Expanding the phenotypic and genotypic spectrum of Bietti crystalline dystrophy

Abstract: The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in CYP4V2, a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging. Four unrelated patients are described with two known variants, c.802‐8_810del17insGC and c.518T > G (p.Leu173Trp), and one novel missense variant, c.1169G > T (p.Arg390Leu). The patient with the novel homozygous variant had the most severe phenotype resulting in macular hole formation and retinal detachment in both eyes. To the best of our knowledge, there is no association of these features with Bietti crystalline dystrophy. Patient 1 was the youngest patient and had the mildest phenotype with crystals in the retina without chorioretinal atrophy and visual complaints. Patients 2 and 3 presented with fewer crystals and chorioretinal atrophy. These three patients presented a classic phenotype. The fourth patient presented with an atypical and severe phenotype. This study reveals a new genotype and new phenotype associated with this disorder. Keywords: bietti crystalline dystrophy; CYP4V2 protein; genetic testing; missense mutation; insertion‐deletion mutatio

Profile of depressive symptoms in women in the perinatal and outside the perinatal period: similar or not?

Purposes To analyze which Beck Depression Inventory-II (BDI-II) and Postpartum Depression Screening Scores (PDSS) total and dimensional scores, as well as symptomatic answers proportions significantly differ between women in the perinatal period (pregnant/postpartum) without major depression, with major depression and women outside the perinatal period. Methods 572 pregnant women in the third trimester completed Beck Depression Inventory-II and Postpartum Depression Screening Scale and were assessed with the Diagnostic Interview for Genetic Studies. 417 of these were also assessed (with the same instruments) at three months postpartum. Ninety non-pregnant women or that did not have a child in the last year (mean age=29.42±7.159 years) also filled in the questionnaires. Results Non-depressed pregnant women showed lower scores than depressed pregnant women and higher scores than women outside the perinatal period in the BDI-II total score and in its Somatic-Anxiety dimension. Non-depressed postpartum women showed significantly higher scores than women outside the perinatal period only at Sleep/Eating Disturbances. Compared to women outside the perinatal period, pregnant women without depression presented higher scores only in the somatic items. Women with vs. without depression in the postpartum period did not significantly differ and both presented higher scores than women outside the perinatal period in the proportions of loss of energy and sleep changes. Limitations Women outside the perinatal period were not diagnosed for the presence of a depressive disorder, but their BDI-II mean score was similar to the figures reported worldwide regarding women in childbearing age. Conclusion In the perinatal period, most particularly at pregnancy, women experience significant somatic changes even if not clinically depressed. Cognitive-affective symptoms are more useful when assessing the presence of perinatal depression

Stem cell-containing hyaluronic acid-based spongy hydrogels for integrated diabetic wound healing

The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplantation into diabetic mice full-thickness wounds. Acellular spongy hydrogels and empty wounds were used as controls. Reepithelialization was attained 4 weeks after transplantation independently of the test groups, whereas a thicker and more differentiated epidermis was observed for the cellular spongy hydrogels. A switch from the inflammatory to the proliferative phase of wound healing was revealed for all the experimental groups 2 weeks after injury, but a significantly higher M2(CD163 þ )/M1(CD86 þ ) subtype ratio was observed in the neurogenic preconditioned group that also failed to promote neoinnervation. A higher number of intraepidermal nerve fibers were observed for the unconditioned group probably due to a more controlled transition from the inflammatory to the proliferative phase. Overall, stem cell-containing spongy hydrogels represent a promising approach to enhance diabetic wound healing by positively impacting re-epithelialization and by modulating the inflammatory response to promote a successful neoinnervation.The authors would like to acknowledge Gene2Skin Project (H2020-TWINN2015-692221) and Fundac¸a˜o para a Cieˆncia e Tecnologia for SFRH/BD/ 78025/2011 (LPdS), SFRH/BPD/96611/2013 (MTC), SFRH/BPD/101886/2014 (RPP), SFRH/BPD/101952/2014 (TCS) grants. Moreover, the authors would also like to acknowledge Teresa Oliveira for histology support, Andreia Carvalho for hASCs supply, Luca Gasperini for cell profiler analysis, and Manuela E. L. Lago and Carla M. Abreu for intraepidermal nerve fiber quantification.info:eu-repo/semantics/publishedVersio

Potential of atlantic codfish (Gadus morhua) skin collagen for skincare biomaterials

Collagen is the major structural protein in extracellular matrix present in connective tissues, including skin, being considered a promising material for skin regeneration. Marine organisms have been attracting interest amongst the industry as an alternative collagen source. In the present work, Atlantic codfish skin collagen was analyzed, to evaluate its potential for skincare. The collagen was extracted from two different skin batches (food industry by-product) using acetic acid (ASColl), confirming the method reproducibility since no significant yield differences were observed. The extracts characterization confirmed a profile compatible with type I collagen, without significant differences between batches or with bovine skin collagen (a reference material in biomedicine). Thermal analyses suggested ASColl’s native structure loss at 25 °C, and an inferior thermal stability to bovine skin collagen. No cytotoxicity was found for ASColl up to 10 mg/mL in keratinocytes (HaCaT cells). ASColl was used to develop membranes, which revealed smooth surfaces without significative morphological or biodegradability differences between batches. Their water absorption capacity and water contact angle indicated a hydrophilic feature. The metabolic activity and proliferation of HaCaT were improved by the membranes. Hence, ASColl membranes exhibited attractive characteristics to be applied in the biomedical and cosmeceutical field envisaging skincare.This work was supported by funds from the European Regional Development Fund (ERDF) under the scope of NORTE 2020, part of the PORTUGAL 2020 Partnership Agreement, through the project ATLANTIDA (Norte-01-0145-FEDER-000040) and the R&D Infrastructure TERM RES-Hub PINFRA/22190/2016 (Norte-01-0145-FEDER-022190), also funded by the Portuguese Foundation for Science and Technology (FCT). Financial support from FCT is also acknowledged for the investigator contract of C.F.M. (CEECIND/04687/2017), the PhD scholarship of A.L.A. (PD/BD/127995/2016) under Doctoral Programme Do*Mar and the PhD scholarship of R.O.S. (PD/BD/150519/2019) under Doctoral Programme in Advanced Therapies for Health, PATH

Enhancing the longevity and functionality of Ti-Ag dry electrodes for remote biomedical applications: a comprehensive study

This study aims to evaluate the lifespan of Ti-Ag dry electrodes prepared using flexible polytetrafluoroethylene (PTFE) substrates. Following previous studies, the electrodes were designed to be integrated into wearables for remote electromyography (EMG) monitoring and electrical stimulation (FES) therapy. Four types of Ti-Ag electrodes were prepared by DC magnetron sputtering, using a pure-Ti target doped with a growing number of Ag pellets. After extensive characterization of their chemical composition and (micro)structural evolution, the Ti-Ag electrodes were immersed in an artificial sweat solution (standard ISO-3160-2) at 37 °C with constant stirring. Results revealed that all the Ti-Ag electrodes maintained their integrity and functionality for 24 h. Although there was a notable increase in electrical resistivity beyond this timeframe, the acquisition and transmission of (bio)signals remained viable for electrodes with Ag/Ti ratios below 0.23. However, electrodes with higher Ag content (Ag/Ti = 0.31) became insulators after 7 days of immersion due to excessive Ag release into the sweat solution. This study concludes that higher Ag/Ti atomic ratios result in heightened corrosion processes on the electrode’s surface, consequently diminishing their lifespan despite the advantages of incorporating Ag into their composition. This research highlights the critical importance of evaluating electrode longevity, especially in remote biomedical applications like smart wearables, where electrode performance over time is crucial for reliable and sustained monitoring and stimulation.This research was funded by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization (COMPETE 2020) under Portugal 2020, in the framework of the NanoStim (POCI-01-0247-FEDER-045908) and NanoID (NORTE-01-0247-FEDER-046985) Projects

Science labs: diagnostic analysis in Portuguese public schools

O presente trabalho enquadra-se no domínio da Educação em Ciências e foca-se na identificação, avaliação e apresentação de propostas para a melhoria dos espaços didáticos de ciência, dada a sua importância para a construção do conhecimento científico e para o desenvolvimento de capacidades associadas ao trabalho prático. Este estudo assumiu um paradigma sócio-crítico de natureza mista para identificar, descrever, aferir e melhorar as infraestruturas destinadas à realização do trabalho prático de ciências, particularmente de índole experimental e laboratorial, nos 152 estabelecimentos de ensino público (do Pré-escolar ao Ensino Secundário) que integram a Comunidade Intermunicipal do Médio Tejo, em Portugal. Os resultados evidenciam que a organização dos laboratórios de ciências parece não potenciar o trabalho colaborativo entre os/as alunos/as. Relativamente aos recursos materiais para o ensino prático de ciências, verificou-se que, apesar da sua diversidade, estes são, por norma, insuficientes para a utilização simultânea por diferentes grupos de trabalho, como desejável. Verificou-se, ainda, a ausência de alguns equipamentos de proteção e emergência considerados vitais para a segurança da comunidade escolar. Os principais contributos deste estudo relacionam-se com a perceção da realidade dos espaços escolares destinados às ciências e com a apresentação de propostas para a sua melhoria. As conclusões incitam à reflexão, por parte dos agentes educativos, sobre o estado atual e a relevância para a qualidade das aprendizagens em ciências dos laboratórios de ciências escolares que devem ser alvo de uma criteriosa e cuidada planificação, construção e apetrechamento.The present work falls within the field of Science Education and focuses on the identification, evaluation and presentation of proposals for the improvement of science didactic infrastructures given its importance for the construction of scientific knowledge and the development of skills associated with practical work. This study assumed a socio-critical paradigm of a mixed nature to identify, describe, evaluate and improve the infrastructures destined to perform practical work of sciences, particularly of experimental and laboratory nature, in 152 public education establishments (from Pre-school to secondary education) that integrate the Comunidade Intermunicipal do Médio Tejo, in Portugal. The results show that the organization of the science labs does not promote collaborative work among students. Regarding the material resources for the practical science teaching, it has been found that, despite their diversity, these are, in general, insufficient for the simultaneous use by the different working groups. It was also verified the absence of some protection and emergency equipment considered vital for the safety of the school community. The main contributions of this study are related to the perception of the reality of school science infrastructures and with the presentation of proposals for their improvement. The conclusions encourage the reflection by educational agents on the current state and relevance of school science labs to the quality of science learning of school science laboratories that must be carefully planned, constructed and equipped.Le présent travail s’inscrit dans le domaine de l’enseignement des sciences et se concentre sur l’identification, l’évaluation et la présentation de propositions d’amélioration des espaces didactiques de la science compte tenu de son importance pour la construction de la connaissance scientifique et le développement des compétences associées au travail pratique. Cette étude a pris un paradigme sociocritique de nature mixte pour identifier, décrire, évaluer et améliorer les infrastructures destinées aux travaux pratique des sciences, en particulier de nature expérimentale et laboratoire, dans les 152 écoles publiques (de l’enseignement préscolaire au secondaire) qui composent la Comunidade Intermunicipal do Médio Tejo, au Portugal. Les résultats montrent que l’organisation des laboratoires scientifiques ne favorise pas le travail collaboratif entre les étudiants. En ce qui concerne les ressources matérielles pour l’enseignement pratique des sciences, il a été constaté que, malgré leur diversité, ils sont, en règle générale, insuffisantes pour l’utilisation simultanée par les différents groupes de travail. Il a également été vérifié l’absence de matériel de protection et d’urgence jugé vital pour la sécurité de la communauté scolaire. Les principales contributions de cette étude sont liées à la perception de la réalité des espaces scolaires des sciences et à présentation de propositions d’amélioration. Les conclusions encouragent à la réflexion des agents éducatifs sur l’état actuel et à l’importance des laboratoires scientifiques scolaires qui doivent être soigneusement planifiés, construits et équipés.publishe

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes

In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.sentation, laboratory findings, histological profile, treatments, and outcomes of children andadolescents with autoimmune hepatitis.Methods: The medical records of 828 children and adolescents with autoimmune hepatitiswere reviewed. A questionnaire was used to collect anonymous data on clinical presentation,biochemical and histological findings, and treatments.Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmunehepatitis-2. The female sex was predominant in both groups. The median age at symptomonset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher forautoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patientswith autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-foldhigher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were sig-nificantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels werelower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochem-ical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6%underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmunehepatitis-2: 2.4%).Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.info:eu-repo/semantics/publishedVersio

New biotextiles for tissue engineering : development, characterization and in vitro cellular viability

This work proposes biodegradable textile-based structures for tissue engineering applications. We describe the use of two polymers, polybutylene succinate (PBS) proposed as a viable multifilamentand silk fibroin (SF), to produce fibre-based finely tuned porous architectures by weft knitting. PBS is here proposed as a viable extruded multifilament fibre to be processed by a textile-based technology. A comparative study was undertaken using a SF fibre with a similar linear density. The knitted constructs obtained are described in terms of their morphology, mechanical properties, swelling capability, degradation behaviour and cytotoxicity. The weft knitting technology used offers superior control over the scaffold design (e.g. size, shape, porosity and fibre alignment), manufacturing and reproducibility. The presented fibres allow the processing of a very reproducible intra-architectural scaffold geometry which is fully interconnected, thus providing a high surface area for cell attachment and tissue in-growth. The two types of polymer fibre allow the generation of constructs with distinct characteristics in terms of the surface physico-chemistry, mechanical performance and degradation capability, which has an impact on the resulting cell behaviour at the surface of the respective biotextiles. Preliminary cytotoxicity screening showed that both materials can support cell adhesion and proliferation. These results constitute a first validation of the two biotextiles as viable matrices for tissue engineering prior to the development of more complex systems. Given the processing efficacy and versatility of the knitting technology and the interesting structural and surface properties of the proposed polymer fibres it is foreseen that the developed systems could be attractive for the functional engineering of tissues such as skin, ligament, bone or cartilage.The authors are grateful to the Portuguese Foundation for Science and Technology (FCT) under the programs POCTI and/or FEDER (post-doctoral fellowship to Ana L Oliveira, SFRH/BPD/39102/2007), and the project TISSUE2TISSUE (PTDC/CTM/105703/2008), founded by FCT agency