Estimation of periodontitis national and regional prevalence based on the study of periodontal health Almada-Seixal

Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas MonizAims: To estimate the risk of periodontitis in the Portuguese population at a regional level and the prevalence of periodontitis in the municipalities that make up the clusters with peri-urban characteristics. Materials and Methods: In this study, we have estimated the periodontitis risk for Portuguese population, at regional/territory-level, based on a multivariate approach, using sociodemographic, economic and health services data. The information was gathered for all 308 Portuguese municipalities and compiled in a large set of 52 variables. Principal Component Analysis (PCA), Factor Analysis (FA) and clustering techniques were used to model the nationwide geographical distribution of the disease. Estimation of periodontitis risk for each municipality was achieved by calculation of a normalized score, obtained as an adjusted linear combination of six independent factors that were extracted through PCA/FA. The municipalities were also classified according to a quartile-based risk grade, in each cluster. Additionally, linear regression was used to estimate the periodontitis prevalence within the peri-urban municipalities clusters, accounting for 30.5% of the Portuguese population. Results: A total of nine municipalities clusters were obtained with the following characteristics: mainly rural/low populated, including small villages (1), partly rural/including small cities (2), partly rural/including small and médium cities (3), mainly urban/peri-urban/including medium to large size cities (4 and 5). Uninominal clusters with their own characteristics were also obtained, grouped in clusters 6,7,8 and 9. The estimated periodontitis prevalence for the 18 municipalities included in the four peri-urban clusters, ranged from 41.2 to 69.0%. Conclusions: Periodontitis proved to be a disease with high prevalence in Portugal. The most affected population tends to be the oldest, with the highest unemployment rate, low income, precarious housing and with less schooling. To counter these values, it is foreseen the need to invest in oral health through the National Health Service.Objetivos: Estimar o risco de periodontite na população portuguesa a nível regional e a prevalência de periodontite dos municípios que integram os clusters com características periurbanas. Materiais e Métodos: Neste estudo, estimou-se o risco de periodontite para a população portuguesa, a nível regional/territorial, com base numa abordagem multivariada, utilizando dados sociodemográficos, económicos e dos serviços de saúde. A informação foi recolhida para todos os 308 municípios portugueses e compilada num conjunto de 52 variáveis. A Análise de Componentes Principais (ACP), Análise Fatorial (AF) e técnicas de agrupamento foram utilizadas para modelar a distribuição geográfica nacional da doença. A estimativa do risco de periodontite para cada município foi obtida pelo cálculo de um score normalizado, obtido como uma combinação linear ajustada de fatores independentes que foram extraídos por ACP/AF. Os municípios também foram classificados de acordo com um grau de risco baseado em quartis, em cada cluster. Adicionalmente, a regressão linear foi utilizada para estimar a prevalência de periodontite nos aglomerados de municípios periurbanos, representando 30,5% da população portuguesa. Resultados: Obteve-se um total de nove aglomerados (clusters) de municípios com as seguintes características: principalmente rural/pouco povoado, incluindo pequenas aldeias (1), parcialmente rural/incluindo pequenas cidades (2), parcialmente rural incluindo pequenas e médias cidades (3), principalmente urbano/periurbano/incluindo cidades de médio a grande porte (4 e 5). Obtiveram-se ainda aglomerados uninominais com caraterísticas próprias agrupados nos clusters 6,7,8 e 9. A prevalência estimada de periodontite para os 18 municípios incluídos nos quatro clusters periurbanos variou de 41,2 a 69,0%. Conclusão: A periodontite mostrou ser uma doença com elevada prevalência em Portugal. A população mais afetada tem tendência a ser a mais envelhecida, com maior taxa de desemprego, baixo rendimento, precariedade habitacional e com menor formação escolar. Para contrariar estes valores prevê-se a necessidade de apostar na saúde oral através do Serviço Nacional de Saúde

Developing an Advanced Therapy Medicinal Product (ATMP) for the treatment of GvHD

Mesenchymal stem/ stromal cells (MSCs) have been proved to be capable to modulate the immune system through direct interactions target cell-MSC and secretion of soluble molecules that are induced or upregulated following cross-talk with target cells. In this study, a full biological characterization of ImmuneSafe® (IS) features including identity, potency and safety which constitute the Critical Quality Attributes (CQAs) of the product was performed with purpose of providing tools that will assure the consistency and robustness of the manufacturing process or demonstrating product/ process comparability after a particular change in the manufacturing process. In order to achieve this goal a (bio) assay panel was developed and applied to IS in two different steps of manufacturing process. IS CQAs allowed a robust and reproducible characterization of the product, demonstrating their potential to be used throughout the production stage. Similar studies were also performed with similar cell types, such as human skin fibroblasts and MSCs differentiated in adipocytes and osteocytes, which were then benchmarked with IS. The results showed that none of these cell types demonstrated a comparable level of therapeutic potency to IS. The patient enrolling protocol for IS clinical trial to treat GvHD will include the administration of immunosuppressive drugs (methylprednisolone or prednisolone) concomitantly with IS administration. The impact of these drugs on IS identity was evaluated through immunophenotype characterization and potency was evaluated through the activation of the different immunomodulatory pathways. The results showed that immunosuppressive drugs tested, methylprednisolone and prednisolone, did not seem to have a beneficial or detrimental interaction with IS. MSCs are commonly stored in cryopreservation conditions before the deliver to the patient. However, recent studies have shown that banked fresh thawed MSCs have impaired immunomodulatory properties compared to MSCs in culture. IS response to an inflammatory microenvironment was compared in different times of release and fresh thawed cells revealed to have several responses compromised under pro-inflammatory environment. Additionally, IS secretome was also affected, since the production of several cytokines were decreased or even switched off, as well as the immunosuppressive activity of the product. For these reasons the implementation of a release culture step was found to be advantageous in order to maximize the therapeutic potency of IS. Another important issue for cell-based therapies is the product delivery to the hospital. Cells should be formulated in a suitable excipient for intravenous infusion capable of maintaining the cell viability and therapeutic potential during the purposed product shelf-life. For this purpose IS was formulated in a saline solution and identity and potency tests were performed. Hypothermosol was capable of maintaining at least 70% of initial cell number population with 80% of viability, as well as its identity and potency features within a 48h-window. These studies enable a comprehensive IS characterization and the set-up of the assays to be used in the manufacturing process under GMP conditions. Additionally, no detrimental effects on the therapeutic potency of IS were associated with the interactions with the immunosuppressive drugs that will be used in the clinical trial, thus indicating the clinical results will not probably be affected by the background therapy applied to patients. The process of product release was also optimized to guarantee a cell product with maximized immunomodulatory properties and a 48-hour shelf-life was determined, which is a critical issue for the planning of IS logistics for the clinical trial

Do GnRH Agonists Really Increase Body Weight Gain? Evaluation of a Multicentric Portuguese Cohort of Patients With Central Precocious Puberty

Funding Information: We would like to thank all the colleagues who collected data for the National Database: Joana Serra, Unidade de Endocrinologia Pediátrica, Hospital Pediátrico de Coimbra, Portugal; Marcelo Fonseca, Unidade de Endocrinologia Pediátrica, Hospital Pedro Hispano, Matosinhos, Portugal; Maria João Oliveira, Unidade de Endocrinologia Pediátrica, Centro Materno Infantil do Norte, Porto, Portugal; Maria Miguel Gomes, Unidade de Endocrinologia Pediátrica, Hospital de Braga, Portugal; Paula Vieira, Serviço de Pediatria, Hospital São Francisco Xavier, Lisbon, Portugal; Rita Silva, Unidade de Endocrinologia Pediátrica, Hospital de São João, Porto, Portugal; Sónia Gomes, Unidade de Endocrinologia Pediátrica, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal; Susana Figueiredo, Serviço de Pediatria, Hospital de Viana de Castelo, Portugal; and Susana Pacheco, Unidade de Endocrinologia Pediátrica, Hospital Fernando da Fonseca, Amadora, Portugal. We also thank all children, adolescents, and their parents for their cooperation and understanding. This investigator-initiated study was supported by an unconditional research grant from Ipsen. Funding Information: We would like to thank all the colleagues who collected data for the National Database: Joana Serra, Unidade de Endocrinologia Pedi?trica, Hospital Pedi?trico de Coimbra, Portugal; Marcelo Fonseca, Unidade de Endocrinologia Pedi?trica, Hospital Pedro Hispano, Matosinhos, Portugal; Maria Jo?o Oliveira, Unidade de Endocrinologia Pedi?trica, Centro Materno Infantil do Norte, Porto, Portugal; Maria Miguel Gomes, Unidade de Endocrinologia Pedi?trica, Hospital de Braga, Portugal; Paula Vieira, Servi?o de Pediatria, Hospital S?o Francisco Xavier, Lisbon, Portugal; Rita Silva, Unidade de Endocrinologia Pedi?trica, Hospital de S?o Jo?o, Porto, Portugal; S?nia Gomes, Unidade de Endocrinologia Pedi?trica, Centro Hospitalar Universit?rio de Lisboa Central, Lisbon, Portugal; Susana Figueiredo, Servi?o de Pediatria, Hospital de Viana de Castelo, Portugal; and Susana Pacheco, Unidade de Endocrinologia Pedi?trica, Hospital Fernando da Fonseca, Amadora, Portugal. We also thank all children, adolescents, and their parents for their cooperation and understanding. This investigator-initiated study was supported by an unconditional research grant from Ipsen. Publisher Copyright: Copyright © 2022 Leite, Galo, Antunes, Robalo, Amaral, Espada, Castro, Simões Dias and Limbert.Introduction: There are several concerns associated with gonadotropin-releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP), such as obesity and changes in body mass index (BMI). We aimed to investigate whether any anthropometric differences exist and if they persist over time. Methods: We conducted an observational study of Portuguese children (both sexes) diagnosed with CPP between January 2000 and December 2017, using a digital platform, in order to analyze the influence of GnRHa treatment on BMI-SD score (BMI-SDS). Results: Of the 241 patients diagnosed with CPP, we assessed 92 patients (8% boys) in this study. At baseline, 39% of the patients were overweight. BMI-SDS increased with treatment for girls but then diminished 1 year after stopping GnRHa therapy (p = 0.018). BMI-SDS variation at the end of treatment was negatively correlated with BMI-SDS at baseline (p < 0.001). Boys grew taller and faster during treatment than did girls (p < 0.001), and therefore, their BMI-SDS trajectory might be different. Conclusions: This study showed an increase of body weight gain during GnRHa treatment only in girls, which reversed just 1 year after stopping treatment. The overall gain in BMI-SDS with treatment is associated with baseline BMI-SDS.publishersversionpublishe

Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1β protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1β protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients

Comparison of two beam angular optimization algorithms guided by automated multicriterial IMRT

To compare two beam angle optimization (BAO) algorithms for coplanar and non-coplanar geometries in a multicriterial optimization framework

Height benefit of GnRH agonists after age 8 in a Portuguese cohort of central precocious puberty

© 2023 John Wiley & Sons Ltd.Objective: Idiopathic central precocious puberty (iCPP) is common in paediatric endocrinology. Gonadotropin-releasing hormone agonists (GnRHa) are safe, but the effect on final height and the ideal timing for treatment remains controversial. This study aims to assess the effectiveness of GnRHa on growth outcomes in girls with iCPP treated before and after the age of 8 years old. Design and patients: This retrospective longitudinal study evaluated data from Portuguese girls with iCPP who completed treatment between 2010 and 2021. Measurements: Auxological and clinical characteristics were compared according to age at treatment onset. Results: A cohort of 134 girls with iCPP, was divided into early treatment (ET) (<8 years, n = 48) and later treatment (LT) groups (≥8 years, n = 86). In both groups, most children presented with Tanner II and III. Tanner IV was more frequent in LT group (p = .003). At the end of treatment, predicted adult height increased in both groups (ET p = .032; LT p = .04) and bone age significantly slowed down in all participants (p = .008, p = .034). The height gain was greater in the ET group, but without significant differences (p = .065). Conclusions: Treatment with GnRHa improved final height in all girls with iCPP, even when initiated after 8 years. To achieve better outcomes, treatment should be provided promptly after diagnosis.info:eu-repo/semantics/publishedVersio

Learning target-based preferences through additive models: An application in radiotherapy treatment planning

This article presents a new Multi-Criteria Decision Aiding preference disaggregation method based on an asymmetric target-based model. The decision maker’s preferences are elicited considering the choices made given a set of comparisons among pairs of solutions (the stimuli). It is assumed that the decision maker has a reference value (target) for the stimulus. Solutions that do not comply with this reference value for some of the criteria dimensions considered will be penalized, and an inferred weight is as- sociated with each dimension to calculate a penalty score for each solution. One of the differentiating features of the proposed model when compared with other existing models is the fact that only solu- tions that do not meet the target are penalized. The target is not interpreted as an ideal solution, but as a set of threshold values that should be taken into account when choosing a solution. The proposed ap- proach was applied to the problem of choosing radiotherapy treatment plans, using a set of retrospective cancer cases treated at the Portuguese Oncology Institute of Coimbra. Using paired comparison choices made by one radiation oncologist, the preference model was built and was tested with in-sample and out-of-sample data. It is possible to conclude that the preference model is capable of representing the radiation oncologist’s preferences, presenting small mean errors and leading, most of the time, to the same treatment plan chosen by the radiation oncologist

Saúde ambiental : caderno de notas soltas III

Junho de 2023 © AutoresNa sua 3.ª edição, o Caderno de Notas Soltas pretende reunir diferentes perspetivas e metodologias, celebrando a sua razão de ser e a nobreza da sua génese intimamente ligada à realidade dos estudantes. Na verdade, passados três anos retomamos uma colaboração firmada desde a primeira hora com a Associação de Estudantes da Faculdade de Medicina de Lisboa (AEFML), num registo de proximidade da comunidade estudantil e dos interesses das gerações futuras.info:eu-repo/semantics/publishedVersio

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora