Browsing by Author "Hoilett, Orlando S."

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    Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis
    (Wiley, 2024) Kaefer, Samuel L.; Zhang, Lujuan; Morrison, Rachel A.; Brookes, Sarah; Awonusi, Oluwaseyi; Shay, Elizabeth; Hoilett, Orlando S.; Anderson, Jennifer L.; Goergen, Craig J.; Voytik-Harbin, Sherry; Halum, Stacey; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Objectives: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. Methods: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. Results: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. Conclusions: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction.
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    Preclinical validation of NeoWarm, a low-cost infant warmer and carrier device, to ameliorate induced hypothermia in newborn piglets as models for human neonates
    (Frontiers Media, 2024-04-03) Bluhm, Nick D. P.; Tomlin, Grant M.; Hoilett, Orlando S.; Lehner, Elena A.; Walters, Benjamin D.; Pickering, Alyson S.; Bautista, Kevin Alessandro; Bucher, Sherri L.; Linnes, Jacqueline C.; Community and Global Health, Richard M. Fairbanks School of Public Health
    Introduction: Approximately 1.5 million neonatal deaths occur among premature and small (low birthweight or small-for gestational age) neonates annually, with a disproportionate amount of this mortality occurring in low- and middle-income countries (LMICs). Hypothermia, the inability of newborns to regulate their body temperature, is common among prematurely born and small babies, and often underlies high rates of mortality in this population. In high-resource settings, incubators and radiant warmers are the gold standard for hypothermia, but this equipment is often scarce in LMICs. Kangaroo Mother Care/Skin-to-skin care (KMC/STS) is an evidence-based intervention that has been targeted for scale-up among premature and small neonates. However, KMC/STS requires hours of daily contact between a neonate and an able adult caregiver, leaving little time for the caregiver to care for themselves. To address this, we created a novel self-warming biomedical device, NeoWarm, to augment KMC/STS. The present study aimed to validate the safety and efficacy of NeoWarm. Methods: Sixteen, 0-to-5-day-old piglets were used as an animal model due to similarities in their thermoregulatory capabilities, circulatory systems, and approximate skin composition to human neonates. The piglets were placed in an engineered cooling box to drop their core temperature below 36.5°C, the World Health Organizations definition of hypothermia for human neonates. The piglets were then warmed in NeoWarm (n = 6) or placed in the ambient 17.8°C ± 0.6°C lab environment (n = 5) as a control to assess the efficacy of NeoWarm in regulating their core body temperature. Results: All 6 piglets placed in NeoWarm recovered from hypothermia, while none of the 5 piglets in the ambient environment recovered. The piglets warmed in NeoWarm reached a significantly higher core body temperature (39.2°C ± 0.4°C, n = 6) than the piglets that were warmed in the ambient environment (37.9°C ± 0.4°C, n = 5) (p < 0.001). No piglet in the NeoWarm group suffered signs of burns or skin abrasions. Discussion: Our results in this pilot study indicate that NeoWarm can safely and effectively warm hypothermic piglets to a normal core body temperature and, with additional validation, shows promise for potential use among human premature and small neonates.
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    Selective Collection of Exhaled Breath Condensate for Noninvasive Screening of Breath Glucose
    (Sage, 2025) Desai, Aditya; Tankasala, Divya; Ng, Gabriel P.; Thakkar, Pankti; Hoilett, Orlando S.; Mather, Kieren J.; Linnes, Jacqueline C.; Medicine, School of Medicine
    Background: Although exhaled breath condensate (EBC) is a promising noninvasive sample for detecting respiratory analytes such as glucose, current EBC collection methods yield inconsistent results. Methods: We developed a custom EBC collection device with a temperature-based algorithm to selectively condense alveolar air for reproducible EBC glucose detection. We characterized the condensate volumes and the corresponding glucose concentrations. We performed a pilot study demonstrating its use during oral glucose tolerance tests. Results: The novel device selectively captured alveolar air resulting in slightly higher and less variable glucose concentrations than the overall EBC. Participants with type 2 diabetes demonstrated significantly higher blood plasma-EBC glucose ratios than normoglycemic participants. Conclusions: Temperature-based selective EBC collection allows EBC glucose measurement and is a promising sampling method to distinguish patients with and without diabetes.