Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy

Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)–poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC–PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy

In silico single strand melting curve: a new approach to identify nucleic acid polymorphisms in Totiviridae

CpG-island promoters of developmental genes are unmethylated. DNA methylation state of CpG islands overlapping and surrounding the promoter region of Pax3 (a) and Pax7 (b) genes in myogenic (MB, MT, MF) and non-myogenic samples (ESC). CpG islands are indicated in green and regions analysed by sodium bisulphite sequencing are shown in red. Each circle represents a CpG dinucleotide and its distance to the gene TSS is indicated below. The colour gradient represents the percentage of methylation indicated in the legend. Abbreviations: ESC, embryonic stem cell; MB, myoblast; MT, myotube; MF, myofiber; TSS, transcription start site. c. DNA methylation state of -5 kb distal regulatory region for MyoD was analysed by sodium bisulphite sequencing in ESC and myoblast samples, and represented as above. (PDF 171 kb

The use of neural network technology to model swimming performance

to identify the factors which are able to explain the performance in the 200 meters individual medley and 400 meters front crawl events in young swimmers, to model the performance in those events using non-linear mathematic methods through artificial neural networks (multi-layer perceptrons) and to assess the neural network models precision to predict the performance. A sample of 138 young swimmers (65 males and 73 females) of national level was submitted to a test battery comprising four different domains: kinanthropometric evaluation, dry land functional evaluation (strength and flexibility), swimming functional evaluation (hydrodynamics, hydrostatic and bioenergetics characteristics) and swimming technique evaluation. To establish a profile of the young swimmer non-linear combinations between preponderant variables for each gender and swim performance in the 200 meters medley and 400 meters font crawl events were developed. For this purpose a feed forward neural network was used (Multilayer Perceptron) with three neurons in a single hidden layer. The prognosis precision of the model (error lower than 0.8% between true and estimated performances) is supported by recent evidence. Therefore, we consider that the neural network tool can be a good approach in the resolution of complex problems such as performance modeling and the talent identification in swimming and, possibly, in a wide variety of sports. Key pointsThe non-linear analysis resulting from the use of feed forward neural network allowed us the development of four performance models.The mean difference between the true and estimated results performed by each one of the four neural network models constructed was low.The neural network tool can be a good approach in the resolution of the performance modeling as an alternative to the standard statistical models that presume well-defined distributions and independence among all inputs.The use of neural networks for sports sciences application allowed us to create very realistic models for swimming performance prediction based on previous selected criterions that were related with the dependent variable (performance).info:eu-repo/semantics/publishedVersio

Survival Analysis of COPD Patients in a 13-Year Nationwide Cohort Study of the Brazilian National Health System

Background: Chronic obstructive pulmonary disease (COPD) has an appreciable socioeconomical impact in low- and middle-income countries, but most epidemiological data originate from high-income countries. For this reason, it is especially important to understand survival and factors associated with survival in COPD patients in these countries. Objective: To assess survival of COPD patients in Brazil, to identify risk factors associated with overall survival, including treatment options funded by the Brazilian National Health System (SUS). Methodology: We built a retrospective cohort study of patients dispensed COPD treatment in SUS, from 2003 to 2015 using a National Database created from the record linkage of administrative databases. We further matched patients 1:1 based on sex, age and year of entry to assess the effect of the medicines on patient survival. We used the Kaplan-Meier method to estimate overall survival of patients, and Cox's model of proportional risks to assess risk factors. Result: Thirty seven thousand and nine hundred and thirty eight patients were included. Patient's survival rates at 1 and 10 years were 97.6% (CI 95% 97.4–97.8) and 83.1% (CI 95% 81.9–84.3), respectively. The multivariate analysis showed that male patients, over 65 years old and underweight had an increased risk of death. Therapeutic regimens containing a bronchodilator in a free dose along with a fixed-dose combination of corticosteroid and bronchodilator seem to be a protective factor when compared to other regimens. Conclusion: Our findings contribute to the knowledge of COPD patients' profile, survival rate and related risk factors, providing new evidence that supports the debate about pharmacological therapy and healthcare of these patients

Um insucesso de desfibrilhação por CDI resolvido de uma forma pouco habitual

Um Cardioversor Desfibrilhador Implantável (CDI) destina-se a detectar arritmias ventriculares potencialmente fatais e a terminá-las, quer por estimulação ventricular rápida quer através de uma descarga eléctrica. Actualmente, é uma terapia aceite na prevenção primária e secundária da morte súbita cardíaca. A configuração típica de um CDI é de um eléctrodo de sensing e de desfibrilhação no ventrículo direito (VD) com dois coils (um distal, no ventrículo e outro próximal, na junção da veia cava superior (VCS) com a aurícula direita) que juntamente com o gerador, forma a designada “tríade ventricular”. Esta configuração embora seja eficaz na maior parte dos doentes, não é a mais racional do ponto de vista eléctrico pois o vector de choque encontra-se deslocado anteriormente em relação à maior parte do ventrículo esquerdo (VE). Descreve-se um caso de incapacidade de desfibrilhação pelo CDI resolvido com a implantação de um eléctrodo adicional numa veia tributária do seio coronário

Targeting Macrophages and Synoviocytes Intracellular Milieu to Augment Anti-Inflammatory Drug Potency

Using a preclinical in vivo model of arthritis and the gold standard disease-modifying anti-rheumatic drug, methotrexate, pH-responsive phosphorylcholine polymersomes, elicit both anti-inflammatory and anti-arthritic therapeutic efficacy, while drastically minimizing off-target toxicity. First, the selective accumulation of polymersomes within synovium of inflamed joints. Second, the polymersomes targeting ability toward activated macrophages and synoviocytes, via scavenger receptors, allow their uptake via endocytosis. And third, the polymersomes pH-responsiveness enables the drug escape from early endosomes and hence its intracellular milieu delivery. On-site augment of methotrexate loaded polymersomes enable the complete abrogation of synovial inflammation and prevent the disease progression and severity. Overall, in vitro and in vivo investigations reveal the potential of polymersomes as a promising nanotherapy for treating arthritic inflammation

Hygrothermal durability of bond in FRP-strengthened masonry

Fiber reinforced polymers (FRPs) are accepted as an efficient material for external strengthening of masonry structures. Previous researches have shown that the bond between FRP and the substrate plays an important role in the effectiveness of this strengthening technique. Extensive investigations have been devoted to the characterization of the short-term bond behavior, while its durability and long-term performance requires further studies. In this regard, a full experimental program for investigating the environmental durability of bond in FRP-strengthened masonry is crucial for understanding the degrading mechanisms. This paper presents the results of an experimental program aimed at investigating the hygrothermal durability of bond in FRP-strengthened bricks. Accelerated ageing tests were performed on the FRP-strengthened brick elements and the bond degradation was periodically investigated by visual inspection and by conventional single-lap shear bond tests. The changes in the properties of material constituents have also been monitored. The obtained results are presented and critically discussed.This work was developed within the framework of the RILEM Technical Committee "223-MSC: Masonry Strengthening with Composite Materials". The financial support from the project FP7-ENV-2009-1-244123-NIKER of the 7th Framework Program of the European Commission is gratefully acknowledged. The first author also acknowledges the financial support of the Portuguese Science Foundation (Fundacao de Ciencia e Tecnologia, FCT), through grant SFRH/BD/80697/2011

Microfluidic systems for the analysis of the viscoelastic fluid flow phenomena in porous media

In this study, two microfluidic devices are proposed as simplified 1-D microfluidic analogues of a porous medium. The objectives are twofold: firstly to assess the usefulness of the microchannels to mimic the porous medium in a controlled and simplified manner, and secondly to obtain a better insight about the flow characteristics of viscoelastic fluids flowing through a packed bed. For these purposes, flow visualizations and pressure drop measurements are conducted with Newtonian and viscoelastic fluids. The 1-D microfluidic analogues of porous medium consisted of microchannels with a sequence of contractions/ expansions disposed in symmetric and asymmetric arrangements. The real porous medium is in reality, a complex combination of the two arrangements of particles simulated with the microchannels, which can be considered as limiting ideal configurations. The results show that both configurations are able to mimic well the pressure drop variation with flow rate for Newtonian fluids. However, due to the intrinsic differences in the deformation rate profiles associated with each microgeometry, the symmetric configuration is more suitable for studying the flow of viscoelastic fluids at low De values, while the asymmetric configuration provides better results at high De values. In this way, both microgeometries seem to be complementary and could be interesting tools to obtain a better insight about the flow of viscoelastic fluids through a porous medium. Such model systems could be very interesting to use in polymer-flood processes for enhanced oil recovery, for instance, as a tool for selecting the most suitable viscoelastic fluid to be used in a specific formation. The selection of the fluid properties of a detergent for cleaning oil contaminated soil, sand, and in general, any porous material, is another possible application