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Abstract Background Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. Methods To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm’s parameters (parameter-based). Results Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). Conclusions By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.

Enquadramento: A exposição dos enfermeiros ao sofrimento e morte dos doentes pode desencadear níveis elevados de sofrimento, dependendo das estratégias de coping utilizadas. Objetivos: Analisar a relação entre o sofrimento e as características sociodemográficas e profissionais identificar as estratégias de coping mais utilizadas; analisar a relação entre o sofrimento e as estratégias de coping. Metodologia: Estudo descritivo, correlacional e transversal. Participaram 26 enfermeiros de uma Unidade Cuidados Intensivos Cardíacos (UCIC). Foi utilizada a Caregiver Grief Scale para avaliar o sofrimento e o Ways of Coping Questionnaire para avaliar as estratégias de coping. Resultados: Não se verifica relação entre o sofrimento e as características sociodemográficas e profissionais. As estratégias de coping mais utilizadas são as centradas no problema (autocontrolo, procura de suporte social). Constata-se uma correlação positiva (r = 0,56) entre o sofrimento e a estratégia de coping distanciamento (p = 0,01). Conclusão: O sofrimento é transversal a todos os enfermeiros de uma UCIC, independentemente das variáveis sociodemográficas e profissionais. Utilizando como estratégia de coping o distanciamento, o sofrimento pode ser maior.

Abstract The objectives of this study were twofold: (1) to identify potential differences in the ruminal and fecal metabolite profiles of Nelore bulls under different nutritional interventions; and (2) to identify metabolites associated with cattle sustainability related-traits. We used different nutritional interventions in the feedlot: conventional (Conv; n = 26), and by-product (ByPr, n = 26). Thirty-eight ruminal fluid and 27 fecal metabolites were significantly different (P

Despite their familiarity with technology, higher education students often lack the critical skills needed to assess the credibility of online health information, potentially impacting their health decisions and well-being. This study aims to validate and assess the e-Health Literacy Scale among those in Portuguese higher education. In addition, this study focused on measuring their e-health literacy levels and investigating how these skills relate to different sociodemographic variables. This cross-sectional study was conducted in two phases. Initially, the test–retest reliability and reproducibility of measured e-health literacy were assessed with a convenience sample of 20 participants. Subsequently, the e-health scale was applied to a group of 245 Portuguese higher education students. The research took place from January 2023 to April 2024. The scale exhibited robust internal consistency and reproducibility. Male gender consistently correlates with higher levels of e-health literacy. Students demonstrate good levels of e-health literacy (24/40), reflecting their ability to effectively navigate and utilize health information online. By integrating strategies to further enhance this literacy into university health programs, students can develop essential skills necessary for making informed decisions about their health. This proactive approach not only empowers students to access reliable health resources but also fosters a culture of health literacy that can positively impact their well-being both during their academic journey and beyond graduation.

Introdução: Apesar dos recentes avanços no tratamento da degenerescência macular da idade (DMI) neovascular (nDMI), a falta de opções terapêuticas para as formas não avançadas (cerca de 90%) e para as formas atróficas avançadas (Corradetti et al., 2021) reforça a necessidade de identificar potenciais biomarcadores como estratégia de saúde pública. (More, Almuhtaseb, Smith, Fraser, & Lotery, 2019) A abordagem multimodal, com o apoio da histologia, tem sido importante na procura de potenciais biomarcadores de AMD. Fatores genéticos têm também sido considerados relevantes, no entanto com apenas 40–60% de correlação com a doença (Fritsche et al., 2014). Por outro lado, a associação com biomarcadores de imagem não invasivos é ainda limitada. Objetivos: Com a crescente importância e impacto da epigenética, o estudo MetAllAMD teve como objetivo caracterizar a expressão génica de modeladores epigenéticos (DNMT1, DNMT2A, DNMT3B) em todos os estádios da DMI e estudar a correlação com os novos biomarcadores de imagem. Material e Métodos: Um total de 14 doentes com DMI, com idades compreendidas entre os 59 e os 90 anos, foram incluídos prospectivamente neste estudo. Os participantes foram classificados em DMI precoce/intermédia (iDMI) e DMI avançada (aDMI). Apenas os casos com um exame oftalmológico completo, fundo de olho digital 133º a cores e avaliações SD-OCT foram incluídos. Através de PCR quantitativo em tempo real (qRT-PCR) procedeu-se à quantificação da transcrição de genes moduladores epigenéticos, nomeadamente, ‎DNA methyltransferases (DNMT1, DNMT2A, DNMT3B) a partir do RNA total dos grupos descriminados. Resultados: Os participantes com aDMI apresentaram uma acuidade visual inferior (p=0,001) ao grupo com iDMI embora sem alterações significativas ao nível da espessura central da retina nem da espessura mínima da fóvea. Na quantificação da transcrição de modeladores epigenéticos verificou-se uma diminuição da DNMT1 (p=0,003), DNMT3A (p=0,004) e DNMT3B (p=0,004) no grupo aDMI. Conclusões: A variação do padrão de expressão de DNA methyltransferases surge alterada nas diferentes fases da DMI podendo constituir um potencial biomarcador a estudar numa das principais causas de cegueira.

Gilthead seabream (Sparus aurata) is an important species in Mediterranean aquaculture. Rapid intensification of its production and sub-optimal husbandry practices can cause stress, impairing overall fish performance and raising issues related to sustainability, animal welfare, and food safety. The advent of next-generation sequencing technologies has greatly revolutionized the study of fish stress biology, allowing a deeper understanding of the molecular stress responses. Here, we characterized for the first time, using RNA-seq, the different hepatic transcriptome responses of gilthead seabream to common aquaculture challenges, namely overcrowding, net handling, and hypoxia, further integrating them with the liver proteome and metabolome responses. After reference-guided transcriptome assembly, annotation, and differential gene expression analysis, 7, 343, and 654 genes were differentially expressed (adjusted p-value < 0.01, log2|fold-change| >1) in the fish from the overcrowding, net handling, and hypoxia challenged groups, respectively. Gene set enrichment analysis (FDR < 0.05) suggested a scenario of challenge-specific responses, that is, net handling induced ribosomal assembly stress, whereas hypoxia induced DNA replication stress in gilthead seabream hepatocytes, consistent with proteomics and metabolomics' results. However, both responses converged upon the downregulation of insulin growth factor signalling and induction of endoplasmic reticulum stress. These results demonstrate the high phenotypic plasticity of this species and its differential responses to distinct challenging environments at the transcriptomic level. Furthermore, it provides significant resources for characterizing and identifying potentially novel genes that are important for gilthead seabream resilience and aquaculture production efficiency with regard to fish welfare.

The demand for efficient and adaptable life support systems in the field of Extracorporeal Life Support (ECLS) is steadily increasing. To meet this growing need, there is a requirement for a versatile extracorporeal life support circuit that can be effectively applied in various medical scenarios, especially in tertiary hospitals where multiple ECLS services are utilized. These services include Extracorporeal Membrane Oxygenation (ECMO) for addressing respiratory or cardiac problems, Ventricular Assist Device (VAD) as a bridge to recovery or heart transplant, and Venovenous Bypass (VVB) for assisting liver transplantation. In light of this, we propose the creation of a multipurpose circuit that integrates multiple extracorporeal life support (ECLS) functions to cater to diverse medical needs. This innovative circuit not only offers cost-effectiveness and enhanced safety but also ensures optimal utilization, thereby revolutionizing the realm of life support technologies.

Abstract Among the most successful Lessepsian invaders is the symbiont-bearing benthic foraminifera Amphistegina lobifera. In its newly conquered habitat, this prolific calcifier and ecosystem engineer is exposed to environmental conditions that exceed the range of its native habitat. To disentangle which processes facilitated the invasion success of A. lobifera into the Mediterranean Sea we analyzed a ~ 1400 bp sequence fragment covering the SSU and ITS gene markers to compare the populations from its native regions and along the invasion gradient. The genetic variability was studied at four levels: intra-genomic, population, regional and geographical. We observed that the invasion is not associated with genetic differentiation, but the invasive populations show a distinct suppression of intra-genomic variability among the multiple copies of the rRNA gene. A reduced genetic diversity compared to the Indopacific is observed already in the Red Sea populations and their high dispersal potential into the Mediterranean appears consistent with a bridgehead effect resulting from the postglacial expansion from the Indian Ocean into the Red Sea. We conclude that the genetic structure of the invasive populations reflects two processes: high dispersal ability of the Red Sea source population pre-adapted to Mediterranean conditions and a likely suppression of sexual reproduction in the invader. This discovery provides a new perspective on the cost of invasion in marine protists: The success of the invasive A. lobifera in the Mediterranean Sea comes at the cost of abandonment of sexual reproduction.

Abstract The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48–71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

OBJECTIVES: To evaluate the outcome of patients with cervical carcinoma submitted to percutaneous nephrostomy due to malignant ureteral obstruction. MATERIAL AND METHODS: Retrospective cohort study with data obtained from medical records of patients diagnosed with cervical carcinoma with renal dysfunction (AKIN = stage 2) undergoing PCN for malignant obstructive uropathy between January 2019 and December 2020 at a tertiary hospital in Recife, Brazil. RESULTS: We evaluated 31 patients submitted to percutaneous nephrostomy. Median age was 50 years, and the majority of women were non-white with an elementary education. Twenty-one patients required hemodialysis before the procedure, and 61.9% of them recovered renal function after nephrostomy. Bleeding and nephrostomytube displacement were the leading causes of complications in the first 30 days (69%). Median overall survival after the procedure was 8.7 months. Survival was significantly worse in patients with anemia, ECOG performance status = 2 (p=0.04), pre-nephrostomy dialysis (p=0.01), and not recovery of renal function after PCN. CONCLUSIONS: Performing urinary diversion through percutaneous nephrostomy seems to offer greater benefits in patients with better functionality. Given the morbidity and complications inherent to percutaneous nephrostomy, the profile of patients who benefit most from the procedureremains unclear. Referrals for the procedure must be individualized and consider the patient's desire, treatment perspectives, and functionality.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

Non-invasive ventilation (NIV) can be used in acute hypoxemic respiratory failure (AHRF); however, verifying the best interface for its use needs to be evaluated in the COVID-19 pandemic scenario. To evaluate the behavior of the PaO2/FiO2 ratio in patients with AHRF with and without COVID-19 undergoing NIV with the conventional orofacial mask and the adapted diving mask. This is a randomized clinical trial in which patients were allocated into four groups: Group 1: COVID-19 + adapted mask (n=12); Group 2: COVID-19 + conventional orofacial mask (n=12); Group 3: non-COVID + adapted mask (n= 2); and Group 4: non-COVID + conventional orofacial mask (n=12]. The PaO2/FiO2 ratio was obtained 1, 24 and 48 h after starting NIV and the success of NIV was evaluated. This study followed the norms of the CONSORT Statement and registered in the Brazilian Registry of Clinical Trials, under registration RBR – 7xmbgsz. Both the adapted diving mask and the conventional orofacial mask increased the PaO2/FiO2 ratio. The interfaces differed in terms of the PaO2/FiO2 ratio in the first hour [309.66 (11.48) and 275.71 (11.48), respectively] (p=0.042) and 48 h [365.81 (16.85) and 308.79 (18.86), respectively] (p=0.021). NIV success was 91.7% in groups 1, 2 and 3, and 83.3% in Group 4. No adverse effects related to interfaces or NIV were observed. NIV through the conventional orofacial mask interfaces and the adapted diving mask was effective in improving the PaO2/FiO2 ratio, however, the adapted mask presented a better PaO2/FiO2 ratio during use. There was no significant difference between interfaces regarding NIV failure.

The use of non-invasive tools in conjunction with artificial intelligence (AI) to detect diseases has the potential to revolutionize healthcare. Near-infrared spectroscopy (NIR) is a technology that can be used to analyze biological samples in a non-invasive manner. This study evaluated the use of NIR spectroscopy in the fingertip to detect neutropenia in solid-tumor oncologic patients. A total of 75 patients were enrolled in the study. Fingertip NIR spectra and complete blood counts were collected from each patient. The NIR spectra were pre-processed using Savitzky–Golay smoothing and outlier detection. The pre-processed data were split into training/validation and test sets using the Kennard–Stone method. A toolbox of supervised machine learning classification algorithms was applied to the training/validation set using a stratified 5-fold cross-validation regimen. The algorithms included linear discriminant analysis (LDA), logistic regression (LR), random forest (RF), multilayer perceptron (MLP), and support vector machines (SVMs). The SVM model performed best in the validation step, with 85% sensitivity, 89% negative predictive value (NPV), and 64% accuracy. The SVM model showed 67% sensitivity, 82% NPV, and 57% accuracy on the test set. These results suggest that NIR spectroscopy in the fingertip, combined with machine learning methods, can be used to detect neutropenia in solid-tumor oncology patients in a non-invasive and timely manner. This approach could help reduce exposure to invasive tests and prevent neutropenic patients from inadvertently undergoing chemotherapy.

Orodispersible films (ODFs) are solid pharmaceutical forms for rapid local or systemic release of active ingredients. They are formed by a water-soluble polymer film that hydrates rapidly, adhering and dissolving immediately when placed on the tongue or in the oral cavity. In this paper, we describe the compatibility and disintegration times of compounded ODFs using OrPhylloTM, a new ready-to-use-vehicle, and APIs from different pharmacological classes, such as 5-hydroxytryptophan (5-HTP) 50 mg, bromopride 5 mg, coenzyme Q10 20 mg, melatonin 3 mg, resveratrol 5 mg, tadalafil 10 mg, vitamin B12 1 mg, or vitamin D3 2000 UI. ODFs were compounded and, subsequently, the samples were assayed using HPLC at initial (t = 0), 7 days (t = 7), 14 days (t = 14), 30 days (t = 30), 60 days (t = 60), 90 days (t = 90), 120 days (t = 120), 150 days (t = 150), and 180 days (t = 180) after compounding. Given the percentage of recovery of the APIs within the films, the beyond-use date of the final products (API + vehicle) was at least 90 days for vitamin D3, 150 days for bromopride and 5-HTP, and 180 days for coenzyme Q10, tadalafil, vitamin B12, resveratrol, and melatonin, when stored at room temperature. The average disintegration time was 46.22 s. This suggests that the OrPhylloTM vehicle is suitable for compounding ODFs with APIs from different pharmacological classes, with good compatibility and fast disintegration.

Abstract Background Carbapenem-resistant Enterobacteriaceae strains have been reported in healthcare facilities with a rising incidence and are a major concern owing to infections that are often severe and can be potentially fatal, with limited therapeutic options. Klebsiella pneumonia represents the most frequently isolated microorganism. Case presentation We report the case of a Caucasian 52-year old Caucasian woman with acute myeloid leukemia was admitted to the inpatient hematology unit at a university referral hospital in Portugal. This hospital has endemic colonization of Carbapenem-resistant Enterobacteriaceae and contention measures are being implemented to reduce spreading of these multidrug resistant bacteria. After receiving first line chemotherapy according to the intermediate-dose cytarabine regimen, in context of deep medullary aplasia, the patient developed a localized infection of the vulva, which progressed to a necrotizing fasciitis. This is a rare, life-threatening, and fulminant infection. Carbapenem-resistant Klebsiella was isolated in both vulvar exudate and blood cultures. The patient underwent multiple schemes of antimicrobials, but progressed with multiorgan compromise and was admitted to the intensive care unit for a short period for stabilization. Surgical debridement was performed twice with clinical improvement and, after 6 weeks, a skin graft was executed with good response. Reevaluation of the hematologic disease showed a complete response to first cycle of induction therapy. Despite success in resolving this complex infection, decisions regarding antibiotic treatment represented a tremendous challenge for the whole team. The importance of multidisciplinary collaboration was key for the patient’s recovery and survival, and therefore, needs to be acknowledged. Conclusions This clinical case raises awareness on a clinical entity that can be life threatening and, therefore, requires a high level of suspicion to assure an early integrated approach to avoid complications. Endemic spreading of carbapenem-resistant Enterobacteriaceae is becoming a reality, and health policies need to be urgently undertaken at the national level to decrease morbidity and mortality because of health facilities-related infections.

Fibular hemimelia is the most frequent congenital defect of the long bones. It has a wide spectrum of clinical and radiological presentations ranging from minor hypoplasia to complete absence of the fibula. Treatment options range between orthotic support, limb reconstruction, and amputation. In the current article, we present a complex clinical case of a young patient with fibular hemimelia. The patient presented a dysmetria of the lower limbs of 21 cm, also an equinovalgus foot position, and several malformations of the foot and toes. She walked with adapted orthosis and crutches, which was proved difficult for her, and esthetically undesirable. Due to the impairment on her quality of life, she was referred initially to bone-lengthening surgery. However, this surgery did not obtain satisfactory results, in both esthetic and functional levels. Hence, the patient was referred to amputation, with a better outcome after. In this clinical case, and reviewing the current literature, we aim to reflect on the implications of the different surgical options in the treatment of fibular hemimelia, and the role of physical medicine and rehabilitation in the functional recovery of these patients. We invite readers to reflect on some questions: Is amputation the best treatment in cases of serious fibular hemimelia? Should a bone-lengthening procedure be attempted before amputation? Should the amputation be delayed? To amputate or not to amputate?

Our objective was to analyze longitudinal cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared to pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection and vaccination timing. PwMS (n = 439) on BCDT (ocrelizumab, rituximab, ofatumumab) or without immunotherapy were recruited for this prospective cohort study between June 2021 and June 2022. SARS-CoV-2 spike-specific antibodies and interferon-γ release of CD4 and CD8 T-cells upon stimulation with spike protein peptide pools were analyzed at different timepoints (after primary vaccination, 3 and 6 months after primary vaccination, after booster vaccination, 3 months after booster). Humoral response to SARS-CoV-2 was consistently lower whereas T-cell response was higher in patients with BCDT compared to controls. Cellular and humoral responses decreased over time after primary vaccination and increased again upon booster vaccination, with significantly higher antibody titers after booster than after primary vaccination in both untreated and B-cell-depleted pwMS. COVID-19 infection further led to a significant increase in SARS-CoV-2-specific responses. Despite attenuated B-cell responses, a third vaccination for patients with BCDT seems recommendable, since at least partial protection can be expected from the strong T-cell response. Moreover, our data show that an assessment of T-cell responses may be helpful in B-cell-depleted patients to evaluate the efficacy of SARS-CoV-2 vaccination.

A prática centrada na pessoa assume um papel preponderante na organização e gestão de sistemas de saúde, bem como na definição de políticas de saúde. Este ensaio teve como objetivo identificar os princípios éticos e estruturas teóricas da prática centrada na pessoa, assim como as diretrizes portuguesas e europeias que sirvam a sua regulamentação. Foi conduzida uma reflexão teórica ancorada na revisão narrativa crítica do estado da arte sobre a prática centrada na pessoa, que visou responder à questão: quais os elementos estruturantes da prática de cuidados centrados na pessoa que a tornam diferenciadora na obtenção de ganhos em saúde? A reflexão crítica contextualiza a mudança de paradigma para a prática centrada na pessoa e identifica os domínios do estado da arte que lhe estão associados: conhecimento filosófico, referenciais teóricos para a prática clínica, ensino e investigação, abordagens para a implementação, e regulamentação. Esses domínios terão de ser necessariamente contemplados para um desenvolvimento e implementação sistemáticos e sustentáveis com efetiva tradução em ganhos em saúde.

Abstract BACKGROUND: Psoriasis is a systemic, immune-mediated disease characterized by inflammatory manifestations in the skin and joints. Vitamin D deficiency is currently considered a pandemic and is associated with comorbidities including psoriasis and psoriatic arthritis (PsA). OBJECTIVES: To determine the prevalence of hypovitaminosis D [25(OH)D] in patients with plaque psoriasis, with and without PsA, and of independent predictors of serum 25(OH)D levels. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, Minas Gerais, Brazil. METHODS: Demographic and clinical data (psoriasis area and severity index [PASI], family history, age at onset, disease duration, and the presence of PsA according to Classification Criteria for Psoriatic Arthritis), skin phototype, and season of the year were reviewed. RESULTS: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in patients with psoriasis with and without PsA (82.2% and 74.9%, respectively). An inverse correlation between PASI and vitamin D was found (without PsA r = –0.59 and, PsA r = –0.52, P < 0.001), and multivariate regression revealed that hypovitaminosis D was associated with disease severity, season, and phototype. It was confirmed by binary logistic regression between PASI and vitamin D deficiency (< 30 ng/mL), (odds ratio, OR 1.78 CI: –0.20–0.53, P < 0.001). CONCLUSION: Hypovitaminosis D (< 30 ng/mL) was highly prevalent in psoriatic patients with and without PsA. Season and skin phototype were associated with 25(OH)D levels. An inverse association between PASI and serum 25(OH)D levels was established.

ABSTRACT BACKGROUND: Hypovitaminosis D is a public health problem associated with several chronic inflammatory and immunological diseases, including psoriasis. OBJECTIVES: This study aimed to determine the prevalence of hypovitaminosis D in patients with plaque psoriasis. A comparison was made between vitamin D levels in patients with psoriasis and those with other non-inflammatory dermatoses without photosensitivity. In addition, it evaluated the effects of the patients’ Fitzpatrick skin phototype and the season of the year on the serum levels of vitamin D. DESIGN AND SETTINGS: A retrospective cross-sectional study was conducted at an outpatient clinic in a university center in Juiz de Fora (MG), Brazil. METHODS: A review of dermatology patients’ demographic data, including skin phototype and serum levels of 25-hydroxyvitamin D [25(OH)D], over 12 months in 2016. RESULTS: This study included 554 patients: 300 patients allocated to the plaque psoriasis group and 254 control patients with other dermatological diseases. Regarding the season of the year, 229, 132, 62, and 131 participants were evaluated in summer, autumn, winter, and spring, respectively. As for the skin phototype, 397, 139, and 18 patients had phototypes III, IV, and V, respectively. The serum levels of 25(OH)D were significantly lower in the psoriasis group (24.91 ± 7.16 ng/mL) than in the control group (30.37 ± 8.14 ng/mL). CONCLUSIONS: Hypovitaminosis D (< 30 ng/mL) was present in 76.66% of patients with psoriasis versus 53.94% of control patients. Vitamin D deficiency (< 20 ng/mL) was observed in 25% of the patients with psoriasis versus 8.66% in the control group (P < 0.001). The season and patient’s skin phototype were independent predictors of serum vitamin D levels.

Ética e investigação constituem-se como dimensões que são cada vez mais interdependentes, pelo que o amplo debate em torno da promoção de uma cultura ética de rigor e de exigente escrutínio corresponde a uma preocupação que é efetivamente transversal a todas as áreas do conhecimento científico. Com este artigo de reflexão teórica pretende-se sinalizar as características e as tendências subjacentes à evolução da regulação ética na investigação científica, mas também proceder a alguns questionamentos críticos em termos das implicações, tensões e desafios que esta realidade comporta. Se, por um lado, se percebe bem a solicitação de formas mais robustas de salvaguarda da integridade científica e da credibilidade da investigação, por outro lado, não deixa também de ser notória a emergência de uma certa tentação do estreitamento da conceção da investigação, no sentido em que o reforço da regulação pode comportar o risco de alguma burocratização e de normalização do escrutínio ético. O desafio para a regulação ética passa por conseguir estabelecer formas de deliberação mais exigentes e melhor adaptadas às novas dinâmicas da investigação científica, mas sem incorrer necessariamente na obstaculização da investigação inovadora ou no estabelecimento de procedimentos de regulação uniformizados que podem, por conseguinte, ser desajustados face à realidade de tradições científicas distintas da investigação clínica e biomédica.

Introduction: The increasing burden of diabetes poses a great challenge to healthcare systems and economy worldwide. Although modern therapeutic strategies for diabetes are widely available, most patients still fail to achieve optimal clinical targets and well-being. The primary objective of this study was to assess and explore potential drivers and successful management of diabetes among people with diabetes, family members and healthcare professionals in Portugal, by applying the protocol of the multinational study “Diabetes, Attitudes, Wishes and Needs (DAWN2)”. Material and Methods: A total of 767 adults, including 417 people with diabetes, 123 family members and 227 healthcare professionals, participated in the study. Surveys assessed health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improvement areas in diabetes care. Results: Diabetes has a negative impact on the physical health and emotional well-being of patients in Portugal and is also a psychological burden for family members. Earlier diagnosis and treatment of diabetes were mentioned as a major area of improvement. Healthcare professionals indicated the need for diabetes self-management education. Conclusion: We have used for the first time in Portugal the DAWN2 protocol to address the wishes, needs, and attitudes of Portuguese diabetes patients, their relatives, and healthcare professionals regarding the disease.

O processo ensino-aprendizagem é estabelecido por um fluxo de informações composto pelos elementos estímulo-resposta-reforço, sendo o feedback uma das principais componentes para que ocorra de maneira eficaz. O feedback extrínseco é a informação emitida por uma fonte externa, que tem como objetivo trazer informações sobre a performance, execução ou resultado de um movimento e/ou tarefa. O nosso objetivo foi compreender a perceção de treinadores de natação do escalão infantil sobre a aplicação do feedback em diferentes contextos. Utilizou-se uma abordagem de investigação qualitativa, de natureza interpretativa e caráter exploratório, tendo participado dez treinadores de natação, selecionados pelo método de amostragem por conveniência. As informações foram obtidas através de entrevista de natureza semiestruturada e os dados foram analisados através de análise temática com técnica indutiva. Em relação ao momento de aplicação do feedback, obteve-se as categorias reuniões pré-treino e reuniões pré-época (com informações acerca do planejamento para o período), durante e/ou logo após o treino (para correções e elogios) e não avaliam o melhor momento por considerarem que a decisão da aplicação é realizada de forma inconsciente. Houve também a perceção negativa em relação a aplicação de feedback logo após uma prova, justificada pelo fato de o nadador ainda se encontrar sob tensão e com pouca atenção para as observações do treinador. Em relação a frequência da aplicação do feedback, os treinadores concordam que deve haver uma adequação de acordo com o nível de performance. Para os treinadores, nadadores mais habilidosos têm maiores condições de assimilação da informação transmitida, podendo receber uma maior quantidade de informações e com maior frequência. Já aqueles que estão iniciando sua trajetória esportiva, devem receber feedbacks mais pontuais, para que sejam capazes de focar e executar. Também foi citado que a menor frequência de aplicação de feedback, permite aos atletas o desenvolvimento de sua autonomia, uma vez que aperfeiçoam sua capacidade de se autoavaliar. Apesar de todos os treinadores citarem ser fundamental a aplicação do feedback, alguns parecem não estabelecer uma organização estruturada para esse momento ou não ter clareza do conceito de feedback, uma vez que ele se refere ao movimento ou tarefa já realizada, não estando relacionada, portanto, às reuniões pré-treino ou pré-época, mas sim, aos momentos ao longo do treino e/ou logo após o término. A não utilização de feedback logo após uma prova vai ao encontro do que a literatura apresenta, assim como o controle da frequência de aplicação do feedback considerando o nível do atleta. Parece ser imprescindível considerar a momento e a quantidade de informações que o atleta conseguirá absorver e interpretar de forma correta, para que de fato seja uma ferramenta qualificada no processo de ensino. A utilização de mídias aumenta as possibilidades de aplicação do feedback, tornando o processo de ensino-aprendizagem ainda mais eficaz.

A universidade tem um papel social extremamente importante quando consegue atingir um equilíbrio entre seus três pilares principais: ensino, pesquisa e extensão. O Grupo de Pesquisa em Ciências dos Esportes Aquáticos (GPCEA) foi idealizado baseado nos pilares de pesquisa e extensão, que são fortemente impulsionados pela Universidade Federal do Rio de Janeiro. No ano de 2021, devido à pandemia do COVID-19, o GPCEA buscou se adequar às medidas restritivas e planejou e promoveu o III Seminário de Ciências dos Esportes Aquáticos (SeCEA) de forma 100% online. Neste contexto, o presente estudo objetivou relatar esta experiência do III SeCEA, a fim de encorajar outras universidades a realizarem mais eventos desta natureza. Foram realizadas reuniões remotas entre os membros do grupo para definição do tema e do conteúdo programático, dos canais de comunicação e divulgação, dos palestrantes, da produção e revisão dos layouts e vídeos, apresentação do material de arte visual, divulgação e período de inscrições. A realização do III SeCEA envolveu 20 alunos do grupo de pesquisa e 12 palestrantes que possuem expertise na área de esportes aquáticos, distribuídos nos dois dias de evento (no mês de maio de 2021). Cada palestrante teve 30 min para sua apresentação com 10 min de intervalo. O alcance total do Seminário foi de 226 pessoas inscritas, com 96 dessas pessoas assistindo a transmissão ao vivo e um total de 1005 visualizações do evento gravado no YouTube nos 30 dias pós-evento. O III SeCEA foi uma forma de desenvolver e pluralizar o conhecimento no âmbito dos esportes aquáticos ao permitir a participação de estudantes e profissionais do mundo todo, por ser realizado de forma online. O evento gravado possibilitou alcançar um número de pessoas que seria inviável se fosse realizado de forma presencial. Dessa forma, encorajamos mais eventos desta natureza.

O processo de formação esportiva de jovens em desenvolvimento apresenta uma natureza não linear. Logo, considerando as variedades de condições existentes, esse processo deve ser pensado em longo prazo. Pensando nisso, entender como um clube de natação competitiva conduz o treinamento em longo prazo de seus nadadores é importante para analisar diversos aspectos que envolvem essa preparação. O nosso objetivo foi investigar se o processo de formação dos nadadores competitivos em clubes da cidade do Rio de Janeiro está de acordo com os fatores biopsicossociais que norteiam o treinamento em longo prazo. Para realização da pesquisa foi elaborado um questionário de característica quali-quantitativa e distribuído para cinco treinadores chefes de natação de clubes do cenário competitivo da cidade do Rio de Janeiro. Estes, por meio da escala Likert, demonstraram o nível de concordância a algumas afirmações acerca do processo de formação competitiva. Dessa maneira, foi traçada a filosofia do clube para a formação de um jovem nadador. Encontrou-se que 20% dos clubes sempre interagem o treinamento da natação como de outros esportes aquáticos, 60% dos clubes sempre flexibilizam o planejamento do treinamento devido à diferença de maturação física entre os atletas, 20% dos clubes sempre flexibilizam o planejamento do treinamento devido às necessidades sociais dos atletas e 20% dos clubes sempre flexibilizam o planejamento do treinamento devido às necessidades emocionais dos atletas. Concluiu-se que os clubes avaliados precisam de alguns ajustes no que se refere à interação entre os esportes aquáticos no período da iniciação esportiva, ao início do treinamento da força muscular e a ampliação do monitoramento e da avaliação para protocolos que mensurem a maturação, o crescimento e o emocional dos jovens atletas, visando atender ao que é prescrito na literatura especializada.

Introduction: The lack of knowledge about the existence, effectiveness, and supply of emergency contraception as well as access to it, its effective duration and the lack of recognition of the need for its use can prevent women from using it. The aim of this study was to ascertain the attitudes, experience, level of knowledge and information sources about emergency contraception of Portuguese female users of healthcare services. Material and Methods: We conducted a multicentre, cross-sectional, observational study among 280 Portuguese women users of health care services through an original and anonymous questionnaire composed of 30 questions. Results: The mean age of the women who replied to the questionnaire was 33.83 ± 8.76 years. Of the observed sample, 27.7% used EC, 50% of whom with no counselling. Despite 92.1% of women claiming knowledge about emergency contraception, only 31.2% of these answered 8 - 10 questions correctly (14 in total). The media were the most frequent source of information (63.4%). Most participants (67.5%) considered that emergency contraception is associated with severe adverse reactions. Furthermore, 76% did not know the time range of effectiveness after unprotected sexual intercourse. Youngest age (p = 0.038), higher education level (p < 0.001), increasing parity (p = 0.051) and previous use of emergency contraception (p = 0.011) were identified as the determinant sociodemographic factors for a higher level of knowledge about emergency contraception. Discussion: The use of emergency contraception after counselling by healthcare professionals was lower than reported in the literature. Conclusion: This study showed that female users of healthcare services were aware of the existence of emergency contraception, but they demonstrated a low level of knowledge about it, especially regarding the correct period of use, place of acquisition and safety issues.

Errorful learning suggests that, when perfect learning has not yet been attained, errors can enhance future learning if followed by corrective feedback. Research on memory updating has shown that after retrieval, memory becomes more malleable and prone to change. Thus, retrieval of a wrong answer might provide a good context for the incorporation of feedback. Here, we tested this hypothesis using sentences including pragmatic sentence implications, commonly used for the study of false memories. Across two experiments with young adults, we hypothesized that corrective feedback would be more efficient at reducing false memories if provided immediately after retrieval, when memory is more malleable than after being exposed to the material. Participants' memory was assessed as a function of the type of learning task (Experiment 1: retrieval vs. restudy; and Experiment 2: active vs. passive recognition); and whether participants received corrective feedback or not. In both experiments, we observed that retrieval not only improved correct recall (replicating the testing effect) but also promoted the correction of false memories. Notably, corrective feedback was more effective when given after errors that were committed during retrieval rather than after restudy (Experiment 1) or after passive recognition (Experiment 2). Our results suggest that the benefits of retrieval go beyond the testing effect since it also facilitates false memories correction. Retrieval seems to enhance memory malleability, thus improving the incorporation of feedback, compared to the mere presentation of the information. Our results support the use of learning strategies that engage in active and explicit retrieval because, even if the retrieved information is wrong-when immediate feedback is provided-memory updating is promoted and errors are more likely to be corrected.

Litsea glutinosa (Lour.) C. B. Robinson, belonging to the family Lauraceae, is a multipurpose and fast-growing evergreen or deciduous tree that has been traditionally used for numerous purposes such as treatment for diarrhea, dysentery, abdominal pain, indigestion, gastroenteritis, edema, traumatic injuries, colds, arthritis, asthma, diabetes, pain relief, and poignant sexual power. This study aimed to summarize the chemical reports, folk values, and phytopharmacological activities of L. glutinosa, based on available information screened from diverse databases. An up-to-date electronic-based search was accomplished to obtain detailed information, with the help of several databases such as Google Scholar, Scopus, SpringerLink, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, Elsevier, BioMed Central, and the USPTO, CIPO, INPI, Google Patents, and Espacenet, using relevant keywords. Outcomes advocate that, up to the present time, alkaloids, glycosides, and terpenoids are abundant in, and the most bioactive constituents of, this natural plant. Results demonstrated that L. glutinosa has various remarkable biological activities, including antioxidant, anti-inflammatory, anti-microbial, anticancer, antipyretic, anti-diabetic, analgesic, hepatoprotective, and wound-healing activity. One study revealed that L. glutinosa exhibited significant aphrodisiac and anti-infertility activity. Nevertheless, no clinical studies have been cited. Taken together, L. glutinosa may be one of the significant sources of bioactive constituents that could potentially lead to different effective pharmacological activities. On the other hand, future research should focus on clinical studies and several toxicity evaluations, such as sub-chronic toxicity, teratogenicity, and genotoxicity.

Enquadramento: As vivências pessoais e em ensino clínico influenciam o modo como os estudantes de enfermagem lidam com a morte. Objetivo: Avaliar as atitudes dos estudantes de enfermagem perante a morte e os cuidados em fim de vida. Metodologia: Estudo descritivo. Os dados foram recolhidos através de um questionário online. Participaram 158 estudantes do curso de licenciatura em Enfermagem. Os dados quantitativos foram analisados com recurso ao programa IBM SPSS Statistics. Foram realizadas análises estatísticas descritivas e exploratórias dos dados através de testes paramétricos e não paramétricos. Resultados: Os estudantes evidenciam maior proximidade com atitudes de neutralidade, medo e aproximação perante a morte e menos proximidade com atitudes de evitamento e escape. Relativamente aos cuidados em fim de vida, os estudantes que já realizaram ensino clínico apresentam atitudes positivas. Conclusão: É importante utilizar metodologias de ensino/aprendizagem que permitam ao estudante expor as suas experiências com a morte e com os cuidados em fim de vida em ensino clínico.

We are looking for playful and effective methodologies for transversal insertion of legal knowledge in high school. It is inquired about how best to conduct the activities in order to assess the feasibility and benefits of transversality or the creation of legal disciplines in the curriculum. Faced with the problem, the legal and pedagogical feasibility of the proposal and its positive consequences are confirmed. The approach through dynamics and interesting discussions facilitates the understanding of the school content under a new perspective that mixes and harmonizes the knowledge so that the learning in the classroom is optimized. It should be emphasized that the discussion of legal issues should be included among the compulsory contents of High School, since it is not only a factor of social inclusion, but also of promoting citizenship.

High altitudes are linked to decreased rates of pulmonary tuberculosis infection, disease and mortality. However, its relevance as a trigger for pulmonary tuberculosis reactivation in immunocompetent patients is not documented. A 28-year-old healthy Nepalese female was admitted in the emergency department with sudden left pleuritic back pain with shortness of breath, two weeks after arriving in Lisbon, having arrived from Kathmandu and undergone a change in altitude of 1400 metres. She also had evening low-grade fever and fatigue since she arrived. Her mother-in-law had died of tuberculosis two years before. Chest radiography and computed tomography scan showed a left upper lobe consolidation. Laboratory analyses were 79 mm/sec. Human immunodeficiency virus serology, blood cultures and urinary antigen testing were negative. Bronchial secretions’ cultures became positive for Mycobacterium tuberculosis complex. The patient was started on anti-tuberculous treatment and made a steady recovery. This case reports a probable reactivation of pulmonary tuberculosis infection that could have been triggered by altitude differences.

Objetivo: Analisar a concepção de velhice dos profissionais de saúde que atuam no ambiente hospitalar. Método: Trata-se de um estudo exploratório descritivo, de abordagem qualitativa, realizado em uma Unidade de Clinica Médica de um Hospital Universitário no Município de Vitória, Espírito Santo. Participaram 22 profissionais de saúde: enfermeiros, médicos, médicos residentes e assistentes sociais. Os dados foram coletados no período de março a abril de 2013, por meio de um questionário e analisados pela técnica de análise de conteúdo proposta por Bardin. Resultados: A análise desses permitiu a construção de quatro categorias: Velhice nas dimensões: biológica; cronológica; psicológica e social. Conclusão: Constatou-se que a concepção de velhice dos profissionais de saúde independe da idade cronológica sendo norteada por fatores como dependência, capacidade funcional e de como o idoso vê a sua condição de velhice.

Introduction Recent randomised clinical trials showed benefit of non-culprit lesion revascularisation in ST-elevation myocardial infarction (STEMI) patients. However, it remains unclear whether revascularisation should be performed at the index procedure or at a later stage.Methods and analysis The instantaneous wave-free ratio (iFR) Guided Multivessel Revascularisation During Percutaneous Coronary Intervention for Acute Myocardial Infarction trial is a multicentre, randomised controlled prospective open-label trial with blinded evaluation of endpoints. After successful primary percutaneous coronary intervention (PCI), eligible STEMI patients with residual non-culprit lesions are randomised, to instantaneous wave-free ratio guided treatment of non-culprit lesions during the index procedure versus deferred cardiac MR-guided management within 4 days to 6 weeks. The primary endpoint of the study is the combined occurrence of all-cause death, recurrent myocardial infarction and hospitalisation for heart failure at 12 months follow-up. Clinical follow-up includes questionnaires at 3 months and outpatient visits at 6 months and 12 months after primary PCI. Furthermore, a cost-effectiveness analysis will be performed.Ethics and dissemination Permission to conduct this trial has been granted by the Medical Ethical Committee of the Amsterdam University Medical Centres (loc. VUmc, ID NL60107.029.16). The primary results of this trial will be shared in a main article and subgroup analyses or spin-off studies will be shared in secondary papers.Trial registration number NCT03298659.

We present the case of a 70-year-old woman with emphysematous cys- titis. She was a diabetic patient and she was on chemotherapy treatment for a breast cancer. She complaint of severe asthenia and pain in her right lower extremity, but no fever or urinary symptoms. A computed tomography (CT) scan was suggestive of severe emphysematous cystitis. Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients. A conservative treatment approach using antibiotics and bladder catheterization is typically suc- cessful, with a complication rate less than 20%.

Introduction: Kikuchi-Fujimoto disease (KFD) is a rare, benign, necrotizing lymphadenitis of unknown aetiology with good prognosis. It is characterized by cervical lymphadenopathy, nocturnal diaphoresis and fever. Surgical excision of the adenopathy, histopathological study and immunophenotyping are crucial for diagnosis. Patients and methods: This paper describes five patients with three different histological subtypes of KFD, including an atypical presentation masquerading as pyelonephritis and two other cases where physicians mistakenly started chemotherapy. In one other case cytomegalovirus was identified as the responsible aetiological agent, while in the remaining patient, KFD evolved into an autoimmune condition. Discussion: KFD, although rare, may mimic infectious, autoimmune and neoplastic diseases. It also poses a risk for the subsequent development of an autoimmune disorder.

La distribución municipal de cánceres de pulmón y de mama en Huelva tiene ciertos patrones. Nuestro objetivo es contrastar la distribución de estos cánceres con dos distritos portugueses que limitan con Huelva: Algarve y Baixo Alentejo. Se incluyeron los casos de muertes por cáncer de pulmón (C33-C34) y cáncer de mama (C50) de residentes de la provincia de Huelva y los distritos de Algarve y Baixo Alentejo durante los años 2002 a 2015. El número de muertes y la población se tomaron de los Institutos Nacionales de Estadística de España y Portugal. La unidad de análisis es el municipio y los riesgos relativos (RR) o las tasas de mortalidad estandarizadas suavizadas se calcularon de acuerdo con el modelo de "convolution prior", propuesto por Besag, York y Mollié, el más utilizado y que incluye como efectos aleatorios la heterogeneidad espacial y la extra-variabilidad no espacial. En el cáncer de pulmón, los RR oscilan entre 0,57 y 1,42, concentrando los valores más altos en la provincia de Huelva. Sin embargo, en el cáncer de mama, no hay grandes diferencias en los RR, que oscilan entre 0,92 y 1,12. Las diferencias y similitudes encontradas en el RR de las áreas estudiadas pueden relacionarse con las diferencias existentes en las poblaciones de factores de protección y de riesgo. Sería necesario profundizar la investigación fronteriza sobre la incidencia del cáncer y la distribución de los factores de riesgo en la población.

Enquadramento: O sofrimento nos enfermeiros advém da prestação de cuidados ao doente em sofrimento e de fatores relacionados com as condições de trabalho. É uma experiência multidimensional que ocorre em situações de perda, dano ou ameaça à integridade da pessoa. Objetivo: Comparar as médias das dimensões do sofrimento (Dor Emocional, Perda Relacional e Evitamento) em função das variáveis sociodemográficas e profissionais dos enfermeiros. Metodologia: Estudo descritivo e transversal de natureza quantitativa. Amostra constituída por 100 enfermeiros. Foi aplicado um questionário de autopreenchimento e para avaliação do sofrimento a Caregiver Grief Scale. Resultados: O sexo feminino com filhos, com companheiro, sem especialização em enfermagem e com mais tempo de serviço apresentou médias mais elevadas de sofrimento. No sexo masculino, as médias mais elevadas verificaram-se nos enfermeiros sem filhos, sem companheiro, com especialização em enfermagem e com mais tempo de serviço. Conclusão: Os enfermeiros apresentaram médias mais elevadas de sofrimento na dimensão Dor Emocional, seguida da Perda Relacional e do Evitamento, sendo maior a expressão do sofrimento no sexo feminino.

Ovarian borderline serous tumors present with peritoneal involvement in 20% of cases, either as non-invasive or invasive implants, the latter also known as extraovarian low-grade serous carcinoma. The coexistence of high-grade serous carcinoma is rare, suggesting a synchronous neoplasia with a distinct and independent tumor biology and behavior. We aim to describe a case of a synchronous ovary-peritoneum neoplasia: serous borderline tumor and primary peritoneal high-grade serous carcinoma. A discussion and literature review concerning the optimal diagnostic and therapeutic approach is provided.

Equitable and efficient distribution of COVID-19 vaccines continues to be a key issue in global health, and a targeted approach is needed to meet the World Health Organization’s world vaccination targets. Although some low- and middle-income countries (LMICs) are developing their own vaccines to address the distribution problem, legal and technical challenges have had a negative impact on productivity. This article explores relevant international legal instruments that can enable faster research and development of COVID-19 vaccines in LMICs, focusing on the role of biosafety standards, biological materials transfer, and key knowledge sharing. Our analysis has established that the potential of existing global health legal instruments has yet to be realized in order to close the productivity gap in LMICs and strengthen their vaccine manufacturing capacity. Additionally, mutual recognition of vaccine efficacy has become a new challenge for achieving global vaccination targets. We argue that the World Health Organization should continue its leading position by developing a more practical and targeted framework to help LMICs overcome challenges arising from technology transfer, knowledge sharing, and politics.

Schwannomas of the female genital tract are extremely uncommon. They are usually benign, and simple excision is the adequate treatment. The case of a 57-year-old woman with a cellular schwannoma of the vagina is described, in addition to a summarized literature review of schwannomas in the female genital tract. Complete excision was performed, and the histological report confirmed to be a vaginal schwannoma. Due to its possibility to occur, even if in a very low incidence scenario, schwannomas should not be excluded from the differential diagnosis of a vaginal mass.

Among the main complications associated with obesity are insulin resistance and altered glucose and lipid metabolism within the liver. It has previously been described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes compared with isoform B (IRB), improving glucose homeostasis in mice lacking liver insulin receptor. Thus, we hypothesized that IRA could also improve glucose and lipid metabolism in a mouse model of high-fat-diet-induced obesity. We addressed the role of insulin receptor isoforms in glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAVs) in a mouse model of diet-induced insulin resistance and obesity. IRA, but not IRB, expression induced increased glucose uptake in the liver and muscle, improving insulin tolerance. Regarding lipid metabolism, we found that AAV-mediated IRA expression also ameliorated hepatic steatosis by decreasing the expression of Fasn, Pgc1a, Acaca and Dgat2 and increasing Scd-1 expression. Taken together, our results further unravel the role of insulin receptor isoforms in hepatic glucose and lipid metabolism in an insulin-resistant scenario. Our data strongly suggest that IRA is more efficient than IRB at favoring hepatic glucose uptake, improving insulin tolerance and ameliorating hepatic steatosis. Therefore, we conclude that a gene therapy approach for hepatic IRA expression could be a safe and promising tool for the regulation of hepatic glucose consumption and lipid metabolism, two key processes in the development of non-alcoholic fatty liver disease associated with obesity. This article has an associated First Person interview with the first author of the paper.

Introduction: There is a paucity of information regarding chronic urticaria patients’ care in a real-world setting. The objective of this study was to report and evaluate the baseline characteristics of Portuguese chronic urticaria patients refractory to H1-antihistamines included in the AWARE study. Material and Methods: This is a non-interventional cohort study. Adult patients with a diagnosis of chronic urticaria with symptoms for at least two months, refractory to H1-antihistamines, consulting one of the 10 participating urticaria centers throughout Portugal have been included in the study. Baseline sociodemographic data, medical history, clinical parameters, medication, weekly urticaria activity score, and dermatology quality of life index have been collected. Results: Seventy six patients were included, of which 76.3% were women. The majority of patients had a diagnosis of chronic spontaneous urticaria (88.2%) and 39.5% had angioedema. Around 91.0% of patients were medicated with non-sedative H1-antihistamines and 35.4% with a third line therapy. Median dermatology quality of life index was 5.0 and median weekly urticaria activity score was 13.0. Discussion: The baseline results suggest that patients with chronic urticaria refractory to H1-antihistamines are being under-treated in the real-world setting. Conclusion: The AWARE study demonstrates the real impact of chronic urticaria on Portuguese patients refractory to H1-antihistamines treatment, and 30% report a very large or extremely large deleterious effect on their quality of life. The follow-up of these patients will allow evaluating strategies aimed at optimizing disease control.