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The chronic shortage of organs and tissues for transplantation represents a dramatic burden on healthcare systems worldwide. Tissue engineering offers a potential solution to address these shortages, but several challenges remain, with prevascularization being a critical factor for in vivo survival and integration of tissue engineering products. Concurrently, a different challenge hindering the clinical implementation of such products, regards their efficient preservation from the fabrication site to the bedside. Hypothermia has emerged as a potential solution for this issue due to its milder effects on biologic systems in comparison with other cold preservation methodologies. Its impact on prevascularization, however, has not been well studied. In this work, 3D prevascularized constructs were fabricated using adipose-derived stromal vascular fraction cells and preserved at 4 °C using Hypothermosol or basal culture media (α-MEM). Hypothermosol efficiently preserved the structural and cellular integrity of prevascular networks as compared to constructs before preservation. In contrast, the use of α-MEM led to a clear reduction in prevascular structures, with concurrent induction of high levels of apoptosis and autophagy at the cellular level. In vivo evaluation using a chorioallantoic membrane model demonstrated that, in opposition to α-MEM, Hypothermosol preservation retained the angiogenic potential of constructs before preservation by recruiting a similar number of blood vessels from the host and presenting similar integration with host tissue. These results emphasize the need of studying the impact of preservation techniques on key properties of tissue engineering constructs such as prevascularization, in order to validate and streamline their clinical application.

Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223.

Bioprospecting actinobacterial secondary metabolism from untapped marine sources may lead to the discovery of biotechnologically-relevant compounds. While studying the diversity and bioactive potential of Actinomycetota associated with Codium tomentosum, a green seaweed collected in the northern Portuguese cost, strain CT-F61, identified as Streptomyces violaceoruber, was isolated. Its extracts displayed a strong anticancer activity on breast carcinoma T-47D and colorectal carcinoma HCT116 cells, being effective as well against a panel of human and fish pathogenic bacteria. Following a bioactivity-guided isolation pipeline, a new analogue of the red-pigmented family of the antibiotics prodigiosins, decylprodigiosin (1), was identified and chemically characterized. Despite this family of natural products being well-known for a long time, we report a new analogue and the first evidence for prodigiosins being produced by a seaweed-associated actinomycete.

Abstract Integrin-binding biomaterials have been extensively evaluated for their capacity to enable de novo formation of capillary-like structures/vessels, ultimately supporting neovascularization in vivo. Yet, the role of integrins as vascular initiators in engineered materials is still not well understood. Here, we show that αvβ3 integrin-specific 3D matrices were able to retain PECAM1+ cells from the stromal vascular fraction (SVF) of adipose tissue, triggering vasculogenesis in vitro in the absence of extrinsic growth factors. Our results suggest that αvβ3-RGD-driven signaling in the formation of capillary-like structures prevents the activation of the caspase 8 pathway and activates the FAK/paxillin pathway, both responsible for endothelial cells (ECs) survival and migration. We also show that prevascularized αvβ3 integrin-specific constructs inosculate with the host vascular system fostering in vivo neovascularization. Overall, this work demonstrates the ability of the biomaterial to trigger vasculogenesis in an integrin-specific manner, by activating essential pathways for EC survival and migration within a self-regulatory growth factor microenvironment. This strategy represents an improvement to current vascularization routes for Tissue Engineering constructs, potentially enhancing their clinical applicability.

In vitro prevascularization is one of the most explored approaches to foster engineered tissue vascularization. We previously demonstrated a benefit in tissue neovascularization by using integrin-specific biomaterials prevascularized by stromal vascular fraction (SVF) cells, which triggered vasculogenesis in the absence of extrinsic growth factors. SVF cells are also associated to biological processes important in cutaneous wound healing. Thus, we aimed to investigate whether in vitro construct prevascularization with SVF accelerates the healing cascade by fostering early vascularization vis-à-vis SVF seeding prior to implantation. Prevascularized constructs delayed re-epithelization of full-thickness mice wounds compared to both non-prevascularized and control (no SVF) groups. Our results suggest this delay is due to a persistent inflammation as indicated by a significantly lower M2(CD163+)/M1(CD86+) macrophage subtype ratio. Moreover, a slower transition from the inflammatory to the proliferative phase of the healing was confirmed by reduced extracellular matrix deposition and increased presence of thick collagen fibers from early time-points, suggesting the prevalence of fiber crosslinking in relation to neodeposition. Overall, while prevascularization potentiates inflammatory cell influx, which negatively impacts the cutaneous wound healing cascade, an effective wound healing was guaranteed in non-prevascularized SVF cell-containing spongy-like hydrogels confirming that the SVF can have enhanced efficacy.

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Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available.

O presente artigo, baseado em análises bibliográficas e documental, busca evidenciar e discutir um conjunto de mudanças institucionais sofrida pela política cultural no Brasil na contemporaneidade, especificamente durante o Governo Bolsonaro. Para tal, inicialmente realizou-se um perpassar histórico sobre a política cultural no país, conforme literatura específica. A seguir, foram discutidas as principais mudanças institucionais impulsionadas pelo referido governo na esfera estatal da cultura, assim como seu impacto conservador.

This paper addresses the development of a novel zero-shot learning method for remote marine litter hyperspectral imaging data classification. The work consisted of using an airborne acquired marine litter hyperspectral imaging dataset that contains data about different plastic targets and other materials and assessing the viability of detecting and classifying plastic materials without knowing their exact spectral response in an unsupervised manner. The classification of the marine litter samples was divided into known and unknown classes, i.e., classes that were hidden from the dataset during the training phase. The obtained results show a marine litter automated detection for all the classes, including (in the worst case of an unknown class) a precision rate over 56% and an overall accuracy of 98.71%.

The successful integration of transplanted three-dimensional tissue engineering (TE) constructs depends greatly on their rapid vascularization. Therefore, it is essential to address this vascularization issue in the initial design of constructs for perfused tissues. Two of the most important variables in this regard are scaffold composition and cell sourcing. Collagens with marine origins overcome some issues associated with mammal-derived collagen while maintaining their advantages in terms of biocompatibility. Concurrently, the freshly isolated stromal vascular fraction (SVF) of adipose tissue has been proposed as an advantageous cell fraction for vascularization purposes due to its highly angiogenic properties, allowing extrinsic angiogenic growth factor-free vascularization strategies for TE applications. In this study, we aimed at understanding whether marine collagen 3D matrices could support cryopreserved human SVF in maintaining intrinsic angiogenic properties observed for fresh SVF. For this, cryopreserved human SVF was seeded on blue shark collagen sponges and cultured up to 7 days in a basal medium. The secretome profile of several angiogenesis-related factors was studied throughout culture times and correlated with the expression pattern of CD31 and CD146, which showed the formation of a prevascular network. Upon in ovo implantation, increased vessel recruitment was observed in prevascularized sponges when compared with sponges without SVF cells. Immunohistochemistry for CD31 demonstrated the improved integration of prevascularized sponges within chick chorioalantoic membrane (CAM) tissues, while in situ hybridization showed human cells lining blood vessels. These results demonstrate the potential of using cryopreserved SVF combined with marine collagen as a streamlined approach to improve the vascularization of TE constructs.

Amyloidosis is a systemic disease, with an incidence of 5-12 people per million per year and autopsy studies suggest the incidence might be higher1. This condition is characterized by deposition of amyloid fibrils, in the extracellular tissue of various organs and systems, and therefore with multiple possible presentations. The causative amyloid fibril deposits are of monoclonal light chain (AL) or transthyretin (TTR) in the vast majority of cases. TTR amyloidosis may be acquired, associated with wild type TTR or hereditary (associated with variants in TTR gene2 (table 1). The AL amyloidosis condition can occur alone or associated with multiple myeloma or other B-cell dyscrasias3. The main affected organs in AL amyloidosis are the heart, kidney, liver, gastrointestinal tract and the peripheral and autonomic nervous systems. Patients often present with non-specific symptoms, such as asthenia, weight loss, palpitations and syncopal attacks4. Thus, diagnosis is usually delayed, and renal and cardiac failure can be forms of presentation. We report a case of a 68-year-old woman, who presented with new onset heart failure as the main presentation form of multiple myeloma with associated cardiac amyloidosis. This case highlights the need of a high level of suspicion in order establish an early diagnosis and initiate specific therapy, and therefore delay the development of this condition.

ABSTRACT Non-renewable chemical products are still the most used for wood protection, however, they have negative aspects. Several problems associated with the extensive use of these substances have been reported, such as intoxication of animals and plants, and environmental contamination. This has led to a search for alternative methods of control that cause less impact on the environment. In this context, the use of natural products extracted from different plants can be an alternative to this industrial activity. The objective of this work was to evaluate the efficiency of andiroba, copaiba and jatropha oils, either pure or enriched with iodine (I2), to improve the biological resistance of Pinus elliottii wood to wood-decay fungi causing brown, white and soft rot. The andiroba and copaiba oils came from the state of Pará and the jatropha oil came from Paraíba. Thus, we performed resistance tests to accelerated decay (brown and white rot fungi) and soft rot tests in the laboratory. We used pure natural oils and those enriched with sublimated iodine in assessing efficiency. In turn, we evaluated the effects of volatilization and leaching on the efficiency of solutions against decaying fungi. Pure andiroba and jatropha oils were the least efficient in controlling the Trametes versicolor fungus in the accelerated decay biological assay. Moreover, the wood treated with pure copaiba oil (normal situation) was classified as non-resistant for controlling Postia placenta fungus. In the soft rot test, we observed that there was a tendency to improve the wood resistance (normal situation) with an increase in the iodine concentration (I2).

This paper addresses the development of a remote hyperspectral imaging system for detection and characterization of marine litter concentrations in an oceanic environment. The work performed in this paper is the following: (i) an in-situ characterization was conducted in an outdoor laboratory environment with the hyperspectral imaging system to obtain the spatial and spectral response of a batch of marine litter samples; (ii) a real dataset hyperspectral image acquisition was performed using manned and unmanned aerial platforms, of artificial targets composed of the material analyzed in the laboratory; (iii) comparison of the results (spatial and spectral response) obtained in laboratory conditions with the remote observation data acquired during the dataset flights; (iv) implementation of two different supervised machine learning methods, namely Random Forest (RF) and Support Vector Machines (SVM), for marine litter artificial target detection based on previous training. Obtained results show a marine litter automated detection capability with a 70–80% precision rate of detection in all three targets, compared to ground-truth pixels, as well as recall rates over 50%.

Introduction: The Management of postoperative pain after abdominal surgery is a major challenge to the anesthesiologist. The optimization of postoperative analgesia improves prognosis contributing also to patient satisfaction and reducing morbidity and mortality. The aim of this randomized control study is to perform the comparative analysis in terms of effectiveness of an unconventional and still poorly technique implemented, continuous wound infusion, and the currently most applied and gold standard technique, epidural analgesia, in the postoperative period after abdominal surgery. Material and Methods: Fifty patients, previously subjected to abdominal surgery by median laparotomy with xifo-pubic incision were randomized to receive postoperative analgesia via epidural (n = 25) or via continuous wound infusion (n = 25) during 48 hours. The primary outcome was analysis of pain at rest (< 4/10 numerical pain scale) after 24 hours postoperatively. Scores of pain at six, 12 and 48 hours and three months after surgery were also evaluated, as well as the incidence of adverse effects 48 hours postoperatively. Results: The proportion of patients with successful control of postoperative pain was 84% against 60% with epidural analgesia and continuous wound infusion, respectively. Within the continuous wound infusion group with uncontrolled pain, all patients rated the pain below 6/10 24 hours postoperatively. The incidence of nausea, vomiting, pruritus or íleus was lower in the continuous wound infusion group, with statistically significant results for recovery of intestinal function. There was one case of systemic local anesthetic toxicity with an episode of frequent ventricular extrasystoles without hemodynamic instability, which ceased after suspension of continuous epidural infusion of local anesthetic. Discussion: This study suggests that continuous wound infusion is the technique with most efficacy and safety, being even better than epidural analgesia in postoperative pain control after major abdominal surgery. This technique is associated with better analgesia, lower incidence of side effects, high level of satisfaction and no residual pain, contributing to enhanced recovery. Conclusion: Continuous wound infusion is an effective technique, which should be implemented for analgesia after major abdominal surgery, with advantages when compared with epidural analgesia, especially low incidence of adverse effects. Registration: Trial not registered.

ABSTRACT Natural products have been studied in order to ensure environmental sustainability, human health, and diminish the use of traditional products. The objective of this study was to evaluate the efficiency of pure andiroba (Carapa guianensis), copaiba (Copaifera langsdorffii) and jatropha (Jatropha curcas) oils and enriched with iodine (I2) on the biological resistance of Pinus elliottii wood to dry-wood termites (Cryptotermes brevis). The oils were enriched with 1%, 3%, and 5% of I2 and impregnated into the wood by cold immersion. The treated samples were subjected to volatilization and leaching. Volatilization and leaching did not affect the loss of mass caused by termites, except for treatments with pure and enriched with 1% iodine copaiba oil. Leached samples were more damaged. The addition of iodine to the oils resulted in a greater efficiency against termites. Andiroba (3% and 5% I2) and jatropha oils (5%) were the most efficient, providing total termite mortality.

This work addresses a hyperspectral imaging system for maritime surveillance using unmanned aerial vehicles. The objective was to detect the presence of vessels using purely spatial and spectral hyperspectral information. To accomplish this objective, we implemented a novel 3-D convolutional neural network approach and compared against two implementations of other state-of-the-art methods: spectral angle mapper and hyperspectral derivative anomaly detection. The hyperspectral imaging system was developed during the SUNNY project, and the methods were tested using data collected during the project final demonstration, in São Jacinto Air Force Base, Aveiro (Portugal). The obtained results show that a 3-D CNN is able to improve the recall value, depending on the class, by an interval between 27% minimum, to a maximum of over 40%, when compared to spectral angle mapper and hyperspectral derivative anomaly detection approaches. Proving that 3-D CNN deep learning techniques that combine spectral and spatial information can be used to improve the detection of targets classification accuracy in hyperspectral imaging unmanned aerial vehicles maritime surveillance applications.

A colagem em peças de madeira por meio de adesivos é realizada desde a época dos faraós. Com o passar dos anos as tecnologias foram desenvolvidas sobretudo nos adesivos e nas diferentes espécies madeireiras existentes, adaptando-se aos diversos usos pretendidos. Neste contexto também se pode inferir sobre os métodos de análises de sua eficácia. O objetivo desse estudo foi avaliar a resistência na linha de cola mediante o uso de dois adesivos em madeira de Paulownia tomentosa (kiri japonês). As juntas coladas foram preparadas com adesivos resorcinol formaldeído e melamina ureia formaldeído. Avaliou-se a interface madeira-adesivo por meio da espessura da linha de cola principal e secundária com uso de fotomicrografias, resistência ao cisalhamento e percentagem de falha na madeira. Os adesivos apresentaram comportamento desuniforme ao longo da linha da cola. O adesivo resorcinol formaldeído penetrou de forma mais incisiva nos elementos de vasos e raios. A madeira de kiri apresentou percentual de falha superior a 92%, independente do adesivo. A eficiência na colagem com ambos adesivos testados possibilita o uso da madeira de Paulownia tomentosa no Brasil em movelaria e construção civil.

Cell Sheet (CS) Engineering is a regenerative medicine strategy proposed for the treatment of injured or diseased organs and tissues. In fact, several clinical trials are underway using CS-based methodologies. However, the clinical application of such cell-based methodologies poses several challenges related with the preservation of CS structure and function from the fabrication site to the bedside. Pausing cells at hypothermic temperatures has been suggested as a valuable method for short-term cell preservation. In this study, we tested the efficiency of two preservation strategies, one using culture medium supplementation with Rokepie and the other using the preservation solution Hypothermosol, in preserving human adipose stromal/stem cells (hASC) CS-like confluent cultures at 4°C, during 3 and 7 days. Both preservation strategies demonstrated excellent ability to preserve cell function during the first 3 days in hypothermia, as demonstrated by metabolic activity results and assessment of extracellular matrix integrity and differentiation potential. At the end of the 7th day of hypothermic incubation, the decrease in cell metabolic activity was more evident for all conditions. Nonetheless, hASC incubated with Rokepie and Hypothermosol retained a higher metabolic activity and extracellular matrix integrity in comparison with unsupplemented cells. Differentiation results for the later time point showed that supplementation with both Rokepie and Hypothermosol rescued adipogenic differentiation potential but only Rokepie was able to preserve hASC osteogenic potential.

Background: Pulse Wave Velocity (PWV) is a measure of arterial stiffness and vascular aging and an important parameter for cardiovascular risk stratification. A previous study showed high prevalence rates of early vascular aging in an adult population from the North of Portugal. The aim of this study was to characterize children from the same region regarding PWV and its relationship with central adiposity indices and blood pressure. Methods: A convenience sample of 285 children aged 10–14 years attending a Northern Portuguese school was used. PWV, height, weight, body mass index (BMI), waist circumference e blood pressure (BP) were measured. Collected data was distributed by gender, age and height specific percentiles. Results: Mean PWV values were 5.4 ± 1.0 for males and 5.1 ± 0.7 for females. We only found statistically significant differences between males and females PWV in the 13’ years old group (p = 0.02). 27.4% of the children (N = 78) had PWV ≥ 90th percentile, 64.1% of which were males (N = 50) and 15.3% (N = 12) were overweight/obese. PWV was significantly higher in children with systolic BP ≥ 90th percentile (p = 0.004). No differences were found in PWV between overweight/obese (BMI ≥ 85th percentile) and healthy weight children. Conclusion: Our study found a high prevalence rate of elevated PWV in children. This is a concerning aspect, taking into account the highly recognized relationship of PWV and cardiovascular outcomes, indicating that healthy policy measures need to be implemented early in life. Future research is needed to establish PWV reference percentile curves specific for Portuguese children.

Background: Arterial stiffening measured by Pulse Wave Velocity (PWV) predicts cardiovascular events and mortality in adults. It advances with age and seems accelerated in children with certain disease conditions such as chronic kidney disease or diabetes. The aim of this study was to determine factors that influence PWV in children. Methods: PWV was captured in 285 children aged 10–14 years attending a Portuguese school. The effects of sex, age, height, weight, body mass index, waist circumference, blood pressure, heart rate and sodium excretion in 24-h urinary samples in PWV were tested. Results: PWV correlated positively with age, height, systolic blood pressure, diastolic blood pressure and heart rate in males and females (p < 0.05) and with weight in males (p < 0.05). Major predictors for PWV in a multivariate regression analysis were gender, height, weight, diastolic blood pressure, heart rate and body mass index. Conclusion: Our study found several determinants of PWV in children, some of them modifiable and interfering with cardiovascular outcomes. Future research may provide clarity to the association between PWV in children and cardiovascular events in adulthood.

Fixed drug eruption (FDE) is a specific drug-induced dermatosis with a characteristic recurrence at the same sites of the skin or mucous membrane. FDE is frequently associated to non-steroid anti-inflammatory drugs exposure. This condition can mimic serious medical conditions such as Stevens-Johnson syndrome when bullae are present. We report a case of a 74-year-old woman, with a non-specified past cutaneous reaction to diclofenac, that developed generalized bullous fixed drug eruption caused by Naproxen.

Background: Marfan's Syndrome (MFS) is a disorder of connective tissue, mainly involving the cardiovascular, musculoskeletal, and ocular systems. The most severe problems include aortic root dilatation and dissection. Anesthetic management is vital for the improvement on perioperative morbidity. Case report: 61-year-old male with MFS, presenting mainly with pectus carinatum, scoliosis, ectopia lens, previous spontaneous pneumothorax and aortal aneurysm and dissection submitted to thoracoabdominal aortic prosthesis placement. Underwent routine laparoscopic cholecystectomy due to lithiasis. Important findings on preoperative examination were thoracolumbar kyphoscoliosis, metallic murmur on cardiac exam. Chest radiograph revealed Cobb angle of 70°. Echocardiogram showed evidence of aortic mechanical prosthesis with no deficits. Discussion: Preoperative evaluation should focus on cardiopulmonary abnormalities. The anesthesiologist should be prepared for a potentially difficult intubation. Proper positioning and limb support prior to induction is crucial in order to avoid joint injuries. Consider antibiotic prophylaxis for subacute bacterial endocarditis. The patient should be carefully positioned to avoid joint injuries. Intraoperatively cardiovascular monitoring is mandatory: avoid maneuvers that can lead to tachycardia or hypertension, control airway pressure to prevent pneumothorax and maintain an adequate volemia to decrease chances of prolapse, especially if considering laparoscopic surgery. No single intraoperative anesthetic agent or technique has demonstrated superiority. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia. Resumo: Justificativa: A síndrome de Marfan (SMF) é uma doença do tecido conjuntivo que envolve principalmente os sistemas: cardiovascular, músculo-esquelético e visual. Os problemas mais graves incluem dilatação da raiz da aorta e dissecção. O manejo anestésico é vital para a melhora da morbidade perioperatória. Relato de caso: Homem de 61 anos com SMF, apresentando-se principalmente com pectus carinatum, escoliose, ectopia da lente, pneumotórax e espontâneo anterior e aneurisma da aorta e dissecção, submetido à colocação de prótese aórtica toracoabdominal. O paciente foi submetido à colecistectomia videolaparoscópica de rotina devido à litíase. Os achados importantes ao exame pré-operatório foram cifoescoliose tóracolombar e murmúrio metálico em exame cardíaco. A radiografia de tórax revelou ângulo de Cobb de 70° e o ecocardiograma mostrou evidência de prótese mecânica aórtica sem alterações. Discussão: A avaliação pré-operatória deve ter como foco as anormalidades cardiopulmonares. O anestesiologista deve estar preparado para uma intubação potencialmente difícil. O posicionamento adequado e apoio para o membro antes da indução são fundamentais para evitar lesões nas articulações. Profilaxia antibiótica deve ser considerada para endocardite bacteriana subaguda. O paciente deve ser cuidadosamente posicionado para evitar lesões das articulações. O monitoramento cardiovascular é obrigatório no período intraoperatório: evitar manobras que podem levar à taquicardia ou hipertensão; controlar a pressão das vias aéreas para evitar pneumotórax e manter uma volemia adequada para diminuir as chances de prolapso, especialmente em caso de laparoscopia. Nenhum agente anestésico ou técnica demonstrou superioridade no período intraoperatório. O tratamento adequado da dor no pós-operatório é de vital importância para evitar os efeitos deletérios da hipertensão e taquicardia. Keywords: Marfan Syndrome, General anesthesia, Perioperative care, Palavras-chave: Síndrome de Marfan, Anestesia geral, Cuidados pré-operatórios

The assessment of solar potential in the urban environment is an important instrument for policy decision regarding renewable energy deployment in the city. This paper presents an experimentally validated 3D solar potential model for rooftops and facades from LIDAR data considering anisotropic diffuse irradiation. The data visualization is rendered in the ArcGIS platform using CityEngine to automatically generate 3D models from 2D geometries. The model is validated against summer and winter measurements of photovoltaic performance on a facade. A case study for two densely packed urban areas in Lisbon, Portugal, are presented. Facades are shown to increase the solar potential by 10 to 15%.

The acceleration of the process of understanding the pharmacological application of new marine bioactive compounds requires identifying the compound protein targets leading the molecular mechanisms in a living cell. The thermal proteome profiling (TPP) methodology does not fulfill the requirements for its application to any bioactive compound lacking chemical and functional characterization. Here, we present a modified method that we called bTPP for bioactive thermal proteome profiling that guarantees target specificity from a soluble subproteome. We showed that the precipitation of the microsomal fraction before the thermal shift assay is crucial to accurately calculate the melting points of the protein targets. As a probe of concept, the protein targets of 132-hydroxy-pheophytin, a compound previously isolated from a marine cyanobacteria for its lipid reducing activity, were analyzed on the hepatic cell line HepG2. Our improved method identified 9 protein targets out of 2500 proteins, including 3 targets (isocitrate dehydrogenase, aldehyde dehydrogenase, phosphoserine aminotransferase) that could be related to obesity and diabetes, as they are involved in the regulation of insulin sensitivity and energy metabolism. This study demonstrated that the bTPP method can accelerate the field of biodiscovery, revealing protein targets involved in mechanisms of action (MOA) connected with future applications of bioactive compounds.

Marine organisms, particularly cyanobacteria, are important resources for the production of bioactive secondary metabolites for the treatment of human diseases. In this study, a bioassay-guided approach was used to discover metabolites with lipid-reducing activity. Two chlorophyll derivatives were successfully isolated, the previously described 132-hydroxy-pheophytin a (1) and the new compound 132-hydroxy-pheofarnesin a (2). The structure elucidation of the new compound 2 was established based on one- and two-dimensional (1D and 2D) NMR spectroscopy and mass spectrometry. Compounds 1 and 2 showed significant neutral lipid-reducing activity in the zebrafish Nile red fat metabolism assay after 48 h of exposure with a half maximal effective concentration (EC50) of 8.9 ± 0.4 µM for 1 and 15.5 ± 1.3 µM for 2. Both compounds additionally reduced neutral lipid accumulation in 3T3-L1 multicellular spheroids of murine preadipocytes. Molecular profiling of mRNA expression of some target genes was evaluated for the higher potent compound 1, which indicated altered peroxisome proliferator activated receptor gamma (PPARγ) mRNA expression. Lipolysis was not affected. Different food materials (Spirulina, Chlorella, spinach, and cabbage) were evaluated for the presence of 1, and the cyanobacterium Spirulina, with GRAS (generally regarded as safe) status for human consumption, contained high amounts of 1. In summary, known and novel chlorophyll derivatives were discovered from marine cyanobacteria with relevant lipid-reducing activities, which in the future may be developed into nutraceuticals.

O compromisso visceral pelo lúpus eritematoso sistémico (LES) estende-se para além do rim e da pele. Lesões pleuropulmonares são reconhecidas e as formas de destruição alveolar difusa e hemorragia alveolar são as mais difíceis de controlar. O compromisso pulmonar na evolução clínica do LES difere nas crianças e nos adultos, tanto nos padrões morfológicos como nas apresentações clínicas, dependendo da imunoincompetência do doente e do tratamento instituído. Um rapaz de 16 anos apresentou um quadro clínico de astenia, cansaço e pequenos gânglios linfáticos cervicais bilaterais e não dolorosos, entendido como infecção pelo EBV, com serologia concordante (IgG e IgM de EBV e EBNA positivos). Os sintomas persistiram durante oito meses e progressivamente instalou-se eritema nasal e malar, discreto e descamativo e também febre persistente, dispneia e estertores basais à auscultação. Foram efectuadas biópsia de um gânglio linfático cervical e biópsia cirúrgica pulmonar. Observou-se hiperplasia folicular no gânglio linfático e ausência de células LMP1 (EBV) positivas. Na biópsia pulmonar eram evidentes fenómenos de bronquiolite e vasculite à custa de células macrofágicas identificadas pelo marcador CD68. Os macrófagos dissociavam as paredes vasculares e bronquiolares e também estavam presentes nos septos interalveolares peribroncovasculares e nos espaços alveolares, observando-se assim um padrão de panbronquiolite difusa e vasculite. Não se identificaram células LMP1 (EBV) positivas. O padrão pulmonar micronodular bilateral observado na TAC resolveu com corticoterapia. O diagnóstico de LES foi confirmado pela positividade dos anticorpos ANA, anti-dsDNA, anti-nDNA e anti-histonas. Este é o primeiro caso divulgado na literatura médica de compromisso pulmonar sob a forma de vasculite e padão de panbronquiolite difusa como primeira manifestação clínica do lúpus eritematosos sistémico.Visceral involvement in systemic lupus erythematosus (SLE) extends beyond renal and cutaneous management. Pleuro-pulmonary lesions have been recognised and diffuse alveolar damage and hemorrhage are the most difficult patterns to control. Pulmonary compromise in clinical evolution of SLE differs from children to adults, both in morphological patterns and in clinical presentation, depending on immunocompetence and the treatment prescribed. A 16-year-old boy presented asthenia, malaise and bilateral cervical painless adenopathies understood as EBV infection as serological EBV IgG, IgM and EBNA were positive. The symptoms persisted for eight months when discrete erythematous and desquamative nasal and malar rash expressed together with persistent fever, dispnoea and bibasilar crackles. Lymph node and pulmonary biopsises were performed. Lymph node presented follicular hyperplasia and LMP1 (EBV) immunostaining was negative. In lung biopsy bronchovascular lesions were consistent with vasculitis and bronchiolitis due to intense macrophage infiltration, validated with CD68 antibody and intra-alveolar macrophages were also present with septal compromise; LMP1 (EBV) positive cells were not visualized. The lung pattern seen in CAT as diffuse micronodules all over the lung parenchyme resolved after corticosteroid therapy. The diagnosis of SLE was confirmed by ANA, anti-dsDNA, anti-nDNA and anti-histones positivity. To the best of our knowledge this is the first reported case of pulmonary SLE involvement with vasculitis and diffuse panbronchiolitis - like pattern as the first clinical sign of the disease.

Resumo: O compromisso visceral pelo lúpus eritematoso sistémico (LES) estende-se para além do rim e da pele. Lesões pleuropulmonares são reconhecidas e as for-mas de destruição alveolar difusa e hemorragia alveolar são as mais difíceis de controlar. O compromisso pulmonar na evolução clínica do LES difere nas crianças e nos adultos, tanto nos padrões morfológicos como nas apresentações clínicas, dependendo da imunoincompe-tência do doente e do tratamento instituído.Um rapaz de 16 anos apresentou um quadro clínico de astenia, cansaço e pequenos gânglios linfáticos cer-vicais bilaterais e não dolorosos, entendido como in-fecção pelo EBV, com serologia concordante (IgG e IgM de EBV e EBNA positivos). Os sintomas persistiram durante oito meses e progressivamente insta-lou-se eritema nasal e malar, discreto e descamativo e também febre persistente, dispneia e estertores basais à auscultação. Foram efectuadas biópsia de um gânglio linfático cervical e biópsia cirúrgica pulmonar.Observouse hiperplasia folicular no gânglio linfático e ausência de células LMP1 (EBV) positivas. Na biópsia pulmonar eram evidentes fenómenos de bronquiolite e vasculite à custa de células macrofágicas identificadas pelo marcador CD68. Os macrófagos dissociavam as paredes vasculares e bronquiolares e também estavam presentes nos septos interalveolares peribroncovascu-lares e nos espaços alveolares, observando-se assim um padrão de panbronquiolite difusa e vasculite. Não se identificaram células LMP1 (EBV) positivas.O padrão pulmonar micronodular bilateral observado na TAC resolveu com corticoterapia. O diagnóstico de LES foi confirmado pela positividade dos anticorpos ANA, anti-dsDNA, anti-nDNA e anti-histonas.Este é o primeiro caso divulgado na literatura médica de compromisso pulmonar sob a forma de vasculite e padão de panbronquiolite difusa como primeira ma-nifestação clínica do lúpus eritematosos sistémico.Rev Port Pneumol 2007; XIII (2): 267-274 Abstract: Visceral involvement in systemic lupus erythematosus (SLE) extends beyond renal and cutaneous management. Pleuro-pulmonary lesions have been recognised and diffuse alveolar damage and hemorrhage are the most difficult patterns to control. Pulmonary compromise in clinical evolution of SLE differs from children to adults, both in morphological patterns and in clinical presentation, depending on immunocompetence and the treatment prescribed.A 16-year-old boy presented asthenia, malaise and bilateral cervical painless adenopathies understood as EBV infection as serological EBV IgG, IgM and EBNA were positive. The symptoms persisted for eight months when discrete erythematous and desquamative nasal and malar rash expressed together with persistent fever, dispnoea and bibasilar crackles. Lymph node and pulmonary biopsi-ses were performed.Lymph node presented follicular hyperplasia and LMP1 (EBV) immunostaining was negative. In lung biopsy bronchovascular lesions were consistent with vasculitis and bronchiolitis due to intense macrophage infiltration, validated with CD68 antibody and intra-alveolar macrophages were also present with septal compromise; LMP1 (EBV) positive cells were not visualized.The lung pattern seen in CAT as diffuse micronodules all over the lung parenchyme resolved after corticos-teroid therapy. The diagnosis of SLE was confirmed by ANA, anti-dsDNA, anti-nDNA and anti-histones positivity.To the best of our knowledge this is the first reported case of pulmonary SLE involvement with vasculitis and diffuse panbronchiolitis â like pattern as the first clinical sign of the disease.Rev Port Pneumol 2007; XIII (2): 267-274 Palavras-chave: LES, bronquiolite, vasculite, panbronquiolite difusa, Key-words: SLE, bronchiolitis, vasculitis, diffuse pan-bronchiolitis

A amiloidose caracteriza-se pela deposição extracelular de substância amilóide em diferentes órgãos e tecidos. O atingimento pulmonar é raro e pode acontecer de forma isolada ou associado a doença sistémica. Descrevem-se dois casos clínicos. Caso 1: Mulher de 71 anos, com antecedentes de bronquiectasias e síndrome de Sjögren, que referia anorexia, emagrecimento e tosse produtiva. O estudo incluiu uma biópsia pulmonar cirúrgica que demonstrou amiloidose localizada ao aparelho respiratório. Caso 2: Homem de 83 anos, ex-fumador, assintomático. Enviado por opacidade nodular em radiografia de tórax de rotina. A biópsia pulmonar transtorácica revelou um tumor amilóide do pulmão (amiloidoma). Estes casos ilustram uma doença rara que no Caso 1 está associada a bronquiectasias e síndrome de Sjögren. O diagnóstico diferencial mais importante é a patologia neoplásica, sendo o diagnóstico definitivo importante, já que a amiloidose pulmonar é geralmente benigna e indolente.

Introduction: In this study, we reviewed a clinical series composed by all malignant lung lesions submitted to computed tomographyguided percutaneous thermal radiofrequency ablation, in our hospital, a rather recent technique that has been gaining scientific recognition. Material and Methods: For data purposes, all radiofrequency ablation and corresponding clinical records were retrospectively analysed. A computed tomography scan was performed before and after each procedure to evaluate the tumour’s features, and at a second step to assess results and complications. The frequency of local recurrence and disease progression were determined based on imaging follow-up. Kaplan–Meier analysis was used to estimate survival. Univariate analysis recognized clinical and pathological factors affecting survival. These were also tested by multivariate analysis. Results: A total of 28 malignant lung lesions, 20 primary and 8 metastatic, from 28 patients (78.6% male; mean age 62 ± 17 years old), were submitted to computed tomography-guided radiofrequency ablation between January 2004 and July 2010. Total necrosis was achieved in 74.1% of the lesions. Immediate radiofrequency ablation-related complications were observed in half of the procedures. Among major complications, death occurred in one patient only. Median overall survival was 43.0 months for a mean 2-years follow-up. Median progression-free survival was 31.6 months. Lesion’s size smaller than 35 mm, stage III disease by the TNM classification and previous treatment attempts were significantly associated with better outcomes. Disease-related mortality was 46.4%. Discussion: This procedure proved to be efficient to treat lung cancerous lesions, with a low-rate of major complications. Conclusions: Computed tomography-guided percutaneous radiofrequency ablation is a minimally invasive procedure that appears to be valuable in the treatment of lung cancer lesions. Keywords: Catheter Ablation; Lung Neoplasms; Tomography, X-Ray Computed.

The study aimed to compare the shaping effects, preservation of the original curvature, and transportation of the apical foramen of Reciproc (VDW, Munich, Germany), UnicOne (Medin, Nové Město na Moravě, Czech Republic), and Protaper Universal (Dentsply Maillefer, Ballaigues, Switzerland) in simulated root canals. Thirty resin blocks with simulated curved root canals were distributed into three groups (n=10), and prepared using Reciproc (RCp), UnicOne (UnO) and the Protaper Universal (PTu). Standardized photographs were taken before and after the instrumentation, after which they were superimposed. Measurements were taken of the quantity of resin removed from the inner and outer walls of the curvature at 6 levels, the curvature angles before and after instrumentation, and the transportation of the apical foramen. RCp obtained the highest values for amount of resin removed from the inner wall while UnO demonstrated similar shaping on both the inner and outer walls. PTu produced the greatest transportation of foramen when compared to the reciprocating instruments. There was no significant difference between the groups in terms of the change in angle (P>0.05). All the instruments were capable of maintaining the original curvature of the root canal; however, the UnO, which used reciprocating movement, produced more conservative shapes with lower foramen transportation.

A new ergosterol analog, talarosterone (1) and a new bis-anthraquinone derivative (3) were isolated, together with ten known compounds including palmitic acid, ergosta-4,6,8(14),22-tetraen-3-one, ergosterol-5,8-endoperoxide, cyathisterone (2), emodin (4a), questinol (4b), citreorosein (4c), fallacinol (4d), rheoemodin (4e) and secalonic acid A (5), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Talaromyces stipitatus KUFA 0207. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis, and in the case of talarosterone (1), the absolute configurations of its stereogenic carbons were determined by X-ray crystallographic analysis. The structure and stereochemistry of cyathisterone (2) was also confirmed by X-ray analysis. The anthraquinones 4a–e and secalonic acid A (5) were tested for their anti-obesity activity using the zebrafish Nile red assay. Only citreorosein (4c) and questinol (4b) exhibited significant anti-obesity activity, while emodin (4a) and secalonic acid A (5) caused toxicity (death) for all exposed zebrafish larvae after 24 h.

Very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (MIM 201475) is a rare inherited disorder with three forms of clinical presentation: a severe early-onset form; an intermediate form with childhood onset; and an adult-onset form, of mild severity. During adolescence and adulthood, exercise intolerance, myalgia and recurrent episodes of rhabdomyolysis are the main clinical features. The authors present a case of a 13-year old female, with severe myalgia and dark urine after prolonged exercise. Analytical evaluation showed marked elevation plasma creatine kinase and myoglobin. The increased levels of tetradecenoyl carnitine in patient’s dried blood spot suggested a VLCAD deficiency, which was confirmed by molecular study. Family history is remarkable for first grade consanguinity of parents and a 19-year old brother with records of repeated similar episodes after moderate intensity physical efforts which was subsequently also diagnosed with VLCAD deficiency. This is one of the first cases of late-onset of disease diagnosed in Portugal.

Background: Hierridin B was isolated from a marine cyanobacterium Cyanobium sp. strain and induced cytotoxicity selectively in HT-29 adenocarcinoma cells. The underlying molecular mechanism was not yet elucidated. Methods: HT-29 cells were exposed to the IC50 concentration of hierridin B (100.2 μM) for 48 h. Non-targeted proteomics was performed using 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The mRNA expression of apoptotic and cell cycle genes were analyzed by real-time PCR. Automated quantification of 160 cytoplasm and mitochondrial parameter was done by fluorescence microscopy using CellProfiler software. Results: Proteomics identified 21 significant different proteins, which belonged to protein folding/synthesis and cell structure amongst others. Increase of VDAC1 protein responsible for formation of mitochondrial channels was confirmed by mRNA expression. A 10-fold decrease of cytoskeleton proteins (STMN1, TBCA) provided a link to alterations of the cell cycle. CCNB1 and CCNE mRNA were decreased two-fold, and P21CIP increased 10-fold, indicative of cell cycle arrest. Morphological analysis of mitochondrial parameter confirmed a reduced mitochondrial activity. Conclusion: Hierridin B is a potential anticancer compound that targets mitochondrial activity and function.

Abstract Background: Marfan's Syndrome (MFS) is a disorder of connective tissue, mainly involving the cardiovascular, musculoskeletal, and ocular systems. The most severe problems include aortic root dilatation and dissection. Anesthetic management is vital for the improvement on perioperative morbidity. Case report: 61-year-old male with MFS, presenting mainly with pectus carinatum, scoliosis, ectopia lens, previous spontaneous pneumothorax and aortal aneurysm and dissection submitted to thoracoabdominal aortic prosthesis placement. Underwent routine laparoscopic cholecystectomy due to lithiasis. Important findings on preoperative examination were thoracolumbar kyphoscoliosis, metallic murmur on cardiac exam. Chest radiograph revealed Cobb angle of 70°. Echocardiogram showed evidence of aortic mechanical prosthesis with no deficits. Discussion: Preoperative evaluation should focus on cardiopulmonary abnormalities. The anesthesiologist should be prepared for a potentially difficult intubation. Proper positioning and limb support prior to induction is crucial in order to avoid joint injuries. Consider antibiotic prophylaxis for subacute bacterial endocarditis. The patient should be carefully positioned to avoid joint injuries. Intraoperatively cardiovascular monitoring is mandatory: avoid maneuvers that can lead to tachycardia or hypertension, control airway pressure to prevent pneumothorax and maintain an adequate volemia to decrease chances of prolapse, especially if considering laparoscopic surgery. No single intraoperative anesthetic agent or technique has demonstrated superiority. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia.