The effect of training on infrared thermographic images of the forelimb and hindlimb joints of healthy racehorses.

The aim of this study was to evaluate the influence of training on body surface temperature over the joints in racehorses, measured by infrared thermography. The study involved monitoring of 14 Thoroughbred racehorses in 6 imaging sessions over a period of 3 months. Temperature measurements of the forelimb and hindlimb joints were made before and just after training. Joint temperature of limbs increased significantly after training. Environmental temperature had a statistically significant influence on surface temperature over the joints. The lowest surface temperatures were recorded over the metacarpophalangeal and metatarsophalangeal joint and the highest temperatures in the shoulder, elbow, hip and stifle joint. The metacarpophalangeal and metatarsophalangeal joints warmed the least during training, but were influenced the most by differences in environmental temperature. The surface temperature difference before and after training is an important indicator of the thermoregulatory response to exercise in racing horses. Understanding surface temperature changes in response to regular training is necessary for future studies on diagnosing injuries of joints.

Prevalence of iatrogenic heart murmurs in a population of apparently healthy cats.

OBJECTIVES: To determine the prevalence of iatrogenic heart murmurs in a population of apparently healthy cats and to investigate factors that may predispose cats to iatrogenic murmurs. MATERIALS AND METHODS: Apparently healthy cats presenting for routine examinations were prospectively enrolled. Following a physical examination to confirm there were no abnormalities, a cardiac examination was performed before and during a provocative manoeuvre performed independently by two clinicians. The provocative manoeuvre was performed on the right side of the chest wall by applying gentle pressure with a stethoscope to ascertain whether a murmur became audible, graded using a modified descriptive scale (soft/moderate). The cat's heart rate before and during the provocative manoeuvre and their age, sex, body condition score and bodyweight were recorded. RESULTS: One hundred and six cats were prospectively enrolled. The average prevalence of iatrogenic murmurs was 28.2% with good interobserver agreement recorded on both the presence (kappa 0.67 and 0.62) and grade of the murmur (kappa 0.6 and 0.53). A significant association was noted between age and body condition score, with iatrogenic murmurs more likely in cats with increasing age and decreasing body condition score. There was no association between heart rate and the presence of an iatrogenic murmur. CLINICAL SIGNIFICANCE: Iatrogenic murmurs are a common finding in cats with increasing prevalence noted in older and lean cats. Iatrogenic murmurs should therefore be considered as a differential diagnosis in a cat when an audible soft systolic right-sided murmur occurs with gentle pressure application to the chest wall during auscultation.

Relationship between maximum eye temperature and plasma cortisol concentration in racehorses during intensive training.

The aim of the study was to determine the utility of maximum eye temperature measured by infrared thermography (IRT) as a stress indicator compared with plasma cortisol concentration in Thoroughbred and Arabian racehorses. The study included thirty racehorses undergoing standard training for racing. Measurements of maximum eye temperature and blood collection for plasma cortisol concentration were carried out before training (BT), and within 5 (5AT) and 120 minutes (120AT) after the end of the each training session in three repetitions, with a monthly interval. Both parameters were elevated at 5AT compared to BT (p⟨0.001). Compared to BT, at 120AT the maximum eye temperature remained elevated (p⟨0.001) and plasma cortisol concentration decreased (p⟨0.001). The study indicated significant weak correlations (r=0.220; p⟨0.001) between both measurements at all time points. The results support the use of IRT technique to monitor the response of horses to stress, potentially improving animal management and welfare.

Designing a survey to monitor multi-scale impacts of agri-environment schemes on mobile taxa.

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available.

Prospective evaluation of treatment response and disease reversibility of paediatric localized scleroderma (morphoea) to steroids and methotrexate using multi-modal imaging.

BACKGROUND: Paediatric localized scleroderma is a severe inflammatory disorder associated with tissue atrophy, often leading to disability. Assessing disease activity and response to treatment has always been challenging and remains an important difficulty in clinical practice. OBJECTIVES: To investigate prospectively the efficacy of systemic treatment with corticosteroids and methotrexate in children with localized scleroderma and the validity of infrared thermography, laser Doppler flowmetry and high-frequency ultrasound in assessing disease activity. METHODS: Children with localized scleroderma were prospectively treated with corticosteroids (initially pulsed IV methylprednisolone 30 mg/kg/day, maximum 500 mg/day and/or oral prednisolone 0.5-1 mg/kg/day) and methotrexate (15 mg/m2 weekly). Treatment response was evaluated using a clinical activity score. Skin temperature, blood flow, dermal thickness and dermal echogenicity of clinically active skin lesions were determined in relation to the unaffected contralateral site at baseline and after 3, 6, 12 and 18 months. Patient charts were later reviewed for long-term follow-up. RESULTS: Twenty-two patients were included [age 6.0 (0.2-14.4] years; female-to-male ratio 3.4 : 1) All responded well to therapy. Disease reversibility was demonstrated in the majority of children with partial resolution of skin sclerosis and regrowth of hair. Laser Doppler flowmetry and high-frequency ultrasound findings correlated with disease activity at baseline. Thermography had no added value in this cohort. The recurrence rate was 36% in the follow-up period. CONCLUSIONS: Corticosteroids and methotrexate are highly effective as first-line therapy in paediatric localized scleroderma, leading to partial reversal of skin manifestations. However, the recurrence rate is substantial and affected children require long-term follow-up. Laser Doppler flowmetry and high-frequency ultrasound correlate with disease activity in the acute phase and may assist decision-making in these patients.

Defined co-cultures of yeast and bacteria modify the aroma, crumb and sensory properties of bread.

AIMS: Yeast and bacterial communities inhabit a sourdough starter to make artisanal bread. This study shows whether the interactions of micro-organisms derived from Australian sourdough starters provide some of the positive flavour, and aroma properties to bread by using defined sourdough cultures as the sole leaven in bread production. METHODS AND RESULTS: An investigation of Australian sourdough starters found that they contained Saccharomyces cerevisiae and Kazachstania exigua yeasts. When these yeasts were inoculated alone to ferment wheat flour in an extended fermentation, the bread had a heterogeneous crumb structure, a deeper colour and a distinctive chemical aroma profile than those made with commercial baker's yeast. When bread was made combining these yeasts individually and in combinations with lactic acid bacteria also isolated from these sourdough starters, including Lactobacillus plantarum, L. brevis, L. rossiae, L. casei, the bread aroma profiles and crumb structure were more distinctive, with compounds associated with sour aromas produced, and preferred by sensory panels. CONCLUSIONS: The use of defined mixed cultures as the leaven in bread making, by exploiting the microbial diversity of artisanal Australian starters, can produce bread with distinctive and attractive aromas. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding and identifying the community ecosystems found in sourdough cultures and using them as the sole leaven in bread production provide novel insights into microbial interactions and how they affect food quality by removing the effects of commercial yeast strains.

Reverse engineering field-derived vertical distribution profiles to infer larval swimming behaviors.

Biophysical models are well-used tools for predicting the dispersal of marine larvae. Larval behavior has been shown to influence dispersal, but how to incorporate behavior effectively within dispersal models remains a challenge. Mechanisms of behavior are often derived from laboratory-based studies and therefore, may not reflect behavior in situ. Here, using state-of-the-art models, we explore the movements that larvae must undertake to achieve the vertical distribution patterns observed in nature. Results suggest that behaviors are not consistent with those described under the tidally synchronized vertical migration (TVM) hypothesis. Instead, we show (i) a need for swimming speed and direction to vary over the tidal cycle and (ii) that, in some instances, larval swimming cannot explain observed vertical patterns. We argue that current methods of behavioral parameterization are limited in their capacity to replicate in situ observations of vertical distribution, which may cause dispersal error to propagate over time, due to advective differences over depth and demonstrate an alternative to laboratory-based behavioral parameterization that encompasses the range of environmental cues that may be acting on planktic organisms.

Application of a directional palladium-103 brachytherapy device on a curved surface.

PURPOSE: The directional planar palladium-103 LDR device (CivaSheet TM ) may be used for intraoperative implantation at the interface between the tumor site and healthy tissue. Its dosimetric properties have been studied in the ideal case of application on a flat surface. The dosimetric impact of implanting this highly directional device on a curved surface that may be encountered in clinical treatments is analyzed. METHODS: CivaSheet is designed as an array of directional palladium-103 sources (CivaDots). From the postoperative computed tomography (CT) scans of three patients, the shape of each implanted CivaSheet was reconstructed. In order to obtain a realistic estimate of the distribution of curvatures, the mean radius of curvature at the location of each CivaDot was calculated. A Monte Carlo simulation (FLUKA) of a single CivaDot was designed, based upon published geometry and material specifications. Both the radial dose function analog and the two-dimensional anisotropy function analog for the CivaDot were validated in comparison with film measurements and benchmarked to published Monte Carlo data. A value for the dose-rate constant Λ = 0.587(19) cGy/h/U for a CivaDot source in water was calculated as well. Knowledge of the dose distribution in the vicinity of each source allowed the dose at any point around CivaSheets of different curvatures and orientations to be calculated. RESULTS: The local radius of curvature was found to be primarily between 2 and 8 cm in all three patient implants. On the unshielded side of an inward-facing curved CivaSheet implant of radius 2 cm, the calculated dose at 0.5 cm depth exceeded the prescribed dose by ∼20%, while on the shielded side the dose increased by a factor of two, thus compromising the shielding efficiency of the original design. On the unshielded side of an outward-facing curved implant, the dose at 0.5 cm depth decreased by ∼20%. CONCLUSIONS: When tumor bed curvature can be estimated from the preplanning CT scan, the results from this study provide quantitative guide for modifying the source strength to achieve the desired clinical results. In many intraoperative cases, however, accurate preplanning based on surface curvature may not be practical. In such situations, knowledge of the dosimetric impact of the surface curvature provides motivation for avoiding implantation geometries that can lead to either over/underdosing the target, or excess dose to healthy tissue.

Temporal Lobe Malformations in Achondroplasia: Expanding the Brain Imaging Phenotype Associated with FGFR3-Related Skeletal Dysplasias.

Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders. Temporal lobe abnormalities have been documented in thanatophoric dysplasia and hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified 13 children with achondroplasia who underwent MR imaging of the brain between 2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR imaging. Further common neuroimaging findings were incomplete hippocampal rotation (12 children), oversulcation of the mesial temporal lobe (11 children), loss of gray-white matter differentiation of the mesial temporal lobe (5 children), and a triangular shape of the temporal horn (6 children). These appearances are very similar to those described in hypochondroplasia, strengthening the association of temporal lobe malformations in FGFR3-associated skeletal dysplasias.

Complexity and health functionality of plant cell wall fibers from fruits and vegetables.

The prevalence of lifestyle-related diseases is increasing in developing countries with the causes for death starting to follow the same pattern in the developed world. Lifestyle factors including inadequate dietary intake of fruits and vegetables and over consumption of nutrient-poor processed foods, are considered to be major causal risk factors associated with increased susceptibility to developing certain diseases (Alldrick, 1998 ; Kiani, 2007 ). Recent epidemiological evidence confirms a strong association between dietary fiber and reduced all-cause mortality risk, as well as a risk reduction for a number of non-communicable diseases (Chuang et al., 2012 ). The relationship between dietary fiber and mortality has been described as "convincing observations that call for mechanistic investigations" (Landberg, 2012 ). In particular, the health protective roles played by dietary fibers of different origin are not well understood. Whilst Hippocrates was the earliest known physician to study the health benefits of fiber derived from grains (Burkitt, 1987 ), the functionality of fruit and vegetable fiber, especially in association with other compounds such as polyphenols and carotenoids, is an area of more recent interest. Hence the objective of this review is to assess the complexity and health-related functional role of plant cell wall (PCW) fibers from fruits and vegetables with a particular emphasis on interactions between cell walls and phytonutrients.

An emerging zoonotic clone in the Netherlands provides clues to virulence and zoonotic potential of Streptococcus suis.

Streptococcus suis is a zoonotic swine pathogen and a major public health concern in Asia, where it emerged as an important cause of bacterial meningitis in adults. While associated with food-borne transmission in Asia, zoonotic S. suis infections are mainly occupational hazards elsewhere. To identify genomic differences that can explain zoonotic potential, we compared whole genomes of 98 S. suis isolates from human patients and pigs with invasive disease in the Netherlands, and validated our observations with 18 complete and publicly available sequences. Zoonotic isolates have smaller genomes than non-zoonotic isolates, but contain more virulence factors. We identified a zoonotic S. suis clone that diverged from a non-zoonotic clone by means of gene loss, a capsule switch, and acquisition of a two-component signalling system in the late 19th century, when foreign pig breeds were introduced. Our results indicate that zoonotic potential of S. suis results from gene loss, recombination and horizontal gene transfer events.

Association of serum VEGF levels with prefrontal cortex volume in schizophrenia.

A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.

A humanized monoclonal antibody targeting the ß7 integrin selectively blocks intestinal homing of T lymphocytes.

BACKGROUND AND PURPOSE: rhuMAb Beta7 is a humanized anti-human ß7 monoclonal antibody currently in phase I in inflammatory bowel disease. rhuMAb Beta7 binds the ß7 subunit of the integrins α4ß7 and αEß7, blocking interaction with their ligands. These integrins play key roles in immune cell homing to and retention in mucosal sites, and are associated with chronic inflammatory diseases of the gastrointestinal tract. The goal of this study was to evaluate the mucosal specificity of rhuMAb Beta7. EXPERIMENTAL APPROACH: We assessed the effect of murine anti-Beta7 on lymphocyte homing in mouse models of autoimmune disease. We also compared the effect of rhuMAb Beta7 on circulating mucosal-homing versus peripheral-homing T cells in naïve non-human primates. KEY RESULTS: In cynomolgus monkeys, occupancy of ß7 integrin receptors by rhuMAb Beta7 correlated with an increase in circulating ß7(+) mucosal-homing lymphocytes, with no apparent effect on levels of circulating ß7(-) peripheral-homing lymphocytes. rhuMAb Beta7 also inhibited lymphocyte homing to the inflamed colons of severe combined immunodeficient mice in CD45RB(high) CD4(+) T-cell transfer models. Consistent with a lack of effect on peripheral homing, in a mouse model of experimental autoimmune encephalomyelitis, anti-ß7 treatment resulted in no amelioration of CNS inflammation. CONCLUSIONS AND IMPLICATIONS: The results presented here suggest that rhuMAb Beta7 selectively blocks lymphocyte homing to the gastrointestinal tract without affecting lymphocyte trafficking to non-mucosal tissues. rhuMAb Beta7 provides a targeted therapeutic approach with the potential for a more attractive benefit:risk ratio than currently available inflammatory bowel disease therapies.

Heterocyclic acetamide and benzamide derivatives as potent and selective beta3-adrenergic receptor agonists with improved rodent pharmacokinetic profiles.

A series of amide derived beta(3)-adrenergic receptor (AR) agonists is described. The discovery and optimization of several series of compounds derived from 1, is used to lay the SAR foundation for second generation beta(3)-AR agonists for the treatment of overactive bladder.

L-Arginine promotes angiogenesis in the chronically hypoxic lung: a novel mechanism ameliorating pulmonary hypertension.

Chronic alveolar hypoxia, whether due to residence at high altitude or lung disease, leads to a sustained increase in pulmonary vascular resistance and pulmonary hypertension (PH). Strategies that augment endogenous nitric oxide production or activity, including l-arginine supplementation, attenuate the development of PH. This action has been attributed to inhibition of vessel wall remodeling, thus preventing structural narrowing of the vascular lumen. However, more recent evidence suggests that structural changes are not responsible for the elevated vascular resistance observed in chronic hypoxic PH, calling into question the previous explanation for the action of l-arginine. We examined the effect of dietary l-arginine supplementation on pulmonary vasoconstriction, structurally determined maximum vascular lumen diameter, and vessel length in rats during 2 wk of exposure to hypoxia. l-Arginine attenuated the development of hypoxic PH by preventing increased arteriolar resistance. It did not alter mean maximal vascular lumen diameter, nor did it augment nitric oxide-mediated vasodilatation, in chronically hypoxic lungs. However, the total length of vessels within the gas exchange region of the hypoxic lungs was significantly increased after l-arginine supplementation. These findings suggest that dietary l-arginine ameliorated hypoxic PH, but not by an effect on the structurally determined lumen diameter of pulmonary blood vessels. l-Arginine enhanced angiogenesis in the hypoxic pulmonary circulation, which may attenuate hypoxic PH by producing new parallel vascular pathways through the lung.

Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children.

BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a benign self-limiting condition confined to the skin and subcutaneous tissue. However, the course of the disease is unpredictable and severe functional and cosmetic disability may result. Drug treatment with systemic corticosteroids in combination with methotrexate has been reported to be beneficial in LS, but data in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of systemic corticosteroids in combination with methotrexate in children with LS. METHODS: Treatment and outcome of 34 patients with LS were retrospectively analysed. Pulsed intravenous methylprednisolone was given, followed by oral prednisolone on a reducing regimen and maintenance treatment with methotrexate. We assessed treatment outcome clinically and by thermography and monitored adverse events. RESULTS: From the onset of treatment, the disease stopped progressing in 94% of the patients. All patients demonstrated significant clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%) patients therapy was discontinued when the disease was considered to be inactive clinically; however, seven (44%) of the 16 developed a relapse, necessitating repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34 patients had completely inactive disease. Observed adverse events were moderate and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest that systemic corticosteroids and methotrexate in combination are beneficial and well tolerated in the treatment of children with LS. Because of the risk of relapse after discontinuing therapy, long-term monitoring is mandatory.

Trisomy of chromosome 18 in the baboon (Papio hamadryas anubis).

Trisomy 18 is usually a lethal chromosomal abnormality and is the second most common autosomal trisomy in humans, with an incidence of 1:8000 live births. It is commonly associated with abnormalities of the lower and upper extremities, having the frequency of 95% and 65%, respectively. A newborn female olive baboon (Papio hamadryas anubis) was diagnosed with intrauterine growth retardation and severe arthrogryposis-like congenital joint deformities. Cytogenetic analysis including G-banding and fluorescence in situ hybridization (FISH) revealed that the congenital abnormalities were associated with chromosomal mosaicism for trisomy 18. Genetic analysis with microsatellites from chromosome 18 confirmed the maternal origin of the extra chromosome 18. This is the first report of trisomy 18 in the baboon, which may be a promising animal model of human disease.

B-cell subsets in blood and lymphoid organs in Macaca fascicularis.

BACKGROUND: Cynomolgus monkeys (Macaca fascicularis) are widely used animal models in biomedical research. However, the phenotypic characteristics of cynomolgus monkey (CM) B cells in peripheral blood (PB) and lymphoid organs are poorly understood. METHODS: FACS analyses of PB-, spleen-, lymph node (LN)-, and bone marrow (BM)-derived B cells were performed. RESULTS: CM peripheral blood B cells have a smaller fraction of CD27(-) (naive) cells ( approximately 40%), as compared to human blood samples ( approximately 70%). Similar to humans, an early activation marker, CD23, is expressed more on CD27(-) CM naive B cells, as compared to CD27(+) B cells. The mean fraction of B cells exhibiting a memory phenotype is similar to that seen in human blood. Unlike humans, CM blood contains a subset of CD20(++)CD80(+)CD21(-)IgM(+/-)CD27(+)CD19(+)FSC(++)BAFF-R(low) B cells that are likely of germinal center origin. Thus, CM blood contains (i) a higher percentage of B cells that express the co-stimulatory molecule CD80, and (ii) a lower fraction of B cells that are CD21(+), as compared to human blood. Due to the relative paucity of information on B-cell subsets in organs of healthy humans, a direct comparison between human and CM lymphoid organ data is limited. The fraction of CD27(+) and CD23(+) B cells appears to be similar, while the fraction of CD80(+) B cells appears to be higher than that seen in human lymphoid organs. CM spleens and to some extent lymph nodes have a distinct subset of CD21(++) cells that are also CD80(+/-)CD23(low)IgM(++)CD27(+/-)FSC(++). This subset is phenotypically similar to the marginal zone B cells present in human spleen and LN samples. We also provide detailed analyses on the fraction of lymphoid organ B cells that express CD21, CD23, CD32, and/or CD80 B-cell markers. CONCLUSIONS: In general, cynomolgus monkey B-cell subsets are similar to those seen in humans, as well as to those seen in other nonhuman primates. However, there are some clear differences between human and cynomolgus monkey B-cell subsets. These findings have direct implications for a variety of in vivo studies in cynomolgus monkeys, ranging from basic research on primate B-cell differentiation to models of infectious diseases and trials of new B-cell targeting therapeutic agents.