Search

The tobacco is one of the biggest public health threats, smoking kills more than 7 million people/year worldwide and more than 890,000 are deaths resulting from exposure to Second Hand Smoke (SHS). In adults, SHS is associated to cardiovascular and respiratory diseases, including coronary heart disease and lung cancer, through pathological and molecular mechanisms not yet understood. We aimed to investigate the SHS effects on airway proteome in exposed workers. Nasal epithelium was collected from hospitality workers (non-smokers=40; smokers=12), long-term exposed and non-exposed to SHS at the workplace. Samples were analyzed by shotgun proteomics using an ESI-LQT Orbitrap XL mass spectrometer. The generated MS raw data was submitted to ‘PatternLab for Proteomics’ for peptide identification and relative quantification by label-free - extracted ion chromatograms (XIC). Golden rules were applied to obtain reliable data: in the identification of a protein at least one unique peptide must had to be present in more than 80% of the individuals, and consequently each inferred protein had to be detected in 80% to 100% of the cohort. Two proteins were found to be differentially expressed in the no-smokers exposed to SHS compared with the control: BPI fold-containing family A member 1 (BPIFA1) and Heat shock Protein Beta-1 (HSPB1). The first protein plays a role in the airway inflammatory response after exposure to irritants substances and the second is associated as a regulator of actin filament dynamics. Our findings support the indication that in non-smokers the prolonged exposure to SHS can lead to airway proteome modulation. When validated, the uncovered proteins can be promising candidates to “susceptibility/risk” and/or “predictive” biomarkers for SHS exposure. Gulbenkian Institute of Science; Fundação para a Ciência e a Tecnologia (FCT); National Institute of Health Dr. Ricardo Jorge; Faculty of Sciences of the University of Lisbon; Protein Technology Laboratory - Department of Immunotecnology, Lund University, Sweden; Center of Toxicogenomics and Human Health. N/A

The role of red blood cells (RBC) in the immune system is increasingly recognized. However, RBC-derived molecules with an immunomodulatory role in health and disease, as well as in vaccine immunogenicity are still poorly investigated. Taking as a model the emergent COVID-19 vaccines, we aimed to investigate whether vaccines induce proteome and/or metabolome changes in RBCs able to affect T-cell immune activity, as a mechanistic test for vaccine immunization regulated by RBCs. Our ultimate goal is to identify RBC immunomodulators as potential co-adjuvants in the formulation of next-generation vaccines with bolstered efficacy and duration. A biobank of blood samples collected longitudinally under ‘omics’ quality control from subjects (n=39) that underwent vaccination for COVID-19 between April and September 2021 was created. This biobank is associated with extensive clinical data, including demographic data, COVID-19 PCR diagnosis, hematological and vaccine effectivity data. Linear Mixed Models, were used to evaluate the association between biometrical characteristics, health related habits, vaccine technology and vaccine effectivity and hematological parameters, along the different time-points (t0-t4) under study, i.e, before and after (24-72h or 30 days) of the first and second dose of vaccine. Statistical analyses were performed using R software version 4.1.2. Results showed significant differences (p

Background: WHO have stated that near 900 000 deaths per year result from exposure to Second- Hand Smoke (SHS). SHS exposure has been linked to cancer, respiratory and cardiovascular diseases and diabetes. However, the associated underlying molecular mechanisms remain to be elucidated. The objective of this proteomics study is to uncover putative key molecules involved in these mechanisms that can be used to predict and monitor diseases risks associated with occupational SHS exposure. Methods: In total, 25 Lisbon restaurants agreed to participate. Nasal epithelium and urine samples were collected from their employees (n=52) for proteomics analysis and cotinine evaluation of SHS exposure, respectively. The subjects were classified as never smoker (N), former smoker (F) and smoker (S); exposed (NE=11; FE=10; SE=4) or non-exposed (N=11; F=8; S=8) to SHS. All subjects were healthy and showed no significant differences in parameters like age, time in the workplace, tobacco smoking habits and spirometry evaluation of pulmonary function. Urine cotinine levels showed significantly elevated in the exposed subjects compared to non-exposed, confirming SHS exposure. Nasal epithelium samples were analyzed by shotgun proteomics using an ESI-LTQOrbitrap mass spectrometer. The “MS raw data” was submitted to “PatternLab for Proteomics” software, with “Comet” search machine algorithm, from where the identified proteins were submitted to a “ClueGO” functional annotation & enrichment analyses in “Cytoscape” software, with the propose to shed some light about the molecular biology involved in the cellular response to the SHS exposition. Results: In NE subjects the SHS is associated with the biologic terms of “Lactate dehydrogenase complex” and “Pentose-Phosphatase Shunt”, also with “Glutathione peroxidase activity” and “Tcell apoptotic process”. At the other end the FE individuals present a specific proteome enriched in biologic information with terms as the “L-Lactate dehydrogenase complex” and the “Peroxisome” as was expected by the results above for the NE cohort; but there were also other different terms as: “Peripheral T cell lymphoma”, “Central carbon metabolism in cancer”, “Myelodysplastic syndrome”, “Monocyte & Granulocyte & Macrophage & Leukocyte Chemotaxis”, Nucleossome, variant H3.1-H2A2-H2B.1&Others” and finally “DNA replication-dependent chromatin assembly”. Conclusions: Proteome of nasal epithelium seems to be modulated by SHS exposure and this is a different and perhaps cumulative process between NE and FE individuals. Acknowledgements: Gulbenkian Foundation and Administração Central do Sistema de Saúde, and ToxOmics Portugal. SN, SP and VMT worked under FCT fellowships. info:eu-repo/semantics/draft

Funding: This work was funded by the Portuguese institutions Fundação Calouste Gulbenkian, Administração Central do Sistema de Saúde (ACSS) and FCT/MCTES through funding to ToxOmics (UIDB/00009/2020; UIDP/00009/2020). Environmental tobacco smoke (ETS) has been recognized as a major health hazard by environmental and public health authorities worldwide. In Portugal, smoke-free laws are in force for some years, banning smoking in most indoor public spaces. However, in hospitality venues such as restaurants and bars, owners can still choose between a total smoke-free policy or a partial smoking restriction with designated smoking areas, if adequate reinforced ventilation systems are implemented. Despite that, a previous study showed that workers remained continuously exposed to higher ETS pollution in Lisbon restaurants and bars where smoking was still allowed, comparatively to total smoke-free venues. This was assessed by measurements of indoor PM2.5 and urinary cotinine, a biomarkers of tobacco smoke exposure, demonstrating that partial smoking restrictions do not effectively protect workers from ETS. The aim of the present work was to characterize effect and susceptibility biomarkers in non-smokers from those hospitality venues occupationally exposed to ETS comparatively to non-exposed ones. A group of smokers was also included for comparison. The sister chromatid exchange (SCE), micronucleus (MN) and comet assays in whole peripheral blood lymphocytes (PBLs) and the micronucleus assay in exfoliated buccal cells, were used as biomarkers of genotoxicity. Furthermore, a comet assay after ex vivo challenge of leukocytes with an alkylating agent, ethyl methanesulfonate (EMS), was used to analyze the repair capacity of those cells. Genetic polymorphisms in genes associated with metabolism and DNA repair were also included. The results showed no clear association between occupational exposure to ETS and the induction of genotoxicity. Interestingly, the leukocytes from non-smoking ETS-exposed individuals displayed lower DNA damage levels in response to the ex vivo EMS challenge, in comparison to those from non-exposed workers, suggesting a possible adaptive response. The contribution of individual susceptibility to the effect biomarkers studied was unclear, deserving further investigation. publishersversion published

Background: We previously showed that Obstructive sleep apnea (OSA), a common public health concern causing deleterious cardiometabolic dysfunction, induced proteomic alterations in red blood cells (RBC) such as changes in the redox-oligomeric state of peroxiredoxin 2 (PRDX2)1-2. Herein, we aimed to investigate whether OSA patients with Type 2 Diabetes Mellitus before and after positive airway pressure (PAP) treatment present similar changes in the RBC antioxidant protein PRDX2 to better understand the molecular basic mechanisms associated with OSA and OSA outcomes. Methods: RBC samples from control snorers (n=22 being 3 diabetics) and OSA patients before and after six month of PAP-treatment (n=29 being 8 diabetics) were analysed by non-reducing western blot using antibody against PRDX2 or PRDXSO2/3 to measure the total and overoxidized levels of monomeric/dimeric/multimeric forms of PRDX2. Results: We confirmed previously data by showing that in OSA RBC the overoxidation on the monomeric forms of PRDX2 was higher compared to controls. After PAP treatment, this overoxidation decreased followed by an increase of multimeric-overoxidized forms of PRDX2 described to be associated with chaperone protective function. In contrast, the level of PRDX2 monomers in RBC diabetic OSA, although higher abundant its overoxidation level was much lower than those observed in OSA without comorbidity and did not significant change after treatment. Moreover, the level of PAP-induced PRDX2-overoxidized-multimers was also lower in these diabetic OSA patients. The level of overoxidized monomeric/dimeric forms of PRDX2 correlated negatively with levels of insulin / triglycerides and HbA1C, respectively. After PAP, the level of (overoxidized) PRDX2SO2/3 multimers correlated positively with adrenaline levels. Conclusions: The redox/oligomeric state of RBC PRDX2 that is regulated by overoxidation of the active cysteines was differentially modulated in diabetic OSA patients compared to OSA without this comorbidity. PAP-induced overoxidized oligo forms of PRDX2 that is associated with chaperone protective function showed decreased in OSA patients with diabetes. The clinical impact of these findings needs further investigation and validation. Project partially supported by Harvard Medical School-Portugal Program (HMSP-ICJ/0022/2011), ToxOmics - Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013). info:eu-repo/semantics/publishedVersion

Sickle-cell disease (SCD) is a clinically heterogeneous autosomal recessive monogenic disorder characterized by recurrent episodes of severe haemolysis, vaso-occlusion and infection. Proteomics promises to offer novel unbiased molecular insights into the pathophysiology of SCD. The objective of this project is to analyze by bioinformatic tools mass spectrometry (MS) proteomics raw data, which has been generated by INSA’s Proteomic Laboratory in order to investigate proteome changes that might be related with SCD vaso-occlusion exacerbation. The MS raw data included in this study was generated by shotgun proteomic analysis on red blood cell (RBC) samples from six child SCD patients at steady-state and vaso-occlusion exacerbation episode and five child control subjects. The RBC samples, the haemoglobin depleted-cytoplasmic fraction and membrane fraction, were analysed by proteomic discovery-based approach using the ESI-LQT Orbitrap XL (Thermo) mass spectrometer. The generated MS raw data files were analysed by the PatternLab for Proteomic 4.0 bioinformatic platform for protein identification and extracted-ion chromatograms (XICs)-based label-free relative quantification. The following “golden parameters” were applied to obtain reliable and trustworthy data: one unique peptide at least should be considered to infer a protein identification, and the identified proteins should be present at least in 80% of the studied groups/conditions. 250 proteins were identified, and the respective normalized ion abundance factor was compared by using the Wilcoxon-T non-parametric statistical test. The differentially expressed proteins in crisis as compared to steady-state (p-value ≤ 5%) were investigated in the light of the Gene Ontology (GO) knowledge base (Database for Annotation, Visualization and Integrated Discovery – DAVID) and Reactome database for protein integration into signaling pathways with biological meaning. The most relevant results indicated that 3 cytoplasmic proteins (Dematin, Moesin and Protein S100-A4) and 9 membrane proteins (Eosinophil cationic protein, Bone marrow proteoglycan, Voltage-dependent anion-selective channel protein 1, Voltage-dependent anion-selective channel protein 2, Reticulon-3, Carbonic anhydrase 2, Haemoglobin subunit alpha, Haemoglobin subunit delta and Eosinophil peroxidase) showed significantly differential expression in crisis as compared to steady-state. Haemoglobin subunit alpha and Carbonic anhydrase 2 (CA2) have been reported as involved in important pathways related with O2/CO2 exchange in erythrocytes. Sickle cell crisis is frequently related to infection, involving Reticulon-3 and Haemoglobin subunit alpha. These proteins were identified to be modulated in the RBC membrane fraction from SCD patients at crisis. The most relevant proteins identified by these computational approaches will be selected for further biochemical verification by using SWATH-MS and/or Western blot methods. These proteins may be promising candidate early biomarkers to identify SCD patients at risk for vaso-occlusion crisis. Fundação para a Ciência e a Tecnologia partially financing this project (Grant PIC/IC/83084/2007 and Doctoral Fellowship - SFRH/BPD/31209/2006). N/A

Obstructive Sleep Apnea (OSA) syndrome is a common public health concern characterized by recurrent episodes of apneas and hypopneas during sleep. These obstructive events result in recurrent intermittent hypoxia and sleep fragmentation that can lead to metabolic and cardiovascular diseases. We recently demonstrated that OSA can cause alterations in the red blood cells (RBC) proteome that may be associated with OSA outcomes1,2. Here we intend to investigate whether the first-line therapy for OSA, the positive airway pressure (PAP) can revert or modulate these proteome alterations. RBCs from Snorers and patients with severe OSA before/after 6 months of PAP treatment (n=10/condition) were depleted of hemoglobin, analyzed by 2D-DIGE using Progenesis SameSpotsv4.5. The differentially abundant proteins were identified by MALDI-MS/MS and protein annotations acquired by DAVIDv6.8. Western blotting (WB) validation was performed for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and (overoxidized) GAPDHSO3 on a new Cohort (n=59). SPSS software was used to correlation studies with peroxiredoxin-2 (PRDX2) redox-oligomeric forms and several clinical parameters. Ten protein spots showed significant differences (Anova p

Introduction: Obstructive Sleep Apnea (OSA) syndrome is characterized by recurrent arousals from sleep and intermittent hypoxemia. We recently demonstrated that OSA can cause alterations in the red blood cells (RBC) proteome that may be associated with OSA outcomes. Here we intend to investigate whether the positive airway pressure (PAP) treatment can revert/modulate these proteome alterations. Project partially supported by Harvard Medical School-Portugal Program (HMSP-ICJ/0022/2011), ToxOmics - Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013). N/A

Introdução: A prevalência da SAOS é elevada em doentes com DMT2. O não tratamento da SAOS pode levar ao agravamento ou desenvolvimento da DMT2. Temos vindo a demonstrar que a SAOS altera o proteoma do glóbulo vermelho (GV). A SAOS aumenta a overoxidação da peroxirredoxina 2 (PRDX2) (enzima antioxidante), o que pode levar à desregulação da homeostasia do GV e ao desenvolvimento de doenças metabólicas. Após tratamento com ventilação não invasiva (PAP), esta overoxidação diminuiu seguida de um aumento de PRDX2 decamérica overoxidada com funções chaperone na proteção celular (Feliciano et al. 2017). No presente estudo, fomos investigar o estado redox/oligomérico da PRDX2 em doentes DMT2 com SAOS, antes/após PAP, para melhor compreender a interligação entre estas patologias. Material e métodos: Amostras de GVs de controles (n=22 sendo 3 DMT2) e doentes SAOS antes/após 6 meses de tratamento com PAP (n=29 sendo 8 DMT2) foram analisadas por western-blot não reduzido, com anticorpo para a PRDX2 e PRDXSO2/3 (overoxidada). Os grupos foram comparados estatisticamente e correlacionados com dados clínicos e bioquímicos. Resultados: Nos GVs de doentes DMT2/SAOS, o nível de monómeros da PRDX2 mostrou-se aumentado e diminuía após PAP. Contudo, o nível destes monómeros PRDXSO2/3 estava diminuído e não se alterou com o tratamento. Após PAP, o nível de decâmeros PRDX2SO2/3 foi também menor nestes doentes. Os níveis de monómeros PRDX2 e PRDX2SO2/3 correlacionaram-se negativamente com os níveis de insulina/triglicéridos e HbA1C, respetivamente. Após PAP, os níveis de decâmeros PRDX2SO2/3 correlacionou-se positivamente com os níveis de adrenalina. Conclusões: O estado redox/oligomérico da PRDX2 do GV é diferencialmente modulado nos doentes DTM2/SAOS em comparação com doentes SAOS. Decâmeros PRDXSO2/3 induzidos pelo tratamento e associadas à função protetora “chaperone” estão diminuídos em doentes DMT2/SAOS. O impacto clínico destas descobertas, necessita de mais investigação e validação. N/A

Introdution:The period of time elapsed after receiving apositive test result, has been previouslyassociated with distress inBRCA1/2carriers.However,there is a need for reliable instruments andprospective data on distress and perception of riskbythose carriers,given the significant increase indemandforBRCA1/2testing.Aim:Tovalidate and implement in clinical practice,an instrumentfor the detection ofdistress andanalysis ofrisk perception,in individuals that test positive for aBRCA1/2test.Materials and Methods:We conducted a prospective study todesign and test an instrument(Distress andRisk PerceptionQuestionnaire-DRP)to evaluate distress andrisk perceptionbyBRCA1/2carriers.Predictivefactors for clinically relevantdistress,were also explored.Results:One hundred and seventy consecutive, newly diagnosedBRCA1/2carrierswere included(pre-test phase: 21 and test:149). Distress was measured with the distress thermometer (DT) andDRP, both applied, bytelephone, one month after test disclosure. Clinically relevant distresswas observed in 40% of the cases.Being a female (OR male vs female=0.37; 95%CI=0.10-1.09) and index patient (OR index vs relative=3.93; 95%CI=1.13-18.37) were independent predictors for distress after adjusting for personal history of cancer.Therisk perceptionwas highand no significant correlation with distress was observed with either DT orDRP(Spearman correlation coefficient0.05 in both).Conclusion:DRPis a new scale, easy to administer bytelephone, whichmeasures distress andrisk perceptioninBRCA1/2carriers.Gender and type of genetic screening(being an index patient or a relative)mayplay a role in the short-term emotional impact of a positiveBRCAtest result.&nbsp, Introdução:ODistressidentificado emportadores demutaçõesBRCA1/2foi previamente associado ao período de tempo, decorrido desde o conhecimento do resultado do teste.Atendendo ao aumento da procura para realizartestes genéticossão necessáriosdados prospectivos sobreoDistresseapercepção de risconosportadores de variantes patogénicasBRCA1/2.Objetivo:Desenvolver evalidarum questionário dirigido para mediroDistresse a percepção de risco em portadores deBRCA1/2.Materiais e Métodos:Neste estudo, decaraterprospectivo, foi elaboradoe testado um instrumento(QuestionáriodeDistressePercepção deRisco-DPR)que avaliaoDistressea percepção de riscoem portadoresdeBRCA1/2.Foram também exploradosfactores preditivos paraoDistressclinicamente relevante.Resultados:Foram analisados cento e setenta portadores deBRCA1/2recém diagnosticados(21 na fase pré-testee149na fase teste),identificados de forma consecutiva. Mediu-se oDistresscom o termómetrodeDistress(DT) ecom oDPR, ambosaplicadosatravés de entrevistatelefónica, um mês após a comunicação dos resultadosdo teste genético. Em 40% dos casos observou-seDistressclinicamente relevante; sendo que o génerofeminino(ORmasculinovsfeminino=0,37; 95%CI=0.10-1.09) easituação de seroprimeiro familiar a ser testado(doenteíndex)(ORindexvsfamiliar=3.93; 95%CI=1.13-18.37)foram identificados como factorespredictoresindependentes paraoDistress.A percepção de risco individual e familiar foi alta e não se observouobservoucorrelação significativadestacomoDistress,medido tantocom DTcomo com o DPR(coeficiente de correlaçãoSpearman0,05 em ambos).Conclusão:OquestionárioDPRé uma escala nova, fácil de administrar por via telefónica, que medeoDistresseapercepçãode risco em portadores BCRA1/2.As doentes mulherese asituação de primeiro familiar a ser testado(doenteindex)são factores preditores do impacto emocional,acurto prazo, de um resultado positivo no teste genéticoBCRA1/2.&nbsp

Funding: Project partially supported by Harvard Medical School-Portugal Program (HMSPICJ/0022/2011), ToxOmics - Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013), FCT/Poly-Annual Funding Program and FEDER/Saúde XXI Program (Portugal) and postdoctoral fellowship (SFRH/BPD/43365/2008) of Fundação para a Ciência e a Tecnologia (FCT), Portugal. We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation. publishersversion published

Environmental tobacco smoke (ETS) is recognized as an occupational hazard in the hospitality industry. Although Portuguese legislation banned smoking in most indoor public spaces, it is still allowed in some restaurants/bars, representing a potential risk to the workers’ health, particularly for chronic respiratory diseases. The aims of this work were to characterize biomarkers of early genetic effects and to disclose proteomic signatures associated to occupational exposure to ETS and with potential to predict respiratory diseases development. A detailed lifestyle survey and clinical evaluation (including spirometry) were performed in 81 workers from Lisbon restaurants. ETS exposure was assessed through the level of PM 2.5 in indoor air and the urinary level of cotinine. The plasma samples were immunodepleted and analysed by 2D-SDSPAGE followed by in-gel digestion and LC-MS/MS. DNA lesions and chromosome damage were analysed innlymphocytes and in exfoliated buccal cells from 19 cigarette smokers, 29 involuntary smokers, and 33 non-smokers not exposed to tobacco smoke. Also, the DNA repair capacity was evaluated using an ex vivo challenge comet assay with an alkylating agent (EMS). All workers were considered healthy and recorded normal lung function. Interestingly, following 2D-DIGE-MS (MALDI-TOF/TOF), 61 plasma proteins were found differentially expressed in ETS-exposed subjects, including 38 involved in metabolism, acute-phase respiratory inflammation, and immune or vascular functions. On the other hand, the involuntary smokers showed neither an increased level of DNA/chromosome damage on lymphocytes nor an increased number of micronuclei in buccal cells, when compared to non-exposed non-smokers. Noteworthy, lymphocytes challenge with EMS resulted in a significantly lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P

This work was approved by the Ethical Committee of INSA.I.P.-Lisboa, Centro Hospitalar Lisboa-Norte., Faculdade de Ciências Médicas da Universidade Nova de Lisboa and Comissão Nacional de Proteção de Dados, Portugal. DIGE images were obtained in ITQB. Obstructive sleep apnea (OSA) is a common public health concern causing metabolic and cardiovascular consequences. Although OSA is a systemic disease, the molecular mechanisms and specific genes/proteins associated with such processes remain poorly defined.To identify dysregulated proteins that could be useful as candidate biomarkers of diagnosis/prognosis of OSA., is the aim of this study Project - Obstructive sleep apnea and associated metabolic/cardiovascular disorders: understanding mechanisms towards early diagnosis and prognosis prediction. Work partially supported by Harvard Medical School-Portugal Program (HMSP-ICJ/0022/2011), FCT/Poly-Annual Funding Program and FEDER/Saúde XXI Program (Portugal)

This work was approved by the Ethical Committee of INSA.I.P.-Lisboa, Centro Hospitalar Lisboa-Norte., Faculdade de Ciências Médicas da Universidade Nova de Lisboa and Comissão Nacional de Proteção de Dados, Portugal. DIGE images were obtained in ITQB. Obstructive sleep apnea (OSA) is a sleep¬related breathing disorder characterized by recurrent episodes of apnea/and hypopnea during sleep with resultant intermittent hypoxia and sleep fragmentation, leading to cardiometabolic diseases. OSA affects 3.7% to 26% of adult population, but frequently is underdiagnosed. By 2DIGE-proteomics approach, we have investigated red blood cells (RBC) in OSA to uncover new insights into putative chronic stress-induced RBC dysfunction that lead to inflammation and metabolic syndrome associated with OSA. A number of proteins as potential candidate biomarkers for OSA, such as the cytosolic antioxidant regulators, catalase (CAT) and peroxiredoxin2 (PRX2) was identified, needing additional biochemical research validation. Project - Obstructive sleep apnea and associated metabolic/cardiovascular disorders: understanding mechanisms towards early diagnosis and prognosis prediction. Work partially supported by Harvard Medical School-Portugal Program (HMSP-ICJ/0022/2011), FCT/Poly-Annual Funding Program and FEDER/Saúde XXI Program (Portugal).

Painful crises are the major sickle-cell disease (SCD) clinical manifestation probably due to significant increase in dense red blood cells (RBC) and reduction of their ability to pass through capillaries. Using proteomic strategies (see figure below), we aimed to discover novel SCD prognosis biomarkers as early predictors of the transition from steady-state to vaso-occlusive crises thus, allowing a prompt and specific therapeutic intervention.

This study reports the mineralogical and chemical characterization of the ceramic body of tiles signed by Gabriel del Barco, which belong to the Palácio Almada in Lisbon [1]. Nowadays, the tile panels are not in its original place and their appearance reflect the constant changes that they have been through. Gabriel del Barco was an important tile painter from the 17th century, who began his career as an oil painter, linked to the most relevant Portuguese baroque artists. The influent Almada family was the owner of the former palace near Rossio, one of the most significant and busy squares in 17th century Lisbon. Gabriel del Barco has been currently under investigation by the authors of this presentation through a FCT funded project [2]. In fact, the painter’s characteristics and his large amount of works (both signed and ascribed), make him a unique artist in the Portuguese tile’s panorama. Powder samples carefully removed from the two panels of the palace were analysed by X-ray diffraction (DRX) and energy-dispersive X-ray spectroscopy (EDS). The results revealed that the mineralogical and chemical compositions are almost the same for the two panels. Chloride is present only in one of the panels. A comparison with the present results is made with a recent work, where signed and nonsigned tiles attributed to the artist, was made [3]. We discuss the several factors that may affect the characteristics of old tiles, which may involve differences in the manufacturing process, or environmental factors as the precipitation of water info:eu-repo/semantics/publishedVersion

Work perfomed by Instituto Nacional Saúde Doutor Ricardo Jorge, Laboratório de Análises de Dopagem, Instituto do Desporto de Portugal, Clínica Universitária Pneumologia, Faculdade Medicina Lisboa, Hospital Santa Maria High concentration of toxic substances emanated from tobacco smoke in entertainment places such as restaurants, bars and nightclubs may compromise indoor air quality (IAQ) generating environments of likelihood health risk. Their employees, particularly those exposed to second-hand smoke, are at increased risk for developing chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. Objectives In this work, we aimed at evaluating relationships between occupational ETS exposure, biological damage (DNA or proteome alterations) and putative respiratory dysfunctions. Materials and Methods A group of restaurants located in Lisbon has been studied, in which fine particles (smaller than 2.5µm; PM2.5), indicative of environmental tobacco smoke (ETS) contamination, were measured. After informed consent, workers were evaluated for acute exposure to ETS based on cotinine levels in urine and clinically evaluated for their respiratory health by spirometry measurements and chestpiece auscultation. Effects of ETS exposure on genotoxic lesions were evaluated by measuring DNA/chromosomes breaks in peripheral blood lymphocytes and buccal mucosa cells. Effects of ETS exposure on plasma proteins is being studied using a 2D-DIGE-MALDI-TOF/TOF approach. To achieve that goal, global proteome characterization is being carried based on the same individual plasma samples collected for genotoxic studies and were pooled according to previous criteria. Results Results have confirmed higher respirable particle levels in smoking-designated areas of those entertainment places, indicating an ETS contamination. Leukocytes from ETS-exposed-workers presented lower levels of genotoxic-induced damage in comparison with non-exposed workers, suggesting an ETS-induced stress adaption response in exposed-workers. By proteomics, we are now to investigating those workers for putative alterations on their plasma proteome to provide additional insights on the adaptative response mechanisms that might be activated by ETS exposition. Conclusion Altogether, this study provides information on indoor air quality of Lisbon smoking entertainment places, in particular ETS contamination, and may provide biomarker candidates for occupational ETS-exposure which might precede respiratory diseases on their employees. Work supported by Fundação Calouste Gulbenkian, Administração Central do Sistema de Saúde, FCT/PolyAnnual Funding Program and FEDER/SaudeXXI Program, Portugal. VDM, SP,NC,BA and TS, are recipients of FCT fellowships.

Submitted by Claudia Graça (claudiasusana@ipt.pt) on 2018-04-16T14:15:58Z No. of bitstreams: 11 capa do cd.pdf: 21295 bytes, checksum: c6247ed2c8cb5bc0dfb1641dcc55e70a (MD5) Capa.pdf: 72596 bytes, checksum: ef2873f4f10cdb4771d43da1444c2f35 (MD5) Capítulo 1.pdf: 161753 bytes, checksum: 0ef1f2f4d58450588e95b368aee932f3 (MD5) Capítulo 2.pdf: 11336981 bytes, checksum: f4b40e6c875e3ff3d792d52dd8900c01 (MD5) Capítulo 3.pdf: 750203 bytes, checksum: df7f78c46ba452bbe3d83f422cb38a9e (MD5) Capítulo 4.pdf: 4664105 bytes, checksum: cc7b279904e69d114b3682e0d96ca503 (MD5) Conclusão.pdf: 50971 bytes, checksum: 653cbd60f9c2bfd05bd13a5ee55e3a05 (MD5) Índice.pdf: 441420 bytes, checksum: 7fe3ab0a6a7559e3d796c260187a860c (MD5) Separador do capítulo 2.pdf: 25206 bytes, checksum: 5c20cfca536b237be4f206408bb5a6b2 (MD5) Separador do capítulo 3.pdf: 25212 bytes, checksum: 8a0c33f7164d68263b8d4f0383d1eb31 (MD5) Subcapa.pdf: 100752 bytes, checksum: d39f7421b97b0c5a3fedb4560f85176f (MD5) Made available in DSpace on 2018-04-16T14:15:58Z (GMT). No. of bitstreams: 11 capa do cd.pdf: 21295 bytes, checksum: c6247ed2c8cb5bc0dfb1641dcc55e70a (MD5) Capa.pdf: 72596 bytes, checksum: ef2873f4f10cdb4771d43da1444c2f35 (MD5) Capítulo 1.pdf: 161753 bytes, checksum: 0ef1f2f4d58450588e95b368aee932f3 (MD5) Capítulo 2.pdf: 11336981 bytes, checksum: f4b40e6c875e3ff3d792d52dd8900c01 (MD5) Capítulo 3.pdf: 750203 bytes, checksum: df7f78c46ba452bbe3d83f422cb38a9e (MD5) Capítulo 4.pdf: 4664105 bytes, checksum: cc7b279904e69d114b3682e0d96ca503 (MD5) Conclusão.pdf: 50971 bytes, checksum: 653cbd60f9c2bfd05bd13a5ee55e3a05 (MD5) Índice.pdf: 441420 bytes, checksum: 7fe3ab0a6a7559e3d796c260187a860c (MD5) Separador do capítulo 2.pdf: 25206 bytes, checksum: 5c20cfca536b237be4f206408bb5a6b2 (MD5) Separador do capítulo 3.pdf: 25212 bytes, checksum: 8a0c33f7164d68263b8d4f0383d1eb31 (MD5) Subcapa.pdf: 100752 bytes, checksum: d39f7421b97b0c5a3fedb4560f85176f (MD5) Previous issue date: 2011 Instituto Politécnico de Tomar

Seminário Internacional de Conservação de Azulejos – Conservation of Glazed Ceramic Tiles – organizado pelo LNEC e realizado em Lisboa de 15-16 de abril de 2009. The main objective of the present work is to establish a correlation between the characteristics of the ceramic body of ancient tiles and the workshop where they were made. The work was carried out with tiles from the Museu Nacional do Azulejo collection, but the aim is to study the most important period of the history of tiles in Portugal, the first quarter of the 18th century, the so called Ciclo dos Mestres (Master’s Cycle). In the present work, we make use of SEM-EDS and DRX to determine the major constituents of the ceramic body, as well as to evaluate the procedure used to produce the tiles. Signed and unsigned tiles were used. The analysis of the chemical composition, mineralogical phases, shape and size of particles combined with historical information allowed to conclude that the tiles of the panel Vista de Lisboa (MNAz inv. 1) and Senhora dos Corações have identical global chemical composition but not the same mineralogical characteristics. Two other tiles featuring King Charles II (MNAz inv. 691) and his wife Queen Catherine of Braganza (MNAz inv. 690), present different properties, which indicate another provenience of the clay materials and, probably, another workshop and painter. info:eu-repo/semantics/publishedVersion

O Instituto Português de Oncologia de Francisco Gentil – Centro Regional Oncológico de Lisboa S.A acolhe anualmente cerca de mulheres portadoras de Cancro Ginecológico. O Serviço de Ginecologia tem, desde a sua criação, fomentado a existência de um Grupo Multidisciplinar dos Tumores Ginecológicos que engloba não só os Ginecologistas como Oncologistas Médicos, Radioterapeutas Oncológicos, Anátomo-Patologistas, Imagiologistas e outros Especialistas com competência em Oncologia Ginecológica. A Comissão de Protocolos de Diagnóstico e de Terapêutica é a emanação prática desta filosofia. Assim, a revisão e actualização dos Protocolos elaborados por esta Comissão e agora publicados traduzem a metodologia usada no Serviço e baseiam-se nos protocolos de Instituições Oncológicas Internacionais de referência e na experiência acumulada na nossa Instituição, considerando a capacidade técnica e meios materiais existentes. Pretendem, tanto quanto possível, uniformizar procedimentos e agilizar a colaboração com todas as Instituições que nos referenciam as suas doentes, tendo como fim último o tratamento correcto do Cancro Ginecológico, com um aproveitamento racional dos recursos humanos e técnicos.

Actualmente existe uma significativa incerteza em relação a várias dimensões essenciais na actividade empresarial, provocando uma redução da confiança entre os actores envolvidos e em consequência, o adiamento de investimentos tão necessários a uma relevante retoma da actividade económica, nacional e comunitária. A responsabilidade social (RS), como sistema de gestão, possui instrumentos adequados para a promoção sistemática do envolvimento destes actores empresariais, maximizando impactes positivos e minimizando impactes negativos, resultantes da actividade empresarial. É assim entendida por alguns autores como fundamental para a conquista de vantagens competitivas organizacionais. A integração dos princípios da RS na estratégia da organização conduz a planos de acção orientados para a satisfação de necessidades das partes interessadas (PI) internas e externas. Quanto maior ligação entre as empresas e a sociedade, com vista a implementar esta estratégia de RS, maior o potencial de confiança e reputação. As organizações socialmente responsáveis vão desempenhar as suas funções, para com as várias PI, tendo em conta princípios de maior transparência, maior envolvimento, foco nas suas necessidades e expectativas, princípios de bom governo, com adequada planificação estratégica e procura por eficiências organizacionais. A área do desenvolvimento de competências é vista como muito relevante para esta promoção da cidadania empresarial socialmente responsável. Neste âmbito, os eventos formativos motivacionais denominados por team buildings comunitários, enquadram-se como grandes promotores do envolvimento entre colaboradores de empresas e algumas associações de solidariedade social. Permitem ajudar de forma significativa estas entidades acolhedoras ao mesmo tempo que potenciam o desenvolvimento de competências sociais e comportamentais nos colaboradores das entidades promotoras. Este artigo, apresenta um estudo de caso de um evento de team building comunitário, no Hospital Dona Estefânia em Lisboa.

Tese de doutoramento, Química (Química-Tecnológica), Universidade de Lisboa, Faculdade de Ciências, 2013 Submitted by amelia Janeiro (ajaneiro@reitoria.ul.pt) on 2013-12-20T17:00:06Z No. of bitstreams: 1 ulsd067045_td_Teresa_Santos.pdf: 16113472 bytes, checksum: 2249e75c55f0e5377779e30d72991d0e (MD5) Made available in DSpace on 2014-01-03T12:05:23Z (GMT). No. of bitstreams: 1 ulsd067045_td_Teresa_Santos.pdf: 16113472 bytes, checksum: 2249e75c55f0e5377779e30d72991d0e (MD5) Fundação para a Ciência e a Tecnologia (FCT, SFRH/BD/48242/2008)