Exploring reasons for MD-PhD trainees' experiences of impostor phenomenon.

BACKGROUND: Acceptance into U.S. MD-PhD dual-degree programs is highly competitive, and the lengthy training program requires transitioning between multiple phases (pre-clinical-, PhD-research-, and clinical-training phases), which can be stressful. Challenges faced during MD-PhD training could exacerbate self-doubt and anxiety. Impostor phenomenon is the experience of feeling like a fraud, with some high-achieving, competent individuals attributing their successes to luck or other factors rather than their own ability and hard work. To our knowledge, impostor phenomenon among MD-PhD trainees has not been described. This study examined impostor phenomenon experiences during MD-PhD training and reasons trainees attributed to these feelings. METHODS: Individuals in science and medicine fields participated in an online survey that included the 20-item Clance Impostor Phenomenon Scale (CIPS); higher scores (range 20-100) indicate more frequent impostor phenomenon. Some respondents who reported experiencing impostor phenomenon also voluntarily completed a semi-structured interview, sharing experiences during training that contributed to feelings of impostor phenomenon. Interview transcripts were coded and analysed using the constant comparative method and analytic induction to identify themes. RESULTS: Of 959 survey respondents (students and professionals in science and medicine), 13 MD-PhD students and residents completed the survey, nine of whom (five male, four female; four white, five other race-ethnicity) also completed an interview. These participants experienced moderate-to-intense scores on the CIPS (range: 46-96). Four themes emerged from the interview narratives that described participants' experiences of IP: professional identity formation, fear of evaluation, minority status, and, program-transition experiences. All reported struggling to develop a physician-scientist identity and lacking a sense of belonging in medicine or research. CONCLUSIONS: Impostor experiences that MD-PhD participants attributed to bias and micro-aggressions in social interactions with peers, faculty, and patients challenged their professional identity formation as physician-scientists. It is important to further examine how MD-PhD-program structures, cultures, and social interactions can lead to feelings of alienation and experiences of impostor phenomenon, particularly for students from diverse and underrepresented populations in medicine.

Delta Rhythm Orchestrates the Neural Activity Underlying the Resting State BOLD Signal via Phase-amplitude Coupling.

Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta (δ) band LFP power negatively, while beta (ß) and gamma (γ) band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of δ LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduced ventral striatal functional connectivity, δ LFP-BOLD correlation, and the PAC effect. These data suggest that different frequency bands of the LFP contribute distinctively to BOLD spontaneous fluctuation and that PAC is the organizing mechanism through which low frequency LFPs orchestrate neural activity that underlies resting state functional connectivity.

Common data elements for epilepsy mobile health systems.

OBJECTIVE: Common data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry-wide standards for mHealth epilepsy data. METHODS: Using a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems. RESULTS: A consensus statement is presented for epilepsy mHealth CDEs. SIGNIFICANCE: Although it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.

Time to response and patient visibility during tonic-clonic seizures in the epilepsy monitoring unit.

OBJECTIVE: There is a high cost associated with recording quality video and electroencephalography (EEG) data in National Association of Epilepsy Center (NAEC) level IV epilepsy monitoring units (EMU). This study considers potential quality measures in EMUs for generalized tonic-clonic (GTC) seizures: types of safety signals, response time, and visibility of patient's limbs for semiology. These quality measures have been summarized across 12 EMUs to estimate response times to GTC seizures and the quality of video data that is captured during admissions. METHODS: Video electroencephalographies (vEEGs) from two prospective regulatory studies for the Brain Sentinel device were reviewed. A total of 232 subjects with a history of GTC seizures underwent routine clinical EMU stays. Fifty-four of the study subjects had 96 GTC seizures. The vEEG of events were reviewed for safety signal used, response time, and visibility of patient's limbs. RESULTS: The average response time from members of the hospital team was 22 s from electrographic generalization (minimum -37 s, maximum 111 s, two no response). For caregivers, average response was 11 s (minimum -15 s, maximum 33 s, 45 not present/no response). In 73% of events, the patient visibility was limited at seizure onset. In 55% of events with limited limb visibility, the visibility was improved (by removing sheets or improving camera angle) >30 s after start of the event. The primary safety signals were as follows: an alert from outside the patient room (54%), button press (23%), hospital team present at seizure start (14%), caregiver vocal alert (6%), and no response (2%). SIGNIFICANCE: The average response time of caregivers was twice as fast as the hospital team, underscoring the importance of having a person in the room during onset of a GTC seizure. Diagnostic yield could be improved with more timely removal of patient coverings. It was observed that when patients experienced a GTC seizure, 40% were fully or partially obscured for more than 30 s during the event, compromising the ability of epileptologists to evaluate semiology during seizure onset. Automated seizure alarms may help staff get to patients more quickly and improve diagnostic characterization.

Detection of generalized tonic-clonic seizures using surface electromyographic monitoring.

OBJECTIVE: A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit (EMU) of an investigational wearable surface electromyographic (sEMG) monitoring system for the detection of generalized tonic-clonic seizures (GTCSs). METHODS: One hundred ninety-nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video-electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. RESULTS: For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61-0.87) of the GTCSs, with a positive predictive value (PPV) of 0.03 and a mean false alarm rate (FAR) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88-1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. SIGNIFICANCE: Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.

Electromyography-based seizure detector: Preliminary results comparing a generalized tonic-clonic seizure detection algorithm to video-EEG recordings.

OBJECTIVE: Automatic detection of generalized tonic-clonic seizures (GTCS) will facilitate patient monitoring and early intervention to prevent comorbidities, recurrent seizures, or death. Brain Sentinel (San Antonio, Texas, USA) developed a seizure-detection algorithm evaluating surface electromyography (sEMG) signals during GTCS. This study aims to validate the seizure-detection algorithm using inpatient video-electroencephalography (EEG) monitoring. METHODS: sEMG was recorded unilaterally from the biceps/triceps muscles in 33 patients (17white/16 male) with a mean age of 40 (range 14-64) years who were admitted for video-EEG monitoring. Maximum voluntary biceps contraction was measured in each patient to set up the baseline physiologic muscle threshold. The raw EMG signal was recorded using conventional amplifiers, sampling at 1,024 Hz and filtered with a 60 Hz noise detection algorithm before it was processed with three band-pass filters at pass frequencies of 3-40, 130-240, and 300-400 Hz. A seizure-detection algorithm utilizing Hotelling's T-squared power analysis of compound muscle action potentials was used to identify GTCS and correlated with video-EEG recordings. RESULTS: In 1,399 h of continuous recording, there were 196 epileptic seizures (21 GTCS, 96 myoclonic, 28 tonic, 12 absence, and 42 focal seizures with or without loss of awareness) and 4 nonepileptic spells. During retrospective, offline evaluation of sEMG from the biceps alone, the algorithm detected 20 GTCS (95%) in 11 patients, averaging within 20 s of electroclinical onset of generalized tonic activity, as identified by video-EEG monitoring. Only one false-positive detection occurred during the postictal period following a GTCS, but false alarms were not triggered by other seizure types or spells. SIGNIFICANCE: Brain Sentinel's seizure detection algorithm demonstrated excellent sensitivity and specificity for identifying GTCS recorded in an epilepsy monitoring unit. Further studies are needed in larger patient groups, including children, especially in the outpatient setting.

Validity of the Neurology Quality-of-Life (Neuro-QoL) measurement system in adult epilepsy.

Epilepsy is a chronic neurological disorder that results in recurring seizures and can have a significant adverse effect on health-related quality of life (HRQL). The Neuro-QoL measurement initiative is an NINDS-funded system of patient-reported outcome measures for neurology clinical research, which was designed to provide a precise and standardized way to measure HRQL in epilepsy and other neurological disorders. Using mixed-method and item response theory-based approaches, we developed generic item banks and targeted scales for adults and children with major neurological disorders. This paper provides empirical results from a clinical validation study with a sample of adults diagnosed with epilepsy. One hundred twenty-one people diagnosed with epilepsy participated, the majority of which were male (62%) and Caucasian (95%), with a mean age of 47.3 (SD=16.9). Baseline assessments included Neuro-QoL short forms and general and external validity measures. The Neuro-QoL short forms that are not typically found in other epilepsy-specific HRQL instruments include Stigma, Sleep Disturbance, Emotional and Behavioral Dyscontrol, and Positive Affect and Well-Being. Neurology Quality-of-Life short forms demonstrated adequate reliability (internal consistency range=.86-.96; test-retest range=.57-.89). Pearson correlations (p<.01) between Neuro-QoL forms of emotional distress (anxiety, depression, stigma) and the QOLIE-31 Emotional Well-Being subscale were in the moderate-to-strong range (r's=.66, .71 and .53, respectively), as were relations with the PROMIS Global Mental Health subscale (r's=.59, .74 and .52, respectively). Moderate correlations were observed between Neuro-QoL Social Role Performance and Satisfaction and the QOLIE-31 Social Function (r's=.58 and .52, respectively). In measuring aspects of physical function, the Neuro-QoL Mobility and Upper Extremity forms demonstrated moderate associations with the PROMIS Global Physical Function subscale (r's=.60 and .61, respectively). Neuro-QoL measures of perceived cognitive function (executive function and general concerns) produced moderate-to-strong correlations with the QOLIE-31 Cognition subscale (r's=.65 and .75, respectively) and moderate relations with the Liverpool Adverse Events Profile (r's=.51 and .69, respectively). Finally, the Neuro-QoL Fatigue measure demonstrated moderate associations with the QOLIE-31 Energy/Fatigue subscale (r=-.65), Liverpool Adverse Events Profile (r=.69), and the Liverpool Seizure Severity Scale (r=.50). Five Neuro-QoL short forms demonstrated statistically significant responsiveness to change at 5-7months, including Fatigue, Sleep Disturbance, Depression, Positive Affect and Well-Being, and Emotional and Behavioral Dyscontrol. Overall, Neuro-QoL instruments showed good evidence for internal consistency, test-retest reliability, convergent validity, and responsiveness to change over several months. These results support the validity of Neuro-QoL to measure HRQL in adults with epilepsy.

Potential mechanisms of sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) accounts for 15% of all deaths in people with epilepsy and 50% in refractory epilepsy. The underlying mechanisms are not well understood, but seizure-induced cardiac and respiratory arrests are involved. The cardiovascular and respiratory systems are subject to precise reflex regulation to ensure appropriate oxygen supply under a wide range of circumstances. Barosensory and chemosensory afferents project into the nucleus tractus solitarius (NTS), which relays systemic data to higher brain centers for integration of homeostatic responses in heart rate, peripheral resistance, respiration, and other autonomic reactions. Being the afferent autonomic gatekeeper, NTS plays a critical role in cardiovascular and respiratory regulation. In the course of studying the kainic acid model, we became aware of progressive neuronal loss in the NTS and noted SUDEP-like deaths in rats with frequent convulsions. Increased autonomic susceptibility with inhalation anesthetics was also observed, often seen after impairment of baroreceptor and chemoreceptor reflex loops. Seizure-induced neuron loss in NTS may play a role impairing the integrative functions of NTS resulting in poor homeostatic responses during seizures and leading to SUDEP.

A collaborative effort to establish a comprehensive epilepsy program in Peru.

We report the achievements obtained, over a period of 4 years, by the collaborative partnering effort of the Epilepsy Program at Western University in Canada and the Instituto of Ciencias Neurologicas in Lima, Peru, building an epilepsy program in Peru.

Gender, Racial, and Ethnic and Inequities in Receipt of Multiple National Institutes of Health Research Project Grants.

Importance: Diversity in the biomedical research workforce is essential for addressing complex health problems. Female investigators and investigators from underrepresented ethnic and racial groups generate novel, impactful, and innovative research, yet they are significantly underrepresented among National Institutes of Health (NIH) investigators. Objective: To examine the gender, ethnic, and racial distribution of super NIH investigators who received 3 or more concurrent NIH grants. Design, Setting, and Participants: This cross-sectional study included a national cohort of NIH-funded principal investigators (PIs) from the NIH Information for Management, Planning, Analysis, and Coordination (IMPAC II) database from 1991 to 2020. Exposures: Self-identified gender, race and ethnicity, annual number of NIH grant receipt, career stage, and highest degree. Main Outcomes and Measures: Distribution of investigators receiving 3 or more research project grants, referred to as super principal investigators (SPIs), by gender, race, and ethnicity. Results: Among 33 896 investigators in fiscal year 2020, 7478 (22.01%) identified as Asian, 623 (1.8%) as Black, 1624 (4.8%) as Hispanic, and 22 107 (65.2%) as White; 21 936 (61.7%) identified as men; and 8695 (35.3%) were early-stage investigators. Between 1991 and 2020, the proportion of SPIs increased 3-fold from 704 (3.7%) to 3942 (11.3%). However, SPI status was unequal across gender, ethnic, and racial groups. Women and Black PIs were significantly underrepresented among SPIs, even after adjusting for career stage and degree, and were 34% and 40% less likely than their male and White colleagues, respectively, to be an SPI. Black women PIs were the least likely to be represented among SPIs and were 71% less likely to attain SPI status than White men PIs (adjusted odds ratio, 0.29; 95% CI, 0.21-0.41). Conclusions and Relevance: In this cross-sectional study of a national cohort of NIH-funded investigators, the gender, ethnic, and racial gaps in receipt of multiple research project grants among NIH investigators was clearly apparent and warrants further investigation and interventions.

Acute Treatment with the M-Channel (Kv7, KCNQ) Opener Retigabine Reduces the Long-Term Effects of Repetitive Blast Traumatic Brain Injuries.

We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2 years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleus to the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of the EGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.

Cerebral small vessel disease burden is associated with decreased abundance of gut Barnesiella intestinihominis bacterium in the Framingham Heart Study.

A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p values < 0.001), as well as better executive function (p values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and ß-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

Variation in Research Experiences and Publications During Medical School by Sex and Race and Ethnicity.

Importance: Diverse research teams are critical to solving complex health problems and producing high-quality medical research. Objective: To examine the associations of student sex and racial and ethnic identity with publication rates during medical school. Design, Setting, and Participants: This cohort study assessed individual-level data of US MD graduates from medical school who matriculated in academic years 2014 to 2015 and 2015 to 2016. Data were obtained from the Association of American Medical Colleges and analyzed from October 2021 to January 2022. Main Outcomes and Measures: Outcomes of interest included students' self-reported participation in unique research experiences, number of publications, and computed publications per research experience. Poisson regressions were constructed to determine the association of sex and racial and ethnic identity with research outcomes using adjusted rate ratios (aRRs). Results: Among 31 474 graduates, 15 159 (48.2%) identified as women and 4344 (13.8%) identified as underrepresented in medicine by race and ethnicity (URIM; including American Indian, Alaska Native, Black, Hawaiian Native, Hispanic/Latinx, and Pacific Islander individuals). Students who attended National Institutes of Health (NIH) top 40 research-ranked schools reported higher number of research experiences and publication counts, resulting in a higher publication rate compared with students from non-top 40 schools (median [IQR] 1.60 [1.00-3.00] vs 1.25 [0.50-2.33]; P < .001). Women reported a higher number of research experiences than men but a significantly lower number of publications (top 40 schools: aRR, 0.89; 95% CI, 0.87-0.90; non-top 40 schools: aRR, 0.93; 95% CI, 0.92-0.95). This resulted in a significantly lower publication rate among women (top 40 schools: aRR, 0.85; 95% CI, 0.83-0.86; non-top 40 schools: aRR, 0.91; 95% CI, 0.90-0.92). Compared with White students, Asian students had higher publication rates at both NIH top 40 schools (aRR, 1.10; 95% CI, 1.08-1.12) and non-top 40 schools (aRR, 1.07; 95% CI, 1.05-1.08), while lower publication rates were reported among Black students (top 40 schools: aRR, 0.83; 95% CI, 0.80-0.86; non-top 40 schools: aRR, 0.88; 95% CI, 0.85-0.95) and Hispanic students attending non-top 40 schools (aRR, 0.93; 95% CI, 0.90-0.95). Conclusions and Relevance: These findings illustrate that inequities in the physician-scientist workforce began early in training and highlight key areas for intervention, such as funding support and mentorship training during undergraduate medical education, that may promote the future success of a diverse physician-scientist workforce.

Trends in U.S. MD-PhD Program Matriculant Diversity by Sex and Race/Ethnicity.

PURPOSE: To examine demographic characteristics of matriculants to U.S. MD-PhD programs by sex and race/ethnicity from academic years (AYs) 2009-2018 and explore the relationships between trends in the percentage of female and underrepresented minority (URM) matriculants to programs with and without Medical Scientist Training Program (MSTP) funding. METHOD: Linear regression and time trend analysis of the absolute percentage of matriculants into all U.S. MD-PhD programs was performed for self-reported sex and race/ethnicity, using Association of American Medical Colleges data for AYs 2009-2018, including an interaction for MSTP funding status (yes/no) and year. Linear regression of the percentage of programs matriculating no female or no URM students between AYs 2009 and 2018 was performed, focusing on programs in the top 3 quartiles by size (i.e., those matriculating 4 or more students per year). RESULTS: Between AYs 2009 and 2018, the percentage of matriculants to all MD-PhD programs who were female (38.0%-46.0%, 1.05%/year, P = .002) or URM (9.8%-16.7%, 0.77%/year, P < .001) increased. The annual percentage gains of URM matriculants were greater at MSTP-funded programs compared with non-MSTP-funded programs (0.50%/year, P = .046). Moreover, among MD-PhD programs in the top 3 quartiles by size, the percentage of programs with no female matriculants decreased by 0.40% per year ( P = .02) from 4.6% in 2009 to 1.6% in 2018, and the percentage of programs with no URM matriculants decreased by 3.41% per year ( P < .001) from 49% in 2009 to 22% in 2018. CONCLUSIONS: A consistent and sustained increase in the percentage of female and URM matriculants to MD-PhD programs from AYs 2009-2018 was observed, but the annual increases in the percentages across groups were small, and the demographics of the MD-PhD workforce still do not reflect the diversity of the U.S. general population.

Neuroprotective Roles of the Adenosine A3 Receptor Agonist AST-004 in Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) remains one of the greatest public health concerns with increasing morbidity and mortality rates worldwide. Our group reported that stimulation of astrocyte mitochondrial metabolism by P2Y1 receptor agonists significantly reduced cerebral edema and reactive gliosis in a TBI model. Subsequent data on the pharmacokinetics (PK) and rapid metabolism of these compounds suggested that neuroprotection was likely mediated by a metabolite, AST-004, which binding data indicated was an adenosine A3 receptor (A3R) agonist. The neuroprotective efficacy of AST-004 was tested in a control closed cortical injury (CCCI) model of TBI in mice. Twenty-four (24) hours post-injury, mice subjected to CCCI and treated with AST-004 (0.22 mg/kg, injected 30 min post-trauma) exhibited significantly less secondary brain injury. These effects were quantified with less cell death (PSVue794 fluorescence) and loss of blood brain barrier breakdown (Evans blue extravasation assay), compared to vehicle-treated TBI mice. TBI-treated mice also exhibited significantly reduced neuroinflammatory markers, glial-fibrillary acidic protein (GFAP, astrogliosis) and ionized Ca2+-binding adaptor molecule 1 (Iba1, microgliosis), both at the mRNA (qRT-PCR) and protein (Western blot and immunofluorescence) levels, respectively. Four (4) weeks post-injury, both male and female TBI mice presented a significant reduction in freezing behavior during contextual fear conditioning (after foot shock). AST-004 treatment prevented this TBI-induced impairment in male mice, but did not significantly affect impairment in female mice. Impairment of spatial memory, assessed 24 and 48 h after the initial fear conditioning, was also reduced in AST-004-treated TBI-male mice. Female TBI mice did not exhibit memory impairment 24 and 48 h after contextual fear conditioning and similarly, AST-004-treated female TBI mice were comparable to sham mice. Finally, AST-004 treatments were found to increase in vivo ATP production in astrocytes (GFAP-targeted luciferase activity), consistent with the proposed mechanism of action. These data reveal AST-004 as a novel A3R agonist that increases astrocyte energy production and enhances their neuroprotective efficacy after brain injury.

Post-traumatic epilepsy: an overview.

Post-traumatic seizures (PTS) and post-traumatic epilepsy (PTE) are complications from traumatic brain injury (TBI). PTE refers to recurrent and unprovoked PTS that occur at least 1 week after TBI. Seizures during the first week after TBI are considered provoked, an acute complication from head injury, while seizures occurring 1 week after TBI are considered a manifestation of PTE and if only a single seizure occurs it is known as late PTS. EEG and neuroimaging help in the diagnosis of PTE. Predictors for PTE include TBI severity, presence of intracranial bleeding and early PTS. Several clinical trials have demonstrated that antiepileptic drugs are effective in reducing the frequency of acute PTS, but do not appear to alter the natural history of late PTS or PTE.

Neuro-QOL and the NIH Toolbox: implications for epilepsy.

The impact of neurological disorders on the lives of patients is often far more complex than what is measured in routine examination. Measurement of this impact can be challenging owing to a lack of brief, psychometrically sound and generally accepted instruments. Two NIH-funded initiatives are developing assessment tools, in English and Spanish, which address these issues, and should prove useful to the study and treatment of epilepsy and other neurological conditions. The first, Neuro-QOL, has created a set of health-related quality of life measures that are applicable for people with common neurological disorders. The second, the NIH Toolbox for the Assessment of Neurological and Behavioral Function, is assembling measures of cognitive, emotional, motor and sensory health and function that can be used across all ages, from 3 to 85 years. This article describes both the projects and their potential value to epilepsy treatment and research.

Changing characteristics of epilepsy interventional clinical trials over the last decade: Clinicaltrials.Gov registry.

INTRODUCTION: Epilepsy affects about 1% of the world's population (over 50 million). Of these, one-third have refractory or medication-resistant epilepsy. This group of people drives the development and testing of new interventions for epilepsy. To better address the needs of people with epilepsy, the characteristics of clinical trials, as well as the gaps in the population of interest, need to be evaluated. METHODS: We searched the www.ClinicalTrials.gov database using the keywords "seizure" or "epilepsy" between 9/1/2008-9/1/2018 and filtering for Interventional Clinical trials. The data were categorized by three equal time intervals (tertiles), and evaluated by type of intervention (behavioral, diet, device, drug, other), primary purpose (treatment, diagnosis, prevention, or basic science), gender, age, phase (Phase1 to Phase 4 trials), length and status of the study, enrollment/recruitment/randomization, location, blinding status, assignment group (single/parallel/crossover/factorial/sequential), and funding. We focused on drugs and devices and used a binary logistic regression model to analyze the role of time, length of study, funding, location, randomization, and age. RESULTS: We found 359 epilepsy clinical trials; of these, 245 (68.2%) clinical trials involved drugs, and 55 (15.3%) were device trials. Over the three tertiles, the percentage of device trials increased while medication trials decreased. Device:drug trial odds ratios increased six times by the third tertile. Also, the results showed that clinical trials for drugs and devices occurred more in adults than children. Industry funding decreased 20% over time. The US contribution to clinical research was stable, but device trials were more likely to occur outside of the US. CONCLUSION: Drugs constitute the substantial fields of interventional trials in epilepsy but decreased in proportion over the last decade, while the presence of the device trials steadily increased. Device trials focused on treatment and diagnosis of seizures and have been more invested in non-US countries.

Creutzfeldt-Jakob Disease: In-hospital demographics report of national data in the United States from 2016 and review of a rapidly-progressive case.

BACKGROUND: This report highlights a rapidly progressive case of Creutzfeldt-Jakob Disease (CJD) whose time from symptom onset to death spanned less than two months. We also explore the most recently available in-patient demographics data for discharges with CJD in the United States. METHODS: We reviewed a CJD case and systematically analyzed a retrospective cohort of CJD discharges using the Healthcare Cost and Utilization Project (HCUP) to evaluate the existing national data on the status of CJD demographics and dispositions in the United States in 2016. RESULTS: An estimated total of 710 hospital discharges with a diagnosis of CJD were seen across the United States in 2016. According to HCUP, the average age of patients was 66.15 ±â€¯11.54 years with 48.6 % female. Average time to intubation from admission to hospital was 4.71 ±â€¯7.32 days with a rate of intubation of 6.34 %. The mean hospital cost was $19,901.25 ± $18,743.48. The rate of in-hospital mortality was 8.45 %. No significant geographical differences were noted (p = 0.49). No significant differences were seen among incidence in specific ethnic groups (p = 0.33) or income quartiles (p = 0.90). CONCLUSIONS: Our data shows that the incidence of CJD in 2016 appears to be equally distributed among individuals in the United States by demographic categories. Additionally, our case-study from 2019 illustrates an important example for diagnosing a rapidly-progressing case of CJD.