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1.
Animals (Basel) ; 13(11)2023 May 29.
Article En | MEDLINE | ID: mdl-37889730

The objective of this study was to validate standing and locomotion lameness scoring, mechanical nociceptive threshold testing, and behavioral profile tools for the diagnosis of naturally occurring lameness etiologies in pigs. A total of 55 crossbred gilts and sows obtained from a commercial farm were enrolled in the study; with sound pigs classified as controls (8) and the remainder as lame due to integumentary (20), musculoskeletal (15), and combinations of integumentary and musculoskeletal (12) etiologies. Standing and locomotion lameness, mechanical nociceptive threshold (MNT) test, pig-human interventions, and latency to complete an obstacle course were evaluated. Standing and locomotion lameness scoring systems, MNT, and pig behavior (latency) were capable of discriminating between animals with mild organic lameness and animals that were sound and may have utility on the farm for staff to use to identify and manage lame animals. In rare instances, the tools used here were able to discriminate between broad categories of lameness etiology.

2.
J Pharmacol Exp Ther ; 382(3): 277-286, 2022 09.
Article En | MEDLINE | ID: mdl-35717448

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B; OMIM #252920) is a lethal, pediatric, neuropathic, autosomal recessive, and lysosomal storage disease with no approved therapy. Patients are deficient in the activity of N-acetyl-alpha-glucosaminidase (NAGLU; EC 3.2.150), necessary for normal lysosomal degradation of the glycosaminoglycan heparan sulfate (HS). Tralesinidase alfa (TA), a fusion protein comprised of recombinant human NAGLU and a modified human insulin-like growth factor 2, is in development as an enzyme replacement therapy that is administered via intracerebroventricular (ICV) infusion, thus circumventing the blood brain barrier. Previous studies have confirmed ICV infusion results in widespread distribution of TA throughout the brains of mice and nonhuman primates. We assessed the long-term tolerability, pharmacology, and clinical efficacy of TA in a canine model of MPS IIIB over a 20-month study. Long-term administration of TA was well tolerated as compared with administration of vehicle. TA was widely distributed across brain regions, which was confirmed in a follow-up 8-week pharmacokinetic/pharmacodynamic study. MPS IIIB dogs treated for up to 20 months had near-normal levels of HS and nonreducing ends of HS in cerebrospinal fluid and central nervous system (CNS) tissues. TA-treated MPS IIIB dogs performed better on cognitive tests and had improved CNS pathology and decreased cerebellar volume loss relative to vehicle-treated MPS IIIB dogs. These findings demonstrate the ability of TA to prevent or limit the biochemical, pathologic, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. SIGNIFICANCE STATEMENT: This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for patients with mucopolysaccharidosis type IIIB (MPS IIIB) by documenting that administration to the central nervous system of MPS IIIB dogs prevents the accumulation of disease-associated glycosaminoglycans in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline.


Mucopolysaccharidosis III , Animals , Brain/metabolism , Child , Disease Models, Animal , Dogs , Enzyme Replacement Therapy , Glycosaminoglycans/metabolism , Heparitin Sulfate/cerebrospinal fluid , Heparitin Sulfate/therapeutic use , Humans , Mucopolysaccharidosis III/drug therapy , Mucopolysaccharidosis III/pathology
3.
Front Vet Sci ; 8: 640751, 2021.
Article En | MEDLINE | ID: mdl-33748216

Obtaining accurate blood pressure measurements in cats is challenging due to the stressful nature of clinic visits. The objective of this study was to evaluate the effects of veterinary clinic waiting experiences and a feline pheromone spray on blood pressure in the cat. We hypothesized that reduced stress associated with bypassing the waiting room and use of synthetic feline facial pheromone (FFP) spray would result in lower blood pressure. A 2 × 2 factorial design involved two rooms and two FFP treatments. Thirty-nine healthy adult cats were recruited and were systematically assigned to four treatment combinations administered over four visits in 2016 and 2017. Cats were kept in the hospital waiting room or were taken directly to the exam room, with or without FFP treatment. All cats were then acclimated to the exam room for an additional 10 min, where vocalizations were recorded manually, before blood pressure measurements were collected using Doppler ultrasonography. Data were analyzed using generalized linear mixed models, with room × FFP interaction, visit, sex, and trial year in the model. There was no significant effect of waiting room by FFP interaction on blood pressure (n = 0.95). Mean blood pressure was significantly higher at visit 1 than visits 2 and 4 (P < 0.01), but higher at visit 3 than visit 2 (n = 0.02). Mean blood pressure was higher in males (n = 0.01), and males were more likely to be categorized as borderline hypertensive/hypertensive or severely hypertensive (n = 0.01). Number of vocalizations was significantly associated with waiting room by FFP interactions (P < 0.01), with fewer vocalizations associated with bypassing the waiting room and when FFP was provided. In conclusion, although we found some behavioral evidence supporting stress reduction when feline patients bypass the waiting room and are provided with FFP, these interventions did not result in lower blood pressure in a clinical setting.

4.
Animals (Basel) ; 11(2)2021 Feb 07.
Article En | MEDLINE | ID: mdl-33562360

There is a strong industry demand for technically simple and highly efficacious alternatives to heat cautery disbudding in goat kids that can be performed as a stand-alone procedure without adjunct anesthesia, and that result in improved overall welfare through reduced acute pain, reduced tissues healing interval, and a consistent safety record. The objective of this study was to consider the net effect of disbudding techniques on goat welfare by examining vocalization frequency, long-term efficacy and animal safety associated with four alternative caprine disbudding methods against sham-disbudded and heat-cautery controls. Sixty-five commercial male dairy kids were disbudded at 3-10 days of age with one of six disbudding treatments (clove oil injection, caustic paste, two cryosurgical methods, heat-cautery, and sham procedure). Heat cautery was 91% effective, caustic paste was 55% effective, and the other treatments were ineffective. Heat cautery and sham procedures resulted in similar vocalization efforts; freezing with a liquid-nitrogen cooled iron resulted in significantly greater vocalization numbers. No unintended paste transfer injuries were observed with short-term application of the caustic paste. Heat cautery resulted in numerous superficial infections but no permanent injury. Clove oil injection was associated with several unexpected and severe complications including unintended tissue necrosis, temporary paresis, skull defects, meningitis, and death. Collectively, we did not find that any of the alternative methods of disbudding provided a feasible option over heat cautery to improve welfare.

5.
Avian Dis ; 60(1): 8-15, 2016 Mar.
Article En | MEDLINE | ID: mdl-26953938

The egg industry is moving away from the use of conventional cages to enriched cage and noncage laying hen housing systems because of animal welfare concerns. In this study, the prevalence and severity of lesions in noncage laying hens from commercial farms in two of the largest egg-producing states, California and Iowa, were evaluated by postmortem examination. Hens that died or were culled were collected during early, mid, and late stages of the laying cycle from 16 houses on three farms. Of the 25 gross lesions identified for study, 22 were observed, with an average of four lesions per hen. Vent cannibalism, reduced feather cover, keel bone deformation, and beak abnormalities were the most frequent lesions, observed in ≥40% of hens. Other common lesions were cloacal prolapse (30.5%), footpad dermatitis (24.3%), and septicemia (23.1%). Beak abnormality and enteric disease had the highest proportion of severe lesions. Pearson chi-square analysis revealed a number of stage-of-lay effects (P ≤ 0.05), some of which differed by state. For both states combined, the lesions observed more frequently during early lay were beak abnormalities, northern fowl mite infestation, and cage layer fatigue, whereas during mid lay, they were poor feather cover, vent cannibalism, footpad dermatitis, keel bone deformation, respiratory disease and roundworms. Feather pecking and cloacal prolapse were most common during late lay. Although differences in hen genetics, farm management practices, and environmental factors could all have affected the results of this study, the information provides a better understanding of hen health in noncage housing systems and could help to identify potential interventions to reduce hen welfare problems.


Animal Welfare , Chickens , Poultry Diseases/epidemiology , Animals , California/epidemiology , Female , Housing, Animal , Incidence , Iowa/epidemiology , Poultry Diseases/etiology , Poultry Diseases/pathology , Prevalence
6.
F1000Res ; 4: 546, 2015.
Article En | MEDLINE | ID: mdl-26949517

Infectious bovine keratoconjunctivitis (IBK) is a common corneal disease of calves that adversely affects animal welfare by causing pain and weight loss. Identifying behavioral indicators of pain and sickness in calves with IBK is necessary for designing studies that aim to identify effective means of pain mitigation. Consistent with principles of the 3Rs for animal use in research, data from a randomized blinded challenge study was used to identify and describe variation of behaviors that could serve as reliable indicators of pain and sickness in calves with corneal injuries. Behavioral observations were collected from 29 Holstein calves 8 to 12 weeks of age randomly allocated to one of three treatments: (1) corneal scarification only, (2) corneal scarification with inoculation with Moraxella bovoculi and (3) corneal scarification with inoculation with Moraxella bovis. Behavior was continuously observed between time 1230 - 1730 h on day -1 (baseline time period) and day 0 (scarification time period). Corneal scarification and inoculation occurred between 0800 - 1000 h on day 0. Frequency of head-directed behaviors (head shaking, head rubbing, head scratching) and durations of head rubbing, feeding, standing with head lifted, lying with head lifted and sleeping were compared between study days and groups. Following scarification, the frequency of head-directed behavior significantly increased (p = 0.0001), as did duration of head rubbing (p=0.02). There was no significant effect of trial, trial day, treatment or treatment-day interaction on other behaviors studied. Our study demonstrated that head-directed behavior, such as head shaking, rubbing and scratching, was associated with scarification of eyes using an IBK challenge model, but sickness behavior was not observed.

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