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Background: Real-world safety profiles of immune checkpoint inhibitors (ICIs) in older adults remain insufficiently characterized. Although ICIs are widely used across tumor types, older patients, particularly those with frailty, multimorbidity, or polypharmacy, are consistently under-represented in clinical trials, limiting the external validity of trial-derived toxicity estimates. Robust real-world data are therefore essential to clarify the incidence, seriousness, and age-related patterns of immune-related adverse events (irAEs) in routine practice. Methods: This is a nationwide retrospective study of spontaneous ICI-related ADRs reported in INFARMED’s Portal RAM (2011–2024). We evaluated the frequency, seriousness, fatality, and organ-specific patterns of ICI-related adverse drug reactions (ADRs) reported to the Portuguese National Pharmacovigilance System. The analytic unit was the ADR case. Endpoints included seriousness (primary), fatality, hospitalization, time-to-onset, and System Organ Class. Multivariable logistic regression adjusted for age, sex, regimen, tumor type, polypharmacy, and calendar period; sensitivity analyses using first ADR per patient were concordant. Results: We identified 2300 eligible ICI-related ADRs (corresponding to 925 patients). Median age at the time of ADR was 65 years (IQR not reported); 33.7% occurred in adults aged ≥70 years, and 62.8% of reports involved male patients. PD-1 inhibitors accounted for 77.5% of ADRs, and monotherapy for 72.9%. Overall, 85.8% of ADRs were classified as serious; 17.9% led to hospitalization and 19.1% were fatal. Serious-event reporting was similar in older and younger adults (≥70 vs. <70 years: 84.5% vs. 86.5%, p = 0.22), and the proportion explicitly labeled immune-related did not differ (9.3% vs. 8.7%, p = 0.56). In contrast, fatal outcomes were significantly more common in older adults (25.3% vs. 16.0%; p < 0.001). Age was associated with distinct organ-specific patterns. Adults ≥ 70 years had higher odds of nervous system disorders (aOR 1.75, 95% CI 1.23–2.48) and immune system disorders (aOR 1.42, 95% CI 1.02–1.98), but lower odds of hepatobiliary (aOR 0.52, 95% CI 0.36–0.76; p = 0.001) and blood/lymphatic disorders (aOR 0.50, 95% CI 0.32–0.79). In multivariable models, age ≥ 70 years did not predict seriousness (aOR 0.98, 95% CI 0.76–1.27), whereas combination therapy remained independently associated with increased seriousness (aOR 1.57, 95% CI 1.13–2.18). Conversely, age ≥ 70 years independently predicted fatal outcomes (aOR 1.66, 95% CI 1.31–2.09). Later calendar periods (2017–2024) were associated with substantially lower fatality (aOR 0.16; 95% CI 0.10–0.27). CTLA-4-containing regimens demonstrated a tendency toward higher fatality (aOR 1.50; 95% CI 0.94–2.37). Conclusions: Chronological age does not seem to increase the likelihood of reporting a serious ICI-related ADR, but, once toxicity occurs, older adults experience higher fatality rates. Age-related phenotypic differences and regimen-specific risks highlight the need for early recognition systems and tailored toxicity management in older populations.

O século XXI é assinalado pelas constantes mudanças na sociedade nas mais diversas áreas da atividade humana. Uma das principais transformações sentidas está associada ao crescente volume de dados disponibilizados.Nesta nova sociedade, denominada de Sociedade de Informação, a informação é vista como uma necessidade, mas também como um recurso para alcançar conhecimento.Porém, o tratamento de grandes quantidades de dados nem sempre é decifrável. Torna-se assim necessário recorrer a mecanismos que permitam processar estes grandes conjuntos de dados de forma que sejam compreendidos e, por conseguinte, forneçam informação útil, nomeadamente para a implementação de estratégias que aumentem a eficácia das organizações no seu meio envolvente.Circulando cada vez mais informação e de acesso cada vez mais fácil, de dia para dia as organizações nos mais diversos setores atuam num ambiente mais concorrencial e inovador – onde o setor da educação não é exceção. Torna-se assim essencial que as Instituições de Ensino Superior (IES) se munam de novas ferramentas e tecnologias que lhes permitam enfrentar os correntes desafios propostos com a nova realidade em que estão inseridas.É neste sentido que o presente trabalho tem como principal objetivo, através de uma ferramenta de Business Intelligence (BI), caracterizar o Ensino Superior em Portugal nos últimos anos letivos. Assim, recorreu-se ao Microsoft Power BI para desenvolverdashboardsque permitem alcançar os objetivos propostos e contribuem de forma positiva para a tomada de decisões das IES.Desta forma, a metodologia CRISP-DM seguida permite desenvolver um relatório onde a informação disponibilizada se encontra percetível em painéis visualmente apelativos, de maneira a contribuir para o melhoramento das decisões dos diferentes Estabelecimentos de Ensino e, por conseguinte, beneficiar de vantagens competitivas perante os restantes e principais rivais.

Introdução: A hipertensão arterial é uma das doenças crónicas que mais afeta a população portuguesa e cuja terapêutica acompanha o doente ao longo de toda a sua vida, desde o momento em que é diagnosticada. É uma doença que pode levar a complicações na saúde do doente se não for devidamente controlada, sendo a adesão um ponto fulcral para o sucesso desta terapêutica. Neste sentido, várias barreiras à adesão e estratégias para melhorá-la têm vindo a ser investigadas. Objetivo: Avaliar o grau de adesão à terapêutica numa amostra de doentes hipertensos através do questionário Maastricht Utrecht Adherence in Hypertension (MUAH), com vista à identificação dos principais aspetos a ter em consideração na promoção da adesão à terapêutica anti-hipertensora. Metodologia: O presente estudo foi realizado em 5 farmácias comunitárias portuguesas. Foram convidados a participar todos os doentes que apresentassem prescrição de, pelo menos, um medicamento anti-hipertensor ou que fizessem terapêutica anti-hipertensora há mais de 3 meses. Na entrevista com o doente foram recolhidos dados sociodemográficos e relativos à terapêutica de cada doente e realizados os questionários Hypertension Knowledge Test (HKT), Beliefs about Medicines Questionnaire (BMQ) e Maastricht Utrecht Adherence in Hypertension (MUAH). O controlo da doença foi avaliado por meio de duas medições da pressão arterial, no início e no fim da entrevista. O tratamento dos dados e a análise estatística foram realizados utilizando o programa SPSS. A aprovação para a realização do projeto foi concedida pela Comissão de Ética da Faculdade de Medicina da Universidade de Coimbra (024-CE-2018). Resultados: Participaram neste estudo 197 doentes, com uma média de idades de 65,82±12,15 anos. A média da pontuação obtida no questionário MUAH foi de 127,84±17,44, num total de 175 pontos. Cada dimensão do MUAH foi analisada individualmente, tendo sido a ‘aversão à medicação’ aquela que se destaca e que mais intervenção necessita, com uma média de 20,35±6,772 num total de 35. Não houve diferenças estatisticamente significativas entre o grau de adesão à terapêutica anti-hipertensora e o sexo, a idade ou o controlo da doença, quer considerando a pontuação total quer cada uma das dimensões do MUAH. Conclusão:O estudo revela que há muito a fazer no campo da adesão, permitindo definir as áreas e estratégias necessárias para otimizar a adesão à terapêutica anti-hipertensora. O farmacêutico atua como um importante elo de ligação entre o doente, o medicamento, um melhor controlo da doença e uma vida mais saudável, podendo intervir tanto a nível comportamental como educacional.

In general, mercury (Hg) undergoes biomagnification in aquatic systems. The absence of Hg biomagnification in a certain aquatic environment constitutes an exceptional finding and this seems to be the case for Sepetiba Bay, in Rio de Janeiro state (RJ), Brazil. There are three distinct ecological populations of Guiana dolphins in the Sepetiba Bay (SB)–Ilha Grande Bay (IGB) Complex, inhabiting: (1) the inner part of SB; (2) SB entrance; and (3) IGB. In addition, there are two other delphinid species, rough-toothed dolphin and Atlantic spotted dolphin, that feed on the SB–IGB Complex. Considering the widely employed use of cetaceans as sentinels of environmental contamination by bioaccumulative toxicants, we have biopsy sampled individuals of the abovementioned ecological populations/species for measuring skin Hg concentrations. Two Bryde’s whales and one humpback whale were biopsied in the SB–IGB Complex as well. Skin Hg concentrations [μg g−1 dry weight (dw)] of Guiana dolphins were the highest in IGB, followed by SB entrance and the inner part of SB (0.99–5.47; 0.09–6.00; 0.08–2.22). Considering all species investigated in the present study, skin Hg concentrations were found in the following order: humpback whale < Bryde's whale < Guiana dolphins from SB inner part < Guiana dolphins from SB entrance < Guiana dolphins IGB = Atlantic spotted dolphins < rough-toothed dolphins. The skin Hg concentrations found in Guiana dolphins from the inner part of Sepetiba Bay (0.08–2.22) and rough-toothed dolphins from the SB–IGB Complex (1.26–20.0) are among the lowest and highest ever reported for dolphins worldwide, respectively.

ABSTRACT This study reports a case series of four pediatric patients with dengue who developed fulminant hepatitis and acute liver failure requiring transplantation. This study aims to enhance early recognition of dengue-related complications, particularly fulminant hepatitis. The series includes two previously healthy girls, aged one and six years; and two boys, aged 12 and 15 years, with pre-existing hemoglobinopathies. A review was conducted to contextualize these cases with prior reports of dengue-associated fulminant hepatitis in children, focusing on diagnosis and management. All four patients underwent liver transplantation, yet their clinical courses and outcomes were varied. Patient 1, a six-year-old girl, had early warning signs and underwent cadaveric liver transplantation nine days after onset. Patient 2, a one--year-old girl, developed severe disease and received living-donor transplantation 20 days after onset. Both had favorable postoperative outcomes. Patient 3, a 12-year-old boy with SC hemoglobinopathy, underwent transplantation on day seven of illness but died on the fifth postoperative day. Patient 4, a 15-year-old boy with sickle cell anemia, underwent transplantation on day four of symptoms but suffered multiple cardiorespiratory arrests during recovery and died on postoperative day 24. Although rare, dengue can lead to fulminant hepatitis in previously healthy children, with worse outcomes in those with comorbidities. Early recognition of severe manifestations is critical for appropriate management. Larger studies are warranted to identify prognostic factors and optimize decision-making for pediatric patients requiring liver transplantation.

Background Genetic variation in host resistance to individual parasites is well documented in cattle; however, the influence of coinfection on these genetic responses to selection remains poorly characterized. In particular, it is unclear how concurrent exposure to multiple parasite species alters phenotypic expression, heritability estimates, or genetic correlations between resistance traits. To address these gaps, we evaluated the impact of coinfection on the genetic architecture of parasite resistance in yearling Nellore calves naturally challenged with ectoparasites (ticks) and endoparasites (gastrointestinal nematodes and Eimeria spp.). Using longitudinal parasite count data, we estimated genetic parameters and examined how coinfection modifies both individual parasite resistance and the genetic correlations among traits. Results Our results confirmed that coinfection is a common phenomenon (almost ¾ of samples contained multiple parasites) and that resistance to individual parasites is a heritable trait. Furthermore, coinfection with Eimeria spp. reduced the phenotypic resistance to nematodes, and vice versa. We observed diverse genetic associations for resistance to different parasites, including positive, negative, and nonsignificant correlations. Notably, coinfection had no significant effect on genetic resistance to individual parasites, nor did it alter genetic variances or associations between resistance to different parasites. Conclusions While coinfection may influence the outcomes of nongenetic parasite control programs, its impact on genetic control strategies appears minimal. In other words, genetic resistance of Nellore cattle to three key parasite species appears to be robust and unaffected by the presence of coinfection.

Delirium is an acute neuropsychiatric syndrome of multifactorial etiology with a high incidence in people admitted to intensive care units. In addition to reversible impairment of cognitive processes, it may be associated with changes in thinking and perception. If, in the past, it was considered an expected complication of severe disease, nowadays, delirium is associated with a poor short-term and long-term prognosis. Knowing that its prevention and early identification can reduce morbidity, mortality, and health costs, it is vital to investigate nursing interventions focused on delirium in critically ill patients. This study aimed to identify nursing interventions in the prevention and management of delirium in critically ill adults. The method used to answer the research question was a scoping review. The literature search was performed in the Medline (via PubMed), CINAHL (via EBSCOhost), Scopus, Web of Science, and JBI databases. The final sample included 15 articles. Several categories of non-pharmacological interventions were identified, addressing the modifiable risk factors that contribute to the development of delirium, and for which nurses have a privileged position in their minimization. No drug agent can, by itself, prevent or treat delirium. However, psychoactive drugs are justified to control hyperactive behaviors through cautious use. Early diagnosis, prevention, or treatment can reduce symptoms and improve the individual’s quality of life. Therefore, nursing professionals must ensure harmonious coordination between non-pharmacological and pharmacological strategies.

Background Resilience reflects coping with pregnancy-specific stress, including physiological adaptations of the maternal organism or factors arising from the socioeconomic context, such as low income, domestic violence, drug and alcohol use, lack of a support network and other vulnerability characteristics. Resilience is a dynamic characteristic that should be comparatively evaluated within a specific context; its association with perceived stress and social vulnerability during pregnancy is still not fully understood. This study aimed at exploring maternal resilience, perceived stress and social vulnerability during pregnancy and its associated factors and outcomes. Methods Prospective multicenter cohort study of nulliparous women in Brazil determining resilience (Resilience Scale; RS) and stress (Perceived Stress Scale; PSS) at 28 weeks of gestation (± 1 week). Resilience and stress scores were compared according to sociodemographic characteristics related to maternal/perinatal outcomes and social vulnerability, defined as having low level of education, being adolescent, without a partner or ethnicity other than white. Results We included 383 women who completed the RS and PSS instruments. Most women showed low resilience scores (median: 124.0; IQR 98–143). Women with a low resilience score (RS < 125) were more likely from the Northeast region, adolescents, other than whites, did not study or work, had a low level of education, low family income and received public antenatal care. Higher scores of perceived stress were shown in the Northeast, other than whites, at low levels of education, low annual family income and public antenatal care. Pregnant women with low resilience scores ( n  = 198) had higher perceived stress scores (median = 28) and at least one vulnerability criterion ( n  = 181; 91.4%). Conclusion Our results reinforce the role of resilience in protecting women from vulnerability and perceived stress. It may prevent complications and build a positive experience during pregnancy.

During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ® software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.

During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ[sup.®] software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.