Being in Virtual Reality and Its Influence on Brain Health-An Overview of Benefits, Limitations and Prospects.

BACKGROUND: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical neuroscience due to their high accuracy, sensitivity and specificity and, above all, high ecological value. OBJECTIVE: Being in a digital world affects the functioning of the body as a whole and its individual systems. The data obtained so far, both from experimental and modeling studies, as well as (clinical) observations, indicate their great and promising potential, but apart from the benefits, there are also losses and negative consequences for users. METHODS: This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across electronic databases (such as Web of Science Core Collection; PubMed; and Scopus, Taylor & Francis Online and Wiley Online Library) to identify beneficial effects and applications, as well as adverse impacts, especially on brain health in human neuroscience. RESULTS: More than half of these articles were published within the last five years and represent state-of-the-art approaches and results (e.g., 54.7% in Web of Sciences and 63.4% in PubMed), with review papers accounting for approximately 16%. The results show that in addition to proposed novel devices and systems, various methods or procedures for testing, validation and standardization are presented (about 1% of articles). Also included are virtual developers and experts, (bio)(neuro)informatics specialists, neuroscientists and medical professionals. CONCLUSIONS: VR environments allow for expanding the field of research on perception and cognitive and motor imagery, both in healthy and patient populations. In this context, research on neuroplasticity phenomena, including mirror neuron networks and the effects of applied virtual (mirror) tasks and training, is of interest in virtual prevention and neurogeriatrics, especially in neurotherapy and neurorehabilitation in basic/clinical and digital neuroscience.

Impact of Virtual Reality Cognitive and Motor Exercises on Brain Health.

Innovative technologies of the 21st century have an extremely significant impact on all activities of modern humans. Among them, virtual reality (VR) offers great opportunities for scientific research and public health. The results of research to date both demonstrate the beneficial effects of using virtual worlds, and indicate undesirable effects on bodily functions. This review presents interesting recent findings related to training/exercise in virtual environments and its impact on cognitive and motor functions. It also highlights the importance of VR as an effective tool for assessing and diagnosing these functions both in research and modern medical practice. The findings point to the enormous future potential of these rapidly developing innovative technologies. Of particular importance are applications of virtual reality in basic and clinical neuroscience.

Temporomandibular joint disorders in patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study is to draw the attention of patients, doctors and therapists to the importance of temporomandibular joint (TMJ) problems in rheumatoid arthritis (RA). MATERIAL AND METHODS: The research was conducted at the National Institute of Geriatrics Rheumatology and Rehabilitation in Warsaw. The study involved 60 subjects. The test group consists of 30 patients with diagnosed RA. The control group (n = 30) consisted of healthy participants of similar age. The study analyzed the occurrence of problems in TMJ joints, acoustic phenomena and the level of pain. Masseter muscle development, range of abduction motion and pain during palpation of soft tissues were assessed on the basis of the joint pain map of Prof. Mariano Rocabado. RESULTS: In the RA group, more than half (56.7%) had problems with the TMJ, 70% of them had masseter hypertrophy and clicks in the TMJ, and 46.7% had tinnitus (in the control group: 10%, 30%, and 30%, respectively). Patients also had a limited range of abduction movement in the TMJ (38.0 ±6.1 mm). Analysis of the pain map of Prof. Mariano Rocabado in RA patients indicates a significantly greater number of pain structures. In the control group no pain was observed in structures such as the posterosuperior synovial and bilaminar zone, posterior ligament, or retrodiscal area. CONCLUSIONS: Temporomandibular joint problems in RA patients were more serious than in the control group and these differences were statistically significant for most tests. The awareness of the problem with the TMJ in RA patients is very low; participants of our study were 100% unaware that the function of the TMJ could be improved. Additionally, there are no guidelines for the treatment and rehabilitation of these joints.

A novel virtual reality approach for functional lateralization in healthy adults.

Functional lateralization relates to a natural asymmetry in the dominance right or left body side, and is a fundamental principle of the brain. The hemispheres of the brain control the contralateral body side, and show subtle, yet striking, anatomical asymmetries and functional lateralization. Innovative technologies, including Virtual Reality (VR), are entering the areas of experimental research, modeling and simulation related to the study of lateralization, with new perspectives of different applications in modern medical practice. Researchers/clinicians note that there are fewer VR studies with healthy participants, and which are important in evaluating/interpreting clinical outcomes, and testing the usefulness, limitations, and sensitivity of VR. The presented influence of the domination of upper/lower limbs on the performance of VR exercises was studied in healthy right-handed adults. Virtual testing sessions were performed independently with both/ dominant/ non-dominant hands, and the similar VR sessions were conduced on a Wii Balance Board (WBB) with the choice of body side, at different levels of the difficulty. The obtained results are consistent with other studies which show that cognitive-motor training in VR with the WBB platform is a very sensitive and promising tool for recognizing/assessing functional asymmetries of the right-left body side not only in disturbed lateralization, but also in the test training of healthy subjects.

Improving the quality of life of patients with rheumatoid arthritis after rehabilitation irrespective of the level of disease activity.

Due to the exacerbation of the disease, the rehabilitation of patients with rheumatoid arthritis is often limited. The aim of the study was to analyze the impact of a comprehensive rehabilitation on a subjective perception of pain and quality of life in patients with rheumatoid arthritis depending on the level of disease activity. The study involved 58 women with rheumatoid arthritis aged 18-60, who underwent a 4-weeks comprehensive rehabilitation program. The assessment included the disease activity level on the DAS28 scale, pain intensity on the 10-point pain scale (VAS) and the value of the CRP protein. The HAQ-DI and KALU questionnaire were used to assess the quality of life. In both groups (group A-DAS28 < 4.2, group B-DAS28 ≥ 4.2) the statistically significant effects in decreasing the level of pain and improvement of quality of life were observed. This indicates the need and effectiveness of rehabilitation regardless of the level of activity of rheumatoid arthritis according to the DAS28 scale. There were no significant changes in the CRP protein level. In conclusion, the rehabilitation of patients with moderate to high disease activity is effective and the success of comprehensive rehabilitation is demonstrated by the decrease of the DAS28 score and the pain level reported by patients, as well as improving self-assessment of health and quality of life.

Effects of whole body cryotherapy in patients with rheumatoid arthritis considering immune parameters.

OBJECTIVES: Whole body cryotherapy (WBC) is widely used in inflammatory diseases of the joints, including rheumatoid arthritis (RA), but the mechanism(s) of its action is not fully understood. The aim of the study was to compare the effects of WBC and conventional rehabilitation (CR) on the clinical and immune status of RA patients. MATERIAL AND METHODS: Rheumatoid arthritis patients were classified into 2 groups according to the rehabilitation method used: the study group (CT, n = 25) and control group (CR, n = 25). To measure disease activity, the disease activity score (DAS28) was used, while to assess the morning stiffness and pain intensity, the visual analogue scale (VAS) was applied. Selected laboratory parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were also determined. The serum concentrations of pro- (interleukin 6 [IL-6], tumor necrosis factor α [TNF-α], macrophage migration inhibitory factor [MIF]) and anti-inflammatory (IL-10) cytokines were measured to assess the patient's immune status. RESULTS: After rehabilitation disease activity (DAS28), morning stiffness and pain intensity (VAS) decreased in both patient groups and no statistically significant differences were observed between them. However, statistically significant improvement in the CRP serum level was observed in the CT group only. No differences were observed in the serum concentrations of tested cytokines either before and after rehabilitation, or between patient groups. CONCLUSIONS: We report that regardless of the type of therapy, comprehensive rehabilitation improves the patient's clinical status, but has no effect on the levels of circulating cytokines, such as IL-6, IL-10, TNF-α, and MIF, despite significant reduction of a systemic inflammatory marker (CRP), especially in the CT group.

Estimation of Posturographic Trajectory Using k-Nearest Neighbors Classifier in Patients with Rheumatoid Arthritis and Osteoarthritis.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic diseases and account for a significant percentage of disability. Posturography is a method that assesses postural stability and quantitatively evaluates postural sways. The objective of this study was to estimate posturographic trajectories applying pattern recognition algorithms. To this end, k-nearest neighbors (k-NN) classifier was used to differentiate between healthy subjects and patients with OA and RA. The following parameters of trajectories were computed: radius of sways, developed area, total length, and two directional components of sways: length of left-right and forward-backward motions. Posturographic tests were applied with eyes open and closed, and with biofeedback control. We found that in RA, the radius of sways, the trajectory area, and the biofeedback coordination were related to the patients' condition. The trajectory dynamics in OA patients were smaller compared to those in RA patients. The smallest misclassification errors were observed after feature selection in the biofeedback test compared with the eyes open and closed tests. We conclude that the estimation of posturographic trajectory with k-NN classifier could be helpful in monitoring the condition of RA patients.

Benefits of wrist splinting in patients with rheumatoid arthritis.

OBJECTIVES: The goal was to present the use of a functional wrist splint and its impact on hand function in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: The study group comprised 104 women aged 18-65 and diagnosed with RA, who were treated in the Rheumatology Clinic and Outpatient Department of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw. The control group consisted of 40 healthy women in the same age group. Assessment of the hand function was the research method. RESULTS: Our results revealed substantially deteriorated function of the rheumatoid hand in relation to the healthy hand. The use of a wrist stabiliser is justified in patients with RA due to its beneficial impact, such as improved hand strength and dexterity and reduced pain. Based on the results obtained, it may be assumed that it is mainly patients with moderate and high disease activity who require stabilisation. The small number of patients in remission and with low disease activity was a limitation of the study. Hands with RA require an individual approach, and the most effective methods slowing down development of deformation should be sought. The results presented in this article may provide a starting point for further research on the most favourable wrist stabilisation in order to improve hand function in RA. CONCLUSIONS: Our study showed that the hand function of women with RA is limited due to deteriorated grip quality and manual dexterity in comparison to healthy persons. Wrist stabilisation improves hand function in patients with RA.

Discriminant Analysis of Intracranial Volumetric Variables in Patients with Normal Pressure Hydrocephalus and Brain Atrophy.

A method was developed for the computerized volumetric assessment of the intracranial cerebrospinal fluid (CSF) distribution. The study involved 62 patients differentiated into two groups: with CSF resorption disorders (normal pressure hydrocephalus - 30 patients) and without CSF resorption disorders (various types of brain atrophy - 32 patients). The goal of the study was to ascertain whether the assessment, depending on the linear discriminant analysis of volumetric brain features, could be an effective tool differentiating the two groups. Volumetric measurements were performed using VisNow software. For each patient, five features were determined and subjected to discriminant analysis: CSF volume in the subarachnoid space and basal cisterns (SV), CSF volume in the intracranial ventricular system (VV), brain volume (BV), total intracranial CSF volume (FV), and total intracranial volume (TV). Discriminant analysis enables the achievement of a high percentage of correct classification of patients to the appropriate group determined on the result of a lumbar infusion test. The discriminator, based on three features: BV, SV, and VV, showed a complete separation of the groups; irrespective of age. The squared Mahalanobis distance was 70.8. The results confirmed the applicability of the volumetric method. Discriminant analysis seems a useful tool leading to the acquisition of a computer-aided method for the differential diagnosis of CSF resorption disorders.

Dysfunctional lamins as mediators of oxidative stress in Emery-Dreifuss muscular dystrophy.

Deficit of lamin A/C or emerin causes genetically transmitted Emery-Dreifuss muscular dystrophy (EDMD). As lamins are considered to be mediators of oxidative stress, the antioxidant/oxidant status was examined. The total oxidant/antioxidant status in serum was examined in 29 cases of Emery-Dreifuss muscular dystrophy. The study included 12 autosomal-dominant laminopathies (AD-EDMD), 17 X-linked emerinopathies (X-EDMD) and 20 age-matched normal subjects. Total oxidant status (TOS) was reduced in all cases, and the total antioxidant capacity (TAC) was found to be decreased in the majority of the patients (in 82.8%). A relationship between TOS level and disease progression was noted. No correlation between TOS/TAC level and cardiological or neurological parameters was detected. The results of the study indicate disturbances of redox balance in EDMD patients. Determination of TOS/TAC might help to assess the progress of the disease and the potential effectiveness of antioxidant therapy.

The beneficial effects of rehabilitation on hand function in patients with rheumatoid arthritis.

OBJECTIVES: The hand is one of the main elements of the rehabilitation of patients with rheumatoid arthritis (RA) due to deformities, which occur in approximately 90% of patients. It is a serious problem, both in the psychological and functional aspect, connected with muscle strength reduction, a limited range of motion and non-acceptance of the changes in the shape of the limb. The study aimed to assess the effect of rehabilitation on the function of the hand in rheumatoid arthritis. MATERIAL AND METHODS: The study group consisted of 40 women with RA. The patients had been previously treated at the Rehabilitation Department of the National Institute of Geriatrics, Rheumatology and Rehabilitation in Warsaw. The study group underwent 3 weeks of rehabilitation involving individual therapy, exercises with equipment, patient education and physical therapy. The control group included women without a diagnosis of RA, hands pain-free and fully mobile. In both groups the hand was assessed for grip value, grip quality and manipulative ability. In the study group the basis of pain intensity was noted. The measurements were performed twice - prior to the rehabilitation and after 3 weeks of rehabilitation in women with RA and once in women without hand problems. RESULTS: The results obtained revealed marked limitation of hand function in patients with rheumatoid arthritis. The treatment resulted in an improvement of all assessed parameters except cylindrical grip, in which only a part of the findings was statistically significant. CONCLUSIONS: The analysis of the study material showed that appropriately adjusted and conducted hand physiotherapy in women with rheumatoid arthritis contributed to the improvement of its function by pain reduction, improved value and quality of grip, and also increased manipulative ability.

Tissue inhibitors of matrix metalloproteinases in serum are cardiac biomarkers in Emery-Dreifuss muscular dystrophy.

BACKGROUND: Tissue inhibitors of matrix metalloproteinases (TIMPs) are known to be involved in cardiovascular diseases. Hitherto, they have not been examined in dilated cardiomyopathy in the course of Emery-Dreifuss muscular dystrophy (EDMD). AIM: To define TIMPs in serum because they might help in defining cardiac dysfunction at the early cardiological stages of this disease and detect preclinical stages of cardiomyopathy. METHODS: Twenty-five EDMD patients connected with lamin A/C (AD-EDMD) or emerin (X-EDMD) deficiency and 20 healthy age-matched controls were examined. The serum levels of the tissue inhibitors TIMP-1, -2, -3 were quantified using the ELISA sandwich immunoassay procedure with appropriate antibodies. RESULTS: Serum levels of TIMP-1 were normal in autosomal AD-EDMD and increased in the majority of X-linked EDMD. The level of TIMP-2 was decreased in 25%/21% of AD-EDMD/X-EDMD cases. TIMP-3 serum level was significantly reduced in all the examined patients. Receiver operating curves indicated that in terms of sensitivity and specificity characteristics the performance of TIMP-3 (less that of TIMP-2) makes them the best markers of cardiac involvement among the examined TIMPs. CONCLUSIONS: Evidence shows that the levels of TIMP-3, and in some cases also TIMP-2, are decreased in EDMD. The decrease might be associated with an adverse effect on matrix metalloproteinases and remodelling of the myocardial matrix. The specific decrease of TIMP-3 indicates that this biomarker might help in early detection of cardiac involvement in EDMD. Up-regulation of TIMP-1 in the majority of patients with X-EDMD indicates increased myocardial extracellular matrix turnover, early onset of tissue remodelling, and may contribute to arrhythmia, frequently occurring in this form of the disease.

The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases.

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified. We decided to explore if the LITAF/SIMPLE gene shared a functional link to the PMP22 gene, whose duplication or deletion results in CMT1A and HNPP, respectively. By studying a large cohort of CMT1A/HNPP-affected patients, we found that the LITAF I92V sequence variant predisposes patients to an earlier age of onset of both the CMT1A and HNPP diseases. Using cell transfection experiments, we showed that the LITAF I92V sequence variant partially mislocalizes to the mitochondria in contrast to wild-type LITAF which localizes to the late endosome/lysosomes and is associated with a tendency for PMP22 to accumulate in the cells. Overall, this study shows that the I92V LITAF sequence variant would be a good candidate for a biomarker in the case of the CMT1A/HNPP disorders.

Posturography in differential diagnosis of normal pressure hydrocephalus and brain atrophy.

Differentiation between normal pressure hydrocephalus (NPH) and brain atrophy is difficult in clinical practice. The purpose of this paper was to apply two advanced statistical, pattern recognition methods: discriminant analysis (DA) and k-nearest neighbour (K-NN) for the classification of NPH and atrophy patients to approach computer aided differential diagnosis. The classification is based on a few measures of the center of foot pressure (COP) movements (radius, area, and length). The posturography method gives a measure of current postural stability by a quantitative evaluation of postural sways. Measurements have been performed in the standing upright position in two conditions: with eyes open (EO) and closed (EC). The study comprises 18 patients (mean age 64 ±13 years) diagnosed as normal pressure hydrocephalus and qualifying for shunt implantation. The patients were evaluated by static posturography twice: before and after surgery. The NPH patients were compared with 36 atrophy patients (mean age 64±13 years) and 47 healthy persons (mean age 60 ±7 years). There were two basic dissimilarities in the NPH patients before surgery in comparison with the other groups: very large sways and their independence from vision. Over 90% of the NPH cases both before and after surgery were correctly classified. There also were over 90% of correctly classified patients if we compared the before surgery NPH and atrophy patients. Further posturographic measurements and data collection are needed to verify these results.

Osteopontin--a fibrosis-related marker--in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy.

BACKGROUND: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). METHODS: Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies--X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. RESULTS: The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. CONCLUSIONS: The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.

Circulating tenascin-C levels in patients with dilated cardiomyopathy in the course of Emery-Dreifuss muscular dystrophy.

BACKGROUND: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is of diagnostic and prognostic value in different heart diseases. One such dilated cardiomyopathy (DCM) with conduction disturbances is one of the most serious manifestations in Emery-Dreifuss muscular dystrophy (EDMD). Herein we therefore detail work to evaluate the potential significance of circulating TN-C in patients with EDMD, speculating that it may define the cardiac dysfunction, especially in patients who may be cardiac asymptomatic, but still be at risk of sudden death. MATERIAL AND METHOD: Serum levels of TN-C were quantified by sandwich immunoassay ELISA in 25 EDMD patients (10 with laminopathy-AD-EDMD and 15 with emerinopathy-X-EDMD), 8 X-EDMD carriers, 9 disease controls (patients with dystrophinopathy), and 15 age-matched healthy controls. Fourteen of the EDMD patients had repeated TN-C examinations after 3 to 7 years. RESULTS: The levels of circulating TN-C were elevated in AD-EDMD and X-EDMD patients, as well as in some X-EDMD carriers, and patients with dystrophinopathy. The correlation between the TN-C level and left end-systolic ventricle diameter (LVDD) was significant in X-EDMD, while those with left atrium diameter (LAD) and the ejection fraction (EF) were not. In "follow-up" studies TN-C levels were not found to change over time in AD-EDMD, while rising in X-EDMD. CONCLUSIONS: The presented results indicate that assessments of circulating TN-C levels may help to identify EDMD patients at risk of dilated cardiomyopathy. TN-C might therefore be considered a candidate for a new biomarker, useful in detecting of cardiomyopathy and in further monitoring of the DCM therapy in patients with EDMD.

The role of AlkB protein in repair of 1,N6-ethenoadenine in Escherichia coli cells.

Etheno (ε) DNA adducts, including 1,N(6)-ethenoadenine (εA), are formed by various bifunctional agents of exogenous and endogenous origin. The AT→TA transversion, the most frequent mutation provoked by the presence of εA in DNA, is very common in critical codons of the TP53 and RAS genes in tumours induced by exposure to carcinogenic vinyl compounds. Here, using a method that allows examination of the mutagenic potency of a metabolite of vinyl chloride, chloroacetaldehyde (CAA), but eliminates its cytotoxicity, we studied the participation of alkA, alkB and mug gene products in the repair of εA in Escherichia coli cells. The test system used comprised the pIF105 plasmid bearing the lactose operon of CC105 origin, which allowed monitoring of Lac(+) revertants that arose by AT→TA substitutions due to the modification of adenine by CAA. The plasmid was CAA-modified in vitro and replicated in E.coli of various genetic backgrounds (wt, alkA, alkB, mug, alkAalkB, alkAmug and alkBmug). To modify the levels of the AlkA and AlkB proteins, mutagenesis was studied in E.coli cells induced or not in adaptive response to alkylating agents. Considering the levels of CAA-induced Lac(+) revertants in strains harbouring the CAA-modified pIF105 plasmid and induced or not in adaptive response, we conclude that the AlkB dioxygenase plays a major role in decreasing the level of AT→TA mutations, thus in the repair of εA in E.coli cells. The observed differences of mutation frequencies in the various mutant strains assayed indicate that Mug glycosylase is also engaged in the repair of εA, whereas the role the AlkA glycosylase in this repair is negligible.

Chloroacetaldehyde-induced mutagenesis in Escherichia coli: the role of AlkB protein in repair of 3,N(4)-ethenocytosine and 3,N(4)-alpha-hydroxyethanocytosine.

Etheno (epsilon) adducts are formed in reaction of DNA bases with various environmental carcinogens and endogenously created products of lipid peroxidation. Chloroacetaldehyde (CAA), a metabolite of carcinogen vinyl chloride, is routinely used to generate epsilon-adducts. We studied the role of AlkB, along with AlkA and Mug proteins, all engaged in repair of epsilon-adducts, in CAA-induced mutagenesis. The test system used involved pIF102 and pIF104 plasmids bearing the lactose operon of CC102 or CC104 origin (Cupples and Miller (1989) [17]) which allowed to monitor Lac(+) revertants, the latter arose by GC-->AT or GC-->TA substitutions, respectively, as a result of modification of guanine and cytosine. The plasmids were CAA-damaged in vitro and replicated in Escherichia coli of various genetic backgrounds. To modify the levels of AlkA and AlkB proteins, mutagenesis was studied in E. coli cells induced or not in adaptive response. Formation of varepsilonC proceeds via a relatively stable intermediate, 3,N(4)-alpha-hydroxyethanocytosine (HEC), which allowed to compare repair of both adducts. The results indicate that all three genes, alkA, alkB and microg, are engaged in alleviation of CAA-induced mutagenesis. The frequency of mutation was higher in AlkA-, AlkB- and Mug-deficient strains in comparison to alkA(+), alkB(+), and microg(+) controls. Considering the levels of CAA-induced Lac(+) revertants in strains harboring the pIF plasmids and induced or not in adaptive response, we conclude that AlkB protein is engaged in the repair of epsilonC and HEC in vivo. Using the modified TTCTT 5-mers as substrates, we confirmed in vitro that AlkB protein repairs epsilonC and HEC although far less efficiently than the reference adduct 3-methylcytosine. The pH optimum for repair of HEC and epsilonC is significantly different from that for 3-methylcytosine. We propose that the protonated form of adduct interact in active site of AlkB protein.

Matrix metalloproteinases in serum of Emery-Dreifuss muscular dystrophy patients.

In the pathogenesis of dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD) matrix metalloproteinases (MMPs) are supposed to be involved and may have diagnostic/prognostic value. Serum levels of MT1-MMP, MMP-2 and MMP-9 were quantified by ELISA and zymography in 22 EDMD patients and 15 age-matched controls. In the autosomal-dominant EDMD MMP-2 and MT1-MMP were increased in all cases, and MMP-9 was increased in two of the eight examined patients. In the X-linked EDMD MMP-2 expression was increased in all the cases, MMP-9 level was elevated in 3 of the 14 cases, and MT1-MMP was decreased in eight of these patients. There was no evident correlation between the MMPs level and the different cardiac parameters including left-ventricular end-diastolic diameter, left atrial diameter and left ventricular ejection fraction in either form of EDMD. The presented results indicate that a changed level of matrix metalloproteinases, especially that of MMP-2 in serum, may be of value for detection of cardiac involvement in EDMD patients, especially in those patients with no evident subjective cardiac symptoms. Further follow-up studies of MMPs are needed to check if their determination is of value for monitoring of the progression of atrial/ventricular dilatation. MMPs determinations may also be useful for monitoring DCM treatment by synthetic MMPs inhibitors.