Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

Dermatomyositis: Muscle Pathology According to Antibody Subtypes

Background and Objectives:Discoveries of dermatomyositis specific antibodies (DMSAs) in dermatomyositis patients raised awareness of various myopathological features among antibody subtypes. However, only perifascicular atrophy and perifascicular myxovirus resistant protein A (MxA) overexpression were officially included as the definitive pathological criteria for dermatomyositis classification. We aimed to demonstrate myopathological features in MxA-positive dermatomyositis to determine characteristic myopathological features in different DMSA subtypes.Method:We performed a retrospective pathology review of muscle biopsies of dermatomyositis patients diagnosed between January 2009 and December 2020 in a tertiary laboratory for muscle diseases. We included all muscle biopsies with sarcoplasmic expression for MxA and seropositivity for DMSAs. MxA-positive muscle biopsies which tested negative for all DMSAs were included as seronegative dermatomyositis. We evaluated histological features stratified according to four pathology domains (muscle fiber, inflammatory, vascular, and connective tissue) and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. We performed ultrastructural studies of 54 available specimens.Result:A total of 256 patients were included. Of these, 249 patients were positive for one of the five DMSAs (seropositive patients: 87 anti-TIF1-γ; 40 anti-Mi-2; 29 anti-MDA5; 83 anti-NXP-2; and 10 anti-SAE DM) and 7 patients were negative for all five DMSAs (seronegative patients). Characteristic myopathological features in each DMSA subtype were as follows: anti-TIF1-γ with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC stain (75.9%, P<.001); anti-Mi-2 with prominent muscle fiber damage (score 4.8±2.1, P<.001), inflammatory cell infiltration (score 8.0±3.0, P=.002), perifascicular atrophy (67.5%, P=.02), perifascicular necrosis (52.5%, P<.001), increased perimysial alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal membrane attack complex deposition (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; anti-NXP2 with microinfarction (26.5%, P<.001); and anti-SAE and seronegative DM with HLA-DR expression (50.0%, P=.02 and 57.1%, P=.02, respectively).Discussion:We described a comprehensive serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. In our study, DMSAs were associated with distinctive myopathological features suggesting different underlying pathobiological mechanisms in each subtype.

The Role of Satellite Cells in Skeletal Muscle Regeneration—The Effect of Exercise and Age

The population of satellite cells (mSCs) is highly diversified. The cells comprising it differ in their ability to regenerate their own population and differentiate, as well as in the properties they exhibit. The heterogeneity of this group of cells is evidenced by multiple differentiating markers that enable their recognition, classification, labeling, and characterization. One of the main tasks of satellite cells is skeletal muscle regeneration. Myofibers are often damaged during vigorous exercise in people who participate in sports activities. The number of satellite cells and the speed of the regeneration processes that depend on them affect the time structure of an athlete’s training. This process depends on inflammatory cells. The multitude of reactions and pathways that occur during the regeneration process results in the participation and control of many factors that are activated and secreted during muscle fiber damage and at different stages of its regeneration. However, not all of them are well understood yet. This paper presents the current state of knowledge on satellite cell-dependent skeletal muscle regeneration. Studies describing the effects of various forms of exercise and age on this process were reviewed.

Fabrication and microstructure evolution of Csf/ZrB2-SiC composites via direct ink writing and reactive melt infiltration

Fiber damage and uniform interphase preparation are the main challenges in conventional short fiber reinforced ceramic matrix composites. In this work, we develop a novel processing route in fabrication of short carbon fiber reinforced ZrB2-SiC composites (Csf/ZrB2-SiC) overcoming the above two issues. At first, Csf preforms with oriented designation and uniform PyC/SiC interphase are fabricated via direct ink writing (DIW) of short carbon fiber paste followed by chemical vapor infiltration. After that, ZrB2 and SiC are introduced into the preforms by slurry impregnation and reactive melt infiltration, respectively. Microstructure evolution and optimization of the composites during fabrication are investigated in detail. The as-fabricated Csf/ZrB2-SiC composites have a bulk density of 2.47 g/cm3, with uniform weak interphase and without serious fiber damage. Consequently, non-brittle fracture occurs in the Csf/ZrB2-SiC composites with widespread toughening mechanisms such as crack deflection and bridging, interphase debonding, and fiber pull-out. This work provides a new opportunity to the material design and selection of short fiber reinforced composites.

Toxicity in Peripheral Nerves: An Overview

Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.

CFTR corrector C17 is effective in muscular dystrophy, in vivo proof of concept in LGMDR3

Limb-girdle muscular dystrophy 3 (LGMDR3) is caused by mutations in the SGCA gene coding for α-sarcoglycan (SG). Together with β- γ- and δ-SG, α-SG forms a tetramer embedded in the dystrophin associated protein complex (DAPC) crucial for protecting the sarcolemma from mechanical stresses elicited by muscle contraction. Most LGMDR3 cases are due to missense mutations, which result in non-properly folded, even though potentially functional α-SG. These mutants are prematurely discarded by the cell quality control. Lacking one subunit, the SG-complex is disrupted. The resulting loss of function leads to sarcolemma instability, muscle fiber damage and progressive limb muscle weakness. LGMDR3 is severely disabling and, unfortunately, still incurable. Here we propose the use of small molecules, belonging to the class of cystic fibrosis transmembrane regulator (CFTR) correctors, for recovering mutants of α-SG defective in folding and trafficking. Specifically, CFTR corrector C17 successfully rerouted the SG-complex containing the human R98H-α-SG to the sarcolemma of hind-limb muscles of a novel LGMDR3 murine model. Notably, the muscle force of the treated model animals was fully recovered. To our knowledge, this is the first time that a compound designated for cystic fibrosis (CF) is successfully tested in a muscular dystrophy and may represent a novel paradigm of treatment for LGMDR3 as well as different other indications in which a potentially functional protein is prematurely discarded as folding-defective. Furthermore, the use of small molecules for recovering the endogenous mutated SG has an evident advantage over complex procedures such as gene or cell transfer.

Cotton fibers bleaching through in situ electrochemical generation of oxidant agents

Cotton is the world’s leading fiber crop and contains natural coloring impurities which need to be removed by bleaching. The most applied bleaching methodology utilizes chemical oxidants, such as hydrogen peroxide. This method is carried out at high temperatures and under strong alkaline conditions, entailing high-energy consumption, strong alkaline effluents and severe fiber damage. The development of milder and greener bleaching processes, in which the fibers are less damaged, is a goal that has long been pursued. Another approach for cotton bleaching is the use of sodium hypochlorite as an oxidant. Several methods applying hypochlorite are known, but they face problems associated with the transport, storage and handling of unstable and hazardous chemicals. Here we present a mild methodology for in situ electrogeneration of hypochlorite from sodium chloride or potassium chloride, and its application in bleaching of cotton, thus reducing the problems associated with the transport and storage of the oxidizing reagent. Our methodology was able to bleach the cotton fibers with a comparable whiteness degree, when compared to the conventional one, and it is carried out in lower reaction times, at room temperature, with no need of addition of hazardous materials and avoiding the production of residual hypochlorite.

INFLUENCE OF THE MESH SHAPE OF THE FINE LITTER CLEANER FOR RAW COTTON ON THE CLEANING EFFECT

Increasing the efficiency of cleaning raw cotton from weeds will ultimately improve the quality of products in the textile industry. It has been established that when using cylindrical mesh on purifiers with peg drums, the exciting force acting on the strips from the side of the net has a stable frequency, determined mainly by the frequency of rotation of the peg drum. This mode of operation of the cleaner does not effectively remove trash impurities. To improve the efficiency of the cleaner, it is proposed to use a grid in the form of a multifaceted prism. It was found that, by design conditions, the minimum number of mesh faces is four. The dependence of the cleaning effect on the number of faces of the perforated mesh of the cleaner has been experimentally obtained. It was found that with an increase in the number of mesh edges, the cleaning effect and fiber damage decrease. With the number of faces equal to six, it is possible to achieve an increase in the cleaning effect by an average of 16 % with a slight increase in fibre damage.