Relatório de atividade clínica

A Saúde Oral é parte integrante e essencial da Saúde e, por isso, deve ser encarada como um bem social, emocional e físico, fundamental para o bem-estar e qualidade de vida do ser humano. Assim sendo, pode-se afirmar que para existir um estado de saúde pleno, é necessário que as pessoas tenham uma cavidade oral sã e sem enfermidades. Neste contexto, a Medicina Dentária, através das suas diversas áreas de atuação (Cirurgia, Dentisteria, Endodontia, Medicina Oral, Oclusão, Odontopediatria, Ortodontia, Periodontologia e Prostodontia) e numa perspetiva multidisciplinar, desempenha um papel fundamental para a manutenção da Saúde e higiene oral da população em geral. O presente Relatório de Atividade Clínica aborda e trata os atos clínicos relativos ao universo de pacientes atendidos pelo meu Trinómio no corrente ano letivo, circunscrito ao período de setembro de 2013 a maio de 2014, destacando a função de operadora ou assistente em que neles intervim. Essa abordagem é centrada numa apresentação gráfica por áreas disciplinares comparando o total dos atos do trinómio com os que pratiquei individualmente. Destacam-se três casos clínicos diferenciados que, por isso, terão uma abordagem diferente dos restantes fazendo-se um desenvolvimento mais pormenorizado dos respetivos planos de tratamentos efetuados. A atividade clínica curricular é um processo de aprendizagem indispensável, na medida em que permite aplicar todos os conhecimentos teóricos adquiridos ao longo do curso, contribuindo não só para o desenvolvimento profissional mas também pessoal.Oral health as an essential health’s part, has to be seen as a social, emotional and physical benefit crucial to the well-being and quality of life. Therefore, to be healthy, people need to have a health’s oral cavity without oral diseases. In this context, Dental Medicine, through its specialties (Surgery, Dentistry, Endodontics, Oral Medicine, Occlusion, Pediatric Dentistry, Orthodontics, Periodontics and Prosthodontics) plays a key role in maintaining oral health and oral hygiene in the general population in a multidisciplinary perspective, This clinical activity report will focus on clinical acts provided to a group of patients held by my group, in a period that extends from September 2013 to May 2014. The respective graphical presentation will be done according to different curricular areas comparing the total of the acts of the group with those who had been practiced individually. In three special cases, in which differentiated clinical aspects were identified, different approaches took place and a more detailed report of the procedures will be presented. In this context, the curricular skills revealed to be a valuable resource, since the theoretical knowledge acquired during the course has effectively contributed to the technical approaches chose for each clinical case as well as for my personal development

Phenotypic Effects of Wild-Type and Mutant SOD1 Expression in N9 Murine Microglia at Steady State, Inflammatory and Immunomodulatory Conditions

Accumulation of mutated superoxide dismutase 1 (mSOD1) in amyotrophic lateral sclerosis (ALS) involves injury to motor neurons (MNs), activation of glial cells and immune unbalance. However, neuroinflammation, besides its detrimental effects, also plays beneficial roles in ALS pathophysiology. Therefore, the targeting of microglia to modulate the release of inflammatory neurotoxic mediators and their exosomal dissemination, while strengthening cell neuroprotective properties, has gained growing interest. We used the N9 microglia cell line to identify phenotype diversity upon the overexpression of wild-type (WT; hSOD1WT) and mutated G93A (hSOD1G93A) protein. To investigate how each transduced cell respond to an inflammatory stimulus, N9 microglia were treated with lipopolysaccharide (LPS). Glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS), known to exert neuroprotective properties, were tested for their immunoregulatory properties. Reduced Fizz1, IL-10 and TLR4 mRNAs were observed in both transduced cells. However, in contrast with hSOD1WT-induced decreased of inflammatory markers, microglia transduced with hSOD1G93A showed upregulation of pro-inflammatory (TNF-α/IL-1β/HMGB1/S100B/iNOS) and membrane receptors (MFG-E8/RAGE). Importantly, their derived exosomes were enriched in HMGB1 and SOD1. When inflammatory-associated miRNAs were evaluated, increased miR-146a in cells with overexpressed hSOD1WT was not recapitulated in their exosomes, whereas hSOD1G93A triggered elevated exosomal miR-155/miR-146a, but no changes in cells. LPS stimulus increased M1/M2 associated markers in the naïve microglia, including MFG-E8, miR-155 and miR-146a, whose expression was decreased in both hSOD1WT and hSOD1G93A cells treated with LPS. Treatment with GUDCA or VS led to a decrease of TNF-α, IL-1β, HMGB1, S100B and miR-155 in hSOD1G93A microglia. Only GUDCA was able to increase cellular IL-10, RAGE and TLR4, together with miR-21, while decreased exosomal miR-155 cargo. Conversely, VS reduced MMP-2/MMP-9 activation, as well as upregulated MFG-E8 and miR-146a, while producing miR-21 shuttling into exosomes. The current study supports the powerful role of overexpressed hSOD1WT in attenuating M1/M2 activation, and that of hSOD1G93A in switching microglia from the steady state into a reactive phenotype with low responsiveness to stimuli. This work further reveals GUDCA and VS as promising modulators of microglia immune response by eliciting common and compound-specific molecular mechanisms that may promote neuroregeneration

Recovery of depleted miR-146a in ALS cortical astrocytes reverts cell aberrancies and prevents paracrine pathogenicity on microglia and motor neurons

Copyright © 2021 Barbosa, Gomes, Sequeira, Gonçalves-Ribeiro, Pina, Carvalho, Moreira, Vaz, Vaz and Brites. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Thus, ALS astrocyte secretome may disrupt cell homeostasis and impact on ALS pathogenesis. Previously, we identified a specific aberrant signature in the cortical brain of symptomatic SOD1-G93A (mSOD1) mice, as well as in astrocytes isolated from the same region of 7-day-old mSOD1 mice, with upregulated S100B/HMGB1/Cx43/vimentin and downregulated GFAP. The presence of downregulated miR-146a on both cases suggests that it can be a promising target for modulation in ALS. Here, we upregulated miR-146a with pre-miR-146a, and tested glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS) for their immunoregulatory properties. VS was more effective in restoring astrocytic miR-146a, GFAP, S100B, HMGB1, Cx43, and vimentin levels than GUDCA, which only recovered Cx43 and vimentin mRNA. The miR-146a inhibitor generated typical ALS aberrancies in wild type astrocytes that were abolished by VS. Similarly, pre-miR-146a transfection into the mSOD1 astrocytes abrogated aberrant markers and intracellular Ca2+ overload. Such treatment counteracted miR-146a depletion in sEVs and led to secretome-mediated miR-146a enhancement in NSC-34-motor neurons (MNs) and N9-microglia. Secretome from mSOD1 astrocytes increased early/late apoptosis and FGFR3 mRNA in MNs and microglia, but not when derived from pre-miR-146a or VS-treated cells. These last strategies prevented the impairment of axonal transport and synaptic dynamics by the pathological secretome, while also averted microglia activation through either secretome, or their isolated sEVs. Proteomic analysis of the target cells indicated that pre-miR-146a regulates mitochondria and inflammation via paracrine signaling. We demonstrate that replenishment of miR-146a in mSOD1 cortical astrocytes with pre-miR-146a or by VS abrogates their phenotypic aberrancies and paracrine deleterious consequences to MNs and microglia. These results propose miR-146a as a new causal and emerging therapeutic target for astrocyte pathogenic processes in ALS.This work was supported by the Research Grant of the Santa Casa Scientific Research Program on ALS, by Santa Casa da Misericórdia de Lisboa (SCML), Portugal, Project Ref. ELA-2015-002 (to DB). Fundação para a Ciência e a Tecnologia (FCT) also supported the project PTDC/MED-NEU/31395/2017 (to DB), PTDC/MED-QUI/30021/2017 (to RM) and iMed. ULisboa (UIDB/04138/2020 and UIDP/04138/2020), together with Programa Operacional Regional de Lisboa and the Programa Operacional Competitividade e Internacionalização (LISBOA-01-0145-FEDER-031395 to DB). Individual fellowships MB (SFRH/BD/129586/2017), CG (SFRH/BD/102718/2014), AV (SFRH/BPD/76590/2011), and JG-R PD/BD/150342/2019 were from FCT. CS was a research fellowship recipient from SCML.info:eu-repo/semantics/publishedVersio

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts

We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.(SFRH/BPD/115169/2016) funded by Fundação para a Ciência e Tecnologia (FCT); ERDF (European Regional Development Fund) through the operations: POCI-01-0145-FEDER-029130 ('mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies') cofunded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).info:eu-repo/semantics/publishedVersio

Especificidade do teste de provocação na Síndrome de Brugada: a queda de um mito

O rastreio de familiares de doentes com Síndrome de Brugada (SB) com ECG basal não diagnóstico deve incluir o teste de provocação farmacológica e se for induzido o padrão de repolarização do tipo 1 o diagnóstico é concluído sem mais corroboração. Este teste é realizado com o pressuposto de não existirem falsos positivos mas a verdadeira especificidade é desconhecida

Morphological and Postural changes in the foot during pregnancy and puerperium : a longitudinal study

The aim of this study is to observe the morphological and postural changes to the foot that take place during pregnancy and the puerperium. Method: In this descriptive, observational, longitudinal study, we analysed 23 pregnant women, with particular attention to morphological and postural aspects of the foot, at three time points during and after pregnancy: in weeks 9-13 of gestation, weeks 32-35 of gestation and weeks 4-6 after delivery. The parameters considered were changes in foot length, the Foot Posture Index (FPI) and the Hernández Corvo Index, which were analysed using a pedigraph and taking into account the Body Mass Index (BMI). The same procedure was conducted in each review. Results: The statistical analyses obtained for each foot did not differ significantly between the three measurement times. A pronator-type footprint was most frequently observed during the third trimester of pregnancy; it was predominantly neutral during the postpartum period. Statistically significant differences between the measurement times were obtained in the right foot for cavus vs. neutral foot type (between the first and third trimesters and also between the first trimester and the puerperium) (in both cases, p < 0.0001). Conclusions: Foot length increases in the third trimester and returns to normal in the puerperium. According to FPI findings, the third trimester of pregnancy is characterised by pronation, while the posture returns to neutrality during the postpartum period. During pregnancy, the plantar arch flattens, and this persists during the puerperium. The incidence of cavus foot increases significantly in the third trimester and in the puerperium