Inflammation and oxidative stress as common mechanisms of pulmonary, autonomic, and musculoskeletal dysfunction after spinal cord injury

One of the etiopathogenic factors frequently associated with generalized organ damage after spinal cord injury corresponds to the imbalance of the redox state and inflammation, particularly of the respiratory, autonomic, and musculoskeletal systems. Our goal in this review was to gain a better understanding of this phenomenon by reviewing both animal and human studies. At the respiratory level, the presence of tissue damage is notable in situations that require increased ventilation due to lower thoracic distensibility and alveolar inflammation caused by higher levels of leptin as a result of increased fatty tissue. Increased airway reactivity, due to loss of sympathetic innervation, and levels of nitric oxide in exhaled air that are similar to those seen in asthmatic patients have also been reported. In addition, the loss of autonomic control efficiency leads to an uncontrolled release of catecholamines and glucocorticoids that induce immunosuppression, as well as a predisposition to autoimmune reactions. Simultaneously, blood pressure regulation is altered with vascular damage and atherogenesis associated with oxidative damage. At the muscular level, chronically elevated levels of prooxidants and lipoperoxidation associated with myofibrillar atrophy are described, with no reduction or reversibility of this process through antioxidant supplementatio

The diagnosis of hereditary angioedema: family caregivers’ experiences

The aim of this study was to understand the experiences of family caregivers in the process of diagnosing hereditary angioedema. An interpretive and qualitative research methodology based on Gadamer’s philosophical hermeneutics was carried out. Data collection took place between May 2015 and August 2016 and included a focus group and in-depth interviews with 16 family caregivers. Two themes define the experiences of family caregivers: “Family life focuses on identifying the problem” and “Discovering and coping with a complex diagnosis.” The process of diagnosis generates fear, anxiety, uncertainty, and incomprehension. Family caregivers are the main support for patients diagnosed with hereditary angioedema. As they share in the patients’ suffering, they need a diagnosis to be established to be able to cope with the disease and offer support. Family health nurses can contribute to improving the coping process in this phase of the disease

Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis

Toll-like receptors (TLRs) are important components of innate immunity. We investigated the association between polymorphisms in the TLR2, TLR4, and TLR9 genes and susceptibility to noninvasive forms of pulmonary aspergillosis. A significant association was observed between allele G on Asp299Gly (TLR4) and chronic cavitary pulmonary aspergillosis (odds ratio [OR], 3.46; P =.003). Susceptibility to allergic bronchopulmonary aspergillosis was associated with allele C on T-1237C (TLR9) (OR, 2.49; P =. 043). No particular polymorphism was associated with severe asthma with fungal sensitization. These findings reinforce the importance of innate immunity in the pathogenesis of different forms of aspergillosis.Fundação para a Ciência e Tecnologia, Portugal (POCI/SAU-ESP/61080/ 2004 and fellowship to A.C., contract SFRH/BD/11837/2003); CAPES (Brazilian government) (grant to A.P); and the Fungal Research Trust, United Kingdom

An Interactive Biobjective Method for Solving a Waste Collection Problem

The aim of this paper is to propose a framework in order to solve the real-world waste collection problem in a city of southern Spain modeled as an Asymmetric Vehicle Routing Problem (AVRP) with side constraints and several variations. In this problem, not only are vehicle capacity and temporal constraints considered but multiple trips are also allowed. Furthermore, two objectives will be considered: the minimization of the total distance and the balance of the working day. Finally, in order to select a single solution among all efficient (or nondominated) solutions, an interactive method is designed using reference points

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression

<p>Abstract</p> <p>Background</p> <p>Previous results showed that over-expression of the <it>WTH3 </it>gene in MDR cells reduced <it>MDR1 </it>gene expression and converted their resistance to sensitivity to various anticancer drugs. In addition, the <it>WTH3 </it>gene promoter was hypermethylated in the MCF7/AdrR cell line and primary drug resistant breast cancer epithelial cells. <it>WTH3 </it>was also found to be directly targeted and up regulated by the <it>p53 </it>gene. Furthermore, over expression of the <it>WTH3 </it>gene promoted the apoptotic phenotype in various host cells.</p> <p>Methods</p> <p>To further confirm <it>WTH3</it>'s drug resistant related characteristics, we recently employed the small hairpin RNA (shRNA) strategy to knockdown its expression in HEK293 cells. In addition, since the <it>WTH3 </it>promoter's p53-binding site was located in a CpG island that was targeted by methylation, we were interested in testing the possible effect this epigenetic modification had on the <it>p53 </it>transcription factor relative to <it>WTH3 </it>expression. To do so, the <it>in vitro </it>methylation method was utilized to examine the <it>p53 </it>transgene's influence on either the methylated or non-methylated <it>WTH3 </it>promoter.</p> <p>Results</p> <p>The results generated from the gene knockdown strategy showed that reduction of <it>WTH3 </it>expression increased <it>MDR1 </it>expression and elevated resistance to Doxorubicin as compared to the original control cells. Data produced from the methylation studies demonstrated that DNA methylation adversely affected the positive impact of <it>p53 </it>on <it>WTH3 </it>promoter activity.</p> <p>Conclusion</p> <p>Taken together, our studies provided further evidence that <it>WTH3 </it>played an important role in MDR development and revealed one of its transcription regulatory mechanisms, DNA methylation, which antagonized <it>p53</it>'s positive impact on <it>WTH3 </it>expression.</p

Enriquecimiento de la hamburguesa Cinta Senese con ácidos grasos omega-3. Efecto del tipo de adición y condición de almacenamiento en las características de calidad

The most beneficial omega-3 PUFAs to human health, EPA and DHA fatty acids, are typically present in fish products, but extraneous to meat. Therefore, Cinta Senese pork burgers were added with microencapsulated (M) and bulk fish oil (F) and subjected to three storage conditions: no storage (T0), chilled (T5) and frozen storage (T30). The physico-chemical and sensory attributes of raw and cooked burgers were investigated. After storage and cooking, EPA and DHA were better preserved in M burgers than in F samples, which showed the highest TBAR values at T0 and T5, while M samples presented scores similar to the control. Panelists observed differences mainly in greasy appearance, odor intensity and cooked meat odor and flavor. The M group showed the best scores at T5 with respect to the control and F burgers. So, fish oil microencapsulation was an effective method to prevent EPA and DHA oxidation while respecting burger quality characteristics.EPA y DHA son los ácidos grasos poliinsaturados omega 3 más beneficiosos para la salud humana, se presentan típicamente en el pescado, y no se encuentran en carnes. Por ello, se elaboraron hamburguesas de cerdo de la especie “Cinta Senese” añadiendo aceite de pescado (F), microcápsulas que contenían aceite de pescado (M) o sólo a base de carne (control (C)) y se mantuvieron bajo las siguientes condiciones de almacenamiento: sin almacenaje (T0), en refrigeración (T5) y congelación (T30). Se estudiaron los atributos sensoriales y físico-químicos de las hamburguesas crudas y cocinadas. En cuanto al almacenamiento y el cocinado, las hamburguesas con microcápsulas preservaron mejor los EPA y DHA que las muestras con aceite de pescado, las cuales presentaron los valores más altos de TBARs en las muestras T0 y T5, mientras que las M mantuvieron unos resultados similares a las de tipo control. En los resultados de la cata realizada se observaron, entre los tratamientos realizados y respecto a las distintas condiciones de almacenamiento, diferencias en la apariencia grasienta, olor y flavor a carne cocida e intensidad de olor. En las hamburguesas M se obtuvieron las mejores puntuaciones frente a las encontradas en F y C en el tipo T5. Por tanto, la microencapsulación de aceite de pescado se verificó como un método efectivo para prevenir la oxidación de EPA y DHA respetando la calidad y características de las hamburguesas

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS