Search

Abstract Background Congenital disorders of glycosylation (CDG) are a growing group of rare genetic disorders. The most common CDG is phosphomannomutase 2 (PMM2)-CDG which often has a severe clinical presentation and life-limiting consequences. There are no approved therapies for this condition. Also, there are no validated disease-specific quality of life (QoL) scales to assess the heterogeneous clinical burden of PMM2-CDG which presents a challenge for the assessment of the disease severity and the impact of a certain treatment on the course of the disease. Aim and methods This study aimed to identify the most impactful clinical signs and symptoms of PMM2-CDG, and specific patient and observer reported outcome measures (PROMs and ObsROMs, respectively) that can adequately measure such impact on patients’ QoL. The most burdensome signs and symptoms were identified through input from the CDG community using a survey targeting PMM2-CDG families and experts, followed by family interviews to understand the real burden of these symptoms in daily life. The list of signs and symptoms was then verified and refined by patient representatives and medical experts in the field. Finally, a literature search for PROMs and ObsROMs used in other rare or common diseases with similar signs and symptoms to those of PMM2-CDG was performed. Results Twenty-four signs/symptoms were identified as the most impactful throughout PMM2-CDG patients’ lifetime. We found 239 articles that included tools to measure those community-selected PMM2-CDG symptoms. Among them, we identified 80 QoL scales that address those signs and symptoms and, subsequently, their psychometric quality was analysed. These scales could be applied directly to the PMM2-CDG population or adapted to create the first PMM2-CDG-specific QoL questionnaire. Conclusion Identifying the impactful clinical manifestations of PMM2-CDG, along with the collection of PROMs/ObsROMs assessing QoL using a creative and community-centric methodology are the first step towards the development of a new, tailored, and specific PMM2-CDG QoL questionnaire. These findings can be used to fill a gap in PMM2-CDG clinical development. Importantly, this methodology is transferable to other CDG and rare diseases with multiple signs and symptoms.

Este artigo descreve o papel que a filosofia desempenha no processo de constituição da astrobiologia como uma ciência legítima. Dirigindo o foco da discussão para os conceitos de vida e habitabilidade, procuramos mostrar de que modo a analogia contribui para que a astrobiologia seja uma disciplina científica. Defendemos que a noção de habitabilidade esclarece adequadamente a função exercida pela filosofia.

Este artigo, elaborado a partir de pesquisa-ação crítico colaborativa, de natureza aplicada e abordagem qualitativa, enfocou processos formativos continuados sobre o ensino da produção textual, envolvendo docentes, gestores de escola e de sistema. Visa à análise de modelo formativo implementado em rede municipal do interior paulista pela exposição das bases teóricas que o sustentaram e apresentação de desdobramentos de encontros formativos. Utiliza dados do questionário aplicado e de filmagens realizadas, analisados pela triangulação de dados. No campo da formação docente, tomaram-se estudos de Eraut (1987), Ferry (1987), Zeichner (1993), Demailly (1997), Pacheco e Flores (1999), Day (2001), Oliveira-Formosinho (2009), Cardoso et. al. (2012), Diniz-Pereira (2014), Shulman (2014), Carnin (2015), Guimarães (2016), Ferreira e Santos (2016). Os resultados, neste recorte, levam à identificação da utilização do livro didático e de propostas disponíveis na Internet para trabalhar a produção de textos, revelando a necessidade de desenvolvimento do olhar crítico dos professores sobre as fontes consultadas. As estratégias formativas utilizadas permitiram o reconhecimento pelos participantes da proximidade entre seus planejamentos e a estrutura dos livros didáticos. Constata-se que a autoria no planejamento docente pode ressignificar o fazer pedagógico. Palavras-chave: Formação Docente; Ensino de Língua Materna; Livro Didático.

Digital Health is a subject of extensive discourse when considering its current and future significance. This significance arises from a convergence of various factors, including the escalating capabilities and cost-effectiveness of computing and communication technology, coupled with the mounting demands and challenges faced by healthcare systems. The integration of health and technology, when studied collectively with the purpose of addressing tangible real-world issues, holds the potential to generate substantial outcomes that greatly influence the provision of clinical and social care, thereby enhancing the overall well-being of both individuals and populations. In this sense, in this paper we propose a collaborative approach, using Open Innovation, where the most relevant stakeholders—health and care professionals, citizens and companies—work together to develop and validate innovative digital solutions for health and care. We have called this approach of value co-creation the Collaborative Ecosystem, and we focus specifically on the potential development of the Regional Ecosystem for Collaborative Innovation in Digital Health and Care, and the envisioned implications of its implementation in economic and social dimensions.

Intracellular heme formation and trafficking are fundamental processes in living organisms. Bacteria and archaea utilize three biogenesis pathways to produce iron protoporphyrin IX (heme b) that diverge after the formation of the common intermediate uroporphyrinogen III (uro’gen III). In this study, we identify and provide a detailed characterization of the enzymes involved in the transformation of uro’gen III into heme in Campylobacter jejuni, demonstrating that this bacterium utilizes the protoporphyrin-dependent (PPD) pathway. In general, limited knowledge exists regarding the mechanisms by which heme b reaches its target proteins after this final step. Specifically, the chaperones necessary for trafficking heme to prevent the cytotoxic effects associated with free heme remain largely unidentified. In C. jejuni, we identified a protein named CgdH2 that binds heme with a dissociation constant of 4.9 ± 1.0 µM, and this binding is impaired upon mutation of residues histidine 45 and 133. We demonstrate that C. jejuni CgdH2 establishes protein–protein interactions with ferrochelatase, suggesting its role in facilitating heme transfer from ferrochelatase to CgdH2. Furthermore, phylogenetic analysis reveals that C. jejuni CgdH2 is evolutionarily distinct from the currently known chaperones. Therefore, CgdH2 is the first protein identified as an acceptor of intracellularly formed heme, expanding our knowledge of the mechanisms underlying heme trafficking within bacterial cells.

This paper presents a model to calculate the opening angle of crack initiation in notched fractures subjected to multiaxial loading. To validate the proposed model, a study was performed on polished AZ31B-F magnesium alloy specimens under multiaxial high-cycle fatigue loading. The specimens exhibited a notch in the smaller cross-sectional area, which was created with a special drilling jig to promote the formation of fatigue cracks in this localized area of the specimen. The load paths used in the experiments and numerical analyses were proportional and non-proportional, resulting in different stress states in the crack front opening, which were determined by finite element analysis to validate the proposed model. To obtain more accurate numerical results for these estimates, these finite element analyses were performed using the nonlinear Chaboche plasticity model of ABAQUS® 2021 software. A sensitivity analysis was also performed to determine which load component—axial or torsional—has a greater influence on the fatigue strength and contributes significantly to the crack opening process. The results show that the type of load path and the stress level of each load component—axial and torsional—has a strong influence on the opening angle of the notch crack and the fatigue lifetime of the specimen. This result is confirmed not only by the experimentally determined fatigue strength, but also by a fractographic analysis performed on the surface of the specimens for both load paths. Moreover, the results show an acceptable correlation between the experimental results and the estimates obtained with the proposed model and the stresses obtained with the finite element analysis.

Onion skin waste (OSW), the primary non-edible byproduct from onion processing, offers a renewable source of bioactive compounds. This study aims to valorize OSW through subcritical water extraction (SWE), aligning with a circular economy and biorefinery principles. SWE was carried out at 145 °C and 50 bar for 50 min in a discontinuous reactor, producing a phenolic-rich extract (32.3 ± 2.6 mg/g) dominated by protocatechuic acid (20.3 ± 2.5 mg/g), quercetin-4′-O-glucoside (7.5 ± 0.2 mg/g), and quercetin (3.2 ± 0.6 mg/g). Additionally, the extract contains sugars (207.1 ± 20.3 mg sucrose-Eq/g), proteins (22.8 ± 1.6 mg BSA-Eq/g), and free amino acids (20.4 ± 1.2 mg arginine-Eq/g). Its phenolic richness determines its scavenging activity against ●NO and O2●− radicals and its α-glucosidase and aldose-reductase inhibition without affecting α-amylase. Notably, the extract demonstrates significant α-glucosidase inhibition (IC50 = 75.6 ± 43.5 µg/mL), surpassing acarbose (IC50 = 129.5 ± 1.0 µg/mL) in both pure enzyme and cell culture tests without showing cytotoxicity to AGS, HepG2, and Caco-2 human cell lines. The extract’s bioactivity and nutritional content make it suitable for developing antioxidant and antidiabetic nutraceutical/food components, highlighting SWE’s potential for OSW valorization without using organic solvents.

Abstract Background Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic. The main aim of this study was to understand current and steer future CDG drug development and approval by collecting and analysing the views and experiences of the CDG community, encompassing professionals and families. An electronic (e-)survey was developed and distributed to achieve this goal. Results A total of 128 respondents (46 CDG professionals and 82 family members), mainly from Europe and the USA, participated in this study. Most professionals (95.0%) were relatively familiar with drug development and approval processes, while CDG families revealed low familiarity levels, with 8.5% admitting to never having heard about drug development. However, both stakeholder groups agreed that patients and families make significant contributions to drug development and approval. Regarding their perceptions of and experiences with specific drug development and approval tools, namely biobanks, disease models, patient registries, natural history studies (NHS) and clinical trials (CT), the CDG community stakeholders described low use and participation, as well as variable familiarity. Additionally, CDG professionals and families shared conflicting views about CT patient engagement and related information sharing. Families reported lower levels of involvement in CT design (25.0% declared ever being involved) and information (60.0% stated having been informed) compared to professionals (60.0% and 85.7%, respectively). These contrasting perceptions were further extended to their insights and experiences with patient-centric research. Finally, the CDG community (67.4% of professionals and 54.0% of families) reported a positive vision of artificial intelligence (AI) as a drug development tool. Nevertheless, despite the high AI awareness among CDG families (76.8%), professionals described limited AI use in their research (23.9%). Conclusions This community-centric study sheds new light on CDG drug development and approval. It identifies educational, communication and research gaps and opportunities for CDG professionals and families that could improve and accelerate CDG therapy development.

Objectives: To evaluate the outcomes of conservative management in young women with high-grade squamous intraepithelial lesion (HSIL). Methods: A retrospective cohort study included women younger than 30 years referred with HSIL (cytology or biopsy) managed conservatively from 2012 to 2019, in Campinas/Brazil. Regression was the outcome when no evidence of HSIL was observed in at least two consecutive follow-ups. Kaplan?Meyer method was used to determine regression probabilities. Other tests were chi-square or Fisher, Mann?Whitney and COX regression. Results: During the study period, 89 patients were included. No progression to microinvasive or invasive cancer was observed. Sixty-one (69%) patients were younger than 25 years, and 28 (31%) were aged 25?30 years. Spontaneous regression was seen in 64 (72%) and persistence in 25 (28%) of the overall sample. The average time to regression was 15.4 months (standard deviation [SD]?=?7.7), and the follow-up time was 31.6 months (SD 19.0). Age, parity, first sexual intercourse, smoking, hormonal contraception, and colposcopy impression were not different among women with regression or persistence. Regression probabilities were, respectively, 28.9%, 60.2%, and 78.1% after 12, 18, and 24 months. Most of the events happened between 12 and 18 months of follow-up. Conclusions: Conservative management in women younger than 30 years was safe: spontaneous regression was observed in 72% of all women younger than 30 with HSIL managed conservatively. No clinical variable was relevant, influencing regression. In 2 years the regression probability was 78%.

PET/MRI technology has expanded the boundaries of investigation in nuclear medicine, supported by the high sensitivity of solid-state PET detectors. Nonetheless, the coil positioning might lead to an increased exposure period of the worker to the injected patient. This procedure does not occur on PET/CT and, therefore, exposure period is reduced on such scanner. The aim of our study was to evaluate the dosimetry of two occupationally exposed individuals (OEI) working at the Center of Nuclear Medicine of Hospital das Clínicas of the University of Sao Paulo. We used thermoluminescent (TLD) dosimeters in pulse, whole-body and crystalline for PET/MRI and PET/CT procedures during five months of clinical and research routine. We also monitored the time for positioning/removing the patient on both scanners. For this study, OEI1 performed 76 PET/MRI studies and 102 PET/CT studies while OEI2 performed 26 and 56 PET/MRI and PET/CT studies, respectively. We found no evidence of differences for the whole-body dose values between both scanners (p = 0.22). The average time of patient management (positioning/removing the patient) was 14.38, and 3.81 minutes for PET/MRI and PET/CT, respectively. When the normalization by the number of PET/CT studies was applied, we found no statistical difference for effective and equivalent dose values. Our study encourages future investigations on nursing staff, which is a critical population that is exposed to ionizing radiation, mainly on dynamic studies, due to the synchronized injection with the protocol starting.

INTRODUÇÃO: Em 2018, um estudo de investigação realizado numa Unidade de Saúde Familiar (USF) estimou uma prevalência de défice cognitivo ligeiro (DCL) de 29,1%, verificando-se uma associação entre o melhor desempenho no teste Montreal Cognitive Assessement (MoCA) com a leitura de jornais e livros e a realização de passatempos. O objetivo do projeto foi melhorar a capacidade cognitiva nos idosos com DCL através de atividades de treino cognitivo. MÉTODOS: Projeto de intervenção realizado numa USF com uma amostra de 20 idosos com DCL. Decorreram sessões presenciais de treino cognitivo e foram entregues cadernos de trabalhos de casa. Foi aplicado o MoCA versão portuguesa aos zero, três e seis meses para avaliação do desempenho cognitivo. RESULTADOS: No início do estudo, a pontuação mediana no MoCA foi 18,5. Após seis meses, registou-se uma pontuação mediana de 23. Verificou-se uma melhoria da pontuação global em todos os domínios cognitivos, com exceção da linguagem e da orientação. CONCLUSÃO: O objetivo foi atingido pela melhoria do desempenho cognitivo após seis meses de estudo. O treino cognitivo tem um potencial efeito benéfico na saúde da população idosa e requer materiais de simples elaboração e baixo custo que podem ser aplicados em lares de idosos e centros de dia através dos cuidadores.

INTRODUCTION: Despite the worldwide dissemination of COVID-19, the epidemiological and clinical patterns of the disease remain uncertain in the pediatric age group. OBJECTIVE: To describe the epidemiological, clinical, laboratory and radiological characteristics of pediatric patients diagnosed with disease caused by SARS-CoV-2, hospitalized in the ward of Hospital Regional João Penido, located in Juiz de Fora, MG. METHODS: A cohort study was carried out, with data collection from the period of hospitalization regarding epidemiological, clinical, laboratory and radiological criteria through a specific form developed for the research of pediatric patients, hospitalized from March 11, 2020 to March 11, 2021, who received a diagnosis of COVID-19, confirmed by RT-PCR or by IgM/IgG serology. RESULTS: Of the patients with COVID-19, 49.2% were aged up to 3 years, 66.2% were male and, among the comorbidities, chronic respiratory disease was the most prevalent (26.9%). Most patients had a clinical respiratory condition (72.7%). Regarding disease severity, 38.5% had mild disease, 23.1% moderate, 23.1% severe and 12.3% critical. In the outcome, 98.5% were discharged from the hospital and only 1 patient, who had several comorbidities, died. CONCLUSION: COVID-19 has varied clinical, radiological and laboratory presentations and, since there is no single or specific treatment, cases must be analyzed and managed individually.

Abstract This study aimed to make a longitudinal analysis of interexaminer calibration reproducibility in diagnosing dental caries in posterior teeth, by examiners without previous experience in epidemiological studies. A group of 11 inexperienced examiners underwent theoretical-practical training and calibration assessments, assisted by a standard examiner. An examiner who did not participate directly in the research selected 5-year-old children with and without caries. The D3 diagnostic threshold was used to evaluate dental caries, based on the World Health Organization (WHO) criteria. The initial calibration (baseline) was performed after the theoretical-practical training session, and consisted of examining 20 children; the second calibration occurred three months later, and involved evaluating another 18 children. The interexaminer agreement was obtained by kappa statistics, and by overall percentage agreement. The paired t-test was applied to compare the values for kappa means and overall percentage agreement between the time points studied. At baseline, the values for kappa (> 0.81) and overall percentage agreement (> 95.63%) were considered high. At the 3-month calibration assessment, all the examiners showed some decrease in both kappa (p < 0.0001) and overall percentage agreement (p = 0.0102). The calibration process currently proposed by the WHO is effective. However, reproducibility was not maintained over time for inexperienced examiners evaluating the posterior teeth of 5-year-old children, under epidemiological conditions.

Abstract Background Congenital Disorders of Glycosylation (CDG) are a complex family of rare metabolic diseases. Robust clinical data collection faces many hurdles, preventing full CDG biological and clinical comprehension. Web-based platforms offer privileged opportunities for biomedical data gathering, and participant recruitment, particularly in rare diseases. The immunology and CDG electronic (e-) questionnaire (ImmunoCDGQ) explores this paradigm, proposing a people-centric framework to advance health research and participant empowerment. Objective The objectives of this study were to: (1) Describe and characterize the ImmunoCDGQ development, engagement, recruitment, participation, and result dissemination strategies; (2) To critically compare this framework with published literature and making recommendations. Methods An international, multistakeholder people-centric approach was initiated to develop and distribute the ImmunoCDGQ, a multi-lingual e-questionnaire able to collect immune-related data directly from patients and family caregivers. An adapted version was produced and distributed among the general “healthy” population (ImmunoHealthyQ), serving as the control group. Literature screening was performed to identify and analyze comparable studies. Results The ImmunoCDGQ attained high participation and inclusion rates (94.6%, 209 out of 221). Comparatively to the control, CDG participants also showed higher and more variable questionnaire completion times as well as increased English version representativeness. Additionally, 20% of the CDG group (42 out of 209) chose not to complete the entire questionnaire in one go. Conditional logic structuring guided participant data provision and accurate data analysis assignment. Multi-channel recruitment created sustained engagement with Facebook emerging as the most followed social media outlet. Still, most included ImmunoCDGQ questionnaires (50.7%, 106 out of 209) were submitted within the first month of the project’s launch. Literature search and analysis showed that most e-questionnaire-based studies in rare diseases are author-built (56.8%, 25 out of 44), simultaneously addressing medical and health-related quality of life (HRQoL) and/or information needs (79.5%, 35 out of 44). Also, over 68% of the studies adopt multi-platform recruitment (30 out of 44) actively supported by patient organizations (52.3%, 23 out of 44). Conclusions The ImmunoCDGQ, its methodology and the CDG Community served as models for health research, hence paving a successful and reproducible road to people-centricity in biomedical research.

In large transdisciplinary research teams finding the balance between using the most appropriate and needed measures for data collection and minimising participant burden is often a significant challenge. This paper aims to describe the development process for selecting a set of determinants of physical activity behaviours in 9–12 years old children. An internal small group (n = 8) worked iteratively with an external large group of experts and stakeholders (n = 30-50) in three steps: 1) External input – Identification through expert opinion; 2) Internal input – Identification and selection via a systematized approach; 3) External validation of the selected measures. During these steps, 113 measures were first identified, then scored, sorted, and selected using evidence-building practices such as systematic literature reviews, peer-review, and consensus discussions. Eighteen measures were agreed and included in the core measures toolkit (child and caregiver questionnaires). In conclusion, pragmatism, implementation concerns, and the experts' experience were key in this process. This process may be considered as a reference to others involved in the challenge of selecting measures in their research. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this work, the pyrolysis process and the characteristics of biochar produced using a bench-scale fixed-bed reactor and a prototype-scale auger reactor were studied. Residual forest biomass (RFB) from acacia, broom, gorse, and giant reed was used as feedstock. Besides information on pyrolysis characteristics of these specific biomass species from the Iberian Peninsula, new knowledge on the understanding of how results from small-scale reactors can be used to predict the behavior of higher-scale and continuous-operation reactors is offered. Batch pyrolysis was carried out using 40 g of biomass sample in a fixed-bed reactor with a heating rate of 20 °C∙min−1, pyrolysis temperature of 450 and 550 °C, and a residence time of 30 min, while for the continuous process it was used a prototype of an auger reactor with continuous operation with a biomass flow rate up to 1 kg/h, with temperatures of 450 and 550 °C, and a solids residence time of 5 min. The biochar yield was in the range of 0.26 to 0.36 kg/kg biomass dry basis, being similar for both types of reactors and slightly lower when using the auger reactor. The proximate analysis of the biochar shows volatile matter in the range 0.10 to 0.27 kg/kg biochar dry basis, fixed carbon in the range 0.65 to 0.84 kg/kg biochar dry basis, and ash in the range 0.04 to 0.08 kg/kg biochar dry basis. The carbon, oxygen, and hydrogen content of the biochar was in the range of 0.71 to 0.81, 0.09 to 0.22, and 0.02 to 0.03 kg/kg biochar dry basis, respectively. The results show that the up-scaling of the reactor and regime of operation does not have an important influence on the yield and characteristics of the biochar produced. The biochar obtained in the two types of reactors has characteristics appropriate for environmental applications, such as an additive to improve soil properties. It is possible to see that the characteristics of the biochar are influenced by the type of biomass and the conditions and parameters of the process; therefore, it is of major importance to control and know of these conditions, especially when considering upscaling scenarios. [ABSTRACT FROM AUTHOR]

Electrogenerated hydrophilic carbon (EHC) nanomaterials emerge as a highly attractive option for mimicking the activity of the superoxide dismutase enzyme (SOD) due to their exceptional water solubility and electron-transfer reversibility. Motivated by these properties, the EHC nanomaterials were utilized to assess the effect of ionic strength on the SOD-like activity. Superoxide anion radicals (O2•−) were generated using the hypoxanthine–xanthine oxidase system, with nitro blue tetrazolium chloride serving as the detecting system. A significant boost in the SOD-like activity was found via the addition of an electrolyte to the as-prepared nanomaterial solution. The effect of the electrolyte cation (Na+ and K+), as well as its counterion (Cl−, CH3COO−, and H2PO4−/HPO42−) were analyzed. Based on these studies, a new formulation for the preparation of the carbon-based nanomaterial was established. It was demonstrated that the SOD-like activity follows an enzyme-type catalytic activity rather than the stoichiometric scavenging of the superoxide anion radical. It was concluded that 12.71 µg/mL of the EHC nanomaterial exhibits catalytic activity comparable to 15.46 µg/mL of the native Cu/Zn-SOD enzyme. This study provides a starting point for the development of a new nanotool to fight the oxidative stress associated with pathophysiological conditions where SOD activity is depleted. [ABSTRACT FROM AUTHOR]

In many countries, quality assurance systems rely on study programme accreditation. As with all quality assurance mechanisms, accreditation should also be continuously improved in order to maintain its relevance as a promoter of study programme quality. A way to move accreditation forward is by taking into account academics' views, interests and needs about the process, since their support for it is paramount for its success and effectiveness. This paper analyses Portuguese academics' knowledge and views on accreditation with the aim of understanding if the process is being supported and is on the right route for being effective. It is based on the analysis of 1484 academics' answers to a questionnaire distributed in 16 higher education institutions. This analysis reveals a moderately positive attitude of academics towards accreditation, reflected in an only moderate knowledge of the process as well as in a mild agreement with its characteristics and implementation features. This suggests that there is room for improvement to bring this quality assurance mechanism closer to academics' expectations and needs and therefore to improve accreditation's effectiveness.

In Europe and beyond, managerialism triggered the rise of "boardism" as a distinctive governance praxis in higher education, involving both normative assumptions and technical and practical elements. In this paper, we examine to what extent strategizing processes in Portuguese higher education institutions reflect the reconfiguration of power relationships at the institutional level. The paper draws on survey data to examine the perceptions of the teaching staff and non-teaching staff in public and private Portuguese higher education institutions. It aims at identifying what strategizing processes reveal about the implications of the decrease of academic self-governance, the increase of managerial governance and the increasing influence of external members in the composition of the governing bodies. The analysis of the Portuguese case contributes to the understanding of governance challenges in managing change in a context of uncertainty with an eye on how governance practitioners might deal with the issues it raises.