FUT7/FUT4 ratios. Additionally, carcinoembryonic antigen (CEA) was identified in only 8 of the 18 tumour tissues; CEA-positive tissues exhibited significantly increased sLex/sLea expression. Tumour tissue areas expressing CEA also expressed sLex/sLea and showed reactivity to E-selectin. Blot rolling assays further demonstrated that CEA immunoprecipitates exhibited sustained adhesive interactions with E-selectin-expressing cells, suggesting CEA acts as a functional protein scaffold for E-selectin ligands in NSCLC. In conclusion, this work provides the first demonstration that sLex/sLea are increased in primary NSCLC due to increased α1,3-FUT activity. sLex/sLea is carried by CEA and confers the ability for NSCLC cells to bind E-selectins, and is potentially associated with bone metastasis. This study contributes to identifying potential future diagnostic/prognostic biomarkers and therapeutic targets for lung cancer.

Extreme weather events, such as marine heatwaves (MHWs), pose serious threats to the aquaculture sector, facilitating the occurrence of disease outbreaks and compromising farmed animals’ welfare and survival. Hence, finding eco-innovative strategies to improve animal immunocompetence is essential to assure aquaculture’s sustainability and resilience in a rapidly changing ocean. This study evaluated the immunostimulatory potential of Laminaria digitata powder (0.3% and 1.5%) and extract (0.3%) in juvenile gilthead seabream (Sparus aurata) exposed to a Vibrio harveyi outbreak during a Category III MHW event (T = 25.7 °C). Overall, L. digitata supplementation did not significantly affect fish immunocompetence under optimal rearing conditions (T = 21.4 °C; no infection), nor did it induce any adverse effects. However, both the powder (1.5%) and extract (0.3%) forms of L. digitata supplementation effectively mitigated the negative impacts prompted by the MHW and Vibrio harveyi infection—evidenced by improvements in fish health indicators, hematological parameters, leukocyte viability, granulocyte proportions, and reductions in peroxidase activity and immunoglobulin M levels. From an economic standpoint, supplementation with 1.5% L. digitata powder emerged as the most promising strategy, offering a practical balance between effectiveness and affordability for large-scale applications. These findings highlight the potential of L. digitata as an immunostimulatory aquafeed supplement, with promising benefits for fish health and resilience under adverse rearing conditions.