Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides

This research was originally published in the Journal of Biological Chemistry. Yusuke Kato, Hisashi Yagi, Yuichi Kaji, Tetsuro Oshika and Yuji Goto. Benzalkonium Chloride Accelerates the Formation of the Amyloid Fibrils of Corneal Dystrophy-associated Peptides. J. Biol. Chem. 2013; 288, 25109-25118. © the American Society for Biochemistry and Molecular Biolog

Texture analysis of myopathy

Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions

Modification of multiple ion channel functions in vivo by pharmacological inhibition : observation by threshold tracking and modeling

Maintenance of axonal excitability relies on complex balance by multiple ion currents, but its evaluation is limited by in vitro single channel neurophysiological study on overall behavior. We sought to evaluate behaviors of multiple ion currents by pharmacological blockade. The threshold tracking technique was used to measure multiple excitability indices on tail sensory nerve of normal male mice before and after administration of either BaCl2 or ivabradine. Mathematical modeling was used to identify the interval changes of the channel parameters. After administration of BaCl2 and ivabradine, the following changes were present : greater threshold changes of both depolarizing and hyperpolarizing threshold electrotonus by both ; additionally, reduced S2 accommodation, reduced late subexcitability and increased superexcitability by BaCl2, increased S3 accommodation by ivabradine. Mathematical modelling implied reduction of slow K+ conductance, along with reduction of H conductance (Ih) by BaCl2 ; and reduction of Ih while augmentation of K+ conductances by ivabradine. Pharmacological blockade of a selective ion channelmay be compensated by other ion channels. Unintended effects by ion channel modification could be caused by secondary current alteration by multiple ion channels

Basic Study of Susceptibility-Weighted Imaging at 1.5T

With the aim of sequence optimization in susceptibility-weighted imaging (SWI), 2 image acquisition parameters (slice thickness and matrix size) and 2 image processing conditions (number of slices per minimum intensity projection (MIP) and Sliding Window) were investigated using a 1.5-T magnetic resonance imaging (MRI) system. The subjects were 12 healthy volunteers and the target region for scanning was the whole brain. Informed consent was obtained from all subjects. First, susceptibility-weighted images were acquired with various slice thicknesses from 1mm to 5mm and various matrix sizes from 256x256 to 512x512, and the images were assessed in terms of the contrast-to-noise ratio (CNR) and were also visually evaluated by three radiologists. Then, the number of slices per MIP and the usefulness of the Sliding Window were investigated. In the study of the optimal slice thickness and matrix size, the results of visual evaluation suggested that a slice thickness of 3mm and a matrix size of 448x448 are optimal, while the results of evaluation based on CNR were not significant. As regards the image processing conditions, the results suggested that the number of slices per MIP should be set to a minimum value of 2 and that the use of Sliding Window is effective. The present study provides useful reference data for optimizing SWI sequences.</p

Effectiveness of Initial Fixation of a Grasping Pin for Proximal Femoral Fractures

We developed a grasping pin with a hook for osteosynthesis of proximal femoral fractures and compared its performance with that of a lag screw. Cyclic compressive tests were performed to simulate cut-outs, and quasi-static torsion, tests were conducted to simulate rotational displacement in polyurethane model bones and femoral heads collected after hip replacement surgery, and cadaveric femoral heads. In the polyurethane model bones and femoral head collected after hip replacement surgery, implant displacement was increased in the cut-out simulation test in both the grasping pin group and lag screw group, deformation was less in the grasping pin group than in the lag screw group. In polyurethane bones and cadaveric bones, the grasping pins showed higher rotational resistance compared with the lag screws in the quasi-static torsion test because of the high compression force generated during implantation. In contrast, in the collected femoral head after hip replacement surgery model, the lag screws destroyed bone tissue, the lag screw group exhibited a higher rotational resistance and a lower risk of rotational displacement than the grasping pin model. The depth of cadaveric femoral heads was 60mm compared with 30mm for femoral heads obtained after surgery; therefore, the pins could be completely inserted up to the octagonal portion in the cadaveric bones, resulting in higher rotational resistance

Sodium Current by Hindlimb Unloading

This study aimed to characterize the excitability changes in peripheral motor axons caused by hindlimb unloading (HLU), which is a model of disuse neuromuscular atrophy. HLU was performed in normal 8-week-old male mice by fixing the proximal tail by a clip connected to the top of the animal's cage for 3 weeks. Axonal excitability studies were performed by stimulating the sciatic nerve at the ankle and recording the compound muscle action potential (CMAP) from the foot. The amplitudes of the motor responses of the unloading group were 51% of the control amplitudes [2.2 ± 1.3 mV (HLU) vs. 4.3 ± 1.2 mV (Control), P = 0.03]. Multiple axonal excitability analysis showed that the unloading group had a smaller strength-duration time constant (SDTC) and late subexcitability (recovery cycle) than the controls [0.075 ± 0.01 (HLU) vs. 0.12 ± 0.01 (Control), P < 0.01; 5.4 ± 1.0 (HLU) vs. 10.0 ± 1.3 % (Control), P = 0.01, respectively]. Three weeks after releasing from HLU, the SDTC became comparable to the control range. Using a modeling study, the observed differences in the waveforms could be explained by reduced persistent Na+ currents along with parameters related to current leakage. Quantification of RNA of a SCA1A gene coding a voltage-gated Na+ channel tended to be decreased in the sciatic nerve in HLU. The present study suggested that axonal ion currents are altered in vivo by HLU. It is still undetermined whether the dysfunctional axonal ion currents have any pathogenicity on neuromuscular atrophy or are the results of neural plasticity by atrophy

Which muscle shows fasciculations by ultrasound in patients with ALS?

The purpose of the present study was to elucidate the relative frequencies of fasciculations assessed by sonography in a large number of muscles in patients with amyotrophic lateral sclerosis (ALS). The patients diagnosed as having ALS were retrospectively assessed by muscle sonography. The frequencies of having fasciculations were compared among the 15 muscles and the subtypes according to the initially affected body region. Overall, approximately half of the muscles had fasciculations (48.8%), in the average of 11.4 muscles per patient. The frequency of fasciculations tended to be lower in the patients with longer disease durations upon testing. Biceps brachii had the highest frequency, followed by extensor digitorum communis, whereas sternocleidomastoid and rectus abdominis had the lowest frequencies. The frequencies of fasciculations were similar among the clinical subtypes. In conclusion, in patients with ALS, fasciculations were detected most frequently in proximal arm muscles by sonography, whereas truncal muscles had lower frequencies. Fasciculations tended to be less evident in the advanced disease stage, possibly reflecting muscle degeneration. Appropriate selection of muscles to observe fasciculations is important for diagnosis of ALS

Sonographic evaluation of cervical nerve roots in ALS and its clinical subtypes

Morphological assessment of peripheral nerves in amyotrophic lateral sclerosis (ALS) has been available by sonography. Detection of possible axonal atrophy could be important in predicting progression. Research on correlation between sonographic findings and clinical presentation has been sparse. The aim of the study was to assess possible motor axon loss in patients with ALS by sonography and to correlate the imaging features with clinical subtypes. Patients with either definite or probable ALS and control subjects had sonographic evaluation of the cervical nerve roots (C5, C6, and C7). Each diameter and their sums were measured. The ALS patients were classified by their clinical onset and progression (arm-onset, leg-onset, bulbar, and flail-arm variant) and the sonographic features were compared. Overall, the cervical nerve roots were thinner in ALS than in the controls, but the diagnostic sensitivity was low. The patients with arm dysfunctions tended to show thinner nerve roots than those with normal or relatively preserved arm functions. The four ALS subtypes showed similar diameters of the nerve roots. There was no correlation between the disease duration and the diameters of the nerve roots. Sonography of the cervical nerve roots showed axonal atrophy in ALS and potentially reflects subtle arm dysfunctions

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study

Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings

Pathological Endogenous α-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy.

Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenousα-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs),and mature oligodendrocytes (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs revealed that α-syn PFFs interfered with the expression of proteins associated with neuromodulation and myelination. Furthermore, we detected cytoplasmic α-syn inclusions in OLGs through differentiation of OPCs pre-incubated with PFFs. Overall, our findings suggest the possibility of endogenous α-syn accumulation in OPCs that contributes to GCI formation and perturbation of neuronal/glial support in multiple system atrophy brains