p.L1795F LRRK2 variant is a common cause of Parkinson's disease in Central Europe.

Pathogenic variants in LRRK2 are one of the most common genetic risk factors for Parkinson's disease (PD). Recently, the lesser-known p.L1795F variant was proposed as a strong genetic risk factor for PD, however, further families are currently lacking in literature. A multicentre young onset and familial PD cohort (n = 220) from 9 movement disorder centres across Central Europe within the CEGEMOD consortium was screened for rare LRRK2 variants using whole exome sequencing data. We identified 4 PD cases with heterozygous p.L1795F variant. All 4 cases were characterised by akinetic-rigid PD phenotype with early onset of severe motor fluctuations, 2 receiving LCIG therapy and 2 implanted with STN DBS; all 4 cases showed unsatisfactory effect of advanced therapies on motor fluctuations. Our data also suggest that p.L1795F may represent the most common currently known pathogenic LRRK2 variant in Central Europe compared to the more studied p.G2019S, being present in 1.81% of PD cases within the Central European cohort and 3.23% of familial PD cases. Together with the ongoing clinical trials for LRRK2 inhibitors, this finding emphasises the urgent need for more ethnic diversity in PD genetic research.

Exploring CJD incidence trends: insights from Slovakia.

Authors are commenting on the evolving geographical incidence trends observed with the genetic form of Creutzfeldt-Jakob disease and discussing the diverse array of factors contributing to the heightened incidence rates observed in specific geographical regions.

Predictors of Outcome after Direct Aspiration of Basilar Artery Occlusion.

Background: Basilar artery occlusion (BAO) is a serious disease with a poor prognosis if left untreated. Endovascular therapy (EVT) is the most effective treatment that is able to reduce mortality and disability. Treatment results are influenced by a wide range of factors that have not been clearly identified. In the present study, direct aspiration was chosen as a first-line treatment. The safety and effectiveness of direct aspiration in BAO were determined, and factors affecting patient outcomes were identified. Methodology: Data for patients with BAO treated between November 2013 and December 2021 were evaluated using a database. The association between clinical and procedural parameters and functional outcome was assessed. Results: A total of 89 patients with BAO were identified. Full recanalization was achieved in 69.7% of cases and partial recanalization in 19.1%. Intracranial hemorrhage was detected in 11 (12.4%) patients, of which, eight (9.0%) patients experienced symptomatic intracranial hemorrhage. Patients with good outcomes presented with milder strokes (mean NIHSS score of 12.58 vs. 24.00, p < 0.001), had higher collateral scores (6.79 vs. 5.88, p = 0.016), more often achieved complete recanalization (87.9% vs. 58.9%, p = 0.009), and more often experienced early neurological improvement (66.7% vs. 26.8%, p < 0.001). On the contrary, patients with worse outcomes had higher serum glucose levels (p = 0.05), occlusion of the middle portion of the basilar artery (MAB) (30.3% vs. 53.6%, p = 0.033), longer thrombus lengths (10.51 vs. 16.48 mm, p = 0.046), and intracranial hemorrhage (p = 0.035). Conclusions: The present study results suggest that direct aspiration is a safe and effective treatment for patients with BAO. We identified several factors affecting the patients' outcome.

Dyskinesia and Pain in Advanced Parkinson's Disease: Post Hoc Analysis from the Phase 3b, Open-Label, Randomized DYSCOVER Study.

INTRODUCTION: The DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD. METHODS: This post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60). RESULTS: Among 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001). CONCLUSIONS: In patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02799381.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Modelling Duchenne muscular dystrophy in vitro with newly generated, blood cell-derived induced pluripotent stem cell line ORIONi003-A.

Here, we present newly derived in vitro model for modeling Duchenne muscular dystrophy. Our new cell line was derived by reprogramming of peripheral blood mononuclear cells (isolated from blood from pediatric patient) with Sendai virus encoding Yamanaka factors. Derived iPS cells are capable to differentiate in vitro into three germ layers as verified by immunocytochemistry. When differentiated in special medium, our iPSc formed spontaneously beating cardiomyocytes. As cardiomyopathy is the main clinical complication in patients with Duchenne muscular dystrophy, the cell line bearing the dystrophin gene mutation might be of interest to the research community.

Analysis of Cdx2 VDR gene polymorphism rs11568820 in association with multiple sclerosis in Slovaks.

Vitamin D deficiency is involved in the pathogenesis of multiple sclerosis (MS), a severe autoimmune demyelinating disease of the central nervous system. The gene polymorphism Cdx-2 (rs11568820, G/A) seriously influences the trancriptional activity of the vitamin D receptor (VDR) that binds the vitamin D responsive elements of target genes including HLA-DRB1*15. The aim of the present study in Slovaks was to analyse the association of Cdx-2 variants with the risk of MS and disability progression, and to assess the DRB1*15:01 allele as a possible confounding factor. In total, 493 MS patients and 417 healthy controls were involved in this study. The genotyping of Cdx-2 was performed using restriction analysis; DRB1*15:01 positivity was determined by a high-resolution melting analysis of its surrogate marker rs3135388 (G/A). Our results did not prove any allelic association between Cdx-2 and a risk of MS (minor allele A - 0.181 in patients vs. 0.161 in controls, OR = 1.15, .95 CI = 0.90-1.47, p = 0.289). The logistic regression analysis, adjusted for sex and age, showed no differences in Cdx-2 genotype counts when using an additive, dominant or recessive genetic model (p = 0.351, 0.150, 0.240 respectively). The Cdx-2 variants were also not associated with disease disability progression, evaluated using the Multiple Sclerosis Severity Score. The HLA-DRB1*15:01 allele was found to strongly increase the risk of MS in our study (0.300 in patients vs. 0.101 in controls, OR = 3.83, .95 CI = 2.94-4.99, p = 1.016 × 10-26, dominant genetic model OR = 4.62, .95 CI = 3.40-6.26, p = 9.1 × 10-23). In summary, we found the Cdx-2 as a single genetic marker not to be associated with MS development or progression in Slovaks, independently of HLA-DRB1*15:01 status.

Biomedical research brings mTBI biomarkers a step closer to the bedside - implementation in clinical practice.

Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of this work is to identify mTBI (mild traumatic brain injury) patients who are unlikely to benefit from CT (computed tomography) scanning. Biomarkers capable of clearly discriminating between CT-positive and CT-negative subjects are needed. Biomarkers hold the potential to document whether a concussion occurred, especially when the history is unclear and neurocognitive sequelae persist. Recently, following advances in proteomics analysis, investigators have introduced ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) as two promising brain injury biomarkers. The authors provide an update on the current knowledge of TBI biomarkers, especially protein biomarkers for neuronal cell body injury (UCH-L1) and astroglial injury (GFAP, S100B), and a focused literature review dealing with implementation of mTBI biomarkers in clinical practice.

Safety and efficacy of simple training protocol in patients after mild traumatic brain injury.

AIMS: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of selected training protocol in patients after mTBI. METHODS: This was a prospective study that included 25 patients with mTBI and 25 matched healthy controls. Assessments were performed in two sessions and included a post-concussion symptoms questionnaire, battery of neurocognitive tests, and magnetic resonance with tractography. Participants were divided into two groups: a passive subgroup with no specific recommendations and an active subgroup with simple physical and cognitive training. RESULTS: The training program with slightly higher initial physical and cognitive loads was well tolerated and was harmless according to the noninferiority test. The tractography showed overall temporal posttraumatic changes in the brain. The predictive model was able to distinguish between patients and controls in the first (AUC=0.807) and second (AUC=0.652) sessions. In general, tractography had an overall predictive dominance of measures. CONCLUSION: The results from our study objectively point to the safety of our chosen training protocol, simultaneously with the signs of slight benefits in specific cognitive domains. The study also showed the capability of machine learning and predictive models in mTBI patient recognition.

Embolization of Ruptured Infratentorial Pial AVM in Pregnancy.

A primigravida 22-year-old woman, at a gestation of 23 weeks, experienced bleeding from a pial arteriovenous malformation (AVM) located in the right cerebellum. After interdisciplinary consensus and with the informed consent of the patient and her family, AVM embolization was performed. Complete occlusion of the AVM was achieved by embolization with PHIL (precipitating hydrophobic injectable liquid). The calculated dose in the uterus was less than 1 µSv, which represents a negligible risk of harmful effects on the fetus. She delivered a baby at 37 weeks of gestation by cesarean section without complications. No congenital disorders were diagnosed by standard screening methods until the age of the newborn was two years. The angiography protocol must be optimized to minimize the radiation dose. Adequate shielding protection of the uterus is important. Premature termination of pregnancy is not necessary. Multidisciplinary care of neurologists, neurosurgeons, interventional radiologists, anesthesiologists, neonatologists, and obstetricians is necessary.

A high-throughput liquid chromatography-tandem mass spectrometry method for simultaneous determination of direct oral anticoagulants in human plasma.

Direct oral anticoagulants are widely used in many indications to prevent thromboembolic events. Routine therapeutic monitoring is not required; however, there is increasing evidence suggesting the benefit of plasma level measurement in some situations. In addition, laboratory monitoring might help improve patient and drug non-compliance and thus individualize therapy. In the present study, we developed a sensitive and high throughput ultra-high-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification of apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma. A one-step extraction procedure in 96-well formate for phospholipid and protein removal was used for sample pre-treatment, and analytes were separated using gradient elution over 4.2 min. Analytes were detected on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode. The method was validated according to the European Medicine Agency guideline for the selectivity, linearity, and lower limit of detection, precision and accuracy, matrix effects, extraction recovery, carryover, dilution integrity, and stability over a concentration range of 3.0-1000 ng/ml for all analytes. The validated method was applied to real clinical samples of patients treated with one of the drugs. Therefore, we can conclude that our method is suitable for therapeutic drug monitoring of direct oral anticoagulants.

Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance.

Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical metabolism; (2) induced proinflammatory processes; and (3) the aggregation of amyloid beta and hyperphosphorylated Tau proteins. Subclinical AD changes are commonly detectable by using radiological and nuclear neuroimaging methods such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Furthermore, other valuable modalities exist (in particular, structural volumetric, diffusion, perfusion, functional, and metabolic magnetic resonance methods) that can advance the diagnostic algorithm of AD and our understanding of its pathogenesis. Recently, new insights into AD pathoetiology revealed that deranged insulin homeostasis in the brain may play a role in the onset and progression of the disease. AD-related brain insulin resistance is closely linked to systemic insulin homeostasis disorders caused by pancreas and/or liver dysfunction. Indeed, in recent studies, linkages between the development and onset of AD and the liver and/or pancreas have been established. Aside from standard radiological and nuclear neuroimaging methods and clinically fewer common methods of magnetic resonance, this article also discusses the use of new suggestive non-neuronal imaging modalities to assess AD-associated structural changes in the liver and pancreas. Studying these changes might be of great clinical importance because of their possible involvement in AD pathogenesis during the prodromal phase of the disease.

Oxidative stress parameters and their relation to motor subtype of Parkinson's disease and levodopa treatment status.

Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome: Treatment approach depends on disease course.

INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare inflammatory central nervous system (CNS) disorder, chiefly involving the brainstem, especially the pons. The diagnosis is challenging, requires careful exclusion of alternative diagnoses and a targeted therapeutic approach. CLIPPERS is known to respond well to corticosteroids, but the treatment needs to be long-term and can cause significant side-effects. Moreover, subsequent corticosteroid withdrawal often leads to a relapse. It has been suggested that anti-CD20 molecules could benefit several antibody-mediated CNS inflammatory diseases, including CLIPPERS. CASE REPORT: This paper describes two cases of CLIPPERS. The first demonstrates the benefit of early introduction of corticosteroids with side effects in cases of long-term use. The second demonstrates the efficacy of ocrelizumab (anti-CD20 molecule) in a severe course of CLIPPERS. CONCLUSION: These two cases bring attention to this rare, often misdiagnosed but treatable disease.

Lesion-Specific Metabolic Alterations in Relapsing-Remitting Multiple Sclerosis Via 7 T Magnetic Resonance Spectroscopic Imaging.

BACKGROUND: Magnetic resonance spectroscopic imaging (MRSI) of the brain enables in vivo assessment of metabolic alterations in multiple sclerosis (MS). This provides complementary insights into lesion pathology that cannot be obtained via T1- and T2-weighted conventional magnetic resonance imaging (cMRI). PURPOSE: The aims of this study were to assess focal metabolic alterations inside and at the periphery of lesions that are visible or invisible on cMRI, and to correlate their metabolic changes with T1 hypointensity and the distance of lesions to cortical gray matter (GM). METHODS: A 7 T MRSI was performed on 51 patients with relapsing-remitting MS (30 female/21 male; mean age, 35.4 ± 9.9 years). Mean metabolic ratios were calculated for segmented regions of interest (ROIs) of normal-appearing white matter, white matter lesions, and focal regions of increased mIns/tNAA invisible on cMRI. A subgroup analysis was performed after subdividing based on T1 relaxation and distance to cortical GM. Metabolite ratios were correlated with T1 and compared between different layers around cMRI-visible lesions. RESULTS: Focal regions of, on average, 2.8-fold higher mIns/tNAA than surrounding normal-appearing white matter and with an appearance similar to that of MS lesions were found, which were not visible on cMRI (ie, ~4% of metabolic hotspots). T1 relaxation was positively correlated with mIns/tNAA ( P ≤ 0.01), and negatively with tNAA/tCr ( P ≤ 0.01) and tCho/tCr ( P ≤ 0.01). mIns/tCr was increased outside lesions, whereas tNAA/tCr distributions resembled macroscopic tissue damage inside the lesions. mIns/tCr was -21% lower for lesions closer to cortical GM ( P ≤ 0.05). CONCLUSIONS: 7 T MRSI allows in vivo visualization of focal MS pathology not visible on cMRI and the assessment of metabolite levels in the lesion center, in the active lesion periphery and in cortical lesions. This demonstrated the potential of MRSI to image mIns as an early biomarker in lesion development.

Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei.

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory demyelinating disease leading not only to physical disability but also to cognitive dysfunction. The aim of our study was to test cognitive functions of MS patients with mild relapsing-remitting form and to find out the relationship between cognitive functions and brain volumetry. METHODS: 52 patients (RRMSp) and 23 age-related healthy participants (CON) were enrolled. Mild disability was defined by mean EDSS 2.4 (≤ 4.0), and by median of disease duration 5.2 years. Cognitive status was tested using Single Digit Modality Test (SDMT). Brain volumetry was processed in FreeSurfer 2.0.0. RESULTS: RRMSp patients showed significantly lower SDMT score than CON. SDMT results correlated positively with volume of thalamus, putamen and nc. caudate, and negatively with optic chiasma volume. Compared with CON, RRMSp presented with significantly lower volume in left and right nc. accumbent, cuneus and insular GM, right putamen, total brain cortical grey matter (GM), white matters hypointensities, and 3rd ventricular widths. CONCLUSION: To our best knowledge, this is the first study that presents results showing a correlation of lower SDMT with higher optic chiasma volume, due to its subclinical chronic demyelination. We confirmed that GM atrophy is involved in cognitive functions in MS (Tab. 3, Fig. 2, Ref. 73).

Alzheimer's Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis.

Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer's disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. CD33 rs3865444 was genotyped in a cohort of 579 patients and 1145 controls and its association with MS risk and clinical phenotypes was analyzed by logistic and linear regression analysis, respectively. Statistical evaluation revealed that rs3865444 reduces the risk of MS in the HLA-DRB1*15:01-positive subpopulation but not in the cohort negative for HLA-DRB1*15:01. A significant antagonistic epistasis between rs3865444 A and HLA-DRB1*15:01 alleles in the context of MS risk was detected by the interaction synergy factor analysis. Comparison of allele and genotype distribution between relapsing-remitting MS, secondary progressive MS, and control groups revealed that rs3865444 C to A substitution may also be associated with a decreased risk of transition of MS to its secondary progressive form, irrespective of the HLA-DRB1*15:01 carrier status. On the other hand, no correlation could be found between rs3865444 and the age of disease onset or MS severity score. Future studies are required to shed more light on the role of CD33 in MS pathogenesis.

Comparison of Restenosis Risk in Single-Layer versus Dual-Layer Carotid Stents: A Duplex Ultrasound Evaluation.

PURPOSE: The aim of this study was to report intermediate-term results of duplex ultrasound follow-up of carotid artery stenting performed with the dual-layer stent as compared to concurrent patients treated with other commercially available single-layer carotid stents. MATERIALS AND METHODS: A single centre, retrospective, nonrandomized study including 162 non-consecutive patients with 199 implanted carotid stents treated over a 7-year period was conducted. Patients with at least one ultrasound examination after treatment were included. Procedural and follow-up data for patients treated with the dual-layer stent implantation (83 stents) vs first-generation carotid stents implantations (116 stents) were compared. RESULTS: The median follow-up time was 24.0 months (IQR 10-32 months) for dual-layer stents and 27.5 months (IQR 10.3-59 months) for single-layer stents. The rate of severe restenosis was significantly higher in the dual-layer stent group than in the single-layer group (13.3% [11/83] vs 3.4% [4/116], p = 0.01). Seven reinterventions were performed in 5 patients with dual-layer stents. The rate of reintervention was significantly higher compared to no reinterventions in single-layer stents (6% [5/83] vs 0% [0/116], p = 0.012). Patients with restenosis had significantly higher presence of dyslipidaemia (100% [12/12] vs 63.3% [95/150], p = 0.009). CONCLUSIONS: In this real-world cohort of patients undergoing carotid artery stenting, the patients treated with low-profile dual-layer micromesh stent showed higher rates of restenosis and reinterventions compared to first-generation single-layer stents.

In vitro modeling of amyotrophic lateral sclerosis with induced pluripotent stem cell technology-derived cell line ORIONi002-A.

We present here a new iPS cell line for modeling sporadic form of ALS. Cell line was generated by reprogramming skin fibroblasts isolated with explant culture technology from skin biopsy, donated by ALS patient. For reprogramming, polycistronic self-replicating RNA vector was used and derived iPS cells were characterized by immunocytochemistry and FACS (pluripotent factors expression), karyotyping, STR fingerprinting analysis and in vitro differentiation assay. New cell line showed normal (46, XY) karyotype and differentiated in vitro into cells from three germ layers. STR analysis proved the origin and originality of the cell line.