Modern In Vitro Techniques for Modeling Hearing Loss.

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.

Knee Joint Preservation in Tactical Athletes: A Comprehensive Approach Based upon Lesion Location and Restoration of the Osteochondral Unit.

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.

Leveraging Technology for Vestibular Assessment and Rehabilitation in the Operational Environment: A Scoping Review.

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.

Treatment of Tendon Injuries in the Servicemember Population across the Spectrum of Pathology: From Exosomes to Bioinductive Scaffolds.

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.

Understanding Primary Blast Injury: High Frequency Pressure Acutely Disrupts Neuronal Network Dynamics in Cerebral Organoids.

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.

Comparison of next generation diagnostic systems (NGDS) for the detection of SARS-CoV-2.

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.

Comparative in vitro study of commercially available products for alveolar ridge preservation.

BACKGROUND: Ridge preservation is performed by placing a biocompatible product, following tooth extraction, to maintain bone volume. However, current ridge preservation therapies do not always maintain the volume required for future implant placement. Variations in surgical technique and material selection contribute to determining clinical outcomes. The wide variety of grafting materials available and conflicting efficacy reports make selecting the appropriate graft materials challenging. To investigate how different commercially available ridge preservation products might perform clinically: Helistat (collagen control) (Material 1), OsteoGen Plug (Material 2), Bio-Oss Collagen (Material 3), and J-Bone (native bone) (Material 4) were evaluated. METHODS: These products underwent field emission scanning electron microscopy, microcomputed tomography, helium pycnometry, and infrared spectra analysis. Human osteosarcomas were incubated on products and proliferation was monitored with CCK-8 and visualized with confocal microscopy. Scaffold osteoconductivity was evaluated through the cellular production of proteins osteocalcin, osteonectin, and osteopontin. RESULTS: Results indicated that products varied in porosity and pore interconnectivity. Although Material 3 was chemically similar to Material 4, Material 2 demonstrated significantly better biocompatibility. Functionally, Material 1 and Material 2 elicited higher osteonectin release than Material 3 and Material 4 which suggests the latter products suppress endogenous osteonectin secretion. Furthermore, osteopontin secretion was minimal for all products, while osteocalcin was elevated. This seems to suggest that high levels of mineralization might be deleterious for bone regeneration. CONCLUSIONS: Although all products are marketed as effective preservation products, the results demonstrated high variability in physical, chemical, and biological effects; however, this study suggests a product with higher ratio of collagen to mineral component may have the most desirable effects for the use in alveolar ridge preservation.

Effective Access to Care in a Crisis Period: Hypertension Control During the COVID-19 Pandemic by Telemedicine.

OBJECTIVE: To assess the effectiveness of telemedicine video visits in the management of hypertensive patients at home during the first year of the COVID-19 pandemic. METHODS: A quantitative analysis was performed of all home video visits coded with a diagnosis of essential hypertension during the first 12 months of the COVID-19 pandemic (March 2020 through February 2021). A total of 10,634 patients with 16,194 hypertension visits were present in our national telemedicine practice database during this time. Among this population, a total of 569 patients who had 1785 hypertension visits met the criteria of having 2 or more blood pressure (BP) readings, with the last BP reading occurring in the report period. We analyzed baseline characteristics and BP trends of these 569 patients during the study period. Voluntarily submitted patient satisfaction ratings, which were systematically requested at the end of each visit, were also analyzed. RESULTS: The mean age of the patients in this study cohort of 569 patients was 43.9 years, and 48.3% (275) were women. More than 62% (355) of the patients had an initial systolic BP (SBP) above 140 mm Hg, and 25.3% (144) had an initial SBP of greater than 160 mm Hg. The average number of visits during the study period was 3.1 visits per patient; an average of 6.4 BP measurements per patient were available. During the study period, 77% (438) of the patients experienced an improvement in either SBP or diastolic BP (DBP), with mean reductions of -9.7 mm Hg and -6.8 mm Hg in SBP and DBP, respectively. A total of 416 patients in the cohort started with a BP above 140/90 mm Hg. For this subset of patients, 55.7% (232) achieved a BP of 140/90 mm Hg or lower by the end of the study period, and the average reductions in SBP and DBP were -17.9 mm Hg and -12.8 mm Hg, respectively, which corresponded to improvements of 11.2% and 12.4%. These improvements did not vary significantly when patients were stratified by age, sex, or geographic region of residence (rural vs urban/suburban). Voluntarily submitted patient surveys indicated a high degree of patient satisfaction, with a mean satisfaction score of 4.94 (5-point scale). CONCLUSION: Clinician-patient relationships established in a video-first telemedicine model were broadly effective for addressing suboptimally controlled hypertension. Patient satisfaction with these visits was high.

Associations between Physiological Biomarkers and Psychosocial Measures of Pregnancy-Specific Anxiety and Depression with Support Intervention.

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.

Where Virtual Care Was Already a Reality: Experiences of a Nationwide Telehealth Service Provider During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has led to an increase in the use of and demand for telehealth services. OBJECTIVE: Here, we describe the utilization of telehealth services provided by Doctor On Demand, Inc., a well-known telehealth company in the United States, before and during the COVID-19 pandemic. We also explore how the number of virtual visits, reasons for visits, and patients served changed over time. METHODS: We reported data as a percentage change from the baseline week during 2 distinct time periods: February-June 2019 and February-June 2020 based on 4 categories of visits: respiratory illness, unscheduled behavioral health, scheduled behavioral health, and chronic illness. RESULTS: In 2020, the total visit volume increased considerably from March through April 7, 2020 (59% above the baseline) and then declined through the week of June 2 (15% above the baseline). Visits for respiratory illnesses increased through the week of March 24 (30% above the baseline) and then steadily declined through the week of June 2 (65% below the baseline). Higher relative increases were observed for unscheduled behavioral health and chronic illness visits through April (109% and 131% above the baseline, respectively) before a decline through the week of June 2 (69% and 37% above the baseline, respectively). Increases in visit volume among rural residents were slightly higher than those among urban residents (peak at 64% vs 58% above the baseline, respectively). CONCLUSIONS: Although this telehealth service provider observed a substantial increase in the volume of visits during the COVID-19 pandemic, it is interesting to note that this growth was not fueled by COVID-19 concerns but by visits for behavioral health and chronic illness. Telehealth services may play a role as a "safety valve" for patients who have difficulty accessing care during a public health emergency.

Structural abnormalities in the temporalis musculo-aponeurotic complex in chronic muscular temporomandibular disorders.

Some forms of chronic pain are thought to be driven and maintained by nociceptive input, which can drive plasticity within nociceptive pathways. We have previously identified abnormalities along the entire nociceptive pathway in chronic myalgic temporomandibular disorders (mTMD), including the trigeminal nerves, brainstem pathways, and in the thalamus and somatosensory cortex. These data suggest that there is a peripheral nociceptive drive in mTMD, but the source of this nociceptive activity remains unknown. Here, our aim was to determine whether structural abnormalities exist in the muscles of mastication of patients with chronic mTMD. Specifically, we tested whether the volume of the temporalis muscle and its tendon-aponeurosis complex (TAC, a structure that dissipates forces in a muscle) in mTMD patients differ compared to age- and sex-matched controls. To do so, we segmented these structures on T1-weighted structural magnetic resonance images. We found that muscle volumes in mTMD were not different to controls. However, the mTMD group had significantly smaller volumes of the bilateral temporalis TAC, and thus a smaller TAC-to-muscle volume ratio. These findings were consistent across 2 independent cohorts of 17 mTMD patients, compared to 17 age- and sex-matched controls. We propose a model where reduced TAC-to-muscle ratio could result in a predisposition to muscle tissue injury. In sum, abnormalities of the temporalis muscles in mTMD supports our hypothesis that chronic mTMD pathophysiology may be related to peripheral nociceptive barrage originating from the muscles of mastication.

Risk of Preterm Birth and Newborn Low Birthweight in Military Women with Increased Pregnancy-Specific Anxiety.

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.

Development of Electrospun Chitosan-Polyethylene Oxide/Fibrinogen Biocomposite for Potential Wound Healing Applications.

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.

Disparate Antibiotic Resistance Gene Quantities Revealed across 4 Major Cities in California: A Survey in Drinking Water, Air, and Soil at 24 Public Parks.

Widespread prevalence of multidrug and pandrug-resistant bacteria has prompted substantial concern over the global dissemination of antibiotic resistance genes (ARGs). Environmental compartments can behave as genetic reservoirs and hotspots, wherein resistance genes can accumulate and be laterally transferred to clinically relevant pathogens. In this work, we explore the ARG copy quantities in three environmental media distributed across four cities in California and demonstrate that there exist city-to-city disparities in soil and drinking water ARGs. Statistically significant differences in ARGs were identified in soil, where differences in blaSHV gene copies were the most striking; the highest copy numbers were observed in Bakersfield (6.0 × 10-2 copies/16S-rRNA gene copies and 2.6 × 106 copies/g of soil), followed by San Diego (1.8 × 10-3 copies/16S-rRNA gene copies and 3.0 × 104 copies/g of soil), Fresno (1.8 × 10-5 copies/16S-rRNA gene copies and 8.5 × 102 copies/g of soil), and Los Angeles (5.8 × 10-6 copies/16S-rRNA gene copies and 5.6 × 102 copies/g of soil). In addition, ARG copy numbers in the air, water, and soil of each city are contextualized in relation to globally reported quantities and illustrate that individual genes are not necessarily predictors for the environmental resistome as a whole.