Novel variants in the NARS2 gene as a cause of infantile-onset severe epilepsy leading to fatal refractory status epilepticus: case study and literature review.

Biallelic variants in the NARS2 gene are the cause of a continuous spectrum of neurodegenerative disorders presenting with various severity-from spastic paraplegia, progressive neurodegeneration to Leigh and Alpers syndrome. Common clinical signs result from a mitochondrial dysfunction based on OXPHOS deficiency. Here, we present a patient with infantile-onset severe epilepsy leading to fatal refractory status epilepticus. Whole exome sequencing with Exomiser analysis based on HPO terms detected two novel NARS2 variants in a compound heterozygous state. To date, 18 different NARS2 disease-causing mutations have been described. Our study adds to the understanding of this mitochondrial disorder.

[A Development and Overview of the Use of Chemotherapy and the Role of Radiotherapy and Surgery in Patients with Newly Diagnosed Pancreatic Tumor and Cancer in the Current 5-year Center Practice]. / Vývoj a prehled vyuzití chemoterapie a role radioterapie a chirurgie u pacientu s nove diagnostikovaným tumorem a karcinomem pankreatu v bezné 5leté praxi centra.

BACKGROUND: Chemotherapy (CHT), surgery and radiotherapy (RT) are essential modalities in the treatment of pancreatic malignancies. Their use in practice may be influenced by a number of factors. PATIENTS AND METHODS: Retrospective analysis of CHT, surgery and RT indications and CHT results in patients reported with pancreatic tumor in Pilsen in 2012-2016. RESULTS: A total of 348 patients with median age 68 (19-89) years with newly diagnosed pancreatic tumor, resp., with histology/cytology verified carcinoma in 74.5% cases, with v. s. carcinoma without verification in 21% and with other malignancy not further analyzed here in 4.5% (mostly neuroendocrine tumor). In patients with generalized malignancy (n = 195), exploratory laparotomy was performed in 23% to get tissue samples or verify staging - palliative anastomoses were done in 25% of operated patients, CHT was performed in 29% of the generalized tumors, palliative RT of tumor was performed in 1 patient, and RT of metastases in 3 patients. In patients with local or regional nodal affection (n = 137) laparotomy was done in 59%, R0 resection in 34 (42%) of 81 operated, R1 in 6%, palliative anastomoses were done in 17% and irreversible electroporation in one patients, CHT or radiochemotherapy after R0 and R1 resections was provided in 61% operated patients. The most commonly used CHT was monotherapy with gemcitabine or FOLFIRINOX. The indication of CHT in cytology/histology verified generalized cancers and with excluding patients refusing CHT was proposed in 2012 to 16%, in 2014 to 49% and in 2016 to 84% of patients. In the case of a local or regional nodal involvement the CHT was proposed to 40, 55 and 86% of patients. Median overall survival in generalized tumor patients receiving CHT (n = 137) vs. not-receiving CHT (n = 56) was 2 vs. 8 months (p = 0.0001), and in the local or regional nodal involvement patients receiving CHT (n = 74) vs. not-receiving CHT (n = 62) was 5 vs. 16 months (p = 0.0001). CONCLUSION: CHT and surgery are the dominant treatment modalities. There has been a marked increase in the CHT and histology/cytology verifications indications, with a major factor being a clinician evaluation of a patient to be fit for CHT and its benefit or to complete pancreatic tumor verification. With still very limited results in pancreatic cancer treatment, a careful assessment of each patients indication, respecting patients desire, is always required, knowing that even in the case of advanced disease, CHT can bring benefit, albeit limited.Key words: pancreas - carcinoma - chemotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This study was supported by the grant of Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806).Submitted: 13. 3. 2018Accepted: 18. 4. 2018.

Synchronization as adjustment of information rates: detection from bivariate time series.

An information-theoretic approach for studying synchronization phenomena in experimental bivariate time series is presented. "Coarse-grained" information rates are introduced and their ability to indicate generalized synchronization as well as to establish a "direction of information flow" between coupled systems, i.e., to discern the driving from the driven (response) system, is demonstrated using numerically generated time series from unidirectionally coupled chaotic systems. The method introduced is then applied in a case study of electroencephalogram recordings of an epileptic patient. Synchronization events leading to seizures have been found on two levels of organization of brain tissues and "directions of information flow" among brain areas have been identified. This allows localization of the primary epileptogenic areas, also confirmed by magnetic resonance imaging and pasitron emission tomography scans.