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A 3-month-old, full term female infant, adequate for gestational age, and exclusively breastfed, was admitted with a 10 day history of generalised scaling erythematous dermatitis, affecting the face (perinasal, nasolabial folds and periauricular), acral and intertriginous areas, with irritability and failure to thrive. Her mother had been treated with isoniazid since the third trimester because of family contact with tuberculosis. Based on a diagnosis of suspected impetiginised eczema, the infant was treated with flucloxacillin and prednisolone, and maternal isoniazid was suspended, with no improvement. Investigations found low serum zinc levels in the infant (33 μg/dL; normal range (NR) >60 μg/dL), normal plasma zinc levels in the mother (111.3 μg/dL; NR 68–120 μg/dL) and lower than the normal range of zinc levels in breast milk (270μg/L; NR 1000–2500 μg/L), suggesting acrodermatitis caused by zinc deficiency. Oral zinc supplementation (3 mg/kg/day) was started with a marked improvement in skin lesions, as well as good weight gain. At the age of 6 months, after food diversification, supplementation was suspended, without any recurrence of symptoms.

tRNAs are a driving force of genome evolution in Yeast and Bacteria. Their deregulation is frequently observed in tumors with Serine tRNAs being often overexpressed. This has important functional consequences, such as increased metabolism and tumor growth. In yeast, time and chemical stimulus boost alterations in the genome driven by tRNA deregulation. Therefore, we hypothesized that tRNA deregulation may contribute to the increased genome instability observed in tumors. To study the effect of tRNA deregulation in tumors, we overexpressed tRNA-Ser-AGA-2-1 in a NSCLC cell line, H460. This cell line and a Mock (control) were xenografted in nude mice and collected at 3 timepoints: T1-Naïve; T2-Treated once with cisplatin/vehicle and; T3) treated twice with cisplatin/vehicle. These tumors were characterized by WES, RNAseq and Mass Spectrometry and the data obtained was integrated. The tumor mutation burden was increased in T3 tRNASerOE tumors, regardless of treatment. Although in T1 Mock and tRNASer tumors have a similar number of variants, in T2&3, tRNASerOE tumors display two times more variants than Mock tumors regardless of treatment. Interestingly, tRNASerOE exclusive variants favor proliferation and therapy resistance, which is in line with the phenotypes observed and supported by RNAseq and proteomics data. In conclusion, tRNASerOE increases the tumor mutation burden and the variants detected favor tumor growth, proving tRNA deregulation is enough to induce adaptive mutations in the genome.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnosis. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NAT) from TCGA repository, and proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D-cells and EVs, but barely expressed in NAT. Moreover, 20 tRFs were expressed in 3D-cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-EV derived samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

The sensitivity of the αβ T-cell receptor (TCR) is enhanced by the coreceptors CD4 and CD8αβ, which are expressed primarily by cells of the helper and cytotoxic T-cell lineages, respectively. The coreceptors bind to major histocompatibility complex (MHC) molecules and associate intracellularly with the Src-family kinase Lck, which catalyzes TCR phosphorylation during receptor triggering. Although coreceptor-kinase occupancy was initially believed to be high, a recent study suggested that most coreceptors exist in an Lck-free state, and that this low occupancy helps to effect TCR antigen discrimination. Here, using the same method, we found instead that the CD4-Lck interaction was stoichiometric (~100%) and that the CD8αβ-Lck interaction was also substantial (~60%). We confirmed our findings in live cells using fluorescence cross-correlation spectroscopy (FCCS) to measure coreceptor-Lck co-diffusionin situ. After introducing structurally guided mutations into the intracellular domain of CD4, we used FCCS to show that stoichiometric Lck coupling required an amphipathic α-helix present in CD4 but not CD8α. In double-positive cells expressing equal numbers of both coreceptors, but limiting amounts of kinase, CD4 out-competed CD8αβ for Lck. In T cells, TCR signaling induced CD4-Lck oligomerization but did not affect the high levels of CD4-Lck occupancy. These findings help settle the question of kinase occupancy and suggest that the binding advantages that CD4 has over CD8 could be important when Lck levels are limiting.Significance statementCD4 and CD8αβ are archetypal coreceptor proteins that potently enhance T-cell antigen sensitivity but how they function is still debated. A fundamental question that remains incompletely resolved is: what fractions of the coreceptors bind the signal-initiating kinase, Lck? Usingin vitroassays and non-invasive fluorescence fluctuation spectroscopy in live cells, we show that most coreceptors are occupied by Lck at the surface of live cells. The structural basis for important differences in the kinase occupancy of CD4 and CD8αβ is also identified. These results provide important context for refining current models of both TCR antigen recognition and cell fate decisions made during thymopoiesis.

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell–substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.

Case Report A short stature 10 year old boy with pes planus, mild hearing loss, failure of exfoliation of the primary dentition, anterior hyperdontia, malocclusion and open anterior fontanelle was observed in Pediatric Orthopedics consultation, and presenting the following alterations (image). Discussion This child has cleidocranial dysplasia (CCD). Is an autosomal dominant disease caused by an heterozygous loss-of-function mutation in the RUNX2 gene, encoding transcription factor CBFA1, on chromosome 6p21, which plays an important role in osteogenesis and differentiation of osteoblasts. The main clinical features include persistently open skull sutures, hypoplasia or aplasia of the clavicles permitting abnormal facility in opposing the shoulders, short middle phalanx of the fifth fingers, dental anomalies (supernumerary teeth, failure of exfoliation of the primary dentition and malocclusion), pes planus, upper respiratory complications, recurrent otitis media, hearing loss and often vertebral malformation (scoliosis). Conclusion The clinical diagnosis of CCD was made during pregnancy, through the detection of aplasia of the clavicles in fetu, in association with the mother having short stature (1.32 meters), persistence of primary teeth and open anterior fontanelle. With 10 years of age, he underwent mendilioma study which revealed the mutation in the RUNX2 gene (c. 747 del (p.(Arg251 Alafs*7))) classified as a pathogenic variant.

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity favouring tumour growth. We developed an EMT model by on/off exposure of epithelial EpH4 cells (E-cells) to TGFβ1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia, by using RNA sequencing, Immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays, as well as cell-xenografts in nude mice. Phenotypic reverted-epithelial cells (RE-cells), obtained after MET induction, presented pure epithelial morphology and proliferation rate resembling E-cells. However, RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a unique and heterogeneous mixture of cell-subpopulations, with high self-renewal ability fed by oxidative phosporylation. RE-cells heterogeneity is stably maintained for long periods after TGFβ1 removal, both in vitro and in large derived tumours in nude mice. Overall, we show that phenotypic reverted-epithelial cells (RE-cells) do not return to the molecular and functional epithelial state, present mesenchymal features related with aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cells reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour-growth promoting factor in vivo.

Henoch–Schönlein purpura (HSP) is characterized by nonthrombocytopenic palpable purpura, arthritis or arthral­gia, and gastrointestinal and/or renal involvement. Gastrointestinal symptoms are reported in 50%-75% and they are related to a previous group A streptococcal infection in 40%. A healthy 5-year-old girl presented with a three-week history of a recurrent purpuric rash on the lower limbs, ar­thralgia and angioedema, without renal involvement. During the third relapse, she had severe, diffuse and persistent abdominal pain and bloody stools. An abdominal ultrasound revealed transmural edema of the last ileal segment, compatible with ileitis. She received prednisolone for five days, with full clinical recovery. Antistreptolysin O titer was elevated. The remaining laboratory tests were normal (antinuclear, anti-neutrophil and anti-Saccharomyces cerevisiae antibodies; rheumatoid factor; stool cultures, parasitological examination and viral antigen tests). One month later, an abdominal ultrasound revealed no abnormalities. Terminal ileitis is a very rare complication of HSP in children but has a good prognosis.

O presente relatório, no âmbito do Mestrado em Ciências da Educação, no domínio de Educação, Comunidades e Mudança Social, apresenta o trabalho de investigação e intervenção realizado na Câmara Municipal de Murça (CMM), especificamente, no Projeto Raízes da Educação para o Futuro (REduF) e na fase de criação do Centro Interdisciplinar, Transfronteiriço e Inter-regional de Memória da Educação de Murça (CITRIME-Murça), com foco na implantação do Serviço Educativo do CITRIME-Murça, instituição que tem como objetivo central a salvaguarda da herança cultural educativa de Murça. Inserido na fase de transição entre o início do projeto REduF e o CITRIME- Murça, o estágio curricular centrou-se na ideia chave do "centro de memória da educação como um espaço de encontro intergeracional" capaz de promover o bem- estar comunitário e incentivar a preservação e a salvaguarda do património cultural e educativo presentes no Concelho de Murça. O estágio e o planeamento de atividades para o serviço educativo do CITRIME-Murça foram marcados por um trabalho colaborativo numa lógica de "trabalhar com" em vez de "intervir em" (Bolivar, 2003), com o propósito de envolver a comunidade o mais possível durante o processo de intervenção. Ao longo deste relatório, além das atividades desenvolvidas, são discutidos conceitos como cultura material escolar (Felgueiras, 2005), herança educativa (Felgueiras, 2010), relações intergeracionais e serviço educativo (Camacho, 2007), entre outros, que sustentam teoricamente a investigação e intervenção realizadas.

At red wine pH, malvidin-3-glucoside (mv-3-glc), the major anthocyanin of red wine, is expected to be present mainly in its non-colored hemiketal form. However, due to copigmentation with flavanols (e.g. epicatechin), the stabilization of the colored forms of mv-3-glc occurs. Some flavanols have been linked to astringency, due to their ability to interact/precipitate salivary proteins, namely proline-rich proteins (PRPs). So, a major question is if this copigmentation interaction could affect the ability of flavanols to interact with SP. To answer this, the effect of the interaction between mv-3-glc and epicatechin with basic and acidic PRPs, was investigated by saturation-tranfer difference (STD)-NMR and isothermal titration calorimetry (ITC). The most relevant result was that epicatechin:mv-3-glc mixture presents a synergic effect toward the interaction with both PRPs when compared to individual polyphenols. Furthermore, was observed that epicatechin interaction was driven by hydrophobic and hydrophilic interactions while mv-3-glc interaction was driven by electrostatic interactions.

The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγε2ζ2 complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution. The antigen-bound complex comprises 11 subunits stabilized by multivalent interactions across three structural layers, with clustered membrane-proximal cystines stabilizing the CD3-εδ and CD3-εγ heterodimers. Extra density sandwiched between transmembrane helices reveals the involvement of sterol lipids in TCR assembly. The geometry of the pMHC/TCR complex suggests that efficient TCR scanning of pMHC requires accurate pre-positioning of T cell and antigen-presenting cell membranes. Comparisons of the ligand-bound and unliganded receptors, along with molecular dynamics simulations, indicate that TCRs can be triggered in the absence of spontaneous structural rearrangements.

Sprengel deformity is a congenital elevation of the scapula. Herein is reported the case of a child with the right scapula at a higher level compared to the left and limited abduction of the right shoulder. Other pathoanatomical anomalies can be associated. Treatment is usually conservative, since surgery is only considered in patients with severe scapular function limitation, neck pain, or to improve cosmesis., A deformidade de Sprengel é uma elevação congénita da omoplata. É descrito o caso de uma criança com a omoplata direita num nível mais elevado do que a esquerda e com abdução limitada do ombro direito. Outras anomalias ou síndromes podem ser associadas a esta deformidade. O tratamento é geralmente conservador, uma vez que a cirurgia é reservada a doentes com severa limitação funcional, dor no pescoço ou para melhoria estética.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): MG and CS were supported by a PhD FCT grant (SFRH/BD/128893/2017) and by an individual grant from CAPES [BEX 0554/14-6], respectively. This work was financially supported by the project POCI-01-0145-FEDER-030011, funded by FEDER, through COMPETE2020-POCI, and by national funds, through FCT/MCTES (PTDC/MEC-CAR/30011/2017). iBiMED is a research unit supported by the Portuguese Foundation for Science and Technology (REF: UID/BIM/04501/2020) and FEDER/Compete2020 funds). Introduction Amyloid-like protein aggregates play a decisive role in the pathology of heart failure. Alterations in protein homeostasis, in particular, the clearance of toxic amyloid-like aggregates are emerging therapeutic targets in cardiovascular medicine. The clinical benefits of cardiac rehabilitation and exercise training are widely accepted in heart failure; however, little is known about the potential benefit of exercise training in amyloid-like protein aggregates. Purpose To assess the effects of a moderate-intensity exercise training program on amyloid-like protein aggregates levels among patients with heart failure with reduced ejection fraction. Methods Eighteen subjects participated in the study; eight patients (age: 66.6 ± 5.9 years; FEVE: 38.4 ± 8.9%) with heart failure with reduced ejection fraction participated in a 3-month exercise training program (2 x 60 min sessions per week of moderate-intensity aerobic and resistance exercise). Ten healthy subjects (age: 68. 4 ± 3.1 years) were recruited to an age-matched reference group. Amyloid-like protein aggregates were assessed before and after 3 months of exercise training. Clinical data, medication, anthropometrics, and cardiorespiratory fitness were also assessed. Thioflavin T (ThT) dye fluorescence was used to quantify the plasma levels of amyloid-like aggregates and the Fourier transform infrared spectroscopy (FTIR) was applied to evaluate the conformation of cross-β-sheet structures characteristic of amyloid protein aggregates. Results Exercise program improved cardiorespiratory fitness by 14.0 ± 17.1% (17.4 ± 3.2 to 19.7 ± 2.9 ml/kg/min) and reduced NT-proBNP levels by 16.5% (34.2) (median concentration of 632 pg/mL (720.8) to 517.5 pg/mL (707.0)) in the heart failure patients. A slight decrease of amyloid-like aggregates levels was observed in post-exercise training samples (a reduction of 3.1%); interestingly, after the exercise training program, the heart failure patients showed levels of amyloid-like aggregates similar to the reference group (1132.0 ± 114.2 vs. 1094.8 ± 132.9 a.u.). Additionally, the PLS-R multivariate analysis of the amide I region of the FTIR spectra revealed enrichment of antiparallel β-sheets (1693 cm-1) assigned to amyloid-like oligomers in the samples of heart failure patients before, but not after, the exercise program. Of note, oligomeric species, as intermediates of amyloid assembly, can contribute to the increase of amyloid burden, but also, some have been reported to be highly reactive and toxic to cells, being key elements of amyloid pathogenesis. Conclusions Our preliminary results indicate that 3 months of exercise training may have significant effects on amyloid-like oligomers, and start hindering the formation of the larger ThT-positive aggregates among patients with heart failure. Abstract Figure.

Introduction With the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. Methods We reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients’ medical history. Demographic and clinical data were collected for patients with identified pathogens. Results A total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. Conclusion We found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.

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Background Pre-infarct angina (PIA) has been shown to reduce reperfusion injury and infarct size in patients with ST-elevation myocardial infarction (STEMI) and currently represents the most efficient form of myocardial conditioning yet discovered. The role of diabetes on ischemic preconditioning remains controversial – while some pre-clinical studies suggest that diabetes blunts ischemic conditioning, clinical studies are lacking. Methods We retrospectively evaluated consecutive patients with STEMI admitted in our hospital from January 2008 to August 2018 who underwent primary angioplasty (PCI). PIA was defined as chest, arm or jaw pain during the preceding 48h before STEMI diagnosis. Peak creatine kinase and peak Troponin T levels were used as a surrogate of infarct size. Ischemic time (IT) was defined as the time between the onset of symptoms to the restoration of flow after either guidewire passage, thrombus aspiration or first balloon inflation. Results Of the 1143 included patients, 74% (n=845) were male and mean age was 62.6±13.1 years. A quarter of STEMI-patients had diabetes (25%, n=285). Almost a third of the patients (32%, n=359) had a history of angina in the preceding 48h before STEMI (PIA). The proportion of PIA was similar between diabetic and non-diabetic patients. In patients with diabetes, PIA was associated with lower creatine kinase (CK) (1144 [500–2212] vs 1715 [908–3309] U/L, p=0.0029) and Troponin T (TnT 3.30 [1.90–6.58] vs 4.88 [2.50–9.58] ng/mL, p=0.0022) despite similar IT as compared to those without PIA (328 [200–554] vs. 258 [180–530] minutes, p=0.1365). In non-diabetic patients, PIA was not significantly associated with infarct size (TnT 3.74 [2.23–7.11] vs 4.56 [2.44–7.77] ng/mL, p=0.1945; CK 1549 [910 - 2909] vs 1793 [996 - 3078] U/L, p=0.0653) even after adjustment for the increased ischemic time (240 [150–550] vs. 210 [140–405] minutes, p=0.0128) (β=−0.12, p=0.085 for CK and β=−0.11, p=0.183 for TnT). A significant interaction was observed between the existence of PIA and diabetes on peak TnT (p=0.026 for interaction) and CK (p=0.047 for interaction), which was independent of the culprit vessel and IT. During a median follow-up period of 18.0 [12.1–25.5] months, 268 (24.0%) MACE events have occurred (165 deaths, 27 strokes, 46 myocardial infarctions and 26 target vessel revascularization). PIA was associated with a significant reduction in the incidence of MACE (HR 0.66 (95% CI: 0.48–0.89)) driven by a reduction on mortality (HR 0.44 (95% CI: 0.28–0.70)). Diabetes was associated with an increased incidence of MACE (HR 1.42 (95% CI: 1.07–1.89)). No interaction was found between diabetes and PIA on their effect on MACCE events. Conclusion PIA is a strong predictor of favourable outcomes in the setting of STEMI. The effect of PIA on myocardial protection in patients with STEMI undergoing primary PCI seems to be modulated by the presence of diabetes. Distribution of Peak CK and Peak TnT Funding Acknowledgement Type of funding source: None

The T-cell coreceptors CD4 and CD8 have well-characterized and essential roles in thymic development, but how they contribute to immune responses in the periphery is unclear. Coreceptors strengthen T-cell responses by many orders of magnitude - beyond a million-fold according to some estimates - but the mechanisms underlying these effects are still debated. T-cell receptor (TCR) triggering is initiated by the binding of the TCR to peptide-loaded major histocompatibility complex (pMHC) molecules on the surfaces of other cells. CD4 and CD8 are the only T-cell proteins that bind to the same pMHC ligand as the TCR, and can directly associate with the TCR-phosphorylating kinase Lck. At least three mechanisms have been proposed to explain how coreceptors so profoundly amplify TCR signaling: (1) the Lck recruitment model and (2) the pseudodimer model, both invoked to explain receptor triggering per se, and (3) two-step coreceptor recruitment to partially triggered TCRs leading to signal amplification. More recently it has been suggested that, in addition to initiating or augmenting TCR signaling, coreceptors effect antigen discrimination. But how can any of this be reconciled with TCR signaling occurring in the absence of CD4 or CD8, and with their interactions with pMHC being among the weakest specific protein-protein interactions ever described? Here, we review each theory of coreceptor function in light of the latest structural, biochemical, and functional data. We conclude that the oldest ideas are probably still the best, i.e., that their weak binding to MHC proteins and efficient association with Lck allow coreceptors to amplify weak incipient triggering of the TCR, without comprising TCR specificity.

Dissertação de Mestrado Integrado em Arquitetura Odivelas evolui, tal como tantas outras cidades europeias, para uma cidade polinucleada. As diferentes centralidades apresentam características únicas e irrepetíveis. O estudo destas centralidades permite uma compreensão do território da cidade como um todo e a clarificação do motivo da segregação por vertentes e por zonas. A segregação territorial está na base de outros problemas. Ao combater o problema de raiz e a reabilitar a imagem que Odivelas apresenta aos seus habitantes e para a Área Metropolitana de Lisboa, procura-se que a cidade evolua organicamente para resolver problemas associados. Em Do Abandono à Centralidade é desenvolvido um discurso crítico que se prende com o existente e o complemento do mesmo com o elemento novo. São exploradas linhas de ação para a intervenção ao nível da reabilitação das fábricas do Senhor Roubado e da inserção do ícone local, o elemento referencial da cidade de Odivelas que corrompe a paisagem e se apropria desta para a sua expressão. O projeto desenvolve-se respeitando os dois tempos, o presente e o passado das fábricas, olhando ao futuro e com vista a impactar positivamente o modo de vida e de experienciar a cidade de Odivelas. N/A

In this work, high-performance liquid chromatography, fluorescence quenching, nephelometry, and sodium dodecyl sulfate polyacrylamide gel electrophoresis were used to study the effect of polysaccharides naturally present in wine [rhamnogalacturonan II (RG II) and arabinogalactan proteins (AGPs)] on the interaction between salivary proteins (SP) together present in saliva and tannins (punicalagin (PNG) and procyanidin B2). In general, the RG II fraction was more efficient to inhibit SP precipitation by tannins, especially for acidic proline-rich proteins (aPRPs) and statherin/P-B peptide, than AGPs. The RG II fraction can act mainly by a competition mechanism in which polysaccharides compete by tannin binding. However, in the presence of Na+ ions in solution, no RG II effect was observed on SP-tannin interactions. On the other hand, dependent upon the saliva sample as well as the tannin studied, AGPs can act by both mechanisms, competition and ternary (formation of a ternary complex with SP-tannin aggregates enhancing their solubility).

O tema do presente trabalho de investigação realiza-se no âmbito do Mestrado de Design & Publicidade e retrata a influência da arte urbana na marca das cidades. A área de intervenção é a cidade da Covilhã, sendo que a arte urbana aqui existente é desenvolvida através do WOOL - Festival de Arte Urbana da Covilhã. Os objetivos são: compreender o impacto do Wool sobre a cidade da Covilhã, perceber se a Covilhã é uma marca-cidade e de que tipo e, por último, saber se a arte urbana desenvolvida pelo festival WOOL é um dos principais motivos que impulsiona a cidade como marca. Para dar resposta aos objetivos, contextualiza-se historicamente a arte urbana e a cidade da Covilhã, expõem-se as características e o percurso inerente ao festival WOOL, assim como a teoria subjacente ao conceito de marca-cidade. Assim, esta investigação desenvolve-se segundo o método qualitativo para permitir um estudo mais abrangente da temática em questão, através da apresentação de um case-study relativo à cidade da Covilhã e de um conjunto de entrevistas não-estruturadas focalizadas efetuadas à população da mesma cidade, aos artistas e à organização do festival covilhanense, na pesquisa de campo realizada durante a sexta edição do WOOL em junho de 2019. No final, conclui-se que a Covilhã é uma marca-cidade em desenvolvimento com grandes potencialidades para evoluir a sua marca através do WOOL - Festival de Arte Urbana da Covilhã. The theme of this research work is carried out under the Master of Design & Advertising and portrays the influence of street art on the brand of cities. The area of intervention is the city of Covilhã where the street art existing is developed through WOOL - Urban Art Festival of Covilhã. The objectives are: to understand the impact of WOOL on the city of Covilhã, to understand if Covilhã is a city brand and what kind and, finally, to know if the street art developed by the WOOL festival is one of the main reasons that drives the city as a brand. In order to reply to the objectives, street art and the city of Covilhã are historically contextualizes, the characteristics and the inherent trajectory of the WOOL festival are exposed, as well as the theory underlying the concept of city brand. Thus, this research is carried out according to the qualitative method to allow a broader study of the subject in question, though the presentation of a case study concerning the city of Covilhã and a set of focused unstructured interviews conducted with the population of the same city, with the artists and with the festival organization, in the field research carried out during the sixth edition of WOOL in June 2019. In the end, it is concluded that Covilhã is a developing city brand with a great potential to evolve its brand through the WOOL - Covilhã Urban Art Festival.

Introduction and Objectives: Acute appendicitis (AA) is one of the most common causes of urgent surgery in children and is still associated with diagnostic difficulties. As the red blood width (RDW) and mean platelet volume (MVP) may be related to inflammatory processes, this study aims to evaluate the diagnostic value of RDW in AA in pediatric population. Methods: A retrospective and observational study was conducted. Data was collected from medical records of all patients with clinical suspicion of AA who underwent appendectomy at a secundary hospital during a period of 36 months. Preoperative analytical values were analyzed and compared with a control group. Results: Medical records of 305 patients with a mean age of 12.1 years were analyzed. Children with simple or perforated appendicitis had significantly higher RDW than those with a normal appendix. Compared with the controls mean RDW was significantly higher in the acute appendicitis group (14.16 ± 1.2% vs.13.09 ± 0.9%, p

Background The supracondylar fracture of the humerus is one of the most common fractures in pediatric age. Many classifications were proposed, with Gartland being the most widely used one and Lagrange and Rigault (L&R) the most used in French-speaking countries. Objectives The goal of this study was to compare the Wilkins-modified Gartland classification with the L&R classification in terms of reproducibility. Methods Three observers with similar training levels classified 35 fractures according to both classifications twice to evaluate both intra and interobserver variation. Results The mean intraobserver variation was 0.78 and 0.77 for Gartland and L&R classifications, respectively, and the mean interobserver variation was 0.55 and 0.62 for Gartland and L&R classifications, respectively. Conclusions Both classifications reveal adequate to usage in clinical and investigational practices, which is consistent with the literature.

Polyphenols may contribute directly to plant-based foodstuffs flavor, in particular to astringency and bitterness. In this work, the bitterness of a small library of polyphenols from different classes [procyanidin dimers type B, ellagitannins (punicalagin, castalagin, and vescalagin) and phenolic acid ethyl esters (protocatechuic, ferulic, and vanillic acid ethyl esters] was studied by a cell-based assay. The bitter taste receptors (TAS2Rs) activated by these polyphenols and the half-maximum effective concentrations (EC50) of each agonist-TAS2Rs pair were determined. Computational methodologies were used to understand the polyphenol molecular region responsible for receptor activation and to get insights into the type of bonds established in the agonist-TAS2Rs pairs. The results show the combinatorial pattern of TAS2Rs activation. TAS2R5 seems to be the only receptor exhibiting a bias toward the activation by condensed tannins, while TAS2R7 seems more tuned for hydrolyzable (ellagi)tannins. Additionally, at the concentrations usually found for these compounds in foodstuffs, they can actively contribute to bitter taste, especially ellagitannins.

Las fracturas por estrés afectan, con mayor frecuencia, a personas físicamente activas con hueso normal y son infrecuentes en los niños con placa de crecimiento abierta. Aun más infrecuentes son las fracturas por estrés del cuello femoral en la población pediátrica. Sin embargo, constituyen entidades muy importantes debido al riesgo de complicaciones graves, como la necrosis avascular. Se describe el caso de una niña de 7 años medicada con metilfenidato que sufrió una fractura por estrés del cuello del fémur atípica. La paciente consulta por dolor inguinal derecho sin limitaciones en las actividades cotidianas. La radiografía muestra una fractura por estrés del cuello del fémur, que se confirma con tomografía. Se instaura un tratamiento conservador, y la paciente está asintomática a las cuatro semanas. Este caso representa una alerta sobre esta infrecuente entidad en la que podrían presentarse errores diagnósticos. Investigaciones recientes también sugieren la posible participación de fármacos, como el metilfenidato, en la desmineralización ósea, que podría constituir un posible factor de riesgo de fractura. AbstractStress fractures most commonly affect physically active individuals with normal bone, and they are rare in children with open growth plates. Even rarer are femoral neck stress fractures in pediatric age. Nevertheless, they constitute a very important entity due to the risk of severe complications, such as avascular necrosis. A seven-year-old girl, treated with methylphenidate, who suffered an atypical femoral neck stress fracture is presented. Patient complained of right inguinal pain without daily life activity limitations. The radiograph showed a stress femoral neck fracture, confirmed by CT imaging. Conservative treatment was instituted and the patient became asymptomatic after 4 weeks.This case report alerts the clinicians about this rare entity that might be misdiagnosed. Recent research also suggests a possible involvement of drugs, such as methylphenidate, in bone demineralization, which might constitute a possible risk factor for fractures.