Antagonism of metabotropic glutamate receptor type 5 prevents levodopa-induced dyskinesia development in a male rat model of Parkinson's disease: Electrophysiological evidence.

Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model). Saline was intraperitoneally administered to dopamine lesioned (DL) rats (n = 6), levodopa/benserazide (L/B) was administered to LID rats (n = 8), and L/B combined with MTEP was administered to MTEP rats (n = 6) twice daily for 14 days. We administered L/B to LID and MTEP rats 48 h after the final administration of MTEP to examine the chronic effect of MTEP. The control and DL groups did not have LID. The MTEP group had less LID than the LID group (p < .01) on day 1 and day 18. The control group had a typical triphasic pattern consisting of early excitation (early-Ex), inhibition, and late excitation (late-Ex). However, the inhibition phase disappeared, was partially observed, and was fully suppressed in the DL, LID, and MTEP groups, respectively. The cortico-striato-entopeduncular pathway is important in the pathophysiology of LID. mGluR5 antagonism suppresses LID progression by preventing physiological changes in the cortico-striato-entopeduncular pathway. Future studies are required to validate these results.

Surveillance of Wastewater to Monitor the Prevalence of Gastroenteritis Viruses in Chiba Prefecture (2014-2019).

BACKGROUND: In Japan, sentinel surveillance is used to monitor the trend of infectious gastroenteritis. Another method of pathogen surveillance, wastewater-based epidemiology, has been used recently because it can help to monitor infectious disease without relying on patient data. Here, we aimed to determine the viral trends reflected in the number of reported patients and number of gastroenteritis virus-positive samples. We focused on gastroenteritis viruses present in wastewater and investigated the usefulness of wastewater surveillance for the surveillance of infectious gastroenteritis. METHODS: Real-time polymerase chain reaction was used for viral gene detection in wastewater. The number of reported patients per pediatric sentinel site and number of viral genome copies were compared for correlation potential. The number of gastroenteritis virus-positive samples reported by National Epidemiological Surveillance of Infectious Disease (NESID) and the status of gastroenteritis viruses detected in wastewater were also evaluated. RESULTS: Genes of norovirus genotype I, norovirus genotype II, sapovirus, astrovirus, rotavirus group A, and rotavirus group C were detected in wastewater samples. Viruses were detected in wastewater during periods when no gastroenteritis virus-positive samples were reported to NESID. CONCLUSION: Norovirus genotype II and other gastroenteritis viruses were detected in wastewater even during periods when no gastroenteritis virus-positive samples were found. Therefore, surveillance using wastewater can complement sentinel surveillance and is an effective tool for the surveillance of infectious gastroenteritis.

Addressing practical issues in the smooth implementation of revised guidelines for non-clinical studies of vaccines for infectious disease prevention.

Herein, we investigated possible practical issues for the smooth implementation of the revised Japanese Guidelines for Non-clinical Studies of Vaccines for the Prevention of Infectious Diseases, which were raised in response to public comments on the proposed guideline revision and a gap analysis of the World Health Organization and European Medicines Agency guidelines. We identified main issues such as the non-clinical safety studies of adjuvants and evaluation of local cumulative tolerance in toxicity studies. The revised Japanese Pharmaceuticals and Medical Devices Agency (PMDA)/Ministry of Health, Labour and Welfare (MHLW) guidelines require non-clinical safety studies for vaccines containing new adjuvants, but additional safety pharmacology studies or safety studies in two animal species may be required if non-clinical safety studies raise any concerns (i.e., systemic distribution). Adjuvant biodistribution studies may aid in understanding vaccine characteristics. The evaluation of local cumulative tolerance in non-clinical studies, which was the focus of the Japanese review, can be omitted by including a warning in the package insert to avoid injection to the same site. The study's findings will be reflected in a Q&A to be released by the Japanese MHLW. We hope that this study will contribute to the global and harmonized development of vaccines.

Enhanced Scanning Electron Microscopy Using Auto-Optimized Image Restoration With Constrained Least Squares Filter for Nanoscience.

The growing demands of nanoscience require the continuous improvement of visualization methods. The imaging performance of scanning electron microscopy (SEM) is fundamentally limited by the point spread function of the electron beam and degrades because of noise. This paper proposes an auto-optimization algorithm based on deconvolution for the restoration of SEM images. This algorithm uses a constrained least squares filter and does not dependent on the user's experience or the availability of nondegraded images. The proposed algorithm improved the quality of the SEM images of 10-nm Au nanoparticles, and achieved balance among the sharpness, contrast-to-noise ratio (CNR), and image artifacts. For the SEM image of 100-nm pitched line patterns, the analysis of the spatial frequencies allowed the 2.5-fold improvement of the intensity of 4-nm information, and the noise floor decreased approximately 32 times. Along with the results obtained by the application of the proposed algorithm to images of tungsten disulfide (WS2) flakes, carbon nanotubes (CNTs), and HeLa cells, the evaluation results confirm that the proposed algorithm can enhance the SEM imaging of nanoscale features that lie close to the microscope's resolution limit.

Exploring the Potential of a Thermionic LaB6 Virtual Source Mode Electron Gun for a High Angular Current Density and a Narrow Energy Distribution.

To date, lanthanum hexaboride (LaB6) thermionic electron sources have not been able fully to capitalize on their inherent potential, resulting in an ambiguous position within the application area. Although they exhibit higher brightness compared with a tungsten filament source, they still fall short of the performance of Schottky electron sources. This study aims to explore the capabilities of the LaB6 electron source under different operating conditions to bridge the gap, ultimately to realize its untapped potential. Simulations in virtual source mode indicated enhanced beam brightness and a reduced beam half-angle with an increase the extraction voltage, promising up to tenfold times higher beam brightness compared with the crossover mode. The energy distribution measured using a prelens retarding field energy analyzer revealed an energy distribution of 0.55 eV and a high angular current density of 33 mA/sr in the virtual source mode. Therefore, the virtual source mode of LaB6 can provide a narrow energy distribution akin to that of a ZrO/W Schottky electron gun (1600 K) while having an angular current density over 2,000 times higher. In addition, the stability of the virtual source mode is ±0.022%, while that of the crossover mode is ±0.138%.

Management of bone loss in acute severe open tibial fractures: a retrospective study of twenty nine cases-a treatment strategy with bone length preservation.

PURPOSE: The present study investigated the outcomes of bone loss associated with acute open tibial fractures classified as Gustilo-Anderson classification grade III B (GIIIB) using a bone length preservation strategy. METHODS: Among acute GIIIB open tibial fractures, 29 limbs of 29 patients requiring bone loss treatment were included. The reconstruction methods for bone loss were selected among the Masquelet technique (MT), bone transport (BT), acute shortening followed by gradual lengthening (ASGL), and free vascularized fibula graft (FVFG). Primary outcome measures were the rate of bone union and time to bone union. RESULTS: The median radiographic apparent bone gap (RABG) was 46.75 mm. Bone loss was treated with ASGL only in two patients in whom it was not possible to cover large soft tissue defects by a single free latissimus dorsi (LD) myocutaneous flap (with the serratus anterior (SA) muscle). The other 27 patients underwent soft tissue reconstruction and bone loss treatment with the preservation of bone length, including the MT for 23, BT for six, and FVFG for one. The bone union rate was 75.9%, and the median time to bone union was six months. Salvage surgeries were performed on all seven patients with nonunion; all of whom eventually achieved bony union. CONCLUSION: Bone loss associated with acute GIIIB open tibial fractures were treated with "bone length preservation" if the size of the soft tissue defect was less than the size that was covered by a single LD myocutaneous flap (with the SA muscle).

Crystal structure and conformational stability of a galectin-1 tandem-repeat mutant with a short linker.

Modification of the domain architecture of galectins has been attempted to analyze their biological functions and to develop medical applications. Several types of galectin-1 repeat mutants were previously reported but, however, it was not clear whether the native structure of the wild type was retained. In this study, we determined the crystal structure of a galectin-1 tandem-repeat mutant with a short linker peptide, and compared the unfolding profiles of the wild type and mutant by chemical denaturation. The structure of the mutant was consistent with that of the dimer of the wild type, and both carbohydrate-binding sites were retained. The unfolding curve of the wild type with lactose suggested that the dimer dissociation and the tertiary structure unfolding was concomitant at micromolar protein concentrations. The midpoint denaturant concentration of the wild type was dependent on the protein concentration and lower than that of the mutant. Linking the two subunits significantly stabilized the tertiary structure. The mutant exhibited higher T-cell growth-inhibition activity and comparable hemagglutinating activity. Structural stabilization may prevent the oxidation of the internal cysteine residue.

Rigid real-time prospective motion-corrected three-dimensional multiparametric mapping of the human brain.

PURPOSE: To develop a rigid real-time prospective motion-corrected multiparametric mapping technique and to test the performance of quantitative estimates. METHODS: Motion tracking and correction were performed by integrating single-shot spiral navigators into a multiparametric imaging technique, three-dimensional quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS). The spiral navigator was optimized, and quantitative measurements were validated using a standard system phantom. The effect of motion correction on whole-brain T1 and T2 mapping under different types of head motion during the scan was evaluated in 10 healthy volunteers. Finally, six patients with Parkinson's disease, which is known to be associated with a high prevalence of motion artifacts, were scanned to evaluate the effectiveness of our method in the real world. RESULTS: The phantom study demonstrated that the proposed motion correction method did not introduce quantitative bias. Improved parametric map quality and repeatability were shown in volunteer experiments with both in-plane and through-plane motions, comparable to the no-motion ground truth. In real-life validation in patients, the approach showed improved parametric map quality compared to images obtained without motion correction. CONCLUSIONS: Real-time prospective motion-corrected multiparametric relaxometry based on 3D-QALAS provided robust and repeatable whole-brain multiparametric mapping.

A Novel Monochromator with Offset Cylindrical Lenses and Its Application to a Low-Voltage Scanning Electron Microscope.

Low-voltage scanning electron microscopes (LV-SEMs) are widely used in nanoscience. However, image resolution for SEMs is restricted by chromatic aberration due to energy spread of the electron beam at low acceleration voltage. This study introduces a new monochromator (MC) with offset cylindrical lenses (CLs) as one solution for LV-SEMs. The MC optics, with highly excited CLs in offset layouts, has advantageous high performance and simple experimental setup, making it suitable for field emission LV-SEMs. In a preliminary evaluation, our MC reduced the energy spread from 770 to 67 meV. The MC was integrated into a commercial SEM equipped with an out-lens (a conventional objective lens without immersion magnetic or retarding electric fields) and an Everhart­Thornley detector. Comparing SEM images under two conditions with the MC turned on or off, the spatial resolution was improved by 58% at 0.5 and 1 keV. The filtering effect of the MC decreased the probe current with a ratio (i.e., transmittance) of 5.7%, which was consistent with estimations based on measured energy spreads. To the best of our knowledge, this is the first report on an effective MC with higher-energy resolution than 100 meV and the results offer encouraging prospects for LV-SEM technology.

High-Performance Compact Pre-Lens Retarding Field Energy Analyzer for Energy Distribution Measurements of an Electron Gun.

The energy distribution of an electron gun is one of the most important characteristics determining the performance of electron beam-based instruments, such as electron microscopes and electron energy loss spectroscopes. For accurate measurements of the energy distribution, this study presents a novel retarding field energy analyzer (RFEA) with the feature of an additional integrated pre-lens, which enables an adjustment of beam trajectory into the analyzer. The advantages of this analyzer are its compact size and simple electrode configuration. According to trajectory simulation theories, the optimum condition arises when the incident electron beam inside the RFEA is focused on the center of a retarding electrode. Comparing I­V curves depending on whether the pre-lens working or not, it is confirmed that the use of the pre-lens dramatically improves the energy resolution and efficiency of the signal acquisition process. The pre-lens RFEA was applied to characterize a Schottky electron gun under various temperatures and extraction voltages as operational conditions. When the tip temperature was increased by 50 K, we were able to measure an energy distribution broadening of 13.8 meV with the proposed pre-lens RFEA. The relative standard deviation of energy distribution was 0.7% for each working condition.

Parkinson's disease: deep learning with a parameter-weighted structural connectome matrix for diagnosis and neural circuit disorder investigation.

PURPOSE: To investigate whether Parkinson's disease (PD) can be differentiated from healthy controls and to identify neural circuit disorders in PD by applying a deep learning technique to parameter-weighted and number of streamlines (NOS)-based structural connectome matrices calculated from diffusion-weighted MRI. METHODS: In this prospective study, 115 PD patients and 115 healthy controls were enrolled. NOS-based and parameter-weighted connectome matrices were calculated from MRI images obtained with a 3-T MRI unit. With 5-fold cross-validation, diagnostic performance of convolutional neural network (CNN) models using those connectome matrices in differentiating patients with PD from healthy controls was evaluated. To identify the important brain connections for diagnosing PD, gradient-weighted class activation mapping (Grad-CAM) was applied to the trained CNN models. RESULTS: CNN models based on some parameter-weighted structural matrices (diffusion kurtosis imaging (DKI)-weighted, neurite orientation dispersion and density imaging (NODDI)-weighted, and g-ratio-weighted connectome matrices) showed moderate performance (areas under the receiver operating characteristic curve (AUCs) = 0.895, 0.801, and 0.836, respectively) in discriminating PD patients from healthy controls. The DKI-weighted connectome matrix performed significantly better than the conventional NOS-based matrix (AUC = 0.761) (DeLong's test, p < 0.0001). Alterations of neural connections between the basal ganglia and cerebellum were indicated by applying Grad-CAM to the NODDI- and g-ratio-weighted matrices. CONCLUSION: Patients with PD can be differentiated from healthy controls by applying the deep learning technique to the parameter-weighted connectome matrices, and neural circuit disorders including those between the basal ganglia on one side and the cerebellum on the contralateral side were visualized.

Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases.

There has been an increasing prevalence of neurodegenerative diseases with the rapid increase in aging societies worldwide. Biomarkers that can be used to detect pathological changes before the development of severe neuronal loss and consequently facilitate early intervention with disease-modifying therapeutic modalities are therefore urgently needed. Diffusion magnetic resonance imaging (MRI) is a promising tool that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, as well as axonal density, order, and myelination, through the utilization of water molecules that are diffused within the tissue, with displacement at the micron scale. Diffusion tensor imaging is the most commonly used diffusion MRI technique to assess the pathophysiology of neurodegenerative diseases. However, diffusion tensor imaging has several limitations, and new technologies, including neurite orientation dispersion and density imaging, diffusion kurtosis imaging, and free-water imaging, have been recently developed as approaches to overcome these constraints. This review provides an overview of these technologies and their potential as biomarkers for the early diagnosis and disease progression of major neurodegenerative diseases.

Spontaneous adenocarcinoma with giant cell formation in the accessory sex glands in a male Sprague-Dawley rat.

In this study, we report the features of an adenocarcinoma with giant cell formation spontaneously occurring in the accessory sex glands of a male 10-month-old Sprague-Dawley rat. A milky white mass was found in the region corresponding to the left seminal vesicle and the left coagulating gland. Histologically, tumor cells exhibited diverse growth patterns, including glandular/trabecular, cystic, and sheet-like growth areas. The tumor cells were pleomorphic, with round- or oval-shaped nuclei and abundant eosinophilic cytoplasm. Mitotic figures were occasionally observed. Giant cells were also prominent in the sheet-like growth area, with intracytoplasmic vacuoles containing eosinophilic material. The stroma was rich in collagen fibers and fibroblasts. Numerous inflammatory cells were observed in the glandular and cystic lumina and stroma. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and proliferating cell nuclear antigen. In the sheet-like growth area, some of the tumor cells and giant cells were positive for vimentin in the cytoplasm adjacent to the nucleus. Electron microscopy revealed that the tumor cells contained a small number of mitochondria and rough endoplasmic reticulum, and had no basement membrane or desmosome. The giant cells occasionally contained variably sized intracytoplasmic lumina and globular filamentous bodies, probably corresponding to vimentin. Considering these morphological features, the tumor was diagnosed as an adenocarcinoma with the formation of giant tumor cells originating from the male accessory sex glands.

Neurocognitive and psychiatric disorders-related axonal degeneration in Parkinson's disease.

Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD.

Evaluation of white matter microstructure in patients with Parkinson's disease using microscopic fractional anisotropy.

PURPOSE: Micro fractional anisotropy (µFA) is more accurate than conventional fractional anisotropy (FA) for assessing microscopic tissue properties and can overcome limitations related to crossing white matter fibres. We compared µFA and FA for evaluating white matter changes in patients with Parkinson's disease (PD). METHODS: We compared FA and µFA measures between 25 patients with PD and 25 age- and gender-matched healthy controls using tract-based spatial statistics (TBSS) analysis. We also examined potential correlations between changes, revealed by conventional FA or µFA, and disease duration or Unified Parkinson's Disease Rating Scale (UPDRS)-III scores. RESULTS: Compared with healthy controls, patients with PD had significantly reduced µFA values, mainly in the anterior corona radiata (ACR). In the PD group, µFA values (primarily those from the ACR) were significantly negatively correlated with UPDRS-III motor scores. No significant changes or correlations with disease duration or UPDRS-III scores with tissue properties were detected using conventional FA. CONCLUSION: µFA can evaluate microstructural changes that occur during white matter degeneration in patients with PD and may overcome a key limitation of FA.

Does TMJ Function and Imaging Tools Help Differentiate Between Condylar Resorption and Mandibular Hypoplasia?

PURPOSE: Differentiating between bilateral condylar resorption (CR) and mandibular hypoplasia (MH) can be challenging owing to the difficulty in chronological observation and establishing standardized measurements. The purpose of the present study was to assess whether temporomandibular joint (TMJ) function can distinguish between CR and MH and clarify the essential diagnostic imaging tools for CR. MATERIALS AND METHODS: We performed a cross-sectional study of patients with mandibular retrognathia. The primary predictor variables were a clinical dysfunction score for the TMJ, mandibular plane angle (MPA), SNA angle, SNB angle, and cortical erosion score in the condylar heads. The demographic variables were age, anterior disc displacement, and previous orthodontic treatment. The anatomic variable was the condylar height (CH). The primary outcome variable was the disease status (CR or MH). The patients were divided into the CR group and MH group. The patients with CR were selected on the basis of a CH value of less than 22 mm. TMJ function was assessed using the Helkimo clinical dysfunction index. The CH on panoramic radiographs was measured using the Kjellberg method. The MPA, SNA angle, and SNB angle were analyzed using cephalometric analysis. Cortical erosion in the condylar head was assessed using computed tomography and magnetic resonance imaging. RESULTS: A total of 23 female participants were enrolled in the present study. The average clinical dysfunction score for the TMJ was 4.4 in the CR group and 0.4 in the MH group (P < .05). The average MPA was 41.2° in the CR group and 35.5° in the MH group (P < .05). CONCLUSIONS: The present investigation has shown that assessing TMJ function and analyzing MPA using a cephalometric radiograph can differentiate CR from MH.

Galectin-9 induces atypical ubiquitination leading to cell death in PC-3 prostate cancer cells.

Galectin-9 is the most potent inducer of cell death in lymphomas and other malignant cell types among the members of the galectin family. We investigated the mechanism of galectin-9-induced cell death in PC-3 prostate cancer cells in comparison with in Jurkat T cells. Galectin-9 induced apoptotic cell death in Jurkat cells, as typically revealed by DNA ladder formation. On the other hand, DNA ladder formation and other features of apoptosis were not apparent in PC-3 cells undergoing galectin-9-induced death. Exogenous galectin-9 was endocytosed and destined to the lysosomal compartment in PC-3 cells. The internalized galectin-9 was resistant to detergent solubilization but was solubilized with lactose. Agents inhibiting actin filament dynamics abolished the internalization and cytocidal effect of galectin-9 in PC-3 but not Jurkat cells. Galectin-9 induced accumulation of ubiquitinated proteins, possibly heterogeneously ubiquitinated and/or monoubiquitinated proteins, in PC-3 cells. PYR-41, an inhibitor of the ubiquitin-activating E1 enzyme, suppressed the cytocidal effect of galectin-9. Although ubiquitination was upregulated also in Jurkat cells by galectin-9, PYR-41 was ineffective against galectin-9-induced cell death. Colocalization of ubiquitinated proteins and LAMP-1 was detectable in PC-3 cells treated with galectin-9. The ubiquitinated proteins were recovered in the insoluble fraction upon cell fractionation. In contrast, ubiquitinated proteins that accumulated after treatment with proteasome inhibitors did not co-localize with LAMP-1 and were mainly recovered in soluble fraction. The results suggest that atypical ubiquitination and accumulation of ubiquitinated proteins in lysosomes play a pivotal role in galectin-9-induced non-apoptotic death in PC-3 cells.

Convolutional neural network-based segmentation can help in assessing the substantia nigra in neuromelanin MRI.

PURPOSE: This study aimed to evaluate the accuracy and diagnostic test performance of the U-net-based segmentation method in neuromelanin magnetic resonance imaging (NM-MRI) compared to the established manual segmentation method for Parkinson's disease (PD) diagnosis. METHODS: NM-MRI datasets from two different 3T-scanners were used: a "principal dataset" with 122 participants and an "external validation dataset" with 24 participants, including 62 and 12 PD patients, respectively. Two radiologists performed SNpc manual segmentation. Inter-reader precision was determined using Dice coefficients. The U-net was trained with manual segmentation as ground truth and Dice coefficients used to measure accuracy. Training and validation steps were performed on the principal dataset using a 4-fold cross-validation method. We tested the U-net on the external validation dataset. SNpc hyperintense areas were estimated from U-net and manual segmentation masks, replicating a previously validated thresholding method, and their diagnostic test performances for PD determined. RESULTS: For SNpc segmentation, U-net accuracy was comparable to inter-reader precision in the principal dataset (Dice coefficient: U-net, 0.83 ± 0.04; inter-reader, 0.83 ± 0.04), but lower in external validation dataset (Dice coefficient: U-net, 079 ± 0.04; inter-reader, 0.85 ± 0.03). Diagnostic test performances for PD were comparable between U-net and manual segmentation methods in both principal (area under the receiver operating characteristic curve: U-net, 0.950; manual, 0.948) and external (U-net, 0.944; manual, 0.931) datasets. CONCLUSION: U-net segmentation provided relatively high accuracy in the evaluation of the SNpc in NM-MRI and yielded diagnostic performance comparable to that of the established manual method.

A clinical predictive score for postoperative myasthenic crisis.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis. METHODS: We studied 393 patients with MG who underwent thymectomy at 6 tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis, and a score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation groups. RESULTS: Multivariate logistic regression identified 3 clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity < 80%, (2) disease duration < 3 months, and (3) bulbar symptoms immediately before thymectomy. The postoperative myasthenic crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66-0.96) in the derivation group and 0.80 (0.62-0.95) in the validation group. INTERPRETATION: A simple scoring system based on 3 preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. Ann Neurol 2017;82:841-849.

Identification of the 7S and 11S globulins as percutaneously sensitizing soybean allergens as demonstrated through epidermal application of crude soybean extract.

Cutaneous exposure to food allergens can predispose individuals to food allergies. Soybean, a major allergenic food, is an ingredient in various cosmetic products. However, the types of soybean proteins that are percutaneously sensitizing in humans or animal models remain unknown. In this study, BALB/c mice were dorsally shaved and epicutaneously exposed to a crude soybean extract including sodium dodecyl sulfate or distilled water alone. Specific IgEs secreted in response to 7S globulin (Gly m 5), 11S globulin (Gly m 6), Gly m 3, and Gly m 4 were measured using enzyme-linked immunosorbent assays or immunoblots. Exposure to soybean extract elicited the secretion of soybean-specific IgEs. Of the soybean proteins, 7S and 11S globulins acted as percutaneous sensitizers in 6/9 mice (67%). Additionally, IgE bound specifically and preferentially to the 7S globulin ß subunit. In conclusion, this is the first report to identify percutaneously sensitizing soybean allergens in a mouse model.