Orexin Facilitates the Peripheral Chemoreflex via Corticotropin-Releasing Hormone Neurons Projecting to the Nucleus of the Solitary Tract.

We previously showed that orexin neurons are activated by hypoxia and facilitate the peripheral chemoreflex (PCR)-mediated hypoxic ventilatory response (HVR), mostly by promoting the respiratory frequency response. Orexin neurons project to the nucleus of the solitary tract (nTS) and the paraventricular nucleus of the hypothalamus (PVN). The PVN contributes significantly to the PCR and contains nTS-projecting corticotropin-releasing hormone (CRH) neurons. We hypothesized that in male rats, orexin neurons contribute to the PCR by activating nTS-projecting CRH neurons. We used neuronal tract tracing and immunohistochemistry (IHC) to quantify the degree that hypoxia activates PVN-projecting orexin neurons. We coupled this with orexin receptor (OxR) blockade with suvorexant (Suvo, 20 mg/kg, i.p.) to assess the degree that orexin facilitates the hypoxia-induced activation of CRH neurons in the PVN, including those projecting to the nTS. In separate groups of rats, we measured the PCR following systemic orexin 1 receptor (Ox1R) blockade (SB-334867; 1 mg/kg) and specific Ox1R knockdown in PVN. OxR blockade with Suvo reduced the number of nTS and PVN neurons activated by hypoxia, including those CRH neurons projecting to nTS. Hypoxia increased the number of activated PVN-projecting orexin neurons but had no effect on the number of activated nTS-projecting orexin neurons. Global Ox1R blockade and partial Ox1R knockdown in the PVN significantly reduced the PCR. Ox1R knockdown also reduced the number of activated PVN neurons and the number of activated tyrosine hydroxylase neurons in the nTS. Our findings suggest orexin facilitates the PCR via nTS-projecting CRH neurons expressing Ox1R.

Detection and characterization of novel luchacoviruses, genus Alphacoronavirus, in saliva and feces of meso-carnivores in the northeastern United States.

IMPORTANCE: Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions.

Paraventricular nucleus projections to the nucleus tractus solitarii are essential for full expression of hypoxia-induced peripheral chemoreflex responses.

The hypothalamic paraventricular nucleus (PVN) is essential to peripheral chemoreflex neurocircuitry, but the specific efferent pathways utilized are not well defined. The PVN sends dense projections to the nucleus tractus solitarii (nTS), which exhibits neuronal activation following a hypoxic challenge. We hypothesized that nTS-projecting PVN (PVN-nTS) neurons contribute to hypoxia-induced nTS neuronal activation and cardiorespiratory responses. To selectively target PVN-nTS neurons, rats underwent bilateral nTS nanoinjection of retrogradely transported adeno-associated virus (AAV) driving Cre recombinase expression. We then nanoinjected into PVN AAVs driving Cre-dependent expression of Gq or Gi designer receptors exclusively activated by designer drugs (DREADDs) to test the degree that selective activation or inhibition, respectively, of the PVN-nTS pathway affects the hypoxic ventilatory response (HVR) of conscious rats. We used immunohistochemistry for Fos and extracellular recordings to examine how DREADD activation influences PVN-nTS neuronal activation by hypoxia. Pathway activation enhanced the HVR at moderate hypoxic intensities and increased PVN and nTS Fos immunoreactivity in normoxia and hypoxia. In contrast, PVN-nTS inhibition reduced both the HVR and PVN and nTS neuronal activation following hypoxia. To further confirm selective pathway effects on central cardiorespiratory output, rats underwent hypoxia before and after bilateral nTS nanoinjections of C21 to activate or inhibit PVN-nTS terminals. PVN terminal activation within the nTS enhanced tachycardic, sympathetic and phrenic (PhrNA) nerve activity responses to hypoxia whereas inhibition attenuated hypoxia-induced increases in nTS neuronal action potential discharge and PhrNA. The results demonstrate the PVN-nTS pathway enhances nTS neuronal activation and is necessary for full cardiorespiratory responses to hypoxia. KEY POINTS: The hypothalamic paraventricular nucleus (PVN) contributes to peripheral chemoreflex cardiorespiratory responses, but specific PVN efferent pathways are not known. The nucleus tractus solitarii (nTS) is the first integration site of the peripheral chemoreflex, and the nTS receives dense projections from the PVN. Selective GqDREADD activation of the PVN-nTS pathway was shown to enhance ventilatory responses to hypoxia and activation (Fos immunoreactivity (IR)) of nTS neurons in conscious rats, augmenting the sympathetic and phrenic nerve activity (SSNA and PhrNA) responses to hypoxia in anaesthetized rats. Selective GiDREADD inhibition of PVN-nTS neurons attenuates ventilatory responses, nTS neuronal Fos-IR, action potential discharge and PhrNA responses to hypoxia. These results demonstrate that a projection from the PVN to the nTS is critical for full chemoreflex responses to hypoxia.

A repeated cross-sectional study of intestinal parasites in Texas shelter dogs using fecal flotation and saline sedimentation.

Estimates of intestinal parasite prevalence in canine populations have largely been based on use of fecal flotation methods only. Dogs in animal shelters are likely at higher risk of intestinal parasite infection because of their previous exposure history. Our objectives were to estimate the prevalence of intestinal parasites among Texas shelter dogs using centrifugal fecal flotation and saline sedimentation techniques, to identify risk factors for infection, and to compare proportions of positive samples detected via fecal flotation vs. saline sedimentation for the most common parasites. Using a repeated cross-sectional study design, we collected fecal samples from dogs on three visits to each of seven Texas animal shelters between May 2013 and December 2014. Fecal flotation and/or saline sedimentation were used to identify parasites in samples. Fecal samples were collected from 529 dogs. The most frequently detected parasites were Ancylostoma caninum (26.4% via fecal flotation, 20.7% via saline sedimentation) and Trichuris vulpis (12.0% via fecal flotation, 14.1% via saline sedimentation). Risk factors for certain parasites were identified; for example, dogs with abnormal fecal consistency were more likely to be shedding T. vulpis eggs than dogs with normal fecal consistency (OR = 1.8, p = 0.005). The addition of fecal sedimentation not only added to the number of parasite species detected in this study, but it also increased the number of dogs diagnosed with the common intestinal parasites that are primarily detected using fecal flotation methods. Texas shelter dogs carry a high burden of intestinal parasites, including those of zoonotic importance.

Veterinary Students' Knowledge and Awareness of Antimicrobial Stewardship before and after Clinical Rotations.

Given the global threat of antimicrobial resistance, it is imperative that veterinary graduates are effective antimicrobial stewards. Veterinary students learn the principles of antimicrobial stewardship explicitly, through pre-clinical coursework, and implicitly, through the cases they each encounter on clinical rotations. We aimed to understand the influence of pre-clinical versus clinical learning on veterinary students' knowledge and awareness of antimicrobial concepts to guide efforts to improve instruction in these areas. To assess knowledge acquisition and to explore student perceptions of antimicrobial stewardship, a standardized online survey was administered to Cornell University veterinary students at two timepoints: in August 2020 before clinical rotations (N = 26 complete responses and N = 24 partial responses) and again in May 2021 after their clinical rotations (N = 17 complete responses and N = 6 partial responses). Overall and section-specific confidence and knowledge scores were calculated, using pairwise deletion for incomplete responses. Students generally had low confidence in antimicrobial topics and correctly answered only half of knowledge questions correctly; they performed the best on antimicrobial resistance knowledge questions. There were no significant differences in knowledge or confidence after clinical rotations. On average, students had only read one antimicrobial stewardship guideline. Students reported that human health care providers contributed more to antimicrobial resistance than veterinarians. In conclusion, graduating veterinary students at our institution have significant knowledge gaps in critical principles that are essential to become antimicrobial stewards. Explicit instruction in antimicrobial stewardship is necessary in the pre-clinical and clinical coursework, and the practical use of antimicrobial stewardship guidelines should be emphasized.

A serotonin-deficient rat model of neurogenic hypertension: influence of sex and sympathetic vascular tone.

Previously we showed that a loss of central nervous system (CNS) 5-hydroxytryptamine (5-HT) (tryptophan hydroxylase 2 knockout; TPH2-/-) leads to hypertension in male rats during wakefulness and REM sleep. Here, we tested the hypotheses that hypertension is also revealed in female TPH2-/- when sex hormones are controlled, and that the especially high arterial blood pressure (ABP) of male TPH2-/- rats is due to increased sympathetic vascular tone. The ABP of females was measured specifically during proestrus or estrus and again following ovariectomy. The ABP of males was measured before and after α-adrenergic blockade. Prior to ovariectomy, the ABP of female TPH2-/- rats was ∼3 mmHg higher than TPH2+/+ during REM sleep while in proestrus/estrus. This difference increased to ∼9 mmHg following ovariectomy (P = 0.047). Hypertension of female TPH2-/- was most obvious upon the transition to rapid eye movement (REM) sleep from the previous state (P < 0.0001). Mean arterial pressure (MAP) of male TPH2-/- rats was ∼14 mmHg higher than male TPH2+/+ (P = 0.02), a difference that was eliminated by α-adrenergic blockade. Male TPH2-/- had normal plasma levels of 5-HT, norepinephrine, and epinephrine, whereas plasma dopamine was reduced by 50% compared with TPH2+/+ (P < 0.0001). From these data, we conclude that: 1) a deficiency of CNS 5-HT leads to hypertension in males and females alike, although in females the effect is mild and possibly obscured by ovarian hormones; 2) hypertension in females, like males, is most apparent in REM sleep, indicating a neural origin, and 3) increased sympathetic vascular tone underlies the elevated ABP of TPH2-/- rats.NEW & NOTEWORTHY We show that hypertension is evident in female 5-HT-deficient TPH2-/- rats when sex hormones are controlled, an effect most evident upon the transition to REM sleep. In addition, our data strongly suggest that increased sympathetic vascular tone contributes to the hypertension present in this 5-HT-deficient model of neurogenic hypertension.

Orexin facilitates the ventilatory and behavioral responses of rats to hypoxia.

Orexin neurons are sensitive to CO2 and contribute to cardiorespiratory homeostasis as well as sensorimotor control. Whether orexin facilitates respiratory and behavioral responses to acute hypoxia is unclear. We hypothesized that orexin neurons are activated by acute hypoxia and that orexin facilitates the hypoxic ventilatory response (HVR), as well as the arterial blood pressure (ABP) and behavioral (movement) responses to acute hypoxia. We further hypothesized that orexin has greater effects in the active phase of the rat circadian cycle, when orexin neurons have high activity. Using whole body plethysmography with EEG, EMG, and the dual-orexin receptor (OxR) antagonist suvorexant (20 mg/kg ip), we determined the effect of OxR blockade on the respiratory, ABP, and behavioral responses of adult rats to acute, graded hypoxia ([Formula: see text]= 0.15, 0.13, 0.11, and 0.09) and hyperoxic hypercapnia ([Formula: see text]= 0.05; [Formula: see text]= 0.95). OxR blockade had no effect on eupnea. OxR blockade significantly reduced the HVR in both inactive and active phases, with a stronger effect in the active phase. OxR blockade reduced the behavioral response to acute hypoxia in the active phase. The central component of the ventilatory and the ABP responses to hypercapnia were reduced by OxR blockade solely in the inactive phase. In the inactive phase, hypoxia activated ∼10% of orexin neurons in the perifornical hypothalamus. These data suggest that orexin neurons participate in the peripheral chemoreflex to facilitate the ventilatory and behavioral responses to acute hypoxia in rats, particularly in the active phase. Orexin also facilitates central chemoreflex responses to CO2 in the inactive phase.

Assessing central and peripheral respiratory chemoreceptor interaction in humans.

NEW FINDINGS: What is the central question of this study? We investigated the interaction between central and peripheral respiratory chemoreceptors in healthy, awake human participants by using a background of step increases in steady-state normoxic fraction of inspired carbon dioxide to alter central chemoreceptor activation and by using the transient hypoxia test to target the peripheral chemoreceptors. What is the main finding and its importance? Our data suggest that the interaction between central and peripheral respiratory chemoreceptors is additive in minute ventilation and respiratory rate, but hypo-additive in tidal volume. Our study adds important new data in reconciling chemoreceptor interaction in awake healthy humans and is consistent with previous reports of simple addition in intact rodents and humans. ABSTRACT: Arterial blood gas levels are maintained through respiratory chemoreflexes, mediated by central chemoreceptors in the CNS and peripheral chemoreceptors located in the carotid bodies. The interaction between central and peripheral chemoreceptors is controversial, and few studies have investigated this interaction in awake, healthy humans, owing, in part, to methodological challenges. We investigated the interaction between the central and peripheral chemoreceptors in healthy humans using a transient hypoxia test (three consecutive breaths of 100% N2 ; TT-HVR), which targets the temporal domain and stimulus specificity of the peripheral chemoreceptors. The TT-HVRs were superimposed upon three randomized background levels of steady-state inspired fraction of normoxic CO2 ( F I , C O 2 ${F}_{{\rm{I,C}}{{\rm{O}}}_{\rm{2}}}$ ; 0, 0.02 and 0.04). Chemostimuli [calculated oxygen saturation ( S cO 2 ${S}_{{\rm{cO}}_{\rm{2}}}$ )] and respiratory variable responses [respiratory rate (RR ), inspired tidal volume (VTI ) and ventilation ( V ̇ I ${{{\dot{V}}}_{\rm{I}}}$ )] were averaged from all three TT-HVR trials at each F I , C O 2 ${F}_{{\rm{I,C}}{{\rm{O}}}_{\rm{2}}}$ level. Responses were assessed as: (1) a change (∆) from baseline; and (2) indexed against Δ S cO 2 $\Delta {S}_{{\rm{cO}}_{\rm{2}}}$ . Aside from a significantly lower ∆VTI response in 0.04 F I , C O 2 ${F}_{{\rm{I,C}}{{\rm{O}}}_{\rm{2}}}$ (P = 0.01), the hypoxic rate responses (∆RR or ∆RR / Δ S cO 2 $\Delta {S}_{{\rm{cO}}_{\rm{2}}}$ ; P = 0.46 and P = 0.81), hypoxic tidal volume response ( Δ V TI / Δ V TI Δ S cO 2 Δ S cO 2 ${{\Delta {V}_{{\rm{TI}}}} \mathord{/ {\vphantom {{\Delta {V}_{{\rm{TI}}}} {\Delta {S}_{{\rm{cO}}_{\rm{2}}}}}} \kern-\nulldelimiterspace} {\Delta {S}_{{\rm{cO}}_{\rm{2}}}}}$ ; P = 0.08) and the hypoxic ventilatory responses ( Δ V ̇ I ${{\Delta {{\dot{V}}}_{\rm{I}}}}$ and Δ V ̇ I / Δ V ̇ I Δ S cO 2 Δ S cO 2 ${{\Delta {{\dot{V}}}_{\rm{I}}} \mathord{/ {\vphantom {{\Delta {{\dot{V}}}_{\rm{I}}} {\Delta {S}_{{\rm{cO}}_{\rm{2}}}}}} \kern-\nulldelimiterspace} {\Delta {S}_{{\rm{cO}}_{\rm{2}}}}}$ ; P = 0.09 and P = 0.31) were not significantly different across F I , C O 2 ${F}_{{\rm{I,C}}{{\rm{O}}}_{\rm{2}}}$ trials. Our data suggest simple addition between central and peripheral chemoreceptors in V ̇ I ${{{\dot{V}}}_{\rm{I}}}$ , which is mediated through simple addition in RR responses, but hypo-addition in VTI responses. Our study adds important new data in reconciling chemoreceptor interaction in awake, healthy humans and is consistent with previous reports of simple addition in intact rodents and humans.

Integrated Surveillance System for Controlling COVID-19 on a University Campus, 2020‒2021.

To minimize the impacts of COVID-19 and to keep campus open, Cornell University's Ithaca, NY, campus implemented a comprehensive process to monitor COVID-19 spread, support prevention practices, and assess early warning indicators linked to knowledge, behaviors, and attitudes of campus community members. The integrated surveillance approach informed leadership and allowed for prompt adjustments to university policies and practices through evidence-based decisions. This approach enhanced healthy behaviors and promoted the well-being and safety of all community members. (Am J Public Health. 2022;112(7):980-984. https://doi.org/10.2105/AJPH.2022.306838).

Eupnea and gasping in vivo are facilitated by the activation of 5-HT2A receptors.

Eupnea and gasping in infancy depend on central nervous system (CNS) serotonin (5-hydroxytryptamine; 5-HT). Although previous in vitro preparations have provided some evidence that 5-HT acts through type 2 A receptors (5-HT2A) to facilitate eupnea and gasping, here the hypothesis addressed is that 5-HT2A receptor activation is necessary for eupnea and the proper generation of gasping in vivo. To test this, we administered 2,5-dimethoxy-4-iodoamphetamine (DOI; 0.25 mg/kg i.p.), a 5-HT2A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.25 mg/kg i.p.), a 5-HT1A agonist, or vehicle (saline) to 7-9-day-old tryptophan hydroxylase 2 knockout (TPH2-/-) mice. A second experiment assessed the effect of MDL-11,939 (MDL; 10 mg/kg i.p.), the specific 5-HT2A antagonist, or vehicle (DMSO) on the gasping of wild-type (TPH2+/+) animals. Drugs were given 15 min prior to five episodes of severe hypoxia that elicited gasping. TPH2-/- breathed more slowly but had the same V̇e and V̇e/V̇o2 compared with TPH2+/+. As previously reported, the gasping of TPH2-/- was significantly delayed (P < 0.001) and occurred at a significantly lower frequency compared with TPH2+/+ (P = 0.04). For both genotypes, DOI hastened eupneic frequency but had no effect on V̇e or V̇e/V̇o2. The gasping of TPH2-/-, although unaffected by 8-OH-DPAT, was indistinguishable from the gasping of TPH2+/+ following DOI. In TPH2+/+, application of MDL led to hypoventilation (P = 0.01), a delay in the appearance of gasping (P = 0.005), and reduced gasp frequency (P = 0.05). These data show that, in vivo, 5-HT2A receptors facilitate both eupnea and gasping. As has been shown in vitro, 5-HT2A probably promotes gasping by exciting hypoxia-resistant pacemaker neurons.NEW & NOTEWORTHY Previous in vitro studies suggest that 5-HT2A receptors contribute to eupnea and are necessary for fictive gasping. The current study shows that the impaired gasping displayed by neonatal TPH2-/- mice, deficient in CNS serotonin, is restored by 5-HT2A receptor activation. Following 5-HT2A blockade, wild-type mice hypoventilated and their gasping resembled that of TPH2-/- mice. This study shows that both eupnea and gasping in vivo rely on the activation of 5-HT2A receptors.

Orexin contributes to eupnea within a critical period of postnatal development.

Orexin neurons are active in wakefulness and mostly silent in sleep. In adult rats and humans, orexin facilitates the hypercapnic ventilatory response but has little effect on resting ventilation. The influence of orexin on breathing in the early postnatal period, and across states of vigilance, have not been investigated. This is relevant as the orexin system may be impaired in Sudden Infant Death Syndrome (SIDS) cases. We addressed three hypotheses: 1) orexin provides a drive to breathe in infancy; 2) the effect of orexin depends on stage of postnatal development; and 3) orexin has a greater influence on breathing in wakefulness compared with sleep. Whole body plethysmography was used to monitor breathing of infant rats at three ages: postnatal days (P) 7-8, 12-14, and 17-19. Respiratory variables were analyzed in wakefulness (W), quiet sleep (QS), and active sleep (AS), following suvorexant (5 mg/kg ip), a dual orexin receptor antagonist, or vehicle (DMSO). Effects of suvorexant on ventilatory responses to graded hypercapnia ([Formula: see text] = 0.02, 0.04, 0.06), hypoxia ([Formula: see text] = 0.10), and hyperoxia ([Formula: see text] = 1.0) at P12-14 were also tested. At P12-14, but not at other ages, suvorexant significantly reduced respiratory frequency in all states, reduced the ventilatory equivalent in QW and QS, and increased [Formula: see text] to ∼5 mmHg. Suvorexant had no effect on ventilatory responses to graded hypercapnia or hypoxia. Hyperoxia eliminated the effects of suvorexant on respiratory frequency at P12-14. Our data suggest that orexin preserves eupneic frequency and ventilation in rats, specifically at ∼2 wk of age, perhaps by facilitating tonic peripheral chemoreflex activity.

Short communication: Oral and intranasal administration of a modified-live Salmonella Dublin vaccine in dairy calves: Clinical efficacy and serologic response.

Our objectives were to evaluate the clinical efficacy of oral and intranasal administration of a commercial modified-live Salmonella Dublin vaccine in dairy calves and to determine the serologic response associated with these extralabel routes of administration. We conducted a randomized field trial with calves from a New York dairy farm following an outbreak of Salmonella Dublin. A total of 399 Holstein calves were allocated by pen to 3 treatment groups: oral vaccination, intranasal vaccination, and an unvaccinated control group. Administration of the vaccine through oral and intranasal routes did not have a significant effect on pneumonia incidence risk or weight gain; however, calves vaccinated orally and intranasally had lower mortality risk as compared with control calves. Among calves tested using a Salmonella Dublin ELISA, vaccination did not induce an increase in antibody production relative to control calves, indicating that oral and intranasal administration will not hinder diagnosis based on this assay.

Reduced risk of pneumonia after changes in anesthetic procedures for dogs receiving repeated anesthesia for radiation treatment.

Radiation therapy requires repeated anesthetic administration to patients who often have multiple comorbidities contributing to an increased rate of anesthetic complications such as pneumonia. This is a retrospective observational study in which data were collected from 146 medical records of dogs receiving repeat anesthesia for radiation treatment from prior to management changes and compared to data from 149 cases treated after completion of management changes. The objective was to determine if changes in case management protocol that were put in place decreased the risk of pneumonia development among these patients. Management changes that were made included the following: decrease in anticholinergic and pure-mu opioid use, change in positioning during intubation and recovery, prophylactic treatment of nausea, timing of cuff inflation and deflation, and aseptic handling of intubation equipment. There was a significant association between diagnosis of pneumonia and the following: pre- vs. post-changes to protocol, presence of a neurologic tumor, presence of respiratory disease, presence of megaesophagus, and number of radiation fractions completed. Diagnosis of pneumonia did not vary significantly by age group, body weight category, or sex. In a multivariable logistic regression model that controlled for the effects of the three concurrent diseases and fractions completed, the odds of being diagnosed with pneumonia were approximately 10 times greater among dogs anesthetized prior to management changes (odds ratio = 9.9, 95% CI = 2.0-48.7, P = 0.005).

Central serotonin and the control of arterial blood pressure and heart rate in infant rats: influence of sleep state and sex.

Sudden infant death syndrome (SIDS) is associated with serotonin (5-HT) neuron abnormalities. There is evidence of autonomic dysfunction during sleep in infants eventually succumbing to SIDS, as well as cardiovascular collapse before death. Neonatal rodents deficient in central 5-HT display hypotension and bradycardia. We hypothesized that central 5-HT reduces cardiac vagal tone and increases sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that these effects are greater in quiet sleep (QS) than in active sleep (AS). We tested these hypotheses using 2-wk-old male and female rat pups lacking tryptophan hydroxylase-2 ( TPH2-/-) and wild-type (WT) littermates. Arterial blood pressure (ABP) and heart rate (HR) were measured over 3 h during periods of QS and AS. We also gave atropine or atenolol (each 1 mg/kg iv), or phentolamine (5, 50, and 500 µg/kg iv) to separate groups to assess the effects 5-HT deficiency on autonomic tone to the heart or sympathetic vascular tone, respectively. Compared with WT, male and female TPH2-/- pups had reduced ABP in QS but not in AS. Atropine induced a greater HR increase in female TPH2-/- than in female WT pups, an effect absent in male TPH2-/- pups. Both genotypes experienced the same atenolol-induced drop in HR. In males only, phentolamine induced a smaller decrease in the ABP of TPH2-/- pups compared with WT. These data suggest that central 5-HT maintains ABP in QS, and HR in both states. In males, central 5-HT facilitates sympathetic vascular tone, and in females it reduces cardiac vagal drive.

Influence of caudal epidural analgesia on cortisol concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy.

OBJECTIVE: To determine the influence of epidural detomidine and morphine on serum corticosteroid concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy. STUDY DESIGN: Blinded prospective study. ANIMALS: Nine university-owned mares. METHODS: Five of 9 horses received caudal epidural detomidine hydrochloride (0.01 mg/kg) and morphine sulfate (0.1 mg/kg) prior to surgery. All horses received local anesthetic around the ovarian pedicle, 0.02 mg/kg butorphanol IV at the start of the procedure and after first ovary removal, were sedated as required throughout the procedure, and were monitored for leg lifting, grunting, and abdominal tensing. Horses were monitored hourly for pain postoperatively. Heart rate was recorded every 4 hours, and photographs were taken to assess pain according to the horse grimace scale (HGS). Control group horses (n = 4) were treated with butorphanol (0.02 mg/kg IV) every 4 hours for 24 hours postoperatively. All horses received oral phenylbutazone 18 hours postoperatively. Serum cortisol was measured prior to the procedure, after first and second ovary removal, and 8 and 24 hours postoperatively. RESULTS: No differences were detected between horses receiving caudal epidural detomidine and morphine and those that received systemic opioids. A decrease in HGS score occurred after phenylbutazone administration. CONCLUSION: Administration of caudal epidural detomidine and morphine resulted in similar pain-related behavior and corticosteroid concentrations as did administration of systemic butorphanol every 4 hours for 24 hours postoperatively. CLINICAL SIGNIFICANCE: Caudal epidural detomidine and morphine may mitigate the requirement for frequent systemic opioid administration after a potentially painful procedure.

α4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling.

Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by α4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that α4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and α4 knockout (KO) mice were exposed to 6 mg·kg-1·day-1 nicotine or vehicle from embryonic day 14 At postnatal day (P) 7 mice were cooled from an ambient temperature (TA) of 32 to 20°C. Body temperature (TB), rate of O2 consumption (V̇o2), ventilation (V̇e), respiratory frequency (FB), and tidal volume (VT) were continually monitored. An absence of α4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in TB was exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in VT, an effect that was absent in α4 KO littermates. We show that PN interacts with α4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period.

Salmonella Prevalence and Antimicrobial Susceptibility Among Dairy Farm Environmental Samples Collected in Texas.

Dairy cattle are a reservoir of several Salmonella serovars that are leading causes of human salmonellosis. The objectives of this study were to estimate the environmental prevalence of Salmonella on dairy farms in Texas and to characterize the antimicrobial susceptibility of the isolates. Eleven dairy farms throughout Texas were sampled from August through October 2013, using a cross-sectional approach. Samples were collected from four locations within each farm (hospital pen, maternity pen, cow housing area, and calf housing area), and feces were collected from cull cows as available. Environmental and fecal samples were processed for Salmonella, and isolates were tested for susceptibility to 15 antimicrobial agents. Serovar characterization was performed on a subset of these isolates. Salmonella was isolated from 67.0% (236/352) of the environmental samples and 64.2% (43/67) of the cull cow fecal samples. Environmental samples from the maternity pen were significantly more likely to be Salmonella positive than samples from the cow and calf housing areas. Multidrug resistance was evident in 11.9% (27/226) of environmental isolates and 19.5% (8/41) of fecal isolates. Salmonella isolates from the calf housing area and maternity pen were significantly more likely to be multidrug resistant (MDR) than isolates from the cow housing area. The most common serovars found among the MDR isolates were Newport, Muenchen, and Typhimurium. These results help provide a focus for efforts to mitigate the burden of antimicrobial-resistant Salmonella at the preharvest level.

THE USE OF SMALL FIELD-OF-VIEW 3 TESLA MAGNETIC RESONANCE IMAGING FOR IDENTIFICATION OF ARTICULAR CARTILAGE DEFECTS IN THE CANINE STIFLE: AN EX VIVO CADAVERIC STUDY.

Noninvasive identification of canine articular cartilage injuries is challenging. The objective of this prospective, cadaveric, diagnostic accuracy study was to determine if small field-of-view, three tesla magnetic resonance imaging (MRI) was an accurate method for identifying experimentally induced cartilage defects in canine stifle joints. Forty-two canine cadaveric stifles (n = 6/group) were treated with sham control, 0.5, 1.0, or 3.0 mm deep defects in the medial or lateral femoral condyle. Proton density-weighted, T1-weighted, fast-low angle shot, and T2 maps were generated in dorsal and sagittal planes. Defect location and size were independently determined by two evaluators and compared to histologic measurements. Accuracy of MRI was determined using concordance correlation coefficients. Defects were identified correctly in 98.8% (Evaluator 1) and 98.2% (Evaluator 2) of joints. Concordance correlation coefficients between MRI and histopathology were greater for defect depth (Evaluator 1: 0.68-0.84; Evaluator 2: 0.76-0.83) compared to width (Evaluator 1: 0.30-0.54; Evaluator 2: 0.48-0.68). However, MRI overestimated defect depth (histopathology: 1.65 ± 0.94 mm; Evaluator 1, range of means: 2.07-2.38 mm; Evaluator 2, range of means: 2-2.2 mm) and width (histopathology: 6.98 ± 1.32 mm; Evaluator 1, range of means: 8.33-8.8 mm; Evaluator 2, range of means: 6.64-7.16 mm). Using the paired t-test, the mean T2 relaxation time of cartilage defects was significantly greater than the mean T2 relaxation time of adjacent normal cartilage for both evaluators (P < 0.0001). Findings indicated that MRI is an accurate method for identifying cartilage defects in the cadaveric canine stifle. Additional studies are needed to determine the in vivo accuracy of this method.

Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons.

The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk-old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ∼20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (V̇e), and metabolic rate (V̇o2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ∼35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (∼6 mmHg), mean arterial pressure (∼5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased V̇e and V̇e/V̇o2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction.

Antimicrobial resistance trends among canine Escherichia coli isolates obtained from clinical samples in the northeastern USA, 2004-2011.

Our objectives were to describe the antimicrobial susceptibility of Escherichia coli isolates from dogs in the northeastern USA and to identify temporal trends in resistance to selected antimicrobial agents. Data were collected retrospectively for all canine E. coli isolates from clinical samples submitted to Cornell University's Animal Health Diagnostic Center between January 1, 2004 and December 31, 2011. Antimicrobial susceptibility testing was performed on 3519 canine E. coli isolates; frequency of resistance to each agent ranged from 0.4% (amikacin) to 34.3% (ampicillin). No trends were evident among urinary isolates, but cephalosporin resistance remained consistently high. Among non-urinary isolates, there was evidence of a significantly increasing trend in prevalence of resistance to several agents, including cephalosporins, enrofloxacin, and tetracycline. These data suggest that some of the most commonly used antimicrobial agents in companion animal practice are becoming less effective against canine E. coli infections outside the urinary tract.

Tendances de la résistance antimicrobienne parmi les isolats canins d'Escherichia coliobtenus dans des échantillons cliniques dans le nord-est des États-Unis de 2004 à 2011. Nos objectifs consistaient à décrire la susceptibilité des isolats d'Escherichia coli chez des chiens dans le nord-est des États-Unis et à identifier les tendances de résistance temporelles aux agents antimicrobiens sélectionnés. Des données ont été recueillies rétrospectivement pour tous les isolats canins d'E. coli provenant d'échantillons cliniques soumis à l'Animal Health Diagnostic Center de l'Université Cornell entre le 1er janvier 2004 et le 31 décembre 2011. Des épreuves de sensibilité antimicrobienne ont été réalisées sur 3519 isolats canins E. coli; la fréquence de résistance à chaque agent allait de 0,4 % (amikacine) à 34,3 % (ampicilline). Aucunes tendances n'étaient évidentes parmi les isolats urinaires, mais la résistance à la céphalosporine demeurait constamment élevée. Parmi les isolats non urinaires, il y avait des preuves d'une tendance significative à la hausse de la prévalence de la résistance à plusieurs agents, y compris les céphalosporines, l'enrofloxacine et la tétracycline. Ces données suggèrent que certains des agents antimicrobiens les plus communément utilisés en pratique des animaux de compagnie deviennent de moins en moins efficaces contre les infections canines par E. coli à l'extérieur des voies urinaires.(Traduit par Isabelle Vallières).