Animal Facilities Research Articles

Decision trees for determining the fate of laboratory animals.

Facilities involved in laboratory animal research often face ethical challenges such as: what should I do with the animals that are no longer suitable for experimental purposes? One of the common answers to this question is to kill them. And while numerous scientifically justifiable reasons exist for killing laboratory animals, we must not overlook our ethical responsibility towards these sentient beings. Animal facility managers and scientists frequently find themselves in a moral dilemma, torn between furthering their research and addressing the well-being of experimental animals required for their studies. We elaborated a concept consisting of six decision trees and recommendations for making informed decisions about the need to kill laboratory animals in research facilities, considering legal and ethical considerations. The concept is based on the German regulatory perspective. However, the measures and decisions for animal welfare can be implemented in all laboratory animal facilities. These recommendations suggest several courses of action, including implementing consistent breeding plans, exploring alternative uses, reassigning surplus animals and their organs, and establishing appropriate housing capacity limits that ensure species-appropriate care. We encourage scientists and animal facility managers to develop and implement decision-making frameworks and procedures tailored to their specific facilities, in the hope that this work will promote a thoughtful and responsible approach to the complex challenges associated with the killing of laboratory animals, advancing scientific progress and the humane treatment of these animals.

Murine astrovirus (MuAstV) infection in mouse facilities in Brazil: First South American report.

This study aimed to investigate the presence of murine astrovirus (MuAstV) in Brazil. Fecal samples from mice belonging to four Brazilian animal facilities were collected and tested for MuAstV using real-time polymerase chain reaction. Of the 162 samples tested, 38 (23.5%) were positive for MuAstV, 33 (91.7%) of which came from specific-pathogen free colonies. Although most of the samples were obtained from asymptomatic animals, three mice presented diarrheal symptoms, and MuAstV was the only agent detected by molecular assay. Phylogenetic analysis revealed similarities between the MuAstV strains from this study and prototypes from the USA. MuAstV's high prevalence, environmental stability, genetic diversity and potential for persistent infections must be considered when evaluating health monitoring programs for laboratory rodents.

Effects of Intermittent Harem Mating on Parturition-induced Stress and Success Rate of Weaning in C57BL/6JNarl Mice.

Improving the effectiveness of mating schemes for large-scale production of mice is an ongoing challenge in animal facilities. Continuous mating, which requires fewer breeding cages than intermittent mating, has traditionally been used to take advantage of postpartum estrus for efficient production. However, the continuous mating scheme lacks flexibility because it cannot immediately accommodate the reduced needs of mice when production levels are high. In this study, we compared reproductive performance, fecal corticosterone metabolite (FCM) level as a stress indicator, and mouse mortality between the continuous trio (CT) and intermittent quad (IQ) mating schemes. The weaning rates in the IQ scheme were higher than those in the CT scheme (98.8% compared with 85.3%). The FCM levels in IQ female breeders were lower during the first 5 d after parturition than those in CT female breeders. The FCM levels in postpartum females housed with 2 adult mice were significantly higher on days 1, 3, and 5 after giving birth than those of females housed alone. This suggests that the presence of cage mates may induce stress responses in postpartum females. Increasing the individual cage area did not reduce the FCM levels of female breeders when accompanied by cage mates after parturition. In addition, the incidence of dystocia and mortality was lower in IQ breeders than in CT breeders. In summary, this breeding trial suggests that compared with the continuous mating scheme, the intermittent mating scheme improves the welfare of postpartum females with normal breeding performance in the C57BL/6JNarl production colony.

The Shadow Bodies of Mice: Invisible Work in Translational Medicine

The clinician-scientist is often viewed as the crucial nexus in the translational processes that turn scientific research into medical technologies, including but not limited to pharmaceuticals. To create a point of contrast, and to consider the theme of invisible labor, this paper foregrounds an alternative actant who has also been deemed a vital nexus in translational medicine within Science and Technology Studies: the laboratory animal as model organism. Based on observational research conducted in an animal facility that was caring for laboratory mice as well as the immunological laboratory that was conducting research regarding ageing and vaccine uptake using those mice, this paper explores how mouse bodies and animal technicians’ knowledge of those mouse bodies are rendered invisible through the everyday flows of translation. I draw on Balka and Star's concept of “shadow bodies” to consider variations in how mouse bodies are understood across the translational process and probe the consequences this has for what knowledge is legitimately produced and by whom. By making the invisible work of mice and of technicians visible, I argue that the organizational filters of translational medicine may inadvertently make the work of animal technicians all the harder, in a manner that reproduces social inequalities.

Examining imidacloprid behaviorally resistant house flies (Musca domestica L.) (Diptera: Muscidae) for neonicotinoid cross-resistance.

The house fly (Musca domestica L.) is a ubiquitous fly species commonly associated with confined animal and urban waste storage facilities. It is known for its pestiferous nature and ability to mechanically vector numerous disease-causing pathogens. Effective control of adult house fly populations has traditionally relied upon insecticidal food baits; however, due to the overuse of insecticides, resistance has proven to yield many insecticidal baits and chemical classes less effective. Imidacloprid, the most widely used neonicotinoid, has been formulated and commonly used in house fly baits for over 2 decades. However, widespread evidence of physiological and behavioral resistance to imidacloprid has been documented. While previous studies have investigated the mechanisms of behavioral resistance to imidacloprid in the house fly, it remains unclear whether behavioral resistance is specific to imidacloprid or if behavioral cross-resistance exists to other compounds within the neonicotinoid class of insecticides. The current study used no-choice and choice-feeding bioassays to examine a lab-selected imidacloprid behaviorally resistant house fly colony for cross-resistance to other insecticides in the neonicotinoid chemical class. All flies exhibited high mortality (97-100%) in no-choice assays, even when exposed to imidacloprid, indicating physiological susceptibility to all tested neonicotinoids. House flies exhibited high mortality (98-100%) in choice assays when exposed to all neonicotinoid insecticides tested besides imidacloprid. These results confirm that imidacloprid behavioral resistance is specific to the compound imidacloprid and that alternative neonicotinoids remain viable options for control. Our study showed no evidence of behavioral cross-resistance to other compounds in the neonicotinoid class.

Statistical design for health monitoring in laboratory animal facilities using sentinel animals.

Regular health monitoring is crucial in laboratory animal facilities to determine the presence or absence of specific pathogens. One common approach to monitoring involves the use of sentinel animals, which are periodically exposed to biological material from the cages being monitored. At a certain point, some of these sentinel animals are tested for pathogens. This article discusses designing an effective sampling scheme to meet desired quality standards. It addresses questions such as the number of sentinel animals required, the frequency of sampling biological material, the selection of cages based on facility set-up, and the optimal frequency and quantity of sentinel animal tests. While existing design formulas are available for simple random sampling, no quantitative recommendation exists for using sentinel animals to the best of our knowledge. We propose a Monte Carlo simulation-based approach in this article to address this. Our algorithm has been implemented in a publicly accessible web page at http://nolan.cnb.csic.es/sentinelcagesmanager.

Retrospective analysis on the occurrence of kidney cysts in mice in a central animal facility in the years 2009-2019.

Kidney cysts in humans are mainly caused by inheritable polycystic kidney disease. Although they are a regular finding in laboratory mice, their occurrence upon dissection has not been systematically investigated, yet. Therefore, the aim of this report was to investigate on prevalence, phenotype and aetiology of spontaneously occurring kidney cysts in mice by retrospectively analysing the laboratory-receipt tables of the in-house laboratory of a central animal facility in North Rhine-Westphalia, Germany, years 2009-2019. A percentage of 0.4% of dissected mice displayed kidney cysts, with more male than female animals affected and average age equal to that of all dissected animals. Preliminary report in half of the cases was distended abdomen, and a few individuals displayed additional pathologic alterations of kidneys, most commonly dilated renal pelvis, or extrarenal comorbidities. Kidney cysts occurred independently of a renal phenotype of the transgenic strain or presence of infectious agents in health monitoring. To conclude, kidney cysts were characterized as harmless for affected mice but, as inheritability is suggested according with the literature, affected animals should be excluded from breeding.

CREATING MEMORABLE TOURISM EXPERIENCES THROUGH SERVICESCAPE DESIGN: A PROPOSED MODEL FOR ZOO NEGARA MALAYSIA

This paper explores how different dimensions that form the overall servicescape of Zoo Negara Malaysia impact visitors’ memorable tourism experiences (MTE). The servicescape concept, which describes the overall physical environment within a service setting that can be controlled by the organization, is adopted for the study. In other words, it is suggested that physical cues such as animal conditions, zoo layout, design and facilities may be used by zoo operators to create memorable tourism experiences. Aspects of MTEconsist of knowledge, hedonism, meaningfulness, refreshment, local culture, novelty and involvement. A conceptual framework is proposed to investigate the relationship between zoo servicescapes and memorable tourism experience. It is expected that this study contributes towards existing academic research related to zoo tourism and provides insight into how zoo operators could design and manage their zoological facilities to increase visitor numbers.

Toward Transparency on Animal Experimentation in Switzerland: Seven Recommendations for the Provision of Public Information in Swiss Law.

In Switzerland, the importance of transparency in animal experimentation is emphasized by the Swiss Federal Council, recognizing the public's great interest in this matter. Federal reporting on animal experimentation indicates a total of 585,991 animals used in experiments in Switzerland in 2022. By Swiss law, the report enables the public to learn about many aspects such as the species and degree of suffering experienced by the animals, but some information of interest to the public is missing, such as the fate of the animals at the end of the experiment (e.g., euthanized, rehomed in a private home, reused in another experiment). When it comes to animals bred in facilities but not used in experiments, further information of interest is not required to be made public according to Swiss law, for example, the number and fate of "surplus" animals (i.e., animals bred but not used in experiments for a variety of reasons such as not carrying the phenotypical properties needed). Considering that the Swiss government has a duty to provide a full accounting of animal experimentation conducted on the public's behalf, further relevant information should be disclosed. While efforts toward transparency, such as the STAAR Agreement, have been made in the scientific community, these mostly reflect the legal requirements already in force. If Switzerland is to move toward more transparency in public information on animal experimentation, an update of the legal requirements is needed. In this article, we give recommendations for Swiss law to move toward more transparency in public information on seven aspects: (1) the fate of the animals at the end of the experiment; (2) the sources of funding for animal experimentation; (3) the harm-benefit analysis performed by researchers and ethics committees to justify an experiment using animals; (4) the number of breeding/surplus animals; (5) the fate of breeding/surplus animals; (6) the harms experienced by animals in facilities; and (7) the funding of animal facilities.

The Veterinarian’s Role in Biocontainment Research Animal Facilities and Prevention of Spread of Pathogens: A Case of Nigeria and South Africa

Infections acquired in research laboratories and unintentional pathogen escapes from breaches in biocontainment pose risks to humans and the environment, necessitating the need for effective biosafety and biosecurity management frameworks in biocontainment research animal facilities (BRAFs). We examine key biosafety issues associated with BRAFs, including inadequate decontamination procedures for wastewater and experimental samples, handling high biosafety level pathogens in lower-level laboratories, risks of animal bites and sharps injuries, contamination of bedding and enrichment materials, and improper management and transportation of biohazard samples. Additionally, we discuss the role of veterinarians in research animal facilities and the challenges they encounter in maintaining biocontainment standards. We emphasise the importance of routine monitoring of effluent water to detect possible disease outbreaks. We recommend a thorough investigation of disease outbreaks to identify potential sources of pathogen release from BRAFs, which could serve as hotspots for future disease outbreaks. Findings from such investigations will inform the development of policies aimed at safeguarding human populations from future pandemics and preventing BRAFs from becoming sources of infectious disease outbreaks.

Microglia undergo molecular and functional adaptations to dark and light phases in male laboratory mice

Microglia are increasingly recognized to contribute to brain health and disease. Preclinical studies using laboratory rodents are essential to advance our understanding of the physiological and pathophysiological roles of these cells in the central nervous system. Rodents are nocturnal animals, and they are mostly maintained in a defined light–dark cycle within animal facilities, with many laboratories investigating the molecular and functional profiles of microglia exclusively during the animals’ light (sleep) phase. However, only a few studies have considered possible differences in microglial functions between the active and sleep phases. Based on initial evidence suggesting that microglial intrinsic clock genes can affect their phenotypes, we sought to investigate differences in transcriptional, proteotype and functional profiles of microglia between light (sleep) and dark (active) phases, and how these changes are affected in pathological models. We found marked transcriptional and proteotype differences between microglia harvested from male mice during the light or dark phase. Amongst others, these differences related to genes and proteins associated with immune responses, motility, and phagocytosis, which were reflected by functional alterations in microglial synaptic pruning and response to bacterial stimuli. Possibly accounting for such changes, we found RNA and protein regulation in SWI/SNF and NuRD chromatin remodeling complexes between light and dark phases. Importantly, we also show that the time of microglial sample collection influences the nature of microglial transcriptomic changes in a model of immune-mediated neurodevelopmental disorders. Our findings emphasize the importance of considering diurnal factors in studying microglial cells and indicate that implementing a circadian perspective is pivotal for advancing our understanding of their physiological and pathophysiological roles in brain health and disease.

Exploring protective potential of Vitamin E in mitigating liver steatosis in alcoholic liver injury.

Objective: To investigate and assess the efficacy of Vitamin E in preventing or reducing fatty liver changes associated with alcoholic liver injury. Study Design: Experimental study. Setting: Department of Anatomy and Animal Facility of Peshawar Medical College, Peshawar. Period: February 2018 to April 2020. Methods: The study involved eighteen male domestic rabbits (Oryctolagus cuniculus), organizing them into categories based on the time frames specified for the research. Animals in "Category E8" were subjected to an 8-week time period, while those in "Category E4" underwent a 4-week experimental duration. Each category was further divided into three groups: "Control Group A" received standard laboratory food and daily access to normal saline as drinking water, "Experimental Group B" received standard nutrition, a 30% ethanol solution in distal water (30ml per kg/day) and normal saline for drinking, and "Experimental Group C" was treated with the necessary standard diet, a 30% ethanol solution in distal water (30ml per kg/day), and "Vitamin E" (50mg dissolved in 2ml distal water per kg/day) via nasogastric tube. Liver tissue specimens from all animals were stained with H&E and Masson’s trichrome stain for quantification of fatty change. Results: A significant difference in steatosis development was observed among the E4 groups and among the E8 groups having a respective p-values of 0.001 and 0.003. This underscored the impact of alcohol within the context of alcohol-induced liver injury. However, no appreciable differences were noted between BI & CI and BII & CII (p-values > 0.05) indicating no significant distinction in liver steatosis between subjects treated with vitamin E and those not receiving vitamin E. Conclusion: In the context of alcohol-induced liver injury, the study failed to deliver anticipated protective benefits of vitamin E. There is a possibility of adverse effects, potentially rendering its use counterproductive.

High Prevalence of Highly Pathogenic Avian Influenza: A Virus in Vietnam's Live Bird Markets.

In recent years, Vietnam has suffered multiple epizootics of influenza in poultry. From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs). Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus. This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.

Mycological air contamination level and biodiversity of airborne fungi isolated from the zoological garden air — preliminary research

The aim of this paper was to evaluate the degree of mycological air contamination and determine the taxonomic diversity of airborne fungi residing in the air of 20 different animal facilities in a zoological garden. The concentrations of fungi in the zoological garden were measured using a MAS-100 air sampler. The collected microorganisms were identified using the combination of molecular and morphological methods. The fungal concentration ranged from 50 to 3.65 × 104 CFU/m3 during the whole study. The quantitative analysis of the fungal aerosol showed that the obtained concentration values were lower than the recommended permissible limits (5 × 104 CFU/m3 for fungi). Environmental factors, including temperature and relative humidity, exerted a varying effect on the presence and concentration of isolated fungi. Relative humidity was shown to correlate positively with the concentration of fungal spores in the air of the facilities studied (rho = 0.57, p < 0.0021). In parallel, no significant correlation was established between temperature and total fungal concentration (rho = − 0.1, p < 0.2263). A total of 112 fungal strains belonging to 50 species and 10 genera were isolated. Penicillium was the dominant genera, including 58.9% of total fungal strains, followed by Aspergillus 25.89%, Cladosporium 3.57%, Talaromyces 3.57%, Mucor 1.78%, Schizophyllum 1.78%, Syncephalastrum 0.89%, Alternaria 0.89%, Absidia 0.89%, and Cunninghamella 0.89%. Our preliminary studies provide basic information about the fungal concentrations, as well as their biodiversity in zoological garden. Further studies are needed to generate additional data from long-term sampling in order to increase our understanding of airborne fungal composition in the zoological garden.

Clinical Islet Xenotransplantation: Development of Isolation Protocol, Anti-Rejection Strategies, and Clinical Outcomes.

Allogeneic islet transplantation has become a standard therapy for unstable type 1 diabetes. However, considering the large number of type 1 diabetic patients, the shortage of donors is a serious issue. To address this issue, clinical islet xenotransplantation is conducted. The first clinical islet xenotransplantation was performed by a Swedish team using fetal pancreatic tissue. Thereafter, clinical trials of islet xenotransplantation were conducted in New Zealand, Russia, Mexico, Argentina, and China using neonatal pig islets. In clinical trials, fetal or neonatal pancreata are used because of the established reliable islet isolation methods. These trials demonstrate the method's safety and efficacy. Currently, the limited number of source animal facilities is a problem in terms of promoting islet xenotransplantation. This limitation is due to the high cost of source animal facilities and the uncertain future of xenotransplantation. In the United States, the first xenogeneic heart transplantation has been performed, which could promote xenotransplantation. In Japan, to enhance xenotransplantation, the 'Medical Porcine Development Association' has been established. We hope that xenogeneic transplantation will become a clinical reality, serving to address the shortage of donors.

Comparative Efficiency Study of Disinfection in Animal Facilities with Phyto-preparation and Virosan F

The welfare of animal facilities depends on the regular and thorough implementation of veterinary preventive measures. Among such measures, disinfection plays a crucial role. Veterinary disinfection is a complex of measures aimed at providing healthy living conditions for animals. Premises where animals and utilities are located require sanitation to prevent the emergence of disease and to eliminate it if it has already appeared. This article presents the results of studies on the effectiveness of disinfection with a plant-based disinfectant and Virosan F under various exposures. Bacteriological control of the sanitary condition of treated surfaces was carried out during the research using generally accepted methods. Comparative disinfection of surfaces with synthetic and natural disinfectants was conducted after mechanical cleaning using two spraying methods. The consumption of working solutions for both disinfectants was 0.3 L/m². The exposure after sanitation was 24 hours, 48 hours, 72 hours, and 7 days. When comparing the effectiveness of disinfectants – Virosan F (No. 1) and Phytopreparation (No. 2), it was established that after 24 hours of exposure, they reduce the level of microbial contamination by 100 %. Laboratory studies have shown that the use of a natural Phytopreparation with a combined action at a concentration of 40 % and the synthetic disinfectant Virosan F is effective for the destruction of S. aureus and E. coli. The new Phytopreparation has high antibacterial activity, is completely safe for the health of animals and humans, and environmentally safe. Disinfection by aerosol method of test objects with exposure of 24 hours, 48 hours, 72 hours, 168 hours with a solution of disinfectant Virosan F and Phytoagent on a plant basis allows achieving equally high-quality sanitary effect of the animal complex under conditions of high initial levels of microbial contamination.

Evaluating possible maternal effect lethality and genetic background effects in Naa10 knockout mice.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting approximately 80% of all human proteins. The human essential X-linked gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. There is extensive genetic variation in humans with missense, splice-site, and C-terminal frameshift variants in NAA10. In mice, Naa10 is not an essential gene, as there exists a paralogous gene, Naa12, that substantially rescues Naa10 knockout mice from embryonic lethality, whereas double knockouts (Naa10-/Y Naa12-/-) are embryonic lethal. However, the phenotypic variability in the mice is nonetheless quite extensive, including piebaldism, skeletal defects, small size, hydrocephaly, hydronephrosis, and neonatal lethality. Here we replicate these phenotypes with new genetic alleles in mice, but we demonstrate their modulation by genetic background and environmental effects. We cannot replicate a prior report of "maternal effect lethality" for heterozygous Naa10-/X female mice, but we do observe a small amount of embryonic lethality in the Naa10-/y male mice on the inbred genetic background in this different animal facility.

Noise as an Extrinsic Variable in the Animal Research Facility.

Animal research facilities are noisy environments. The high air change rates required in animal housing spaces tend to create higher noise levels from the heating and cooling systems. Housing rooms are typically constructed of hard wall material that is easily cleaned but simultaneously highly reverberant, meaning that the sound cannot be controlled/attenuated so the sounds that are generated bounce around the room uncontrolled. (Soft, sound-absorbing surfaces generally cannot be used in animal facilities because they collect microbes; various wall surface features and sound control panel options are available, although rarely used.) In addition, many of our husbandry tasks such as cage changing, animal health checks, cleaning, and transporting animals produce high levels of noise. Finally, much of the equipment we have increasingly employed in animal housing spaces, such as ventilated caging motors, biosafety, or procedure cabinets, can generate high levels of background noise, including ultrasound. These and many additional factors conspire to create an acoustic environment that is neither naturalistic nor conducive to a stress-free environment. The acoustic variability both within and between institutions can serve as an enormous confounder for research studies and a threat to our ability to reproduce studies over time and between research laboratories. By gaining a better appreciation for the acoustic variables, paired with transparency in reporting the levels, we might be able to gain a better understanding of their impacts and thereby gain some level of control over such acoustic variables in the animal housing space. The result of this could improve both animal welfare and study reproducibility, helping to address our 3Rs goals of Replacement, Reduction, and Refinement in the animal biomedical research enterprise.

Gut microbiome is dispensable for normal respiratory function and respiratory chemoreflex

Increasing evidence indicates that gut microbiota can influence changes in respiratory homeostasis. Alterations to the gut microbiome have been hypothesized to play roles in autoimmune diseases, social behavioral deficits, and metabolic diseases such as diabetes and cardiovascular disease. We therefore aimed to determine if a model of gut dysbiosis, the absence of a gut microbiome, would result in alterations to respiratory homeostasis. After 5 days of habituation inside the Gnotobiotic animal facility, we assayed 8-week-old C57Bl/6J germ-free (GF, n=24) and specific-pathogen-free (SPF, n=24) control mice under normoxic (21% O2,79% N2) conditions, followed by a hypercapnic challenge (5% CO2, 21% O2, 74% N2) and hypoxic challenge (10% O2, 90% N2). Importantly, this germfree model does not involve treatment with high-dose antibiotics, which have been implicated in neurotoxic sequela. Whole-body flow through plethysmography was used to monitor respiratory function and metabolic demand in conscious and unrestrained animals. Recordings were interrogated using our newly published open-source software, Breathe Easy, for breath cycle duration, respiratory rate (Vf), tidal volume (VT), minute ventilation (VE), oxygen consumption (VO2), and minute ventilation normalized by oxygen consumption (VE/VO2) during room air, initial hypoxic and hypercapnic exposures, and steady-state hypoxic and hypercapnic respiratory responses. A linear mixed effects model with a Tukey post-hoc test was performed to test for significant differences wherein respiratory outcomes were dependent variables, and strain and sex were independent variables. In male mice, there was a significant decrease in breath cycle duration during room air in GF compared to SPF controls. We also saw a significant decrease in ventilatory equivalents of oxygen in the initial hypoxic response in GF mice compared to SPF controls in males, but not in the steady-state of hypoxic exposure. Finally, we note a significant increase in oxygen consumption in females during room air measurements. Of note, female mice showed significant irregularity in all respiratory parameters except oxygen consumption whereas males only showed significant irregularity in breath cycle duration during hypoxic steady-state and the hypercapnic steady-state, and tidal volume in the initial hypoxic response. While there are significant changes, it remains to be determined what the underlying mechanisms are and how they may play a contributory role in pathophysiologies co-morbid with gut microbiome dysregulation. Taken together, these results suggest that the gut microbiome is largely dispensable for normal respiratory function and respiratory chemoreflexes in adult mice and that the lack of a gut microbiome, a model of gut dysbiosis, does not result in broad significant changes in respiratory homeostasis. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear.

To investigate the impact of sound exposure, with the resultant windows vibration on perilymphatic concentrations following intratympanic (IT) dexamethasone and gentamicin in an animal model. Animal model blinded study. Animal facility of a tertiary medical center. Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1external auditory canal plugged (contralateral control). Following noise exposure, perilymph was obtained from both ears. Drug concentrations were measured using ultrahigh-performance liquid chromatography-mass spectrometer. For dexamethasone, the average (±SD) perilymphatic steroidal concentration was 0.417 µg/mL (±0.549) in the control ears versus 0.487 µg/mL (±0.636) in the sound-exposed ears (P = .008). The average (±SD) gentamicin perilymphatic concentration was 8.628 µg/mL (±2.549) in the sound-exposed ears, compared to 4.930 µg/mL (±0.668) in the contralateral control (nonsound exposed) ears. Sound exposure promoted steroidal and gentamicin diffusion to the inner ear by an averaged (±SD) factor of 1.431 and 1.730 (±0.291 and 0.339), respectively. Low-intensity noise (30 dB SPL) was found to enhance dexamethasone phosphate and gentamicin diffusion to the inner ear (by an averaged factor of ∼1.4 and 1.7, respectively) in a murine model.