BackgroundWe identified the most useful variables for prediction of difficult laryngoscopy in patients with cervical spondylosis according to physical indicators and preoperative skeletal X‐ray and soft tissue MRI measurements. We hypothesized that there was a closer association between difficult laryngoscopy and radiologic indicators.MethodsWe randomly enroled 315 patients undergoing elective cervical spine surgery and analysed the radiological and physical data in predicting difficult laryngoscopy.ResultsWe identified five variables that were most useful in predicting difficult laryngoscopy: the inter‐incisor gap (P = 0.006), modified Mallampati test score (P = 0.004), distance from the highest point of the hyoid bone to the mandibular body (P < 0.001), most antero‐inferior point of the upper central incisor tooth (P < 0.001), and length of the epiglottis (P = 0.002). Binary multivariate logistic regression analyses identified three factors that were independently associated with difficult laryngoscopy: the Mallampati score, distance from the hyoid bone to the mandibular body, and the anterior–inferior point of the upper central incisor tooth. The odds ratios and 95% confidence intervals were 1.547 (1.029–2.327), 1.222 (1.139–1.310), and 1.224 (1.133–1.322), respectively. The AUC for hyoid bone distance to mandibular body (0.832) was larger than that of anterior‐inferior point of the upper central incisor tooth (0.802, P > 0.05) and that of modified Mallampati test (0.602, P < 0.05).ConclusionDistance from the highest point of the hyoid bone to the mandibular body appears to be the most accurate indicator for difficult laryngoscopy in patients with cervical spondylosis.
In a majority of patients with myasthenia gravis (MG), anti-acetylcholine receptor (AChR) antibodies target postsynaptic AChR clusters and thus compromise the membrane integrity of neuromuscular junctions (NMJs) and lead to muscle weakness. Antibody-induced endocytosis of AChRs in the postsynaptic membrane represents the initial step in the pathogenesis of MG; however, the molecular mechanisms underlying AChR endocytosis remain largely unknown. Here, we developed an approach to mimic the pathogenic antibodies for inducing the crosslinking and internalization of AChRs from the postsynaptic membrane. Using biotin-α-bungarotoxin and quantum dot (QD)-streptavidin, cell-surface and internalized AChRs could be readily distinguished by comparing the size, fluorescence intensity, trajectory, and subcellular localization of the QD signals. QD-induced AChR endocytosis was mediated by clathrin-dependent and caveolin-independent mechanisms, and the trafficking of internalized AChRs in the early endosomes required the integrity of microtubule structures. Furthermore, activation of the agrin/MuSK (muscle-specific kinase) signaling pathway strongly suppressed QD-induced internalization of AChRs. Lastly, QD-induced AChR crosslinking potentiated the dispersal of aneural AChR clusters upon synaptic induction. Taken together, our results identify a novel approach to study the mechanisms of AChR trafficking upon receptor crosslinking and endocytosis, and demonstrate that agrin-MuSK signaling pathways protect against crosslinking-induced endocytosis of AChRs.
BackgroundThe formation of acetylcholine receptor (AChR) cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non-neuronal stimulus, is also highly effective in causing AChRs to cluster along the cathode-facing edge of muscle cells.Methodology/Principal FindingsTo understand its molecular mechanism, quantum dots (QDs) were used to follow the movement of AChRs as they became clustered under the influence of electric field. From analyses of trajectories of AChR movement in the membrane, it was concluded that diffuse receptors underwent Brownian motion until they were immobilized at sites of cluster formation. This supports the diffusion-mediated trapping model in explaining AChR clustering under the influence of this stimulus. Disrupting F-actin cytoskeleton assembly and interfering with rapsyn-AChR interaction suppressed this phenomenon, suggesting that these are integral components of the trapping mechanism induced by the electric field. Consistent with the idea that signaling pathways are activated by this stimulus, the localization of tyrosine-phosphorylated forms of AChR β-subunit and Src was observed at cathodal AChR clusters. Furthermore, disrupting MuSK activity through the expression of a kinase-dead form of this enzyme abolished electric field-induced AChR clustering.ConclusionsThese results suggest that DC electric field as a physical stimulus elicits molecular reactions in muscle cells in the form of cathodal MuSK activation in a ligand-free manner to trigger a signaling pathway that leads to cytoskeletal assembly and AChR clustering.
The study aims to determine whether light microscopy can be used to accurately measure the diameters of intercellular spaces between squamous epithelial cells in the lower esophagus, and whether changes in this outcome measure can be used as a diagnostic marker for gastroesophageal reflux disease (GERD). The study has two parts. Part 1 involves 42 asymptomatic controls and 119 patients with typical symptoms of GERD, including 58 with erosive esophagitis (EE), and 61 patients with nonerosive gastroesophageal reflux disease (NERD). All biopsies were taken from the lower esophagus. All samples were observed using an immersion objective, after which diameters were measured by computer-assisted morphometry. Part 2 involves 61 individuals who were randomly selected from part 1, including 19 controls, 13 with NERD and 29 with EE. Diameter measurements using both light microscopy and transmission electron microscopy (TEM) were performed for samples of 61 individuals. Samples from a total of 61 individuals (31 male, 30 female, mean age 44.3 ± 16.0 years) were observed using both light microscopy and TEM. Both methods showed significant differences between control and disease groups; the outcomes from the two methods had a certain correlation (r = 0.605, P = 0.000). Morphometric analysis of all 161 individuals (83 males, 78 females, mean age 41.4 ± 15.7) showed mean diameters from light microscopy to be 0.58 ± 0.16 µm for controls, 1.07 ± 0.30 µm for NERD, and 1.29 ± 0.20 µm for EE; differences between control and disease groups were significant (P<0.05). The optimal cut-off value from receiver operator characteristic analysis was 0.85 µm. Diagnoses were validated using the combination of symptoms of GERD, endoscopy, and 24 h ambulatory pH monitoring as the gold standard. At the optimal cutoff, sensitivity was 93.3% and specificity was 100%. The diameters of the intercellular spaces in squamous epithelium of lower esophagus from controls and in patients with GERD can be quantitatively measured using light microscopy. Dilated diameters can serve as a sensitive, specific, and objective indicator for diagnosis of GERD.
The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non-erosive reflux disease (NERD), Barrett's esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H-C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD-like symptoms was significantly wider compared with the H-C. No significant differences were observed between NERD and FH. Results from 24-hour pH-impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 μm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS.
During osteoarticular reconstruction of the distal radius with the proximal fibula, congruity between the two articular surfaces is an important factor in determining the quality of the outcome. In this study, a three-dimensional model and a coordinate transformation algorithm were developed on computed tomography scanning. Articular surface matching was performed and parameters for the optimal position were determined quantitatively. The mean radii of best-fit spheres of the articular surfaces of the distal radius and proximal fibula were compared quantitatively. The radial inclination and volar tilt following reconstruction by an ipsilateral fibula graft, rather than the contralateral, best resembles the values of the native distal radius. Additionally, the ipsilateral fibula graft reconstructed a larger proportion of the distal radius articular surface than did the contralateral. The ipsilateral proximal fibula graft provides a better match for the reconstruction of the distal radius articular surface than the contralateral, and the optimal position for graft placement is quantitatively determined.
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