Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

This deposit is composed by the main article, and it hasn't any supplementary materials associated.The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.Fundação para a Ciência e a Tecnologia grants: (SFRH/BPD/92860/2013, PTDC/BIM-MEC/4665/2014); European Research Council grants: (ERC-2014-CoG 647888-iPROTECTION).info:eu-repo/semantics/publishedVersio

Thermal performance of a PCM firefighting suit considering transient periods of fire exposure, post - fire exposure and resting phases

Firefighting scenarios may be characterized by various transient periods (i.e. phases), which consist of diverse environmental conditions. Firefighters usually encounter fire exposure, post fire exposure and resting phases. Development of new and improved protective clothing must be able to provide protection throughout all these phases, as burnouts may still occur after fire exposure due to accumulation of heat in the garment. The incorporation of phase change materials (PCMs) in firefighting garments has been shown to minimize the potential of heat hazards only during fire exposure. Thus to get more knowledge on their thermal performance, in the present study, the effect of PCM incorporation in post fire and resting phases were also numerically studied. The numerical code was validated for all phases. Five potential PCM candidates were considered. Exposure phases were characterized by high- medium and low- heat flux intensities (84, 12 and 5 kW.m(-2)) with variable exposure times whilst post -exposure and resting phases where characterized by different wind speeds (i.e. ambient convective coefficients). Optimal PCM masses, times to second and third - degree burns as well as PCM suit cooling times were calculated to reflect thermal protective performance in each respective phase. The data generated allows for PCM short-listing from a set of potential PCM candidates along with its geometrical parameters, considering a wide range of characteristics of the various phases that consist a typical firefighting scenario

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness

BioRePortAP, an electronic clinical record coupled with a database : an example of its use in a single

Aims: To evaluate the efficacy and safety of the treatment of psoriatic arthritis (PsA) patients with tumor necrosis factor (TNF) antagonists in the Rheumatology Department of Hospital de Santa Maria using the BioRePortAP. Methods: The Portuguese Society of Rheumatology (SPR) developed an electronic medical chart coupled with a database for the follow up of PsA patients, the BioRePortAP, which was launched in May 2009. This evaluation was based on all the PsA patients that were on active treatment with TNF antagonists in September 2009 and were registered in the BioRePortAP. All the previous data on these patients were introduced in BioRePortAP using the prospective paper based follow up protocol that this Department was using since 1999. Only patients with more than 9 months of treatment were analyzed. Results: Forty-two patients with PsA, actively treated with anti-TNF agents in September 2009, for at least 9 months, were analyzed in BioRePortAP. Twenty-three patients were male (55%) and nineteen were female (45%). The average age of these patients was 49.8±10.9 years old, the average disease duration was of 10.7±5.6 years and the mean duration of biological therapy was of 37.8±27.8 months. For the 81% of patients with peripheral joint disease there was a mean reduction of more than 80% in the swollen and tender joint counts, and almost 50% in the health assessment questionnaire (HAQ) value. In the 19% of the patients with axial involvement the reduction of BASDAI and BASFI was not statistically significative. On top of that, PASI score suffered a reduction of 64%. Fourteen patients (33.3%) had to switch their TNF antagonist treatment. 58.8% of the switches were due to adverse effects and 41.2% due to therapy failure. Regarding the 56 adverse reactions registered, only one was a severe reaction. The remaining adverse reactions were not severe and 67% of them were due to infections. Discussion: The results of this first report of the use of the BioRePortAP in clinical practice confirm the efficacy and safety of TNF antagonist treatment in PsA. The results shown here elucidate the potential applications of BioRePortAP as a tool for efficacy and safety assessment of PsA patients treated with biotechnological drugs

The impact of water on firefighter protective clothing thermal performance and steam burn occurrence in firefighters

Exposure to oscillating heat fluxes while having variable water contents in the thermal protective clothing (T.P. C) is possible in a real firefighting scenario. The occurrence of steam burns becomes inevitable in certain conditions which are still unidentified in the literature. In light of such, in this study, the effect of water distribution on thermal protective clothing (T.P.C) performance is studied for various environmental conditions (i.e., fixed and transient values of heat flux). A numerical approach is used to simulate heat and mass transport in the T.P.C.. Parametric studies are performed, where the exposure heat flux (0-80 kW/m(2)) and initial quantities of water in the T.P.C. are varied and correlated with second-degree burn times. The presence of water in the outer shell increases second-degree burn times, while water in the inner layer has the opposite effect for high heat fluxes. For the tested heat fluxes, burns obtained are majorly of a scald nature. The results generated allow for identifying environmental and protective clothing conditions where steam burns may become a potential hazard. This study can directly impact the proceedings for firefighters to take in certain environmental conditions and aid in the design of more effective firefighting protective suits

Thoracic wall reconstruction using ultrasound images to model/bend the thoracic prosthesis for correction of pectus excavatum

Pectus excavatum is the most common congenital deformity of the anterior thoracic wall. The surgical correction of such deformity, using Nuss procedure, consists in the placement of a personalized convex prosthesis into sub-sternal position to correct the deformity. The aim of this work is the CT-scan substitution by ultrasound imaging for the pre-operative diagnosis and pre-modeling of the prosthesis, in order to avoid patient radiation exposure. To accomplish this, ultrasound images are acquired along an axial plane, followed by a rigid registration method to obtain the spatial transformation between subsequent images. These images are overlapped to reconstruct an axial plane equivalent to a CT-slice. A phantom was used to conduct preliminary experiments and the achieved results were compared with the corresponding CT-data, showing that the proposed methodology can be capable to create a valid approximation of the anterior thoracic wall, which can be used to model/bend the prosthesis.Fundação para a Ciencia e Tecnologia (FCT

CAMILA: formal software engineering supported by functional programming

This paper describes two experiences in teaching a formal approach to software engineering at undergraduate level supported by Camila a functional programming based tool Carried on in diferent institutions each of them addresses a particular topic in the area requirement analysis and generic systems design in the first case specification and implementation development in the second Camila the common framework to both experiences animates a set based language extended with a mild use of category theory which can be reasoned upon for program calculation and classification purpose. The project afiliates itself to but is not restricted to the research in exploring Functional Programming as a rapid prototyping environment for formal software model. Its kernel is fully connectable to external applications and equipped with a component repository and distribution facilities. The paper explains how Camila is being used in the educational practice as a tool to think with providing a kind of cross fertilization between students under standing of diferent parts of the curriculum. Furthermore it helps in developinga number of engineering skills namely the ability to analyze and classify information problems and models and to resort to the combined use of diferent programming frameworks in approaching them

Validation of percutaneous puncture trajectory during renal access using 4D ultrasound reconstruction

"Progress in Biomedical Optics and Imaging, vol. 16, nr. 43"Background: An accurate percutaneous puncture is essential for disintegration and removal of renal stones. Although this procedure has proven to be safe, some organs surrounding the renal target might be accidentally perforated. This work describes a new intraoperative framework where tracked surgical tools are superimposed within 4D ultrasound imaging for security assessment of the percutaneous puncture trajectory (PPT). Methods: A PPT is first generated from the skin puncture site towards an anatomical target, using the information retrieved by electromagnetic motion tracking sensors coupled to surgical tools. Then, 2D ultrasound images acquired with a tracked probe are used to reconstruct a 4D ultrasound around the PPT under GPU processing. Volume hole-filling was performed in different processing time intervals by a tri-linear interpolation method. At spaced time intervals, the volume of the anatomical structures was segmented to ascertain if any vital structure is in between PPT and might compromise the surgical success. To enhance the volume visualization of the reconstructed structures, different render transfer functions were used. Results: Real-time US volume reconstruction and rendering with more than 25 frames/s was only possible when rendering only three orthogonal slice views. When using the whole reconstructed volume one achieved 8-15 frames/s. 3 frames/s were reached when one introduce the segmentation and detection if some structure intersected the PPT. Conclusions: The proposed framework creates a virtual and intuitive platform that can be used to identify and validate a PPT to safely and accurately perform the puncture in percutaneous nephrolithotomy.The authors acknowledge to Foundation for Science and Technology (FCT) - Portugal for the fellowships with references: SFRH/BD/74276/2010.info:eu-repo/semantics/publishedVersio

A new machine for acquire pavement texture

This paper presents a prototype machine for the acquisition and characterization of the macrotexture and megatexture of road surfaces. The development stages of the prototype machine involved: 3D data acquisition system configuration and calibration - based on laser triangulation technique, 3D surface reconstruction of the road surface and texture characterization using appropriated indicators, such as the Mean Profile Depth (MPD) and the Texture Profile Level (L), by applying different and complementary mathematical techniques. The prototype machine created is able to work in laboratory and in field, allowing an acquisition accuracy of 0.5 mm. The contribution of this research is in developing a prototype machine capable of acquiring an extensive area road surface with high precision 3D data.(undefined