Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Validation of a new three-dimensional imaging system using comparative craniofacial anthropometry

Abstract Background The aim of this study is to validate a new three-dimensional craniofacial stereophotogrammetry imaging system (3dMDface) through comparison with manual facial surface anthropometry. The null hypothesis was that there is no difference between craniofacial measurements using anthropometry vs. the 3dMDface system. Methods Facial images using the new 3dMDface system were taken from six randomly selected subjects, sitting in natural head position, on six separate occasions each 1 week apart, repeated twice at each sitting. Exclusion criteria were excess facial hair, facial piercings and undergoing current dentofacial treatment. 3dMDvultus software allowed facial landmarks to be marked and measurements recorded. The same measurements were taken using manual anthropometry, using soluble eyeliner to pinpoint landmarks, and sliding and spreading callipers and measuring tape to measure distances. The setting for the investigation was a dental teaching hospital and regional (secondary and tertiary care) cleft centre. The main outcome measure was comparison of the craniofacial measurements using the two aforementioned techniques. Results The results showed good agreement between craniofacial measurements using the 3dMDface system compared with manual anthropometry. For all measurements, except chin height and labial fissure width, there was a greater variability with the manual method compared to 3D assessment. Overall, there was a significantly greater variability in manual compared with 3D assessments (p < 0.02). Conclusions The 3dMDface system is validated for craniofacial measurements

A randomised trial into the effect of an isolated hip abductor strengthening programme and a functional motor control programme on knee kinematics and hip muscle strength

Background: Dynamic knee valgus and internal femoral rotation are proposed to be contributory risk factors for patellofemoral pain and anterior cruciate ligament injuries. Multimodal interventions including hip abductor strengthening or functional motor control programmes have a positive impact of pain, however their effect on knee kinematics and muscle strength is less clear. The aim of this study was to examine the effect of isolated hip abductor strengthening and a functional motor control exercise on knee kinematics and hip abductor strength. Methods: This prospective, randomised, repeated measures design included 29 asymptomatic volunteers presenting with increase knee valgus and femoral internal rotation. Participants completed either isolated hip abductor strengthening or a functional motor control exercise for 5 weeks. Knee kinematics were measured using inertial sensors during 2 functional activities and hip abductor strength measured using a load cell during isometric hip abduction. Results: There were no significant differences in dynamic knee valgus and internal rotation following the isolated hip abductor or functional motor control intervention, and no significant differences between the groups for knee angles. Despite this, the actual magnitude of reduction in valgus was 10° and 5° for the functional motor control group and strengthening group respectively. The actual magnitude of reduction in internal rotation was 9° and 18° for the functional motor control group and strengthening group respectively. Therefore there was a tendency towards clinically significant improvements in knee kinematics in both exercise groups. A statistically significant improvement in hip abductor strength was evident for the functional motor control group (27% increase; p = 0.008) and strengthening group (35% increase; p = 0.009) with no significant difference between the groups being identified (p = 0.475). Conclusions: Isolated hip strengthening and functional motor control exercises resulted in non-statistically significant changes in knee kinematics, however there was a clear trend towards clinically meaningful reductions in valgus and internal rotation. Both groups demonstrated similar significant gains in hip abductor strength suggesting\ud either approach could be used to strengthen the hip abductors

Shh Signaling from the Nucleus Pulposus Is Required for the Postnatal Growth and Differentiation of the Mouse Intervertebral Disc

Intervertebral discs (IVD) are essential components of the vertebral column. They maintain separation, and provide shock absorbing buffers, between adjacent vertebrae, while also allowing movements between them. Each IVD consists of a central semi-liquid nucleus pulposus (NP) surrounded by a multi-layered fibrocartilagenous annulus fibrosus (AF). Although the IVDs grow and differentiate after birth along with the vertebral column, little is known about the mechanism of this. Understanding the signals that control normal IVD growth and differentiation would also provide potential therapies for degenerative disc disease, which is the major cause of lower back pain and affects a large proportion of the population. In this work, we show that during postnatal growth of the mouse, Sonic hedgehog (Shh) signaling from the NP cells controls many aspects of growth and differentiation of both the NP cells themselves and of the surrounding AF, and that it acts, at least partly, by regulating other signaling pathways in the NP and AF. Recent studies have shown that the NP cells arise from the embryonic notochord, which acts as a major signaling center in the embryo. This work shows that this notochord-derived tissue continues to carry out a major signaling function in the postnatal body and that the IVDs are signaling centers, in addition to their already known functions in the mechanics of vertebral column function

Time- and Dose-Dependent Induction of HSP70 in Lemna minor Exposed to Different Environmental Stressors

The objective of this study was to examine the influence of different stressors, including cadmium (heavy metal), anthracene (polycyclic aromatic hydrocarbon—PAH) and chloridazon (herbicide), on population growth and biosynthesis of cytoplasmic HSP70 in Lemna minor (duckweed) in short (4 h)- and long (7 days)-term tests. A heat shock response was confirmed in Lemna exposed to high temperature: 35, 37.5, 40, or 42.5°C in short-term (4 h) treatments. The chemicals tested stimulated the biosynthesis of the cytoplasmic HSP70 protein in a concentration-dependent way (0.5–5 μM), higher in fronds exposed to lower doses of stressors. Additionally, production of HSP70 was greater after 4 h of incubation than after 7 days. The results suggest that HSP70 could be applied as a non-specific and sensitive detector of stress induced by different chemicals at concentrations below those that produce the type of response observed in classical cytotoxicity tests, such as growth inhibition

Research priorities for the COVID-19 pandemic and beyond: A call to action for psychological science

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020. The most pressing need is to research the negative biopsychosocial impacts of the COVID-19 pandemic to facilitate immediate and longer-term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. We call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high-quality, open, and rigorous research standards

RNase L Mediated Protection from Virus Induced Demyelination

IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL−/−) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL−/− mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination

Identification of modifiable factors associated with owner-reported equine laminitis in Britain using a web-based cohort study approach

Equine laminitis is a complex disease that manifests as pain and lameness in the feet, often with debilitating consequences. There is a paucity of data that accounts for the multifactorial nature of laminitis and considers time-varying covariates that may be associated with disease development; particularly those that are modifiable and present potential interventions. A previous case-control study identified a number of novel, modifiable factors associated with laminitis which warranted further investigation and corroboration. The aim of this study was to identify factors associated with equine laminitis in horses/ponies in Great Britain (GB) using a prospective, web-based cohort study design, with particular interest in evaluating modifiable factors previously identified in the case-control study

Role of Visible Light-Activated Photocatalyst on the Reduction of Anthrax Spore-Induced Mortality in Mice

BACKGROUND: Photocatalysis of titanium dioxide (TiO(2)) substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO(2) substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. Their anti-spore activity against Bacillus anthracis, however, remains to be investigated. We evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Standard plating method was used to determine the inactivation of anthrax spore by visible light-induced photocatalysis. Mouse models were further employed to investigate the suppressive effects of the photocatalysis on anthrax toxin- and spore-mediated mortality. We found that anti-spore activities of visible light illuminated nitrogen- or carbon-doped titania thin films significantly reduced viability of anthrax spores. Even though the spore-killing efficiency is only approximately 25%, our data indicate that spores from photocatalyzed groups but not untreated groups have a less survival rate after macrophage clearance. In addition, the photocatalysis could directly inactivate lethal toxin, the major virulence factor of B. anthracis. In agreement with these results, we found that the photocatalyzed spores have tenfold less potency to induce mortality in mice. These data suggest that the photocatalysis might injury the spores through inactivating spore components. CONCLUSION/SIGNIFICANCE: Photocatalysis induced injuries of the spores might be more important than direct killing of spores to reduce pathogenicity in the host