Stephen Felt, DVM, MPH

All Publications

• Pebble to the Metal: A Boulder Approach to Enrichment for Danio rerio. PloS one Byrd, K. A., Theil, J. H., Geronimo, J. T., Ahloy-Dallaire, J., Gutierrez, M. F., Hui, E. I., Felt, T. K., Coden, K. M., Ratuski, A. S., Felt, S. A., Chu, D. K., Garner, J. P. 2024; 19 (5): e0298657

  Abstract

  Zebrafish are an established and widely used animal model, yet there is limited understanding of their welfare needs. Despite an increasing number of studies on zebrafish enrichment, in-tank environmental enrichment remains unpopular among researchers. This is due to perceived concerns over health/hygiene when it comes to introducing enrichment into the tank, although actual evidence for this is sparse. To accommodate this belief, regardless of veracity, we tested the potential benefits of enrichments presented outside the tank. Thus, we investigated the preferences and physiological stress of zebrafish with pictures of pebbles placed underneath the tank. We hypothesized that zebrafish would show a preference for enriched environments and have lower stress levels than barren housed zebrafish. In our first experiment, we housed zebrafish in a standard rack system and recorded their preference for visual access to a pebble picture, with two positive controls: visual access to conspecifics, and group housing. Using a crossover repeated-measures factorial design, we tested if the preference for visual access to pebbles was as strong as the preference for social contact. Zebrafish showed a strong preference for visual access to pebbles, equivalent to that for conspecifics. Then, in a second experiment, tank water cortisol was measured to assess chronic stress levels of zebrafish housed with or without a pebble picture under their tank, with group housing as a positive control. Cortisol levels were significantly reduced in zebrafish housed with pebble pictures, as were cortisol levels in group housed zebrafish. In fact, single housed zebrafish with pebble pictures showed the same cortisol levels as group housed zebrafish without pebble pictures. Thus, the use of an under-tank pebble picture was as beneficial as being group housed, effectively compensating for the stress of single housing. Pebble picture enrichment had an additive effect with group housing, where group housed zebrafish with pebble pictures had the lowest cortisol levels of any treatment group.

  View details for DOI 10.1371/journal.pone.0298657

  View details for PubMedID 38713725

  View details for PubMedCentralID PMC11075867

• Propofol Immersion as a Euthanasia Method for Adult Zebrafish (Danio rerio). Comparative medicine Davis, A. K., Garner, J. P., Chu, D. K., Felt, S. A. 2022

  Abstract

  The exponential rise of the zebrafish (Danio rerio) as a model organism in biomedical research has far outstripped our understanding of basic husbandry and welfare for this species. As a case in point, here we investigate the efficacy and welfare impact of different euthanasia methods for zebrafish. Not only is a humane death central to welfare and the 3Rs, but stress during euthanasia can change scientific outcomes. However, the most frequently used methods of euthanasia have multiple shortcomings with regard to animal welfare and human safety. In this study, we propose the use of propofol for immersion euthanasia of adult zebrafish. Propofol has been known to rapidly induce anesthesia in many species, including zebrafish, but its efficacy as a euthanasia agent for zebrafish has not fully been explored. In this study, adult zebrafish were euthanized by immersion on one of 5 different preparations: ice bath, 250 ppm MS222, 600 ppm lidocaine hydrochloride, 100 ppm propofol, or 150 ppm propofol for 20 or 30 min. Display of aversive behaviors, time to loss of righting reflex, time to cessation of opercular movement, and time to recovery after transfer to clean tank water were assessed and recorded. Propofol at both concentrations induced loss of righting reflex and loss of opercular movement more quickly than did MS222 or lidocaine hydrochloride and caused no display of aversive behaviors as seen with ice bath or lidocaine exposure. However, fish exposed to propofol at either concentration for 20 min sometimes recovered, whereas a 30-min exposure was sufficient for euthanasia of all fish tested. These findings suggest that exposure to propofol for a duration of at least 30 min quickly and effectively euthanizes adult zebrafish without compromising end of-life welfare.

  View details for DOI 10.30802/AALAS-CM-22-000050

  View details for PubMedID 35701076

• Mitochondrial Gene Diversity and Host Specificity of Isospora in Passerine Birds. Frontiers in veterinary science Kubiski, S. V., Witte, C., Burchell, J. A., Conradson, D., Zmuda, A., Barbon, A. R., Vilches-Moure, J. G., Felt, S. A., Rideout, B. A. 2022; 9: 847030

  Abstract

  Isospora infections are common in both wild and captive passerine species. Many bird species have been shown to have co-evolved with a particular species of Isospora. Disease can range from subclinical to severe and fatal, making infection and transmission of this parasite a concern for birds under managed care, particularly in institutions housing endangered species for breeding and reintroduction purposes. Whether birds in mixed-species enclosures represent a risk factor for severe isosporiasis due to infection with non-host-adapted strains is of concern for institutions managing these populations. To begin answering this question, we sought to characterize the host-specificity of Isospora spp. in a large number of passerine birds via retrospective sequencing of mitochondrial gene cytochrome c oxidase subunit I (COI). Despite outliers, Isospora sequences largely grouped by host species and/or host family. Additional research is warranted into the degree of interspecies transmission and host-switching of Isospora parasites, and risk factors for the development of severe disease in passerine birds.

  View details for DOI 10.3389/fvets.2022.847030

  View details for PubMedID 35847651

• Ascorbic Acid and Iron Supplement Treatment Improves Stem Cell-Mediated Cartilage Regeneration in a Minipig Model. The American journal of sports medicine Theruvath, A. J., Mahmoud, E. E., Wu, W., Nejadnik, H., Kiru, L., Liang, T., Felt, S., Daldrup-Link, H. E. 2021: 3635465211005754

  Abstract

  BACKGROUND: The transplantation of mesenchymal stem cells (MSCs) into cartilage defects has led to variable cartilage repair outcomes. Previous in vitro studies have shown that ascorbic acid and reduced iron independently can improve the chondrogenic differentiation of MSCs. However, the combined effect of ascorbic acid and iron supplementation on MSC differentiation has not been investigated.PURPOSE: To investigate the combined in vivo effects of ascorbic acid and a US Food and Drug Administration (FDA)-approved iron supplement on MSC-mediated cartilage repair in mature Gottingen minipigs.STUDY DESIGN: Controlled laboratory study.METHODS: We pretreated bone marrow-derived MSCs with ascorbic acid and the FDA-approved iron supplement ferumoxytol and then transplanted the MSCs into full-thickness cartilage defects in the distal femurs of Gottingen minipigs. Untreated cartilage defects served as negative controls. We evaluated the cartilage repair site with magnetic resonance imaging at 4 and 12 weeks after MSC implantation, followed by histological examination and immunofluorescence staining at 12 weeks.RESULTS: Ascorbic acid plus iron-pretreated MSCs demonstrated a significantly better MOCART (magnetic resonance observation of cartilage repair tissue) score (73.8 ± 15.5), better macroscopic cartilage regeneration score according to the International Cartilage Repair Society (8.6 ± 2.0), better Pineda score (2.9 ± 0.8), and larger amount of collagen type II (28,469 ± 21,313) compared with untreated controls (41.3 ± 2.5, 1.8 ± 2.9, 12.8 ± 1.9, and 905 ± 1326, respectively). The obtained scores were also better than scores previously reported in the same animal model for MSC implants without ascorbic acid.CONCLUSION: Pretreatment of MSCs with ascorbic acid and an FDA-approved iron supplement improved the chondrogenesis of MSCs and led to hyaline-like cartilage regeneration in the knee joints of minipigs.CLINICAL RELEVANCE: Ascorbic acid and iron supplements are immediately clinically applicable. Thus, these results, in principle, could be translated into clinical applications.

  View details for DOI 10.1177/03635465211005754

  View details for PubMedID 33872071

• The epidemiology of fighting in group-housed laboratory mice. Scientific reports Theil, J. H., Ahloy-Dallaire, J., Weber, E. M., Gaskill, B. N., Pritchett-Corning, K. R., Felt, S. A., Garner, J. P. 2020; 10 (1): 16649

  Abstract

  Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most commonpotentially preventablemorbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression induced by introducing a stimulus mouse into the home-cageof a singly housed mouse (i.e. the resident/intruder test). However, fighting occurring in mice living together in long-term groups under standard laboratory housing conditions has barely been studied. We performed a point-prevalence epidemiological survey of fighting at a research institution with an approximate 60,000 cage census. A subset of cages was sampled over the course of a year and factors potentially influencing home-cage fighting were recorded. Fighting was almost exclusively seen in group-housed male mice. Approximately 14% of group-housed male cages were observed with fighting animals in brief behavioral observations, but only 14% of those cages with fighting had skin injuries observable from cage-side. Thus simple cage-side checks may be missing the majority of fighting mice. Housing system (the combination of cage ventilation and bedding type), genetic background, time of year, cage location on the rack, and rack orientation in the room were significant risk factors predicting fighting. Of these predictors, only bedding type is easily manipulated to mitigate fighting. Cage ventilation and rack orientation often cannot be changed in modern vivaria, as they are baked in by cookie-cutter architectural approaches to facility design. This study emphasizes the need to invest in assessing the welfare costs of new housing and husbandry systems before implementing them.

  View details for DOI 10.1038/s41598-020-73620-0

  View details for PubMedID 33024186

• The Stability and Efficacy of Tricaine Methanesulfonate (MS222) Solution After Long-Term Storage JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Katz, E. M., Chu, D. K., Casey, K. M., Jampachaisri, K., Felt, S. A., Pacharinsak, C. 2020; 59 (4): 393–400

  Abstract

  Tricaine methanesulfonate (MS222) is widely used for the anesthesia and euthanasia of laboratory zebrafish. Fresh solutions have been recommended for each use; however, researchers often mix and store concentrated stock solutions for convenience and to reduce occupational exposure and environmental waste. While this is common practice, published guidelines are often inconsistent. Thus, the objective of this study was to evaluate the stability and anesthetic efficacy of MS222 after long-term storage and to develop specific storage parameters. Stock solutions (100 mg/mL MS222) were mixed and stored in amber jars at 4 °C and -20 °C for 2- and 6-mo. Stability of the solutions was analyzed using liquid chromatography-ion trapmass spectrometry and compared with fresh MS222. Fifty adult (30 male, 20 female) wildtype AB zebrafish (Danio rerio) wererandomly anesthetized with 150 mg/L of one of the following MS222 solutions to evaluate anesthetic efficacy: 1) freshly prepared(0m); 2) 2 mo at 4 °C (2m4); 3) 2 mo at -20 °C (2m-20); 4) 6 mo at 4 °C (6m4); 5) 6 mo at -20 °C (6m-20). Time to cessation of swimming, loss of equilibrium, lack of response to von Frey (VF) stimulation, return of equilibrium, and resumption of swimming were compared between groups. Two fish from each group were euthanized at 24-h and 2-wk after anesthesia, and histopathology was performed. All solutions were determined to be stable under all storage conditions. No clinically significant differences were observed between the fresh and stored stock groups during anesthetic testing. No evidence ofanesthetic-related histologic changes were noted in the gills, skin, kidneys, muscle, and central nervous system. Hepatic megalocytosis and a reduction in hepatic vacuolation were seen to varying degrees across all groups, but did not follow a treatment-related trend. Therefore, 100 mg/mL solutions of MS222 can be stored in amber jars at 4 °C or -20 °C for 6 mo and still used to effectively anesthetize zebrafish.

  View details for DOI 10.30802/AALAS-JAALAS-19-000067

  View details for Web of Science ID 000569144100009

  View details for PubMedID 32532365

  View details for PubMedCentralID PMC7338872

• Hamsters and Gerbils EXOTIC ANIMAL LABORATORY DIAGNOSIS McKeon, G. P., Nagamine, C. M., Felt, S. A., Heatley, J. J., Russell, K. E. 2020: 113-128

  View details for Web of Science ID 000714150500008

• Biodegradable Fluorescent Nanoparticles for Endoscopic Detection of Colorectal Carcinogenesis ADVANCED FUNCTIONAL MATERIALS Rogalla, S., Flisikowski, K., Gorpas, D., Mayer, A. T., Flisikowska, T., Mandella, M. J., Ma, X., Casey, K. M., Felt, S. A., Saur, D., Ntziachristos, V., Schnieke, A., Contag, C. H., Gambhir, S. S., Harmsen, S. 2019; 29 (51)

  View details for DOI 10.1002/adfm.201904992

  View details for Web of Science ID 000516572400007

• Ultrasound/microbubble-mediated targeted delivery of anticancer microRNA-loaded nanoparticles to deep tissues in pigs. Journal of controlled release : official journal of the Controlled Release Society Di Ianni, T., Bose, R. J., Sukumar, U. K., Bachawal, S., Wang, H., Telichko, A., Herickhoff, C., Robinson, E., Baker, S., Vilches-Moure, J. G., Felt, S. A., Gambhir, S. S., Paulmurugan, R., Dahl, J. D. 2019

  Abstract

  In this study, we designed and validated a platform for ultrasound and microbubble-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have been shown to reprogram tumor cells and sensitize them to clinically used chemotherapy. To overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into nanocarriers. Focused ultrasound combined with gas-filled microbubbles provides a noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded particles. A single handheld, curvilinear ultrasound array was used in this study for image-guided therapy with clinical-grade SonoVue contrast agent. First, we validated the platform on phantoms to optimize the microbubble cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA nanoparticles co-loaded with antisense-miRNA-21 and antisense-miRNA-10b to pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the ultrasound treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles to visually assess nanoparticle extravasation. Fluorescent microscopy suggested the presence of nanoparticles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that the proposed platform may be used to safely and noninvasively enhance the delivery of miRNA-loaded nanoparticles to target regions in deep organs in large animal models.

  View details for DOI 10.1016/j.jconrel.2019.07.024

  View details for PubMedID 31326463

• Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI RADIOLOGY Theruvath, A. J., Nejadnik, H., Lenkov, O., Yerneni, K., Li, K., Kuntz, L., Wolterman, C., Tuebel, J., Burgkart, R., Liang, T., Felt, S., Daldrup-Link, H. E. 2019; 292 (1): 129–37

  View details for DOI 10.1148/radiol.2019182176

  View details for Web of Science ID 000472154500021

• Structural Equation Modeling (SEM) of Cysticercosis in School-Aged Children in Tibetan Rural Farming Areas of Western China: Implications for Intervention Planning. International journal of environmental research and public health Zhou, H., Wang, Q., Zhou, J., Li, T., Medina, A., Felt, S. A., Rozelle, S., Openshaw, J. J. 2019; 16 (5)

  Abstract

  Neurocysticercosis (NCC) significantly contributes to morbidity in developing countries. We recently published a study of prevalence and risk factors in school-aged children in three mountainous areas in Sichuan province of western China. Using structural equation modeling (SEM) on data from that study to guide intervention planning, here we examine risk factors grouped into three broad interventional categories: sociodemographics, human behavior, and sources of pork and pig husbandry. Because neuroimaging is not easily available, using SEM allows for the use of multiple observed variables (serological tests and symptoms) to represent probable NCC cases. Data collected from 2608 students was included in this analysis. Within this group, seroprevalence of cysticercosis IgG antibodies was 5.4%. SEM results showed that sociodemographic factors (beta = 0.33, p < 0.05), sources of pork and pig husbandry (beta = 0.26, p < 0.001), and behavioral factors (beta = 0.33, p < 0.05) were all directly related to probable NCC in school-aged children. Sociodemographic factors affected probable NCC indirectly via sources of pork and pig husbandry factors (beta = 0.07, p < 0.001) and behavioral variables (beta = 0.07, p < 0.001). Both sociodemographic factors (beta = 0.07, p < 0.05) and sources of pork and pig husbandry factors (beta = 0.10, p < 0.01) affected probable NCC indirectly via behavioral variables. Because behavioral variables not only had a large direct effect but also served as a critical bridge to strengthen the effect of sociodemographics and sources of pork and pig husbandry on probable NCC, our findings suggest that interventions targeting behavioral factors may be the most effective in reducing disease.

  View details for PubMedID 30836642

• Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Bachawal, S. V., Park, J. M., Valluru, K. S., Loft, M. D., Felt, S. A., Vilches-Moure, J. G., Saenz, Y. F., Daniel, B., Iagaru, A., Sonn, G., Cheng, Z., Spielman, D. M., Willmann, J. K. 2019

  Abstract

  PURPOSE: To assess whether simultaneous hyperpolarized C-13 magnetic resonance spectroscopy (MRS)/positron emission tomography (PET)/multiparametric magnetic resonance (mpMR) imaging is feasible in an orthotopic canine prostate cancer (PCa) model using a clinical PET/MR system and whether the combined imaging datasets can be fused with transrectal ultrasound (TRUS) in real time for multimodal image fusion-guided targeted biopsy of PCa.PROCEDURES: Institutional Animal Care and Use Committee approval was obtained for this study. Canine prostate adenocarcinoma (Ace-1) cells were orthotopically injected into the prostate of four dogs. Once tumor engraftment was confirmed by TRUS, simultaneous hyperpolarized C-13 MRS of [1-13C]pyruvate, PET (2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), [68Ga]NODAGA-SCH1), and mpMR (T2W, DWI) imaging was performed using a clinical PET/MR system. Multimodality imaging data sets were then fused with TRUS and image-guided targeted biopsy was performed. Imaging results were then correlated with histological findings.RESULTS: Successful tumor engraftment was histologically confirmed in three of the four dogs (dogs 2, 3, and 4) and simultaneous C-13 MRS/PET/mpMR was feasible in all three. In dog 2, C-13 MRS showed increased lactate signal in the tumor (lactate/totalC=0.47) whereas mpMR did not show any signal changes. In dog 3, [18F]FDG-PET (SUVmean=1.90) and C-13 MRS (lactate/totalC=0.59) showed elevated metabolic activity in the tumor. In dog 4, [18F]FDG (SUVmean=2.43), [68Ga]NODAGA-SCH1 (SUVmean=0.75), and C-13 MRS (Lac/totalC=0.53) showed elevated uptake in tumor compared to control tissue and multimodal image fusion-guided biopsy of the tumor was successfully performed.CONCLUSION: Simultaneous C-13 MRS/PET/mpMR imaging and multimodal image fusion-guided biopsy is feasible in a canine PCa model.

  View details for PubMedID 30793241

• Hamsters and Gerbils Exotic Animal Laboratory Diagnosis McKeon, G., Nagamine, C., Felt, S. Wiley-Blackwell. 2019; 1
• Influence of Pain and Analgesia on Orthopedic and Wound-healing Models in Rats and Mice. Comparative medicine Huss, M. K., Felt, S. A., Pacharinsak, C. n. 2019

  Abstract

  The surgical stress response and resulting physiologic changes can lead to postoperative complications and negatively impact animal welfare. Although appropriate pain management is crucial to reduce the pain and stress response to surgery,analgesic choice can significantly affect bone and wound healing. This review aims to summarize data from rat and mouse studies and to provide recommendations for integrating analgesia into orthopedic and wound healing models in these species. Data from other species, such as humans, rabbits and other rodents, is included, where available. From these data, we conclude that for orthopedic surgical models, opioids, local anesthetics and dissociative agents have minimal impact onfracture healing; cyclooxygenase 2 (COX2) selective nonsteroidal antiinflammatory drugs (NSAID) may be used in the shortterm;and steroids should be avoided. For wound healing models, short-term systemic or topical opioids have negligible impact on wound healing; NSAID or local anesthetics may be used short-term; and systemic steroids should be avoided. Alternative analgesics such as tramadol, gabapentin, ketamine, and acetaminophen warrant consideration and further evaluation for both orthopedic and wound healing models. In all cases, researchers and veterinarians should work together todetermine the appropriate analgesic plan to minimize pain, as well as to minimize unwanted effects on the orthopedic and wound healing models themselves.

  View details for DOI 10.30802/AALAS-CM-19-000013

  View details for PubMedID 31561753

• High prevalence of taeniasis and Taenia solium cysticercosis in children in western Sichuan, China. Acta tropica Li, T. n., Chen, X. n., Wang, H. n., Openshaw, J. J., Zhong, B. n., Felt, S. A., Ito, A. n., Luby, S. P. 2019: 105133

  Abstract

  Data in China on human Taenia infections, including Taenia solium cysticercosis, is largely lacking. We aimed to determine the prevalence of taeniasis with all three human Taenia species as well as T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, China. During April 2016 to December 2017, we did a cross-sectional study in five western Sichuan Province primary schools in Liangshan (3 schools), Ganzi (1 school) and Aba (1 school) prefectures. Diagnosis of taeniasis was made by stool microscopy for presence of Taenia eggs, as well as recovery of taeniid tapeworms or proglottids by medicinal treatment followed by species identification using multiplex PCR. Diagnosis of T. solium cysticercosis was made serologically using an ELISA with low-molecular-weight antigens purified from T. solium cyst fluid to detect specific IgG antibodies. A total of 1,672 children were screened for taeniasis and 1,639 were evaluated for cysticercosis antibodies. Overall prevalence of taeniasis was 7.5% but was as high as 15.6% at one school site (e.g., Shuiluo). Of the three known human Taenia species, adult T. solium tapeworms were detected in 42 children from four of the five schools (all three schools in Liangshan and one in Aba), giving a prevalence of T. solium taeniasis of 2.5% (95% confidence interval 0-6.7%). Cysticercosis antibody seropositivity by school varied from 2.3% to 15.6% (overall 7.5%). T. solium taeniasis carriers were more likely to have cysticercosis antibodies than chlidren without T. solium taeniasis (43.6% vs 6.6%). Schools with higher prevalences of T. solium taeniasis were more likely to have children with human cysticercosis IgG antibodies. This study discloses a high prevalence of taeniasis and T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, suggesting an urgent necessity for school-based disease control.

  View details for DOI 10.1016/j.actatropica.2019.105133

  View details for PubMedID 31415736

• A Bird's-Eye View of Regulatory, Animal Care, and Training Considerations Regarding Avian Flight Research. Comparative medicine Baker, S. W., Tucci, E. R., Felt, S. A., Zehnder, A. n., Lentink, D. n., Vilches-Moure, J. G. 2019

  Abstract

  A thorough understanding of how animals fly is a central goal of many scientific disciplines. Birds are a commonly usedmodel organism for flight research. The success of this model requires studying healthy and naturally flying birds in a laboratory setting. This use of a nontraditional laboratory animal species presents unique challenges to animal care staff and researchers alike. Here we review regulatory, animal care, and training considerations associated with avian flight research.

  View details for DOI 10.30802/AALAS-CM-18-000033

  View details for PubMedID 30764892

• US Molecular Imaging of Acute Ileitis: Anti-Inflammatory Treatment Response Monitored with Targeted Microbubbles in a Preclinical Model. Radiology Wang, H., Hyvelin, J., Felt, S. A., Guracar, I., Vilches-Moure, J. G., Cherkaoui, S., Bettinger, T., Tian, L., Lutz, A. M., Willmann, J. K. 2018: 172600

  Abstract

  Purpose To evaluate whether dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in an acute terminal ileitis model in swine. Materials and Methods The Institutional Animal Care and Use Committee approved all animal studies. Fourteen swine with chemically induced acute terminal ileitis (day 0) were randomized into the following groups: (a) an anti-inflammatory treatment group (n = 8; meloxicam, 0.25 mg per kilogram of body weight; prednisone, 0.5 mg/kg) and (b) a control group (n = 6; saline). US molecular imaging was performed with a clinical US machine after intravenous injection of clinically translatable dual P- and E-selectin-targeted microbubbles (5 * 108/kg). Three inflamed bowel segments per swine were imaged at baseline, as well as on days 1, 3, and 6 after treatment initiation. At day 6, bowel segments were analyzed ex vivo for selectin expression levels by using quantitative immunofluorescence. Results After induction of inflammation, US molecular imaging signal increased at day 1 in both animal groups (P < .001). At day 3, signal in the treatment group decreased (P < .001 vs day 1), while signal in control animals did not significantly change (P = .18 vs day 1) and was higher (P = .001) compared with that in the treatment group. At day 6, signal in the treatment group further decreased and remained lower (P = .02) compared with that in the control group. Immunofluorescence confirmed significant (P ≤ .04) downregulation of both P- and E-selectin expression levels in treated versus control bowel segments. Conclusion Dual-selectin-targeted US molecular imaging allows longitudinal monitoring of anti-inflammatory treatment effects in a large-animal model of acute ileitis. This supports further clinical development of this quantitative and radiation-free technique for monitoring inflammatory bowel disease.

  View details for PubMedID 30040040

• A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS Charthad, J., Chang, T., Liu, Z., Sawaby, A., Weber, M. J., Baker, S., Gore, F., Felt, S. A., Arbabian, A. 2018; 12 (2): 257–70

  Abstract

  A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm3, 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm2 optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.

  View details for DOI 10.1109/TBCAS.2018.2799623

  View details for Web of Science ID 000428547600001

  View details for PubMedID 29578414

• Prevalence and risk factors for Taenia solium cysticercosis in school-aged children: A school based study in western Sichuan, People's Republic of China. PLoS neglected tropical diseases Openshaw, J. J., Medina, A. n., Felt, S. A., Li, T. n., Huan, Z. n., Rozelle, S. n., Luby, S. P. 2018; 12 (5): e0006465

  Abstract

  Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment during formative school years. While previous epidemiologic studies have suggested high prevalence in rural China, the prevalence in children as well as risk factors and impact of disease in low-resource areas remain poorly characterized.Utilizing school based sampling, we conducted a cross-sectional study, administering a questionnaire and collecting blood for T. solium cysticercosis antibodies in 2867 fifth and sixth grade students across 27 schools in west Sichuan. We used mixed-effects logistic regression models controlling for school-level clustering to study associations between risk factors and to characterize factors influencing the administration of deworming medication. Overall prevalence of cysticercosis antibodies was 6%, but prevalence was significantly higher in three schools which all had prevalences of 15% or higher. Students from households owning pigs (adjusted odds ratio [OR] 1.81, 95% CI 1.08-3.03), from households reporting feeding their pigs human feces (adjusted OR 1.49, 95% CI 1.03-2.16), and self-reporting worms in their feces (adjusted OR 1.85, 95% CI 1.18-2.91) were more likely to have cysticercosis IgG antibodies. Students attending high prevalence schools were more likely to come from households allowing pigs to freely forage for food (OR 2.26, 95% CI 1.72-2.98) and lacking a toilet (OR 1.84, 95% CI 1.38-2.46). Children who were boarding at school were less likely to have received treatment for gastrointestinal worms (adjusted OR 0.58, 95% CI 0.42-0.80).Our study indicates high prevalences of cysticercosis antibodies in young school aged children in rural China. While further studies to assess potential for school-based transmission are needed, school-based disease control may be an important intervention to ensure the health of vulnerable pediatric populations in T. solium endemic areas.

  View details for PubMedID 29738570

  View details for PubMedCentralID PMC5959190

• Safety Considerations When Working with Humanized Animals ILAR JOURNAL Villano, J. S., Vleck, S. E., Felt, S. A., Myers, D. D., Lester, P. A. 2018; 59 (2): 150–60

  View details for DOI 10.1093/ilar/ily012

  View details for Web of Science ID 000491467100005

• EVIDENCE CONSISTENT WITH SCHOOL BASED TRANSMISSION OF <it>TAENIA SOLIUM</it> CYSTICERCOSIS IN PRIMARY SCHOOLS, SOUTHWEST CHINA Openshaw, J., Chedid, C., Medina, A., Felt, S., Li, T., Huan, Z., Rozelle, S., Luby, S. AMER SOC TROP MED & HYGIENE. 2018: 7

  View details for Web of Science ID 000461386602022

• Anatomical Road Mapping Using CT and MR Enterography for Ultrasound Molecular Imaging of Small Bowel Inflammation in Swine. European radiology Wang, H. n., Felt, S. A., Guracar, I. n., Taviani, V. n., Zhou, J. n., Sigrist, R. M., Zhang, H. n., Liau, J. n., Vilches-Moure, J. G., Tian, L. n., Saenz, Y. n., Bettinger, T. n., Hargreaves, B. A., Lutz, A. M., Willmann, J. K. 2018; 28 (5): 2068–76

  Abstract

  To evaluate the feasibility and time saving of fusing CT and MR enterography with ultrasound for ultrasound molecular imaging (USMI) of inflammation in an acute small bowel inflammation of swine.Nine swine with ileitis were scanned with either CT (n = 3) or MR (n = 6) enterography. Imaging times to load CT/MR images onto a clinical ultrasound machine, fuse them to ultrasound with an anatomical landmark-based approach, and identify ileitis were compared to the imaging times without anatomical road mapping. Inflammation was then assessed by USMI using dual selectin-targeted (MBSelectin) and control (MBControl) contrast agents in diseased and healthy control bowel segments, followed by ex vivo histology.Cross-sectional image fusion with ultrasound was feasible with an alignment error of 13.9 ± 9.7 mm. Anatomical road mapping significantly reduced (P < 0.001) scanning times by 40%. Localising ileitis was achieved within 1.0 min. Subsequently performed USMI demonstrated significantly (P < 0.001) higher imaging signal using MBSelectin compared to MBControl and histology confirmed a significantly higher inflammation score (P = 0.006) and P- and E-selectin expression (P ≤ 0.02) in inflamed vs. healthy bowel.Fusion of CT and MR enterography data sets with ultrasound in real time is feasible and allows rapid anatomical localisation of ileitis for subsequent quantification of inflammation using USMI.• Real-time fusion of CT/MRI with ultrasound to localise ileitis is feasible. • Anatomical road mapping using CT/MRI significantly decreases the scanning time for USMI. • USMI allows quantification of inflammation in swine, verified with ex vivo histology.

  View details for PubMedID 29170798

• High prevalence of Taenia solium taeniasis and cysticercosis in Tibetan schoolchildren in western Sichuan, China: a cross-sectional study Li, T., Openshaw, J. J., Chen, X., Medina, A. C., Felt, S. A., Zhou, H., Rozelle, S. D., Luby, S. P. ELSEVIER SCIENCE INC. 2017: S89

  View details for Web of Science ID 000440459400090

• Acute and Chronic Outcomes of Gas-Bubble Disease in a Colony of African Clawed Frogs (Xenopus laevis) COMPARATIVE MEDICINE Tsai, J. Y., Felt, S. A., Bouley, D. M., Green, S. L. 2017; 67 (1): 4-10

  Abstract

  Gas-bubble disease occurs in aquatic species that are exposed to water that is supersaturated with gases. In February 2007, municipal water supersaturated with gas was inadvertently pumped into the vivarium's aquatic housing systems and affected approximately 450 adult female Xenopus laevis. The inflow of supersaturated water was stopped immediately, the holding tanks aggressively aerated, and all experimental manipulations and feeding ceased. Within the first 6 h after the event, morbidity approached 90%, and mortality reached 3.5%. Acutely affected frogs showed clinical signs of gas-bubble disease: buoyancy problems, micro- and macroscopic bubbles in the foot webbing, hyperemia in foot webbing and leg skin, and loss of the mucous slime coat. All of the frogs that died or were euthanized had areas of mesenteric infarction, which resulted in intestinal epithelial necrosis and degeneration of the muscular tunic. Over the subsequent 2 wk, as gas saturation levels returned to normal, the clinical symptoms resolved completely in the remaining frogs. However, 3 mo later, 85% of them failed to lay eggs or produce oocytes, and the remaining 15% produced oocytes of low number and poor quality, yielding cytosolic extracts with poor to no enzymatic activity. Histology of the egg mass from a single 2- to 3-y-old frog at 3 mo after disease resolution revealed irregularly shaped oocytes, few large mature oocytes, and numerous small, degenerating oocytes. At 6 mo after the incident, the remaining frogs continued to fail to produce eggs of sufficient quantity or quality after hormonal priming. The researchers consequently opted to cull the remainder of the colony and repopulate with new frogs.

  View details for Web of Science ID 000394079600001

  View details for PubMedCentralID PMC5310619

• Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Kang, S. C., Jampachaisri, K., Seymour, T. L., Felt, S. A., Pacharinsak, C. 2017; 56 (1): 63-68

  View details for Web of Science ID 000392258600010

• Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Seymour, T. L., Adams, S. C., Felt, S. A., Jampachaisri, K., Yeomans, D. C., Pacharinsak, C. 2016; 55 (3): 300-305

  Abstract

  Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  View details for Web of Science ID 000375510400008

  View details for PubMedID 27177563

• A "Pedi" Cures All: Toenail Trimming and the Treatment of Ulcerative Dermatitis in Mice PLOS ONE Adams, S. C., Garner, J. P., Felt, S. A., Geronimo, J. T., Chu, D. K. 2016; 11 (1)

  Abstract

  Ulcerative Dermatitis (UD) is the most common cause of unplanned euthanasia in mice used in research, with prevalence rates reported between 4 and 21%. UD is characterized by a deep, ulcerative lesion that appears most commonly over the dorsal neck and is attendant with an intense pruritus. The underlying cause of UD is currently unknown, and as a consequence, there are no directed therapies that resolve lesions reliably. However, there is a growing body of evidence that suggests a behavioral component to the onset, maintenance, and progression of UD lesions. Scratching behavior in response to the intense pruritus associated with UD lesions may be an effective target for interventional therapies. We hypothesized that interfering with scratching behavior by trimming the toenails of mice with UD, would resolve UD lesions. To test this hypothesis, we first evaluated the efficacy of toenail trims with a single application of Vetericyn at the time of treatment versus our previous standard of care, topical Tresaderm applied daily. We found that toenail trims were significantly more effective at resolving lesions (n = 39 toenail trims, n = 100 Tresaderm, p<0.0001) with 93.3% of animals healing by 14 days (median time to lesion resolution). Furthermore, dorsal neck lesions did not recur by 42 days after a single toenail trim (n = 54); however, flank lesions did not resolve and the outcome of the two lesion distributions following treatment were significantly different (p<0.0001). Finally, we implemented toenail trims at an institutional level and found similar efficacies (approximately 90%) for toenail trims regardless of one-time topical supplement used (triple antibiotic ointment, Tresaderm, and Vetericyn, n = 55, 58, 18, p = 0.63). This is the first report of a highly effective treatment for one of the most serious welfare issues in laboratory mice.

  View details for DOI 10.1371/journal.pone.0144871

  View details for Web of Science ID 000367805100014

  View details for PubMedCentralID PMC4703297

• Systematic Literature Review of Risk Factors and Treatments for Ulcerative Dermatitis in C57BL/6 Mice. Comparative medicine Chu, D. K., Adams, S. C., Felt, S. A., Geronimo, J. n., Garner, J. P. 2016; 66 (2): 89

  View details for PubMedID 27053561

  View details for PubMedCentralID PMC4825956

• Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent RADIOLOGY Wang, H., Felt, S. A., Machtaler, S., Guracar, I., Luong, R., Bettinger, T., Tian, L., Lutz, A. M., Willmann, J. K. 2015; 276 (3): 809-817

  Abstract

  Purpose To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin-targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard. Materials and Methods The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin-targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 10(8) MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis. Results Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 10(8) MB/kg and plateaued between a dose of 10 and a dose of 20 × 10(8) MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin). Conclusion Quantitative measurements of inflammation obtained by using dual-selectin-targeted US are reproducible and correlate well with the extent of inflammation at histologic examination in a porcine acute ileitis model as a next step toward clinical translation. (©) RSNA, 2015 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2015142478

  View details for PubMedID 25965901

• A Real-Time Clinical Endoscopic System for Intraluminal, Multiplexed Imaging of Surface-Enhanced Raman Scattering Nanoparticles PLOS ONE Garai, E., Sensarn, S., Zavaleta, C. L., Loewke, N. O., Rogalla, S., Mandella, M. J., Felt, S. A., Friedland, S., Liu, J. T., Gambhir, S. S., Contag, C. H. 2015; 10 (4)

  Abstract

  The detection of biomarker-targeting surface-enhanced Raman scattering (SERS) nanoparticles (NPs) in the human gastrointestinal tract has the potential to improve early cancer detection; however, a clinically relevant device with rapid Raman-imaging capability has not been described. Here we report the design and in vivo demonstration of a miniature, non-contact, opto-electro-mechanical Raman device as an accessory to clinical endoscopes that can provide multiplexed molecular data via a panel of SERS NPs. This device enables rapid circumferential scanning of topologically complex luminal surfaces of hollow organs (e.g., colon and esophagus) and produces quantitative images of the relative concentrations of SERS NPs that are present. Human and swine studies have demonstrated the speed and simplicity of this technique. This approach also offers unparalleled multiplexing capabilities by simultaneously detecting the unique spectral fingerprints of multiple SERS NPs. Therefore, this new screening strategy has the potential to improve diagnosis and to guide therapy by enabling sensitive quantitative molecular detection of small and otherwise hard-to-detect lesions in the context of white-light endoscopy.

  View details for DOI 10.1371/journal.pone.0123185

  View details for Web of Science ID 000353711600032

  View details for PubMedID 25923788

  View details for PubMedCentralID PMC4414592

• IACUC and Laboratory Animal Resources The Care and Feeding of an IACUC: The Organization and Management of an Institutional Animal Care and Use Committee Felt, S. A., Green, S. CRC Press. 2015; 2
• Egyptian Fat-tailed Jird The Laboratory Rabbit, Guinea Pig, Hamster and Other Rodents Felt, S., Guirguis, F., Hussein, H., Merrril, N. Academic Press. 2015; 1
• Effect of Intratonsillar Injection of Steroids on the Palatine Tonsils of Rabbits LARYNGOSCOPE Cho, D., Sinha, S. R., Gardner, J. M., Schaller, M. P., Pamnani, R. D., Felt, S. A., Barral, J. K., Messner, A. H. 2014; 124 (12): 2811-2817

  Abstract

  Nasal steroids may significantly improve nasal obstructive symptoms with a reduction of adenoid size in children, but they do not consistently yield the same concurrent effect on enlarged palatine tonsils. Failure of nasal steroids to decrease the size of palatine tonsils is believed to be attributable to location and washout by saliva. The purpose of this study was to determine if direct application of steroid via intratonsillar injection would reduce the size of palatine tonsils in the rabbit model.Prospective animal study.Eight rabbits (16 tonsils) were administered intratonsillar injections of fluticasone (n = 8, 1 mg/ml) or saline (n = 8, 0.1 ml) on days 0, 3, 7, 10, 14, and 17. Two rabbits (4 tonsils) received a single steroid injection to compare single versus multiple steroid injections. The rabbit's tonsil size was measured before each injection. After the fifty injections, the tonsils were harvested for histologic analysis.A total of 16 tonsils were analyzed. After five steroid injections, the reduction (-7.7 mm(2)  ± 4.27) in size was statistically significant when compared to reduction (6.12 mm(2)  ± 6.57) in the saline injected group (P = 0.001). Repeated steroid injection was more potent than a single injection (-3.00 mm(2)  ± 3.08) in reducing the size (P = 0.006). In histologic analysis, tonsils after repeated steroid injections were significantly smaller than saline-injected tonsils (P = 0.014), without obvious lymphoid follicles.Repeated focal tonsillar injections of corticosteroids significantly reduced the size of palatine tonsils as compared to saline-injected controls. A single injection of corticosteroids appears to be effective, but not as effective, as multiple injections.N/A.

  View details for DOI 10.1002/lary.24396

  View details for Web of Science ID 000345344200034

• Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus). Journal of the American Association for Laboratory Animal Science Chum, H. H., Jampachairsri, K., McKeon, G. P., Yeomans, D. C., Pacharinsak, C., Felt, S. A. 2014; 53 (2): 193-197

  Abstract

  Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  View details for PubMedID 24602547

• Tissue Distribution of Enrofloxacin in African Clawed Frogs (Xenopus laevis) after Intramuscular and Subcutaneous Administration JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Felt, S., Papich, M. G., Howard, A., Long, T., McKeon, G., Torreilles, S., Green, S. 2013; 52 (2): 186-188

  Abstract

  As part of an enrofloxacin pharmacokinetic study, concentrations of enrofloxacin and ciprofloxacin (metabolite) were measured in various tissues (brain, heart, kidney, liver, lung, and spleen) collected from treated (subcutaneous delivery, n = 3; intramuscular delivery, n = 3; untreated controls, n = 2) adult female Xenopus laevis by using HPLC. Enrofloxacin was rapidly absorbed after administration by either route and readily diffused into all sampled tissues. Enrofloxacin and ciprofloxacin were present in the tissue samples collected at 8 h. The highest average tissue concentrations for enrofloxacin were found in kidney, with the lowest concentrations in liver. Ciprofloxacin tissue concentrations paralleled but were always lower than those of enrofloxacin for all time points and tissues except brain and kidney. These results, together with previously published pharmacokinetic data and known minimal inhibitory concentrations of common pathogenic bacteria, provide a strong evidence-based rationale for choosing enrofloxacin to treat infectious diseases in X. laevis.

  View details for Web of Science ID 000316159700010

  View details for PubMedID 23562103

• Prevalence of Batrachochytrium dendrobatidis in Xenopus Collected in Africa (1871-2000) and in California (2001-2010). PloS one Vredenburg, V. T., Felt, S. A., Morgan, E. C., McNally, S. V., Wilson, S., Green, S. L. 2013; 8 (5)

  Abstract

  International trade of the invasive South African clawed frog (Xenopus laevis), a subclinical carrier of the fungal pathogen Batrachochytrium dendrobatis (Bd) has been proposed as a major means of introduction of Bd into naïve, susceptible amphibian populations. The historical presence of Bd in the indigenous African population of Xenopus is well documented. However, there are no reports documenting the presence of Bd in wild Xenopus populations in the US, particularly in California where introduced populations are well-established after intentional or accidental release. In this report, a survey was conducted on 178 archived specimens of 6 species of Xenopus collected in Africa from 1871-2000 and on 23 archived specimens (all wild-caught Xenopus laevis) collected in California, USA between 2001 and 2010. The overall prevalence rate of Bd in the tested Xenopus was 2.8%. The earliest positive specimen was X. borealis collected in Kenya in 1934. The overall prevalence of Bd in the X. laevis collected in California was 13% with 2 positive specimens from 2001 and one positive specimen from 2003. The positive Xenopus (3/23) collected in California were collected in 2001 (2/3) and 2003 (1/3). These data document the presence of Bd-infected wild Xenopus laevis in California. The findings reported here support the prevailing hypothesis that Bd was present as a stable, endemic infection in Xenopus populations in Africa prior to their worldwide distribution likely via international live-amphibian trade.

  View details for DOI 10.1371/journal.pone.0063791

  View details for PubMedID 23691097

  View details for PubMedCentralID PMC3655066

• Biology, behavior, and environmental enrichment for the captive African clawed frog (Xenopus spp) APPLIED ANIMAL BEHAVIOUR SCIENCE Chum, H., Felt, S., Garner, J., Green, S. 2013; 143 (2-4): 150-156

  View details for DOI 10.1016/j.applanim.2012.10.013

  View details for Web of Science ID 000316154100009

• Maternal antibodies or nonproductive infections confound the need for rederivation. Journal of the American Association for Laboratory Animal Science Nagamine, C. M., Chen, L., Ho, W. Q., Felt, S. A. 2013; 52 (4): 495-498

  Abstract

  After rederivation of a mouse parvovirus (MPV)-contaminated transgenic mouse strain, serology and PCR testing of the surrogate dam showed it to be infected with mouse parvovirus strain 1 (MPV-1). The rederived pups (n = 3) also were MPVpositive, according to serology. Despite MPV seropositivity, fecal PCR tests of the pups were negative, as were serologic results from direct-contact sentinels. Only one rederived pup survived, and this male was bred successfully. None of its mates or progeny seroconverted to MPV. At 14.5 mo of age, the rederived male mouse was euthanized; tissues were collected and submitted for MPV testing; both serologic tests and PCR analysis of mesenteric lymph nodes were MPV-negative. One explanation for the rederived pups' MPV seropostivity is passive transfer of maternal antibodies or a nonproductive MPV infection. This case illustrates that although routine serological testing of surrogate mothers and pups is appropriate, any positive results should be further investigated by using transmissibility testing (fecal PCR or contact sentinels or both) prior to repeat rederivation.

  View details for PubMedID 23849450

• Analgesic Effects of Sustained Release Buprenorphine in an Incisional Model of Hyperalgesia in Rats (Rattus norvegicus) Chum, H., McKeon, G., Yeomans, D. C., Jampachaisri, K., Pacharinsak, C., Felt, S. AMER ASSOC LABORATORY ANIMAL SCIENCE. 2012: 692–92

  View details for Web of Science ID 000313303300260

• Mortality and Morbidity in African Clawed Frogs (Xenopus laevis) Associated with Construction Noise and Vibrations JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Felt, S. A., Cowan, A. M., Luong, R., Green, S. L. 2012; 51 (2): 253-256

  Abstract

  In Spring 2008, 175 adult female Xenopus laevis were exposed to construction-related vibrations that caused overt water rippling in the frog tanks. The 3 affected tanks were custom-built static, 300-gal 'pond-style' tanks that sat on the floor of the housing room. The water in the tank developed visible ripples as a result of the vibrations transmitted through the floor during jack-hammering in an adjacent room that was approximately 10 ftaway. All frogs in the tanks displayed buoyancy problems, excessive air gulping, and skin sloughing; ultimately 7 frogs died. In addition, these 7 animals were bloated, and 5 of these 7 had regurgitated and everted their stomach and distal esophagus into the oral cavity, resulting in airway obstruction and death. Gross pathologic findings included regurgitation and eversion of the stomach of the distal portion of the esophagus into the oral cavity, obstruction of the airway, and lung overinflation. No significant histologic lesions were observed. Construction vibrations transmitted through the water appeared to have disrupted the mechanoreceptive function of the lateral line system, resulting in overstimulation of the noxious feeding response, regurgitation, and eversion of the stomach and distal esophagus into the oral cavity and subsequent suffocation due to airway obstruction. After immediate cessation of the jack-hammering and relocation of the remaining frogs, no additional morbidities or mortalities occurred.

  View details for Web of Science ID 000306772200016

  View details for PubMedID 22776127

• Carbon Dioxide and Oxygen Levels in Disposable Individually Ventilated Cages after Removal from Mechanical Ventilation JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Nagamine, C. M., Long, C. T., McKeon, G. P., Felt, S. A. 2012; 51 (2): 155-161

  Abstract

  Disposable individually ventilated cages have lids that restrict air exchange when the cage is not mechanically ventilated. This design feature may cause intracage CO2 to increase and O2 to decrease (hypercapnic and hypoxic conditions, respectively) when the electrical supply to the ventilated rack fails, the ventilated rack malfunctions, cages are docked in the rack incorrectly, or cages are removed from the ventilated rack for extended periods of time. We investigated how quickly hypercapnic and hypoxic conditions developed within disposable individually ventilated cages after removal from mechanical ventilation and compared the data with nondisposable static cages, disposable static cages, and unventilated nondisposable individually ventilated cages. When disposable individually ventilated cages with 5 adult mice per cage were removed from mechanical ventilation, CO2 concentrations increased from less than 1% at 0 h to approximately 5% at 3 h and O2 levels dropped from more than 20% at 0 h to 11.7% at 6 h. The breathing pattern of the mice showed a prominent abdominal component (hyperventilation). Changes were similar for 4 adult mice per cage, reaching at least 5% CO2 at 4 h and 13.0% O2 at 6 h. For 3 or 2 mice per cage, values were 4.6% CO2 and 14.7% O2 and 3.04% CO2 and 17.1% O2, respectively, at 6 h. These results document that within disposable individually ventilated cages, a hypercapnic and hypoxic microenvironment develops within hours in the absence of mechanical ventilation.

  View details for Web of Science ID 000306772200003

  View details for PubMedID 22776114

• Serum Clinical Biochemical and Hematologic Reference Ranges of Laboratory-Reared and Wild-Caught Xenopus laevis JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Wilson, S., Felt, S., Torreilles, S., Howard, A., Behan, C., Moorhead, R., Green, S. 2011; 50 (5): 635-640

  Abstract

  The South African clawed frogs Xenopus laevis and X. tropicalis are fully aquatic amphibians and well-established animal models. Because genetically engineered laboratory Xenopus are now being produced, the establishment of normal reference ranges for serum biochemical and hematologic parameters is essential for phenotyping and as a diagnostic aide. We determined normal reference ranges for hematologic values from 3 populations of X. laevis: wild-caught frogs (n = 43) and frogs from 2 commercial sources (A, n = 166; B, n = 109). For serum biochemistry, we determined normal reference ranges for frogs from source A and wild-caught frogs divided by sex and season. Significant differences across populations were found in WBC and RBC counts, hemoglobin concentration, hematocrit, mean corpuscular hemoglobin concentration, and mean corpuscular volume. Among serum biochemical analytes, significant differences were found for albumin:globulin ratio, anion gap, and concentrations of albumin, globulin, total protein, lipase, alanine transaminase, γ-glutamyl transpeptidase; creatine phosphokinase; indirect, direct, and total bilirubin; cholesterol, low-density lipoprotein lipase, carbon dioxide, glucose, lactacte dehydrogenase, calcium, chloride, and sodium. We hypothesize that these differences can be attributed to differences in water quality, habitat, ambient temperature, diet, sex, recent transport or shipment, and genetic background. However, testing that hypothesis is beyond the scope of the current study. In addition, clinical chemistry and hematologic reference range values Xenopus laevis are quite distinct from those for other species and are most consistent with the only values published for another fully aquatic amphibian, the Eastern hellbender (Cryptobranchus alleganiensis).

  View details for Web of Science ID 000296070000004

  View details for PubMedID 22330708

• A far-reaching career LAB ANIMAL Felt, S. A. 2011; 40 (5): 162-163

  Abstract

  An interview with Stephen A. Felt, DVM, MPH, DACLAM, DACVPM, Attending Veterinarian, Assistant Professor, Department of Comparative Medicine, Associate Director, Veterinary Service Center, Director, Laboratory Animal Medicine Residency Program, Stanford University, Stanford, CA.

  View details for Web of Science ID 000289998600018

  View details for PubMedID 21508955

• Comparison of rectal and tympanic core body temperature measurement in adult Guyanese squirrel monkeys (Saimiri sciureus sciureus) JOURNAL OF MEDICAL PRIMATOLOGY Long, C. T., Pacharinsak, C., Jampachaisri, K., McKeon, G. P., Howard, A. M., Albertelli, M. A., Felt, S. A. 2011; 40 (2): 135-141

  Abstract

  Measuring core body temperature in a manner that is safe for animals and veterinary personnel is an important part of a physical examination. For nonhuman primates, this can involve increased restraint, additional stress, as well as the use of anesthetics and their deleterious effects on body temperature measurements. The purpose of this study was to compare two non-invasive methods of infrared tympanic thermometry to standard rectal thermometry in adult squirrel monkeys.Tympanic temperatures were collected from 37 squirrel monkeys and compared to rectal temperatures using a human and veterinary infrared tympanic thermometer.Compared with rectal temperature measurements, the human tympanic thermometer readings were not significantly different, while the veterinary tympanic thermometer measurements were significantly higher (P<0.05). There were no differences between sexes.The tympanic thermometer designed for use in humans can be used in adult squirrel monkeys as an alternative to rectal thermometry for assessing core body temperature.

  View details for DOI 10.1111/j.1600-0684.2010.00449.x

  View details for Web of Science ID 000287965500009

  View details for PubMedID 20946145

• Cross-Species Surveillance of Leptospira in Domestic and Pen-Domestic Animals in Mahalla City, Gharbeya Governorate, Egypt AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Felt, S. A., Wasfy, M. O., El-Tras, W. F., Samir, A., Rahaman, B. A., Boshra, M., Parker, T. M., Hatem, M. E., El-Bassiouny, A. A., Murray, C. K., Pimentel, G. 2011; 84 (3): 420-425

  Abstract

  A survey of 179 animals (black rats, dogs, sheep, buffaloes, cattle, donkeys, weasels, and cats) for Leptospira infection was conducted in Mahalla City (Lower Egypt). Blood, urine, and kidney were collected and tested by culture, microscopic agglutination test (MAT), and/or polymerase chain reaction (PCR). Among rats, 26% were positive by PCR, including 7% that were also positive by culture for L. interrogans serovars Grippotyphosa, Pyrogenes, and Icterohaemorrhagiae. L. borpetersenii serovar Polonica was isolated for the first time in Egypt in three rats. MAT titers ≥ 1:800 were observed in 11% of rats and 12% of dogs. L. interrogans serovar Grippotyphosa was detected in one cat. Sheep and donkeys were negative for leptospirosis by all methods. Buffaloes and cattle were seropositive in 20% and 44% of animals, respectively. Data indicate that several pathogenic serovars are circulating in the animals, which may pose exposure risks and account for high rates of acute febrile illness.

  View details for DOI 10.4269/ajtmh.2011.10-0393

  View details for Web of Science ID 000287995600011

  View details for PubMedID 21363980

  View details for PubMedCentralID PMC3042818

• EFFECTS OF RAINFALL, HOST DEMOGRAPHY, AND MUSTH ON STRONGYLE FECAL EGG COUNTS IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA) IN NAMIBIA JOURNAL OF WILDLIFE DISEASES Thurber, M. I., O'Connell-Rodwell, C. E., Turner, W. C., Nambandi, K., KINZLEY, C., Rodwel, T. C., Faulkner, C. T., Felt, S. A., Bouley, D. M. 2011; 47 (1): 172-181

  Abstract

  Wild African elephants (Loxodonta africana) are commonly infected with intestinal strongyle parasites. Our objective was to determine baseline fecal strongyle egg counts for elephants in the northeast region of Etosha National Park, Namibia and determine if these numbers were affected by annual rainfall, elephant demography (age of individuals and composition of groups), and hormonal state of males. We found that matriarchal family group members have significantly higher fecal egg counts than male elephants (bulls). Among family group members, strongyle egg counts increased with age, whereas among bulls, strongyle egg counts decreased with age. Years of higher rainfall were correlated with decreased numbers of strongyle eggs among bulls. Finally, bulls were not affected by their physiologic (hormonal) status (musth vs. nonmusth). These results suggest that infection by strongyle parasites in Namibian African elephants is a dynamic process affected by intrinsic and extrinsic factors including host demography and rainfall.

  View details for Web of Science ID 000287280200016

  View details for PubMedID 21270006

• Analgesic Effects of Tramadol, Tramadol-Gabapentin, and Buprenorphine in an Incisional Model of Pain in Rats (Rattus norvegicus) Journal of the American Association for Laboratory Animal Science McKeon, G., Pacharinsak, Cholawat; Long, Charles T.; Howard, Antwain M.; Jampachaisri, Katechan; Yeomans, David C; Felt, Stephen A. 2011; 50 (2): 192-197
• The Pharmacokinetics of Enrofloxacin in Adult African Clawed Frogs (Xenopus laevis) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Howard, A. M., Papich, M. G., Felt, S. A., Long, C. T., McKeon, G. P., Bond, E. S., Torreilles, S. L., Luong, R. H., Green, S. L. 2010; 49 (6): 800-804

  Abstract

  Pharmacokinetics of enrofloxacin, a fluoroquinolone antibiotic, was determined in adult female Xenopus laevis after single-dose administration (10 mg/kg) by intramuscular or subcutaneous injection. Frogs were evaluated at various time points until 8 h after injection. Plasma was analyzed for antibiotic concentration levels by HPLC. We computed pharmacokinetic parameters by using noncompartmental analysis of the pooled concentrations (naive pooled samples). After intramuscular administration of enrofloxacin, the half-life was 5.32 h, concentration maximum was 10.85 μg/mL, distribution volume was 841.96 mL/kg, and area under the time-concentration curve was 57.59 μg×h/mL; after subcutaneous administration these parameters were 4.08 h, 9.76 μg/mL, 915.85 mL/kg, and 47.42 μg×h/mL, respectively. According to plasma pharmacokinetics, Xenopus seem to metabolize enrofloxacin in a manner similar to mammals: low levels of the enrofloxacin metabolite, ciprofloxacin, were detected in the frogs' habitat water and plasma. At necropsy, there were no gross or histologic signs of toxicity after single-dose administration; toxicity was not evaluated for repeated dosing. The plasma concentrations reached levels considered effective against common aquatic pathogens and suggest that a single, once-daily dose would be a reasonable regimen to consider when treating sick frogs. The treatment of sick frogs should be based on specific microbiologic identification of the pathogen and on antibiotic susceptibility testing.

  View details for Web of Science ID 000284791700002

  View details for PubMedID 21205443

• A Bistable Switch and Anatomical Site Control Vibrio cholerae Virulence Gene Expression in the Intestine PLOS PATHOGENS Nielsen, A. T., Dolganov, N. A., Rasmussen, T., Otto, G., Miller, M. C., Felt, S. A., Torreilles, S., Schoolnik, G. K. 2010; 6 (9)

  Abstract

  A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP) and cholera toxin (CT) were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co-localize with virulence gene expression. Significant heterogeneity in the expression of tcpA, the repeating subunit of TCP, was observed late in the infectious process. The expression of tcpA, studied in single cells in a homogeneous medium, demonstrated unimodal induction of tcpA after addition of bicarbonate, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal master regulator of virulence gene expression also exhibited the bifurcation phenotype. The bifurcation phenotype was found to be reversible, epigenetic and to persist after removal of bicarbonate, features consistent with bistable switches. The bistable switch requires the positive-feedback circuit controlling ToxT expression and formation of the CRP-cAMP complex during entry into stationary phase. Key features of this bistable switch also were demonstrated in vivo, where striking heterogeneity in tcpA expression was observed in luminal fluid in later stages of the infection. When this fluid was diluted into artificial seawater, bacterial aggregates continued to express tcpA for prolonged periods of time. The bistable control of virulence gene expression points to a mechanism that could generate a subpopulation of V. cholerae that continues to produce TCP and CT in the rice water stools of cholera patients.

  View details for DOI 10.1371/journal.ppat.1001102

  View details for PubMedID 20862321

• COMPARISON OF GASTROGRAFIN TO BARIUM SULFATE AS A GASTROINTESTINAL CONTRAST AGENT IN RED-EARED SLIDER TURTLES (TRACHEMYS SCRIPTA ELEGANS) VETERINARY RADIOLOGY & ULTRASOUND Long, C. T., Page, R. B., Howard, A. M., McKeon, G. P., Felt, S. A. 2010; 51 (1): 42-47

  Abstract

  Red-eared slider turtles (Trachemys scripta elegans) commonly develop intestinal obstruction. The gastrointestinal transit time in turtles tends to be longer than in other animals, making a rapid diagnosis of obstruction difficult. Fifteen red-eared sliders were given either Gastrografin or 30% w/v barium sulfate orally to compare ease of administration, transit time, and image quality. Each contrast medium was easy to administer but barium sulfate had to be administered more slowly (mean = 40s) than Gastrografin (mean = 20s) to prevent regurgitation. The mean transit and emptying time of Gastrografin was at least 9 h faster than barium sulfate at all time points except gastric transit. Both contrast media had a smooth, uniform appearance that outlined the mucosa with well-defined margins within the stomach and proximal small intestine. Dilution of Gastrografin occurred as it progressed through the intestines, resulting in decreased opacity in the distal small intestine and colon. Pre-administration packed cell volume and total serum protein levels of four turtles receiving Gastrografin were compared with levels at 24-, 96-, and 168-hours postadministration as well as to four control turtles not receiving contrast medium. Packed cell volume and total serum protein levels did not significantly differ among the Gastrografin and control group. From a clinical perspective, administration of Gastrografin allows for quicker results with only minor hematologic changes in red-eared sliders, but visualization of this contrast medium in the lower gastrointestinal tract may be insufficient for an accurate diagnosis.

  View details for DOI 10.1111/j.1740-8261.2009.01619.x

  View details for Web of Science ID 000273372200007

  View details for PubMedID 20166392

• ACARIASIS IN CAPTIVE FAT-TAILED JIRDS (PACHYUROMYS DUPRASI) JOURNAL OF ZOO AND WILDLIFE MEDICINE Felt, S. A. 2009; 40 (1): 217-219

  Abstract

  This case report describes acariasis in captive, wild-caught, fat-tailed jirds (Pachyuromys duprasi). All animals within the cage (n = 4) were examined for pruritus and alopecia and subsequently found to be infested with the mite Pyroglyphis morgan ii. All life stages of the mite were identified on animals and within the nesting materials. Treatment, including repeated subcutaneous ivermectin administration and husbandry practice modifications, proved effective in eradicating the mites and in subsequent amelioration of clinical signs.

  View details for Web of Science ID 000264775800035

  View details for PubMedID 19368268

• An Effective Venipuncture Technique and Normal Serum Biochemistry Parameters of the Captive Fat-Tailed Jird (Pachyuromys duprasi) JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE Felt, S. A., Guirguis, F. I., Wasfy, M. O., Howard, J. S., Domingo, N. V., Hussein, I. H. 2009; 48 (1): 57-60

  Abstract

  Thirty-nine captively reared fat-tailed jirds (Pachyuromys duprasi) were enrolled in a minimally invasive study to determine an effective venipuncture technique and establish normal serum biochemistry parameters. A jugular venipuncture technique using chemical restraint (ketamine, 30 mg/kg; xylazine, 6 mg/kg; acepromazine, 1 mg/kg) administered intraperitoneally was safe and consistently yielded at least 0.3 mL of blood. Of the biochemical indicators measured (glucose, total protein, albumin, globulin, alkaline phosphatase, alanine transferase, total bilirubin, amylase, BUN, creatinine, calcium, phosphorous, sodium and potassium), amylase and glucose levels differed significantly between male and female fat-tailed jirds.

  View details for Web of Science ID 000263137800010

  View details for PubMedID 19245752

• Tacrolimus Ointment: An Effective Topical Treatment of Localized Atopic Dermatitis in a Rhesus Macaque (Macaca mulatta) JAALAS Torreilles SL, Luong RH, Felt SA, McClure DE 2009; 48 (3): 307-311
• Biology, breeding, husbandry and diseases of the captive Egyptian fat-tailed jird (Pachyuromys duprasi natronensis) LAB ANIMAL Felt, S. A., Hussein, H. I., Helmy, I. M. 2008; 37 (6): 256-261

  Abstract

  The fat-tailed jird, a small North African rodent with a distinctive club-shaped tail, is a convenient research subject and an emerging model for Old World leishmaniasis. The authors present the natural history and biology of the Egyptian fat-tailed jird and provide guidelines for the breeding and husbandry of this species on the basis of their experience raising a colony from wild stock in Cairo, Egypt. They also discuss the diseases they encountered in wild and captive-bred jirds.

  View details for Web of Science ID 000256765800008

  View details for PubMedID 18496544

• Cutaneous Leishmaniasis in the Volta District of Ghana: an Uncertain Reservoir for Focal Disease Outbreak Libyan Journal of Infectious Diseases Raczniak G, Villinski JT, Puplampu N, Mechta S, Klena JD, Felt S, Abbassy M, Hanafi H, Hoel DF, Wilson M, Boakye 2008; 1: 50-59
• A Multispecies Disease Outbreak of Highly Pathogenic Avian Influenza in Grd Jotyar, Iraq Libyan Journal of Infectious Diseases Felt SA, Saad MD, Yingst SL 2008; 1: 43-49
• Qinghai-like H5N1 from Domestic Cats, Northern Iraq EID Yingst SL, Saad MD, Felt SA 2006; 12 (8)
• A comparison of non-contact, subcutaneous, and rectal temperatures in captive owl monkeys (Aotus sp.) J Med Primatol Shelton LJ, White CE, Felt SA 2006; 5: 346-351
• Evaluation of a timed and repeated perianal tape test for the detection of pinworms (Trypanoxyuris microon) in owl monkeys (Aotus nancymae) J Med Primatol Felt SA, White CE. 2005; 34 (4): 209-214