Variabilidade e reprodutibilidade da análise das medições ecocardiográficas na estenose valvular aórtica

Background: Doppler echocardiography is the most frequent method for detecting and evaluating the severity of valvular aortic stenosis. The aim of this study was to assess the variability and reproducibility of echocardiographic parameters including aortic valve area (AVA), peak aortic jet velocity (Vmax), velocity ratio (VLVOT/Vmax), peak gradient (Gmax) and mean gradient (Gmean) in aortic stenosis (AS) patients. Methods: Doppler echocardiograms were obtained from 150 randomly selected patients (56.7% male; mean age 73±9 years) with asymptomatic moderate aortic valve stenosis. The echocardiographic measurements were performed by two independent level III (expert) blinded observers. To assess intra-observer variability, we evaluated parameters of AS progression at two different times (mean of two weeks after the first examination). Results: For intra-observer variability (observer 1), the variation and reproducibility coefficients were, respectively, 1.88% and 0.16 m/s for Vmax, 2.08% and 0.14 for VLVOT/Vmax, 2.05% and 0.18 cm2 for AVA, 3.89% and 5.18 mmHg for Gmax and 7.87% and 6.30 mmHg for Gmean. For inter-observer variability, the variation and reproducibility coefficients were, respectively, 2.00% and 0.14 m/s for Vmax, 2.91% and 0.14 for VLVOT/Vmax, 7.67% and 0.16 cm2 for AVA, 8.53% and 7.06 mmHg for Gmean and 3.90% and 5.58 mmHg for Gmax. Both intra- and inter-observer studies showed excellent intraclass correlation coefficients (ICC) for all echocardiographic parameters (ICC ranged from 0.943 to 0.990 for intra-observer variability and from 0.955 to 0.992 for interobserver variability). Conclusion: Doppler echocardiographic measurements of AVA, Vmax, Gmax and Gmean are highly reproducible when performed by expert observers. Of all echocardiographic parameters, Vmax and VLVOT/Vmax showed the best variability and reproducibility, and thus constitute reliable tools for clinical and research purposes in aortic stenosis diagnosis and follow-up.Introdução: A ecocardiografia Doppler é o método mais frequente de detecção e avaliação da gravidade da estenose valvular aórtica. O objectivo deste estudo foi avaliar a variabilidade e reprodutibilidade dos parâmetros ecocardiográficos como a área valvular aórtica (AVA), velocidade pico (Vmax), relação de velovidades (VLVOT/Vmax), gradiente pico (Gmax) e gradiente médio (Gmédio) nos doentes com estenose aórtica. Métodos: Um ecocardiograma Doppler foi realizado em 60 doentes consecutivos seleccionados aleatoriamente (da população do estudo RAAVE) com estenose aórtica moderada a grave assintomática (56.7% sexo masculino; idade média 73 ± 9 anos). As medidas ecocardiográficas foram efectuadas por dois ecocardiografistas de nível III numa estratégia de dupla ocultação. Para o estudo da variabilidade intra-observador, avaliamos os prâmetros de progressão da estenose aórtica em dois momentos diferentes (média de duas semanas após o 1.º exame). Resultados: No que respeita à variabilidade intra-observador (observador 1), os coeficientes de variação e reprodutibilidade foram, respectivamente, 1.88% e 0.16 m.s-1 para a Vmax, 2.08% e 0.14 cm2 para a VLVOT/Vmax, 2.05% e 0.18 ms-1 para a AVA, 3.89% e 5.18 mmHg para Gmax and 7.87% e 6.30 mmHg para o Gmédio. No que respeita à variabilidade inter- -observador, os coeficientes de variação e reprodutibilidade foram, respectivamente, 2.00% e 0.14 m.s-1 para a Vmax, 2.91% e 0.14 m.s-1 para a relação VLVOT/Vmax, 7.67% e 0.16 cm2 para a AVA, 8.53% e 7.06 mmHg para o Gmédio e 3.90% e 5.58 mmHg para o Gmax. Os estudos intra-observador e inter-observador mostraram ter excelentes coeficientes de correlação intra-classe (CCI), para todos os parâmetros ecocardiográficos (CCI varia de 0.943 até 0.990 para a variabilidade intra- -observador e de 0.955 até 0.992 para a variabilidade inter-observador). Conclusões: As medições ecocardiográficas da AVA, Vmax, Gmax and Gmédio são altamente reprodutíveis quando realizadas por ecocardiografistas experientes. De todos os parâmetros ecocardiográficos a Vmax e a relação VLVOT/Vmax apresentam os melhores valores de variabilidade e reprodutibilidade e assim constituem provavelmente a melhor ferramenta no diagnóstico e seguimento criterioso dos doentes com estenose valvular aórtica.info:eu-repo/semantics/publishedVersio

Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U) is a diterpene compound isolated from Plectranthus grandidentatus with an antiproliferative effect on several human cancer cell lines. Herein, we studied the modulatory activity of coleon U on individual isoforms of the three protein kinase C (PKC) subfamilies, classical (cPKC-α and -βI), novel (nPKC-δ and -ɛ) and atypical (aPKC-ζ), using a yeast PKC assay. The results showed that, whereas the PKC activator phorbol-12-myristate-13-acetate (PMA) activated every PKC tested except aPKC, coleon U had no effect on aPKC and cPKCs. Besides, the effect of coleon U on nPKCs was higher than that of PMA. This revealed that coleon U was a potent and selective activator of nPKCs. The isoform-selectivity of coleon U for nPKC-δ and -ɛ was confirmed using an in vitro PKC assay. Most importantly, while PMA activated nPKCs inducing an isoform translocation from the cytosol to the plasma membrane and a G2/M cell cycle arrest, coleon U induced nPKCs translocation to the nucleus and a metacaspase- and mitochondrial-dependent apoptosis. This work therefore reconstitutes in yeast distinct subcellular translocations of a PKC isoform and the subsequent distinct cellular responses reported for mammalian cells. Together, our study identifies a new isoform-selective PKC activator with promising pharmacological applications. Indeed, since coleon U has no effect on cPKCs and aPKC, recognised as anti-apoptotic proteins, and selectively induces an apoptotic pathway dependent on nPKC-δ and -ɛ activation, it represents a promising compound for evaluation as an anti-cancer drug.We are grateful to Dr. Nigel Goode for providing YEplac181-PKC-α, PKC-βI, PKC-δ, -PKC-ɛ and -PKC-ζ; to Dr. Heimo Riedel for providing YEp52-PKC-α and Yep51-PKC-βI; to Dr. Charles Rudin for providing pOW4-Bcl-xL; to Dr. Stéphen Manon for providing pCLbGFP-mt-GFP; to Joana Tavares for her help and technical advice in some experiments; to Cristina G-Marques for the previous isolation of coleon U; to Helena Vasconcelos for critical reading of the manuscript. We thank REQUIMTE/CEQUP and FCT (I&D No 8/94), POCTI (QCA III) and FEDER for financial support. I. Coutinho is recipient of a PhD fellowship from FCT (SFRH/BD/36066/2007).info:eu-repo/semantics/publishedVersio

Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity

Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have previously been ascribed largely to its inhibitory actions on phosphodiesterase. However, more recent studies suggest an additional role in affecting the activity of the mammalian target of rapamycin (mTOR), a master regulator of myeloid cell translational pathways, although detailed molecular events underlying its mode of action have not been elucidated. Here, we report the cellular uptake of caffeine, without metabolisation, by healthy and malignant hematopoietic myeloid cells including monocytes, basophils and primary acute myeloid leukaemia mononuclear blasts. Unmodified caffeine downregulated mTOR signalling, which affected glycolysis and the release of pro-inflammatory/pro-angiogenic cytokines as well as other inflammatory mediators. In monocytes, the effects of caffeine were potentiated by its ability to inhibit xanthine oxidase, an enzyme which plays a central role in human purine catabolism by generating uric acid. In basophils, caffeine also increased intracellular cyclic adenosine monophosphate (cAMP) levels which further enhanced its inhibitory action on mTOR. These results demonstrate an important mode of pharmacological action of caffeine with potentially wide-ranging therapeutic impact for treating non-infectious disorders of the human immune system, where it could be applied directly to inflammatory cells

Neutron spectra and dosimetric assessment around a neutron Howitzer container

The neutron Howitzer container at the Neutron Measurements Laboratory of the Nuclear Engineering Department of the Polytechnic University of Madrid (UPM), is equipped with a 241Am-Be neutron source of 74 GBq in its center. The container allows the source to be in either the irradiation or the storage position. To measure the neutron fluence rate spectra around the Howitzer container, measurements were performed using a Bonner spheres spectrometer and the spectra were unfolded using the NSDann program. A calibrated neutron area monitor LB6411 was used to measure the ambient dose equivalent rates, H*(10). Detailed Monte-Carlo simulations were performed to calculate the measured quantities at the same positions. The maximum relative deviation between simulations and measurements was 19.53%. After validation, the simulated model was used to calculate the equivalent dose rate in several key organs of a voxel phantom. The computed doses in the skin and lenses of the eyes are within the ICRP recommended dose limits, as is the H*(10) value for the storage position

O Evento FCNC 2005 e o Turismo

Este relatório foi elaborado com base num estudo que decorreu entre Julho e Dezembro de 2005. O objectivo geral do projecto que se desenvolveu traduziu-se na tentativa de aprofundar o conhecimento sobre o perfil dos visitantes não residentes no Algarve que participaram nos eventos culturais da Faro, Capital Nacional da Cultura, assim como as suas motivações, actividades e impressões. Além deste objectivo o Centro de Estudos da Escola Superior de Gestão Hotelaria e Turismo (ESGHT) da Universidade do Algarve tinha em mente a prossecução de outros fins que se prendiam com a criação de uma linha de investigação nos domínios do Património, da Cultura e do Turismo dado que possui um conjunto de docentes com formação especializada nesta área. Acresce que esta instituição é membro da ATLAS - Association for Tourism and Leisure Studies agremiação que desenvolve, com regularidade, estudos sobre o Perfil do Turista Cultural, a nível mundial, em parceria com estabelecimentos de ensino superior, nos quais nós temos vindo a participar com a colaboração de algumas câmaras municipais do Algarve. Para concretizar os objectivos propostos, foi realizada, numa primeira fase, recolha de informação relativa a estudos desenvolvidos no âmbito de eventos anteriores, nomeadamente: Cidades e Capitais Europeias da Cultura; Porto, Capital Europeia da Cultura; Coimbra, Capital Nacional da Cultura; entre outros. A investigação primária teve por base principal um inquérito aplicado junto de uma amostra de visitantes/turistas participantes na programação de Faro Capital Nacional da Cultura, tendo-se previsto uma amostragem mínima de 500 inquéritos a visitantes de várias nacionalidades. Estes inquéritos foram administrados por dois estagiários recrutados entre os alunos finalistas da ESGHT. O inquérito que se aplicou teve por base o já produzido pela ATLAS (Association for Tourism and Leisure Education) para estudar eventos associados ao turismo e estava disponível em quatro idiomas: português, inglês, alemão e espanhol. Na amostragem desenvolvida tentou-se aplicar os questionários em diferentes tipos de eventos, para que a amostra fosse representativa (ver capítulo 6) das várias actividades programadas: exposições; eventos de rua (concertos, festivais); eventos em recinto fechado (teatro, dança, concerto); atracções (museus, monumentos). No final da investigação teve lugar uma apresentação pública dos resultados a que se seguiu a elaboração do relatório que se passa a apresentar. Este é constituído por sete capítulos sendo que no primeiro se estabelece a relação entre turismo e cultura, no segundo sumaria-se a evolução do turismo cultural na Europa e traça- se o perfil do turista cultural, no terceiro expõe-se a ligação entre turismo e eventos, (com maior relevo para os eventos culturais), no quarto descreve-se o conceito de cidade e de capital europeia da cultura, no quinto caracteriza-se a Faro capital da Cultura, no sexto explica-se a metodologia seguida, e por fim, no sétimo apresentam-se os resultados obtidos e tecem-se as considerações finais

Anorexia nervosa: divergent validity of a prototype narrative among anorexia relatives

The objective of this ex post facto study was to test the divergent validity (degree of discrimination) of anorexia prototype narrative according to anorectic close confidents (relatives), as well as explore different characteristics of the participants which may be associated with the degree of prototype discrimination. Sixty-four relatives of individuals with anorexia nervosa participated in the study and were asked to indicate their degree of identification, according to their relative, with five different narrative prototypes (depressive, agoraphobia, anorexic, alcoholic, and drug addiction prototypes). Results did not confirm the divergent validity of the anorexic prototype narrative. The participants tended to identify primarily their relative with the agoraphobia prototype. Once again, no significant differences were found between the identification with the anorexic prototype and depression, agoraphobia and alcoholism prototype. The only significant differences found were for the comparison between the anorexic and drug addiction prototype. However, anorectic mothers and illness duration were found to be associated with the degree of identification of prototype narrative. Results were discussed in terms of a systemic versus a prototype approach to the eating disorders.El objetivo de este estudio ex post facto fue analizar la validez divergente (grado de discriminación) de la narrativa prototipo de la anorexia nerviosa de acuerdo a los familiares significativos de los pacientes anoréxicos y explorar distintas características de los participantes que pueden estar asociadas con el grado de discriminación de la narrativa prototipo. Participaron 64 personas significativas de los individuos con anorexia nerviosa, a los que se les pidió que indicasen el grado de identificación, de acuerdo con su familiar, con cinco narrativas prototipo distintas (depresión, agorafobia, anorexia, alcoholismo y tóxico-dependencia). Los resultados no confirmaron la validez divergente de la narrativa prototipo de la anorexia. Los participantes mostraron tendencia a identificar en primer lugar a sus familiares con el prototipo de la agorafobia. Además, no se encontraron diferencias significativas entre la identificación con el prototipo de la anorexia y el de la depresión, de la agorafobia y del alcoholismo. La única diferencia significativa encontrada fue en la comparación entre el prototipo de la anorexia y el de la tóxico-dependencia. No obstante, las madres de las anoréxicas y la duración del trastorno se asocian al grado de identificación con la narrativa prototipo de la anorexia. Se discuten los resultados en términos de una aproximación sistémica versus prototipo de las perturbaciones del comportamiento alimentario.Foundation for Science and Technology, Portugal (FCT) - POCTI/33252/99

Anorexia nervosa e construção de significado: validação divergente de uma narrativa protótipo

O estudo que apresentamos vem na sequência de um outro em que foi construída a narrativa protótipo da anorexia nervosa e analisada a sua validade convergente (grau de verosimilhança). Desenvolvemos dois estudos empíricos cujos objectivos centrais são: a) analisar a validade divergente (grau de discriminação) da narrativa protótipo da anorexia, b) explorar aspectos da história dos sujeitos e dos seus significativos (familiares) que possam estar associados a uma diferença de intensidade na identificação com a narrativa da anorexia e c) proceder a um estudo exploratório do poder preditivo de algumas das variáveis descritivas das amostras. Estas foram constituídas por 70 sujeitos com anorexia nervosa e 64 significativos, respectivamente. Os resultados não confirmam a validação divergente da narrativa protótipo da anorexia, colocando em causa a hipótese da sua prototipia. Ao nível dos participantes com anorexia, foi encontrada uma tendência para uma identificação mais elevada com a narrativa da depressão. Os seus significativos mostraram tendência para uma identificação mais elevada dos seus familiares com a narrativa da agorafobia. Ambos os participantes discriminaram a narrativa protótipo da anorexia apenas em relação à narrativa da toxicodependência. O padrão de resultados observado nos dois estudos a respeito da narrativa da anorexia é o mesmo, sendo que em ambos aquela narrativa assume o segundo lugar em termos de ordem média de identificação. De entre os significativos, é com mães que os sujeitos com anorexia convergem na avaliação que fazem a respeito da identificação com a narrativa protótipo da anorexia.The current paper emerges in continuity with another study in which the anorectic prototype narrative was constructed and its convergent validity (degree of similitude) was analyzed.We developed two empirical studies in which the principal goals were: a) to study the divergent validity (degree of discrimination) of the anorectic prototype narrative, b) to explore some aspects of the history of participants and their close confidents (relatives) that may be associated to the difference in which they identify themselves or their relatives with the anorectic prototype narrative, and c) to study the predictive power of some descriptive variables of the sample. Seventy subjects diagnosed with anorexia and 64 relatives participated in the study. The results did not confirm the divergent validation of the anorectic prototype narrative and, therefore, the prototype hypothesis. The anorectic participants displayed tendency to a higher identification with the depression prototype narrative. Their relatives showed a tendency to a higher identification with the agoraphobia prototype narrative. The anorectic prototype narrative was discriminated by both participant groups from the drug abuse prototype narrative. A similar pattern of results with respect to the anorectic prototype narrative was found in both studies with that narrative achieving the second place of identification. Within the group of relatives it is with their mothers that the anorectic subjects converge with respect to the identification with the anorectic prototype narrative

Exploring triazene derivative's antimicrobial activity and its incorporation onto 3D-printed coatings

Acknowledgments The authors would like to thank the Portuguese government, Fundação para a Ciência e Tecnologia (FCT), for the financial support through national funds: PTDC/BTMSAL/29335/2017. Publisher Copyright: © 2024 The AuthorsAntimicrobial resistance has emerged as a significant health concern demanding the urgent development of new active molecules. Furthermore, within healthcare settings, medical devices can be the cause of microorganisms’ proliferation leading to infection. Thus, nowadays the need for novel antimicrobial biomaterials is mandatory. In this work different 1,3-diaryltriazenes were synthesized for incorporation as antimicrobials onto 3D-printed hydrogel coatings for polydimethylsiloxane (PDMS) substrates used in the production of different medical devices. Symmetric and asymmetric aryltriazenes were synthesized and characterized by spectroscopic methods. Antimicrobial activity was screened and the most active triazene was selected to be incorporated into the 3D-printed coatings that were further characterized by contact angle measurements, FTIR-ATR, SEM, drug release, antimicrobial activity, and cytocompatibility. The 1,3-bis (4-nitro-2-(trifluoromethyl)phenyl) triazene showed activity against Staphylococcus aureus with a minimum inhibitory concentration of 1 μg/mL and revealed no cytotoxicity towards HaCat cells. 3D-printed hydrogel coatings (comprising chitosan/starch and sodium alginate) loaded triazene were successfully produced for PDMS substrates. Triazene coatings presented high wettability and smoothness and revealed antimicrobial and antibiofilm activity (i.e., 96 % reduction) towards S. aureus. Additionally, the produced coatings showed no cytotoxicity under the tested conditions. This study marks the initial proof that incorporating triazenes into 3D-printed hydrogel-based coatings can diminish biofilm formation on widely used biomaterials, such as PDMS surfaces. Herein achieved outcomes have allowed us to confirm and propose a novel type of hybrid construct as an antimicrobial hydrogel coating.publishersversionpublishe

Hyaluronic acid-amphotericin B nanocomplexesa: a promising anti-leishmanial targeted drug delivery system

Leishmaniasis has been classified as one of the most neglected tropical diseases, causing 50 thousand deaths and 1.5 to 2 million new cases every year, according to the World Health Organization. This disease, promoted by protozoan parasites of the genus Leishmania, has a high incidence affecting 89 countries worldwide. Nowadays, current treatment strategies still rely on the antifungal agent amphotericin B (AmB) but are rather inadequate due to the high prevalence of the disease within low-income population of sub-developed regions, the intracellular location of the parasite and the emergence of parasite resistance. Thus, other strategies have been pursued to improve the therapeutic efficacy and to reduce the toxicity of AmB such as the use of biocompatible polysaccharides as carriers. In this work, a simple and inexpensive production process using hyaluronic acid (HA, 50 kDa) was used in order to develop water-soluble hyaluronic acid-amphotericin B nanocomplex (HA-AmB). HA is the main ligand of CD44 receptor, thus being favorably internalized by macrophages that overexpress this receptor upon infection. Therefore, HA arises as a suitable polysaccharide to target the AmB delivery to the leishmania-infected macrophages. The nanocomplex, obtained by simply processing the mixture of the polysaccharide with the drug in a nanospray dryer (HA-AmB SD), was characterized in terms of size/zeta potential (DLS) and morphology (SEM and Cryo-SEM). Furthermore, an HPLC-MS detection method was optimized and used to determine the AmB content in the nanocomplex. Also, to ascertain the interaction between AmB and the HA, FTIR, DSC and PXRD analysis were performed. Cytotoxic and hemolytic effects were assessed on different cell lines through the resazurin test and in dogs blood, respectively. Anti-leishmanial activity was assessed in vitro in axenic cultures of Leishmania by resazurin and in infected bone marrow-derived macrophages (BMM) stained with different fluorescent probes using high-content microscopy. Our results shown that the produced material has a spherical morphology in aqueous solution with a mean hydrodynamic diameter of 318.4 ± 34.7 nm and low polydispersity (0.239 ± 0.02). Moreover, this material that presents an AmB content of 13.56 ± 3.49 %, has a good colloidal stability due to the highly negative surface charge (-39.45 ± 1.12 mV). DSC and PXRD analysis strongly suggested the formation of an amorphous inclusion complex between AmB and the complex polysaccharide chain networks, explaining the high solubility of the drug in water. The in vitro assays showed that compared to free-AmB, the nanocomplex had significantly less cytotoxicity against BMM and HEK293T cell lines, significant less hemolytic effect and inhibited the infection in the Leishmania-infected BMM. Exploratory in vivo assays are being conducted in mice. In conclusion, this work has shown that the hyaluronic acid-AmB nanocomplex is a promising system for the treatment of Leishmaniasis, possessing similar effects to the free-AmB against Leishmania-infected macrophages and Leishmania axenic cultures, with reduced cytotoxicity. Given the affordability, simplicity, low-toxicity and facile scale up of the developed formulation, the hyaluronic acid-AmB nanocomplex may represent an alternative to the expensive nanoformulations available.The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) for supporting this study under the scope of the strategic funding of UID/BIO/04469 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01- 0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Ricardo Silva-Carvalho also acknowledges FCT for the PhD scholarship SFRH/BD/118880/2016.info:eu-repo/semantics/publishedVersio

Dietary intake of young portuguese handball players

The aim of this study was to analyse dietary intake (macronutrients and micronutrients) in young female and male handball athletes. A transversal study was performed with young handball players from sub 16 and 18 Portuguese Handball Federation, who volunteered to participate in this study. Anthropometric (weight and height measure), nutritional intake (using food frequency questionnaire) and position in the game were evaluated. The final sample comprised 64 athletes (48.4% female and 51.6% male). The mean age was 16± 1 years, average body mass index was higher in females (24.1± 3.5kg/m2) than males (23.8± 3.0 kg/m2). Mean energy intake per day was significantly lower in females than males 2167.4± 1185.0 and 2952.9± 1315.8 kcal/day (p= 0.015, 95CI), respectively. According to the recommendations from food, most of the young handball athletes reported a generally higher dietary intake (protein intake was near to the upper recommendation limit; the carbohydrate intake was below and the fat intake higher) and a lower for some micronutrients. A process to identify the athletes that need nutritional support should be considered by handball coaches to optimise their performance and safeguard their healthTo all athletes and their coaches who contributed to the study and to the Portuguese Handball Federationinfo:eu-repo/semantics/publishedVersio