CIIS - Contribuições em Revistas Científicas / Contribution to Journals
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- Tumor stage-dependent expression of autophagy proteins in adrenocortical carcinomaPublication . Oliveira, Sofia B.; Sousa, Diana; Costa, Madalena; Rios, Elisabete; Silva, Tiago Nunes da; Leite, Valeriano; Pereira, Sofia S.; Pignatelli, DuarteIntroduction: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor yet heterogeneous prognosis, mostly due to its complex and incompletely understood molecular background. Autophagy is a multi-step catabolic process with a dual role in tumorigenesis, acting either as a tumor suppressor or promoter in a context-dependent manner. Therefore, our aim was to investigate the expression of key proteins involved in different autophagy steps in both adrenocortical adenomas (ACA) and ACC, to further understand the role of autophagy in this type of tumors, particularly its involvement in the pathophysiology of ACC. Methods: Autophagy status was evaluated in ACA (n=20) and ACC (n=29) by assessing the expression of autophagy-related protein 5 (ATG5), microtubule associated protein 1 light chain 3 beta (LC3B), and sequestosome 1 (p62/SQSTM1), using immunohistochemistry. Additionally, in vitro experiments, including migration and invasion assays, were conducted in JIL-2266 and H295R cell lines to investigate the impact of autophagic flux inhibition in ACC cell behavior. Results: LC3B punctate staining was present in 89% of ACC and 25% of ACA, with significantly higher LC3B expression in ACC compared to ACA (14.81 ± 2.26% vs 2.05 ± 1.00%, p < 0.0001). ACC with ENSAT stage of 1–2 exhibited significantly higher LC3B expression compared to ACC with ENSAT 3-4 (19.17 ± 1.05% vs 12.62 ± 4.00%, p = 0.02). Similarly, non-metastatic ACC showed a significantly higher percentage of LC3B positive cells than metastasized ACC (18.77 ± 3.52% vs 5.83 ± 1.70%, p = 0.004). In vitro, inhibition of autophagy significantly reduced cell migration and invasion in ACC cells. Higher cytoplasmic p62/SQSTM1 levels were found in ACC with advanced disease (ENSAT 3–4 vs ENSAT 1-2: 72.07 ± 3.61% vs 51.33 ± 9.24%, p = 0.02). No significant differences were observed for ATG5. Discussion: Our findings indicate a tumor stage-dependent role of autophagy in ACC and show that autophagy may play a role in ACC molecular pathophysiology. A punctate LC3B expression accumulation, associated with less aggressive malignant features, namely absence of metastasis, appears to result from a blockade at the late stages of autophagy. Whereas active autophagy may be associated with a more aggressive cellular phenotype in ACC, particularly by promoting migration and invasion.
- Correction: what's a migraine day? Towards a consensus definition for clinical care and research - a Delphi panel-based studyPublication . Loose, Luna De; Paemeleire, Koen; Deligianni, Christina I.; Lampl, Christian; Uluduz, Derya; Tronvik, Erling; Coppola, Gianluca; Schytz, Henrik; Schoenen, Jean; Rio, Margarita Sanchez del; Martelletti, Paolo; Pozo-Rosich, Patricia; Gil-Gouveia, Raquel; Ryliskiene, Kristina; Sacco, Simona; Ekizoglu, Esme; Petrusic, Igor; Fronczek, Rolf; Holland, Phil; Reuter, Uwe; Goadsby, Peter J.; MaassenVanDenBrink, Antoinette; Versijpt, Jan
- EHA recommendations for preconceptual and antenatal screening and prenatal diagnosis for hemoglobinopathiesPublication . Montalembert, Mariane de; Cappellini, Maria D.; Iolascon, Achille; Franceschi, Lucia de; Ömur, Eda; Saad, Michele Abi; Andolfo, Immacolata; Bento, Celeste; Berghs, Maria; Bonnet, Doris; Glenthoj, Andreas; Gulbis, Beatrice; Dolai, Tuphan K.; Lima, Jorge; Motta, Irene; Russo, Roberta; Taher, Ali; Tshilolo, Leon; Almeida, Antonio; Rees, DavidThalassemia and sickle cell disease (SCD) are among the most common monogenic disorders worldwide. They cause chronic hemolytic anemia, the consequences and prognosis of which vary considerably depending on the genetic characteristics of patients and the healthcare system in their country of residence. Both diseases are autosomal recessive in their transmission, with carriers generally being asymptomatic. Informing carriers of thalassemia or SCD about reproductive risks and choices, while taking into account cultural and religious considerations, is a priority within global strategies to improve outcomes for these diseases. The European Hematology Association (EHA)'s Topic In Focus (TIF) Hemoglobinopathies Group created a focus group of hematologists, patients, anthropologists, and an obstetrician from Europe, the Middle East, India, and Africa. The Group considered that preconceptual screening tests would correspond to tests conducted before pregnancy (screening for carriers before marriage/conception), antenatal screening referred to tests completed on pregnant women, and prenatal diagnosis referred to tests performed on the fetus. It proposed guidelines addressing optimal timing of screening, appropriate laboratory tests, and communication strategies, taking into account the great diversity of regions and cultures where thalassemia and SCD are present. A main discussion point was that no recommendations would be given for couples about reproductive decisions, and that the aim was to present the existing and available options in different countries. Eight questions were examined using available literature, leading to the formulation of seven recommendations, which were submitted to a vote using the Delphi method. Consensus agreement was obtained for all recommendations.
- Hope as a therapeutic resource in pregnancy after loss: operationalising woman-centred support in midwifery carePublication . Filipa da Palma Correia, Andreia; Antunes, Mónica Sofia do CoutoBackground: Pregnancy after loss constitutes a particularly vulnerable period characterised by the paradoxical coexistence of fear and hope. Despite growing recognition of this phenomenon, significant gaps remain in understanding how hope can be operationalised as a structured therapeutic resource in midwifery practice. Aim: This paper argues that hope can and should be operationalised as a structured, evidence-informed therapeutic intervention in midwifery practice, particularly in the care of women experiencing pregnancy after loss. Discussion: Drawing on contemporary theories of hope as a cognitive-motivational process and trauma-informed care principles and illustrated through a single practice-based clinical vignette, this paper advances a theoretically informed conceptual model for operationalising hope in pregnancy after loss. The discussion explores how woman-centred interventions can support the coexistence of fear and hope, foster adaptive meaning-making, and facilitate emotional engagement with the ongoing pregnancy, while maintaining clinical coherence and transferability across maternity care settings. Implications for Practice: This paper proposes that structured, evidence-informed interventions may meaningfully support women's emotional well-being during pregnancy after loss. The model challenges common practices of premature reassurance and suggests that fear and hope are not mutually exclusive. Midwives and maternity care providers can use hope-centred approaches to support women in reconstructing their parental project whilst honouring the memory of previous losses. Conclusion: Hope is not a passive emotional state but an active therapeutic resource that may be intentionally cultivated through structured midwifery interventions, advanced communication skills, and the capacity to tolerate uncertainty.
- Transgenerationality in nursing care: implications for person-centered practice and hospital-to-home transitionsPublication . Almeida, António; Tomás, João; Maravilha, André; Sousa, Luís; Pontífice-Sousa, PatríciaTransgenerationality refers to the psychological and behavioral elements transmitted across generations. It is intrinsically linked to unelaborated content—such as trauma, grief, secrets, conflicts, and shame—operating through implicit and partially unconscious pathways that manifest in individual behavior. In the context of nursing, transgenerationality explores how nursing care is influenced by these dynamics and how the concept can be utilized to achieve superior health-related outcomes, such as facilitating more effective healthcare transitions. Specifically, it examines how experiences, vulnerabilities, resilience factors, and health-related patterns transmitted across generations affect overall health. As a humanistic profession rooted in person-centered care, nursing must remain cognizant of the impact of this concept on healthcare. This is particularly relevant in clinical settings where nurses are pivotal practitioners, such as mental health, health literacy, chronic disease management, and healthcare transitions. Healthcare transitions represent critical periods in a person’s life, and nurses are present across all contexts to facilitate these shifts. A primary example is the transition from hospital to home, which illustrates the importance of understanding transgenerationality within the roles of both patients and caregivers. Understanding how this concept impacts healthcare allows for the perception of transition as a holistic process. Awareness of these transgenerational operations leads to more personalized care, fostering healthier and more seamless healthcare transitions. The general purpose of this paper is to define and operationalize the concept of transgenerationality within nursing care, emphasizing its critical role in achieving better health outcomes, particularly during hospital-to-home transitions.
- Impact of sarcopenia on prognosis, treatment toxicity and surgical complications in locally advanced gastric cancerPublication . Dias, David da Silva; Luz, Paulo; Fortuna, Ana; Águas, Ana; Machado, Mafalda; Gosalbez, Beatriz; Farate, Rosa; Pinho, Rita Clemente; Valente, Ana Carmo; Mendes, José Leão; Seladas, Marta Maria; Trabulo, Carolina; Ravasco, PaulaBackground: Weight loss and skeletal muscle wasting are frequent in cancer and may influence treatment tolerance and outcomes. Computed tomography (CT) based body composition analysis at the third lumbar vertebra (L3) is an accurate method to quantify skeletal muscle in routine oncology care. Methods: We performed a multicenter retrospective cohort study including 202 adults with locally advanced (stage IB–III) gastric cancer treated in four Portuguese hospitals (January 2020–December 2022). Skeletal muscle area (SMA) was assessed on baseline CT at the L3 vertebral level, using Data Analysis Facilitation Suite (DAFS) software v3.11.2, and skeletal muscle index (SMI) was subsequently calculated. Patients with low muscle quantity were classified as sarcopenic (below sex-specific SMI mean). We evaluated associations with relapse-free survival (RFS), overall survival (OS), FLOT chemotherapy dose-limiting toxicities (DLTs), and postoperative complications after gastrectomy. Results: Mean age was 69 years, 65% had ECOG PS 0, 53% received FLOT chemotherapy protocol. Mean SMI was 49.6 cm 2/m 2 in males and 40.9 cm 2/m 2 in females and correlated positively, though moderately, with BMI (p < 0.01; r = 0.424). Sarcopenia was not significantly associated with RFS (p = 0.186) or OS (p = 0.168) at 30-month follow-up. Although numerical differences were observed (64% vs. 56% of patients did not relapse and 74% vs. 63% were alive, for non-sarcopenic vs. sarcopenic patients). Sarcopenia was associated with a higher risk of DLTs (p = 0.021; OR 2.56, 95% CI 1.15–5.73) and postoperative complications (p = 0.024; OR 2.16, 95% CI 1.11–4.21). Conclusions: Sarcopenia significantly increases the risk of chemotherapy toxicity and postoperative complications in locally advanced gastric cancer. However, its effect on OS and RFS was not statistically significant at 30-month follow-up. Standardization of CT-based sarcopenia cut-offs remains a major barrier to clinical implementation.
- Restoring physiological normoxia as an adjuvant strategy to improve cancer treatment outcomesPublication . Bermejo, Carlos Mas; Gómez, Carlos Mas; Sevilla-García, Ma-Agustina; O’Connor-Reina, Carlos; Ramos, Susana Falardo; Alonso-Romero, José Luis; Bravo-González, Luis-AlbertoHypoxia is a central driver of cancer progression, immune evasion, and resistance to anticancer therapies. While hypoxia has traditionally been considered an intrinsic feature of the tumor microenvironment, growing evidence indicates that chronic intermittent hypoxia—particularly that occurring during sleep—represents a systemic and potentially modifiable contributor to hypoxia-driven oncogenic signaling. Sleep-disordered breathing is the most prevalent cause of nocturnal intermittent hypoxia and induces oxidative stress, inflammation, metabolic reprogramming, and immune dysregulation through mechanisms that overlap with those observed in hypoxic tumors.This narrative review synthesizes current experimental, translational, and clinical evidence supporting the concept that restoration of physiological normoxia, especially during sleep, may attenuate hypoxia-mediated cancer biology and improve responsiveness to standard anticancer therapies. We examine the biological effects of normoxia restoration on hypoxia-inducible signaling, redox homeostasis, tumor metabolism, and antitumor immunity, highlighting its potential role as a host-directed, adjuvant strategy rather than a direct tumor-targeting intervention.We further review sleep and airway-centered therapeutic approaches capable of reducing nocturnal hypoxic burden, including continuous positive airway pressure, mandibular advancement devices, upper airway surgery, myofunctional therapy, and respiratory physiotherapy. Although these interventions are not cancer-specific, their ability to stabilize nocturnal oxygenation positions them as clinically relevant tools within a multidisciplinary framework aimed at hypoxia normalization.Collectively, the evidence suggests that nocturnal normoxia is a biologically meaningful and clinically actionable target. Integrating sleep and airway interventions into cancer care pathways may represent a novel avenue to mitigate hypoxia-driven treatment resistance and enhance therapeutic outcomes. Prospective clinical studies incorporating objective measures of hypoxic burden are warranted to validate this integrative approach.Restoration of physiological normoxia is therefore proposed as a host-directed, adjuvant strategy aimed at mitigating hypoxia-driven oncogenic pathways and improving responsiveness to standard anticancer therapies.
- Material properties of composite resins used for orthodontic attachments in clear aligner therapy: a systematic reviewPublication . Frias, Lara; Fidalgo-Pereira, Rita; Noites, Rita; Correia, Maria J.; Gomes, Ana T. P. C.; Lopes, Pedro C.Clear aligner therapy has become increasingly widespread in contemporary orthodontics, relying on composite resin attachments to enhance force transmission and improve the predictability of tooth movement. The physicochemical and mechanical properties of these biomaterials play a crucial role in attachment durability, dimensional stability, and esthetic performance during treatment. This systematic review aimed to evaluate how different composite resin types influence the mechanical, optical, and functional performances of orthodontic attachments used in clear aligner therapy. A systematic literature search was conducted in the PubMed, Scopus, and Cochrane databases for studies published between 2015 and 2025, following PRISMA guidelines. In vitro studies and clinical trials evaluating composite resins used for attachment fabrication were included. Fifteen studies met the eligibility criteria, including eleven laboratory investigations and four clinical studies. The evaluated outcomes comprised shear bond strength, wear resistance, surface roughness, microhardness, color stability, and accuracy of attachment reproduction. Overall, all evaluated composite resins demonstrated shear bond strength values within clinically acceptable ranges. However, significant differences were observed in the material performances depending on the resin composition and viscosity. Nanohybrid and high-viscosity composite resins were generally associated with improved mechanical resistance, reduced wear, and greater dimensional stability, although SBS outcomes should be interpreted in light of the bonding protocols used. In contrast, flowable composite resins showed improved handling and adaptation to attachment molds but presented higher susceptibility to surface degradation and discoloration. The findings suggest that the composition and properties of composite resins significantly influence the mechanical and optical behavior of orthodontic attachments. Optimizing material selection according to biomechanical demands and esthetic requirements may improve attachment longevity and treatment predictability in clear aligner therapy. Clinicians should prioritize nanohybrid or high-viscosity composite resins for high-load attachments and use flowable composite resins materials when adaptation and esthetics are critical.
- Improving care for cognitive impairment in schizophrenia: current perspectives and opportunities in Portugal (a consensus development conference)Publication . Madeira, Nuno; Bessa, João M.; Castelão, Joaquina; Constante, Miguel; Durães, Miguel; Fonseca, Ana Rosário; Freire, Pedro; Paus, Carmen; Rebelo, Ana Maria; Rodrigues, Patricia; Silveira, Celeste; Couto, Frederico Simões doBackground: Cognitive impairment is a key contributor to the functional disability seen in schizophrenia, yet it remains one of the most underdiagnosed and poorly managed aspects of the disorder. In Portugal, schizophrenia imposes a significant socio-economic burden, with notable gaps in the assessment and treatment of cognitive impairment.Method: A panel of Portuguese healthcare professionals, including six psychiatrists with clinical and academic expertise, a neuropsychologist, a psychiatric nurse, and two representatives from patient associations, reviewed current evidence and practices for managing cognitive impairment in schizophrenia. The panel addressed three primary clinical questions using a consensus development conference methodology (1): What is the current state of CIAS (cognitive impairment associated with schizophrenia) assessment and management in Portugal? (2) What are the major barriers to optimal care? (3) What recommendations can improve CIAS care within the Portuguese healthcare system?Results: Several challenges hinder the routine assessment and treatment of cognitive impairment in Portugal, including the lack of validated assessment tools, the absence of national guidelines, insufficient trained healthcare professionals, and limited access to cognitive remediation therapy (CRT). Key opportunities that could improve care include establishing national guidelines for cognitive assessment and management, using validated and practical assessment tools, training healthcare professionals, integrating CRT into standard care pathways, engaging caregivers, and strengthening collaboration between healthcare institutions.Conclusion: Despite significant challenges, the Portuguese healthcare system has numerous opportunities to improve the management of cognitive impairment in schizophrenia. Critical unresolved issues include the need for additional validated Portuguese assessment instruments and the establishment of cost-effectiveness data for CRT implementation in the Portuguese context.
- Early development of clinical reasoning through virtual patient simulation: nursing students' perceptions of collaborative decision-makingPublication . Sales, Leila; Ferreira, Maria; Pereira, Raquel; Lucas, Isabel; Marques, Rita; Bento, InêsSimulation is increasingly recognised as a strategic approach in nursing education for developing clinical competencies within safe learning environments. However, there is limited understanding of how virtual patient simulation supports the early development of clinical reasoning from the perspective of nursing students. Aim: To explore the perceptions of first-year undergraduate nursing students regarding the development of clinical reasoning and collaborative decision-making through virtual patient simulation. Methods: A qualitative, descriptive, and exploratory design was adopted. Semi-structured focus groups were conducted with 73 first-year undergraduate nursing students. Data were analysed using thematic content analysis following Bardin’s approach. Results: Students perceived virtual patient simulation as a meaningful and high-impact learning strategy. Realism, interactivity, and group collaboration emerged as key strengths. Engagement with dynamic clinical scenarios supported the integration of theoretical knowledge into practice, enhanced prioritisation skills, and promoted structured clinical reasoning. Collaborative learning facilitated shared reflection and collective problem-solving, while immediate feedback enabled learning through error within a psychologically safe environment. Participants also reported increased confidence and autonomy in decision-making. At the same time, students identified limitations related to software constraints and the alignment between automated assessment and their reasoning processes. Conclusions: Group-based virtual simulation appears to support the early structuring of clinical reasoning, extending beyond technical skill acquisition to foster reflective and collaborative practice. Its educational value, however, depends on intentional curricular integration and strong pedagogical alignment including structured facilitation, alignment between assessment and learning objectives, and opportunities for guided reflection. These findings contribute to a process-oriented understanding of how novice learners make sense of clinical reasoning in simulated contexts.