RÉSUMÉ
Traumatic brain injury (TBI) is a leading cause of morbidity, disability, and mortality worldwide. Motor and cognitive deficits and emotional disturbances are long-term consequences of TBI. A lack of effective treatment for TBI-induced neural damage, functional impairments, and cognitive deficits makes it challenging in the recovery following TBI. One of the reasons may be the lack of knowledge underlying the complex pathophysiology of TBI and the regulatory factors involved in the cellular and molecular mechanisms of inflammation, neural regeneration, and injury repair. These mechanisms involve a change in the expression of various proteins encoded by genes whose expression is regulated by transcription factors (TFs) at the transcriptional level and microRNA (miRs) at the mRNA level. In this pilot study, we performed the RNA sequencing of injured tissues and non-injured tissues from the brain of Yucatan miniswine and analyzed the sequencing data for differentially expressed genes (DEGs) and the TFs and miRs regulating the expression of DEGs using in-silico analysis. We also compared the effect of the electromagnetic field (EMF) applied to the injured miniswine on the expression profile of various DEGs. The results of this pilot study revealed a few DEGs that were significantly upregulated in the injured brain tissue and the EMF stimulation showed effect on their expression profile.
RÉSUMÉ
Traumatic brain injury (TBI) due to a direct blow or penetrating injury to the head damages the brain tissue and affects brain function. Primary and secondary damage to the brain tissue increases disability, morbidity, and mortality and costs millions of dollars in treatment. Injury to the brain tissue results in the activation of various inflammatory and repair pathways involving many cellular and molecular factors. Increased infiltration of immune cells to clear the debris and lesion healing, activation of Schwann cells, myelination, oligodendrocyte formation, and axonal regeneration occur after TBI to regenerate the tissue. However, secondary damage to brain tissue results in behavioral symptoms. Repair and regeneration are regulated by a complex cascade involving various cells, hormones, and proteins. A change in the expression of various proteins due to altered gene expression may be the cause of impaired repair and the sequelae in TBI. In this pilot study, we used a Yucatan miniswine model of TBI with and without electromagnetic field (EMF) stimulation and investigated the differential gene expression between injured and non-injured cortex tissues. We found several differentially expressed genes including INSC, TTR, CFAP126, SEMA3F, CALB1, CDH19, and SERPINE1. These genes are associated with immune cell infiltration, myelination, reactive oxygen species regulation, thyroid hormone transportation, cell proliferation, and cell migration. There was a time-dependent effect of EMF stimulation on the gene and protein expression. The findings support the beneficial effect of EMF stimulation in the repair process following TBI.
RÉSUMÉ
Traumatic brain injury is a leading cause of disability and death worldwide and represents a high economic burden for families and national health systems. After mechanical impact to the head, the first stage of the damage comprising edema, physical damage, and cell loss gives rise to a second phase characterized by glial activation, increased oxidative stress and excitotoxicity, mitochondrial damage, and exacerbated neuroinflammatory state, among other molecular calamities. Inflammation strongly influences the molecular events involved in the pathogenesis of TBI. Therefore, several components of the inflammatory cascade have been targeted in experimental therapies. Application of Electromagnetic Field (EMF) stimulation has been found to be effective in some inflammatory conditions. However, its effect in the neuronal recovery after TBI is not known. In this pilot study, Yucatan miniswine were subjected to TBI using controlled cortical impact approach. EMF stimulation via a helmet was applied immediately or two days after mechanical impact. Three weeks later, inflammatory markers were assessed in the brain tissues of injured and contralateral non-injured areas of control and EMF-treated animals by histomorphometry, immunohistochemistry, RT-qPCR, Western blot, and ELISA. Our results revealed that EMF stimulation induced beneficial effect with the preservation of neuronal tissue morphology as well as the reduction of inflammatory markers at the transcriptional and translational levels. Immediate EMF application showed better resolution of inflammation. Although further studies are warranted, our findings contribute to the notion that EMF stimulation could be an effective therapeutic approach in TBI patients.
RÉSUMÉ
Background and objective Traumatic brain injury (TBI) has been associated with aberrations in neural circuitry attributable to the pathology resulting in electromagnetic field (EMF) changes. These changes have been evaluated in a variety of settings including through novel induction sensors with an ultra-portable shielded helmet and EMF channels with differences identified by comparing pre-injury and post-injury states. Modulation of the EMF has undergone cursory evaluation in neurologic conditions but has not yet been fully evaluated for clinical effects in treatment. Target EMF stimulation using EMF-related changes preoperatively to postoperatively has not yet been attempted and has not been completed using induction sensor technology. Our objectives in this study were twofold: we wanted to test the hypothesis that targeted stimulation using an EMF signal generator and stimulator to abnormal thresholds identified by real-time measurement of EMFs may enable early resolution of EMF changes and treatment of the TBI as modeled through controlled cortical impact (CCI); we also aimed to assess the feasibility of attempting this using real-time measurements with an EMF shielded helmet with EMF channels and non-contact, non-invasive induction sensors with attached EMF transmitters in real-time. Methods A singular Yucatan miniswine was obtained and baseline EMF recordings were obtained. A CCI of TBI and postoperative assessment of cortical EMF in a non-invasive, non-contact fashion were completed. Alterations in EMF were evaluated and EMF stimulation using those abnormal frequencies was completed using multiple treatments involving three minutes of EMF stimulation at abnormal frequencies. Stimulation thresholds of 2.5 Hz, 3.5 Hz, and 5.5 Hz with 1 V signal intensity were evaluated using sinusoidal waves. Additionally, stimulation thresholds using differing offsets to the sine wave at -500 mV, 0 mV, and 500 mv were assessed. Daily EMF and post-stimulation EMF measurements were recorded. EMF patterns were then assessed using an artificial intelligence (AI) model. Results AI modeling appropriately identified differences in EMF signal in pre-injury, post-injury, and post-stimulation states. EMF stimulation using a positive offset of 500 mV appeared to have maximal beneficial effects in return to baseline. Similarly targeted stimulation using thresholds of 2.5 Hz and 5.5 Hz with a positive 500 mV offset at 1 V allowed for recovery of EMF patterns post-injury towards patterns seen in baseline EMF measurements on stimulation day seven (postoperative day 17). Conclusion Stimulation of neural circuits with targeted EMF in a sinusoidal pattern with targeted thresholds after measurement with induction sensors with shielding isolated to a Mu-metal and copper mesh helmet and EMF channels is efficacious in promoting neuronal circuit recovery to preoperative baselines in the TBI miniswine model. Similarly, our findings confirm the appropriateness of this translational model in the evaluation of brain neuronal circuit EMF and that preoperative and post-trauma differences can be appropriately assessed with this technology.
RÉSUMÉ
Background Traumatic brain injury (TBI) is a global cause of disability and mortality. Treatment depends on mitigation of secondary injury resulting in axonal injury, necrosis, brain dysfunction, and disruption of electrical and chemical signaling in neural circuits. To better understand TBI, translational models are required to study physiology, diagnostics, and treatments in homologous species, such as swine. Electromagnetic fields (EMFs) from altered neural circuits can be measured and historically have been reliant on expensive shielding and supercooling in magnetoencephalography. Using proprietary induction sensors, it has been found that a non-invasive, non-contact approach with an engineered Mu-metal and copper mesh-shielded helmet effectively measures EMFs. This has not yet been investigated in swine models. We wished to evaluate the efficacy of this technology to assess TBI-dependent EMF changes in swine to describe the efficacy of these sensors and this model using a gravity-dependent controlled cortical impact (CCI). Methods A Yucatan miniswine was evaluated using non-contact, non-invasive proprietary induction sensors with an engineered dual-layer Mu-metal and interlaced copper mesh helmet with sensors within EMF channels connected to a helmet. Swine EMF recordings were obtained prior to induced gravity-dependent CCI followed by post-TBI measurements. Behavioral changes and changes in EMF measurements were assessed. EMF measurements were evaluated with an artificial intelligence (AI) model. Results Differences between room "noise" EMF measurements and pre-TBI swine electromagnetic field measurements were identified. Morphological characteristics between pre-injury and post-injury measurements were noted. AI modeling differentiated pre-injury and post-injury patterns in the swine EMF. Frequently identified frequencies seen post-injury were peaks at 2.5 Hz and 6.5 Hz and a valley at 11 Hz. The AI model identified less changes in the slope and thus decreased variation of EMF measurements post-TBI between 4.5 Hz and 7 Hz. Conclusions For the first time, it was identified that cortical function in a swine can be appropriately measured using novel induction sensors and shielding isolated to a helmet and EMF channels. The swine model can be appropriately differentiated from the external noise signal with identifiably different pre-injury and post-injury EMFs. Patterns can be recognized within the post-injury EMF due to altered neural circuits that can be measured using these sensors continuously, non-invasively, and in real time.
RÉSUMÉ
Context Medical students and graduates apply for post-graduate year-one positions every year through the Single Accreditation System (SAS) National Residency Match Program (NRMP). New opportunities have arisen for osteopathic graduates through the transition to a single match. There is a paucity of information evaluating the effects of this single match on osteopathic (DO) and allopathic (MD) candidates in relation to match rates in competitive surgical sub-specialties such as neurosurgery, thoracic surgery, vascular surgery, otolaryngology (ENT), plastic surgery, orthopedic surgery, and general surgery. Objectives This paper utilizes published data to accomplish three tasks. Firstly, it investigates the effects of the SAS on DO and MD match rates in surgical subspecialties of neurosurgery, thoracic surgery, vascular surgery, ENT, plastic surgery, orthopedic surgery, and general surgery. Secondly, it investigates whether program director credentials and impressions correlate with the match rates of DO or MD candidates in each of these specialties. Finally, it discusses solutions for addressing ways to improve match outcomes for all candidates. Methods Previously published NRMP, National Matching Services, and Accreditation Council for Graduate Medical Education websites were queried for the number of DO and MD senior applicants for each position, match success rates, program director impressions, and program director credentials for the years 2018-2023. Match success rates were defined as a ratio of the number of candidates that applied to the number who successfully matched. Data were analyzed using descriptive statistics, chi-squared testing, student t-tests, and linear regression where appropriate. A p-value of less than 0.05 was considered significant. Results From 2020-2023, an increasing proportion of DO residents applied for the selected surgical subspecialties, increasing from 599 applicants in 2020 to 743 candidates in 2023. Overall match rates for DOs remain significantly lower than MD match rates for each of these specialties as well as overall (p-values all <0.05) with summative match rates of 52.89% for DOs compared to 73.61% for MDs in 2023 for the selected surgical subspecialties. From 2020 to 2023 match rates were 30.88% for DOs compared to 74.82% for MDs in neurosurgery, 16.67% versus 46.45% (DO vs MD) in thoracic surgery, 4.17% vs 68.84% (DO vs MD) in plastic surgery, 57.62% vs 73.18% (DO vs MD) in general surgery, 23.21% vs 74.18% (DO vs MD) in vascular surgery, 53.10% vs 72.57% (DO vs MD) for ENT, and 56.92% vs 72.51% (DO vs MD) for orthopedics. There was a statistically significant correlation between the proportion of DO program directors with the rate of DOs matching in the associated specialty (p=0.012). Conclusion There were significantly lower rates for DO candidates compared to MD candidates matching into selected surgical subspecialties of neurosurgery, thoracic surgery, vascular surgery, ENT, plastic surgery, orthopedic surgery, and general surgery. This may be addressed through increasing advocacy at local and national levels, improving mentorship, increasing DO medical student exposure to surgical subspecialties, and ensuring increasing selected surgical subspecialty involvement in teaching these diverse DO applicants in order to strengthen medicine and continue to address predicted growing physician shortages.
RÉSUMÉ
This paper presents a comprehensive review of the extant literature from 1980 through 2023 on the role and utility of Electromagnetic Fields (EMF) in the treatment of brain trauma and brain neuropathology resulting from disease. Brain trauma resulting from accident, injury and disease is a significant contributor to short and long-term morbidity, as well as a leading cause of mortality globally. To date, limited effective treatments strategies exist, and are focused primarily on symptom relief, not restoring primary preinjury function and structure. Much of the current clinical literature is based on retrospective case reports and limited animal model prospective trials exploring core etiology and alterations in post-injury clinical phenotypes. The current findings reported in the scientific literature suggest that electromagnetic therapy may hold promise as a potential non-invasive treatment for traumatic brain injury and neuropathology. Although promising, well designed clinical trials are needed to better determine its potential clinical effectiveness in this diverse patient population. Future trials will need to determine the impact of clinical variables, such as sex, age, type and extent of injury and pathology, pre-injury baseline health status and a comprehensive biopsychosocial assessment to determine a more effective personalized approach to patient care. Although initially showing promise, much work needs to be done.
