A survey of antimicrobial use practices on veal farms in the United States.

Neonatal veal calves are highly susceptible to bacterial diseases. Occasional sub-optimal early-life care and long-distance transportation result in high disease burden and antimicrobial treatment incidence. Nonetheless, judicious use of antimicrobials is necessary to mitigate the animal and human health impacts of antimicrobial resistance. The objective of this cross-sectional study was to use a clinical vignette-based survey approach to evaluate the potential for reduced group or individual therapeutic antimicrobial use. The survey included items probing the adherence to veterinary-written protocols, antimicrobial use (AMU) at the calf- and group-level, and the treatment actions to case vignettes of calf diarrhoea, pneumonia, and navel infection. The survey was mailed to all veal calf producers within two U.S. production companies (n = 32 producers in Company 1; n = 70 producers in Company 2) in February and December 2019, respectively. The overall survey response rate was 36% (21/59). Although 95% of producers reported having veterinary-written treatment protocols for diarrhoea, pneumonia, and navel infection, veal producers infrequently (<50% of the time) referenced these protocols. Veal producers were primarily trained for disease identification and treatment by observing other personnel "on-the-job" (81%). Veal producers reported a high incidence of calf diarrhoea relative to pneumonia and naval infection, a lower percentage (≤40%) of diarrhoea cases being treated individually with antimicrobials. Using clinical vignettes, our results suggest that AMU decisions among veal producers depend on the severity of clinical signs for diarrhoea and pneumonia, while navel infections are often treated with antimicrobials regardless of sign severity. Nearly two-thirds of veal producers reported treating uncomplicated cases of diarrhoea (watery stool with normal body temperature, activity, and appetite), more than previously reported from dairy producers (37.1%). Findings from this survey suggest that calf producer-focused training to guide antimicrobial treatment decisions and improve producer adherence to veterinary-written treatment protocols may have important impacts on judicious antimicrobial use.

Time-dependent and selective microglia-mediated removal of spinal synapses in neuropathic pain.

Neuropathic pain is a debilitating condition resulting from damage to the nervous system. Imbalance of spinal excitation and inhibition has been proposed to contribute to neuropathic pain. However, the structural basis of this imbalance remains unknown. Using a preclinical model of neuropathic pain, we show that microglia selectively engulf spinal synapses that are formed by central neurons and spare those of peripheral sensory neurons. Furthermore, we reveal that removal of inhibitory and excitatory synapses exhibits distinct temporal patterns, in which microglia-mediated inhibitory synapse removal precedes excitatory synapse removal. We also find selective and gradual increase in complement depositions on dorsal horn synapses that corresponds to the temporal pattern of microglial synapse pruning activity and type-specific synapse loss. Together, these results define a specific role for microglia in the progression of neuropathic pain pathogenesis and implicate these immune cells in structural remodeling of dorsal horn circuitry.

Distinct and sex-specific expression of mu opioid receptors in anterior cingulate and somatosensory S1 cortical areas.

ABSTRACT: The anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. Using the Oprm1-mCherry mouse line, we performed selective patch clamp recordings of MOR+ neurons, as well as immunohistochemistry with validated neuronal markers, to determine the identity and laminar distribution of MOR+ neurons in ACC and S1. We found that the electrophysiological signatures of MOR+ neurons differ significantly between these 2 areas, with interneuron-like firing patterns more frequent in ACC. While MOR+ somatostatin interneurons are more prominent in ACC, MOR+ excitatory neurons and MOR+ parvalbumin interneurons are more prominent in S1. Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.

Antimicrobial Use and Resistance in Surplus Dairy Calf Production Systems.

Surplus calves, which consist predominately of male calves born on dairy farms, are an underrecognized source of antimicrobial-resistant (AMR) pathogens. Current production systems for surplus calves have important risk factors for the dissemination of pathogens, including the high degree of commingling during auction and transportation and sometimes inadequate care early in life. These circumstances contribute to an increased risk of respiratory and other infectious diseases, resulting in higher antimicrobial use (AMU) and the development of AMR. Several studies have shown that surplus calves harbor AMR genes and pathogens that are resistant to critically important antimicrobials. This is a potential concern as the resistant pathogens and genes can be shared between animal, human and environmental microbiomes. Although knowledge of AMU and AMR has grown substantially in dairy and beef cattle systems, comparable studies in surplus calves have been mostly neglected in North America. Therefore, the overall goal of this narrative review is to summarize the existing literature regarding AMU and AMR in surplus dairy calf production, highlight the management practices contributing to the increased AMU and the resulting AMR, and discuss potential strategies and barriers for improved antimicrobial stewardship in surplus calf production systems.

Prevalence and Sources of Salmonella Lymph Node Infection in Special-Fed Veal Calves.

ABSTRACT: Peripheral lymph nodes (LNs) have been implicated as potential contaminants of ground beef, yet the source and timing of Salmonella LN infection in cattle is still unclear, limiting targeted intervention. The aim of this study was to leverage the vertical integration of special-fed veal production to identify preharvest environmental exposures, specifically in livestock trailers and harvest facility holding pens where calves spend 30 min to 4 h, that result in Salmonella LN infection. Ten cohorts of 80 to 82 veal calves were followed through the harvest process, and environmental samples were collected in barns, trailers, and holding pens. Mesenteric LNs from 35 calves were collected at harvest, and 25 prefemoral LNs per cohort were pooled. Within the same cohort, for 12 samples for which the serovar of the environmental and calf LN Salmonella isolates matched, the isolates were submitted for whole genome sequencing to determine whether environmental exposure resulted in LN infection. Cohort-level Salmonella mesenteric LN prevalence ranged from 0% (0 of 35 samples) to 80% (28 of 35 samples), and pooled prefemoral LNs were positive for Salmonella in 3 of the 10 cohorts. Salmonella prevalence in samples from barns, livestock trailers, and harvest facility holding pens was 22% (13 of 60 samples), 74% (59 of 80 samples), and 93% (74 of 80 samples), respectively. Some environmental and LN isolates were multidrug resistant. Four instances of Salmonella transmission from trailers and/or holding pens to calf LNs were supported by sequence data. Salmonella serovars Agona, Give, and Muenster were identified in transmission events. One instance of transmission from the livestock trailer, two instances from holding pens, and one instance from either trailer or holding pens were observed. Further research is needed to evaluate the extent of environmental Salmonella transmission in cattle and to determine whether targeted interventions in trailers or holding pens could reduce novel Salmonella LN infection in veal calves before harvest.

Perspectives on the Management of Surplus Dairy Calves in the United States and Canada.

The care of surplus dairy calves is a significant issue for the United States and Canadian dairy industries. Surplus dairy calves commonly experience poor welfare as evidenced by high levels of mortality and morbidity, and negative affective states resulting from limited opportunities to express natural behaviors. Many of these challenges are a result of a disaggregated production system, beginning with calf management at the dairy farm of origin and ending at a calf-raising facility, with some calves experiencing long-distance transportation and commingling at auction markets or assembly yards in the interim. Thus, the objectives of this narrative review are to highlight specific challenges associated with raising surplus dairy calves in the U.S. and Canada, how these challenges originate and could be addressed, and discuss future directions that may start with refinements of the current system, but ultimately require a system change. The first critical area to address is the management of surplus dairy calves on the dairy farm of origin. Good neonatal calf care reduces the risk of disease and mortality, however, many dairy farms in Canada and the U.S. do not provide sufficient colostrum or nutrition to surplus calves. Transportation and marketing are also major issues. Calves can be transported more than 24 consecutive hours, and most calves are sold through auction markets or assembly yards which increases disease exposure. Management of calves at calf-raisers is another area of concern. Calves are generally housed individually and fed at low planes of nutrition, resulting in poor affective states and high rates of morbidity and mortality. Strategies to manage high-risk calves identified at arrival could be implemented to reduce disease burden, however, increasing the plane of nutrition and improving housing systems will likely have a more significant impact on health and welfare. However, we argue the current system is not sustainable and new solutions for surplus calves should be considered. A coordinated and holistic approach including substantial change on source dairy farms and multiple areas within the system used to market and raise surplus dairy calves, can lead to more sustainable veal and beef production with improved calf outcomes.

A focus group study of Ontario dairy producer perspectives on neonatal care of male and female calves.

Providing optimal calf care remains a challenge on many dairy farms and has important implications for the future health, welfare, and productivity of male and female calves. Recent research suggests that male dairy calves receive a lower quality of care early in life than female calves, but further investigation is required to determine the factors that influence this disparity. The objectives of this study were to understand dairy producer perspectives on neonatal calf care practices and explore differences between male and female calf care. Overall, 23 dairy producers in Ontario, Canada, participated in 4 focus groups about calf care practices that were recorded and evaluated qualitatively using thematic analysis. Major barriers for good calf care included lack of knowledge about the best management practices for calf care and the prioritization of farm resources toward the milking herd. Some producers also noted that farm infrastructure (particularly during challenging weather) and employee training were important limitations. The economic cost of providing good neonatal calf care was important primarily for male calves and acted as a motivation or a barrier depending on the producer's beliefs about calf care and how they chose to market their calves. The primary source of knowledge producers used to develop calf care practices was their own experience, although many also relied on dairy-industry advisors, most often veterinarians. Producers were motivated by social norms, along with intrinsic pride and obligation to provide good calf care, and these motives were influenced by their emotional state. Producers expressed beliefs about which aspects of calf care are most important-notably colostrum management-and appreciated simple and economical solutions to calf-rearing challenges. Calf care practices were varied, and we identified a diversity of knowledge, motivations, and barriers to adopting best management practices, which sometimes differed between male and female calves. Some producers said that they did not know what happened to their male calves after they left the farm and tended to prioritize the care of female over male calves in subtle ways, such as less timely provision of colostrum. The infrastructure investment and other costs associated with caring for male calves often limited their care, but producers were still motivated to provide adequate care for male calves. These findings represent potential targets for additional research and intervention strategies to improve calf care practices on dairy farms.

Dorsal horn disinhibition and movement-induced behaviour in a rat model of inflammatory arthritis.

OBJECTIVES: Alterations beyond joint inflammation such as changes in dorsal horn (DH) excitability contribute to pain in inflammatory arthritis (IA). More complete understanding of specific underlying mechanisms will be important to define novel targets for the treatment of IA pain. Pre-clinical models are useful, but relevant pain assays are vital for successful clinical translation. For this purpose, a method is presented to assess movement-induced pain-related behaviour changes that was subsequently used to investigate DH disinhibition in IA. METHODS: IA was induced by intra-articular injection of complete Freund's adjuvant (CFA) in male rats, and weight distribution was assessed before and after walking on a treadmill. To confirm increased activity in nociception-related pathways, fos expression was assessed in the superficial DH, including in nociceptive neurons, identified by neurokinin 1 (NK1) immunoreactivity, and interneurons. Inhibitory terminal density onto NK1+ neurons was assessed and lastly, a cohort of animals was treated for 3 days with gabapentin. RESULTS: At 4 weeks post-CFA, walking reduced weight distribution to the affected joint and increased DH fos expression, including in NK1+ neurons. Neuronal activity in inhibitory cells and inhibitory terminal density on NK1+ neurons were decreased in CFA-treated animals compared with controls. Treatment with gabapentin led to recovered behaviour and DH neuronal activity pattern in CFA-treated animals. CONCLUSION: We describe an assay to assess movement-induced pain-related behaviour changes in a rodent IA model. Furthermore, our results suggest that disinhibition may contribute to pain related to movement in IA.

Peripheral and central nervous system alterations in a rat model of inflammatory arthritis.

It is consistently reported that in inflammatory arthritis (IA), pain may continue despite well-controlled inflammation, most likely due to interactions between joint pathology and pain pathway alterations. Nervous system alterations have been described, but much remains to be understood about neuronal and central non-neuronal changes in IA. Using a rat model of IA induced by intra-articular complete Freund's adjuvant injection, this study includes a thorough characterization of joint pathology and objectives to identify peripheral innervation changes and alterations in the spinal dorsal horn (DH) that could alter DH excitatory balancing. Male and female rats displayed long-lasting pain-related behavior, but, in agreement with our previous studies, other pathological alterations emerged only at later times. Cartilage vascularization, thinning, and decreased proteoglycan content were not detectable in the ipsilateral cartilage until 4 weeks after complete Freund's adjuvant. Sympathetic and peptidergic nociceptive fibers invaded the ipsilateral cartilage alongside blood vessels, complex innervation changes were observed in the surrounding skin, and ipsilateral nerve growth factor protein expression was increased. In the DH, we examined innervation by peptidergic and nonpeptidergic nociceptors, inhibitory terminal density, the KCl cotransporter KCC2, microgliosis, and astrocytosis. Here, we detected the presence of microgliosis and, interestingly, an apparent loss of inhibitory terminals and decreased expression of KCC2. In conclusion, we found evidence of anatomical, inflammatory, and neuronal alterations in the peripheral and central nervous systems in a model of IA. Together, these suggest that there may be a shift in the balance between incoming and outgoing excitation, and modulatory inhibitory tone in the DH.

Functional differences between neurochemically defined populations of inhibitory interneurons in the rat spinal dorsal horn.

In order to understand how nociceptive information is processed in the spinal dorsal horn we need to unravel the complex synaptic circuits involving interneurons, which constitute the vast majority of the neurons in laminae I-III. The main limitation has been the difficulty in defining functional populations among these cells. We have recently identified 4 non-overlapping classes of inhibitory interneuron, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) and parvalbumin, in the rat spinal cord. In this study we demonstrate that these form distinct functional populations that differ in terms of sst(2A) receptor expression and in their responses to painful stimulation. The sst(2A) receptor was expressed by nearly all of the nNOS- and galanin-containing inhibitory interneurons but by few of those with NPY and none of the parvalbumin cells. Many galanin- and NPY-containing cells exhibited phosphorylated extracellular signal-regulated kinases (pERK) after mechanical, thermal or chemical noxious stimuli, but very few nNOS-containing cells expressed pERK after any of these stimuli. However, many nNOS-positive inhibitory interneurons up-regulated Fos after noxious thermal stimulation or injection of formalin, but not after capsaicin injection. Parvalbumin cells did not express either activity-dependent marker following any of these stimuli. These results suggest that interneurons belonging to the NPY, nNOS and galanin populations are involved in attenuating pain, and for NPY and nNOS cells this is likely to result from direct inhibition of nociceptive projection neurons. They also suggest that the nociceptive inputs to the nNOS cells differ from those to the galanin and NPY populations.