Genetics of upper and lower airway diseases in the horse.

Genetic predispositions for guttural pouch tympany, recurrent laryngeal neuropathy and recurrent airway obstruction (RAO) are well documented. There is also evidence that exercise-induced pulmonary haemorrhage and infectious diseases of the respiratory tract in horses have a genetic component. The clinical expression of equine respiratory diseases with a genetic basis results from complex interactions between the environment and the genetic make-up of each individual horse. The genetic effects are likely to be due to variations in several genes, i.e. they are polygenic. It is therefore unlikely that single gene tests will be diagnostically useful in these disorders. Genetic profiling panels, combining several genetic factors with an assessment of environmental risk factors, may have greater value, but much work is still needed to uncover diagnostically useful genetic markers or even causative variants for equine respiratory diseases. Nonetheless, chromosomal regions associated with guttural pouch tympany, recurrent laryngeal neuropathy and RAO have been identified. The association of RAO with other hypersensitivities and with resistance to intestinal parasites requires further study. This review aims to provide an overview of the available data and current thoughts on the genetics of equine airway diseases.

Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide.

BACKGROUND Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. STUDY DESIGN AND METHODS In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. RESULTS While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. CONCLUSION We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.

Systematic analysis of the intravoxel incoherent motion threshold separating perfusion and diffusion effects: Proposal of a standardized algorithm

PURPOSE To systematically evaluate the dependence of intravoxel-incoherent-motion (IVIM) parameters on the b-value threshold separating the perfusion and diffusion compartment, and to implement and test an algorithm for the standardized computation of this threshold. METHODS Diffusion weighted images of the upper abdomen were acquired at 3 Tesla in eleven healthy male volunteers with 10 different b-values and in two healthy male volunteers with 16 different b-values. Region-of-interest IVIM analysis was applied to the abdominal organs and skeletal muscle with a systematic increase of the b-value threshold for computing pseudodiffusion D*, perfusion fraction Fp , diffusion coefficient D, and the sum of squared residuals to the bi-exponential IVIM-fit. RESULTS IVIM parameters strongly depended on the choice of the b-value threshold. The proposed algorithm successfully provided optimal b-value thresholds with the smallest residuals for all evaluated organs [s/mm2]: e.g., right liver lobe 20, spleen 20, right renal cortex 150, skeletal muscle 150. Mean D* [10(-3) mm(2) /s], Fp [%], and D [10(-3) mm(2) /s] values (±standard deviation) were: right liver lobe, 88.7 ± 42.5, 22.6 ± 7.4, 0.73 ± 0.12; right renal cortex: 11.5 ± 1.8, 18.3 ± 2.9, 1.68 ± 0.05; spleen: 41.9 ± 57.9, 8.2 ± 3.4, 0.69 ± 0.07; skeletal muscle: 21.7 ± 19.0; 7.4 ± 3.0; 1.36 ± 0.04. CONCLUSION IVIM parameters strongly depend upon the choice of the b-value threshold used for computation. The proposed algorithm may be used as a robust approach for IVIM analysis without organ-specific adaptation. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Is mental practice an effective adjunct therapeutic strategy for upper limb motor restoration after stroke?

Stroke is one of the most common conditions requiring rehabilitation, and its motor impairments are a major cause of permanent disability. Hemiparesis is observed by 80% of the patients after acute stroke. Neuroimaging studies showed that real and imagined movements have similarities regarding brain activation, supplying evidence that those similarities are based on the same process. Within this context, the combination of MP with physical and occupational therapy appears to be a natural complement based on neurorehabilitation concepts. Our study seeks to investigate if MP for stroke rehabilitation of upper limbs is an effective adjunct therapy. PubMed (Medline), ISI knowledge (Institute for Scientific Information) and SciELO (Scientific Electronic Library) were terminated on 20 February 2015. Data were collected on variables as follows: sample size, type of supervision, configuration of mental practice, setting the physical practice (intensity, number of sets and repetitions, duration of contractions, rest interval between sets, weekly and total duration), measures of sensorimotor deficits used in the main studies and significant results. Random effects models were used that take into account the variance within and between studies. Seven articles were selected. As there was no statistically significant difference between the two groups (MP vs Control), showed a – 0.6 (95% CI: –1.27 to 0.04), for upper limb motor restoration after stroke. The present meta-analysis concluded that MP is not effective as adjunct therapeutic strategy for upper limb motor restoration after stroke.

Effects of sample mass and macrofossil type on radiocarbon dating of arctic and boreal lake sediments

Dating lake sediments by accelerator mass spectrometry (AMS) 14C analysis of terrestrial plant macrofossils overcomes one of the main problems associated with dating bulk sediment samples, i.e., the presence of old organic matter. Even so, many AMS dates from arctic and boreal sites appear to misrepresent the age of the sediment. To understand the nature of these apparent dating anomalies better, we conducted a series of 14C dating experiments using samples from Alaskan and Siberian lake-sediment cores. First, to test whether our analytical procedures introduced a sample-mass bias, we obtained 14C dates for different-sized pieces of single woody macrofossils. In these sample-mass experiments, statistically equivalent ages were found for samples as small as 0.05 mg C. Secondly, to assess whether macrofossil type influenced dating results, we conducted sample-type experiments in which 14C dates were obtained for different macrofossil types sieved from the same depth in the sediment. We dated materials from multiple levels in sediment cores from Upper Capsule Lake (North Slope, northern Alaska) and Grizzly Lake (Copper River Basin, southern Alaska) and from single depths in other records from northern Alaska. In several of the experiments there were significant discrepancies between dates for different plant tissues, and in most cases wood and charcoal were older than other macrofossil types, usually by several hundred years. This pattern suggests that 14C dates for woody macrofossils may misrepresent the age of the sediment by centuries, perhaps because of their longer terrestrial residence time and the potential in-built age of longlived plants. This study identifies why some 14C dates appear to be inconsistent with the overall age-depth trend of a lake-sediment record, and it may guide the selection of 14C samples in future studies.

Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China – A comprehensive perspective

The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1-hydroxypyrene was detected in bile of fish from all sites. All endpoints in combination with the chemical data suggest a pivotal role of PAHs in the observed ecotoxicological impacts.

Cultivation strategies to enhance productivity of Pichia pastoris: A review.

Pichia pastoris, a methylotrophic yeast, is an established system for the production of heterologous proteins, particularly biopharmaceuticals and industrial enzymes. To maximise and optimise the production of recombinant products, recent molecular research has focused on numerous issues including the design of expression vectors, optimisation of gene copy number, co-expression of secretory proteins such as chaperones, engineering of glycosylation and secretory pathways, etc. However, the physiological effects of different cultivation strategies are often difficult to separate from the molecular effects of the gene construct (e.g., cellular stress through over-expression or incorrect post-translational processing). Hence, overall system optimisation is difficult, even though it is urgently required in order to describe and understand the behaviour of new molecular constructs. This review focuses on particular aspects of recombinant protein production related to variations in biomass growth and their implications for strain design and screening, as well as on the concept of rational comparisons between cultivation systems for the development of specific production processes in bioreactors. The relationship between specific formation rates of secreted recombinant proteins, qp, and specific growth rates, μ, has been analysed in a conceptual attempt to compare different systems, particularly those based on AOX1/methanol and GAP/glucose, and this has now evolved into a pivotal concept for bioprocess engineering of P. pastoris.

Intensification of tropical Pacific biological productivity due to volcanic eruptions

Major volcanic eruptions generate widespread ocean cooling, which reduces upper ocean stratification. This effect has the potential to increase nutrient delivery into the euphotic zone and boost biological productivity. Using externally forced last millennium simulations of three climate/Earth System models (Model for Interdisciplinary Research On Climate (MIROC), Community Earth System Model (CESM), and LOch-Vecode-Ecbilt-CLio-agIsm Model (LOVECLIM)), we test the hypothesis that large volcanic eruptions intensify nutrient-driven export production. It is found that strong volcanic radiative forcing enhances the likelihood of eastern Pacific El Niño-like warming in CESM and LOVECLIM. This leads to an initial reduction of nutrients and export production in the eastern equatorial Pacific. However, this initial response reverses after about 3 years in association with La Niña cooling. The resulting delayed enhancement of biological production resembles the multiyear response in MIROC. The model simulations show that volcanic impacts on tropical Pacific dynamics and biogeochemistry persist for several years, thus providing a new source for potential multiyear ecosystem predictability.

Treatment for superficial infusion thrombophlebitis of the upper extremity.

BACKGROUND Although superficial thrombophlebitis of the upper extremity represents a frequent complication of intravenous catheters inserted into the peripheral veins of the forearm or hand, no consensus exists on the optimal management of this condition in clinical practice. OBJECTIVES To summarise the evidence from randomised clinical trials (RCTs) concerning the efficacy and safety of (topical, oral or parenteral) medical therapy of superficial thrombophlebitis of the upper extremity. SEARCH METHODS The Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). Clinical trials registries were searched up to April 2015. SELECTION CRITERIA RCTs comparing any (topical, oral or parenteral) medical treatment to no intervention or placebo, or comparing two different medical interventions (e.g. a different variant scheme or regimen of the same intervention or a different pharmacological type of treatment). DATA COLLECTION AND ANALYSIS We extracted data on methodological quality, patient characteristics, interventions and outcomes, including improvement of signs and symptoms as the primary effectiveness outcome, and number of participants experiencing side effects of the study treatments as the primary safety outcome. MAIN RESULTS We identified 13 studies (917 participants). The evaluated treatment modalities consisted of a topical treatment (11 studies), an oral treatment (2 studies) and a parenteral treatment (2 studies). Seven studies used a placebo or no intervention control group, whereas all others also or solely compared active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, the risk of bias in individual trials was moderate to high, although poor reporting hampered a full appreciation of the risk in most studies. The overall quality of the evidence for each of the outcomes varied from low to moderate mainly due to risk of bias and imprecision, with only single trials contributing to most comparisons. Data on primary outcomes improvement of signs and symptoms and side effects attributed to the study treatment could not be statistically pooled because of the between-study differences in comparisons, outcomes and type of instruments to measure outcomes.An array of topical treatments, such as heparinoid or diclofenac gels, improved pain compared to placebo or no intervention. Compared to placebo, oral non-steroidal anti-inflammatory drugs reduced signs and symptoms intensity. Safety issues were reported sparsely and were not available for some interventions, such as notoginseny creams, parenteral low-molecular-weight heparin or defibrotide. Although several trials reported on adverse events with topical heparinoid creams, Essaven gel or phlebolan versus control, the trials were underpowered to adequately measure any differences between treatment modalities. Where reported, adverse events with topical treatments consisted mainly of local allergic reactions. Only one study of 15 participants assessed thrombus extension and symptomatic venous thromboembolism with either oral non-steroidal anti-inflammatory drugs or low-molecular-weight heparin, and it reported no cases of either. No study reported on the development of suppurative phlebitis, catheter-related bloodstream infections or quality of life. AUTHORS' CONCLUSIONS The evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality. Data appear too preliminary to assess the effectiveness and safety of topical treatments, systemic anticoagulation or oral non-steroidal anti-inflammatory drugs.

Transgenerational effects of land use on offspring performance and growth in Trifolium repens

entral European grasslands vary widely in productivity and in mowing and grazing regimes. The resulting differences in competition and heterogeneity among grasslands might have direct effects on plants, but might also affect the growth and morphology of their offspring through maternal effects or adaptive evolution. To test for such transgenerational effects, we grew plants of the clonal herb Trifolium repens from seeds collected in 58 grassland sites differing in productivity and mowing and grazing intensities in different treatments: without competition, with homogeneous competition, and with heterogeneous competition. In the competition-free treatment, T. repens from more productive, less frequently mown, and less intensively grazed sites produced more vegetative offspring, but this was not the case in the other treatments. When grown among or in close proximity to competitors, T. repens plants did not show preferential growth towards open spaces (i.e., no horizontal foraging), but did show strong vertical foraging by petiole elongation. In the homogeneous competition treatment, petiole length increased with the productivity of the parental site, but this was not the case in the heterogeneous competition treatment. Moreover, petiole length increased with mowing frequency and grazing intensity of the parental site in all but the homogeneous competition treatment. In summary, although the expression of differences between plants from sites with different productivities and land-use intensities depended on the experimental treatment, our findings imply that there are transgenerational effects of land use on the morphology and performance of T. repens.

Towards science-based sediment quality standards-Effects of field-collected sediments in rainbow trout (Oncorhynchus mykiss).

Sediments can act as long-term sinks for environmental pollutants. Within the past decades, dioxin-like compounds (DLCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) have attracted significant attention in the scientific community. To investigate the time- and concentration-dependent uptake of DLCs and PAHs in rainbow trout (Oncorhynchus mykiss) and their associated toxicological effects, we conducted exposure experiments using suspensions of three field-collected sediments from the rivers Rhine and Elbe, which were chosen to represent different contamination levels. Five serial dilutions of contaminated sediments were tested; these originated from the Prossen and Zollelbe sampling sites (both in the river Elbe, Germany) and from Ehrenbreitstein (Rhine, Germany), with lower levels of contamination. Fish were exposed to suspensions of these dilutions under semi-static conditions for 90 days. Analysis of muscle tissue by high resolution gas chromatography and mass spectrometry and of bile liquid by high-performance liquid chromatography showed that particle-bound PCDD/Fs, PCBs and PAHs were readily bioavailable from re-suspended sediments. Uptake of these contaminants and the associated toxicological effects in fish were largely proportional to their sediment concentrations. The changes in the investigated biomarkers closely reflected the different sediment contamination levels: cytochrome P450 1A mRNA expression and 7-ethoxyresorufin-O-deethylase activity in fish livers responded immediately and with high sensitivity, while increased frequencies of micronuclei and other nuclear aberrations, as well as histopathological and gross pathological lesions, were strong indicators of the potential long-term effects of re-suspension events. Our study clearly demonstrates that sediment re-suspension can lead to accumulation of PCDD/Fs and PCBs in fish, resulting in potentially adverse toxicological effects. For a sound risk assessment within the implementation of the European Water Framework Directive and related legislation, we propose a strong emphasis on sediment-bound contaminants in the context of integrated river basin management plans.

Effects of team Knowledge and ecological constraints on decisional processes in customized football game scenarios

Several theories assume that successful team coordination is partly based on knowledge that helps anticipating individual contributions necessary in a situational task. It has been argued that a more ecological perspective needs to be considered in contexts evolving dynamically and unpredictably. In football, defensive plays are usually coordinated according to strategic concepts spanning all members and large areas of the playfield. On the other hand, fewer people are involved in offensive plays as these are less projectable and strongly constrained by ecological characteristics. The aim of this study is to test the effects of ecological constraints and player knowledge on decision making in offensive game scenarios. It is hypothesized that both knowledge about team members and situational constraints will influence decisional processes. Effects of situational constraints are expected to be of higher magnitude. Two teams playing in the fourth league of the Swiss Football Federation participate in the study. Forty customized game scenarios were developed based on the coaches’ information about player positions and game strategies. Each player was shown in ball possession four times. Participants were asked to take the perspective of the player on the ball and to choose a passing destination and a recipient. Participants then rated domain specific strengths (e.g., technical skills, game intelligence) of each of their teammates. Multilevel models for categorical dependent variables (team members) will be specified. Player knowledge (rated skills) and ecological constraints (operationalized as each players’ proximity and availability for ball reception) are included as predictor variables. Data are currently being collected. Results will yield effects of parameters that are stable across situations as well as of variable parameters that are bound to situational context. These will enable insight into the degree to which ecological constraints and more enduring team knowledge are involved in decisional processes aimed at coordinating interpersonal action.