Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

Aim: To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Methods: Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Results: Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p = 0.0203) in animals treated with LLLT (864.70 U.l−1, SEM 226.10) than placebo (1708.00 U.l−1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (p<0.05): TNF-α (placebo-control = 0.51 µg/µl [SEM 0.12], - LLLT = 0.048 µg/µl [SEM 0.01]), IL-1β (placebo-control = 2.292 µg/µl [SEM 0.74], - LLLT = 0.12 µg/µl [SEM 0.03]), IL-6 (placebo-control = 3.946 µg/µl [SEM 0.98], - LLLT = 0.854 µg/µl [SEM 0.33]), IL-10 (placebo-control = 1.116 µg/µl [SEM 0.22], - LLLT = 0.352 µg/µl [SEM 0.15]), and COX-2 (placebo-control = 4.984 µg/µl [SEM 1.18], LLLT = 1.470 µg/µl [SEM 0.73]). Conclusion: Irradiation of superpulsed LLLT on successive days five times per week for 14 weeks decreased morphological changes, skeletal muscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy

A genome-wide study of Hardy–Weinberg equilibrium with next generation sequence data

Statistical tests for Hardy–Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes. Observed disequilibrium is, in about 60% of the cases, due to heterozygote excess. We suggest that most excess disequilibrium can be explained by sequencing problems, and hypothesize mechanisms that can explain exceptional heterozygosities. We report higher rates of disequilibrium for the MHC region on chromosome 6, regions flanking centromeres and p-arms of acrocentric chromosomes. We also detected long-range haplotypes and areas with incidental high disequilibrium. We report disequilibrium to be related to read depth, with variants having extreme read depths being more likely to be out of equilibrium. Disequilibrium rates were found to be 11 times higher in segmental duplications and simple tandem repeat regions. The variants with significant disequilibrium are seen to be concentrated in these areas. For next generation sequence data, Hardy–Weinberg disequilibrium seems to be a major indicator for copy number variation.Peer ReviewedPostprint (published version

Physiological Costs of Repetitive Courtship Displays in Cockroaches Handicap Locomotor Performance

Courtship displays are typically thought to have evolved via female choice, whereby females select mates based on the characteristics of a display that is expected to honestly reflect some aspect of the male’s quality. Honesty is typically enforced by mechanistic costs and constraints that limit the level at which a display can be performed. It is becoming increasingly apparent that these costs may be energetic costs involved in the production of dynamic, often repetitive displays. A female attending to such a display may thus be assessing the physical fitness of a male as an index of his quality. Such assessment would provide information on his current physical quality as well as his ability to carry out other demanding activities, qualities with which a choosy female should want to provision her offspring. In the current study we use courtship interactions in the Cuban burrowing cockroach, Byrsotria fumigata to directly test whether courtship is associated with a signaler’s performance capacity. Males that had produced courtship displays achieved significantly lower speeds and distances in locomotor trials than non-courting control males. We also found that females mated more readily with males that produced a more vigorous display. Thus, males of this species have developed a strategy where they produce a demanding courtship display, while females choose males based on their ability to produce this display. Courtship displays in many taxa often involve dynamic repetitive actions and as such, signals of stamina in courtship may be more widespread than previously thought

Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01–0145-FEDER-000008:BrainHealth 2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P., under projects PTDC/SAU-NEU/104100/2008, EXPL/NEU-NMC/0541/2012 and UID/NEU/04539/2013. This work was also funded by Marie Curie Actions - International reintegration grant #249288, 7th Framework programme, EU. Partially funded by Prémios Santa Casa Neurociências - Prize Melo e Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology (IF Development Grant to A.J.S.); NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme; by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The authors would also like to acknowledge Prof. J.E. Davies from the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, Canada, for kindly providing some of the HUCPVCs lots used in the present workinfo:eu-repo/semantics/publishedVersio

Rab27a and Rab27b control different steps of the exosome secretion pathway

Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo

Assessing research trends related to Sustainable Development Goals: local and global issues

© 2018 Elsevier Ltd The Sustainable Development Goals agreed by the United Nations in September 2015 comprise 17 goals and 169 targets aimed at integrating matters related to sustainable development into the overall economic, environmental and social frameworks of countries. Whereas the SDGs have a global dimension, their action implementation depends on the level of priority different countries give to them, and on how sustainability issues compete with a country's main problems. The aim of this paper was to identify the main Sustainable Development Goals approached by experts from different geographic regions, according to their experience and research area, and to discuss the relation between these goals and the main local issues and challenges of each region. The methodology starts with snowball sampling to collect information from experts from all geographic regions, through contact networks of universities in different countries. With the information about the goals researched by the participating experts, an analysis of the relation between the study focus and the geographical regions of origin was conducted. A total of 266 specialists from North America, Latin America/Caribbean, Africa, Asia, Europe and Oceania participated in the survey. Based on the sample used, it can be said that there is a relation between the local problems or challenges observed in some regions and the main areas of interest of the surveyed experts, with a general emphasis on the study of goals 4, 11 and 13. Based on the data gathered, the paper presents a set of examples of positive and negative situations in the various regions, and considers the extent to which some Sustainable Development Goals are being pursued by research on a worldwide basis

Sustainable development goals: a framework for deploying indicators for higher education institutions

Purpose: This paper aims to analyse the extent to which the sustainable development goals (SDGs) are being considered at higher education institutions (HEIs) and propose and test the possible acceptance of a list of indicators to evaluate the contribution of HEIs to the SDGs. Design/methodology/approach: The methodology consisted of the collection of indicators of sustainable development based on the existing bibliography. Afterwards, a set of indicators related to the SDGs were selected, based on the most frequent SDGs’ expressions found in the selected indicators. A sample of researchers was also asked to indicate to which extent this set of indicators is perceived as relevant. Findings: The results indicated an initial list with 432 indicators, of which 268 were selected for having at least one of the keywords searched for, related to the SDG descriptions and targets. Thus, redundant indicators were excluded and, when necessary, indicators were aggregated, resulting in a final list of 61 indicators. Originality/value: The set of indicators resulted from this analysis was considered appropriate to evaluate the contribution of HEIs towards the SDGs, demonstrating that it might not be necessary to create new indicators for that purpose

Quality control of B-lines analysis in stress Echo 2020

Background The effectiveness trial “Stress echo (SE) 2020” evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. Purpose To provide web-based upstream quality control and harmonization of B-lines reading criteria. Methods 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. Results All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). Conclusions Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.info:eu-repo/semantics/publishedVersio

The distinct category of healthcare associated bloodstream infections

<p>Abstract</p> <p>Background</p> <p>Bloodstream infections (BSI) have been traditionally classified as either community acquired (CA) or hospital acquired (HA) in origin. However, a third category of healthcare-associated (HCA) community onset disease has been increasingly recognized. The objective of this study was to compare and contrast characteristics of HCA-BSI with CA-BSI and HA-BSI.</p> <p>Methods</p> <p>All first episodes of BSI occurring among adults admitted to hospitals in a large health region in Canada during 2000-2007 were identified from regional databases. Cases were classified using a series of validated algorithms into one of HA-BSI, HCA-BSI, or CA-BSI and compared on a number of epidemiologic, microbiologic, and outcome characteristics.</p> <p>Results</p> <p>A total of 7,712 patients were included; 2,132 (28%) had HA-BSI, 2,492 (32%) HCA-BSI, and 3,088 (40%) had CA-BSI. Patients with CA-BSI were significantly younger and less likely to have co-morbid medical illnesses than patients with HCA-BSI or HA-BSI (p < 0.001). The proportion of cases in males was higher for HA-BSI (60%; p < 0.001 vs. others) as compared to HCA-BSI or CA-BSI (52% and 54%; p = 0.13). The proportion of cases that had a poly-microbial etiology was significantly lower for CA-BSI (5.5%; p < 0.001) compared to both HA and HCA (8.6 vs. 8.3%). The median length of stay following BSI diagnosis 15 days for HA, 9 days for HCA, and 8 days for CA (p < 0.001). Overall the most common species causing bloodstream infection were <it>Escherichia coli, Staphylococcus aureus</it>, and <it>Streptococcus pneumoniae</it>. The distribution and relative rank of importance of these species varied according to classification of acquisition. Twenty eight day all cause case-fatality rates were 26%, 19%, and 10% for HA-BSI, HCA-BSI, and CA-BSI, respectively (p < 0.001).</p> <p>Conclusion</p> <p>Healthcare-associated community onset infections are distinctly different from CA and HA infections based on a number of epidemiologic, microbiologic, and outcome characteristics. This study adds further support for the classification of community onset BSI into separate CA and HCA categories.</p

Polyomavirus Nephropathy: Ten-Year Experience

BACKGROUND: Polyomavirus nephropathy (BKVN) is an important cause of chronic allograft dysfunction (CAD). Recipient determinants (male sex, white race, and older age), deceased donation, high-dose immunosuppression, diabetes, delayed graft function (DGF), cytomegalovirus infection, and acute rejection (AR) are risk factors. Reducing immunosuppression is the best strategy in BKVN. The objective of our study was to evaluate CAD progression after therapeutic strategies in BKVN and risk factors for graft loss (GL). METHODS: Retrospective analysis of 23 biopsies, from patients with CAD and histological evidence of BKVN, conducted over a period of 10 years. Glomerular filtration rate was <30 mL/min in 16 patients at the time of the BKVN diagnosis. RESULTS: BKVN was histologically diagnosed in 23 recipients (19 men, 4 women). All patients were white, with age of 51.2 ± 12.1 years (6 patients, age >60 years), and 22 had a deceased donor. Diabetes affected 4 patients, DGF occurred in 3, cytomegalovirus infection in 2, and AR in 15. All patients were medicated with calcineurin inhibitors (CNI) (95.7% tacrolimus) and corticoids, and 16 also received an antimetabolite. One year after antimetabolite reduction/discontinuation and/or CNI reduction/switching and/or antiviral agents, graft function was decreased in 11 patients, increased/stabilized in 10, and unknown in 2. GL occurred in 9 patients. Older age (hazard ratio, 1.76; 95% confidence interval, 0.94-3.28) and DGF (hazard ratio, 2.60; 95% confidence interval, 0.54-12.64) were the main risk factors for GL. The lower GFR at the time of the BKVN diagnosis was associated with an increased risk of initiation of dialysis. CONCLUSIONS: GL occurred in 39.1% of patients with BKVN and DGF; older age and lower GFR at the time of diagnosis were important risk factors. Early diagnosis of BKVN is essential to prevent GL.info:eu-repo/semantics/publishedVersio