Patient characteristics affect hip contact forces during gait.

OBJECTIVE: To examine hip contact force (HCF), calculated through multibody modelling, in a large total hip replacement (THR) cohort stratified by patient characteristics such as body mass index (BMI), age and function. METHOD: 132 THR patients undertook one motion capture session of gait analysis at a self-selected walking speed. HCFs were then calculated using the AnyBody Modelling System. Patients were stratified into three BMI groups, five age groups, and finally three functional groups determined by their self-selected gait speed. By means of statistical parametric mapping (SPM), statistical analyses of the 1-dimensional time series were performed to separately evaluate the influence of age, BMI and functionality on HCF. RESULTS: The mean predicted HCFs were comparable to HCFs measured with instrumented prostheses reported in the literature. The SPM analysis revealed a statistically significant positive linear correlation between BMI and HCF, indicating that obese patients are more likely to experience higher HCF during most of the stance phase, while a statistically significant negative correlation with age was found only during the late swing-phase. Patients with higher functional ability exhibited significantly increased peak HCF, while patients with lower functional ability demonstrated lower HCFs overall and a pathological flattening of the typical double hump force profile. CONCLUSION: HCFs experienced at the bearing surface are highly dependent on patient characteristics. BMI and functional ability were determined to have the biggest influence on contact forces. Current preclinical testing standards do not reflect this.

AAVMC Internship Program Guidelines 2018.

Veterinary internships are common 1-year post-graduate clinical training programs that are offered both at veterinary colleges and in private practice settings. To promote the quality of these training programs, the American Association of Veterinary Medical Colleges (AAVMC) charged a working group to develop these internship guidelines, which were approved by the AAVMC in 2018 and have also been endorsed by the American Association of Veterinary Clinicians. These guidelines are intended to be applicable to all internships, in both academic and private practice settings, and they place particular emphasis on three aspects of internship training programs: competency-based education, intern well-being, and program outcome.

Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro.

BACKGROUND: Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. OBJECTIVES: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. STUDY DESIGN: In vitro assay, crossover design, multiple drug testing. METHODS: In vitro modified infectious centre assay using immortalised carotid artery endothelial cells or primary brain endothelial cells with plaque counts per well as outcome. Cells were either anti-inflammatory drug treated or left untreated. RESULTS: Significant reduction of plaque count when cells were treated compared with untreated cells. No dose-dependent effect when drug concentrations were increased to 10× dose. Treatment of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is required for significant plaque count reduction. MAIN LIMITATIONS: In vitro study. CONCLUSIONS: Anti-inflammatory drugs decrease infection of endothelial cells likely by reducing contact between EHV-1 infected PBMC and endothelial cells in vitro. The role of adhesion molecules in this process needs further investigation. In vitro results suggest anti-inflammatory drug therapy during EHV-1 infection and viraemia in horses could be clinically relevant.

A comparative study of tracheal diameter in Caucasian and Chinese patients.

Ethnicity may be considered a factor when considering what size endotracheal tube to insert. In particular it has been suggested that Chinese patients have a smaller tracheal diameter, justifying the selection of smaller endotracheal tubes. We systematically evaluated transverse tracheal diameters in Chinese and Caucasian patients, utilising archived computer tomography images. A convenience sample of 100 Caucasian patients from Australia was compared with 100 Chinese patients from Hong Kong. Patients over 18 years of age who had undergone a computerised tomography scan of the neck and thorax, and also had accurate body height and weight recorded, were studied. The mean transverse diameter of the trachea measured at three levels was similar between the Chinese and Caucasian patients. At the narrowest measurement point, the immediate subcricoid transverse diameter, the unadjusted mean difference between male Chinese and Caucasian patients was small (1 mm, standard deviation 0.83 mm, P=0.01), and similarly small between female Chinese and Caucasian patients (1.5 mm, standard deviation 0.8 mm, P <0.01). Multivariate analysis demonstrated only a small influence related to ethnicity (12% relative contribution to the overall variance [R2] of the model), but substantial influence of height (40%) and sex (41%). Our findings do not support the practice of routinely selecting a smaller endotracheal tube size for Chinese patients on the basis that there is a difference related to the Chinese ethnic phenotype. Considerations regarding choice of endotracheal tube size should rather focus on patient sex and height.

Abnormal frontostriatal connectivity in adolescent-onset schizophrenia and its relationship to cognitive functioning.

BACKGROUND: Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is hypothesised, in part, to reflect functional dysconnectivity between the frontal cortex and the striatum, although structural abnormalities consistent with this hypothesis have not yet been demonstrated in adolescence. OBJECTIVE: To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS. DESIGN: A MRI volumetric and diffusion tensor imaging study. PARTICIPANTS: Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects. OUTCOME MEASURES: Using probabilistic tractography, cortical regions with the highest connection probability for each striatal voxel were determined, and correlated with IQ and specific cognitive functions after co-varying for age and sex. Fractional anisotropy (FA) from individual tracts was a secondary measure. RESULTS: Bayesian Structural Equation modeling of FA from 12 frontostriatal tracts showed processing speed to be an intermediary variable for cognition. AOS patients demonstrated generalised cognitive impairment with specific deficits in verbal learning and memory and in processing speed after correction for IQ. Dorsolateral prefrontal cortex connectivity with the striatum correlated positively with these measures and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdalohippocampal complex, right anterior cingulate cortex, left medial orbitofrontal cortex and right dorsolateral prefrontal cortex. CONCLUSIONS: Frontostriatal dysconnectivity in large WM tracts that can explain core cognitive deficits are evident during adolescence. Processing speed, which is affected by alterations in WM connectivity, appears an intermediary variable in the cognitive deficits seen in schizophrenia.

Detection of bacteraemia and host response in healthy neonatal foals.

REASONS FOR PERFORMING THE STUDY: Neonatal sepsis is a common problem in foals and is a primary cause of death in the post natal period. Transient bacteraemia and subsequent host responses have not been described in the equine neonate. OBJECTIVES: The primary objective of this study was to determine if transient bacteraemia occurs in foals within the first 72 h of life. Additional objectives included description of bacterial organisms associated with transient bacteraemia and concurrent cytokine gene expression in healthy foals. STUDY DESIGN: Prospective observational study in healthy foals. METHODS: Blood was aseptically collected for bacterial culture from observed spontaneously born foals at birth and 1, 2, 3, 4, 8, 12, 24, 48 and 72 h following birth. Samples taken at birth, 4, 12, 24, 48 and 72 h were analysed for interferon gamma (IFNγ), interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10, IL-18 and monocyte chemotactic protein 1 (MCP1) cytokine gene expression quantified by RT-PCR. RESULTS: Bacteria were cultured from 9 of 70 samples submitted for blood culture. The positive samples were from 4 of the 7 foals, all of which remained healthy throughout and subsequent to the study. All positive blood cultures were from blood samples obtained at 12 h of age or earlier and IL-10 elevation coincided with positive blood cultures in healthy foals. Cytokine gene expression fluctuated with age. CONCLUSIONS: Positive blood cultures suggest transient bacteraemia may occur in healthy foals early in the post natal period. Age corrected normal values may be necessary to interpret cytokine concentration in diseased populations.

Plasma D-dimer concentrations during experimental EHV-1 infection of horses.

BACKGROUND: Central nervous system blood vessel thrombosis is a part of the pathogenesis of equid herpesvirus-associated myeloencephalopathy (EHM). D-dimers (DD) are stable breakdown products of cross-linked fibrin, and increased DD-plasma concentrations could reflect the degree of systemic coagulation during EHV-1 infection. HYPOTHESIS: We hypothesized that blood DD concentrations will be increased during periods of EHV-1 fever and viremia, reflecting an activated coagulation cascade with fibrinolysis. ANIMALS: Twenty-eight equids were infected with EHV-1 in 3 experimental infection studies. Three (uninfected) horses were included in a separate study to evaluate methodology for DD concentration measurements. METHODS: Clinical data and quantitative viremia were evaluated, and DD concentrations were measured in blood samples on the day before the infection and during days 1-12 postchallenge. Uninfected horses were sampled every 3 hours for 48 hours. Logistic and linear regression was used to investigate the potential association between the fever and viremia with the presence or absence of DD concentrations in peripheral blood. RESULTS: DD concentrations were increased for 1-8 days in the majority of infected animals. Both viremia (odds ratio [OR] 6.3; 95% confidence interval [CI] 3.4-11.8; P = .0013) and fever (OR 4.9; CI 2.3-10.1; P = .001) were strongly associated with the likelihood of detecting DD in peripheral blood. CONCLUSIONS AND CLINICAL IMPORTANCE: EHV-1 viremia is associated with increases in DD concentration in horses and ponies. This indicates that EHV-1 viremia can lead to an activation of coagulation and fibrinolysis.

Fiber type composition of the architecturally distinct regions of human supraspinatus muscle: a cadaveric study.

The human supraspinatus muscle is clinically important as it is frequently injured in older adults and the elderly. We have previously shown that the supraspinatus has a complex architecture with two distinct regions each consisting of three parts. Further we have found dynamic changes in architectural parameters such as fiber bundle length markedly vary between these regions. Fiber types of the supraspinatus have not been thoroughly investigated throughout its volume and are of interest to clinicians treating supraspinatus pathologies. In this study we investigated the distribution of fiber types within the distinct regions and parts of supraspinatus. Samples of supraspinatus were excised from six distinct parts of each muscle from five formalin embalmed specimens (one male, four female; mean age 77±11.1 years) free of tendon pathology. Samples were frozen in liquid nitrogen and then cryosectioned. Serial sections were labeled using immunohistochemical techniques and antibodies against fast or slow myosin heavy chain isoforms. The mean percentage of Type I (slow) fibers ranged from 56.73% to 63.97%. Results demonstrated significant variations in fiber type distribution. The middle part of the anterior region has a significantly greater percentage of Type I fibers compared to that of the posterior. The superficial part of the anterior region has a greater percentage of Type II (fast) fibers compared to the middle and deep parts. Findings aid in highlighting the distinct functions of the anterior and posterior regions, and prompt the need to re-evaluate assessment and treatment techniques established on a limited understanding of the fiber type distribution.

Nasal shedding of equine herpesvirus-1 from horses in an outbreak of equine herpes myeloencephalopathy in Western Canada.

BACKGROUND: There is little information on the duration of nasal shedding of EHV-1 from horses with naturally occurring equine herpesvirus myeloencephalopathy (EHM). OBJECTIVES: To evaluate the duration of nasal shedding of EHV-1 in horses affected by EHM. ANIMALS: One hundred and four horses naturally exposed to EHV-1, 20 of which had clinical signs of EHM. METHODS: All horses on affected premises were monitored. Those horses developing EHM were sampled in a longitudinal outbreak investigation. Nasal swabs were collected daily from 16 of 20 horses affected by EHM. A qPCR was performed on 98 of 246 nasal swab samples to determine nasal shedding duration. Historical and clinical information was analyzed to evaluate potential risk factors for developing EHM and duration of shedding during this outbreak. RESULTS: The last day shedding was detected in any horse was Disease Day 9. EHV-1 was detected in two-thirds of horses tested on Disease Days 0-3. The amount of EHV-1 DNA found in nasal swabs varied markedly and was not associated with disease severity or age. The odds of developing EHM were greater for febrile horses (OR = 20.3; 95% CI 3.4-390.3; P = .01) as well as for horses attending the riding clinic (OR = 4.1; 95% CI 0.84-21.65; P = .08). CONCLUSIONS AND CLINICAL IMPORTANCE: Biosecurity measures should be implemented for a minimum of 14 days beyond the onset of clinical signs of EHM. Animal managers cannot rely on the severity of clinical signs to predict the duration of EHV-1 shedding.

Fitting dynamic models with forcing functions: application to continuous glucose monitoring in insulin therapy.

The artificial pancreas is an emerging technology to treat type 1 diabetes (T1D). It has the potential to revolutionize diabetes care and improve quality of life. The system requires extensive testing, however, to ensure that it is both effective and safe. Clinical studies are resource demanding and so a principle aim is to develop an in silico population of subjects with T1D on which to conduct pre-clinical testing. This paper aims to reliably characterize the relationship between blood glucose and glucose measured by subcutaneous sensor as a major step towards this goal. Blood-and sensor-glucose are related through a dynamic model, specified in terms of differential equations. Such models can present special challenges for statistical inference, however. In this paper we make use of the BUGS software, which can accommodate a limited class of dynamic models, and it is in this context that we discuss such challenges. For example, we show how dynamic models involving forcing functions can be accommodated. To account for fluctuations away from the dynamic model that are apparent in the observed data, we assume an autoregressive structure for the residual error model. This leads to some identifiability issues but gives very good predictions of virtual data. Our approach is pragmatic and we propose a method to mitigate the consequences of such identifiability issues.

Effect of long-term fluticasone treatment on immune function in horses with heaves.

BACKGROUND: Corticosteroids currently are the most effective pharmacological treatment available to control heaves in horses. Systemically administered corticosteroids have been shown to alter immune response in horses, humans, and other species. Aerosolized administration theoretically minimizes systemic adverse effects, but the effect of inhaled corticosteroids on immune function has not been evaluated in horses. OBJECTIVES: To evaluate the effects of prolonged administration of inhaled fluticasone on the immune system of heaves-affected horses. ANIMALS: Heaves-affected horses were treated with inhaled fluticasone (n = 5) for 11 months or received environmental modifications only (n = 5). METHODS: Prospective analysis. Clinical parameters and CBC, lymphocyte subpopulations and function, and circulating neutrophil gene expression were sequentially measured. Primary and anamnestic immune responses also were evaluated by measuring antigen-specific antibodies in response to vaccination with bovine viral antigen and tetanus toxoid, respectively. RESULTS: No clinical adverse effects were observed and no differences in immune function were detected between treated and untreated horses. CONCLUSIONS AND CLINICAL IMPORTANCE: The treatment of heaves-affected horses with inhaled fluticasone at therapeutic dosages for 11 months has no significant detectable effect on innate and adaptive (both humoral and cell-mediated) immune parameters studied. These results suggest that prolonged administration of fluticasone would not compromise the systemic immune response to pathogens nor vaccination in adult horses.

Cardiac troponin I concentrations in ponies challenged with equine influenza virus.

BACKGROUND: Myocarditis is thought to occur secondary to equine influenza virus (EIV) infections in horses, but there is a lack of published evidence. HYPOTHESIS/OBJECTIVES: We proposed that EIV challenge infection in ponies would cause myocardial damage, detectable by increases in plasma cardiac troponin I (cTnI) concentrations. ANIMALS: Twenty-nine influenza-naïve yearling ponies: 23 were part of an influenza vaccine study (11 unvaccinated and 12 vaccinated), and were challenged with 108 EID50 EIV A/eq/Kentucky/91 6 months after vaccination. Six age-matched healthy and unvaccinated ponies concurrently housed in a separate facility not exposed to influenza served as controls. METHODS: Heparinized blood was collected before and over 28 days after infection and cTnI determined. Repeated measures analysis of variance, chi-square, or clustered regression analyses were used to identify relationships between each group and cTnI. RESULTS: All EIV-infected ponies developed clinical signs and viral shedding, with the unvaccinated group displaying severe signs. One vaccinated pony and 2 unvaccinated ponies had cTnI greater than the reference range at 1 time point. At all other times, cTnI was < 0.05 ng/mL. All control ponies had normal cTnI. There were no significant associations between cTnI and either clinical signs or experimental groups. When separated into abnormal versus normal cTnI, there were no significant differences among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated no evidence of severe myocardial necrosis secondary to EIV challenge with 108 EID50 EIV A/eq/Kentucky/91 in these sedentary ponies, but transient increases in cTnI suggest that mild myocardial damage may occur.

Infection of central nervous system endothelial cells by cell-associated EHV-1.

Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late-term abortions and equine herpesvirus myeloencephalitis (EHM). Our understanding of EHM pathogenesis is limited except for the knowledge that EHV-1 infected, circulating peripheral blood mononuclear cells (PBMC) transport virus to the central nervous system vasculature causing endothelial cell infection leading to development of EHM. Our objective was to develop a model of CNS endothelial cell infection using EHV-1 infected, autologous PBMC. PBMCs, carotid artery and brain endothelial cells (EC) from 14 horses were harvested and grown to confluency. PBMC or ConA-stimulated PBMCs (ConA-PBMCs) were infected with EHV-1, and sedimented directly onto EC monolayers ('contact'), or placed in inserts on a porous membrane above the EC monolayer ('no contact'). Cells were cultured in medium with or without EHV-1 virus neutralizing antibody. Viral infection of ECs was detected by cytopathic effect. Both brain and carotid artery ECs became infected when cultured with EHV-1 infected PBMCs or ConA-PBMCs, either in direct contact or no contact: infection was higher in carotid artery than in brain ECs, and when using ConA-PBMCs compared to PBMCs. Virus neutralizing antibody eliminated infection of ECs in the no contact model only. This was consistent with cell-to-cell spread of EHV-1 infection from leucocytes to ECs, demonstrating the importance of this mode of infection in the presence of antibody, and the utility of this model for study of cellular interactions in EHV-1 infection of ECs.

Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations during viremia.

Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late term abortions and equine herpesvirus myeloencephalitis (EHM) and remains an important problem in horses worldwide. Despite increasing outbreaks of EHM in recent years, our understanding of EHM pathogenesis is still limited except for the knowledge that a cell-associated viremia in peripheral blood mononuclear cells (PBMCs) is a critical link between primary respiratory EHV-1 infection and secondary complications such as late-term abortion or EHM. To address this question our objective was to identify which PBMC subpopulation(s) are infected during viremia and may therefore play a role in transmitting the virus to the vascular endothelium of the spinal cord or pregnant uterus. PBMCs from 3 groups of animals were collected between days 4 and 9 following experimental infection with EHV-1 strain Findlay/OH03 or strain Ab4. PBMCs were labeled with primary antibodies selective for CD4+ or CD8+ T lymphocytes, B-lymphocytes, or monocytes and positively selected using magnetic bead separation. Cell numbers and EHV-1 genome numbers in each subpopulation were then determined using quantitative PCR for ß-actin and the EHV-1 glycoprotein B, respectively. Viral genomic DNA was found in all PBMC subpopulations; the CD8+ lymphocytes were most frequently positive for viral DNA, followed by B-lymphocytes. These differences were statistically significant in horses infected with the EHV-1 strain Findlay/OH03, and ponies with Ab4. These results differ from what has been reported in in vitro studies, and indicate that different PBMC subpopulations may play different roles in EHV-1 viremia.