Publications

The autonomic nervous system (ANS) coordinates the body's response to stress. Proinflammatory cytokines [e.g., tumor necrosis factor-alpha (TNFα)], released in response to different stressors, may influence underlying pathophysiology involving autonomic dysfunction. The present study evaluated the impact of peripheral TNFα on cellular activation in brain stem nuclei associated with autonomic function, including the dorsal vagal complex (DVC) and the ventral lateral medulla (VLM). Mice received a single intraperitoneal injection of TNFα and were processed 2 h later to identify immunoreactive c-Fos in brain stem nuclei as a measure of cellular activity. The number of c-Fos-immunoreactive cells increased after TNFα challenge within the DVC and VLM. Cells immunoreactive for c-Fos were concentrated lateral to the area postrema (AP), a circumventricular organ medial to the subdivision of the caudal portion of the nucleus of the solitary tract (cNTS) within the DVC. To examine the role of microglia in mediating cellular responses to peripheral TNFα, minocycline was administered into the fourth ventricle to decrease microglial function. Minocycline treatment reduced ionized calcium binding adapter molecule 1 (IBA-1) immunoreactivity in the AP and cNTS. When animals were challenged with TNFα after receiving minocycline, fewer c-Fos-positive cells were induced in the DVC and selectively in the rostral VLM. These findings highlight the spatial selectivity of cells in the brain stem to increased peripheral proinflammatory signaling, as well as the impact of resident microglia on autonomic circuitry responses.NEW & NOTEWORTHY This study investigates how peripheral tumor necrosis factor-alpha (TNFα) affects neuronal activity in autonomic nuclei of the brain stem and how microglia contribute to this response. Peripheral TNFα increased neuronal activation (c-Fos expression) in the dorsal vagal complex (DVC) and ventrolateral medulla (VLM), particularly near the area postrema. Inhibiting microglia with intracerebroventricular minocycline reduced both microglial markers and TNFα-induced neuronal activity, suggesting that microglia play a key role in modulating cytokine-driven autonomic signaling in the brain stem.

OBJECTIVE: To investigate the effects of a collegiate ice hockey season and the repetitive head impacts (RHI) experienced on the neurologic health using a multifaceted assessment battery.

DESIGN: Cross-sectional.

SETTING: Research laboratory.

PARTICIPANTS: Thirty-six male collegiate club ice hockey players.

INDEPENDENT VARIABLES: Time (preseason, midseason, postseason) and head impact measures (number of impacts, mean linear acceleration).

MAIN OUTCOME MEASURES: Athletes wore Smart Impact Monitor (SIM-G) accelerometers throughout 1 season and completed testing at preseason, midseason, and postseason. The battery included a 22-item graded symptom checklist, Standardized Assessment of Concussion, Balance Error Scoring System, Trails A & B, King-Devick, Near Point Convergence, Clinical Reaction Time, Tandem Gait (single- and dual-task), and computerized neurocognitive testing (ImPACT).

RESULTS: There was a significant main effect of time, with improved performance, on the Standardized Assessment of Concussion (F(2, 70) = 4.43, P = 0.015), Trails A (F(2, 67) = 7.16, P = 0.002), Trails B (F(2,71) = 5.19, P = 0.008), King-Devick (F(2, 72) = 4.31, P = 0.017), Clinical Reaction Time (F(2, 69) = 4.54, P = 0.014), ImPACT Verbal Memory (F(2, 76) = 3.82, P = 0.026), and Tandem Gait (ST: F(2, 76) = 6.11, P = 0.003; DT: F(2, 78) = 4.65, P = 0.012). Multiple regression analyses identified an association between the overall head impact model and Visual Motor score (R2 = 0.354, F(2, 29) = 3.698, P = 0.016), whereby increased head kinematics corresponded to higher (better) Visual Motor performance.

CONCLUSIONS: A season of collegiate ice hockey RHI did not negatively affect multifaceted clinical assessments. Additional investigation is warranted to determine the effect of RHI sustained during collegiate hockey participation later in life.

PURPOSE: Uncorrected refractive error (URE) is the leading cause of vision impairment, especially in rural, underserved areas. We previously evaluated the accuracy of a smartphone app for measuring spherical equivalent refraction. In this study, we evaluated the benefits of vision correction based on the prescription given by the app.

METHODS: The app estimates myopic refractive error by measuring the far point distances for reading 20/20 Tumbling E letters. Trial lenses rounded to 0.25 diopter (D) were fitted to 100 patients (myopic refractive error, astigmatism < 1.5 D) visiting MCM Eye Unit in Addis Ababa, Ethiopia. The age range of the participants was 10 to 68 years (mean = 31.3 ± 13.0 years). The refraction measurement and visual acuity (VA) tests were all performed without cycloplegia.

RESULTS: The range of spherical equivalent refractive error was -0.5 D to -6 D (interquartile range [IQR] = -2.25 D to -0.95 D), and the range of astigmatism was 0 to -1.25 D (IQR = -0.5 D to 0 D), according to subjective refraction performed by a study optometrist. On average, the uncorrected VA of the 200 eyes was 0.57 ± 0.32 logMAR. With the spherical equivalent correction based on the refraction app, their VA was improved significantly to 0.03 ± 0.09 logMAR-more than 5 lines of improvement, on average.

CONCLUSIONS: This study indicates that using the app to determine the spherical equivalent prescription for vision correction addresses the URE problem, whereas its effect for prominent astigmatism is yet to be evaluated.

TRANSLATIONAL RELEVANCE: This approach, which requires minimal training, has potential in fighting avoidable blindness in underserved areas lacking optometry services, such as remote Sub-Saharan Africa.

OBJECTIVE: To propose a mechanistic framework for the use of transcranial photobiomodulation (tPBM) as an adjunctive treatment in Rett syndrome (RTT).

BACKGROUND DATA: RTT is a severe X-linked neurodevelopmental disorder caused mainly by MECP2 variants, with limited disease-modifying therapies. tPBM delivers red-to-near-infrared light to the brain and shows promising effects in several neurocognitive and neuropsychiatric conditions.

METHODS: We reviewed key cellular mechanisms of RTT, namely mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired synaptic plasticity, and summarized established bioenergetic, redox, anti-inflammatory, and neurotrophic actions of tPBM.

RESULTS: The convergence between these pathways suggests that tPBM could partially compensate for bioenergetic and signaling abnormalities in RTT, acting as a multi-target, pathophysiology-informed neuromodulation strategy.

CONCLUSIONS: Although speculative, this mechanistic convergence supports prioritizing preclinical studies in Mecp2-deficient models and early-phase feasibility trials of tPBM in individuals with RTT.

BACKGROUND: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals and is increasingly diagnosed in childhood. Growing evidence suggests an association between CD and metabolic syndrome (MetS), potentially mediated by chronic inflammation, intestinal dysbiosis, oxidative stress, and micronutrient deficiencies. In addition, although a gluten-free diet (GFD) is essential for intestinal recovery, its frequent reliance on ultra-processed, energy-dense products may adversely affect metabolic health, particularly in pediatric patients.

OBJECTIVE: This narrative review aims to examine the relationship between CD and MetS, with a specific focus on pediatric populations, by analyzing shared pathophysiological mechanisms, the metabolic impact of a GFD, and preventive nutritional strategies to reduce long-term cardiometabolic risk.

METHODS: A narrative review was performed using PubMed and Scopus databases, focusing on studies published in the past 15 years. Search terms included "Celiac Disease," "Metabolic Syndrome," "Child," "Adolescent," "Risk Factors," and "Prevention." Among 229 identified papers, 43 were selected after critical appraisal. Evidence was synthesized on epidemiology, mechanisms, dietary effects, and preventive strategies.

RESULTS: Studies indicate that MetS prevalence in CD ranges from 3 to 11% at diagnosis and may rise to 14-29% after 1 year on a GFD, particularly in adults. In children, complete MetS is rare, though isolated components, central adiposity, dyslipidemia, and hypertension, are increasingly observed. Mechanistically, gluten-induced barrier disruption, inflammation, dysbiosis, and nutritional imbalances contribute to systemic metabolic alterations. Adherence to a Mediterranean-style GFD emphasizing whole, naturally gluten-free foods reduces cardiometabolic risk.

CONCLUSION: CD and MetS share interconnected inflammatory and metabolic pathways. While GFD remains essential for CD management, it necessitates tailored nutritional guidance and metabolic monitoring. Early lifestyle-based interventions-promoting balanced diet quality, micronutrient adequacy, and physical activity, offer key opportunities to prevent metabolic complications in children with CD.

PURPOSE: Many rare genetic conditions manifest soon after birth and result in admission to the Neonatal Intensive Care Unit (NICU), where prior research suggests that parents experience high levels of stress and uncertainty. However, further insight into parent-reported, longer-term outcomes for these infants and their families is needed.

METHODS: We undertook a qualitative analysis of parent-reported experiences with genomic care over the course of their NICU admission and beyond, after an initial quantitative study of 110 families who received genetic evaluation in the NICU, in a mixed-methods approach. Twenty families participated in individual semistructured interviews eliciting the impact of the NICU experience and genetic diagnostic odyssey on the infant and family.

RESULTS: We identified 4 main themes: (1) Rare Disease as "Culture Shock," (2) Parental Trauma and Stressors, (3) Family Resiliency, and (4) Hospital System Recommendations. Early, rapid, and broad genomic testing was appreciated by parents, although additional genomic- and nongenomic supports after NICU discharge were desired. Stressors in the NICU related to uncertainty and critical illness occurred independent of genetic testing applications or results. Parents reported adapting their expectations regarding the benefits of a genetic diagnosis over time, ultimately focusing on day-to-day care and finding pride in medical and social resilience.

CONCLUSION: The NICU experience, particularly for infants with rare conditions, has long-lasting impact on the family. Enhanced attention to longitudinal supports from NICU to home may be beneficial for families undergoing genetic diagnostic odysseys.

BACKGROUND: The Accident and Emergency (A&E) unit is a key entry point for healthcare in Nigeria, yet data on its functionality and capacity for emergency care remain limited. This study evaluates the functional capacity of A&E units in Nigeria using a modified Emergency Care Assessment Tool (ECAT).

METHODS: A cross-sectional study was conducted from September to October 2020 in seven tertiary hospitals across Nigeria. Six hospitals, one from each of the country's six geopolitical zones, were randomly selected, while the seventh-Nigeria's main trauma center located in the capital-was purposively included. Doctors and nurses routinely working in A&E units were interviewed using a modified Emergency Care Assessment Tool (ECAT), which evaluates the availability of essential medical interventions (signal functions) for managing six common, life-threatening sentinel conditions: Maternal and Child emergencies, Respiratory failure, Trauma, Shock, Altered mental status, and Severe pain.

RESULTS: Among 503 healthcare providers surveyed (393 doctors and 110 nurses), significant differences were observed in the performance of signal functions across all six sentinel conditions (p < 0·001) and across the seven study sites (p < 0·001). The overall average capacity score was 2·69 out of 3. Federal Medical Center Katsina (North-West zone) recorded the highest mean score of 2·92 (95% CI: 2·77 - 3·07), while UCTH (South-South zone) had the lowest at 2.44 (95% CI: 2·27 - 2·60). Among the conditions assessed, respiratory failure had the lowest mean score at 2·55 (1·88-3·21).

CONCLUSION: This study reveals a higher-than-expected national average A&E capacity score (2·69 out of 3) in Nigerian tertiary hospitals but highlights ongoing challenges, particularly in managing respiratory emergencies. Notable regional disparities were observed, with the Northern region outperforming others. Findings emphasize the need for objective, on-site evaluations and broader inclusion of facilities, along with targeted, region-specific investments to improve equitable emergency care nationwide.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity, contributing to long term adverse respiratory outcomes that persist across the life course. However, it remains unclear how childhood opportunity impacts the underlying risk for developing BPD and post-discharge respiratory health, both of which may impact long term outcomes.

METHODS: Observational cohort of 845 children born very preterm (≤32 weeks), followed for post-prematurity respiratory disease. We derived childhood opportunity index (COI) from the census tract corresponding to each subject's address. Linear regression was used to identify the impact of COI on neonatal and childhood respiratory outcomes. In a secondary analysis, we examined differences in outcomes between races (White, non-White), across quartiles of COI.

RESULTS: Children residing in neighborhoods with lower COI were born at a significantly smaller birth weight, earlier gestation, and spent longer duration on mechanical ventilation (MV) in the NICU. No direct association was observed between COI and longer-term respiratory outcomes. Racial disparities in birth outcomes within COI quartiles became more pronounced at higher levels of opportunity. Longer duration of MV in the NICU was significantly associated with longer-term outcomes including increased hospital readmissions in early life and lower FEV1 and FVC % predicted in childhood.

CONCLUSION: Low COI is associated with longer duration of MV in the NICU, which itself is associated with increased healthcare utilization and reduced functional respiratory outcomes. Racial disparities in birth outcomes within similar neighborhood contexts demonstrate the need for targeted interventions to advance health equity in this population of vulnerable infants.

The topics of ethics and professionalism in anatomy have only recently gained prominence within the discipline, reflecting trends in medical and health professions education and an increasing awareness of societal expectations around the use of the dead. Educators in anatomy have had limited access to specific resources and no established communities of practice to support their understanding and teaching of these subjects. This article traces the journey of three anatomy educators who addressed this gap by developing dedicated educational resources for use in anatomy teaching. The initiative began in 2020 with the creation of a suite of freely available resources designed to provide accessible, engaging content for educators. Next, the project expanded to include quarterly webinars to facilitate dialog and knowledge exchange, as well as in person sessions at anatomical conferences that have fostered professional networking and collaborations. Over time, what began as a resource-driven initiative evolved into a broader movement. By 2025, this journey has culminated in the establishment of an active community of practice and the adoption of the moniker "Bioethics Unicorns" that has come to represent the initiative. This article reflects on the stages of this journey, the development of the resources and community of practice, and provides advice for those wishing to develop educational initiatives for education in their own communities.