Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A.

INTRODUCTION: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control. Therefore, the comparative effectiveness of valoctocogene roxaparvovec vs FVIII prophylaxis was evaluated using propensity scoring (PS). METHODS: This post hoc analysis compared 112 participants from GENEr8-1 (treated cohort) to 73 participants in 270-902 who did not enroll in GENEr8-1 (control cohort). The primary analysis used standardized mortality ratio weighting to re-weight baseline characteristics of the control cohort to better match the treated cohort. Mean annualized bleeding rates (ABR) for treated and all bleeds were compared between cohorts along with the proportion of participants with zero bleeds (treated and all bleeds). Sensitivity and scenario analyses were also conducted. RESULTS: PS adjustments reduced differences in baseline characteristics between cohorts. Mean treated (4.40 vs 0.85; P < 0.001) and all (5.01 vs 1.54; P < 0.001) ABR were significantly lower, and the proportions of participants with zero treated bleeds (82.1% vs 32.9%; P < 0.001) and all bleeds (58.0% vs 28.5%; P < 0.001) were significantly higher in GENEr8-1. CONCLUSIONS: PS-adjusted analyses were consistent with prior intra-individual comparisons. Compared with participants receiving prophylactic FVIII, the participants receiving valoctocogene roxaparvovec experienced lower ABR, and a higher proportion had zero bleeds. TRAIL REGISTRATION: ClinicalTrials.gov identifier, NCT03370913.

Hemophilia A is a bleeding disorder where blood is unable to clot properly because of a missing protein called factor VIII (FVIII). Individuals with hemophilia A have an increased risk of prolonged bleeding episodes that can be deadly. To prevent bleeding, people with severe hemophilia A need to routinely inject treatment into the skin or vein (prophylaxis). While effective, some people find the time and effort needed to maintain frequent injections difficult, since some forms of the prophylaxis must be administered in a hospital setting. Valoctocogene roxaparvovec is a gene therapy where a single injection provides instructions to the liver of individuals with hemophilia A to make the missing protein (FVIII). Then, their own liver cells can produce FVIII protein and prevent bleeding episodes. The valoctocogene roxaparvovec clinical trial compared the number of treated bleeding episodes participants had prior to gene therapy, while using prophylaxis, with the number of treated bleeding episodes after gene therapy. On average, after gene therapy, participants had 4.1 fewer treated bleeding episodes per year. In this study, mathematical models were used to explore how differences in participant's physical characteristics, such as body weight or medical history, might influence the effectiveness of gene therapy. Even when considering differences in the participants' physical characteristics, the gene therapy reduced treated bleeding episodes by 3.6 events per year. This study confirms results originally presented from the valoctocogene roxaparvovec clinical trial and reinforces confidence in the ability of valoctocogene roxaparvovec to reduce bleeding outcomes for participants with hemophilia A.

Adrenalectomy attenuates hyperalgesia but does not regulate muscle wasting in a female rat model of fibromyalgia.

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.

CHEK2 germline variants identified in familial nonmedullary thyroid cancer lead to impaired protein structure and function.

Approximately 5 to 15% of nonmedullary thyroid cancers (NMTC) present in a familial form (familial nonmedullary thyroid cancers [FNMTC]). The genetic basis of FNMTC remains largely unknown, representing a limitation for diagnostic and clinical management. Recently, germline mutations in DNA repair-related genes have been described in cases with thyroid cancer (TC), suggesting a role in FNMTC etiology. Here, two FNMTC families were studied, each with two members affected with TC. Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing, revealing two germline CHEK2 missense variants (c.962A > C, p.E321A and c.470T > C, p.I157T), which segregated with TC in each FNMTC family. p.E321A, located in the CHK2 protein kinase domain, is a rare variant, previously unreported in the literature. Conversely, p.I157T, located in CHK2 forkhead-associated domain, has been extensively described, having conflicting interpretations of pathogenicity. CHK2 proteins (WT and variants) were characterized using biophysical methods, molecular dynamics simulations, and immunohistochemistry. Overall, biophysical characterization of these CHK2 variants showed that they have compromised structural and conformational stability and impaired kinase activity, compared to the WT protein. CHK2 appears to aggregate into amyloid-like fibrils in vitro, which opens future perspectives toward positioning CHK2 in cancer pathophysiology. CHK2 variants exhibited higher propensity for this conformational change, also displaying higher expression in thyroid tumors. The present findings support the utility of complementary biophysical and in silico approaches toward understanding the impact of genetic variants in protein structure and function, improving the current knowledge on CHEK2 variants' role in FNMTC genetic basis, with prospective clinical translation.

Carbapenem-producing Enterobacteriaceae in mothers and newborns in southeast Gabon, 2022.

Introduction: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) pose a significant threat, leading to severe morbidity and mortality among newborns. Methods: This study, conducted at Franceville hospital's maternity and neonatology wards from February 22nd to June 20th, 2022, investigated the prevalence of CPE in 197 parturients and 203 newborns. Rectal swabs were taken from parturients before delivery and from newborns 30 minutes after birth. Blood culture samples were collected if signs of infection were observed in newborns during a 28-day follow-up. A total of 152 environmental samples were obtained, comprising 18 from sinks, 14 from incubators, 27 from cradles, 39 from maternal beds, 14 from tables and desks, four from the two baby scales and 36 from bedside furniture. Results: None of the 203 newborns were found to be CPE carriers 30 minutes after delivery. CPE carriage was found in 4.6% of mothers. When comparing colonized and uncolonized parturients, well-established risk factors for CPE carriage, such as recent hospitalization and antibiotic therapy, were more frequently observed among CPE carriers (33.3 vs 10.6% for hospitalization in the past 15 days; 55.5 vs 30.3% for hospitalization during pregnancy, and 55.5 vs 35.1% for antibiotic therapy during pregnancy). Notably, the prevalence of treatment with amoxicillin and clavulanic acid was 44.4% in CPE carriers compared to 17.0% in non-carriers. The incidence density of CPE-associated bloodstream infection was 0.49 per 100 newborns, accounting for a fatal case of CPE-associated bacteremia identified in one of the 203 newborns. Seven environmental samples returned positive for CPE (5 sinks and two pieces of furniture). Whole genome sequencing, performed on the 25 CPE isolates, revealed isolates carrying blaNDM-7 (n=10), blaNDM-5 (n=3), blaOXA181 (n=10), blaOXA48 (n=2) or blaOXA244 (n=1), along with genetic traits associated with the ability to cause severe and difficult-to-treat infections in newborns. Core genome comparison revealed nine CPE belonging to three international high-risk clones: E. coli ST410 (four mothers and a sink), two E. coli ST167 (a mother and a piece of furniture), and K. pneumoniae ST307 (a sink and a piece of furniture), with highly similar genetic backgrounds shared by maternal and environmental isolates, suggesting maternal contamination originating from the environment. Discussion: Our study reveals key findings may guide the implementation of infection control measures to prevent nosocomial infections in newborns: the prevalence of CPE carriage in one out of 20 parturients, an infection occurring in one out of 400 newborns, substantial contamination of the care environment, clinical and environmental CPE isolates possessing genetic traits associated with the ability to cause severe and challenging infections, and clonal relationships between clinical and environmental isolates suggesting CPE spread within the wards, likely contributing to the acquisition and colonization of CPE by parturients during pregnancy.

Prevalência e Fatores de risco associados ao tabagismo e outras formas de consumo de tabaco em acadêmicos da saúde em Goiânia, Goiás / Prevalence and risk factors associated with smoking and other forms of tobacco consumption among health students in Goiânia, Goiás

Introdução: O presente estudo teve como objetivo investigar e identificar a prevalência e fatores de risco associados ao tabagismo e outras formas de consumo de tabaco entre acadêmicos da saúde. Métodos: A pesquisa contou com 407 acadêmicos dos cursos de Biomedicina, Educação Física, Enfermagem, Farmácia, Fisioterapia e Nutrição de uma Instituição de Ensino Superior. A coleta de dados foi realizada no mês de maio de 2020, por um formulário eletrônico, disponibilizado em e-mail institucional, grupos de estudos e redes sociais. O procedimento ocorreu após aprovação pelo Comitê de Ética, cujo parecer 3.966.951. Resultados: A maioria dos participantes (79,6%) eram do sexo feminino, solteiros (75,2%) com idade média de 25,32 anos. O consumo de tabaco foi confirmado por 10,8% participantes. Quanto ao consumo de produtos derivados de tabaco 24,1% dos entrevistados já consumiram produto de tabaco, 8,6% assumiram tabagismo ocasional, e 4,2% tabagismo ativo. Conclusões: A associação entre tabagismo e as variáveis sociodemográficas demonstrou que alunos do curso de Farmácia (OR: 5,25 [IC:1,34-20,22] p=0,017), homens (OR: 1,71 [IC: 1,01 ­ 2,91]), estudantes turno matutino (OR: 1,96 [IC:1,02-3,78] p=0,04) e que residem com tabagistas (OR:4,44 [IC: 2,24-8,80]) apresentaram maiores chances de serem tabagista. A associação em relação ao consumo de derivados do tabaco, os homens apresentaram maiores prevalências de consumo de derivados de tabaco (OR: 1,71 [IC: 1,01 ­ 2,91] p=0,045) bem como, alunos do curso de Farmácia (OR: 6,40 [IC:2,31-17,7] P<0,01), que estudam no turno Noturno (OR:1,85 [IC:1,16-8,82] p=0,009) e entre os que residem com tabagistas (OR: 4,49 [IC:2,24-8,80] p<0,001).

Introduction: The present study aimed to investigate and identify the prevalence and risk factors associated with smoking and other forms of tobacco consumption among health academics. Methods: The survey involved 407 students from Biomedicine, Physical Education, Nursing, Pharmacy, Physiotherapy and Nutrition courses at a Higher Education Institution. Data collection was carried out in May 2020, through an electronic form, available in institutional email, study groups and social networks. The entire procedure took place after approval by the Ethics Committee. Results: Most participants (79.6%) were female, single (75.2%) with a mean age of 25.32 years. Tobacco consumption was confirmed by 10.8% of the participants. As for the consumption of tobacco products, 24.1% of the interviewees had already consumed some tobacco product, 8.6% assumed occasional smoking, and 4.2% active smoking. Conclusions: The association between smoking and sociodemographic variables showed that Pharmacy students (OR: 5.25 [CI:1.34-20.22] p=0.017), men (OR: 1.71 [CI: 1.01 ­ 2.91]), morning shift students (OR: 1.96 [CI:1.02-3.78] p=0.04) and those who live with smokers (OR:4.44 [CI : 2.24-8.80]) were more likely to be smokers. The association in relation to the consumption of tobacco derivatives, men had a higher prevalence of consumption of tobacco derivatives (OR: 1.71 [CI: 1.01 ­ 2.91] p=0.045) as well as Pharmacy students (OR: 6.40 [CI:2.31-17.7] P<0.01), those who study the night shift (OR:1.85 [CI:1.16-8.82] p=0.009 ) and among those who live with smokers (OR: 4.49 [CI:2.24-8.80] p<0.001).

Association between Socioeconomic Factors, Food Insecurity, and Dietary Patterns of Adolescents: A Latent Class Analysis.

Socioeconomic factors and food insecurity play a fundamental role in the food choices of adolescents, and in addition to influencing access to food, they also have significant effects on dietary patterns. The objectives of this study were to identify the dietary patterns of adolescents through the application of latent class analysis and to evaluate their association with socioeconomic variables and food insecurity. This cross-sectional study was conducted with adolescents aged between 11 and 17 years from public schools. Latent class analysis was used to identify the dietary patterns. Associations between socioeconomic factors, food insecurity and dietary patterns were assessed using multinomial logistic regression (odds ratio (OR); 95% confidence interval (CI)). Among the 1215 participants in the study, four dietary patterns were identified: "Mixed", "Low consumption", "Prudent" and "Diverse". A "Diverse" dietary pattern was associated with a lower economic stratum (OR:2.02; CI:1.26-3.24). There was no association between food insecurity and identified dietary patterns. These results highlight the importance of promoting healthy eating in this age group at all socioeconomic levels, especially the lowest level.

Extract2Chip-Bypassing Protein Purification in Drug Discovery Using Surface Plasmon Resonance.

Modern drug discovery relies on combinatorial screening campaigns to find drug molecules targeting specific disease-associated proteins. The success of such campaigns often relies on functional and structural information of the selected therapeutic target, only achievable once its purification is mastered. With the aim of bypassing the protein purification process to gain insights on the druggability, ligand binding, and/or characterization of protein-protein interactions, herein, we describe the Extract2Chip method. This approach builds on the immobilization of site-specific biotinylated proteins of interest, directly from cellular extracts, on avidin-coated sensor chips to allow for the characterization of molecular interactions via surface plasmon resonance (SPR). The developed method was initially validated using Cyclophilin D (CypD) and subsequently applied to other drug discovery projects in which the targets of interest were difficult to express, purify, and crystallize. Extract2Chip was successfully applied to the characterization of Yes-associated protein (YAP): Transcriptional enhancer factor TEF (TEAD1) protein-protein interaction inhibitors, in the validation of a ternary complex assembly composed of Dyskerin pseudouridine synthase 1 (DKC1) and RuvBL1/RuvBL2, and in the establishment of a fast-screening platform to select the most suitable NUAK family SNF1-like kinase 2 (NUAK2) surrogate for binding and structural studies. The described method paves the way for a potential revival of the many drug discovery campaigns that have failed to deliver due to the lack of suitable and sufficient protein supply.

Impact of a training strategy on improving compliance of hand hygiene and gloving during the placement of a short peripheral venous catheter: the multicentre study CleanHand4.

BACKGROUND: Patients who have short peripheral venous catheters (PVC) face an elevated risk of developing bloodstream infections. Preventing catheter-related infections relies on implementing multiple measures, including practicing proper hand hygiene (HH) during catheter placement. METHODS: We conducted a four-part study: (1) an evaluation of HH practices through direct observation of PVC placements, coupled with the study of the microbial flora of the HCWs fingers just before the placement; (2) the development of an educational tool based on the collected observational and microbiological data; (3) the training to the HCWs observed during the first part, using this tool; and (4) the subsequent observation of the trained HCWs to measure the impact of the training on practice improvement. RESULTS: Compliant HH was observed in 23.5% of the 647 HCWs observed during PVC placement before training. The microbiological study revealed fewer pathogens on the fingertips of the HCWs practicing compliant HH compared other HCWs (2.6 vs 11,7%; p = 0.003). The comparison of practices before and after training, assessed among 180 HCWs, showed an increase in the proportion of HCWs performing compliant HH (25.0 vs 63.2%; p < 0.001). CONCLUSIONS: Training HCWs using our educational tool, which combines reminders of best practices and risk factors associated with PVC-related infections, engaging HCWs (presentation of practice evaluation), identifying professionals deviating from best practices (simulation videos), and objectively assessing fingertip contamination (microbiological study), significantly improved compliance with HH gestures and glove usage. We encourage infection control teams to utilize this tool to raise awareness among HCWs responsible for PVC placement about the risk of infection associated inadequate hand hygiene.

Academic trajectory of Prof. Ana Marlúcia Oliveira: contributions to the field of food and nutrition in Brazil. / Trajetória acadêmica da Profa. Ana Marlúcia Oliveira: contribuições para o campo da alimentação e nutrição no Brasil.

It will be presented the main academic contributions of Professor Ana Marlúcia Oliveira (AMO) (in memoriam), nutritionist, professor at the School of Nutrition at the Federal University of Bahia, Ph.D. in epidemiology and CNPQ Researcher level A, from 1980 to 2021. Professor Ana accumulated, throughout her academic career, scientific articles published in national and international journals; book and book chapters authored by her; papers presented at scientific events, in addition to guiding scientific projects, dissertations and theses. She has coordinated several research projects in the field of food and nutrition in public health, with a focus on nutritional epidemiology. The scope of the subjects addressed in her scientific production expressed the concern that mobilized her around the production of knowledge to face the complex health and nutrition problems in Brazil. Her way of being in the world, welcoming and caring for people who approached her seeking qualification opportunities, her example, words and teachings influenced, and still influence, the trajectory and training of nutritionists, professors and researchers at ENUFBA and other national and international institutions. She was a Brazilian researcher and intellectual committed to the health of the most vulnerable populations and the fight against malnutrition and hunger in our country. Her wide and fruitful work left us a legacy to be remembered and continued. Some of her friends, colleagues and collaborators pay this tribute to her memory, to her example and to the legacy she left for all of us and future generations.

São apresentadas neste artigo as principais contribuições acadêmicas da Profa. Marlúcia Oliveira (AMO) (in memoriam), nutricionista, docente da Escola de Nutrição da Universidade Federal da Bahia, Doutora em Epidemiologia e Pesquisadora A do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ), no período de 1980 a 2021. A Profa. Ana acumulou, ao longo de sua carreira acadêmica, artigos científicos publicados em periódicos nacionais e internacionais; livro e capítulos de livro de sua autoria; trabalhos apresentados em eventos científicos, além de ter orientado projetos de iniciação científica, dissertações e teses. Coordenou vários projetos de pesquisa no campo da alimentação e nutrição em saúde coletiva, com foco na epidemiologia nutricional. O escopo dos assuntos abordados na sua produção científica expressou a inquietude que a mobilizava em torno da produção de conhecimentos para o enfrentamento dos complexos problemas de saúde e nutrição do Brasil. Sua forma de ser no mundo, acolhendo e cuidando das pessoas que se aproximavam em busca de oportunidades de qualificação, seu exemplo, suas palavras e ensinamentos influenciaram, e ainda influenciam, a trajetória e a formação de nutricionistas e de professores e pesquisadores na Escola de Nutrição da Universidade Federal da Bahia (ENUFBA) e em outras instituições nacionais e internacionais. Trata-se de uma pesquisadora e intelectual brasileira comprometida com a saúde das populações mais vulneráveis e com o combate contra a desnutrição e a fome no nosso país. Sua vasta e fecunda obra nos deixou um legado a ser lembrado e continuado. Alguns dos seus amigos, colegas e colaboradores prestam este tributo à sua memória e ao legado que ela deixou para todos nós e para as próximas gerações.

Non-canonical Ca2+- Akt signaling pathway mediates the antiproteolytic effects induced by oxytocin receptor stimulation in skeletal muscle.

Although it has been previously demonstrated that oxytocin (OXT) receptor stimulation can control skeletal muscle mass in vivo, the intracellular mechanisms that mediate this effect are still poorly understood. Thus, rat oxidative skeletal muscles were isolated and incubated with OXT or WAY-267,464, a non-peptide selective OXT receptor (OXTR) agonist, in the presence or absence of atosiban (ATB), an OXTR antagonist, and overall proteolysis was evaluated. The results indicated that both OXT and WAY-267,464 suppressed muscle proteolysis, and this effect was blocked by the addition of ATB. Furthermore, the WAY-induced anti-catabolic action on protein metabolism did not involve the coupling between OXTR and Gαi since it was insensitive to pertussis toxin (PTX). The decrease in overall proteolysis induced by WAY was probably due to the inhibition of the autophagic/lysosomal system, as estimated by the decrease in LC3 (an autophagic/lysosomal marker), and was accompanied by an increase in the content of Ca2+-dependent protein kinase (PKC)-phosphorylated substrates, pSer473-Akt, and pSer256-FoxO1. Most of these effects were blocked by the inhibition of inositol triphosphate receptors (IP3R), which mediate Ca2+ release from the sarcoplasmic reticulum to the cytoplasm, and triciribine, an Akt inhibitor. Taken together, these findings indicate that the stimulation of OXTR directly induces skeletal muscle protein-sparing effects through a Gαq/IP3R/Ca2+-dependent pathway and crosstalk with Akt/FoxO1 signaling, which consequently decreases the expression of genes related to atrophy, such as LC3, as well as muscle proteolysis.

A Deep Learning Neural Network to Classify Obesity Risk in Portuguese Adolescents Based on Physical Fitness Levels and Body Mass Index Percentiles: Insights for National Health Policies.

The increasing prevalence of overweight and obesity among adults is a risk factor for many chronic diseases and death. In addition, obesity among children and adolescents has reached unprecedented levels and studies show that obese children and adolescents are more likely to become obese adults. Therefore, both the prevention and treatment of obesity in adolescents are critical. This study aimed to develop an artificial intelligence (AI) neural network (NNET) model that identifies the risk of obesity in Portuguese adolescents based on their body mass index (BMI) percentiles and levels of physical fitness. Using datasets from the FITescola® project, 654 adolescents aged between 10-19 years old, male: 334 (51%), female: n = 320 (49%), age 13.8 ± 2 years old, were selected to participate in a cross-sectional observational study. Physical fitness variables, age, and sex were used to identify the risk of obesity. The NNET had good accuracy (75%) and performance validation through the Receiver Operating Characteristic using the Area Under the Curve (ROC AUC = 64%) in identifying the risk of obesity in Portuguese adolescents based on the BMI percentiles. Correlations of moderate effect size were perceived for aerobic fitness (AF), upper limbs strength (ULS), and sprint time (ST), showing that some physical fitness variables contributed to the obesity risk of the adolescents. Our NNET presented a good accuracy (75%) and was validated with the K-Folds Cross-Validation (K-Folds CV) with good accuracy (71%) and ROC AUC (66%). According to the NNET, there was an increased risk of obesity linked to low physical fitness in Portuguese teenagers.

Antioxidants and cardioprotective effects of ethyl acetate fraction of Canavalia rosea leaves in myocardial ischemia-reperfusion injury.

Different degrees in the biological activities of Canavalia rosea had been previously reported . In this study, our group assessed the cardioprotective effects of the ethyl acetate fraction (EAcF) of the Canavalia rosea leaves. Firstly, it was confirmed, by in vitro approach, that the EAcF has high antioxidant properties due to the presence of important secondary metabolites, as flavonoids. In order to explore their potential protector against cardiovascular disorders, hearts were previously perfused with EAcF (300 µg.mL-1) and submitted to the global ischemia followed by reperfusion in Langendorff system. The present findings have demonstrated that EAcF restored the left ventricular developed pressure and decreased the arrhythmias severity index. Furthermore, EAcF significantly increased the glutathiones peroxidase activity with decreased malondialdehyde and creatine kinase levels. EAcF was effective upon neither the superoxide dismutase, glutationes reductase nor the catalase activities. In addition, the Western blot analysis revealed that ischemia-reperfusion injury significantly upregulates caspase 3 protein expression, while EAcF abolishes this effect. These results provide evidence that the EAcF reestablishes the cardiac contractility and prevents arrhythmias; it is suggested that EAcF could be used to reduce injury caused by cardiac reperfusion. However more clinical studies should be performed, before applying it in the clinic.

Physical Activity and Sedentary Behavior in Adults from Penafiel, Portugal: A Cross-Sectional Study.

The aim of this study was to compare the physical activity (PA) and sedentary behavior (SB) levels of young and middle-aged adults living in and around the municipality of Penafiel and to determine whether they meet PA recommendations. The researchers used the "International Physical Activity Questionnaire" (IPAQ) to measure moderate to vigorous PA and time spent on sedentary behavior (high vs. low). A prospective observational cross-sectional sample of 1105 adults aged 18-63 years, living in the municipality of Penafiel and its surroundings (45% women, 55% men), was used. The results indicated that more than half of the population was inactive (53.8%) and sedentary (54.0%). Men were more likely to be sedentary (59.2%) and inactive (55.6%) than women (inactive: 51.7%, high SB: 47.7%). Regarding daily PA and SB levels, women had higher levels of walks (3.8 ± 2.3; p = 0.034) and vigorous PA (2.2 ± 1.8 min; p = 0.005) per days/week, as well as vigorous PA per minutes/week (75.4 ± 82.1 min; p = 0.034). The time spent on vigorous PA per day was also higher in women (26.2 ± 22.8 min; p = 0.030). However, men had higher values in walking minutes per day (26.3 ± 17.1 min; p = 0.030), SB for weekdays (429.2 ± 141.2 min; p = 0.001), SB for weekends (324.7 ± 163.7 min; p = 0.033) and time spent on SB per minutes/week (2795.6 ± 882.0 min; p = 0.001). The results also showed that the older the adults, the lower the frequency and total time of vigorous PA per week. Young adults (18-28 years) had higher levels of vigorous PA (p = 0.005) than the other age groups (29-39; 40-50 and 51-63 years). Finally, the study found no significant correlation between individual level factors, such as number of children, marital status and monthly income, and PA or SB. Conversely, a significant and negative correlation between SB and levels of PA was found, indicating that the higher the level of PA practice, the lower the SB level. The authors suggest that promoting new PA habits and healthy lifestyles is an important future challenge for sustainability and improving the quality of life in public health.

Matching-adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis.

INTRODUCTION: Head-to-head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared. AIM: To compare bleeding rates in trials evaluating 6 × 1013  vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.5 mg/kg emicizumab dosed every week (HAVEN 3; NCT02847637), and FVIII prophylaxis (270-902) in participants with severe haemophilia A (FVIII ≤1 IU/dL). METHODS: Valoctocogene roxaparvovec versus emicizumab and FVIII prophylaxis as used in 270-902 versus emicizumab cross-trial comparisons were performed using matching-adjusted indirect comparison (MAIC). Individual participant data from GENEr8-1 and 270-902 were weighted to equalise aggregate participant baseline characteristics from HAVEN 3. After MAIC weighting, annualised bleeding rates (ABR) and proportions of participants without bleeds were compared for treated bleeds, all bleeds, treated joint bleeds, and treated spontaneous bleeds. RESULTS: After MAIC weighting, ABR for all bleeds was statistically significantly lower with valoctocogene roxaparvovec than emicizumab (rate ratio [95% CI], .55 [.33-.93]). Additionally, significantly higher proportions of participants had no treated joint bleeds (odds ratio [95% CI], 2.75 [1.20-6.31]) and no treated bleeds (3.25 [1.53-6.90]) with valoctocogene roxaparvovec versus emicizumab. When compared with the mainly standard half-life FVIII prophylaxis regimens in 270-902, mean ABRs (except for all bleeds) were significantly lower, and significantly higher proportions reported 0 bleeds for all outcomes with emicizumab. CONCLUSION: Valoctocogene roxaparvovec provided generally lower bleeding rates and higher probability of no bleeds, including treated joint bleeds, than emicizumab. Emicizumab was more effective than FVIII prophylaxis regimens used in 270-902.

Obesity Status and Physical Fitness Levels in Male and Female Portuguese Adolescents: A Two-Way Multivariate Analysis.

Obesity and decreasing fitness levels among the youth are growing concerns in Portugal, similar to other developed countries, with implications for health and psychomotor development. Understanding the influence of health determinants such as sex and age are crucial for developing effective public health strategies. This study aimed to analyze the association between sex and chronological age with obesity status and physical fitness in Portuguese adolescents. A total of 170 adolescents (85 males and 85 females) were evaluated for body mass index, abdominal adiposity, aerobic fitness, abdominal resistance, upper limb resistance, lower limb power, and maximal running speed in a 40 m sprint using the FITescola® physical fitness battery, a Portuguese government initiative. The general model, analyzed using Pillai's trace, showed a significant effect of age and sex on body mass index, abdominal circumference, aerobic fitness, abdominal resistance, upper limb resistance, lower limb power, and maximal running speed (V = 0.99, F (7) = 10,916.4, p < 0.001, partial η2, sex = 0.22; age = 0.43, sex and age interaction = 0.10). Boys had higher physical fitness levels than girls in most tests, but both sex groups had a significantly higher proportion of non-fit adolescents, with boys showing the highest number of participants classified as non-fit.

The Relationship of Oral Reading Fluency Endurance to Comprehension in an Intermediate Depth Orthography / [La relación entre la resistencia en la fluidez lectora y la comprensión en una ortografía de profundidad intermedia]

One-minute oral reading fluency (ORF) tests are widely used, but concerns have been raised regarding whether readers are able to maintain their performance if asked to read for a larger period. The main goals of this study were to investigate whether students are able to maintain their ORF performance in a three-minute task and whether scores measured at one and at three minutes are equally good predictors of the performance in a standardized reading comprehension measure. The sample was composed of 159 Portuguese primary school students (grades 2-4). The results suggested that the number of words read correctly (WRC) declined across reading time and that three-minute mean score underestimated fluency in all grade levels compared to a one-minute reading score. The WRC measured either at one minute or using a three-minute average score was an equal predictor of reading comprehension in all grades. Implications for theory and practice are discussed.(AU)

Las pruebas de fluidez lectora de un minuto son muy utilizadas, pero se ha planteado la preocupación de si los lectores son capaces de mantener su rendimiento si se les pide que lean durante un período más largo. Los objetivos principales de este estudio han sido investigar si los estudiantes son capaces de mantener su rendimiento de fluidez lectora en una tarea de tres minutos y si las puntuaciones medidas a uno y a tres minutos son igualmente predictoras del rendimiento en una medida estandarizada de comprensión lectora. La muestra estaba compuesta por 159 alumnos portugueses de primaria (2º a 4º curso). Los resultados sugieren que el número de palabras leídas correctamente (PLC) disminuyó a lo largo del tiempo de lectura y que la puntuación media a los tres minutos subestimó la fluidez en todos los cursos en comparación con la puntuación de un minuto de lectura. El PLC medido ya sea en un minuto o utilizando una puntuación media de tres minutos fue un predictor igual de la comprensión lectora en todos los cursos. Se discuten las implicaciones para la teoría y la práctica.(AU)

A referenciação dos doentes sem perspetiva de cura para uma unidade de cuidados paliativos de uma instituição privada / Referral of patients with no prospect of cure to a palliative care unit of a private institution

Na medida em que os Cuidados Paliativos pretendem ser uma resposta ativa aos problemas multidimensionais gerados pela progressão da doença crónica e incurável, é essencial que a dicotomia cuidados curativos/paliativos seja esbatida, no sentido de proporcionar cuidados de saúde mais humanizados. As intervenções devem estar centradas na qualidade de vida da pessoa doente e família. Esta é o "lugar" onde cada pessoa doente procura o apoio necessário para ultrapassar as situações difíceis que enfrenta. Enfrentar a vida e a morte, a felicidade e a infelicidade, o bem e o mal, são situações presentes no quotidiano profissional do/a enfermeiro/a que exigem respostas multidimensionais e efetivas, para minimizar o sofrimento que possa estar presente. Neste sentido, pretendendo desenvolver competências científicas, técnicas e humanas no âmbito da enfermagem à pessoa em situação paliativa, optamos por realizar em Estágio de Natureza Profissional numa unidade de cuidados paliativos, de forma a um cuidar com qualidade, centrado nas necessidades efetivas da pessoa com doença incurável. No decurso do estágio desenvolvemos competências especializadas no âmbito da prestação de cuidados, atendendo às componentes essenciais dos cuidados paliativos: gestão de sintomas, comunicação, apoio à família, acompanhamento no processo de luto e trabalho em equipa. Delineamos intervenções de âmbito multidimensional que tinham como propósito serem uma resposta ativa aos problemas presentes gerados pela progressão da doença crónica e incurável. A gestão adequada dos sintomas, a gestão de uma perda, o apoio à família, exigem do enfermeiro saber-saber, saber ser, saber estar e saber fazer. É fundamental, identificar os fatores preditores de complicações facilitando o planeamento de intervenções preventivas focadas na pessoa e, consequentemente, a sua referenciação atempada. No domínio da investigação, verificamos através do diagnóstico de situação e da nossa experiência profissional, a necessidade de investigar a referenciação dos doentes sem perspetiva de cura para uma unidade de cuidados paliativos de uma instituição privada, com o objetivo de identificar o processo da referenciação dos doentes sem perspetiva de cura, de uma instituição com financiamento privado, tendo como finalidade contribuir para cuidados humanizados. Estudo de natureza quantitativo, do tipo observacional, longitudinal, descritivo em que a recolha de dados foi efetuada a partir dos registos dos doentes internados na UCP Hospital Porto, em 2021, no Sistema Informação. Os dados foram tratados recorrendo ao programa IBM ­ Statistical Package for the Social Sciences (SPSS), versão 26. Foram respeitados todos os princípios éticos e legais. Verificamos, que os doentes foram referenciados predominantemente para controlo sintomático, existindo apenas uma situação de descanso do cuidador e outra de quimioterapia paliativa. A via de referenciação mais predominante, foi o sistema de informação (Glintt). Quanto à origem do doente, maioritariamente os doentes provêm do exterior: atendimento permanente, domicílio, transferido de outra unidade hospitalar. Predomina o internamento do foro oncológico, constatando-se o domínio da neoplasia do pulmão seguido da neoplasia da mama e do cólon. No que se refere à duração do internamento, a maioria dos doentes estiveram internados de 1 a 5 dias o que contribuiu para a melhoria do estado de saúde da pessoa doente. Neste sentido, torna-se primordial apostar na referenciação precoce das pessoas doentes para as equipas de cuidados paliativos, de forma a usufruir da gama completa destes cuidados. No domínio da formação, desenvolvemos atividades quer como formadora quer como formanda. No domínio da gestão, foi detetada a necessidade na organização do 2º Encontro de Cuidados Paliativos, que decorreu entre 7 e 8 de outubro de 2022. Todas estas atividades, permitiram desenvolver competências especializadas, contribuindo para uma prestação de cuidados com qualidade à pessoa. É de realçar, que para uma adequada gestão dos cuidados à pessoa em situação paliativa e seus familiares, é essencial um trabalho em equipa e em colaboração.

As Palliative Care aims to be an active response to the multidimensional problems generated by the progression of a chronic and incurable disease the curative/palliative care dichotomy must be is blurred to provide more humanised health care. Interventions should be focused on the quality of life of the sick person and family. This is the "place" where each sick person seeks the necessary support to overcome the difficult situations the come across. Facing life and death, happiness and unhappiness, good and evil, are actual situations in the daily professional life of nurses that require multidimensional and effective responses to minimise the suffering that may be present. Therefore, to develop scientific, technical, and human skills in nursing care provided to people in palliative states, we chose to conduct a Professional Internship in a palliative care unit to provide quality care focused on the effective needs of people with an incurable disease. During the internship, we developed specialised skills in care provision, taking into account the essential components of palliative care: symptom management, communication, family support, mourning process support and teamwork. We designed multidimensional interventions that were intended as an active response to the problems generated by the progression of chronic and incurable diseases. The adequate management of symptoms, the management of a loss, the support to the family, requires a nurse know-how, know how to act and know how to do. Identifying the predictors of complications is essential, facilitating the planning of preventive interventions focused on the person and, consequently, their prompt referral. In the area of research, through the diagnosis of the situation and our professional experience, we identified the need to investigate the referral of patients with no prospect of cure to a palliative care unit of a private institution, to identify the process of referral of patients with no prospect of cure, from a privately funded institution, with the purpose of contributing to humanised care. This is a quantitative, observational, longitudinal, descriptive study, in which data were collected from the records of patients admitted to the UCP Porto Hospital in 2021 in the Information System. Data were processed using the IBM - Statistical Package for the Social Sciences (SPSS), version 26. All ethical and legal principles were followed. We found that patients were predominantly referred for symptomatic control, with only one situation of caregiver respite and another of palliative chemotherapy. The most predominant means of referral was the information system (Glintt). As regards the origin of the patient, most patients came from outside the hospital: permanent attendance, home, transferred from another hospital unit. There was a predominance of oncological hospitalisation, with lung cancer being the most common, followed by breast and colon cancer. According to the duration of hospitalization, most users were hospitalized for 1 to 5 days, which contributed to the improvement of the patient's health status. In this sense, it is essential to focus on the early referral of patients to palliative care teams, so that they can benefit from the full range of this care. In the field of training, we developed activities both as trainers and trainees. In the management area, the need was detected for the organisation of the 2nd Palliative Care Meeting, which took place between 7 and 8 October 2022. All these activities allowed the development of specialised skills, contributing to the provision of quality care to the person. It should be noted that teamwork and collaboration are essential for adequate management of the care provided to palliative patients and their families.

Sinusitis and Late-Onset Asthma: A Red Flag of Eosinophilic Granulomatosis With Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic disease that develops with necrotizing granulomatous inflammation and is characterized by eosinophilia, asthma, and small vessel vasculitis. We report the case of a 74-year-old woman with a history of asthma, admitted to the Emergency Room with fever, headache, general malaise, weight loss and night sweats with one-month evolution, previously medicated with antibiotics without improvement. She presented with sinus palpation tenderness and lower leg bilateral sensitivity impairment. Laboratory tests showed neutrophilia and eosinophilia, normocytic anemia and elevated erythrocyte sedimentation rate and C-reactive protein. A computed tomography revealed sphenoid and maxillary sinusitis. Blood cultures and lumbar puncture were innocent. An extended autoimmune panel exposed a strong positive perinuclear anti-neutrophil cytoplasmic antibody - myeloperoxidase (pANCA-MPO). Sinus biopsy showed tissue infiltration by eosinophils, confirming EGPA. Corticosteroid (1 mg/kg/day) treatment was started with gradual improvement. Six months later there were no signs of active disease under prednisolone 10 mg and azathioprine 50 mg/day. This case highlights that refractory sinusitis in the presence of constitutional syndrome and peripheral eosinophilia should alert clinicians to the possibility of EGPA, particularly in patients with late-onset asthma.

Gallstone Ileus: A Rare Cause of Mechanical Bowel Obstruction.

A gallstone ileus is a rare cause of mechanical bowel obstruction, accounting for 1% to 4% of all cases. Twenty-five percent of the patients are 65 years of age or older and often present previous significant medical conditions. The authors report the case of an 87-year-old male patient, admitted with the diagnosis of community-acquired pneumonia, who later developed frequent episodes of biliary vomiting, intermittent constipation, and abdominal distension. Abdominal imaging (ultrasound and computed tomography (CT)) showed evidence of a localized inflammatory process in a small bowel loop but excluded vesicular lithiasis. After a failure in the medical approach with antibiotics, an exploratory laparotomy was performed, identifying the intestinal occlusion area, followed by an enterolithotomy at the specific area, and extraction of a 4 cm stone of acellular material. Posteriorly, the patient was treated for three weeks with a carbapenem and physical rehabilitation was promptly initiated with full recovery of his previous status. Gallstone ileus is a very challenging diagnosis and surgery is the treatment of choice. In elderly patients, it is important to promote prompt physical rehabilitation to prevent prolonged bed rest.