Pharmacokinetics and physiologic/behavioral effects of buprenorphine administered sublingually and intravenously to neonatal foals

Buprenorphine is absorbed following sublingual administration, which would be a low‐stress delivery route in foals. However, the pharmacokinetics/pharmacodynamics are not described in foals. Six healthy foals <21 days of age participated in a blinded, randomized, 3‐period, 5‐sequence, 3‐treatment crossover prospective study. Foals received 0.01–0.02 mg/kg buprenorphine administered SL or IV with an equivalent volume of saline administered by the opposite route. Blood was collected from the cephalic vein for pharmacokinetic analysis. Physiologic parameters (HR, RR, body temperature, GI sounds), locomotion (pedometer), and behavioral data (activity level, nursing time, response to humans) were recorded. Plasma concentration of buprenorphine exceeded a presumed analgesic level (0.6 ng/ml) in five foals in the IV group and one in the SL group but only for a very brief time. Pharmacokinetic analysis following IV administration demonstrated a short elimination half‐life (t_1/2β 1.95 ± 0.7 hr), large volume of distribution (6.46 ± 1.54 L/kg), and a high total clearance (55.83 ± 23.75 ml/kg/min), which differs from adult horses. Following SL administration, maximum concentrations reached were 0.61 ± 0.11 ng/ml and bioavailability was 25.1% ± 10.9%. In both groups, there were minor statistical differences in HR, RR, body temperature, locomotion, and time spent nursing. However, these differences were clinically insignificant in this single dose study, and excitement, sedation, or colic did not occur.     

Influence of landscape structure,topography, and forest type on spatial variation in historical fire regimes,Central Oregon,USA

Context

In the interior Northwest, debate over restoring mixed-conifer forests after a century of fire exclusion is hampered by poor understanding of the pattern and causes of spatial variation in historical fire regimes.

Objectives

To identify the roles of topography, landscape structure, and forest type in driving spatial variation in historical fire regimes in mixed-conifer forests of central Oregon.

Methods

We used tree rings to reconstruct multicentury fire and forest histories at 105 plots over 10,393 ha. We classified fire regimes into four types and assessed whether they varied with topography, the location of fuel-limited pumice basins that inhibit fire spread, and an updated classification of forest type.

Results

We identified four fire-regime types and six forest types. Although surface fires were frequent and often extensive, severe fires were rare in all four types. Fire regimes varied with some aspects of topography (elevation), but not others (slope or aspect) and with the distribution of pumice basins. Fire regimes did not strictly co-vary with mixed-conifer forest types.

Conclusions

Our work reveals the persistent influence of landscape structure on spatial variation in historical fire regimes and can help inform discussions about appropriate restoration of fire-excluded forests in the interior Northwest. Where the goal is to restore historical fire regimes at landscape scales, managers may want to consider the influence of topoedaphic and vegetation patch types that could affect fire spread and ignition frequency.

     

Oncolytic reovirus therapy: Pilot study in dogs with spontaneously occurring tumours

Oncolytic virotherapy is a novel treatment involving replication‐competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 10⁸ to 5.0 × 10⁹ TCID₅₀ given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group‐ Common Terminology Criteria for Adverse Events (VCOG‐CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti‐reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post‐treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well‐tolerated and can be given safely to tumour‐bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours.     

Multilocus-sequence typing analysis reveals similar populations of Streptococcus uberis are responsible for bovine intramammary infections of short and long duration

Multilocus-sequence typing (MLST) was used to analyse Streptococcus uberis isolates from a single herd associated with long duration (50-260 days) and rapidly cleared (less than 1 month) bovine intramammary infections to determine whether the bacterial type had any impact on the duration of infection. Most chronic infections (24 of 33) were due to continuous infection of the mammary quarter with the same sequence type, and infections were found to persist for many months. The remaining quarters were re-infected with a different sequence type within a single lactation. No particular sequence type or clonal complex (lineage) was associated with persisting infections, indicating that the outcome of intramammary infections with S. uberis is more likely to be dependent on host factors than on inter-strain differences. Analysis of these strains alongside others obtained from the same herd at a later date revealed the shift in the predominant genotypes with time.     

Pattern recognition receptors in companion and farm animals - the key to unlocking the door to animal disease?

The innate immune system is essential for host defence and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, such as macrophages and dendritic cells, diverse signalling pathways are activated that combine to define inflammatory responses that direct sterilisation of the threat and/or orchestrate development of the adaptive immune response. Innate immune signalling must be carefully controlled and regulation comes in part from interactions between activating and inhibiting signalling receptors. In recent years, an increasing number of pattern recognition receptors (PRRs), including C-type lectin receptors and Toll-like receptors (TLRs), has been described that participate in innate recognition of microbes, especially through the so called pathogen-associated molecular patterns (PAMPs). Recent studies demonstrate strong interactions between signalling through these receptors. Whereas useful models to study these receptors in great detail in the murine and human system are now emerging, relatively little is known regarding these receptors in companion and farm animals. In this review, current knowledge regarding these receptors in species of veterinary relevance is summarised.     

Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering

Chitosan nanofiber membranes are recognized as functional antimicrobial materials, as they can effectively provide a barrier that guides tissue growth and supports healing. Methods to stabilize nanofibers in aqueous solutions include acylation with fatty acids. Modification with fatty acids that also have antimicrobial and biofilm-resistant properties may be particularly beneficial in tissue regeneration applications. This study investigated the ability to customize the fatty acid attachment by acyl chlorides to include antimicrobial 2-decenoic acid. Synthesis of 2-decenoyl chloride was followed by acylation of electrospun chitosan membranes in pyridine. Physicochemical properties were characterized through scanning electron microscopy, FTIR, contact angle, and thermogravimetric analysis. The ability of membranes to resist biofilm formation by S. aureus and P. aeruginosa was evaluated by direct inoculation. Cytocompatibility was evaluated by adding membranes to cultures of NIH3T3 fibroblast cells. Acylation with chlorides stabilized nanofibers in aqueous media without significant swelling of fibers and increased hydrophobicity of the membranes. Acyl-modified membranes reduced both S. aureus and P. aeruginosa bacterial biofilm formation on membrane while also supporting fibroblast growth. Acylated chitosan membranes may be useful as wound dressings, guided regeneration scaffolds, local drug delivery, or filtration.     

A Community Forestry Model Linking Research,Management, Education,and Stakeholder Engagement: Case Study Results from the Town of Weston,Massachusetts, USA

Forested land in the eastern United States is owned by a complex mix of public and private owners, often with highly varied objectives and uses. There is an increasing trend at local scales of community forestry programs that use community-based decision making to determine what type of management will occur on town-owned forests. Within the suburban town of Weston, Massachusetts, this type of coordinated approach has been ongoing for nearly 4 decades. This article describes the integration of forest ecology and management research, including a forest inventory and long-term monitoring program, to educate townspeople about their forests, engage students in ecological research, and provide data that the town can use to make informed management decisions. This article presents a novel model for a research-based community forestry program, results from the first inventory and plot measurement period, and describes how other towns can use this type of program to supplement existing active forest management, or provide a baseline for future management. Results are applicable to municipalities that own forest land, as well as land trusts or other private entities that wish to manage their forests using a community based forestry model.     

Small Area Estimation of Proportions with Constraint for National Resources Inventory Survey

Motivated by the need to produce small area estimates for the National Resources Inventory survey, we develop a spatial hierarchical model based on the generalized Dirichlet distribution to construct small area estimators of compositional proportions in several mutually exclusive and exhaustive landcover categories. At the observation level, the standard design-based estimators of the proportions are assumed to follow the generalized Dirichlet distribution. After proper transformation of the design-based estimators, beta regression is applicable. We consider a logit mixed model for the expectation of the beta distribution, which incorporates covariates through fixed effects and spatial effect through a conditionally autoregressive process. In a design-based evaluation study, the proposed model-based estimators are shown to have smaller root-mean-square error and relative root-mean-square error than design-based estimators and multinomial model-based estimators. Supplementary materials accompanying this paper appear online.     

Stem growth during seed production in soybean: Implications for pod yield

In soybean (Glycine max (L.) Merr.), stems remain a competitive carbon resource sink during reproduction. Radial stem expansion after termination of axial stem growth requires resources to produce secondary cell walls in secondary vascular tissues. The impact of both the timing and extent of secondary growth in stems on fruit production in soybean is unknown. We hypothesized that cultivars gaining higher amounts of secondary vascular tissues during seed filling would experience lower reproductive output. Four determinate cultivars were grown in a greenhouse and harvested at the beginning and ending of seed filling for biomass determination and tissue composition measurement (ImageJ-Fiji). Cultivar ‘Hanover’ entered seed filling with the lowest amount of secondary phloem. It produced the largest increase in radial stem expansion, largest seeds, and fewest undeveloped (aborted) fruits. The physiological role of active secondary phloem production in stems for seed production in soybean reproduction is unclear. We reject our initial hypothesis and propose that high fitness may require the concomitant growth of vegetative and reproductive organs.