Histological inflammation in the endoscopically uninflamed mucosa is associated with worse outcomes in limited ulcerative colitis

Background: The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed.Methods: This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation).Results: Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05- 13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04).Conclusions: The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.peer-reviewe

Arbustus unedo essence: morphological and genetic characterization of the strawberry tree of Castelo de Paiva

O medronheiro é um arbusto da região mediterrânica que pode ser encontrada por todo o país. Ao contrário do que verifica na região sul do país, no concelho de Castelo de Paiva é atribuída uma reduzida importância económica a esta espécie. Com o intuito de preservar e potenciar a produção desta espécie e contribuir para a dinamização da economia do concelho, procedeu-se à caracterização morfológica e genética de uma amostra da população de medronheiros de Castelo de Paiva. A caracterização morfológica e genética foi realizada para um total de 10 genótipos. Para tal recolheram-se 70 folhas aleatoriamente em cada árvore. Em 40 folhas mediu-se o comprimento, largura, comprimento do pedúnculo, peso fresco, peso seco e determinou-se a área foliar. Dos caracteres morfológicos analisados, aqueles que se revelaram mais úteis na distinção dos vários genótipos foram: comprimento do pedúnculo, peso fresco e peso seco. As restantes 30 folhas foram utilizadas para a caracterização genética. Esta caracterização foi realizada recorrendo a um marcador de DNA, ISSR. Os 5 primeiros exemplaresutilizados na técnica de ISSR demonstraram-se polimórficos. Os resultados da caracterização genética sugerem que a variabilidade genética na população é média a alta.The strawberry tree is a shrub native in the Mediterranean region and it can be found throughout Portugal. Unlike the case in the southern region of the country, in Castelo de Paiva a minor economic importance is given to this species. In order to preserve, to enhance the production of this species and to contribute to the boosting of the economy of the region, we proceeded to the characterization of a small sample population of this fruit tree of Castelo de Paiva in what concerns to its morphology and genetics. The morphological and genetic characterization was performed for a total of 10 genotypes. For this, 70 leaves were randomly collected from each tree. For 40 leaves, it was measured the length, the width, the peduncle length, the wet weight, the dry weight and determined the leaf area. Of the morphological characteristics analyzed, the ones that proved most useful in distinguishing the various genotypes were: the length peduncle, the wet weight and the dry weight. The remaining 30 leaves were used in the genetic characterization. This characterization was performed using a DNA marker, the ISSR. The 5 primers used in the ISSR technique proved to be polymorphic. The results from the genetic characterization suggest that variability in population genetics is medium to high

Livro Verde dos Montados

O Livro Verde dos Montados apresenta diversos objectivos que se interligam: Em primeiro lugar, o Livro Verde pretende reunir e sistematizar, de uma forma simples e acessível ao público, o conhecimento produzido em Portugal pelos investigadores e técnicos de várias instituições de investigação ou de gestão que estudam o Montado. Assume-se como uma oportunidade de caracterizar o sistema tendo em conta as suas várias dimensões, identificando as principais ameaças à sua preservação assim como os caminhos que podem ajudar à sua sustentabilidade. Não sendo um documento científico, baseia-se no conhecimento científico e pretende constituir a base para uma plataforma de organização, tanto dos investigadores como do conhecimento científico actualmente produzido em Portugal sobre o Montado.Em segundo lugar, o Livro Verde deverá contribuir para um entendimento partilhado do que é o Montado, por parte do público, de técnicos e de especialistas, conduzindo a uma classificação mais clara do que pode ser considerado Montado e de quais os tipos distintos de Montados que podem ser identificados. Em terceiro lugar, o Livro Verde estabelece as bases para uma estratégia coordenada de disponibilização de informação sobre o sistema Montado, visando o seu conhecimento, apreciação e valorização pela sociedade portuguesa no seu conjunto. Deste modo, o Livro Verde poderá constituir um instrumento congregador e inspirador para a realização de acções de sensibilização e informação sobre o Montado. Em quarto lugar, pretende-se que o Livro Verde contribua para um maior reconhecimento e valorização do Montado como sistema, a nível do desenho das políticas nacionais por parte dos vários sectores envolvidos.Finalmente, o Livro Verde constituirá um documento parceiro do Livro Verde das Dehesas, produzido em Espanha em 2010, de forma a reforçar o reconhecimento e a devida valorização destes sistemas silvo-pastoris no desenho das estratégias e políticas relevantes pelas instituições europeias. Em suma, os autores pretendem que o Livro Verde dos Montados se afirme como o primeiro passo para uma efectiva definição e implementação de uma estratégia nacional para os Montados

Identificação de Problemas e Propostas para Melhoria

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COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Supressão da patogénese da doença de Machado-Joseph através da modulação da sinalização serotoninérgica: contribuição dos receptores de serotonina

Tese de Doutoramento em Ciências da SaúdeA doença de Machado-Joseph (DMJ) é uma doença debilitante caracterizada pela perda progressiva do equilíbrio e da coordenação motora. A nível molecular, a DMJ está associada à expansão da repetição de Citosina-Adenina-Guanina (CAG) no gene da ataxina-3. Isto traduz-se num segmento expandido de poliglutaminas na proteína ataxina-3 (ATXN3), que é propenso à auto-associação, sendo a agregação desta proteína uma característica da doença. Apesar dos vários esforços efectuados, não existe cura para esta doença fatal. A modulação da sinalização serotoninérgica foi anteriormente descrita como potencial estratégia terapêutica para a DMJ. O tratamento com citalopram (CIT), um inibidor seletivo da recaptação de serotonina, suprimiu a patogénese da DMJ em vários modelos animais, sendo o efeito do CIT dependente do transportador de serotonina, o seu alvo molecular, com provável contribuição dos receptores serotoninérgicos 5-HT1A/SER-4 e 5-HT2/SER-1. No entanto, o papel de cada receptor serotoninérgico na supressão da proteotoxicidade da ATXN3 mutante não foi ainda elucidado. Aqui, com o objetivo de determinar a contribuição de cada receptor de serotonina (5-HTR) na supressão da proteotoxicidade da ATXN3 usámos um modelo de C. elegans que recapitula as principais características da DMJ, seguindo abordagens químico-genéticas, farmacológicas e bioquímicas, bem como técnicas de microscopia in vivo. Inicialmente, explorámos a contribuição do receptor 5-HT1A usando befiradol, um agonista potente e altamente específico destes receptores. A administração crónica e aguda deste composto melhorou a função motora dos mutantes, sendo o ortólogo do receptor 5-HT1A no nematode, o SER-4, necessário para a sua ação. De forma a aprofundar o conhecimento sobre o impacto do tratamento com befiradol na proteotoxicidade da ATXN3, optimizámos ensaios de retardação em filtro e fracionamento bioquímico para avaliar as espécies agregadas da ATXN3, demonstrando-se que ambas as modalidades de tratamento afectaram a solubilidade desta proteína. De realçar que, usando químicogenética e medições de atividade neuronal, foi-nos possível definir os auto- e hetero-receptores 5- HT1A/SER-4 como essenciais para o efeito terapêutico do befiradol e propor o receptor 5-HT1A como novo alvo terapêutico para a DMJ. Além disso, identificámos uma contribuição parcial dos receptores 5- HT6/SER-5 e 5-HT7/SER-7 para a ação do CIT. Surpreendentemente, o antagonismo dos receptores 5- HT2/SER-1, 5-HT6/SER-5 e 5-HT7/SER-7 mostrou-se benéfico para a função motora de animais mutantes, o que é consistente com dados de perfil de expressão de RNA e farmacoterapia multimodal obtidos no nosso laboratório. Embora promissores, são necessários mais estudos para reforçar estes achados e elucidar as vias específicas pelas quais cada 5-HTR individual afecta a proteotoxicidade da ATXN3.Machado-Joseph disease (MJD) is a debilitating disease mainly characterized by a progressive loss of balance and motor coordination. At the molecular level, this autosomal dominant disease is associated with an expansion of the Cytosine-Adenine-Guanine (CAG) repeat in the ataxin-3 gene. This translates into a pathologic polyglutamine tract in the ataxin-3 protein (ATXN3) that is prone to selfassociate, aggregation of ATXN3 being a hallmark of the disease. Although several efforts have been made, no cure is yet available for this fatal disorder. Serotonergic signalling modulation, by selective serotonin reuptake inhibitors (SSRIs), was previously described as a potential therapeutical strategy for MJD. Treatment with citalopram (CIT), a SSRI used in the clinics to treat depression, suppressed MJD pathogenesis in a disease-modifying manner, in several animal models. CIT’s effect was dependent on its molecular target, the serotonin transporter SERT, likely with the additional need of the serotonin receptors 5-HT1AR/SER-4 and 2-HT2R/SER-1. However, the exact role of each serotonin receptor (5-HTR) in the suppression of mutant ATXN3 proteotoxicity remains to be fully elucidated. Here, we aimed at determining the contribution of each of the 5-HTRs in the suppression of ATXN3 proteotoxicity using a C. elegans model that recapitulates major hallmarks of MJD, by employing chemical genetics, pharmacological- and biochemical- approaches, as well as in vivo dynamic imaging techniques. First, we explored the contribution of the 5-HT1AR using a highly specific and potent agonist of these receptors, befiradol. Chronic and acute administration of befiradol rescued the motor function of mutant animals, the 5-HT1AR orthologue in the nematode, SER-4, being required for its action. To further explore the impact of befiradol treatment in ATXN3 proteotoxicity, we optimised filter retardation and biochemical fractionation assays to assess mutant ATXN3 aggregation states, and we showed that both treatment modalities impacted ATXN3 solubility. Importantly, using chemical genetics and single neuron neuronal activity measurements, we defined 5-HT1AR/SER-4 auto- and heteroreceptors’ function to be essential to befiradol therapeutic outcome, and the 5-HT1AR as a novel therapeutic target for MJD. Additionally, we found a partial contribution of 5-HT6R/SER-5 and 5-HT7R/SER-7 for CIT action and, surprisingly, antagonism of 5-HT2R/SER-1, 5-HT6R/SER-5 and 5-HT7R/SER-7 showed to be beneficial for motor function of mutant animals, which is consistent with RNA-expression profiling and multimodal pharmacotherapy results obtained in our laboratory. Although promising, further studies are needed to support these findings and to elucidate the specific pathways by which each individual serotonin receptor impacts ATXN3 proteotoxicity.The work presented in this thesis was performed at the Life and Health Sciences Research Institute (ICVS) and at the Bn’ML – Behavioral & Molecular Lab, at the School of Medicine, University of Minho. Financial support was provided by grants from the Portuguese Foundation for Science and Technology (FCT): Doctoral Programme in Applied Health Sciences fellowship (PD/BDE/127834/2016) to J. Pereira-Sousa; and by FEDER, through the Competitiveness Internationalization Operational Programme (POCI) under the scope of the project POCI-01-0145-FEDER-031987 to A. Teixeira-Castro, supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and by ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER022122); and by National funds, through the FCT - project UIDB/50026/2020 and UIDP/50026/2020. This work was also funded through the National Ataxia Foundation (NAF), USA

Ureteroneocystostomy after failed dextranomer/hyaluronic acid copolymer injection for vesicoureteral reflux treatment

To report our experience of open ureteroneocystostomy after failed endoscopic treatment.Purpose To report our experience of open ureteroneocystostomy after failed endoscopic treatment. Material and methods Clinical charts of 787 children who entered our dextranomer/hyaluronic acid copolymer (DxHA) endoscopic injection program for vesicoureteral reflux (VUR) treatment between May 2000 and December 2009 were reviewed. Fifty-one of these patients were submitted to open ureteroneocystostomy for complete resolution of VUR. Results Twenty-eight patients (55%) were female. Median age at surgery was 65 months (range: 26–182). Median time going from first endoscopic injection until open surgery was 13 months (range 1–58). Surgical ureteral reimplantation was bilateral in 62.7% of the cases. Of a total of 83 operated ureters, nine were duplex ureters, nine were megaureters, six were ectopic, and two had periureteral diverticulum. Mean operative time was 70 min (range 45–120 min). There were no intra-operative complications. Follow-up VCUG showed complete resolution of VUR in 98% of patients. There was only one right-sided grade III VUR that persisted after bilateral reimplantation. It resolved with a single subureteral DxHA injection. Conclusions Ureteroneocystostomy after a failed endoscopic treatment can achieve successful results in a high percentage of patients with minimal complications

Meleis’s Transition Theory in Gerontogeriatric Nursing and the Future Need for Specialized Care

With an ageing global population, healthcare systems confront challenges unique to the elderly. Current care models primarily manage health–illness shifts but frequently miss developmental transitions, particularly for older adults. Meleis’s transition theory offers an underutilized framework to rejuvenate our gerontogeriatric nursing approach. This article aims to articulate and advocate the value of Meleis’s transition theory as a framework for gerontogeriatric nursing, focusing on developmental transitions, thereby seeking a transformative change in the quality of elderly care. The article delves into Meleis’s transition theory’s vital components—transition types, conditions, and nursing therapeutics. It explores how these can be a multifaceted guide for gauging and overseeing ageing’s developmental shifts; adopting this theoretical perspective deepens our comprehension and bears tangible implications. Nurses versed in this theory could appreciate the benefits of a nuanced approach to the elderly, distinguishing it from the conventional biomedical stance. As the demands of an ageing populace grow, the integration of Meleis’s transition theory into nursing practices is not merely beneficial but imperative, setting a new standard for comprehensive and specialized elderly care

Effects of anodal multichannel transcranial direct current stimulation (tDCS) on social-cognitive performance in healthy subjects: A randomized sham-controlled crossover pilot study

Recent studies suggest that temporoparietal junction (TPJ) modulation can influence attention and social cognition performance. Nevertheless, no studies have used multichannel transcranial direct current stimulation (tDCS) over bilateral TPJ to estimate the effects on these neuropsychological functions. The project STIPED is using optimized multichannel stimulation as an innovative treatment approach for chronic pediatric neurodevelopmental disorders, namely in children/adolescents with Autism Spectrum Disorder (ASD). In this pilot study, we aim to explore whether anodal multichannel tDCS coupled with a Joint Attention Task (JAT) influences social-cognitive task performance relative to sham stimulation, both in an Emotion Recognition Task (ERT) and in a Mooney Faces Detection Task (MFDT), as well as to evaluate this technique's safety and tolerability. Twenty healthy adults were enrolled in a randomized, single-blinded, sham-controlled, crossover study. During two sessions, participants completed the ERT and the MFDT before and after 20min of sham or anodal tDCS over bilateral TPJ. No significant differences on performance accuracy and reaction time were found between stimulation conditions for all tasks, including the JAT. A significant main time effect for overall accuracy and reaction time was found for the MFDT. Itching was the most common side effect and stimulation conditions detection was at chance level. Results suggest that multichannel tDCS over bilateral TPJ does not affect performance of low-level emotional recognition tasks in healthy adults. Although preliminary safety and tolerability are demonstrated, further studies over longer periods will be pursued to investigate the clinical efficacy in children/adolescents with ASD, where social cognition impairments are preponderant