The effects of irradiation on the biological and biomechanical properties of an acellular porcine superflexor tendon graft for cruciate ligament repair

Acellular xenogeneic tissues have the potential to provide ‘off‐the‐shelf’ grafts for anterior cruciate ligament (ACL) repair. To ensure that such grafts are sterile following packaging, it is desirable to use terminal sterilization methods. Here, the effects of gamma and electron beam irradiation on the biological and biomechanical properties of a previously developed acellular porcine superflexor tendon (pSFT) were investigated. Irradiation following treatment with peracetic acid was compared to peracetic acid treatment alone and the stability of grafts following long‐term storage assessed. Irradiation did not affect total collagen content or biocompatibility (determined using a contact cytotoxicity assay) of the grafts, but slightly increased the amount of denatured collagen in and decreased the thermal denaturation temperature of the tissue in a dose dependant fashion. Biomechanical properties of the grafts were altered by irradiation (reduced ultimate tensile strength and Young's modulus, increased failure strain), but remained superior to reported properties of the native human ACL. Long term storage at 4°C had no negative effects on the grafts. Of all the conditions tested, a dose of minimum 25 kGy of gamma irradiation had least effect on the grafts, suggesting that this dose produces a biocompatible pSFT graft with adequate mechanical properties for ACL repair

Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion in mice

Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. Here we report that neural fold elevation during mouse spinal neurulation is vulnerable to deletion of the VANGL planar cell polarity protein 2 (Vangl2) gene in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves diminished myosin-II localisation on neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted neuroepithelial cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap localisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects

Impaired glucose tolerance in adults with Duchenne and Becker muscular dystrophy

The aim of this study was to determine the response to an oral glucose tolerance test (OGTT) in adult males with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD), and to investigate whether body composition contributes to any variance in the glucose response. Twenty-eight adult males with dystrophinopathy (BMD, n = 13; DMD, n = 15) and 12 non-dystrophic controls, ingested 75 g oral anhydrous glucose solution. Fingertip capillary samples were assessed for glucose at 30-min intervals over 2-h post glucose ingestion. Fat free mass relative to body mass (FFM/BM) and body fat (BF%) was assessed using bioelectrical impedance. Vastus lateralis muscle anatomical cross sectional area (VL ACSA) was measured using B-mode ultrasonography. Blood glucose was higher in MD groups than control at 60, 90 and 120 min post ingestion of glucose. Compared to controls, FFM/BM and VL ACSA were lower in MD groups compared to controls (p < 0.001). Glucose tolerance values at 120 min were correlated with FFM/BM and BF% in the BMD group only. Our results suggest that glucose tolerance is impaired following OGTT in adult males with BMD and DMD. It is recommended that adults with BMD and DMD undertake routine glucose tolerance assessments to allow early detection of impaired glucose tolerance

Integration and functional performance of a decellularised porcine superflexor tendon graft in an ovine model of anterior cruciate ligament reconstruction

The objective was to evaluate the performance of decellularised porcine superflexor tendon (pSFT) as an anterior cruciate ligament (ACL) reconstruction device. The ACL of adult sheep was reconstructed with decellularised pSFT or ovine allograft SFT and animals sacrificed at 4, 12 and 26 weeks (n = 4 per group) for biological evaluation and 26 weeks (n = 6) for biomechanical evaluation of the grafts. Both grafts showed good in vivo performance with no major differences at macroscopic evaluation post euthanasia. Histopathology revealed an inflammatory reaction to both grafts at 4 weeks, which reduced by 26 weeks. There was advanced cellular ingrowth from 12 weeks, ligamentisation of intra-articular grafts, ossification and formation of Sharpey's fibers at the graft/bone junctions. Immunohistochemistry showed that at 4 and 12 weeks, the host response was dominated by CD163+ M2 macrophages and a cell infiltrate comprising α-SMA + myofibroblasts, CD34+ and CD271+ progenitor cells. At 26 weeks the biomechanical properties of decellularised pSFT and oSFT grafts were comparable, with all grafts failing in the intra-articular region. This study provides new insight into constructive remodelling of tendons used for ACL replacement and evidence of integration and functional performance of a decellularised xenogeneic tendon with potential as an alternative for ACL reconstruction

NBC update: The addition of viral and fungal databases to the Naïve Bayes classification tool

<p>Abstract</p> <p>Background</p> <p>Classifying the fungal and viral content of a sample is an important component of analyzing microbial communities in environmental media. Therefore, a method to classify any fragment from these organisms' DNA should be implemented.</p> <p>Results</p> <p>We update the näive Bayes classification (NBC) tool to classify reads originating from viral and fungal organisms. NBC classifies a fungal dataset similarly to Basic Local Alignment Search Tool (BLAST) and the Ribosomal Database Project (RDP) classifier. We also show NBC's similarities and differences to RDP on a fungal large subunit (LSU) ribosomal DNA dataset. For viruses in the training database, strain classification accuracy is 98%, while for those reads originating from sequences not in the database, the order-level accuracy is 78%, where order indicates the taxonomic level in the tree of life.</p> <p>Conclusions</p> <p>In addition to being competitive to other classifiers available, NBC has the potential to handle reads originating from any location in the genome. We recommend using the Bacteria/Archaea, Fungal, and Virus databases separately due to algorithmic biases towards long genomes. The tool is publicly available at: <url>http://nbc.ece.drexel.edu</url>.</p

Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees

Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one’s own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made

Genome-Scale Methods Converge on Key Mitochondrial Genes for the Survival of Human Cardiomyocytes in Hypoxia

BACKGROUND: Any reduction in myocardial oxygen delivery relative to its demands can impair cardiac contractile performance. Understanding the mitochondrial metabolic response to hypoxia is key to understanding ischemia tolerance in the myocardium. We used a novel combination of 2 genome-scale methods to study key processes underlying human myocardial hypoxia tolerance. In particular, we hypothesized that computational modeling and evolution would identify similar genes as critical to human myocardial hypoxia tolerance. METHODS AND RESULTS: We analyzed a reconstruction of the cardiac mitochondrial metabolic network using constraint-based methods, under conditions of simulated hypoxia. We used flux balance analysis, random sampling, and principal component analysis to explore feasible steady-state solutions. Hypoxia blunted maximal ATP (−17%) and heme (−75%) synthesis and shrank the feasible solution space. Tricarboxylic acid and urea cycle fluxes were also reduced in hypoxia, but phospholipid synthesis was increased. Using mathematical optimization methods, we identified reactions that would be critical to hypoxia tolerance in the human heart. We used data regarding single-nucleotide polymorphism frequency and distribution in the genomes of Tibetans (whose ancestors have resided in persistent high-altitude hypoxia for several millennia). Six reactions were identified by both methods as being critical to mitochondrial ATP production in hypoxia: phosphofructokinase, phosphoglucokinase, complex II, complex IV, aconitase, and fumarase. CONCLUSIONS: Mathematical optimization and evolution converged on similar genes as critical to human myocardial hypoxia tolerance. Our approach is unique and completely novel and demonstrates that genome-scale modeling and genomics can be used in tandem to provide new insights into cardiovascular genetics

Factors affecting Removal of Bacterial Pathogens from Healthcare Surfaces during Dynamic Wiping

Wiping of surfaces contaminated with pathogenic bacteria is a key strategy for combatting transmission of healthcare associated infections. It is essential to understand the extent to which removal of bacteria is modulated by fibre properties, biocidal liquid impregnation and applied hand pressure. The influence of intrinsic and extrinsic factors on the removal efficiencies of pathogenic bacteria was studied. Nonwoven wipes made of either hydrophobic (polypropylene) or hygroscopic (lyocell) fibres were manufactured and dynamic removal efficiency of bacteria studied. The single most important parameter affecting bacterial removal efficiency was impregnation with biocidal liquid (p <0.05). For inherently hygroscopic 100% regenerated cellulose (lyocell) wipes impregnated with biocidal liquid, removal of E. coli, S. aureus and E. faecalis improved by increasing the fabric surface density and wiping pressure to their maximal values - 150 g.m-2 and 13.80 kN.m-2 respectively. For inherently hydrophobic 100% polypropylene nonwoven wipes, the same conditions maximised the removal efficiency of S. aureus, but for E. coli and E. faecalis a reduction in the wiping pressure to 4.68 kN.m-2 was required. Best practice involves the use of higher surface density wipes (150 g m-2) containing regenerated cellulose fibres loaded with liquid biocide, and applied with the greatest possible wiping pressure

Pathological and ecological host consequences of infection by an introduced fish parasite

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite