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Aerodynamics and Laryngeal Kinematics Following Anterior (Wendler) Glottoplasty: A Case Study
(Wiley, 2026-02-24) McKenna, Victoria S.; Dion, Gregory R.; Patel, Rita; Gustin, Renee L.; Madzia, Jules; Stryker, Shanna D.; Pickle, Sarah; Wilkens, Mary E.; Otolaryngology -- Head and Neck Surgery, School of Medicine
A transgender woman underwent anterior (Wendler) glottoplasty and was followed for 1-year. We found desired pitch improvements, but also undesired changes to intensity, vocal efficiency, laryngeal vibratory kinematics, and vocal effort. This case highlights the importance of considering multimodal assessment in clinical follow-up and outcome analysis for these patients.
Classification of tauopathies from human brain homogenates through salt‐modulated tau amplification
(Wiley, 2026) Santambrogio, Alessia; Metrick, Michael A., II; Xu, Peifeng; Gallagher, Nicholas C. T.; Koga, Shunsuke; Ghetti, Bernardino; Dickson, Dennis W.; Caughey, Byron; Vendruscolo, Michele; Pathology and Laboratory Medicine, School of Medicine
Introduction: Tauopathies are a heterogeneous group of neurodegenerative disorders defined by abnormal aggregation of tau protein. Although cryogenic electron microscopy (cryo-EM) has uncovered disease-specific tau structures, translating these insights into diagnostic tools remains difficult.
Methods: We developed a heparin-free, salt-modulated real-time quaking-induced conversion (RT-QuIC) assay using K12 and K11 tau substrates, targeting aggregation-prone regions. This current method improves on previous methodology by minimising the number of required substrates by modulating reaction salt content in order to differentiate yet-undistinguished tauopathy strains. Thioflavin T fluorescence kinetics and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) spectroscopy were used to classify tau aggregates from human brain homogenates.
Results: This method differentiated eight tauopathies, including Alzheimer's disease, Pick disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), argyrophilic grain disease (AGD), frontotemporal dementia with parkinsonism associated with chromosome 17 with N279K mutation (FTDP-17 N279K), and globular glial tauopathies types II and III. Subclassification of 4R tauopathies was achieved by modulating salt conditions and analyzing aggregation profiles. FTIR confirmed preservation of conformational differences.
Discussion: This salt-modulated, heparin-free RT-QuIC platform enables sensitive tauopathy classification based on strain-specific kinetics and structure. It offers a practical tool for diagnostic development, mechanistic studies, and therapeutic screening.
The Scientific Case for Animal Models: A Perspective From Musculoskeletal Researchers
(Wiley, 2026-02-09) Hadjiargyrou, Michael; Hildreth, Blake E., III; Ko, Frank; Sankar, Uma; Yang, Tao; Anatomy, Cell Biology and Physiology, School of Medicine
The National Institutes of Health (NIH) has launched a major initiative to expand human-based New Approach Methodologies (NAMs) in biomedical research and reduce reliance on animal models. While NAMs offer powerful complementary tools, animal-based research remains indispensable in musculoskeletal science for understanding complex cellular and systemic processes, disease onset and progression, and developing effective therapies. Foundational knowledge of embryonic development, disease mechanisms, tissue regeneration, gene function, and systemic pharmacology has emerged from animal models and will continue to do so. This review underscores the essential role of animal models in five key areas of musculoskeletal biology: osteoporosis, osteoarthritis, bone fracture repair and regeneration, bone cancer, and Inherited Skeletal Disorders (ISDs). We also examine NAMs including organoids, engineered scaffolds, organ-on-chip platforms, and Artificial Intelligence (AI)/computational modeling, highlighting their strengths in mechanistic and high-throughput studies but also their limitations in replicating in vivo structural, physiological, biomechanical, and systemic complexity. Animal models remain the gold standard for exploring disease mechanisms, testing preclinical therapeutic and diagnostic efficacy and safety, and translating discoveries into clinical practice. Rather than replacing animal research, NAMs should be integrated as complementary approaches to advance understanding and innovation. Curtailing animal research would jeopardize medical progress and hinder life-saving interventions for humans and animals alike. This review aims to inform the public and policymakers on the continued necessity of ethically conducted animal research as a cornerstone of musculoskeletal health.
Decline in Applicants to Obstetrics and Gynecology Fellowships: Influence on Match Rates and Competitiveness
(Wolters Kluwer, 2026-02-19) Humphries, Leigh A.; Shah, Divya K.; Shanks, Anthony L.; Hofler, Lisa G.; Temming, Lorene A.; Morris, Stephanie N.; Dotters-Katz, Sarah K.; Obstetrics and Gynecology, School of Medicine
Although applications to fellowships in obstetrics and gynecology have declined in recent years, match rates have increased as most programs continue to fill available positions.
Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction
(bioRxiv, 2026-01-27) Chen, Renren; Stockwell, Imogen; Pierce, Jessica C.; Peak-Chew, Sew-Yeu; Huang, Melissa; Newell, Kathy; Ghetti, Bernardino; Cousin, Michael A.; Greger, Ingo H.; Ryskeldi-Falcon, Benjamin; Pathology and Laboratory Medicine, School of Medicine
The assembly of TAR DNA-binding protein 43 (TDP-43) into amyloid filaments within neurons is a hallmark of multiple neurodegenerative diseases, including motor neuron diseases (MND), frontotemporal dementias (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). These diseases result from the deterioration and loss of neurons, with synaptic dysfunction and neuronal hyperexcitability being prominent early events. Pathogenic mutations in the TDP-43 gene, TARDBP, that promote filament formation have established a causal role for TDP-43 assembly in neurodegenerative diseases. However, the molecular mechanisms underlying filament accumulation and their contribution to neurodegeneration are poorly understood. TDP-43 filaments can propagate between neurons in a prion-like manner, which may underlie the progressive spread and accumulation of TDP-43 pathology in disease. Here, we studied early stages of TDP-43 filament accumulation following internalisation of patient-derived TDP-43 filaments by mouse and human cortical neurons. Using proximity labelling, we identified molecular environments and putative interactions of TDP-43 filaments. We found that TDP-43 filaments accumulated at synapses, particularly in proximity to the presynaptic active zone, which we confirmed in FTD patient brain sections. Electron cryo-tomography (cryo-ET) directly visualised abundant TDP-43 filaments spanning the presynaptic cytoplasm in situ, which contacted synaptic vesicles and the plasma membrane. Functional measurements revealed that the accumulation of TDP-43 filaments led to presynaptic dysfunction and subsequent neuronal hyperexcitability. These findings suggest that synapses are a major early site of TDP-43 filament accumulation, relevant to their propagation, and directly link TDP-43 filament gain of function to synaptic dysfunction.