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Category: Bunion; Basic Sciences/Biologics Introduction/Purpose: It is generally accepted that failure of the medial supporting soft tissue structure of the metatarsophalangeal joint plays an important role in the development of hallux valgus. The metatarsosesamoid ligament (MSL), a component of the medial soft tissue, is an important structure that connects the metatarsal head and the sesamoid complex. The sesamoid complex works as a dynamic stabilizer of the metatarsal head. We hypothesized that the failure of the medial MSL causes instability of the first metatarsal bone, which leads to hallux valgus deformities. Therefore, the present study aimed to describe the detailed structure and degenerative findings of MSL and to clarify the mechanical stress of the MSL enthesis, considering the mechanism of failure of the medial supporting soft tissue structure. Methods: The first metatarsal heads and sesamoid bones with soft tissue were collected from twelve cadavers. Serial 4-μm thick section4-μm intervals and stained with toluidine blue (Fig. 1a). We described the detailed histological structures and degenerative findings of MSL. In addition, morphometric comparisons were made between the medial and lateral MSL entheses at the metatarsal head to evaluate the mechanical stress they. First, we measured the thickness of the uncalcified fibrocartilage (UF thickness) following a protocol adopted previously (Fig. 1b). Second, the degree of irregularity of the interface between the zones of calcified fibrocartilage and bone (CFB) at each enthesis was assessed as the ratio between the lengths of the CFB and the enthesis (CFB/ E ratio) (Fig. 1c). The differences in these parameters were evaluated using the paired T test and Wilcoxon signed-rank test (P < 0.05). Results: We identified that the MSL entheses were fibrocartilaginous entheses, which consisted of four tissue zones. The region in which the MSL wraps around the articular surface of the metatarsal head contains a metachromatic area accompanied by fibrocartilage cells at the deep surface of the MSL, called the sesamoid fibrocartilage. At the MSL enthesis, pathological findings indicating enthesopathy were observed. One specimen showed the tear of the MSL at the wrap around region. The MSL enthesis tear was observed in two specimens with hallux valgus. Both UF thickness (P = 0.12, effect size r = 0.89) and CFB/E ratio (P = 0.17, effect size d = 0.35) were significantly greater in the medial MSL enthesis than those in the lateral MSL enthesis. Conclusion: In the present study, the MSL showed enthesis protecting structures such as enthesis fibrocartilage which contributes to dissipating bending forces during insertional angle change, complexed CFB interface which guards an enthesis against shearing forces and wrap around region which contributes to dissipating the shearing force to the enthesis. However, the medial MSL subject to the greater forces and the degenerative findings of enthesopathy were observed. On top of that, all four hallux valgus specimens with sesamoid complex dislocation showed MSL enthesis tear. Enthesopathy, particularly at the medial MSL, may be the cause of hallux valgus.

Abstract INTRODUCTION Brain arteriovenous malformations (bAVMs) are a rupture-prone tangle of blood vessels with direct shunting between arterial and venous circulations. The mechanisms contributing to bAVM pathogenesis in sporadic lesions remains elusive. Studies have focused on endothelial cells and the contributions of other cell types have yet to be studied. Pericytes are multi-functional cells which regulate brain angiogenesis and vascular stability. Here, we analyze the abundance of brain pericytes and their association with vascular changes in human bAVMs METHODS bAVMs and non-vascular lesion epilepsy tissue were surgically resected. Immunofluorescent staining was performed to quantify pericytes (platelet derived growth factor receptor beta (PDGFRbeta) and N-aminopeptidase (CD13)) and hemoglobin. Hemosiderin deposits were quantified with Prussian blue staining. Syngo-iFlow processing was utilized to measure blood flow on pre-intervention angiograms. RESULTS >Immunofluorescent analysis demonstrated a 68% reduction in vascular pericyte number in bAVMs (P < 0.01). Analysis demonstrated 52% and 50% reduction in the vascular surface area covered by CD13- and PDGFRbeta-positive pericyte cell processes, respectively, in bAVMs (P < 0.01). Reductions in pericyte coverage were greatest in ruptured bAVMs (P < 0.05), and correlated negatively with microhemorrhage-derived extravascular hemoglobin in unruptured cases (CD13: r = −0.93, P < 0.01; PDGFRbeta: r = −0.87, P < 0.01). A similar negative correlation was observed with pericyte coverage and Prussian-blue positive hemosiderin deposits. Pericyte coverage correlated positively with mean transit time of blood flow through the bAVM nidus (CD13: r = 0.60, P < 0.05; PDGFRbeta: r = 0.63, P < 0.05). CONCLUSION Pericytes are reduced in sporadic bAVMs and are lowest in cases with prior rupture or with greatest mircohemorrhage burden. Pericytes also correlate with rate of blood flow through the bAVM nidus. This suggests that pericytes are associated with and may contribute to vascular fragility and hemodynamic changes in bAVMs Future studies are needed to better characterize the role of pericytes in AVM pathogenesis.

Abstract Background Simultaneous analyses of peripheral and mucosal immune compartments can yield insight into the pathogenesis of mucosal-associated diseases. Although methods to preserve peripheral immune cells are well established, studies involving mucosal immune cells have been hampered by lack of simple storage techniques. Methods Here we provide a method to immediately cryopreserve intestinal tissue with retention of viability and functionality of both immune and epithelial cells allowing for subsequent transcriptional and cellular analysis. To test preservation of immune cells by this methodology, we employed mass cytometry to generate high-dementional maps of immune cells residing in the intestine. To test the ability of this methodology to preserve epithelial stem cells, we generated enteroids from cryopreserved tissue. Finally, to test the preservation of the transcriptome we employed RNAseq analysis. Results We show that cryopreserved tissue can be used to (1) generate single cell suspensions of live immune cells with maintenance of immune make up and cytokine expression upon stimulation (Fig 1A-C) and (2) to generate enteroids (Fig 1 D-E). Furthermore, this methodology allows for preservation of the transcriptional profile of the tissue with retention of expression of differentially regulated genes (DEGs) between inflamed and uninflamed tissue (Fig 1 F-G). Finally, in a pilot cohort of IBD patients, we employ this protocol and mass cytometry for in depth immune analysis of cryopreserved GI tissue. This integrative approach not only allowed for validation of several hallmarks of Crohn's disease and ulcerative colitis but also the identification of novel mucosal cell populations distinguishing these two diseases (Fig 2). Conclusions These methods will facilitate translational studies allowing for batch analysis of mucosal tissue to investigate diseases pathogenesis, biomarker discovery and treatment responsiveness.

Characteristics of the disease were represented as following; high incidence in elder women, low rate of undeveloped mastoid air cell system, severe destruction of the stapes, and complex extension pathway.

Cerebellar mutism syndrome (CMS) is a prevalent postoperative complication in children following posterior fossa tumor surgery, with a significantly variable incidence rate across different pathological types of tumors, being highest in medulloblastoma (24%-30%). The pathogenesis of CMS remains to be elucidated, but it is believed to be associated with damage to the cerebellocerebral circuits, harm to the fastigial nuclei of cerebellum and periaqueductal gray matter of the midbrain, and alterations in brain networks. Predictive models constructed based on the risk factors of CMS have not yet demonstrated the anticipated stability and have not been widely adopted in clinical settings. Pharmacological treatments are primarily based on clinical experience, yet their efficacy requires further validation, hence there is currently a lack of a clearly effective treatment method; non⁃pharmacological treatments, such as physical therapy, occupational therapy, and speech therapy, have shown some effect on improving the