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Listeria monocytogenes, a foodborne pathogen causing listeriosis, poses substantial societal, economic, and public health challenges due to its resistance, persistence, and biofilm formation in the food industry. Exploring subinhibitory concentrations of compounds to target virulence inhibition and increase susceptibility to adverse conditions presents a promising strategy to mitigate its impact of L. monocytogenes and unveils new potential applications. Thus, this study aims to explore the effect of linalool on virulence factors of L. monocytogenes and potential use in the reduction in its tolerance to stressful conditions. This action was analysed considering the use of two sub-inhibitory concentrations of linalool, 0.312 and 0.625 mg/mL. We found that even with the lowest tested concentrations, a 65% inhibition of violacein production by Chromobacterium violaceum, 55% inhibition in biofilm formation by L. monocytogenes and 62% reduction on haemolysis caused by this bacterium were observed. In addition to its impact on virulence factors, linalool diminished the tolerance to osmotic stress (up to 4.3 log reduction after 24 h with 12% NaCl), as well as to high (up to 3.8 log reduction after 15 min at 55 °C) and low temperatures (up to 4.6 log reduction after 84 days with 12% NaCl at 4 °C). Thus, this study paves the way to further investigation into the potential utilization of linalool to mitigate the threat posed by L. monocytogenes in the field of food safety and public health.

Introduction: With only 39 reported cases in the literature, carriers of a small supernumerary marker chromosome (sSMC) derived from chromosome 11 represent an extremely rare cytogenomic condition.Methods: Herein, we present a review of reported sSMC(11), add 18 previously unpublished cases, and closely review eight cases classified as ‘centromere-near partial trisomy 11’ and a further four suited cases from DECIPHER.Results and discussion: Based on these data, we deduced the borders of the pericentric regions associated with clinical symptoms into a range of 2.63 and 0.96 Mb for chromosome 11 short (p) and long (q) arms, respectively. In addition, the minimal pericentric region of chromosome 11 without triplo-sensitive genes was narrowed to positions 47.68 and 60.52 Mb (GRCh37). Furthermore, there are apparent differences in the presentation of signs and symptoms in carriers of larger sSMCs derived from chromosome 11 when the partial trisomy is derived from different chromosome arms. However, the number of informative sSMC(11) cases remains low, with overlapping presentation between p- and q-arm-imbalances. In addition, uniparental disomy (UPD) of ‘normal’ chromosome 11 needs to be considered in the evaluation of sSMC(11) carriers, as imprinting may be an influencing factor, although no such cases have been reported. Comprehensively, prenatal sSMC(11) cases remain a diagnostic and prognostic challenge.

Otolith microstructure analysis is a valuable tool to evaluate the relationship between larval age and growth and how it relates to environmental variability. Otolith growth and daily increment deposition were analyzed in sardine (Sardina pilchardus) larvae reared in the laboratory under different temperatures (13, 15, and 17 °C), with a diet rich in microalgae, rotifers, and copepods Acartia grani. The number and width of growth increments, first-check and otolith diameter were determined in the otoliths and then related to larval age and total length. At hatching, the sagittal otoliths consisted of a lenticular core with a diameter of 10.56 μm (±1.07 μm SD). Somatic growth increased with the increasing temperature and the growth rate of larvae reared at 13 and 15 °C was significantly lower than for larvae reared at 17 °C. At 17 °C, otoliths exhibited a higher diameter with wider increments than at 13 °C. There was a high variability of increment counts-at-age for larvae reared within the same temperature treatment. The increase of growth increments with larval size was higher for larvae reared at 17 °C until 35 days post-hatching than those growing at 15 °C. Scanning electronic microscopy confirmed that increments are deposited daily, with an average width smaller than 1 µm and as low as 0.33 μm, therefore impossible to distinguish using light microscopy. At colder temperatures, larval otoliths had thinner and less marked increments and lower growth rates, which can lead to incorrect age determinations. The effect of temperature on the otolith microstructure can help in identifying strong temperature gradients experienced by wild sardine larvae.

Sexuality is defined as a multidimensional experience that involves genital, mental, and bodily components. It is also assumed as a basic condition inherent to the human existence that encourages the search for love, intimacy, sex, and proximity to others. The main objective of this study is to assess the relationship between cues of sexual desire and sexual attitudes in Portuguese women. This is a cross-sectional study with 804 Portuguese women to whom the protocol was applied. It included an informed consent, a sociodemographic questionnaire, a questionnaire related to intimacy, a scale of sexual attitudes, and the scale of cues of sexual desire. The protocol was applied via Google Forms due to the current pandemic situation (COVID-19). Differences were found in sexual attitudes and the cues of sexual desire in terms of sociodemographic characteristics, as well as in terms of women’s intimacy. Significant correlations were found between the brief sexual attitudes scale (BSAS) and the cues of sexual desire scale (CSDS). Age, sexual orientation, relation nature, sexual practices, visual proximity cues, erotic explicit cues, and sensory explicit cues explain, altogether, 25% of the total sexual attitudes. Additionally, age, sexual orientation, the relation’s nature, sexual practices, visual proximity cues, emotional bonding cues, romantic implicit cues, erotic explicit cues, and sensory explicit cues explain, altogether, 30% of the permissiveness. Sexual attitudes are developed under the influence of sociodemographic variables, variables related to women’s intimacy, and cues of sexual desire, which are new data in the study of sexual attitudes and have implications at the level of gender issues.

Aliarcobacter butzleri is a Gram-negative bacterium associated with infections of the gastrointestinal tract and widely distributed in various environments. For successful infection, A. butzleri should be able to tolerate various stresses during gastrointestinal passage, such as bile. Bile represents an antimicrobial host barrier that acts against external noxious agents and consists of a variety of bile salts. The intestinal bile salts act as detergents involved in the antimicrobial host defense; although, on the bacterial side, they could also serve as a signal to activate virulence mechanisms. The aim of this work was to understand the effects of bile salts on the survival and virulence of A. butzleri. In our study, A. butzleri was able to survive in the presence of human physiological concentrations of bile salts. Regarding the virulence features, an increase in cellular hydrophobicity, a decrease in motility and expression of flaA gene, as well as an increase in biofilm formation with a concomitant change in the type of biofilm structure were observed in the presence of sub-inhibitory concentration of bile salts. Concerning adhesion and invasion ability, no significant difference was observed. Overall, the results demonstrated that A. butzleri is able to survive in physiological concentrations of bile salts and that exposure to bile salts could change its virulence mechanisms.

Staphylococcus aureus can exhibit resistance to various antibiotics. Among its resistance mechanisms, the active efflux of antibiotics can be seen as relevant. This study aimed to evaluate the ability of resveratrol to modulate norfloxacin resistance in S. aureus. The antimicrobial activity of resveratrol was assessed using the broth microdilution method to determine the minimum inhibitory concentration (MIC). Then, the modulatory effect of resveratrol was evaluated using the MIC determination for the antibiotic or ethidium bromide in the presence and absence of resveratrol at a sub-MIC level. The MIC of norfloxacin against S. aureus SA1199B (NorA-overexpressing strain) decreased 16-fold when in the presence of resveratrol, with a similar behavior being observed for ethidium bromide. An evaluation of the ethidium bromide accumulation was also performed, showing that in the presence of resveratrol, the SA1199B strain had augmented fluorescence due to the accumulation of ethidium bromide. Altogether, the results suggested that resveratrol may act by inhibiting NorA. These in vitro data were supported by docking results, with interactions between resveratrol and the NorA efflux pump predicted to be favorable. Our findings demonstrated that resveratrol may modulate norfloxacin resistance through the inhibition of NorA, increasing the effectiveness of this antibiotic against S. aureus.

Rice culture is one of the most important crops in the world, being the most consumed cereal grain (755 million tons in 2020). Since rice is usually produced under flooding conditions and water performs several essential functions for the crop, estimating its water needs is essential. Remote sensing techniques have shown effectiveness in estimating and monitoring the water use in crop fields. An estimation from satellite data is a challenge, but could be very useful, in order to spatialize local estimates and operationalize production models. This study intended to derive an approach to estimate the actual crop evapotranspiration (ETa) in rice paddies from a temporal series of satellite images. The experimental data were obtained in the Lis Valley Irrigation District (central coast of Portugal), during the 2019 to 2021 rice growing seasons. The average seasonal ETa (FAO56) resulted 586 ± 23 mm and the water productivity (WP) was 0.47 ± 0.03 kg m−3. Good correlations were found between the crop coefficients (Kc) proposed by FAO and the NDVI evolution in the control rice fields, with R2 ranging between 0.71 and 0.82 for stages II+III (development + middle) and between 0.76 and 0.82 for stage IV (late). The results from the derived RS-assisted method were compared to the ETa values obtained from the surface energy balance model METRIC, showing an average estimation error of ±0.8 mm d−1, with a negligible bias. The findings in this work are promising and show the potential of the RS-assisted method for monitoring ETa and water productivity, capturing the local and seasonal variability in rice growing, and then predicting the rice yield, being a useful and free tool available to farmers.

R E S U M O As folhas das bromélias, dispostas em forma de roseta, possuem a capacidade de acumular água proporcionando um microambiente particular capaz de suportar uma comunidade de diferentes organismos adaptados a estas condições específicas. Presentes em ambientes urbanos, as bromélias podem apresentar uma condição ambiental ainda mais estressante (p.ex. altas temperaturas e poluição) para os organismos que ocupam os seus tanques. Neste sentido, questionamos sobre a capacidade destes locais apresentarem o desenvolvimento de massas macroscópicas (visíveis a olho nu) de algas. Os resultados mostraram ser possível, embora com baixa riqueza de espécies. Apenas duas espécies foram registradas: Rhizoclonium hieroglyphicum e Oedogonium sp., que estiveram presentes em mais da metade (53,3%) das plantas avaliadas. Possivelmente, características particulares presente nestas espécies de algas (p.ex. estrutura morfológica simples e resistência à dessecação) e sua condição cosmopolita devem ter favorecido sua ocupação e desenvolvimento nestes ambientes fitotélmicos bromelícolas. Palavras-chave: Algas, Bromélia, Ambiente alterado. Macroalgae in urban bromeliad phytotelmic environments. It's possible? A B S T R A C T The leaves of bromeliads, arranged in a spiral shape, have the ability to accumulate water can provide a microenvironmen capable of a community of organisms adapted to these specific conditions. Present in urban environments, bromeliads can present an even more stressful environmental condition (eg. Hight temperatura and pollution) for the organisms that occupy their tanks. In this sense, we questioned the capacity of these sites to present the development of macroscopic algae masses. The results showed to be possible, although with low species richness. Only two species were registered: Rhizoclonium hieroglyphicum and Oedogonium sp., which were present in 53.3% of the evaluated plants. Possibly, particular characteristics present in these species (simple morphological structure and resistance to desiccation) and their cosmopolitan condition must have favored their occupation and development in these bromeliad phytotelmic environments. Keywords: Algae, Bromeliad, Altered environment.

Organic farming can play an important role in rural development and food production, by reinforcing the trend toward sustainable agriculture and its purpose of ecosystem conservation. The agribusiness of organic farming is particularly relevant in family farming, given the labor availability and the short marketing circuits. The innovative techniques of organic farming, namely with soil fertility, weed and pest control, opens a wide range of possibilities in its development and extension. The expectation of organic farming profitability in small-scale family farming, supported by known successful examples, were the theme of a field study on Lis Valley Irrigation District to assess the constraints to its expansion in order to outline the procedures for the acquisition of technical knowledge, the adaptation of technologies, the support for the conversion of production models, and the specialized training of farmers for action. Results revealed that the: (i) farmer’s land structure, (ii) their mature age, (iii) low education level, and (iv) markets, are the main constrains for organic farming development. Furthermore, other uncertainties were identified, namely: (i) the certification process, (ii) the knowledge of new technologies, especially of crop protection, and (iii) the marketing problems to guaranteeing profitability. This study concludes that organic farming has significant potential for development in the Lis Valley and that the efforts and resources of the various stakeholders, namely the state, need to be harmonized to deliver effective support to farmers to promote organic farming that prioritizes: (i) rural development policies, (ii) supporting land restructuring, (iii) modernization of irrigation, (iv) stimulation of young farmers, (v) conversion and implementation of innovative technologies, (vi) the organization of farmers for better productive efficiency, and (vii) to facilitate market access.

Irrigation districts play a decisive role in Portuguese agriculture and require the adaptation to the new water management paradigm through a change in technology and practices compatible with farmers’ technical know-how and economic sustainability. Therefore, improvement of water management, focusing on water savings and increasing farmers’ income, is a priority. In this perspective, an applied research study is being carried out on the gravity-fed Lis Valley Irrigation District to assess the performance of collective water supply, effectiveness of water pumping, and safety of crop production due to the practice of reuse of drainage water. The water balance method was applied at irrigation supply sectors, including gravity and Pumping Irrigation Allocation. The average 2018 irrigation water allocated was 7400 m3/ha, being 9.3% by pumping recharge, with a global efficiency of about 67%. The water quality analysis allowed identifying some risk situations regarding salinization and microbiological issues, justifying action to solve or mitigate the problems, especially at the level of the farmers’ fields, according to the crops and the irrigation systems. Results point to priority actions to consolidate improved water management: better maintenance and conservation of infrastructure of hydraulic infrastructures to reduce water losses and better flow control; implementation of optimal operational plans, to adjust the water demand with distribution; improvement of the on-farm systems with better water application control and maintenance procedures; and improvement of the control of water quality on the water reuse from drainage ditches. The technological innovation is an element of the modernization of irrigation districts that justifies the development of multiple efforts and synergies among stakeholders, namely farmers, water users association, and researchers.

The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.

Aliarcobacter butzleri is considered a ubiquitous microorganism and emergent pathogen, for which increasing rates of multidrug resistance have been described. In line with this, the present work aimed to evaluate for the first time the contribution of an ABC efflux system, the YbhFSR, in the resistance and virulence of this bacterium. Following the in silico characterization of the YbhFSR transporter, a mutant strain was constructed by inactivating the gene responsible for ATP-binding. After ensuring that the mutation did not have an impact on bacterial growth, the resistance profile of parental and mutant strains to different antimicrobial agents was evaluated. The results suggest that the efflux pump may influence the resistance to benzalkonium chloride, ethidium bromide, and cadmium, and several other compounds were identified as potential substrates. Regarding the evaluation of the accumulation of ethidium bromide, a slight increase was observed for the mutant strain, demonstrating a potential role of the YbhFSR efflux pump in the extrusion of toxic compounds from A. butzleri. Subsequently, the role of this efflux pump on the A. butzleri known virulence properties was evaluated, but no difference was seen among mutant and parental strains for the motility, biofilm formation ability, susceptibility to oxidative stress, or the ability to adhere and invade Caco-2 cells. However, in contrast to the parental strain, the mutant strain showed a resistance to human serum. Overall, the results support the role of efflux pumps in A. butzleri resistance to antimicrobials, highlighting the particular role of the YbhFSR system.

Arcobacter butzleri is an emergent gram-negative enteropathogenic bacterium widespread in different environments and hosts. During the colonization of the gastrointestinal tract, bacteria face a variety of environmental conditions to successfully establish infection in a new host. One of these challenges is the fluctuation of oxygen concentrations encountered not only throughout the host gastrointestinal tract and defences but also in the food industry. Oxygen fluctuations can lead to modulations in the virulence of the bacterium and possibly increase its pathogenic potential. In this sense, eight human isolates of A. butzleri were studied to evaluate the effects of microaerobic and aerobic atmospheric conditions in stressful host conditions, such as oxidative stress, acid survival, and human serum survival. In addition, the effects on the modulation of virulence traits, such as haemolytic activity, bacterial motility, biofilm formation ability, and adhesion and invasion of the Caco-2 cell line, were also investigated. Overall, aerobic conditions negatively affected the susceptibility to oxygen reactive species and biofilm formation ability but improved the isolates’ haemolytic ability and motility while other traits showed an isolate-dependent response. In summary, this work demonstrates for the first time that oxygen levels can modulate the potential pathogenicity of A. butzleri, although the response to stressful conditions was very heterogeneous among different strains.

Abstract Introduction Rheumatoid arthritis (RA) is a well-documented independent risk factor for cardiovascular disease. Obesity may provide an additional link between inflammation and accelerated atherosclerosis in RA. Objective To evaluate the association between obesity and disease parameters and cardiovascular risk factors in RA patients. Method Cross-sectional study of a cohort of RA patients from three Brazilian teaching hospitals. Information on demographics, clinical parameters and the presence of cardiovascular risk factors was collected. Blood pressure, weight, height and waist circumference (WC) were measured during the first consultation. Laboratory data were retrieved from medical records. Obesity was defined according to the NCEP/ATPIII and IDF guidelines. The prevalence of obesity was determined cross-sectionally. Disease activity was evaluated using the DAS28 system (remission 5.1). Results The sample consisted of 791 RA patients aged 54.7 ± 12.0 years, of whom 86.9% were women and 59.9% were Caucasian. The mean disease duration was 12.8 ± 8.9 years. Three quarters were rheumatoid factor-positive, the mean body mass index (BMI) was 27.1 ± 4.9, and the mean WC was 93.5 ± 12.5 cm. The observed risk factors included dyslipidemia (34.3%), type-2 diabetes (15%), hypertension (49.2%) and family history of premature cardiovascular disease (16.5%). BMI-defined obesity was highly prevalent (26.9%) and associated with age, hypertension and dyslipidemia. Increased WC was associated with diabetes, hypertension, dyslipidemia and disease activity. Conclusion: Obesity was highly prevalent in RA patients and associated with disease activity.

Reseña de libro: López-Sala, Ana y Godenau, Dirk (coords.). Estados de contención, estados de detención: El control de la inmigración irregular en España. Anthropos Editorial, 2017. 256 págs.

The Cre-Lox system allows high spatiotemporal control of genetic modifications. Here the authors present iSuRe-Cre that significantly increases Cre activity in reporter expressing cells, which ultimately increases the efficiency and reliability of Cre-dependent reporter and gene function analysis.

Resumo: A agricultura biológica cria um mercado para bens e serviços ambientais, e os produtores podem ser recompensados pela sua gestão agroambiental através de preços premium e pela Política Agrícola Comum (PAC). O objetivo deste trabalho foi caracterizar os agricultores da Região Centro de agricultura do ponto de vista socioeconómico, além de avaliar a propensão para a mudança do modo produtivo para a agricultura biológica e identificar as principais dificuldades para a mudança. Foi realizado o estudo dos efeitos das políticas agrícolas na evolução da agricultura biológica. Foram realizados estudos através de entrevistas presenciais resultando em dois estudos de caso. Os estudos de caso apresentam metodologias distintas, mas complementares. O trabalho revelou que a PAC contribuiu para o desenvolvimento deste setor e os dados alcançados permitem aos investigadores desenvolver técnicas para que os agricultores possam superar os obstáculos e aumentar a competitividade da cadeia de valor. A renovação geracional e o aumento da dimensão da exploração são factores a considerar para o progresso da agricultura biológica. É necessário gerar formação adequada às necessidades e fornecer informações precisas e reais sobre as dificuldades e benefícios desse modo de agricultura.

Rice irrigation by continuous flooding is highly water demanding in comparison with most methods applied in the irrigation of other crops, due to a significant deep percolation and surface drainage of paddies. The pollution of water resources and methane emissions are other environmental problems of rice agroecosystems, which require effective agronomic changes to safeguard its sustainable production. To contribute to this solution, an experimental study of alternate wetting and drying flooding (AWD) was carried out in the Center of Portugal in farmer’s paddies, using the methodology of field irrigation evaluation. The AWD results showed that there is a relevant potential to save about 10% of irrigation water with a reduced yield impact, allowing an additional period of about 10 to 29 days of dry soil. The guidelines to promote the on-farm scale AWD automation were outlined, integrating multiple data sources, to get a safe control of soil water and crop productivity. The conclusions point out the advantages of a significant change in the irrigation procedures, the use of water level sensors to assess the right irrigation scheduling to manage the soil deficit and the mild crop stress during the dry periods, and the development of paddy irrigation supplies, to allow a safe and smart AWD.

O presente estudo se insere no confronto da população do Baixo Araguaia em proclamar seus direitos básicos numa longa história de luta, permeada de violência e aos olhos vendados da Justiça e do Estado. Nos sertões do Baixo Araguaia ainda são notórios a imposição do ‘mais forte’, o silenciar pelo medo, porém, hoje, não mais se calam os gritos dos oprimidos. Nesse estudo de revisão bibliográfica, inicialmente é realizada uma reflexão sobre os sertões na República Federativa do Brasil. Também se discute sobre o faroeste sertanejo no Baixo Araguaia (MT) e por fim é apresentada a educação como ferramenta libertadora, que, com a presença de inúmeros sujeitos históricos desde meados da década de 1960, provocaram mudanças significativas na vida dos moradores dessa região.

Desde a chegada dos portugueses no Brasil, a escravidão foi a força de trabalho mais utilizada pelos proprietários rurais. Com a abolição da escravatura, ainda no século XIX, não houve equiparação social tampouco cessou a exploração de pessoas menos favorecidas. Isso resultou em conflitos e resistências que permanecem até os dias atuais, e infelizmente parece que a força do mais forte ainda prevalece. Essa pesquisa teve como finalidade compreender de que forma ocorrem as relações de exploração do trabalho análogo ao escravo, bem como verificar se a falta de escolarização de crianças, jovens e adultos contribui para a ocorrência dessa situação na Região do Baixo Araguaia. Trata-se de uma pesquisa exploratória, de natureza básica e para que o objetivo fosse atingido, foi realizada uma revisão bibliográfica e documental. Verificou-se que o trabalho análogo ao escravo está presente no Brasil contemporâneo, bem como na região em estudo e que a maioria dos trabalhadores resgatados não tem escolaridade o que contribui ainda mais para as ocorrências. Espera-se que por meio da realização desse estudo seja possível denunciar e trazer à tona essa grave prática que ainda acontece em nosso meio. Além disso, o estudo vem somar-se às lutas de vários indivíduos, geralmente reprimidas, que por décadas tem buscado modificar a situação de trabalhadores na região do Baixo Araguaia, localizada no Estado de Mato Grosso.

This study estimates the association between temperature and self-reported mental health. We match individual-level mental health data for over three million Americans between 1993 and 2010 to historical daily weather information. We exploit the random fluctuations in temperature over time within counties to identify its effect on a 30-day measure of self-reported mental health. Compared to the temperature range of 60-70°F, cooler days in the past month reduce the probability of reporting days of bad mental health while hotter days increase this probability. We also find a salience effect: cooler days have an immediate effect, whereas hotter days tend to matter most after about 10 days. Using our estimates, we calculate the willingness to pay to avoid an additional hot day in terms of its impact on self-reported mental health.

Background: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. Methods: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. Findings: By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. Interpretation: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity. Keywords: Chemoradiotherapy, Colorectal cancer, Zebrafish avatars, Personalized medicine, Radiotherapy

Members of the family Arcobacteraceae are distributed widely in aquatic environments, and some of its species have been associated with human and animal illness. However, information about the diversity and distribution of Arcobacteraceae in different water bodies is still limited. In order to better characterize the health risk posed by members in the family Arcobacteraceae, a systematic review and meta-analysis-based method was used to investigate the prevalence of Arcobacteraceae species in aquatic environments based on available data published worldwide. The database search was performed using related keywords and considering studies up to February 2021. The pooled prevalence in aquatic environments was 69.2%, ranging from 0.6 to 99.9%. These bacteria have a wide geographical distribution, being found in diverse aquatic environments with the highest prevalence found in raw sewage and wastewater treatment plants (WWTP), followed by seawater, surface water, ground water, processing water from food processing plants and water for human consumption. Assessing the effectiveness of treatments in WWTP in eliminating this contamination, it was found that the wastewater treatment may not be efficient in the removal of Arcobacteraceae. Among the analyzed Arcobacteraceae species, Al. butzleri was the most frequently found species. These results highlight the high prevalence and distribution of Arcobacteraceae in different aquatic environments, suggesting a risk to human health. Further, it exposes the importance of identifying and managing the sources of contamination and taking preventive actions to reduce the burden of members of the Arcobacteraceae family.

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft-tissue infections to more serious and life-threatening infections such as sepsis, meningitis and endocarditis, which may be exacerbated by antibiotic resistance. Plant products may be seen as an alternative as antibacterial agents, namely, against S. aureus. Thus, the aim of this work was to characterize the chemical composition and evaluate the bioactive properties of the T. zygis essential oil (EO), with a focus on antimicrobial activity against S. aureus. Gas chromatography coupled with mass spectrometry was used to assess the chemical composition of the T. zygis EO, and the antioxidant activity was evaluated using the DPPH method and β-carotene-bleaching assay. The antimicrobial activity against S. aureus strains, the interaction with different antibiotics and the attenuation of this bacterium’s virulence were evaluated. The T. zygis EO showed antioxidant activity acting through two different mechanisms and antibacterial activity against S. aureus, with antibiofilm and antihaemolytic properties. This EO also demonstrated synergistic or additive interactions in combination with ampicillin, ciprofloxacin or vancomycin against S. aureus strains and, in some cases, changed the antibiotic-resistance phenotype from resistant to susceptible. Therefore, the present work demonstrates the good bioactive properties of the EO of T. zygis, mainly the antimicrobial activity against S. aureus, revealing its potential to be used as an antibacterial agent.

Aliarcobacter butzleri is an emergent enteropathogen that can be found in a range of environments. This bacterium presents a vast repertoire of efflux pumps, such as the ones belonging to the resistance nodulation cell division family, which may be associated with bacterial resistance, as well as virulence. Thus, this work aimed to evaluate the contribution of three RND efflux systems, AreABC, AreDEF and AreGHI, in the resistance and virulence of A. butzleri. Mutant strains were constructed by inactivation of the gene that encodes the inner membrane protein of these systems. The bacterial resistance profile of parental and mutant strains to several antimicrobials was assessed, as was the intracellular accumulation of the ethidium bromide dye. Regarding bacterial virulence, the role of these three efflux pumps on growth, strain fitness, motility, biofilm formation ability, survival in adverse conditions (oxidative stress and bile salts) and human serum and in vitro adhesion and invasion to Caco-2 cells was evaluated. We observed that the mutants from the three efflux pumps were more susceptible to several classes of antimicrobials than the parental strain and presented an increase in the accumulation of ethidium bromide, indicating a potential role of the efflux pumps in the extrusion of antimicrobials. The mutant strains had no bacterial growth defects; nonetheless, they presented a reduction in relative fitness. For the three mutants, an increase in the susceptibility to oxidative stress was observed, while only the mutant for AreGHI efflux pump showed a relevant role in bile stress survival. All the mutant strains showed an impairment in biofilm formation ability, were more susceptible to human serum and were less adherent to intestinal epithelial cells. Overall, the results support the contribution of the efflux pumps AreABC, AreDEF and AreGHI of A. butzleri to antimicrobial resistance, as well as to bacterial virulence.

Aliarcobacter butzleri is an emergent enteropathogen, showing high genetic diversity, which likely contributes to its adaptive capacity to different environments. Whether natural transformation can be a mechanism that generates genetic diversity in A. butzleri is still unknown. In the present study, we aimed to establish if A. butzleri is naturally competent for transformation and to investigate the factors influencing this process. Two different transformation procedures were tested using exogenous and isogenic DNA containing antibiotic resistance markers, and different external conditions influencing the process were evaluated. The highest number of transformable A. butzleri strains were obtained with the agar transformation method when compared to the biphasic system (65% versus 47%). A. butzleri was able to uptake isogenic chromosomal DNA at different growth phases, and the competence state was maintained from the exponential to the stationary phases. Overall, the optimal conditions for transformation with the biphasic system were the use of 1 μg of isogenic DNA and incubation at 30 °C under a microaerobic atmosphere, resulting in a transformation frequency ~8 × 10−6 transformants/CFU. We also observed that A. butzleri favored the transformation with the genetic material of its own strain/species, with the DNA incorporation process occurring promptly after the addition of genomic material. In addition, we observed that A. butzleri strains could exchange genetic material in co-culture assays. The presence of homologs of well-known genes involved in the competence in the A. butzleri genome corroborates the natural competence of this species. In conclusion, our results show that A. butzleri is a naturally transformable species, suggesting that horizontal gene transfer mediated by natural transformation is one of the processes contributing to its genetic diversity. In addition, natural transformation can be used as a tool for genetic studies of this species.

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

Background: Fabry disease (FD) causes cerebrovascular disease (CVD) even if asymptomatic, and this is why it is important to identify non-invasive methods to monitor the disease. We evaluated the usefulness of the cerebral autoregulation, vasoreactivity, and neurovascular coupling assessed by transcranial Doppler (TCD) in FD. Methods: Ten adult patients with classic phenotype FD, without clinical expression of CVD, and ten healthy controls, were included. We monitored cerebral blood flow velocity with TCD in the middle and posterior cerebral arteries, blood pressure, heart rate, and non-invasive expired carbon dioxide (CO2). Cerebral autoregulation was calculated from the spontaneous oscillations of blood pressure, cerebral vasoreactivity through CO2 inhalation and hyperventilation and neurovascular coupling by the flow velocity change to visual stimulation. Results: FD male patients showed blunted vasoreactivity in posterior circulation (0.70 ± 0.36%/mmHg vs. 1.09 ± 0.18%/mmHg CO2, p = 0.01) and impaired neurovascular coupling (overshoot 15 ± 2.9% vs. 28 ± 6.1%, p < 0.01). Cerebral autoregulation was similar to controls. Conclusion: Male patients with FD classic phenotype and hitherto clinical expression of CVD already show impairment of cerebral vasoreactivity and neurovascular coupling. It supports the notion of an early dysfunction of cerebral microvascular in a presymptomatic stage of CVD in FD and that TCD could be useful in its assessment.

Peritoneal dialysis-related infections are important morbidity/mortality causes, being staphylococci the most prevalent agents. Since Staphylococcus aureus nasopharynx carriage is a known risk factor for PD infections and the oral cavity is a starting point for systemic diseases development, we aimed at comparing the oral staphylococci colonization between PD patients and controls and studying the association with PD-related infections. Saliva samples were plated in Mannitol salt, and isolates were identified by DnaJ gene sequencing. Staphylococci PD-related infections were recorded throughout the 4-year period following sample collection. Staphylococcus colonization was present in >90% of the samples from both groups (a total of nine species identified). PD patients presented less diversity and less prevalence of multispecies Staphylococcus colonization. Although all patients presenting Staphylococcus epidermidis PD-related infections were also colonized in the oral cavity by the same agent, only 1 out of 7 patients with ESI caused by S. aureus presented S. aureus oral colonization. Staphylococci are highly prevalent in the oral cavity of both groups, although PD patients presented less species diversity. The association between oral Staphylococcus carriage and PD-related infections was present for S. epidermidis but was almost inexistent for S. aureus, so, further studies are still necessary to evaluate the infectious potential of oral Staphylococcus carriage in PD.

Resveratrol is a plant secondary metabolite commonly found in peanuts and grapevines with significant health benefits. Recombinant organisms can produce large amounts of resveratrol and, in this work, Escherichia coli BW27784 was used to produce resveratrol in bioreactors while monitoring cell physiology and plasmid stability through flow cytometry and real-time qPCR, respectively. Initially, the influence of culture conditions and precursor addition was evaluated in screening assays and the data gathered was used to perform the bioreactor assays, allowing the production of 160 μg/mL of resveratrol. Cellular physiology and plasmid instability affected the final resveratrol production, with lower viability and plasmid copy numbers associated with lower yields. In sum, this study describes new tools to monitor the bioprocess, evaluating the effect of culture conditions, and its correlation with cell physiology and plasmid segregational stability, in order to define a viable and scalable bioprocess to fulfill the need for larger quantities of resveratrol.

Publicaciones recientes han desafiado la visión convencional sobre la naturaleza benigna de la infección por el virus de Chikungunya (VCHIK). Las manifestaciones clínicas son muy variables y pueden ser graves en algunos casos. Los estudios sugieren que la forma grave de la infección por el VCHIK puede ser asociada con disfunción orgánica múltiple, hepatitis, meningitis, nefritis, encefalitis, dermatitis ampollosa, miocarditis, arritmias cardiacas, entre otras. La fisiopatología subyacente para algunas de las complicaciones de la enfermedad por el VCHIK sigue siendo poco clara. Sin embargo, de acuerdo con las características clínicas de los casos graves o atípicos descritos a la fecha, el desarrollo de complicaciones podría agruparse principalmente en tres categorías: la exacerbación de condiciones médicas subyacentes, el deterioro de un trastorno no reconocido previamente y la respuesta inmunológica inadecuada a la infección. Se ha encontrado asociación entre las manifestaciones graves de la infección, niveles elevados de citoquinas y algunas secuencias genómicas específicas del VCHIK. La inmunoterapia pasiva puede constituir una estrategia eficaz en el tratamiento de individuos expuestos al VCHIK con riesgo de infección grave. Actualmente no existe evidencia clínica que soporte el uso de antivirales en la prevención o tratamiento de la infección por el VCHIK.

The current migratory crisis in the Mediterranean questions the European Union’s (EU) capacity to manage migratory flows. So far, the EU has placed a particular emphasis on border management, given a lack of political will that continues to prevent more in depth institutional responses. The current situation in the Mediterranean, and the EU’s response is a cause of concern due to the risk it represents to the human security of migrants, and the questions it raises regarding the management of migratory flows within the EU. The major question to emerge during this crisis is: How does the EU manage irregular migration flows while safeguarding migrants’ human rights?

A esclerose tuberosa (ET) é uma doença rara, esporádica ou transmitida de forma autossómica dominante. Caracteriza-se pela tríade convulsões, atraso mental e angiofibromas faciais. O envolvimento pulmonar é raro e, quando ocorre, é mais frequente no sexo feminino. Os autores apresentam o caso de uma doente de 52 anos, não fumadora, com antecedentes conhecidos de epilepsia na infância e angiomiolipomas renais. Assintomática e sem alterações ao exame objectivo. Em tomografia do tórax realizada para avaliação da doença, foram detectadas formações microquísticas dispersas em ambos os campos pulmonares. Exame funcional respiratório normal. A ressonância magnética cerebral evidenciou tuberosidades corticais e nódulos subependimários calcificados. Concluiu-se pelo diagnóstico de ET (linfangioleiomiomatose, tuberosidades corticais, nódulos subependimários e angiomiolipomas renais). Os autores apresentam o caso pela raridade da doença e do envolvimento pulmonar, ainda que em fase assintomática.Tuberous sclerosis (TS) is a rare, sporadic or autosomal dominant disease characterized by the triad of seizures, mental retardation and angiofibromas. Lungs are rarely involved in TS, and pulmonary involvement is almost always found in females. We report the case of a 52 year-old female, nonsmoker, with a history of seizures in childhood and renal angiomyolipomas. She presented no complaints and her physical exam was normal. Chest CT performed for the evaluation of the disease detected thin-walled pulmonary cysts in both lungs. Lung function tests were normal. Cortical tubers and calcified subependymal nodules were seen in cerebral magnetic resonance. Tuberous sclerosis was diagnosed (lymphangioleiomyomatosis, cortical tubers, calcified subependymal nodules and angiomyiolipomas). The authors present this case because of its rarity and the existence of pulmonary involvement, while still asymptomatic.

Resumo: A estenose traqueal surge na sequência de agressões à mucosa traqueal (isquémicas, traumáticas ou outras).O tratamento das estenoses traqueais continua a representar um desafio em termos de técnicas endoscópicas e cirurgia, apesar de todos os recentes avanços nesta área. O processo de cicatrização e a reestenose são as principais causas de falência terapêutica.Os autores apresentam dois casos clínicos de doentes com estenose traqueal como consequência de entuba ção orotraqueal prolongada/traqueostomia, em que o tratamento foi bem sucedido com dilatação com broncoscopia rígida e laser, complementada por aplicação tópica de mitomicina C.Rev Port Pneumol 2010; XVI (1): 149-156 Abstract: Tracheal stenosis follows any injury to the airway mucosa, such as ischaemic, traumatic and other injuries.The treatment of tracheal stenosis remains a challenging problem despite all the advances in endoscopic and surgical techniques. Scar formation and reestenosis are the main causes of treatment failure.The authors present two cases of successful treatment of a tracheal stenosis after tracheal injury from pro longed oro-tracheal intubation / tracheostomy following dilatation with rigid broncoscope and laser therapy, associated with topical application of mitomycin C as an adjuvant treatment.Rev Port Pneumol 2010; XVI (1): 149-156 Palavras-chave: Mitomicina C, estenoses traqueais, broncoscopia, terapêutica com laser, Key-words: Mitomycin C, tracheal stenosis, bronchoscopy, laser therapy

A estenose traqueal surge na sequência de agressões à mucosa traqueal (isquémicas, traumáticas ou outras). O tratamento das estenoses traqueais continua a representar um desafio em termos de técnicas endoscópicas e cirurgia, apesar de todos os recentes avanços nesta área. O processo de cicatrização e a reestenose são as principais causas de falência terapêutica. Os autores apresentam dois casos clínicos de doentes com estenose traqueal como consequência de entubação orotraqueal prolongada/traqueostomia, em que o tratamento foi bem sucedido com dilatação com broncoscopia rígida e laser, complementada por aplicação tópica de mitomicina C.Tracheal stenosis follows any injury to the airway mucosa, such as ischaemic, traumatic and other injuries. The treatment of tracheal stenosis remains a challenging problem despite all the advances in endoscopic and surgical techniques. Scar formation and reestenosis are the main causes of treatment failure. The authors present two cases of successful treatment of a tracheal stenosis after tracheal injury from pro-longed oro-tracheal intubation / tracheostomy following dilatation with rigid broncoscope and laser therapy, associated with topical application of mitomycin C as an adjuvant treatment.

A ventilação não invasiva (VNI) consiste na aplicação de um suporte ventilatório sem recorrer a métodos invasivos, evitando desta forma as complicações associadas à entubação orotraqueal e ventilação mecânica invasiva. Esta técnica já demonstrou ser eficaz em diversos tipos de insuficiência respiratória aguda ou crónica agudizada. Neste artigo, os autores fazem uma revisão dos benefícios, vantagens e limitações da VNI, interfaces utilizadas e principais indicações desta técnica na insuficiência respiratória aguda (IRA) e na insuficiência respiratória crónica agudizada.Non-invasive ventilation (NIV) is a technique that delivers mechanical ventilation avoiding side effects and complications associated with endotracheal intubation and invasive mechanical ventilation. This technique has proved to be effective in different types of respiratory failure. In this article, the authors revise the advantages and limitations of NIV, interfaces used and indications in acute and acute-on-chronic respiratory failure.

Resumo: A ventilação não invasiva (VNI) consiste na aplicação de um suporte ventilatório sem recorrer a métodos invasivos, evitando desta forma as complicações associadas à entubação orotraqueal e ventilação mecânica invasiva. Esta técnica já demonstrou ser eficaz em diversos tipos de insuficiência respiratória aguda ou crónica agudizada. Neste artigo, os autores fazem uma revisão dos benefícios, vantagens e limitações da VNI, interfaces utilizadas e principais indicações desta técnica na insuficiência respiratória aguda (IRA) e na insuficiência respiratória crónica agudizada.Rev Port Pneumol 2009; XV (4): 655-667 Abstract: Non-invasive ventilation (NIV) is a technique that delivers mechanical ventilation avoiding side effects and complications associated with endotracheal intubation and invasive mechanical ventilation. This technique has proved to be effective in different types of respiratory failure. In this article, the authors revise the advantages and limitations of NIV, interfaces used and indications in acute and acute-on-chronic respiratory failure.Rev Port Pneumol 2009; XV (4): 655-667 Palavras-chave: Ventilação não invasiva, insuficiência respiratória, edema agudo do pulmão, doenças pulmonares obstrutivas, asma, bronquiectasias, fibrose quística, entubação orotraqueal, Key-words: Noninvasive ventilation, respiratory failure, pulmonary edema, obstructive lung diseases, asthma, bronchiectasis, cystic fibrosis, endotracheal intubation

Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave e progressiva potencialmente fatal em poucos anos. Até à década de 90, o único tratamento eficaz para esta entidade era o transplante pulmonar/cardiopulmonar. Nos últimos anos assistiu-se ao aparecimento de novos fármacos que vieram alterar o curso da doença. Objectivos: Caracterização dos doentes com HAP observados no Centro Hospitalar de VN Gaia no período de 2000 a 2006. Alertar para esta entidade. Material e métodos: Análise retrospectiva de todos os doentes com HAP ou doença tromboembólica crónica em tratamento no CHVN Gaia. Resultados: No referido período foram observados 11 doentes, 7 mulheres e 4 homens, com média etária de 43 anos. Cinco doentes com HAP idiopática, três com doença tromboembólica crónica, dois com HAP associada a comunicação interauricular e um com HAP associada a S. CREST. Ao diagnóstico, a maioria encontrava-se em classe funcional NYHA/OMS III/IV, a pressão sistólica média da artéria pulmonar foi de 98±32mmHg e a distância média percorrida na 6-MWT foi de 401m. Terapêutica inicial: Três doentes iloprost por via inalatória; dois treprostinil subcutâneo; três bosentan per os; um sildenafil per os e dois doentes foram submetidos a cirurgia. O tempo médio de follow-up é de 28,1±20.3 meses. Cinco doentes melhoraram, três mantiveram-se estáveis, um agravou e dois faleceram. Conclusão: A HAP é uma doença grave que requer uma abordagem multidisciplinar com necessidade de terapêuticas complexas e dispendiosas. O diagnóstico em estádios precoces é essencial, de modo a permitir uma terapêutica atempada.Introduction: Pulmonary arterial hypertension (PAH) is a serious and progressive disease, potentially fatal in a few years. Until the 1990s the only effective treatment for this disease was pulmonary/cardiopulmonary transplant. Over the last few years several drugs have emerged that have modified the course of the disease. Aims: To characterise patients with PAH followed at Centro Hospitalar de V.N.Gaia between 2000 and 2006. To raise awareness of this entity. Material and methods: Retrospective analysis of all patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) followed at our Hospital. Results: In this period 11 patients were observed, 7 women and 4 men, with a mean age of 43 y. Five patients had idiopathic PAH, three had CTEPH, two had PAH associated with interauricular communication and one had PAH associated with CREST Syndrome. At the time of diagnosis most patients were in NYHA//WHO Functional Class III/IV, mean systolic pulmonary artery pressure was 98±32mmHg and mean distance walked in the 6-minute walk test was 401m. Initial treatment: Three patients had inhaled iloprost, two subcutaneous treprostinil, three oral bosentan, one oral sildenafil and two patients underwent surgery. Mean follow-up time was 28.1 months. Five patients recovered, three are stable, one worsened and two died. Conclusions: PAH is a serious illness which requires a multidisciplinary approach with the need for complex and expensive therapies. Diagnosis in initial stages is essential for an effective treatment.

Resumo: Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave e progressiva potencialmente fatal em poucos anos. Até à década de 90, o único tratamento eficaz para esta entidade era o transplante pul-monar/cardiopulmonar. Nos últimos anos assistiu-se ao aparecimento de novos fármacos que vieram alte-rar o curso da doença.Objectivos: Caracterização dos doentes com HAP observados no Centro Hospitalar de VN Gaia no período de 2000 a 2006. Alertar para esta entidade.Material e métodos: Análise retrospectiva de todos os doentes com HAP ou doença tromboembólica crónica em tratamento no CHVN Gaia.Resultados: No referido período foram observados 11 doentes, 7 mulheres e 4 homens, com média etária de 43 anos. Cinco doentes com HAP idiopática, três com doença tromboembólica crónica, dois com HAP associada a comunicação interauricular e um com HAP associada a S. CREST. Ao diagnóstico, a maioria en-contravase em classe funcional NYHA/OMS III/IV, a pressão sistólica média da artéria pulmonar foi de 98±32 mmHg e a distância média percorrida na 6-MWT foi de 401 m. Terapêutica inicial: Três doentes iloprost por via inalatória; dois treprostinil subcutâneo; três bosentan per os; um sildenafil per os e dois doentes foram submetidos a cirurgia. O tempo médio de follow-up é de 28,1±20.3 meses. Cinco doentes melhoraram, três mantiveram-se estáveis, um agravou e dois faleceram.Conclusão: A HAP é uma doença grave que requer uma abordagem multidisciplinar com necessidade de terapêuticas complexas e dispendiosas. O diagnóstico em estádios precoces é essencial, de modo a permitir uma terapêutica atempada.Rev Port Pneumol 2007; XIII (2): 239-254 Abstract: Introduction: Pulmonary arterial hypertension (PAH) is a serious and progressive disease, potentially fatal in a few years. Until the 1990s the only effective treatment for this disease was pulmonary/cardiopulmo-nary transplant. Over the last few years several drugs have emerged that have modified the course of the disease.Aims: To characterise patients with PAH followed at Centro Hospitalar de V.N.Gaia between 2000 and 2006. To raise awareness of this entity.Material and methods: Retrospective analysis of all patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) followed at our Hospital.Results: In this period 11 patients were observed, 7 women and 4 men, with a mean age of 43 y. Five patients had idiopathic PAH, three had CTEPH, two had PAH associated with interauricular communication and one had PAH associated with CREST Syndrome.At the time of diagnosis most patients were in NYHA/ /WHO Functional Class III/IV, mean systolic pulmonary artery pressure was 98±32 mmHg and mean distance walked in the 6-minute walk test was 401 m. Initial treatment: Three patients had inhaled iloprost, two subcutaneous treprostinil, three oral bosentan, one oral sildenafil and two patients under-went surgery. Mean follow-up time was 28.1 months. Five patients recovered, three are stable, one worsened and two died.Conclusions: PAH is a serious illness which requires a multidisciplinary approach with the need for complex and expensive therapies. Diagnosis in initial stages is essential for an effective treatment.Rev Port Pneumol 2007; XIII (2): 239-254

This paper examines how major earthquakes affected the returns and volatility of aggregate stock market indices in thirty-five financial markets over the last twenty years. Results show that global financial markets are resilient to shocks caused by earthquakes even if these are domestic. Our analysis reveals that, in a few instances, some macroeconomic variables and earthquake characteristics (gross domestic product per capita, trade openness, bilateral trade flows, earthquake magnitude, a tsunami indicator, distance to the epicenter, and number of fatalities) mediate the impact of earthquakes on stock market returns, resulting in a zero net effect. However, the influence of these variables is market-specific, indicating no systematic pattern across global capital markets. Results also demonstrate that stock market volatility is unaffected by earthquakes, except for Japan.

Atherosclerotic carotid disease represents approximately 20% of the causes of ischemic stroke. Effective treatment options, such as endovascular or surgical revascularization procedures, are available. Doppler Ultrasound (DUS) is a non-invasive, inexpensive, routine exam used to evaluate the presence of internal carotid artery (ICA) stenosis. We retrospectively analysed the prevalence of severe atherosclerotic carotid disease in a population of patients with acute ischemic stroke/transitory ischemic attacks (TIAs), and the role of DUS in the detection of ICA stenosis and treatment decisions in these patients.A total of 318 patients with ischemic stroke or TIAs was admitted to our stroke unit, and 260 patients were studied by DUS. ICA stenosis was evaluated by DUS according to peak systolic velocity. All DUS exams were performed by the same operator. ICA stenosis was further assessed in 43 patients by digital subtraction angiography (DSA) using NASCET criteria.Of the total 318 patients, 260 (82%) had DUS evaluation. Of the total 520 ICAs studied by DUS, degrees of ICA stenosis were: 0-29% n= 438 (84%); 30-49% n= 8 (2%); 50-69% n= 27 (5%); 70-89% n= 15 (3%); 90-99% n= 20 (4%); oclusão n= 14 (2%). Of the total 260 patients studied, 43 (16.5%) underwent DSA. Sensibility and specificity of DUS in the diagnosis of carotid stenosis over 70% were, respectively, 91% e 84%. Of the total 31 patients with significant carotid stenosis (70-99%), 23 (74%) underwent subsequent carotid revascularization procedures.DUS is an important screening test in our stroke unit, justifying its use as a routine exam for all patients with ischemic stroke/TIAs. Moreover, our results show the relevance of severe carotid disease in a population with acute ischemic stroke/TIAs (16.5%), with a total of 9% of patients being submitted to carotid revascularization procedures.