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Introduction: Dystonia is a syndrome characterized by sustained muscle contractions frequently causing twisting and repetitive movements of the relative part of the body or abnormal postures. The precise pathophysiology of idiopathic dystonia is still unclear. Systematic investigation of involuntary movements characterized by constant laterality of posture and motion has not yet been done. The aim of our study was to determine the symmetry of the density of dopamine D2 receptors with 123I-IBZM SPECT in relation to the head rotation in patients suffering from unilateral or lateralized dystonia. Methods: Seventeen patients with a clinical diagnosis of cervical dystonia participated in our study. There were 11 men and 6 women. The mean age was 48 years (25 to 64). Structural lesions of the brain were excluded by CT or MRI. The dopamine D2 receptor ligand used was 123I-IBZM. Imaging was performed with a dual-head SPECT gamma camera. We quantified the area as well as radioactivity accumulation within the striatum and its symmetry using five different methods. We assessed reliability by intraobserver and interobserver (2 readers) variability as well as methodological variability. Results: From all the tested methods used for symmetry/asymmetry of 123I-IBZM uptake evaluation in striatum no one is more reproducible than the others including the most simple visual assessment. The correspondence with clinical findings was better for quantitative methods. In our study in 13 of 17 patients with (rotational) cervical dystonia the dopamine D2 receptors density predominated in the striatum ipsilateral to the rotation of the head. Conclusions: The asymmetric accumulation of dopamine D2 receptors corresponding to the side of motor and postural asymmetry supports the view that the direction of circling behavior in animals and the direction of cervical dystonia in human beings might be predisposed. [ABSTRACT FROM AUTHOR]

Background. Experience with Intraoperative monitoring using neurophysiological and haemodynamic indices in 500 operations for carotid endarterectomy is reported. Methods. Transcranial Doppler technique (TCD), electroencephalogram (EEG) and bilateral median somatosensory evoked potentials (SEP) were performed. Latency and amplitude of SEP, spectral analysis of EEG signal and blood flow velocity in the medial cerebral artery (MCA) were continuously measured. Findings. After two consecutive drops of N20/P25 complex of more than 50%, a warning was given, and when the decrease continued, an the alarm raised. Abnormal EEG changes, if any, appeared after a significant decrease in the N20/P25 amplitude. A mean blood flow velocity drop below 40% of the reference value after cross clamping was rated as a significant warning event. A warning as a result of a decrease in N20/P25 amplitude occurred in 80 operations (16.0%), after an spectral edge frequency decrease in 2 cases (0.4%) and after a Vmean decrease in 21 cases (4.2%). False negative results were experienced in 2 patients (0.4%). A shunt was inserted in 2.8% of the operations. The overall mortality/morbidity rate was 2.4%. Conclusion. A decrease of more than 50% in the amplitude of the thalamocortical somatosensory evoked potential complex N20/P25 proved to be the most reliable warning of danger of ischaemia during carotid endarterectomy. [ABSTRACT FROM AUTHOR]

The introduction of the first tyrosine kinase inhibitor imatinib into clinical practice has been associated with dramatical change in chronic myeloid leukaemia treatment over the past 20 years. It represents one of the biggest achievements in haematology and oncology per se. Imatinib was followed by second- and third generation tyrosine kinase inhibitors (nilotinib, dasatinib, bosutinib and ponatinib) resulting in newly dia­gnosed chronic myeloid leukaemia patients having almost the same life expectancy as the general population. Nevertheless, this often-lifelong treatment can be associated with side effects, which in extraordinary cases may be life threatening. Vascular adverse events are also included among such serious adverse events and their incidence varies over a wide range from 0.32–47.8%, most frequently in association with nilotinib or ponatinib treatment. Their incidence in daily clinical practice in the Czech Republic was evaluated in a retrospective analysis of the INFINITY database. From January 2005 to August 2020, chronic myeloid leukaemia was dia­gnosed in 1029 patients, with 1007 having valid records for analysis. Of these, 964 patients were in chronic phase. At least one vascular adverse event occurred in 82 patients (8.5%) in chronic phase during tyrosine kinase inhibitors therapy, most frequently in patients receiving nilotinib (10.8%) and ponatinib (8.3%). During first-line tyrosine kinase inhibitor treatment, 60 patients (6.3%) experienced at least one vascular adverse event. In direct comparison of first line imatinib and nilotinib therapy, we found a significantly higher incidence of cardiovascular (2.6 vs. 7.2%; P = 0.013), cerebrovascular (1.4 vs. 4.8%; P = 0.019), and peripheral vascular adverse events (0.2 vs. 4.0%; P = 0.001) in nilotinib treated patients, respectively. This paper offers a more detailed overview of vascular adverse event incidence in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors in clinical practice in the Czech Republic and its comparison with available literature. [ABSTRACT FROM AUTHOR]

Background: Our MIND database was initiated on May 1, 2013, with the primary objective of collecting data from patients with Ph negative myeloproliferative neoplasms (Ph-MPN) in Czech haematological centres. The principal aim was to analyse and compare our patient data with published data. Patients and Methods: A total of 641 valid Ph-MPN patients registered in MIND were analysed from 2013 to 2020. Epidemiology, dia-gnostics, therapy and prognosis were evaluated. Results: With a 35-month median follow-up, the most common dia-gnosis was polycythaemia vera- PV (34%) followed by primary myelofibrosis, PMF (31%) and essential thrombocythemia, ET (22%). At the time of dia-gnosis, patients suffered mostly from fatigue (52%), night sweats (32%), weakness (30%) and itching (27%). Splenomegaly occurred in more than half of PMF patients (54%). The JAK2 V617F mutation was present in 90% of PV, 65% of PMF and 62% of ET, respectively. The CALR mutation was found in 22% of ET and 16% of PMF, respectively. Cytogenetic abnormalities were significantly more frequently documented in both PMF and PV compared to ET (17 and 15 vs. 3% of examined patients, respectively; P ≤ 0.005). Thrombosis (22%) and bleeding (10%) were the most common complications at dia-gnosis with no significant difference in frequency among PV, ET, and PMF, respectively (P > 0.017). In PV, hydroxyurea was the most frequently used drug as both 1st and 2nd line treatment (72 and 65%, respectively). Anagrelide was used in both lines in ET (52 and 82%, respectively) and hydroxyurea was used as 1st line treatment with ruxolitinib as 2nd line treatment in PMF (70 and 30%, respectively). Leukemic transformation was detected in 3% of Ph-MPN and only in MF (10%). 17% of our patients died, most from PMF (53%). Median overall survival was not attained in ET, contrasting with the lowest median in secondary MF (2.5 years). In PMF, median overall survival was decreased by dotage, higher IPSS, and JAK2 V617F mutation presence. Conclusion: We have recognized a recurring definitive frequency of symptoms that exacerbate patient quality of life. A higher incidence of additional cytogenetic abnormalities was recorded more frequently with both PMF and PV compared to ET. During dia-gnosis, thrombotic and bleeding events were present with no significant difference in frequency among PV, ET, and PMF. Overall survival median was the longest in PV, compared to MF with the most frequent leukemic transformations and the lowest survival. In PMF, higher age, higher IPSS and JAK2 V617F presence were shown as factors shortening survival. [ABSTRACT FROM AUTHOR]

Experimental model based on the C5 ventral root avulsion was used to evaluate the efficacy of brain-derived neurotrophic factor (BDNF) and Cerebrolysin treatment on motor neuron maintenance and survival resulted in the functional reinnervation of the nerve stump. In contrast to vehicle, BDNF treatment reduced the loss and atrophy of motor neurons and enhanced the regrowth axon sprouts into the distal stump of musculocutaneous nerve. However, the axon diameter of the myelinated fibers was smaller than those of control rats. The morphometric results were related to a low score in behavioral test similar to vehicle-treated rats. Cerebrolysin treatment greatly protected the motor neurons against cell death. Moreover, morphometric features of myelinated axons were better than those of rats treated with vehicle or BDNF. The mean score of grooming test suggested better results of the functional motor reinnervation than after BDNF administration. The majority of rescued motor neurons regenerating their axons through nerve graft in both BDNF- and Cerebrolysin-treated rats expressed choline acetyltransferase immunostaining. The results demonstrate that BDNF has more modest effects in preventing the death of motor neurons and functional recovery of injured motor nerve after root avulsion than Cerebrolysin. [ABSTRACT FROM AUTHOR]

The results of 13 patients with end-to-side anastomosis of the axillary nerve to various donor nerves were presented. The results were evaluated by means of functional and electrophysiological methods following avulsion and subsequent reconstruction of the brachial plexus. End-to-side anastomosis of the rat musculocutaneous nerve (n=12), with the ulnar one, was used in the experimental model. The retrograde tracers were applied to prove the reinnervation.Fair and good results were achieved in neurotization of the axillary nerve in 75% of patients with follow-up longer than 24 months. Electrophysiology proved reinnervation in 100% of the patients. The average muscle strength, according to the muscle test, was 3.80. The functional recovery started within 7–12 months postoperatively.Retrograde staining in the experimental model demonstrated the reinnervation of the rat bicep muscles after 3 months from end-to-side anastomosis, mainly by collateral reinnervation from the ulnar nerve. The ulnar nerve motoneurons (70±13) were able to send off collateral sprouts from their intact axons into the musculocutaneous nerve. Other motoneurons of the same pool (21±4) regenerated axons directly into the musculocutaneous nerve without collateral sprouting, probably due to the axonotmesis of the motor fibers during the preparation of the perineurial window.Our results demonstrated that end-to-side anastomosis of the peripheral nerve might successfully be used for reinnervation procedures of a brachial plexus injury, mainly in cases with insufficient sources of motor nerve fibers from neighboring intact motor nerves. [Copyright &y& Elsevier]

Borrelia are microaerophilic spirochetes capable of causing multisystemic diseases such as Lyme disease and Relapsing Fever. The ubiquitous Fe/Mn-dependent superoxide dismutase (SOD) provides essential protection from oxidative damage by the superoxide anion. Borrelia possess a single SOD enzyme - SodA that is essential for virulence, providing protection against host-derived reactive oxygen species (ROS). Here we present a method for recombinant expression and purification of Borrelia burgdorferi SodA in E. coli. Metal exchange or insertion into the Fe/Mn-SOD is inhibited in the folded state. We therefore present a method whereby the recombinant Borrelia SodA binds to Mn under denaturing conditions and is subsequently refolded by a reduction in denaturant. SodA purified by metal affinity chromatography and size exclusion chromatography reveals a single band on SDS-PAGE. Protein folding is confirmed by circular dichroism. A coupled enzyme assay demonstrates SOD activity in the presence of Mn, but not Fe. The apparent molecular weight determined by size exclusion corresponds to a dimer of SodA; a homology model of dimeric SodA is presented revealing a surface Cys distal to the dimer interface. The method presented of acquiring a target metal under denaturing conditions may be applicable to the refolding of other metal-binding proteins. Image 1 • Recombinant Borrelia burgdorferi SodA is active in the presence of Mn, but not Fe. • B. burgdorferi SodA is a homodimer. • Recombinant B. burgdorferi SodA can be refolded from 8 M urea in the presence of Mn. [ABSTRACT FROM AUTHOR]