Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as a promising platform for modeling hearing loss and developing novel therapeutic strategies. SNHL primarily results from the irreversible loss or dysfunction of cochlear mechanosensory hair cells (HCs) and spiral ganglion neurons (SGNs), emphasizing the need for innovative solutions. Current interventions offer symptomatic relief but do not address the root causes. Otic organoids, three-dimensional multicellular constructs that mimic the inner ear's architecture, have shown immense potential in several critical areas. They enable the testing of gene therapies, drug discovery for sensory cell regeneration, and the study of inner ear development and pathology. Unlike traditional animal models, otic organoids closely replicate human inner ear pathophysiology, making them invaluable for translational research. This review discusses methodological advances in otic organoid generation, emphasizing the use of human pluripotent stem cells (hPSCs) to replicate inner ear development. Cellular and molecular characterization efforts have identified key markers and pathways essential for otic organoid development, shedding light on their potential in modeling inner ear disorders. Technological innovations, such as 3D bioprinting and microfluidics, have further enhanced the fidelity of these models. Despite challenges and limitations, including the need for standardized protocols and ethical considerations, otic organoids offer a transformative approach to understanding and treating auditory dysfunctions. As this field matures, it holds the potential to revolutionize the treatment landscape for hearing and balance disorders, moving us closer to personalized medicine for inner ear conditions.
The unique physical demands of tactical athletes put immense stress on the knee joint, making these individuals susceptible to injury. In order to ensure operational readiness, management options must restore and preserve the native architecture and minimize downtime, while optimizing functionality. Osteochondral lesions (OCL) of the knee have long been acknowledged as significant sources of knee pain and functional deficits. The management of OCL is predicated on certain injury characteristics, including lesion location and the extent of subchondral disease. Techniques such as marrow stimulation, allograft and autologous chondrocyte implantation are examined in detail, with a focus on their application and suitability in tactical athlete populations. Moreover, the restoration of the osteochondral unit (OCU) is highlighted as a central aspect of knee joint preservation. The discussion encompasses the biomechanical considerations and outcomes associated with various cartilage restoration techniques. Factors influencing procedure selection, including lesion size, location, and patient-specific variables, are thoroughly examined. Additionally, the review underscores the critical role of post-operative rehabilitation and conditioning programs in optimizing outcomes. Strengthening the surrounding musculature, enhancing joint stability, and refining movement patterns are paramount in facilitating the successful integration of preservation procedures. This narrative review aims to provide a comprehensive resource for surgeons, engineers, and sports medicine practitioners engaged in the care of tactical athletes and the field of cartilage restoration. The integration of advanced preservation techniques and tailored rehabilitation protocols offers a promising avenue for sustaining knee joint health and function in this demanding population.
INTRODUCTION: The vestibular system, essential for gaze and postural stability, can be damaged by threats on the battlefield. Technology can aid in vestibular assessment and rehabilitation; however, not all devices are conducive to the delivery of healthcare in an austere setting. This scoping review aimed to examine the literature for technologies that can be utilized for vestibular assessment and rehabilitation in operational environments. MATERIALS AND METHODS: A comprehensive search of PubMed was performed. Articles were included if they related to central or peripheral vestibular disorders, addressed assessment or rehabilitation, leveraged technology, and were written in English. Articles were excluded if they discussed health conditions other than vestibular disorders, focused on devices or techniques not conducive to the operational environment, or were written in a language other than English. RESULTS: Our search strategy yielded 32 articles: 8 articles met our inclusion and exclusion criteria whereas the other 24 articles were rejected. DISCUSSION: There is untapped potential for leveraging technology for vestibular assessment and rehabilitation in the operational environment. Few studies were found in the peer-reviewed literature that described the application of technology to improve the identification of central and/or peripheral vestibular system impairments; triage of acutely injured patients; diagnosis; delivery and monitoring of rehabilitation; and determination of readiness for return to duty. CONCLUSIONS: This scoping review highlighted technology for vestibular assessment and rehabilitation feasible for use in an austere setting. Such technology may be leveraged for prevention; monitoring exposure to mechanisms of injury; vestibular-ocular motor evaluation; assessment, treatment, and monitoring of rehabilitation progress; and return-to-duty determination after vestibular injury. FUTURE DIRECTIONS: The future of vestibular assessment and rehabilitation may be shaped by austere manufacturing and 3D printing; artificial intelligence; drug delivery in combination with vestibular implantation; organ-on-chip and organoids; cell and gene therapy; and bioprinting.
Tendon injuries in military servicemembers are one of the most commonly treated nonbattle musculoskeletal injuries (NBMSKIs). Commonly the result of demanding physical training, repetitive loading, and frequent exposures to austere conditions, tendon injuries represent a conspicuous threat to operational readiness. Tendon healing involves a complex sequence between stages of inflammation, proliferation, and remodeling cycles, but the regenerated tissue can be biomechanically inferior to the native tendon. Chemical and mechanical signaling pathways aid tendon healing by employing growth factors, cytokines, and inflammatory responses. Exosome-based therapy, particularly using adipose-derived stem cells (ASCs), offers a prominent cell-free treatment, promoting tendon repair and altering mRNA expression. However, each of these approaches is not without limitations. Future advances in tendon tissue engineering involving magnetic stimulation and gene therapy offer non-invasive, targeted approaches for improved tissue engineering. Ongoing research aims to translate these therapies into effective clinical solutions capable of maximizing operational readiness and warfighter lethality.
Blast exposure represents a common occupational risk capable of generating mild to severe traumatic brain injuries (TBI). During blast exposure, a pressure shockwave passes through the skull and exposes brain tissue to complex pressure waveforms. The primary neurophysiological response to blast-induced pressure waveforms remains poorly understood. Here, we use a computer-controlled table-top pressure chamber to expose human stem cell-derived cerebral organoids to varied frequency of pressure waves and characterize the neurophysiological response. Pressure waves that reach a maximum amplitude of 250 kPa were used to model a less severe TBI and 350 kPa for a more severe blast TBI event. With each amplitude, a frequency range of 500 Hz, 3000 Hz, and 5000 Hz was tested. Following the 250 kPa overpressure a multi-electrode array recorded organoid neural activity. We observed an acute suppression neuronal activity in single unit events, population events, and network oscillations that recovered within 24 h. Additionally, we observed a network desynchronization after exposure higher frequency waveforms. Conversely, organoids exposed to higher amplitude pressure (350k Pa) displayed drastic neurophysiological differences that failed to recover within 24 h. Further, lower amplitude "blast" (250 kPa) did not induce cellular damage whereas the higher amplitude "blast" (350 kPa) generated greater apoptosis throughout each organoid. Our data indicate that specific features of pressure waves found intracranially during blast TBI have varied effects on neurophysiological activity that can occur even without cellular damage.
Blast Injuries , Brain Injuries, Traumatic , Humans , Organoids , Explosions , Neurons/physiology
INTRODUCTION: The World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020. Initially, supply chain disruptions and increased demand for testing led to shortages of critical laboratory reagents and inadequate testing capacity. Thus, alternative means of biosample collection and testing were essential to overcome these obstacles and reduce viral transmission. This study aimed to 1) compare the sensitivity and specificity of Cepheid GeneXpert® IV and BioFire® FilmArray® 2.0 next generation detection systems to detect SARS-CoV-2, 2) evaluate the performance of both platforms using different biospecimen types, and 3) assess saline as an alternative to viral transport media (VTM) for sample collection. METHODS: A total of 1,080 specimens consisting of nasopharyngeal (NP) swabs in VTM, NP swabs in saline, nasal swabs, oropharyngeal (OP) swabs, and saliva were collected from 216 enrollees. Limit of detection (LoD) assays, NP VTM and NP saline concordance, and saliva testing were performed on the BioFire® FilmArray® 2.0 Respiratory Panel 2.1 and Cepheid GeneXpert® Xpress SARS-CoV-2/Flu/RSV assays. RESULTS: LoD and comparative testing demonstrated increased sensitivity with the Cepheid compared with the BioFire® in detecting SARS-CoV-2 in NP VTM and saline, nasal, and OP swabs. Conversely, saliva testing on the Cepheid showed statistically significant lower sensitivity compared to the BioFire® . Finally, NP swabs in saline showed no significant difference compared with NP swabs in VTM on both platforms. CONCLUSION: The Cepheid and BioFire® NGDS are viable options to address a variety of public health needs providing rapid and reliable, point-of-care testing using a variety of clinical matrices.
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Nasopharynx , Saliva , Sensitivity and Specificity , Specimen Handling
Stress and anxiety significantly impact the hypothalamic-pituitary axis, and in pregnancy, the subsequent maternal-fetal response can lead to poor outcomes. The objective of this study was to assess the association between psychosocial measures of pregnancy-specific anxiety and physiologic inflammatory responses. Specifically, to determine the effectiveness of the Mentors Offering Maternal Support (M-O-M-STM) program to reduce psychosocial anxiety and associated inflammatory response. In conjunction with measures of pregnancy-specific anxiety and depression, serum biomarkers (IL-2, IL-6, IL-10, IL1-B, TNF-α, CRH, CRP, and cortisol) were analyzed for each trimester throughout pregnancy. Results demonstrated that women receiving the M-O-M-STM intervention had longitudinally sustained lower TNF-α/IL-10 ratios than the control group, and it was significantly associated with psychosocial measures of anxiety, specifically for fears of labor and spouse/partner relationships. Additionally, the anxiety of spouse/partner relationships was significantly associated with IL-6/IL-10 ratios. The findings highlight the important counter-regulatory relationship between anti- and pro-inflammatory cytokines and provide insight into the distinct physiologic responses to pregnancy-specific anxiety with early prenatal intervention.
Depression , Pregnancy Complications , Anxiety , Anxiety Disorders , Biomarkers , Female , Humans , Pregnancy , Stress, Psychological
INTRODUCTION: Prenatal maternal anxiety and depression have been implicated as possible risk factors for preterm birth (PTB) and other poor birth outcomes. Within the military, maternal conditions account for 15.3% of all hospital bed days, and it is the most common diagnostic code for active duty females after mental disorders. The majority of women (97.6%) serving on active duty are women of childbearing potential. Understanding the impact that prenatal maternal anxiety and depression can have on PTB and low birthweight (LBW) in a military population is critical to providing insight into biological pathways that alter fetal development and growth. The purpose of the study was to determine the impact of pregnancy-specific anxiety and depression on PTB and LBW within a military population. MATERIAL AND METHODS: Pregnancy-specific anxiety and depression were measured for 246 pregnant women in each trimester. Individual slopes for seven different measures of pregnancy anxiety and one depression scale were calculated using linear mixed models. Logistic regression, adjusted and unadjusted models, were applied to determine the impact on PTB and LBW. RESULTS: For each 1/10 unit increase in the anxiety slope as it related to well-being, the risk of LBW increased by 83% after controlling for parity, PTB, and active duty status. Similarly, a 1/10 unit rise in the anxiety slope related to accepting pregnancy, labor fears, and helplessness increased the risk of PTB by 37%, 60%, and 54%, respectively. CONCLUSIONS: Pregnancy-specific anxiety was found to significantly increase the risk of PTB and LBW in a military population. Understanding this relationship is essential in developing effective assessments and interventions. Results emphasize the importance of prenatal maternal mental health to fetal health and birth outcomes. Further research is needed to determine the specific physiological pathways that link prenatal anxiety and depression with poor birth outcomes.
Military Personnel , Premature Birth , Anxiety/complications , Anxiety/epidemiology , Birth Weight , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome , Premature Birth/epidemiology , Premature Birth/etiology , Risk Factors
Normal wound healing is a highly complex process that requires the interplay of various growth factors and cell types. Despite advancements in biomaterials, only a few bioactive wound dressings reach the clinical setting. The purpose of this research was to explore the feasibility of electrospinning a novel nanofibrous chitosan (CS)-fibrinogen (Fb) scaffold capable of sustained release of platelet-derived growth factor (PDGF) for the promotion of fibroblast migration and wound healing. CS-Fb scaffolds were successfully electrospun using a dual-spinneret electrospinner and directly evaluated for their physical, chemical, and biological characteristics. CS-polyethylene/Fb scaffolds exhibited thinner fiber diameters than nanofibers electrospun from the individual components while demonstrating adequate mechanical properties and homogeneous polymer distribution. In addition, the scaffold demonstrated acceptable water transfer rates for wound healing applications. PDGF was successfully incorporated in the scaffold and maintained functional activity throughout the electrospinning process. Furthermore, released PDGF was effective at promoting fibroblast migration equivalent to a single 50 ng/mL dose of PDGF. The current study demonstrates that PDGF-loaded CS-Fb nanofibrous scaffolds possess characteristics that would be highly beneficial as novel bioactive dressings for enhancement of wound healing.
