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The presented research was intended to seek new optical methods to investigate the demineralization process of bones. Optical examination of the bone condition could facilitate clinical trials and improve the safety of patients. The authors used a set of complementary methods: polarization-sensitive optical coherence tomography (PS-OCT) and Raman spectroscopy. Chicken bone samples were used in this research. To stimulate in laboratory conditions the process of demineralization and gradual removal of the hydroxyapatite, the test samples of bones were placed into 10% acetic acid. Measurements were carried out in two series. The first one took two weeks with data acquired every day. In the second series, the measurements were made during one day at an hourly interval (after 1, 2, 3, 5, 7, 10, and 24 h). The relation between the content of hydroxyapatite and images recorded using OCT was analyzed and discussed. Moreover, the polarization properties of the bones, including retardation angles of the bones, were evaluated. Raman measurement confirmed the disappearance of the hydroxyapatite and the speed of this process. This work presents the results of the preliminary study on the possibility of measuring changes in bone mineralization by means of the proposed methods and confirms their potential for practical use in the future.

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Clinical, electrophysiological, neuroradiological, and morphological data of 84 patients were analyzed. Genetic studies of mitochondrial DNA (mtDNA) were performed in all patients. Among nuclear DNA (nDNA) genes POLG was sequenced in 41 patients, TWNK ( C10orf2 ) in 13 patients, and RNASEH1 in 2 patients. Total of 27 patients were included in the chronic progressive external ophthalmoplegia (CPEO) group, 24 in the CPEO+ group. Twenty-six patients had mitochondrial encephalomyopathy (ME), six patients Kearns-Sayre syndrome (KSS), and one patient sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic analysis of nDNA genes revealed the presence of pathogenic or possibly pathogenic variants in the POLG gene in nine patients, the TWNK gene in five patients and the RNASEH1 gene in two patients. Detailed patients' history and careful assessment of family history are essential in the diagnostic work-up. Genetic studies of both mtDNA and nDNA are necessary for the final diagnosis of progressive external ophthalmoplegia and for genetic counseling.

The main goal of this research was to assess if it is possible to evaluate the thickness of thin layers (both thin films on the surface and thin layers below the surface of the tested object) and foils using optical coherence tomography (OCT) for thickness assessment under the resolution of the standard commercially available OCT measurement system. In the proposed solution, light backscattered from the evaluated thin layer has been expressed as a multiple beam interference. Therefore, the OCT system was modeled as a two-beam interferometer (e.g., Michelson), in which one beam propagates from the reference arm and the other comes from a Fabry-Pérot interferometer. As a consequence, the mathematical model consists of the main Michelson interferometer, in which the measuring arm represents the Fabry-Pérot interferometer. The parameters of the layer (or foil) are evaluated by analyzing the minimum value of the interference contrast. The model developed predicts the behavior of the thin layers made from different materials (with different refractive indexes) with different thickness and located at different depths. To verify the correctness of the proposed model, an experiment with a wedge cell has been carried out. The wedge cell was shifted across the scanning beam using a linear translation stage with a micrometer screw under the scanning head. The relationship between the thickness of the gap of the wedge cell and the OCT output signal is presented. For the additional verification of the proposed model, the results of the measurements of the thickness of the thin foil were compared with the theoretical results of the simulations. The film thickness was evaluated based on the calculated positions of the minimum value of interference contrast. A combination of the standard potentialities of OCT with the proposed approach to analyzing the signal produces new metrological possibilities. The method developed allows us to evaluate thickness under the resolution of the system and the location of the layer as well. This produces the possibility of measuring a layer which is covered by another layer. Moreover, it is possible to create a thickness map with high sensitivity to thickness changes. These experiments and simulations are the culmination of preliminary research for evaluating the potential of the proposed measurement method.

Introduction: Clinically oriented diagnostic criteria can be as specific for diagnosis of sporadic inclusion body myositis (sIBM) as pathological criteria, especially at the time of presentation. EMG may provide an convincing proof that a muscle biopsy should be performed., Aims: To compare the EMG results in patients with sIBM divided into subgroups based on the newest ENMC criteria for sIBM and to obtain the utility of EMG in the diagnostic process at the time of presentation., Methods: We retrospectively analysed 16 patients with sIBM for motor unit action potential (MUAP) morphology as well as occurrence and distribution of abnormal spontaneous activity (SA) in muscles., Results: Abnormal SA was recorded in 62.5% of sIBM patients. We found statistically significant differences between subgroups in the incidence of polyphasic MUAPs and high amplitude outliers which were more commonly seen in the "clinico-pathologically defined sIBM". Duration of MUAP in the tibialis anterior was significantly shorter in "probable sIBM"., Discussion: "Pseudo-neurogenic" MUAPs, mainly in lower limb muscles, are more commonly seen in "clinico-pathologically defined sIBM" while myopathic MUAPs with prominent abnormal SA are recorded in patients diagnosed with "probable sIBM". Both EMG patterns may be suggestive of sIBM and be an indication for further diagnosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

BAG3 belongs to BAG family of molecular chaperone regulators interacting with HSP70 and anti-apoptotic protein Bcl-2. It is ubiquitously expressed with strong expression in skeletal and cardiac muscle, and is involved in a panoply of cellular processes. Mutations in BAG3 and aberrations in its expression cause fulminant myopathies, presenting with progressive limb and axial muscle weakness, and respiratory insufficiency and neuropathy. Herein, we report a sporadic case of a 15-years old girl with symptoms of myopathy, demyelinating polyneuropathy and asymptomatic long QT syndrome. Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy. We did not find a mutation in any known LQT syndrome genes. Analysis of muscle biopsy revealed profound disintegration of Z-discs with extensive accumulation of granular debris and large inclusions within fibers. We demonstrated profound alterations in BAG3 distribution as the protein localized to long filamentous structures present across the fibers that were positively stained not only for α-actinin but also for desmin and filamin indicating that those disintegrated Z-disc regions contained also other sarcomeric proteins. The mutation caused a decrease in the content of BAG3 and HSP70, and also of α-actinin desmin, filamin and fast myosin heavy chain, confirming its severe effect on the muscle fiber morphology and thus function. We provide further evidence that BAG3 is associated with Z-disc maintenance, and the Pro209Leu mutation may occur worldwide. We also provide a summary of cases associated with this mutation reported so far.

Introduction: Multisystem manifestations of myotonic dystrophies type 1 (DM1) and 2 (DM2) are well known. Peripheral nerve involvement has been reported in DM1 but not in genetically confirmed DM2. The aim of our study was to assess peripheral nerve involvement in DM2 using nerve conduction studies and to compare these results with findings in DM1., Methods: We prospectively studied patients with genetically confirmed DM2 (n=30) and DM1 (n=32). All patients underwent detailed neurological examination and nerve conduction studies., Results: Abnormalities in electrophysiological studies were found in 26.67% of patients with DM2 and in 28.13% of patients with DM1 but the criteria of polyneuropathy were fulfilled in only 13.33% of patients with DM2 and 12.5% of patients with DM1. The polyneuropathy was subclinical, and no correlation was found between its presence and patient age or disease duration., Conclusions: Peripheral nerves are quite frequently involved in DM2, but abnormalities meeting the criteria of polyneuropathy are rarely found. The incidence of peripheral nerve involvement is similar in both types of myotonic dystrophy., (Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other myosins, towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis, intracellular trafficking, cell migration, and transcription. In mammalian skeletal muscles it localizes mainly to sarcoplasmic reticulum and is also present within the muscle nuclei and at the neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228). We have also shown that in denervated rat hindlimb muscle the MVI expression level is significantly increased and its localization is changed, indicating an important role of MVI in striated muscle pathology. Here, we addressed this problem by examining the distribution and expression levels of myosin VI in biopsies of skeletal muscles from patients with different myopathies. We found that, particularly in myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. Also, since a mutation within the human MVI gene was shown to be associated with cardiomyopathy, we assessed MVI localization and expression level in cardiac muscle using wild type and MLP(-/-) mice, a dilated cardiomyopathy model. No significant difference in MVI expression level was observed for both types of animals. MVI was found at intercalated discs and also at the sarcoplasmic reticulum. In the knockout mice, it was also present in ring-like structures surrounding the nuclei. The data indicate that in striated muscle MVI could be engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular transport, signal transmission and possibly in gene transcription., (© 2014 Wiley Periodicals, Inc.)

Mitochondrial diseases may cause a wide range of central and peripheral nervous system disorders, as well as muscle disorders. The diagnostic workup routinely includes electrophysiological, morphological, neuroimaging and genetic studies. In some cases, the diagnosis may be ascertained only when mitochondrial DNA (mtDNA) examination in the muscle is performed. We report on a case of a 24-year-old woman, with a 7-year history of slowly progressive cerebellar syndrome and bilateral ptosis. Mitochondrial encephalomyopathy was suspected, based on the clinical picture and results of examinations, but the typical red ragged fibers were not found in the muscle biopsy. The results of molecular analysis of mtDNA showed a mtDNA deletion in the muscle and, on a level detectable only with polymerase chain reaction method, in blood leukocytes. This case emphasizes the important role of mtDNA studies in muscle in nonspecific multisystem mitochondrial disorders, even without clinical muscle involvement., (Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background and Purpose: Mitoxantrone (MTX) has been shown to reduce progression of disability and number of clinical exacerbations in patients with progressive multiple sclerosis (MS). Prolonged administration of MTX, however, is limited by the risk of cardiotoxicity. Cardiac monitoring in MTX-treated patients includes usually measurement of left ventricular ejection fraction (LVEF) by means of echocardiography. The N-terminal pro-brain natriuretic peptide (NT-proBNP) represents a novel diagnostic tool in the assessment of heart failure. This study was aimed to evaluate the usefulness of NT-proBNP for early detection of MTX-induced cardiotoxicity in MS patients., Materials and Methods: We measured the NT-proBNP plasma levels in 45 MS patients who completed 24-month MTX therapy and in 37 MS patients of control group., Results: The median NT-proBNP plasma value was 15.12pg/mL. In 12 MTX-treated patients (27%), NT-proBNP plasma values were elevated, though this subgroup of patients neither clinical showed evidence of myocardial damage nor had the LVEF value <50%. In five patients with normal NT-proBNP, we observed LVEF decline >10%. We did not observe correlations between the NT-proBNP levels and patient age, MS duration, relapses index, Extended Disability Status Scale (EDSS), MTX single dose and the total cumulative dose of MTX. In 8 patients (22%) from control group, NT-proBNP plasma levels were also elevated., Conclusions: The results of our study confirm that MTX therapy is safe for carefully selected and closely monitored MS patients. We believe that serial evaluation of NT-proBNP levels (before, during and after MTX therapy) can identify MS patients at high risk for MTX-induced cardiotoxicity., (Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background and Purpose: At present, more than 20 different forms of limb-girdle muscular dystrophies (LGMDs) are known (at least 7 autosomal dominant and 14 autosomal recessive). Although these different forms show some typical phenotypic characteristics, the existing clinical overlap makes their differential diagnosis difficult. Limb-girdle muscular dystrophy type 2 (LGMD2A) is the most prevalent LGMD in many European as well as Brazilian communities and is caused by mutations in the gene CAPN3. Laboratory testing, such as calpain immunohistochemistry and Western-blot analysis, is not totally reliable, since up to 20% of molecularly confirmed LGMD2A show normal content of calpain 3 and a third of LGMD2A biopsies have normal calpain 3 proteo-lytic activity in the muscle. Thus, genetic testing is considered as the only reliable diagnostic criterion in LGMD2A., Material and Methods: In an attempt to find a correlation between genotype and muscle pathology in limb-girdle muscular dystrophy 2A we performed histopathological investigation of a group of 31 patients subdivided according to the type of pathologic CAPN3 gene mutation., Results: In all biopsies typical features of muscular dystrophy such as fiber necrosis and regeneration, variation in fiber size and fibrosis were noted. Lobulated fibers were often encountered in the muscle biopsies of LGMD2A patients. Such fibers were more frequent in patients with 550delA mutation., Conclusions: These findings may be helpful in establishing diagnostic strategies in LGMD.

We report two adult familial cases of inclusion body myopathy (IBM) with desmin storage in skeletal muscle. Clinically, both patients presented late-onset, progressive, symmetrical, both proximal and distal muscle weakness. Muscle biopsy findings were identical in both cases and consisted of marked variability in fiber size, increased number of central nuclei and vacuolation involving 10% of fibers. Single or multiple vacuoles were located subsarcolemmally or in the center, and were rimmed by basophilic material. At the ultrastructural level, tubulofilamentous nuclear and cytoplasmic inclusions of 16-21 nm in diameter were frequently observed. In addition, large subsarcolemmal and central deposits composed of electron-dense granular material were present in many fibers. Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within both inclusions and vacuolated fibers. Possible structural and functional associations between these two types of muscle changes remain unclear. They may either represent two coexistent disease processes or merely reflect an abnormal form of muscle fiber degradation, with unidentifiable specificity.