What supports and services post COVID-19 do children with disabilities and their parents need and want, now and into the future?

Introduction: Children and youth with disabilities and special healthcare needs, and their families, have been uniquely affected by the COVID-19 pandemic. However, the voices of children themselves are still not well represented in the existing literature. Methods: This qualitative descriptive study used a combination of visual methods and interviews to learn about the experiences of Canadian children with disabilities (n=18) and their parents (n=14) during the COVID pandemic and into the post-pandemic period. Data collection was carried out between January and July 2023. The aim was to identify the supports and services children and families need at present and moving forward. Results: Families' pandemic experiences were complex and nuanced. For many, the pandemic complicated and disrupted everyday activities and supports. These disruptions were largely buffered by parents. However, some families also identified unexpected benefits. Key themes pertaining to present and future needs included the need for services that are flexible; consistent; conducive to relationship-building; comprehensive; coordinated across sectors; and designed to support the needs of the whole family. Discussion: Implications for policy and practice are outlined.

The influence of pain, kinesiophobia and psychological comorbidities on the accuracy of rating of perceived exertion in UK military spinal rehabilitation.

INTRODUCTION: Chronic low back pain (CLBP) is a leading cause of disability in the UK Military. Pain and psychological comorbidities have been reported to influence the rating of perceived exertion (RPE). Exercise rehabilitation can be monitored using RPE; however, the accuracy of RPE in inpatient CLBP rehabilitation is unknown. METHODS: A prospective cohort correlation study of 40 UK Military inpatients with CLBP was completed. Disability (ODI), kinesiophobia (TSK), anxiety (GAD-7) and depression (PHQ-9) were subjectively reported at the beginning and end of a 3 week intervention. Pain (VAS) and HR were recorded in the first aerobic exercise (AE) session (T1) and the final aerobic exercise session (T2). RPE was reported for each AE session. RESULTS: At T1, a positive correlation was observed between RPE accuracy (-7.2±20.9), and pre-exercise pain (2.7 mm ±1.6 mm) (p>0.001) and ODI (31.0±16.9) (p>0.05), and a negative relationship between RPE accuracy and average HR (135 bpm ±22 bpm) (p>0.001) was observed. At T2, there was no significant correlation between RPE accuracy (-4.4±22.6) and pre-exercise pain (2.8 mm ±1.6 mm) or ODI (34.0±16.5) (p>0.05). The strong negative relationship between RPE accuracy and average HR (137 bpm ±20 bpm) remained at T2. Improved RPE accuracy over the 3-week rehabilitation programme was correlated to the change in average HR (r=-0.314, p<0.05). CONCLUSIONS: Comorbidities may negatively affect RPE accuracy in CLBP, but the magnitude of the influence reduces over intensive rehabilitation.

Evaluation of a comprehensive diabetic foot ulcer care quality model.

AIMS: Diabetes-related amputations are typically preceded by a diabetic foot ulcer (DFU) but models to assess the quality of care are lacking. We investigated a model to measure inpatient and outpatient quality. METHODS: Cohort study among adults hospitalized with a DFU to a safety-net hospital during 2016. We measured adherence to DFU-related quality metrics based on guidelines during and 12 months following hospitalization. Inpatient metrics included ankle-brachial index measurement during or 6 months prior to hospitalization, receiving diabetes education and a wound offloading device prior to discharge. Outpatient metrics included wound care ≤30 days of discharge, in addition to hemoglobin A1c (HbA1c) ≤8%, tobacco cessation, and retention in care (≥2 clinic visits ≥90 days apart) 12 months following discharge. RESULTS: 323 patients were included. Regarding inpatient metrics, 8% had an ankle brachial index measurement, 37% received diabetes education, and 20% received offloading prior to discharge. Regarding outpatient metrics, 33% received wound care ≤30 days of discharge. Twelve months following discharge, 34% achieved a HbA1c ≤8%, 13% quit tobacco, and 52% were retained in care. Twelve-month amputation-free survival was 71%. CONCLUSIONS: Our model demonstrated large gaps in DFU guideline-adherent care. Implementing measures to close these gaps could prevent amputations.

Mycobacterium avium paratuberculosis infection of calves - The impact of dam infection status.

Johne's disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic condition of dairy cattle, and is endemic in the UK. Lack of understanding of the relative importance of different transmission routes reduces the impact of control scheme recommendations. The long incubation period for Johne's disease makes evaluation of control schemes difficult, and so this long-term cohort study offers a rare and valuable insight into the disease epidemiology. A longitudinal study was carried out following a cohort of 440 UK dairy cows in 6 herds recruited in 2012-2013. Individuals entering the milking herd were routinely monitored for the presence of MAP using quarterly milk ELISA testing. Using a Cox proportional-hazards regression model the relationship between time until first detection of infection and dam MAP status was investigated. We then compared the magnitude of the effect of dam status with that of other risk factors in order to understand its relative importance. Dam status was found to be the only observed factor that was significantly associated with time to an individual testing MAP-positive (p = 0.012). When compared to negative dams, we found a marginally significant effect of having a positive dam at time of calving, that increased the hazard of an individual testing positive by a factor of 2.6 (95% confidence interval: 0.89-7.79, p = 0.081). Further positive associations were found with dams becoming positive after the birth of the subject; a dam seroconverting within 12 months post parturition being associated with a 3.6 fold increase in hazard (95% confidence interval: 1.32-9.77, p = 0.013), and dams seroconverting more than a year after calving increased the hazard by a factor of 2.8 (95% confidence interval: 1.39-5.76, p = 0.004). These results suggest that cows may be transmitting MAP to their offspring at an earlier stage than had previously been thought, and so raise important questions about how this transmission may be occurring. The results of the study may have important practical implications for the management on-farm of the offspring of MAP-positive animals, with the potential to vastly reduce the time required to eliminate this chronic disease.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions.

OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

The time course of adaptations in thermoneutral maximal oxygen consumption following heat acclimation.

PURPOSE: This study investigated the effects of a 10-day heat acclimation (HA) programme on the time course of changes in thermoneutral maximal oxygen uptake ([Formula: see text]O2max) during and up to 10 days post-HA. METHODS: Twenty-two male cyclists were assigned to a HA or control (Con) training group following baseline ramp tests of thermoneutral [Formula: see text]O2max. Ten days of fixed-intensity (50% baseline [Formula: see text]O2max) indoor cycling was performed in either ~ 38.0 °C (HA) or ~ 20 °C (Con). [Formula: see text]O2max was re-tested on HA days 5, 10 and post-HA days 1, 2, 3, 4, 5 and 10. RESULTS: [Formula: see text]O2max initially declined across time in both groups during training (P < 0.05), before increasing in the post-HA period in both groups (P < 0.05). However, [Formula: see text]O2max was higher than control by post-HA day 4 in the HA group (P = 0.046). CONCLUSIONS: The non-linear time course of [Formula: see text]O2max adaptation suggests that post-testing should be performed 96-h post-training to identify the maximal change for most individuals. In preparation for training or testing, athletes can augment their aerobic power in thermoneutral environments by performing 10 days HA, but the full effects will manifest at varying stages of the post-HA period.

An improved treatment planning and quality assurance process for Collaborative Ocular Melanoma Study eye plaque brachytherapy.

PURPOSE: To develop a treatment planning platform for episcleral Collaborative Ocular Melanoma Study plaque therapy in an established treatment planning software and to improve an existing quality assurance (QA) process for nonuniformly loaded plaques that measures air kerma strengths (AKSs) and loading profile. MATERIALS AND METHODS: Treatment planning is performed in Pinnacle using scripts that let the planner choose plaque size and notching. Scripts load seed positions for each plaque and five source groups corresponding to available stock seeds that can be placed into each seed position. Contours are loaded that display the model eye and the plaque itself. Plaque QA is performed using a modification of our previous pinhole apparatus by replacing x-ray film exposure with an optical camera and scintillating film system. The captured image is processed to remove background and to correct the intensity of seeds on the plaque periphery. Measured total optical counts provide an estimate of total plaque AKS. RESULTS: Treatment planning of eye plaques using Pinnacle, in conjunction with our stock inventory of seeds, is established as standard practice at our center. Planned plaques can vary from uniformly loaded to asymmetrically loaded notched plaques. Using the optical camera system for assessment of the seed loadings has decreased QA time from 40 min/plaque to 10 min/plaque. Total AKS of each plaque can be measured using the optical camera with an accuracy of 10%. CONCLUSIONS: Treatment planning is performed on a Health Canada-approved software that accommodates nonuniform plaque loading. Optical imaging of the plaque provides absolute total AKS and the relative seed arrangement in the plaque.

Interface pressure, perceptual, and mean arterial pressure responses to different blood flow restriction systems.

This study examined the cuff to limb interface pressure during blood flow restriction (BFR), and the perceptual and mean arterial pressure responses, in different BFR systems. Eighteen participants attended three experimental sessions in a randomised, crossover, counterbalanced design. Participants underwent inflations at 40% and 80% limb occlusive pressure (LOP) at rest and completed 4 sets of unilateral leg press exercise at 30% of one repetition maximum with BFR at 80% LOP. Different BFR systems were used each session: an automatic rapid-inflation (RI), automatic personalized tourniquet (PT) and manual handheld pump and sphygmomanometer (HS) system. Interface pressure was measured using a universal interface device with pressure sensors. Perceived exertion and pain were measured after each set, mean arterial pressure (MAP) was measured pre-, 1-minute post- and 5-minutes post-exercise. Interface pressure was lower than the set pressure in all BFR systems at rest (P < .05). Interface pressure was, on average, 10 ± 8 and 48 ± 36 mm Hg higher than the set pressure in the RI and HS system (P < .01), with no differences observed in the PT system (P > .05), during exercise. Pain and exertion were greater in sets 3 and 4 in the RI and HS system compared to the PT system (P < .05). MAP was higher in the RI and HS system compared to the PT system at 1-minute and 5-minutes post-exercise (P < .05). BFR systems applying higher pressures amplify mean arterial pressure and perceptual responses. Automatic BFR systems appear to regulate pressure effectively within an acceptable range during BFR exercise.

A tale of two countries: all-cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada.

OBJECTIVES: We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. METHODS: Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. RESULTS: A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). CONCLUSIONS: Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission.

A systematic review and meta-analysis of the post-operative adverse effects associated with mosquito net mesh in comparison to commercial hernia mesh for inguinal hernia repair in low income countries.

PURPOSE: Abdominal wall hernia is a common surgical condition, with more than 20 million estimated to be repaired each year. Mesh repair is the standard for most repairs; however, the mesh material itself may be a barrier to care, the cost prohibitively high for some populations and healthcare systems. The aim of this systematic review and meta-analysis was to produce a pooled comparison between the adverse event rate associated with mosquito net mesh and commercial hernia mesh. METHODS: A systematic review was carried out in accordance with PRISMA guidelines. PubMed, Ovid Embase/Medline, SCOPUS, Web of Science and the Cochrane library were searched. In addition, the ISRCTN register, ClinicalTrials.gov, ICTR Platform and EU Clinical Trials Register were searched. RESULTS: Five randomised controlled trials (RCTs) were identified. The RCTs were deemed to have similar sample populations after inspection of their sample parameters. Therefore, the adverse effects were compared individually (reoccurrence, haematoma, seroma, infection, and serous discharge) and pooled. A total of 313 mosquito net meshes were included in the study, there was no significant difference between the intervention and control groups for pooled adverse effects or individually. CONCLUSIONS: There is not a significant difference between the commercial mesh group and the mosquito net mesh group for pooled [odds ratio 0.93 (0.63, 1.35)] and individual adverse event rates. However, the 95% confidence intervals of these results are still wide. To reduce this uncertainty sample sizes must increase in future studies.

Exploring the short-term impact of community water fluoridation cessation on children's dental caries: a natural experiment in Alberta, Canada.

OBJECTIVES: Dental caries (tooth decay) is common and can be serious. Dental caries is preventable, and community water fluoridation is one means of prevention. There is limited current research on the implications of fluoridation cessation for children's dental caries. Our objective was to explore the short-term impact of community water fluoridation cessation on children's dental caries, by examining change in caries experience in population-based samples of schoolchildren in two Canadian cities, one that discontinued community water fluoridation and one that retained it. STUDY DESIGN: We used a pre-post cross-sectional design. METHODS: We examined dental caries indices (deft [number of decayed, extracted, or filled primary teeth] and DMFT [number of decayed, missing, or filled permanent teeth]) among grade 2 schoolchildren in 2004/05 and 2013/14 in two similar cities in the province of Alberta, Canada: Calgary (cessation of community water fluoridation in 2011) and Edmonton (still fluoridated). We compared change over time in the two cities. For Calgary only, we had a third data point from 2009/10, and we considered trends across the three points. RESULTS: We observed a worsening in primary tooth caries (deft) in Calgary and Edmonton, but changes in Edmonton were less consistent and smaller. This effect was robust to adjustment for covariates available in 2013/14 and was consistent with estimates of total fluoride intake from biomarkers from a subsample. This finding occurred despite indication that treatment activities appeared better in Calgary. The worsening was not observed for permanent teeth. For prevalence estimates only (% with >0 deft or DMFT), the three data points in Calgary suggest a trend that, though small, appears consistent with an adverse effect of fluoridation cessation. CONCLUSIONS: Our results suggest an increase in dental caries in primary teeth during a time period when community fluoridation was ceased. That we did not observe a worsening for permanent teeth in the comparative analysis could reflect the limited time since cessation. It is imperative that efforts to monitor these trends continue.

Neurotoxins from Clostridium botulinum (serotype A) isolated from the soil of Mendoza (Argentina) differ from the A-Hall archetype and from that causing infant botulism.

The type A of neurotoxin produced by Clostridium botulinum is the prevalent serotype in strains of Mendoza. The soil is the main reservoir for C.botulinum and is possibly one of the infection sources in infant botulism. In this study, we characterized and compared autochthonous C. botulinum strains and their neurotoxins. Bacterial samples were obtained from the soil and from fecal samples collected from children with infant botulism. We first observed differences in the appearance of the colonies between strains from each source and with the A Hall control strain. In addition, purified neurotoxins of both strains were found to be enriched in a band of 300 kDa, whereas the A-Hall strain was mainly made up of a band of ∼600 kDa. This finding is in line with the lack of hemagglutinating activity of the neurotoxins under study. Moreover, the proteolytic activity of C. botulinum neurotoxins was evaluated against SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins from rat brain. It was observed that both, SNAP 25 (synaptosomal-associated protein 25) and VAMP 2 (vesicle-associated membrane protein) were cleaved by the neurotoxins isolated from the soil strains, whereas the neurotoxins from infant botulism strains only induced a partial cleavage of VAMP 2. On the other hand, the neurotoxin from the A-Hall strain was able to cleave both proteins, though at a lesser extent. Our data indicate that the C.botulinum strain isolated from the soil, and its BoNT, exhibit different properties compared to the strain obtained from infant botulism patients, and from the A-Hall archetype.

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors.

In vivo vaccination studies are conventionally conducted in a single mouse strain with results, only reflecting responses to a single immunogenetic background. We decided to examine the immune response to an HIV transgene (gag, pol and nef fusion protein) in 3 strains of mice (CBA, C57BL/6 and BALB/c) to determine the spectrum of responses and in addition to determine whether the serotype of the adenoviral vector used (ChAd3 and ChAd63) impacted the outcome of response. Our results demonstrated that all three strains of mice responded to the transgene and that the magnitude of responses were different between the strains. The C57BL/6 strain showed the lowest range of responses compared to the other strains and, very few responses were seen to the same peptide pool in all three strains of mice. In CBA and BALB/c mice there were significant differences in IFNγ production dependent on the adenoviral vector used. Our results suggest that employing a single strain of mouse may underestimate the efficacy and efficiency of vaccine products.

Reliability of a food menu to measure energy and macronutrient intake in adolescents.

BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the reliability of a food menu to measure energy and macronutrient intake within the laboratory and under real-life conditions in adolescents. SUBJECTS/METHODS: A total of 12 boys and 8 girls (age 14.3 (s.d. 2.4) years, body mass index (BMI) 20.8 (s.d. 4.0) kg/m(2)) completed two identical in-laboratory sessions (ILS) and two out-of-laboratory sessions (OLS). During the ILS, participants had ad libitum access to a variety of foods (74 items in total), which they chose from a menu every hour, for 5 h (0800-1300 h). For the OLS (1300 h until bedtime), the foods were chosen from the same menu at 1300 h and packed into containers to bring home with them. RESULTS: Test-retest analysis of energy and macronutrient intake revealed no significant differences (ILS and OLS). Intra-class correlations ranged between 0.69 and 0.83 (ILS) and between 0.48 and 0.73 (OLS) for energy and macronutrient intake (all P<0.01). Within-subject coefficients of variation ranged between 12.9% and 23.5% for the ILS and between 24.0% and 37.7% for the OLS. Bland-Altman plots showed acceptable agreement. Finally, the food menu was well appreciated by the participants with a 75% appreciation rate on a visual analog scale. CONCLUSIONS: This food menu provides a reasonably reliable measure of energy and macronutrient intake in adolescents, irrespective of sex and BMI, especially inside the laboratory setting. Despite the difficulties in capturing a stable measure of energy intake in research, this tool could be a useful addition to the methods currently used to assess ad libitum food intake in youth.

Analysis of T cell responses to chimpanzee adenovirus vectors encoding HIV gag-pol-nef antigen.

Adenoviruses have been shown to be both immunogenic and efficient at presenting HIV proteins but recent trials have suggested that they may play a role in increasing the risk of HIV acquisition. This risk may be associated with the presence of pre-existing immunity to the viral vectors. Chimpanzee adenoviruses (chAd) have low seroprevalence in human populations and so reduce this risk. ChAd3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. Although the route of injection did not influence the magnitude of immune responses to either chAd vector, the dose of vector did. Taken together these results demonstrate that chimpanzee adenoviruses are suitable vector candidates for the delivery of HIV proteins and could be used for an HIV vaccine and furthermore the chAd3 vector produces a broader response to the HIV transgene.

Pharmacological characterization and antidiabetic activity of a long-acting glucagon-like peptide-1 analogue conjugated to an antithrombin III-binding pentasaccharide.

AIMS: To examine the biological characteristics of a novel glucagon-like peptide-1 (GLP-1) conjugate, in which an antithrombin III (ATIII)-binding pentasaccharide is conjugated to d-Ala(8) GLP-1 using a tetraethylene glycol linker. METHODS: We assessed GLP-1 receptor binding, cAMP generation and insulin secretory activity of the GLP-1 conjugate in vitro. Circulating half-life, glucose homeostatic and subchronic therapeutic effectiveness were then examined in vivo. RESULTS: The half-life of the GLP-1 conjugate in mice was ∼11 h. In vitro insulin secretion from clonal ß cells and islets was increased (p < 0.001) by the conjugate. The conjugate had half maximum effective concentration values of 1.3 × 10(-7) and 9.9 × 10(-8) M for displacement of (125) I-GLP-1 in competitive GLP-1 receptor binding and cAMP generation, respectively. Glucose tolerance in normal mice, immediately and 4 h after conjugate injection, resulted in significant (p < 0.001) improvements in blood glucose. These effects persisted for >48 h after administration. Daily treatment (21 days) of high-fat-fed and ob/ob mice with 25 nmol/kg conjugate resulted in significant improvement in glucose tolerance (p < 0.001) and reductions in glycated haemoglobin (HbA1c; p < 0.01) equivalent to or better than with exenatide or liraglutide. Treatment of C57BL/KsJ db/db mice for 15 days with 100 nmol/kg conjugate significantly (p < 0.001) reduced glucose and raised plasma insulin. Oral glucose tolerance was significantly (p < 0.001) improved and both 24-h glucose profile (p < 0.001) and HbA1c levels (p < 0.001) were reduced. Islet size (p < 0.001) and pancreatic insulin content were increased without change of islet cell proliferation or apoptosis. CONCLUSION: These data show that d-Ala(8) GLP-1(Lys(37) ) pentasaccharide exerts significant antidiabetic actions and has a projected pharmacokinetic/pharmacodynamic profile that merits further evaluation in humans for a possible once-weekly dosing regimen.

Natural selection and glucocorticoid physiology.

Glucocorticoid hormones are considered potent modulators of trade-offs between reproduction and survival. As such, selection should affect glucocorticoid physiology, although relatively little is known about how selection may act on glucocorticoid profiles. In general, the evolution of physiology is less studied and less well understood than morphological or life history traits. Here, we used a long-term data set from a population of mountain white-crowned sparrows to estimate natural selection on glucocorticoid profiles. Our study suggests that survival selection favours higher hormone concentrations for multiple components of glucocorticoid physiology (both baseline and stress-induced glucocorticoid levels). Fecundity selection varies depending on the component of hypothalamic-pituitary-adrenal physiology; greater reproductive output was associated with higher baseline glucocorticoid levels, but lower stress-induced glucocorticoid levels. Additionally, the selection gradient was greater for glucocorticoids than for a morphological trait (wing length). These results support the hypothesis that stress-induced glucocorticoids increase survival over reproduction within a wild population (the CORT-trade-off hypothesis). Taken together, these results add to our knowledge of how selection operates on physiological traits and also provide an evolutionary and ecological perspective on several key open issues in the field of glucocorticoid physiology.

Zebrafish (Danio rerio) as a screen for attenuation of Lancefield group C streptococci and a model for streptococcal pathogenesis.

Group C streptococci are highly contagious pyogenic bacteria responsible for respiratory tract, lymph node, urogenital tract, and wound infections. Wild-type strains of Streptococcus equi ssp equi (S. equi) and Streptococcus equi ssp zooepidemicus (S. zoo) as well as a commercially available modified live vaccine strain of S. equi were evaluated for virulence in zebrafish. Survival times, histologic lesions, and relative gene expression were compared among groups. Based on the intramuscular route of infection, significantly shorter survival times were observed in fish infected with wild-type strain when compared to modified live vaccine and S. zoo strains. Histologically, S. zoo-infected fish demonstrated a marked increase in inflammatory infiltrates (predominantly macrophages) at the site of infection, as well as increased cellularity in the spleen and renal interstitium. In contrast, minimal cellular immune response was observed in S. equi-injected fish with local tissue necrosis and edema predominating. Based on whole comparative genomic hybridization, increased transcription of positive acute-phase proteins, coagulation factors, and antimicrobial peptides were observed in S. equi-injected fish relative to S. zoo-injected fish, while mediators of cellular inflammation, including CXC chemokines and granulin, were upregulated in S. zoo-injected fish relative to S. equi-injected fish. In a screen of 11 clinical isolates, S. equi strains with a single nucleotide deletion in the upstream region of szp, a known virulence factor of streptococci, were found to be significantly attenuated in zebrafish. These collective findings underscore the value of the zebrafish as a model of streptococcal pathogenesis.

Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree.

REASONS FOR PERFORMING STUDY: We hypothesised that seasonal pasture myopathy (SPM), which closely resembles atypical myopathy (AM), was caused by ingestion of a seed-bearing plant abundant in autumn pastures. OBJECTIVES: To identify a common seed-bearing plant among autumn pastures of horses with SPM, and to determine whether the toxic amino acid hypoglycin A was present in the seeds and whether hypoglycin metabolites were present in SPM horse serum or urine. METHODS: Twelve SPM cases, 11 SPM pastures and 23 control farms were visited to identify a plant common to all SPM farms in autumn. A common seed was analysed for amino acid composition (n = 7/7) by GC-MS and its toxic metabolite (n = 4/4) identified in conjugated form in serum [tandem mass spectrometry (MS/MS)] and urine [gas chromatography (GC) MS]. Serum acylcarnitines and urine organic acid profiles (n = 7) were determined for SPM horses. RESULTS: Seeds from box elder trees (Acer negundo) were present on all SPM and 61% of control pastures. Hypoglycin A, known to cause acquired multiple acyl-CoA dehydrogenase deficiency (MADD), was found in box elder seeds. Serum acylcarnitines and urine organic acid profiles in SPM horses were typical for MADD. The hypoglycin A metabolite methylenecyclopropylacetic acid (MCPA), known to be toxic in other species, was found in conjugated form in SPM horse serum and urine. Horses with SPM had longer turn-out, more overgrazed pastures, and less supplemental feeding than control horses. POTENTIAL RELEVANCE: For the first time, SPM has been linked to a toxin in seeds abundant on autumn pastures whose identified metabolite, MCPA, is known to cause acquired MADD, the pathological mechanism behind SPM and AM. Further research is required to determine the lethal dose of hypoglycin A in horses, as well as factors that affect annual seed burden and hypoglycin A content in Acer species in North America and Europe.