BACKGROUND: The driving behavior of patients with mild Alzheimer's disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. OBJECTIVE: To compare driving performance in APOE4 carriers and matched non-carriers. METHODS: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. RESULTS: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. CONCLUSION: The lower speed variability of APOE4 carriers in the absence of neuropsychological test differences indicates reduced speed adaptations, possibly as a compensatory strategy. Simulated driving may be a sensitive method for detecting performance differences in the absence of cognitive differences

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine's (EFLM) proposed Common Training Framework for non-medical Specialists in Laboratory Medicine is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive's enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM's position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission

BACKGROUND: The purpose of this study is the development and validation of a novel and robust genotyping method for a new lysyl oxidase-like 1 (LOXL1) intronic polymorphism (rs11638944, C > G) and the investigation of its potential association with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) in a Greek population. MATERIAL AND METHODS: 242 DNA samples from 49 PXS, 64 PXG, 50 primary open-angle glaucoma (POAG) patients and 79 healthy age-matched controls were analyzed. Novel methodologies were developed and optimized, in order to genotype the intronic LOXL1 polymorphism: a) a real-time qPCR and melting curve analysis in the Light Cycler platform for rapid and cost-effective analysis and, b) a conventional PCR-RFLP method for analysis of a small number of samples. In selected samples, validity was checked with the reference DNA Sequencing method. RESULTS: The real-time qPCR methodology was reliable, demonstrating good efficiency, reproducibility, accuracy in genotyping (100% concordance with the PCR-RFLP method and DNA Sequencing), with good allele discrimination (Tm = 53.26 degrees C for C allele, Tm = 61.83 degrees C for G allele, DeltaTm = 8.57 degrees C). The results were characterized by Hardy-Weinberg equilibrium in all groups. An increase from 18% in healthy controls to 61% in PXS patients was detected for the G/G homozygote thus, the C allele is protective for PXS with OR = 0.22 (95%CI: 0.11-0.42, p < .0001). Moreover, an increase from 18% in healthy controls to 70% in PXG patients was detected for the G/G homozygote thus, the C allele is protective for PXG with OR = 0.13 (95%CI: 0.06-0.25, p < .0001). CONCLUSIONS: A statistically significant association was verified for the intronic LOXL1 polymorphism rs11638944 and PXS/PXG in a Greek population

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are part of the same pathophysiological spectrum and have common genetic and cerebrospinal fluid (CSF) biomarkers. Our aim here was to identify causative gene variants in a cohort of Greek patients with FTD, ALS and FTD-ALS, to measure levels of CSF biomarkers and to investigate genotype-phenotype/CSF biomarker associations. In this cohort of 130 patients (56 FTD, 58 ALS and 16 FTD-ALS), we performed C9orf72 hexanucleotide repeat expansion analysis, whole exome sequencing and measurement of "classical" (Abeta(42), total tau and phospho-tau) and novel (TDP-43) CSF biomarkers and plasma progranulin. Through these analyses, we identified 14 patients with C9orf72 repeat expansion and 11 patients with causative variants in other genes (three in TARDBP, three in GRN, three in VCP, one in FUS, one in SOD1). In ALS patients, we found that levels of phospho-tau were lower in C9orf72 repeat expansion and MAPT c.855C>T (p.Asp285Asp) carriers compared to non-carriers. Additionally, carriers of rare C9orf72 and APP variants had lower levels of total tau and Abeta(42), respectively. Plasma progranulin levels were decreased in patients carrying GRN pathogenic variants. This study expands the genotypic and phenotypic spectrum of FTD/ALS and offers insights in possible genotypic/CSF biomarker associations

The ISO 15189:2012 standard section 5.9.1 requires laboratories to review results before release, considering quality control, previous results, and clinical information, if any, and to issue documented procedures about it. While laboratory result reporting is generally regarded as part of the post-analytical phase, the result release process requires a general view of the total examination process. Reviewing test results may follow with troubleshooting and test repetition, including reanalyzing an individual sample or resampling. A systematic understanding of the result release may help laboratory professionals carry out appropriate test repetition and ensure the plausibility of laboratory results. In this paper, we addressed the crucial steps in the result release process, including evaluation of sample quality, critical result notification, result reporting, and recommendations for the management of the result release, considering quality control alerts, instrument flags, warning messages, and interference indexes. Error detection tools and plausibility checks mentioned in the present paper can support the daily practice of results release

BACKGROUND: A significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed to mutations in major genes such as GRN, MAPT and C9orf72. Our previous report on a Greek FTD cohort revealed the presence of the single nucleotide polymorphism (SNP) p.I383V (rs80356740) in the TARDBP gene in three unrelated patients. Our objective was to develop a novel, fast and accurate method for the detection of this particular SNP and evaluate the assay in a larger cohort. METHODS AND RESULTS: A real-time qPCR-melting curve analysis method was developed, validated and tested in 142 FTD patients and 111 healthy control subjects. The SNP was detected in another two patients raising its yield in FTD patients to 3.5% (5 out of 142 patients) while one in 111 healthy controls was found to be a carrier. However, its frequency in the general population has been reported extremely low in international SNP databases (0.002%). CONCLUSION: This fact along with the indicated pathogenicity of this SNP in some bioinformatics tools, suggest that TARDBP p.I383V is recurrent and likely pathogenic for the Greek FTD population. Our high-throughput method could be used for genotyping in other larger patient cohorts and in other populations. Additionally, functional in vitro studies are required for the final adjudication of this TARDBP alteration as a pathogenic alteration