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Leucite and zirconia are commonly used in the production of prosthetic dental materials. Leucite presents attractive optical properties but low toughness and wear resistance, which limits its use. Zirconia has much higher toughness, but due to aesthetic reasons and ageing issues, needs to be glass veneered. Chipping of such veneer is usually responsible for the abnormal wear induced on the antagonist teeth. Leucite reinforced with 25% of nano-zirconia is a promising alternative to overcome these issues, allowing the production of dental restorations without veneer. This study aims to investigate if leucite-zirconia composites have suitable optical, mechanical and tribological properties to be used in dental restoration. Samples with different compositions of leucite and/or nano-zirconia were produced by unidirectional compression and characterized concerning density, surface morphology, roughness, hardness, toughness, and translucency. Wear tests were performed in a chewing simulator using human cusps as counterbodies. Tests were also performed in glazed zirconia for comparison. 25% ZrO2 leads to the lowest wear of the tribological pair among the studied systems, except 100% ZrO2. This can be attributed to the toughening effect of zirconia and reduced size of third body particles. Abrasion was the main wear mechanism observed in this pair. In addition, this was the composite that presented the highest translucency.

SUMMARY INTRODUCTION: The interplay between eating disorders and psychosis is a challenging field to which little attention has been paid. Its study raises conceptual and methodological questions in both areas, making the diagnosis and management of patients difficult. Such questions are addressed and illustrated with a review and case report. METHODS: The authors present the case of a woman with Anorexia Nervosa and with comorbid Shared Psychotic Disorder, based on a literature review regarding the comorbidity between eating disorders and psychosis. The authors conducted a non-systematic review by searching the PubMed database, using the Mesh Terms “anorexia nervosa”, “bulimia nervosa”, “comorbidity” and “psychotic disorders”. RESULTS: The findings suggest that studies on the subject are limited by issues regarding data on the prevalence of comorbidities, phenomenological aspects of eating disorders, and the interface and integration with psychotic symptoms. CONCLUSIONS: The case presented illustrates the difficulties in managing a patient with a comorbid eating disorder and psychosis. In order to ensure a rigorous assessment of both psychotic and eating disorder symptoms, the focus should be on the pattern of appearance or emergence of symptoms, their phenomenology, clinical and family background of the patient, and clinical status on follow-up. RESUMO INTRODUÇÃO: A interface entre perturbação do comportamento alimentar e psicose é um campo desafiador para o qual pouca atenção foi direcionada. O seu estudo levanta algumas questões conceituais e metodológicas em ambas as áreas, dificultando o diagnóstico e o manejo dos pacientes. Essas questões são abordadas e ilustradas neste trabalho com uma revisão e um relato de caso. MÉTODOS: Os autores apresentam o caso de uma mulher com anorexia nervosa e perturbação psicótica partilhada comórbida, com base numa revisão da literatura sobre a comorbilidade entre perturbação do comportamento alimentar e psicose. Os autores realizaram uma revisão não sistemática, por meio de pesquisa no banco de dados PubMed, utilizando os termos “anorexia nervosa”, “bulimia nervosa”, “comorbilidade” e “perturbações psicóticas”. RESULTADOS: Os resultados sugerem que os estudos sobre o tema são limitados por questões inerentes a escassos dados sobre prevalência de comorbilidades, aspectos fenomenológicos das perturbações alimentares, e sua interface e integração com sintomas psicóticos. CONCLUSÕES: O caso apresentado ilustra as dificuldades no manejo de uma paciente com perturbação alimentar e psicose. A fim de garantir uma abordagem rigorosa dos sintomas psicóticos e alimentares, a avaliação do paciente deve focar o padrão de emergência dos sintomas, a sua fenomenologia, antecedentes clínicos e familiares e o seu status clínico.

Progress in the design of G-quadruplex (G4) binding ligands relies on the availability of approaches that assess the binding mode and nature of the interactions between G4 forming sequences and their putative ligands. The experimental approaches used to characterize G4/ligand interactions can be categorized into structure-based methods (circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography), affinity and apparent affinity-based methods (surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and mass spectrometry (MS)), and high-throughput methods (fluorescence resonance energy transfer (FRET)-melting, G4-fluorescent intercalator displacement assay (G4-FID), affinity chromatography and microarrays. Each method has unique advantages and drawbacks, which makes it essential to select the ideal strategies for the biological question being addressed. The structural- and affinity and apparent affinity-based methods are in several cases complex and/or time-consuming and can be combined with fast and cheap high-throughput approaches to improve the design and development of new potential G4 ligands. In recent years, the joint use of these techniques permitted the discovery of a huge number of G4 ligands investigated for diagnostic and therapeutic purposes. Overall, this review article highlights in detail the most commonly used approaches to characterize the G4/ligand interactions, as well as the applications and types of information that can be obtained from the use of each technique.

Dermoid and epidermoid cysts are rare in the head and neck, specially in the oral cavity, accounting for 1.6 %. It represents an even smaller percentage of all the oral cysts, less than 0.01%. Usually asymptomatic, however, occasionally, obstructive symptoms like dysphagia or speech difficulties are found. We present a case of a 32 years old female patient with a sublingual epidermoid cyst. The patient was referred to our ENT department with complaints of an oral mass, speech difficulties and solid food dysphagia for 1 month. Physical examination revealed a well circumscribed symmetrical mass on the floor of the mouth with no inflammatory signs, tender and fluctuant on palpation. Computed tomography (CT) was requested. CT scan showed a sublingual cystic mass inferiorly limited by the mylohyoid muscle. Aspiration was performed to improve symptoms until surgery. The liquid that resulted from aspiration showed a granulated white cheesy material. Enucleation of the cyst was performed intraorally in the operating room. Histopathologic investigation confirmed the diagnosis of epidermoid cyst. The patient fully recovered and there was no recurrence. Although rare, cases like this exist. There are several differential diagnoses and a high level of suspicion is necessary for a correct workup, diagnosis and follow-up. Surgical excision is usually necessary and curative.

Biomedical research often relies on identification and isolation of specific cell types using molecular biomarkers and sorting methods such as fluorescence or magnetic activated cell sorting. Labelling processes potentially alter the cells’ properties and should be avoided, especially when purifying cells for clinical applications. A promising alternative is the label-free identification of cells based on their physical properties. Sorting real-time deformability and fluorescence cytometry (soRT-FDC) is a microfluidic technique for label-free analysis and sorting of single cells. In soRT-FDC, bright-field images of cells are analyzed by a deep neural net (DNN) to obtain a sorting decision, but sorting was so far only demonstrated for blood cells which show clear morphological differences and are naturally in suspension. Most cells, however, grow in tissues, requiring dissociation before cell sorting which is associated with additional challenges including survival, changes in morphology, or presence of aggregates. Here, we introduce methods for robust analysis and sorting of single cells from mammalian nervous tissue and provide DNNs which are capable of distinguishing visually similar cells. Exemplarily, we employ the DNN for image-based sorting to enrich photoreceptor cells from dissociated retina for transplantation into the mouse eye. Results provide evidence that the combination of machine learning and soRT-FDC allows label-free enrichment of target cells from dissociated tissues.

Lactobacillus spp. and Bifidobacterium spp. was used to protect against gastrointestinal disorders. The present study evaluated the effects of probiotic mixture (PM) containing Lactobacillus spp. a...

Season length estimation is the task of identifying the number of observations in the dominant repeating pattern of seasonal time series data. As such, it is a common pre-processing task crucial for various downstream applications. Inferring season length from a real-world time series is often challenging due to phenomena such as slightly varying period lengths and noise. These issues may, in turn, lead practitioners to dedicate considerable effort to preprocessing of time series data since existing approaches either require dedicated parameter-tuning or their performance is heavily domain-dependent. Hence, to address these challenges, we propose SAZED: spectral and average autocorrelation zero distance density. SAZED is a versatile ensemble of multiple, specialized time series season length estimation approaches. The combination of various base methods selected with respect to domain-agnostic criteria and a novel seasonality isolation technique, allow a broad applicability to real-world time series of varied properties. Further, SAZED is theoretically grounded and parameter-free, with a computational complexity of $$\mathcal {O}(n\log n)$$ , which makes it applicable in practice. In our experiments, SAZED was statistically significantly better than every other method on at least one dataset. The datasets we used for the evaluation consist of time series data from various real-world domains, sterile synthetic test cases and synthetic data that were designed to be seasonal and yet have no finite statistical moments of any order.

Distinct cell‐types within the retina are mainly specified by morphological and molecular parameters, however, physical properties are increasingly recognized as a valuable tool to characterize and distinguish cells in diverse tissues. High‐throughput analysis of morpho‐rheological features has recently been introduced using real‐time deformability cytometry (RT‐DC) providing new insights into the properties of different cell‐types. Rod photoreceptors represent the main light sensing cells in the mouse retina that during development forms apically the densely packed outer nuclear layer. Currently, enrichment and isolation of photoreceptors from retinal primary tissue or pluripotent stem cell‐derived organoids for analysis, molecular profiling, or transplantation is achieved using flow cytometry or magnetic activated cell sorting approaches. However, such purification methods require genetic modification or identification of cell surface binding antibody panels. Using primary retina and embryonic stem cell‐derived retinal organoids, we characterized the inherent morpho‐mechanical properties of mouse rod photoreceptors during development based on RT‐DC. We demonstrate that rods become smaller and more compliant throughout development and that these features are suitable to distinguish rods within heterogenous retinal tissues. Hence, physical properties should be considered as additional factors that might affect photoreceptor differentiation and retinal development besides representing potential parameters for label‐free sorting of photoreceptors. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Choosing a surgical specialty can be a hard decision for a medical student. Several studies present data showing that most medical students fear the surgical field and end up switching to another specialty. For cardiovascular surgery, the scenario is very similar. In the last decades, the interest in cardiovascular surgery has been decreasing worldwide and the cardiothoracic surgical societies across the globe have been trying to understand the factors that push away medical students and general surgical residents from the specialty. In this regard, our work aims to focus on describe the access of students to cardiovascular surgery, especially during medical school, as well as to provide a brief report of our current data regarding the specialty.

Objective: To investigate whether hybrid repair has supremacy over conventional open repair in aortic arch diseases. Methods: A comprehensive search was undertaken in two major databases (PubMed and MEDLINE) to identify all studies comparing the two surgical techniques in five years, up to December 2018, that met the established criteria in this study. The search returned 310 papers, and 305 were selected after removing duplicates. The abstracts of the remaining articles were assessed, resulting in 15 studies that went to full-text analysis. After application of the inclusion and exclusion criteria, 8 papers remained for the final revision. Results: Eight studies met the criteria, with the inclusion of 1,837 patients. From a short-term perspective, hybrid repair and conventional open repair had similar outcomes in terms of postoperative mortality and acute neurological events. Hybrid repair was associated with less respiratory complications and risk of new intervention, as well as reduced hospital length of stay. Conventional open repair showed better mid- and long-term outcomes. Conclusion: Hybrid repair should be used in selected patients, with a high risk or very high-risk profile for conventional surgery. Finally, since most of the current data were obtained from limited to large samples, with narrow follow-up and had great heterogeneity, the best approach to the aortic arch is still variable. Therefore, the decision of the approach should be individualized and evaluated by the whole Heart Team, considering the expertise of the surgical team.

C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.

Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers.

Human nucleolin (NCL) is a multifunctional protein that is involved in diverse pathological processes. Recent evidences have shown that NCL is markedly overexpressed on the surface of most human cancer cells when compared to normal cells, being overexpressed in several malignant cells. Based on the exposed, the purpose of this pilot study is to investigate the expression pattern of NCL in canine malignant neoplasia and control groups. NCL expression at both messenger RNA and protein levels in the subcellular fractions were respectively detected by RT-PCR and western blotting, allowing to infer the NCL positivity rate in canine neoplasia. The identity of NCL amplicons obtained by RT-PCR was confirmed by Sanger sequencing and found to correspond to Canis lupus familiaris. Using flow cytometry, the blood cells expressing NCL from canine neoplasms were also identified using several cell surface markers and their levels quantified. These results showed that NCL expressed in lymphocytes, monocytes and neutrophils in dogs with malignant neoplasia is higher (> 50%) when compared with the control group. We found an increased expression of surface and cytoplasmic NCL in canine malignant neoplasia group, while nuclear NCL is predominantly found in the control group. Overall, this study discloses and identifies for the first time the presence of NCL in canine blood.

Background: Gastrointestinal disorders are frequently reported in patients with Parkinson’s disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained. Aim: To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways. Methods: Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit. Results: Parkinson’s disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders. Conclusion: Parkinson’s disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.

Calcium plays a vital key role in cardiac automatism and excitation-contraction coupling, with low serum levels associated with myocardial contractility compromise especially if myocardial sarcoplasmic reticulum is unable to maintain enough calcium content to initiate normal cardiac contraction. We present a 42-year-old woman with postsurgical untreated hypoparathyroidism and severe hypocalcaemia manifested as acute heart failure, without underlying known cardiac disease. Hypocalcaemia is a rare and potentially reversible cause of cardiomyopathy, with very few cases reported in the literature. Restoration to normal serum calcium levels usually leads to a rapid improvement of cardiac function. This rare case report highlights the importance of considering hypocalcaemia as a potentially reversible cause of severe cardiac dysfunction. Exclusion of hypocalcemia due to surgical hypoparathyroidism is mandatory in any individual with acute heart failure previously subjected to thyroidectomy.

The environment is one of the main reservoirs of antibiotic resistance genes (ARGs) but multidrug resistant (MDR) environmental isolates are barely characterised. As suggested by the name, Pedobacter species have been predominantly isolated from soils, but are also recovered from water (including drinking water), chilled food, fish, compost, sludge, glaciers and other extreme environments. The susceptibility phenotype of Pedobacter lusitanus NL19 (isolated from a deactivated uranium mine), its closely related species and the genus type strain were investigated. All strains are MDR bacteria, resistant to β-lactams, colistin, aminoglycosides and ciprofloxacin. Therefore, Pedobacter spp. are likely intrinsically resistant to β-lactams (including ertapenem) and to other three classes of antibiotics. 6%–8% of their total protein-encoding genes encode a diverse collection of putative ARGs, including β-lactamases. These enzymes are highly abundant in all the other Pedobacter strains with sequenced genomes, especially class C, class B3 and class A. LUS-1 and PLN-1 were further characterised in E. coli. LUS-1 is a class A β-lactamase and it conferred an increase in the MIC of cefotaxime, albeit very low. PLN-1 is a class B3 β-lactamase with carbapenemase activity, conferring resistance to ertapenem and a 66x and 16x increase in the MIC of imipenem and meropenem, respectively. PLN-1 also hydrolyses ampicillin, 1st and 3rd generation cephalosporins, and at a lower extent cephamycins and 4th generation cephalosporins. Therefore, Pedobacter spp. encode a large and diverse arsenal of resistance mechanisms that make them environmental superbugs.

Submitted by José Pereira (jro.pereira@gmail.com) on 2021-06-11T11:34:02Z No. of bitstreams: 1 Evidence Associated with the Use of Oxazolidinones.pdf: 132566 bytes, checksum: ea115639e273b679042b0fc2b70e2d50 (MD5) Made available in DSpace on 2021-06-11T11:34:02Z (GMT). No. of bitstreams: 1 Evidence Associated with the Use of Oxazolidinones.pdf: 132566 bytes, checksum: ea115639e273b679042b0fc2b70e2d50 (MD5) Previous issue date: 2020-02-03 info:eu-repo/semantics/publishedVersion

Workers involved in urban solid waste collection may be exposed to various environmental contaminants, including chemical pollutants, which might be mutagenic and increase the risk of diseases such as cancer. Evaluation of DNA damage in workers in this field are still scarce. This study aims to evaluate mutagenic and cytotoxic effects in workers involved in the collection and segregation of urban solid waste generated in southern Brazil. Municipal solid waste collectors were recruited in two municipalities of the state of Rio Grande do Sul. The control group was composed of workers of the education and commerce areas, with no exposure to known genotoxic agents. Slides of exfoliated buccal cells were analyzed to estimate the frequency of micronuclei (MN) as well as other nuclear abnormalities, such as broken-egg/bud, binucleation and karyorrhexis. The analyses of 44 workers and 45 control subjects have shown that the frequencies of MN, binucleated cells and karyorrhexis in the exposed workers were significantly higher than in the control group. In the exposed group, frequencies of MN and binucleated cells showed a significant positive correlation. The other cytogenetic parameters were not correlated among each other or with age and exposure time. These results indicate that the workers involved in urban solid waste collection are exposed to mutagenic and cytotoxic agents.

Objetivou-se analisar o perfil epidemiológico de 442 pacientes com leishmaniose tegumentar americana no município de Ilhéus entre os anos de 2007 a 2012. A coleta de dados foi realizada na vigilância epidemiológica do município Ilhéus, utilizando como banco de dados os casos notificados e digitados no sistema nacional de notificação de agravos de leishmaniose tegumentar americana. Foram analisadas informações sobre, sexo, faixa etária, escolaridade, critério de confirmação, tipo da leishmaniose, medicação utilizada, conclusão do caso. No município de Ilhéus a letalidade em leishmaniose tegumentar americana foi nula durante o período de estudo e a partir do ano de maior ocorrência houve um decréscimo dos casos positivos. Os indivíduos mais propícios à doença são do sexo masculino, entre 20 a 49 anos, residente em áreas rurais, pardos, autóctone. A forma mais incidente é a cutânea e a droga mais utilizada para o tratamento é a antimonial pentavalente. Não foi confirmada a sazonalidade da doença entre os meses e anos observados e nenhum surto da doença durante o período estudado no município de Ilhéus – Bahia. As informações deste estudo servirão para auxiliar o planejamento de ações epidemiológicas de saúde pública, visando medidas particulares de proteção conforme caracterização local. A partir destes resultados, espera-se mostrar a importância da notificação de investigação, diagnóstico precoce e tratamento eficaz para reduzir sequelas, bem como contribuir para a prevenção e controle da doença na cidade.

We have investigated the expression of nucleolin (NCL) in liquid biopsies of prostate cancer (PCa) patients and healthy controls to determine its correlation with tumor prognosis. To detect NCL we used a modified AS1411 aptamer designated by AS1411-N5. In presence of NCL, AS1411-N5 increases the fluorescence by assuming a G-quadruplex (G4) structure, while in the absence of NCL the fluorescence signal remains quenched. The structural characterization of AS1411-N5 was performed by biophysical studies, which demonstrated the formation of G4 parallel conformation in the presence of 100 mM K+ and the ability to recognize NCL with high affinity (KD = 138.1 ± 5.5 nM). Furthermore, the clinical relevance of NCL in PCa liquid biopsies was assessed by using an NCL-based ELISA assay. The protein was measured in the peripheral blood mononuclear cells (PBMCs) cell lysate of 158 individuals, including PCa patients and healthy individuals. The results depicted a remarkable increase of NCL levels in the PBMC's lysate of PCa patients (mean of 626.1 pg/mL whole blood) when compared to healthy individuals (mean of 198.5 pg/mL whole blood). The ELISA results also provided evidence for the usefulness of determining NCL levels in advanced PCa stages. Furthermore, a microfluidic assay showed the ability of AS1411-N5 in recognizing NCL in spiked human plasma samples.

Stroke is a leading cause of death in adult life, closely behind ischemic heart disease, and causes a significant and abiding socioeconomic burden. However, current therapies are not able to ensure full neurologic and/or sequelae-free recovery to all stroke survivors. We believe treatment efficacy and patient rehabilitation could be enhanced significantly by targeting blood-brain barrier (BBB) deregulation and inflammation-induced barrier loss that occurs after stroke. In this pathological context, bone marrow-derived endothelial progenitor cells (EPC) enter the bloodstream towards the lesion site, but their insufficient numbers and impaired angiogenic ability compromise neurovascular regeneration. In this context, cell-based therapies have become increasingly appealing since treating patients with large numbers of mesenchymal or hematopoietic stem/progenitor cells alone may boost repair. However, this approach could be met with several challenges in terms of logistics and cost; hence, the development of a drug delivery system suitable for intravenous administration and functionalized for selective uptake by circulating EPC could enhance their restorative potential without perceived complications. The ability to encapsulate proangiogenic and anti-inflammatory agents, such as retinoic acid, and to safely and easily deliver them systemically may open new therapeutic perspectives for the treatment of cerebrovascular disorders. Copyright © 2017 John Wiley & Sons, Ltd.

In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task. Mice deficient in LCN2 present an increase in the NSCs population, as a consequence of a G0/G1 cell cycle arrest induced by increased endogenous oxidative stress. Of notice, supplementation with the iron-chelating agent deferoxamine rescues NSCs oxidative stress, promotes cell cycle progression and improves contextual fear conditioning. LCN2 is, therefore, a novel key modulator of neurogenesis that, through iron, controls NSCs cell cycle progression and death, self-renewal, proliferation and differentiation and, ultimately, hippocampal function., AC Ferreira is a recipient of PhD fellowship and B Sampaio-Marques is a recipient of postdoctoral fellowship from the Foundation for Science and Technology (FCT, Portugal)/FEDER. F Marques is an assistant researcher IF/00231/2013 of the Foundation for Science and Technology (FCT, Portugal). This work was supported by Foundation for Science and Technology (FCT) and COMPETE through the project EXPL/NEU-OSD/2196/2013 (to F Marques) and by the Bial Foundation through Grant 217/12 (to JC Sousa). The work at ICVS/3B's has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and funded by FEDER funds through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The work at CICS-UBI has the support of FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by Foundation for Science and Technology (Project UID/Multi /00709/2013)., info:eu-repo/semantics/publishedVersion

According to recent models of recovery in psychosis, the patients’ perspectives about their own difficulties, symptoms and goals (health-related and in other areas) are of major importance in intervention. Self-report measures have been increasingly studied and several authors have pointed out their validity, reliability and clinical utility in people with psychotic-disorders. The present study sought to review and critically analyse the available self-report instruments for assessing delusions. Four instruments met the inclusion criteria: Characteristics of Delusions Rating Scale; Beliefs Rating Scale; Peters Delusions Inventory; and Conviction of Delusional Beliefs Scale. All scales assess delusions in a multidimensional perspective and present adequate psychometric properties, although with high variability within studies. Refining the psychometric studies of the existing instruments (mainly confirmatory factor analysis, reliability and diagnostic accuracy analyses) and developing new instruments focused on coping are future areas of research interest., As perspetivas dos pacientes acerca das suas próprias dificuldades, sintomas e objetivos (relacionados com a sua saúde e outras áreas) são de extrema importância para as intervenções, principalmente tendo em conta modelos recentes baseados na recuperação (no original recovery) das perturbações psicóticas. Cada vez mais os instrumentos de autorresposta têm sido estudados, sendo que vários autores têm defendido a sua validade, fiabilidade e utilidade clínica para pessoas com o diagnóstico de uma perturbação psicótica. Este estudo teve como objetivo rever e analisarde forma crítica os instrumentos de autorresposta existentes para a avaliação da ideação delirante. Quatro instrumentos preencheram os critérios de inclusão: a escala de características dos delírios (Characteristics of Delusions Rating Scale), a escala de avaliação das crenças (Beliefs Rating Scale), o inventário de delírios de Peters (Peters Delusions Inventory) e a escala de convicção nas ideias delirantes (Conviction of Delusional Beliefs Scale). Todas as escalas avaliam as ideias delirantes de uma perspetiva multidimensional e todas apresentam propriedades psicométricas adequadas. Noentanto elevada variablidade foi encontrada entre os estudos. O refinar dos estudos psicométricos destes instrumentos (principalmente o investimento em análises de estrutura factorial, fiabilidade e acuidade diagnóstica) e o desenvolvimento de novos instrumentos focados no coping com os delírios são áreas de investigação de interesse para o futuro.

ZusammenfassungSehbeeinträchtigungen und Erblindung aufgrund des Verlusts von Photorezeptoren stellen einen der Hauptgründe für Behinderungen in industrialisierten Gesellschaften dar. Während Stäbchenphotorezeptoren Seheindrücke unter schwachen Lichtverhältnissen vermitteln, liefern Zapfenphotorezeptoren fokussierte visuelle Eindrücke bei Tageslicht und erlauben die Wahrnehmung von Farben. Verschiedene therapeutische Strategien, zu denen auch zellbasierte Interventionen zählen, werden derzeit zur Behandlung eines Sehverlusts entwickelt. Während der letzten Dekade konnten große Fortschritte im Ersatz von Photorezeptoren in vorklinischen Tiermodellen erzielt werden. Dies beinhaltete die Klärung notwendiger Voraussetzungen, wie dem optimalen ontogenetischen Stadium für transplantierbare Photorezeptoren, zellspezifische Anreicherungsmethoden und robuste Transplantationstechniken. Außerdem konnten erste Studien Hinweise auf funktionale Verbesserungen nach Photorezeptortransplantation in Mausmodelle mit retinaler Dysfunktion liefern. Des Weiteren erlauben bedeutende Fortschritte in der Zellkulturtechnik die Generierung von photorezeptorenthaltenden retinalen Organoiden, die aus pluripotenten Stammzellen gewonnen werden und eine theoretisch unbegrenzte Quelle zur Produktion von Photorezeptortransplantaten darstellen. Interessanterweise könnte der kürzlich beschriebene Transfer von zytoplasmatischem Material zwischen Spender- und Empfängerphotorezeptoren eine weitere Behandlungsoption für Ansätze zur Zelltransplantation darstellen. In dieser Übersicht fokussieren wir uns auf die wichtigsten Entwicklungen innerhalb des Feldes der Photorezeptortransplantation, wobei wir Fortschritte, Herausforderungen und Hürden zur Entwicklung von Photorezeptortransplantationen hin zu klinischen Anwendungen diskutieren.

Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP) as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2). RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state), promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.

PROPOSE: To study CCDC103 expression profiles and understand how pathogenic variants in CCDC103 affect its expression profile at mRNA and protein level. METHODS: To increase the knowledge about the CCDC103, we attempted genotype-phenotype correlations in two patients carrying novel homozygous (missense and frameshift) CCDC103 variants. Whole-exome sequencing, quantitative PCR, Western blot, electron microscopy, immunohistochemistry, immunocytochemistry, and immunogold labelling were performed to characterize CCDC103 expression profiles in reproductive and somatic cells. RESULTS: Our data demonstrate that pathogenic variants in CCDC103 gene negatively affect gene and protein expression in both patients who presented absence of DA on their axonemes. Further, we firstly report that CCDC103 is expressed at different levels in reproductive tissues and somatic cells and described that CCDC103 protein forms oligomers with tissue-specific sizes, which suggests that CCDC103 possibly undergoes post-translational modifications. Moreover, we reported that CCDC103 was restricted to the midpiece of sperm and is present at the cytoplasm of the other cells. CONCLUSIONS: Overall, our data support the CCDC103 involvement in PCD and suggest that CCDC103 may have different assemblies and roles in cilia and sperm flagella biology that are still unexplored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01509-7) contains supplementary material, which is available to authorized users.