Faculty Bibliography

BACKGROUND/UNASSIGNED:Tapia's syndrome is a rare neurological condition defined by concurrent unilateral paralysis of the vagus (cranial nerve X) and hypoglossal (cranial nerve XII) nerves. It is most commonly reported as an iatrogenic complication of procedures involving airway manipulation, such as orotracheal intubation. This report describes a unique case of Tapia's syndrome with a temporal association to the initiation of noninvasive continuous positive airway pressure (CPAP) therapy. CASE PRESENTATION/UNASSIGNED:A 66-year-old female presented with a four-day history of acute-onset dysphonia, dysphagia, and right-sided tongue deviation. Her symptoms began shortly after initiating CPAP therapy with a full-face mask for newly diagnosed obstructive sleep apnea. She had also recently received multiple vaccinations. Clinical examination revealed right-sided vagus and hypoglossal nerve palsies, and laryngoscopy confirmed right vocal cord paralysis. Extensive diagnostic evaluation, including magnetic resonance imaging and angiography of the brain and neck, effectively excluded central nervous system pathologies such as stroke, demyelinating disease, or mass lesions and diagnosis of Tapia's syndrome was made. The patient was managed by discontinuing CPAP and administering a course of oral corticosteroids, alongside speech and swallowing therapy. She experienced a near-complete resolution of her symptoms over 6 weeks. CONCLUSION/UNASSIGNED:This case suggests that Tapia's syndrome can be a rare complication of noninvasive airway support. A multifactorial etiology involving mechanical nerve compression from the CPAP apparatus, potentially compounded by an immune-mediated nerve sensitization from recent vaccinations, should be considered in the differential diagnosis of lower cranial neuropathies.

BACKGROUND:Individuals with inflammatory bowel disease (IBD) have an elevated risk of colorectal neoplasia (CRN), including colorectal dysplasia and cancer (CRC). Despite surveillance strategies to prevent CRC, the clinical course of dysplasia types remains poorly understood. METHODS:We conducted a nationwide cohort study using the Swedish Patient Register and the ESPRESSO histopathology cohort to identify patients diagnosed with IBD between 1969 and 2023. Patients were classified according to their first (baseline) incident episode of dysplasia (no dysplasia, ND; indefinite, IND; low-grade, LGD; high-grade, HGD). Our primary outcome was future advanced CRN (HGD or CRC) during follow-up. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS:We identified 54,534 patients with IBD, including 1,320 with a first (baseline) episode of dysplasia (264 IND, 1031 LGD, 25 HGD), and 53,214 with ND. Over a median follow-up of 13.3 years, 2.3% of ND patients had future advanced CRN compared to 5.3% of IND patients (aHR 1.85, 95% CI 1.09-3.15) and 8.3% of LGD patients (aHR 3.51, 95% CI 2.77-4.45). Of those with HGD, 40% developed CRC (aHR 47.88, 95% CI 25.53-89.80). Risk factors for future dysplasia included male sex, younger age at diagnosis, extensive colitis, primary sclerosing cholangitis, and histologic inflammation. CONCLUSION/CONCLUSIONS:Patients with IBD and dysplasia have a significantly increased risk of future dysplasia, particularly among patients with HGD. Personalized surveillance strategies based on risk factors are critical for preventing advanced CRN.

INTRODUCTION/BACKGROUND:As new psychoactive substances (NPS) continue to emerge both in the US and globally, research is needed to determine the extent of adverse effects associated with NPS use beyond poisonings or mortality to inform prevention and harm reduction efforts in this population. METHODS:Data were from the National Drug Early Warning System Rapid Street Reporting study, which uses a venue-intercept design to survey adults (≥ 18 years) in US cities over weekend periods. Between January 2022 and November 2023, 6039 individuals were surveyed in 20 cities regarding their use of a range of NPS and other common drugs. Those reporting past 12-month use of a drug were asked if they experienced a harmful or very unpleasant effect after use. RESULTS:Overall, among those reporting any past 12-month NPS use (n = 259), over a quarter (27.03%) reported experiencing an adverse effect related to the use of at least one NPS in the past 12 months. Among those reporting NPS use, those who also reported past 12-month opioid use had over two times the prevalence of reporting an adverse effect related to NPS use (adjusted prevalence ratio 2.66, 95% confidence interval 1.41, 5.01). Symptom profiles were broadly similar between NPS and common drug classes. DISCUSSION AND CONCLUSIONS/CONCLUSIONS:Adverse effects from NPS appear to be common among those self-reporting NPS use, particularly among those reporting polysubstance use. More data are needed to determine event-specific adverse outcomes involving the use of NPS and other drugs.

The gut microbiota can affect neuronal excitability, inflammation, and oxidative balance via the gut-brain axis, shaping seizure susceptibility. To translate these findings into clinical approaches, a synthesis of preclinical microbiome-based evidence is needed. This systematic review and meta-analysis examined the putative anticonvulsant, anti-inflammatory, antioxidant, and neuroprotective effects of probiotics in rodent models. An extensive systematic search up to July 2025 identified eligible animal studies in which probiotics were administered in seizure models. Reported outcomes included seizure latency, duration, severity, and frequency, as well as inflammation, oxidative stress, and behavioral measures. Of the 24 studies that met the inclusion criteria, 19 provided sufficient data to be included in the meta-analysis. The most frequently used strains belonged to the Lactobacillus (e.g., acidophilus, casei, fermentum) and Bifidobacterium genera (e.g., bifidum, longum), with occasional synbiotic combinations. Probiotics significantly increased seizure latency (MD = 22.09; 95 % CI: 10.52 to 33.67) and reduced seizure severity (MD = -1.08; 95 % CI: -1.39 to -0.76) and duration (MD = -23.19; 95 % CI: -35.56 to -10.82). Probiotics significantly reduced IL-1β, IL-6, and TNF-α levels while MDA showed a nonsignificant trend toward reduction (p = 0.076). Behaviorally, improvements in spatial learning (p < 0.05) and reduced anxiety-like behavior (p < 0.001) were observed. Probiotic supplementation appears to exert anticonvulsant, anti-inflammatory, antioxidant, and behavioral benefits in preclinical epilepsy models, although the evidence is heterogeneous and limited to animal studies. Mechanistic evidence indicates modulation of the gut-brain axis, enhanced GABAergic signaling, and improved mitochondrial function. These findings support further investigation of specific probiotic formulations as promising adjunct candidates in well-designed, mechanism-driven clinical trials.

BACKGROUND:The obesity epidemic in the United States affects not only adults, but children and adolescents. SOURCES OF MATERIAL/UNASSIGNED:An extensive review of the literature including 85 articles has been completed with the aim of providing the most current definitions and recommendations for this chronic condition. ABSTACT OF FINDINGS/UNASSIGNED:This article reviews the definition of pediatric obesity, the increasing prevalence of obesity in children and adolescents, genetic and environmental risk factors, as well as the unique aspects and implications of this condition and its associated comorbidities for this population in comparison to adults. Current management recommendations are also discussed which include Intensive Health Behavioral and Lifestyle Treatment (IHBLT), metabolic surgery, and pharmacologic therapy including glucago-like peptide-1 receptor agonists (GLP-1RAs). CONCLUSION/CONCLUSIONS:Childhood obesity is a unique condition in its progression and management requirements, and should be approached with a focus on prevention as well as on the high-risk individual.

Autophagy, a programmed self-eating process, underlies the progression of multifactorial diseases like pancreatic ductal adenocarcinoma (PDA). Except for nutrient availability, the contribution of microenvironmental factors to autophagy regulation is not well understood. Through integrating functional genomics and tumor-like 3D cultures, we show that human PDA cells regulate their autophagy levels by sensing the extracellular matrix (ECM) via the integrinα3-Hippo-YAP1 axis. The spatial proximity of PDA cells to the ECM shapes their intracellular autophagy levels, leading to heterogeneous biological responses. Specifically, PDA cells with low autophagy levels are proliferative, whereas those with high autophagy levels display better tolerance to chemotherapies. Targeting the ECM-mediated autophagy regulation reduces autophagic heterogeneity, alters PDA growth, and shapes antitumor responses to FDA-approved therapies. In summary, we have characterized a non-metabolic regulation of autophagy through ECM sensing, opening the possibility to investigate and target ECM-specific outputs in diseases.

Centromeres ensure accurate chromosome segregation, yet their DNA evolves rapidly across eukaryotes leaving the origins of new centromere architectures unclear^1-4. The brewer's yeast Saccharomyces cerevisiae exemplifies this long-standing puzzle. Its centromeres shifted ancestrally from large, repeat-rich, epigenetically specified forms to the compact, genetically defined 'point' centromeres^1,5. How this transition occurred has remained unresolved⁶. Here we identify evolutionarily related 'proto-point' centromeres that provide a resolution to the evolutionary origins of point centromeres. Proto-point centromeres contain a single centromeric nucleosome positioned over an AT-rich core, accompanied by relaxed organization and sequence variability of flanking cis-elements. In two species, these proto-point centromeres lie within retrotransposon-derived repeat clusters, linking ancestral repeat-rich centromeres to genetically encoded ones. Comparative and phylogenetic analyses indicate that proto-point and point centromeres evolved in an ancestor with retrotransposon-rich centromeres. These results identify long-terminal-repeat retrotransposons, specifically Ty5 sequences, as the genetic substrate for point-centromere evolution and provide a mechanistic route by which an epigenetic centromere can become genetically specified. More broadly, they show how selfish elements can be co-opted to perform essential chromosomal functions.