Loss of ADAR1 protein induces changes in small RNA landscape in hepatocytes.

In recent years, numerous evidence has been accumulated about the extent of A-to-I editing in human RNAs and the key role ADAR1 plays in the cellular editing machinery. It has been shown that A-to-I editing occurrence and frequency are tissue-specific and essential for some tissue development, such as the liver. To study the effect of ADAR1 function in hepatocytes, we have created Huh7.5 ADAR1 KO cell lines. Upon IFN treatment, the Huh7.5 ADAR1 KO cells show rapid arrest of growth and translation, from which they do not recover. We analyzed translatome changes by using a method based on sequencing of separate polysome profile RNA fractions. We found significant changes in the transcriptome and translatome of the Huh7.5 ADAR1 KO cells. The most prominent changes include negatively affected transcription by RNA polymerase III and the deregulation of snoRNA and Y RNA levels. Furthermore, we observed that ADAR1 KO polysomes are enriched in mRNAs coding for proteins pivotal in a wide range of biological processes such as RNA localization and RNA processing, whereas the unbound fraction is enriched mainly in mRNAs coding for ribosomal proteins and translational factors. This indicates that ADAR1 plays a more relevant role in small RNA metabolism and ribosome biogenesis.

Spontaneous spinal epidural haematoma: management and main risk factors in era of anticoagulant / antiplatelet treatment.

AIM OF THE STUDY: Spontaneous spinal epidural haematomas (SSEH) are rare nosological units wherein acute collections of blood develop in the spinal canal. SSEH are usually manifested by sudden severe back pain accompanied by the development of neurological symptoms. In this study, we retrospectively describe management and the main risk factors of SSEH in a series of 14 cases. MATERIAL AND METHODS: Between 2010 and 2019, we examined 14 patients (age range 17-89 years, 10 women) diagnosed with SSEH. Eight cases were patients using anticoagulant therapies (six warfarin, one dabigatran, one apixaban) and two others were using ASA of 100 mg/day. The exact localisation and extent of changes was determined from acute magnetic resonance imaging. Three people using warfarin had INR values higher than 3.0 at the time of their diagnosis. RESULTS: Ten patients (71%) were taking oral anticoagulants or antiplatelet agents. In seven patients, SSEH were localised in the lower cervical/thoracic spine. Ten patients (71%) had arterial hypertension. Six patients underwent acute surgery due to rapidly developing spinal cord compression. Eight patients (57%) with slight or mild neurological symptoms were successfully managed without surgery. CONCLUSIONS: SSEH should be suspected in any patient receiving anticoagulant/antiplatelet agents who complains of sudden, severe back pain accompanied by neurological symptoms. SSEH is mostly localised in the lower cervical/thoracic spine. Arterial hypertension appears to be a risk factor of SSEH. Early decompression is an important therapeutic approach; in cases with minor neurological deficits, conservative treatment may be chosen.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Transverse Myelitis.

Antibodies against myelin oligodendrocyte glycoprotein cause inflammatory lesions of central myelin - in optic nerves, of the brainstem, and spinal cord. There are characteristic changes of CNS white matter, protein-cytological association in cerebrospinal fluid, MOG IgG antibodies, a very important differential diagnosis and a relatively mild course.

Diverse origin of mitochondrial lineages in Iron Age Black Sea Scythians.

Scythians were nomadic and semi-nomadic people that ruled the Eurasian steppe during much of the first millennium BCE. While having been extensively studied by archaeology, very little is known about their genetic identity. To fill this gap, we analyzed ancient mitochondrial DNA (mtDNA) from Scythians of the North Pontic Region (NPR) and successfully retrieved 19 whole mtDNA genomes. We have identified three potential mtDNA lineage ancestries of the NPR Scythians tracing back to hunter-gatherer and nomadic populations of east and west Eurasia as well as the Neolithic farming expansion into Europe. One third of all mt lineages in our dataset belonged to subdivisions of mt haplogroup U5. A comparison of NPR Scythian mtDNA linages with other contemporaneous Scythian groups, the Saka and the Pazyryks, reveals a common mtDNA package comprised of haplogroups H/H5, U5a, A, D/D4, and F1/F2. Of these, west Eurasian lineages show a downward cline in the west-east direction while east Eurasian haplogroups display the opposite trajectory. An overall similarity in mtDNA lineages of the NPR Scythians was found with the late Bronze Age Srubnaya population of the Northern Black Sea region which supports the archaeological hypothesis suggesting Srubnaya people as ancestors of the NPR Scythians.

Evaluation of Lumbar Spine Load by Computational Method in Order to Acknowledge Low-back Disorders as Occupational Diseases.

AIM: The aim of the study was to develop a computational module for the prediction of compressive force on the L4/L5 disc suitable for use in field settings. METHOD: The value of compressive force is intended to be used as a proxy measure of the mechanical burden of low-back when performing work activities. The compressive force predicted by the module in a particular worker should be compared with the NIOSH limit value of 3,400 N for the assessment of lumbar spine load during manual lifting tasks. Exceeding the limit will be considered as the fulfilment of "hygienic criterion" that should be met to acknowledge low-back disorder as an occupational disease. To develop the computational module we used the ergonomic software TECNOMATIX Classic Jack taking into account the anthropometric parameters of a worker and ergonomic parameters of his/her work activity. RESULTS: We calculated compressive forces on the L4/L5 disc in about 1,300 simulated combinations of various factors influencing compressive force. Parameters which turned out to be crucial for the compression of L4/L5 disc were included in the computational algorithm. CONCLUSION: Our study was primarily aimed at the assessment of lumbar disorders as occupational diseases. Moreover, the study can contribute to the recommendation of preventive measures to decrease health risks in occupations associated with the overload of low-back region. The graphic maps generated by the computational module enable a fast and exact analysis of particular job.

LOW-BACK PAIN DISORDERS AS OCCUPATIONAL DISEASES IN THE CZECH REPUBLIC AND 22 EUROPEAN COUNTRIES: COMPARISON OF NATIONAL SYSTEMS, RELATED DIAGNOSES AND EVALUATION CRITERIA.

AIM: Low-back pain diseases (LBPD) belong to the most frequent diagnoses determined by general practitioners, and constitute one of the most common reasons for sick leave and permanent disability pension in the Czech Republic and other European countries. Epidemiological studies have shown a statistically significant association between LBPD and certain types of occupational burden. However, in the Czech Republic, LBPD caused by overload and/or whole-body vibrations have not yet been included in the list of occupational diseases. The aim of this study was to collect and compare the systems, criteria and diagnoses used to recognize LBPD as occupational diseases in other European countries. METHODS: A questionnaire focused on LBPD was distributed and answered by specialists in occupational diseases in European countries. It included items concerning LBPD in the national list of occupational diseases, and work-related and diagnostic criteria that need to be fulfilled for recognizing LBPD as occupational diseases and possible awarding compensations to the patients. RESULTS: In 13 countries out of the 23 countries studied, LBPD caused by overload can be recognized as occupational, providing that the diagnosis is sufficiently proven and exposure criteria and/or listed occupation are met and duration of exposure is confirmed (Belgium, Denmark, France, Germany, Hungary, Italy, Lithuania, Macedonia, Netherlands, Romania, Slovakia, Sweden, and Switzerland). LBPD due to vibrations can be also recognized as occupational in 14 countries. In 8 countries LBPD are not accepted as occupational unless they are caused by an injury at work. Specific criteria to evaluate occupational exposure of patients with LBPD were set in Belgium, Denmark, France, Germany, Lithuania, Macedonia, Netherlands, and Slovakia. In other countries, the evaluation is done at an individual basis. CONCLUSIONS: In practice, the assessment of occupational overload and its contribution to the development of LBPD as well as its inclusion in the compensation system are important for several reasons. Firstly, it may be considered essentially preventable. Secondly, cases with a significant contribution of occupational aetiology may be viewed as occupational diseases for which compensation may be claimed, as it is the case in many European countries. Importantly, inclusion of LBPD in the list of occupational diseases or another system of compensation may be viewed as a preventive measure as it increases the visibility of this problem not only for the workers, but especially for the employers.

Development of the Brief Bedside Dysphagia Screening Test - Revised: a Cross-Sectional Czech Study.

AIM: The purpose of this study was to develop a revised version of the Brief Bedside Dysphagia Screening Test for determining penetration/aspiration risk in patients prone to dysphagia. The priority was to achieve high sensitivity and negative predictive value. METHODS: The study screeners conducted bedside assessment of the swallowing function in 157 patients with a neurological (mainly stroke) or an ear, nose, and throat diagnosis (mainly head and neck cancer). The results were compared with a gold standard, flexible endoscopic examination of swallowing. RESULTS: For the neurological subgroup (N = 106), eight statistically significant bedside assessment items were combined into the Brief Bedside Dysphagia Screening Test-Revised (BBDST-R). Cut-off score 1 produced the highest sensitivity (95.5%; 95% confidence interval CI [CI]: 84.9-98.7%) and negative predictive value (88.9%; 95% CI 67.2-96.9%). CONCLUSION: The BBDST-R is suitable for dysphagia screening in departments caring for patients with neurological conditions.

Painful lumbosacral plexopathy: a case report.

Patients frequently suffer from lumbosacral plexus disorder. When conducting a neurological examination, it is essential to assess the extent of muscle paresis, sensory disorder distribution, pain occurrence, and blocked spine. An electromyography (EMG) can confirm axonal lesions and their severity and extent, root affliction (including dorsal branches), and disorders of motor and sensory fiber conduction. Imaging examination, particularly gadolinium magnetic resonance imaging (MRI) examination, ensues. Cerebrospinal fluid examination is of diagnostic importance with radiculopathy, neuroinfections, and for evidence of immunoglobulin synthesis. Differential diagnostics of lumbosacral plexopathy (LSP) include metabolic, oncological, inflammatory, ischemic, and autoimmune disorders.In the presented case study, a 64-year-old man developed an acute onset of painful LSP with a specific EMG finding, MRI showing evidence of plexus affliction but not in the proximal part of the roots. Painful plexopathy presented itself with severe muscle paresis in the femoral nerve and the obturator nerve innervation areas, and gradual remission occurred after 3 months. Autoimmune origin of painful LSP is presumed.We describe a rare case of patient with painful lumbar plexopathy, with EMG findings of axonal type, we suppose of autoimmune etiology.

Rare case of a localized radial nerve amyloid neuropathy.

We report the case of a 55-year-old woman with a 6-month history of progressive paresis of the right radial nerve. Perioperative imaging detected a spindle-shaped expansion of the radial nerve caused by an isolated local deposit of amyloid (amyloidoma). The deposit was resected in 2 phases and the resulting defect was bridged by a sural nerve autograft. Overall internal and hematological examination did not reveal systemic amyloidosis or lymphoproliferative disorder. The reason for our report is that localized forms of amyloid neuropathy are very rare.

Myasthenia gravis, Castleman disease, pemphigus, and anti-phospholipid syndrome.

INTRODUCTION: Myasthenia gravis is an autoimmune disease marked by neuromuscular transmission failure at the neuromuscular junction. Castleman disease is a rare lymphoproliferative disease characterized by non-cancerous angiofolicular hyperplasia of lymphatic tissue. METHODS AND RESULTS: We describe a young man with rapid, successive manifestations of myasthenia gravis, a solitary form of Castleman disease, pemphigus vulgaris, and anti-phospholipid syndrome, which resulted in 2 ischemic cerebrovascular events that caused a severe central neurological deficit. DISCUSSION: We were unable to find a similar case in the literature, but we hypothesize that the temporal concidence of these clinical entities may be related to a common immunological pathway, such as B-cell activation. Therefore, we treated the patient with an immunosuppressant and anticoagulant treatment, as well as rituximab, a monoclonal antibody therapy against CD20+.

The potential benefit of intracarpal pressure measurement in endoscopic carpal tunnel syndrome surgery--an analysis of EMG findings and pressure values.

Endoscopic carpal tunnel syndrome surgery is a modern minimally invasive method of carpal tunnel decompression. However, the method does also have its critics, who emphasize that there is an increased rate of complications in comparison to open procedures. To further improve and optimize results of endoscopic surgery we used an intracarpal pressure sensor to verify the effect of carpal tunnel decompression. The endoscopic single portal approach was used in all cases. Median nerve conduction studies were performed prior to and 3 months after surgery. Two groups, those with pressure studies and those without, were then compared according to several EMG parameters such as: median nerve distal motor latency, amplitude of motor response, sensory nerve conduction velocity to the index finger, and amplitude of sensory nerve action potential. In both groups, we observed similarly significant improvements in all conduction parameters, except the amplitude of motor response, which did not change in either group, i.e. no difference in postoperative EMG between the two groups was observed. Despite this fact, intracarpal pressure measurement is still useful in localising the point in which the median nerve is compressed and provides valuable functional information on the level decompression achieved.