Alzheimer’s disease (AD) presents a public health challenge due to its progressive neurodegeneration, cognitive decline, and memory loss. The amyloid cascade hypothesis, which postulates that the accumulation of amyloid-beta (Aβ) peptides initiates a cascade leading to AD, has dominated research and therapeutic strategies. The failure of recent Aβ-targeted therapies to yield conclusive benefits necessitates further exploration of AD pathology. This review proposes the Mitochondrial–Neurovascular–Metabolic (MNM) hypothesis, which integrates mitochondrial dysfunction, impaired neurovascular regulation, and systemic metabolic disturbances as interrelated contributors to AD pathogenesis. Mitochondrial dysfunction, a hallmark of AD, leads to oxidative stress and bioenergetic failure. Concurrently, the breakdown of the blood–brain barrier (BBB) and impaired cerebral blood flow, which characterize neurovascular dysregulation, accelerate neurodegeneration. Metabolic disturbances such as glucose hypometabolism and insulin resistance further impair neuronal function and survival. This hypothesis highlights the interconnectedness of these pathways and suggests that therapeutic strategies targeting mitochondrial health, neurovascular integrity, and metabolic regulation may offer more effective interventions. The MNM hypothesis addresses these multifaceted aspects of AD, providing a comprehensive framework for understanding disease progression and developing novel therapeutic approaches. This approach paves the way for developing innovative therapeutic strategies that could significantly improve outcomes for millions affected worldwide.

Advances in neuro-oncology have transformed the diagnosis and management of brain tumors, which are among the most challenging malignancies due to their high mortality rates and complex neurological effects. Despite advancements in surgery and chemoradiotherapy, the prognosis for glioblastoma multiforme (GBM) and brain metastases remains poor, underscoring the need for innovative diagnostic strategies. This review highlights recent advancements in imaging techniques, liquid biopsies, and artificial intelligence (AI) applications addressing current diagnostic challenges. Advanced imaging techniques, including diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS), improve the differentiation of tumor progression from treatment-related changes. Additionally, novel positron emission tomography (PET) radiotracers, such as ¹⁸F-fluoropivalate, ¹⁸F-fluoroethyltyrosine, and ¹⁸F-fluluciclovine, facilitate metabolic profiling of high-grade gliomas. Liquid biopsy, a minimally invasive technique, enables real-time monitoring of biomarkers such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating tumor cells (CTCs), and tumor-educated platelets (TEPs), enhancing diagnostic precision. AI-driven algorithms, such as convolutional neural networks, integrate diagnostic tools to improve accuracy, reduce interobserver variability, and accelerate clinical decision-making. These innovations advance personalized neuro-oncological care, offering new opportunities to improve outcomes for patients with central nervous system tumors. We advocate for future research integrating these tools into clinical workflows, addressing accessibility challenges, and standardizing methodologies to ensure broad applicability in neuro-oncology.

The human gut microbiome represents a complex ecosystem comprising numerous microorganisms critical to basic physiological processes. The gut microbiome’s composition and functionality influence surgical outcomes following orthopedic procedures. The purpose of this study was to evaluate the gut microbiota on critical aspects of orthopedic surgical outcomes. A comprehensive literature search was conducted via PubMed, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), Google Scholar, Cochrane Library, Medline, and Web of Science. A total of 18 research articles of the 599 retrieved results were included in this study. Significant correlations were identified between microbial composition and surgical outcomes, including infection rates, inflammatory responses, and postoperative complications. Bacterial genera like Alistipes and Helicobacter increased postoperative cognitive dysfunction (POCD) risk, while short-chain fatty acid (SCFA)-producing bacteria showed negative correlations with inflammatory markers. Probiotic interventions reduced POCD incidence from 16.4% to 5.1% and modulated inflammatory responses. Additionally, bacterial composition was associated with critical surgical parameters such as bone healing, infection rate, and recovery trajectory. Inflammation, healing processes, and recovery trajectories are influenced by microbial composition in surgical settings. Targeted interventions, such as probiotics, show promise in reducing surgical risks and improving patient recovery.

Medical schools are increasingly reducing required contact hours and incorporating self-directed learning strategies, yet the impact of these curricular changes on academic performance remains uncertain. This retrospective cohort study compared performance on NBME-based organ system examinations across three consecutive pre-clerkship cohorts at a U.S. allopathic medical school that experienced different levels of required instructional time. Cohorts included 178 students and differed in total required contact hours from 306 to 412 h. Mean MCAT scores did not differ significantly among cohorts (510.4 ± 5.4, 509.6 ± 6.3, and 510.0 ± 4.9; p = 0.74). Significant differences in the proportion of students scoring above the national reference value were observed in the Pulmonology (p = 0.003), Gastroenterology (p = 0.020), and Endocrinology (p = 0.003) blocks; however, these differences did not demonstrate a consistent relationship with contact hour totals. Across cohorts experiencing different contact-hour requirements and concurrent curricular changes, examination performance did not demonstrate a consistent pattern corresponding to the amount of required instructional time. These findings demonstrate that lower contact-hour requirements were not accompanied by consistently poorer short-term standardized outcomes in these cohorts; however, the independent contribution of contact hours cannot be separated from concurrent curricular changes.

BACKGROUND First-generation, low-income (FGLI) students are underrepresented in U.S. medical education and face persistent barriers across the training continuum. Although institutional programs exist to support students, the scope, focus, and timing of these interventions for FGLI students pursuing medical education have not been comprehensively synthesized. OBJECTIVE To characterize institutional programs and policies supporting FGLI students and identify gaps in intervention focus. METHODS Studies were identified from inception to March 5, 2025. U.S. based, peer-reviewed studies describing institutional interventions for FGLI premedical and medical students were included. RESULTS Nineteen institutional programs met inclusion criteria. Most interventions targeted premedical students (n=14), with fewer programs designed for medical students (n=7). Academic preparation (n=14) and mentorship or advising (n=10) were the most common interventions, primarily concentrated in the K-12 and premedical stages. Healthcare exposure was frequently incorporated in programs (n=10). In contrast, financial support (n=2) and structural reforms (n=3) were less frequently reported. CONCLUSIONS Institutional support for FGLI students is concentrated in early pipeline programs emphasizing academic preparation and mentorship, whereas financial assistance, structural reforms, and wellness initiatives for matriculated medical students remain limited. Expanding comprehensive, longitudinal support beyond admissions is essential to promote equity, retention, and success among FGLI medical trainees. CLINICALTRIAL https://doi.org/10.17605/OSF.IO/SUZ28 INTERNATIONAL REGISTERED REPORT RR2-10.1016/j.glmedi.2026.100228