The effects of exhaustive swimming and probiotic administration in trained rats: Oxidative balance of selected organs, colon morphology, and contractility

The duration and intensity of exercise are significant factors in oxidative, morphological, and functional changes of the gastrointestinal tract. This study aimed to investigate the effects of both exhaustive swimming and probiotic VSL#3 on rats that had been previously trained with moderate swimming. The rats were divided into four groups labeled: control (C), probiotic (P), exercise (E), and probiotic–exercise (PE). Groups P and PE were fed with probiotic mixture VSL#3. Groups E and PE had a 5-week moderate swimming program (1 h/day for 5 days/week), followed by a 1-week exhaustive swimming program (trained like in moderate program but 3 times with 150 min resting sessions, for 5 days/week). At the end of the program, the rats were euthanized. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels were measured in tissue samples from the gastrocnemius muscle, heart, liver, kidney, and colon. In vitro contractile activity and histomorphology of the colon were also determined. Exercise and/or probiotic decreased the oxidative stress and also increased the level of one or more of the antioxidant enzymes in some of the organs. Probiotics had more pronounced effects on colon morphology than exercise but unexpectedly this effect was non-trophic. In the colon, the thickness of the tunica muscularis and the number of goblet cells were not affected; however, probiotic administration decreased the crypt depth and tunica mucosa thickness. Exercise increased the Emax value of acetylcholine (ACh), while decreased its sensitivity. These findings suggest that exhaustive swimming does not cause oxidative stress and that probiotic consumption improves oxidative balance in trained rats. The probiotic intake does not alter the effect of exercise on the contractile activity of the colon. Colon mucosal changes induced by probiotics are independent of exercise

The effects of swimming exercise and probiotic vsl#3 on zonulin and some inflammatory and oxidative parameters in rats

Moderate exercise stimulates immune system whereas intensive exercise may display immune-suppressive effect associated with the disruption of intestinal barrier. With this study, we tested the effects of moderate and intensive swimming exercises on some cytokines and oxidant variables and zonulin, an intestinal barrier marker, in rats. We also tested possible ameliorative effects of probiotic VSL#3 in both moderate and intensive exercise regimens. Twenty eight rats were randomly divided into 4 equal groups: Control-C, Probiotic-P, Exercise-E, Probiotic+Exercise-PE. The rats in group E and PE underwent moderate swimming exercise for 5 weeks. Following this period, intensive swimming exercise was performed for 5 days. The rats in group C and group P were sedentary. Probiotic VSL#3 was given to group P and PE in the water. At the end of the experiments, serum zonulin, TNF-α, IL-6, IL-10, TGF-β, MDA, and protein carbonyl levels were determined. Evidences obtained from present study indicate that moderate swimming exercise improves barrier integrity of intestine and decreases oxidative stress. During the moderate swimming experiment, probiotic VSL#3 supplementation may also improve inflammatory response. On the other hand, intensive exercise does not led changes in the inflammatory response and oxidative stress, but beneficial responses of moderate exercise on the selected parameters probably disappear due to the intense exercise-induced mild stress

Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered

Decrease in thyroid adenoma associated (THADA) expression is a marker of dedifferentiation of thyroid tissue

<p>Abstract</p> <p>Background</p> <p><it>Thyroid adenoma associated (THADA) </it>has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive. The aim of this study was to quantify <it>THADA </it>gene expression in normal tissues and in thyroid hyper- and neoplasias, using real-time PCR.</p> <p>Methods</p> <p>For the analysis <it>THADA </it>and 18S rRNA gene expression assays were performed on 34 normal tissue samples, including thyroid, salivary gland, heart, endometrium, myometrium, lung, blood, and adipose tissue as well as on 85 thyroid hyper- and neoplasias, including three adenomas with a 2p21 translocation. In addition, <it>NIS </it>(<it>sodium-iodide symporter</it>) gene expression was measured on 34 of the pathological thyroid samples.</p> <p>Results</p> <p>Results illustrated that <it>THADA </it>expression in normal thyroid tissue was significantly higher (<it>p </it>< 0.0001, exact Wilcoxon test) than in the other tissues. Significant differences were also found between non-malignant pathological thyroid samples (goiters and adenomas) and malignant tumors (<it>p </it>< 0.001, Wilcoxon test, t approximation), anaplastic carcinomas (ATCs) and all other samples and also between ATCs and all other malignant tumors (<it>p </it>< 0.05, Wilcoxon test, t approximation). Furthermore, in thyroid tumors <it>THADA </it>mRNA expression was found to be inversely correlated with <it>HMGA2 </it>mRNA. <it>HMGA2 </it>expression was recently identified as a marker revealing malignant transformation of thyroid follicular tumors. A correlation between <it>THADA </it>and <it>NIS </it>has also been found in thyroid normal tissue and malignant tumors.</p> <p>Conclusions</p> <p>The results suggest <it>THADA </it>being a marker of dedifferentiation of thyroid tissue.</p

Experimental and numerical analysis of short sisal fiber-cement composites produced with recycled matrix

"Published online: 02 Jan 2017"The proper use of renewable or recycled source materials can contribute significantly to reducing the environmental impact of construction industry. In this work, cement based composites reinforced with natural fibers were developed and their mechanical behavior was characterized. To ensure the composite sustainability and durability, the ordinary Portland cement matrix was modified by adding metakaolin and the natural aggregate was substituted by 10% and 20% of recycled concrete aggregate. Compression and splitting tensile tests indicated that mechanical strength did not seem to be affected by recycled content. Flat sheets were cast in a self-compacted cement matrix and bending tests were performed to determine the first crack, postpeak strength and cracking behavior of the composites. The use of short sisal fiber as reinforcement of recycled cement matrices results in a composite with multiple cracking and increment of strength after first crack. The modeling of composites using finite element method allowed to determine the tensile stress-strain behavior of material and to design possible applications of this new sustainable material.This research was supported by CAPES (PVE Program: Project 047/2012) and CNPqinfo:eu-repo/semantics/publishedVersio

Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers:Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data

Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting

Multidirectional Subspace Expansion for One-Parameter and Multiparameter Tikhonov Regularization

Tikhonov regularization is a popular method to approximate solutions of linear discrete ill-posed problems when the observed or measured data is contaminated by noise. Multiparameter Tikhonov regularization may improve the quality of the computed approximate solutions. We propose a new iterative method for large-scale multiparameter Tikhonov regularization with general regularization operators based on a multidirectional subspace expansion. The multidirectional subspace expansion may be combined with subspace truncation to avoid excessive growth of the search space. Furthermore, we introduce a simple and effective parameter selection strategy based on the discrepancy principle and related to perturbation results

Impaired Functions of Peripheral Blood Monocyte Subpopulations in Aged Humans

Aging is associated with increased susceptibility to microbial infections, and monocytes play an important role in microbial defense. In this study, we have identified and compared four subpopulations of monocytes (CD14++(high)CD16−, CD14+(low)CD16−, CD14++(high)CD16+, and CD14+(low)CD16+) in the peripheral blood of young and aged subjects with regard to their numbers, cytokine production, TLR expression, and phosphorylation of ERK1/2 in response to pam3Cys a TLR-1/2 ligand. Proportions and numbers of CD14++(high)CD16+ and CD14+(low)CD16+ monocytes were significantly increased, whereas proportions of CD14+(low)CD16− monocytes were decreased in aged subjects as compared to young subjects. In aged subjects, IL-6 production by all four subsets of monocytes was significantly decreased, whereas TNF-α production was decreased in monocyte subsets, except the CD14+(low)CD16− subset. A significantly reduced expression of TLR1 was observed in CD14++(high)CD16+ and CD14+(low)CD16+ monocyte subsets in aged subjects. Furthermore, following pam3Cys stimulation, ERK1/2 phosphorylation was significantly lower in CD14+(low)CD16+, CD14++(high)CD16+, and CD14+(low)CD16− subsets of monocytes from aged subjects. This is the first study of four subpopulations of monocytes in aging, which demonstrates that their functions are differentially impaired with regard to the production of cytokines, expression of TLR, and signaling via the ERK–MAPK pathway. Finally, changes in the number of monocyte subsets, and impairment of TLR1 expression, TNF-α production, and EK1/2 phosphorylation was more consistent in CD16+ monocyte subsets regardless of expression of CD14high or CD14+low, therefore highlighting the significance of further subdivision of monocytes into four subpopulations

Effective null Raychaudhuri equation

The effects on Raychaudhuri's equation of an intrinsically-discrete or particle nature of spacetime are investigated. This is done through the consideration of null congruences emerging from, or converging to, a generic point of spacetime, i.e. in geometric circumstances somehow prototypical of singularity issues. We do this from an effective point of view, that is through a (continuous) description of spacetime modified to embody the existence of an intrinsic discreteness on the small scale, this adding to previous results for non-null congruences. Various expressions for the effective rate of change of expansion are derived. They in particular provide finite values for the limiting effective expansion and its rate of variation when approaching the focal point. Further, this results in a non-vanishing of the limiting cross-sectional area itself of the congruence.Comment: 7 pages; v2: some comparisons with other approaches adde