Association of intronic variants of the KCNAB1 gene with lateral temporal epilepsy.

The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy

Vegetation and flow rate impact on in-stream longitudinal dispersion and retention processes

This paper is an attempt to explain influence of vegetation and flow rate in natural stream (Epre, Germany) on mixing and transport processes. For this purpose, we conducted two tracer tests in Germany using rhodamine WT (RWT) as a fluorescence dye. Both tests were performed under different vegetation and flow rate conditions. The STIR (Solute Transport In Rivers) code was used for calibration of dispersion coefficients, exchange rates and residence times. We used the STIR model to separate short—and long—time retention. Our tracer test results confirm previous findings and also reveal a correlation between storage zone exchanges rate and reach lengths, strong influence of vegetation and flow rate on transport and mixing parameters, and the significance of the equipment on storage domain characterisation

Using Interaction Design to Improve Usability of a PHR User Interface Based on Visual Elements

e Markle Foundation’s Connecting for Health working group in its report “Connecting Americans to their healthcare” (Markle Foundation, 2004) defines Personal Health Record (PHR) as: “an electronic application through which individuals can access, manage and share their health information in a secure and confidential manner.” (p. 13). In the last years PHR has been gaining great attention from healthcare institutions and organizations due its potential for a more active involvement of citizens in they care and improvement of relationships and communication between patients and their health care providers (Brailer, 2004; Cohn, 2007). Recently, in its report on the prevention of medication errors (IOM, 2007), the Institute of Medicine has identified PHR systems as a viable technology to support consumers’ self-management.Worldwide research institutions, government and healthcare authorities have identified PHR as a top priority, established broad areas for research and evaluation of PHR systems, and acknowledged the necessity of demonstration and pilot projects as a critical next step to address and exploit the full potential of PHR-based systems and services (Brailer, 2004; Cohn, 2007; Markle Foundation, 2004; Tang, 2006). In order to design a working system, the involvement of final users is a crucial phase even though it is often undervalued (Nielsen, 1993). For example, in health care settings it has been demonstrated that also the most innovative project could fail because of a rushed interface design (i.e. an interface limited to a subjective taste) that can compromise the user’s acceptability, strongly influencing the use of a system (Bates, 2003). This seems to be particularly true in the context of development of a PHR-based system, since we are dealing with citizens, a deeply inhomogeneous group due to the disparity of age, cultural level, living context, health-care and computer literacy. Interaction design emphasizes the importance of involving final users throughout the whole process of design of the product or system within an iterative design-evaluation process. Preece & al (2002) state that a user-centered approach to development “forms a central plank” (p. 170) of interaction design process and “the real user and their goals, not just technology, should be the driving force behind development a product” (p. 285). In the last years, several groups have applied user-centered approaches and usability testing in health care settings for the design and implementation of clinical information systems (Coble, 1997; Kushniruk et al, 1996; Kushniruk & Patel, 2004; Zhang et al, 2003). To our knowledge, only few studies have applied a user-centered approach to design and development of a PHR system (Tran, 2005).During the last year, the Department of Health of the Autonomous Province of Trento (NE Italy) has promoted a feasibility study on the design of a PHR-based system. One of the preliminary research questions of the study was to explore whether and how visual design solutions can promote user’s usability and acceptance of a PHR-based system. A first requirement for using a visual approach in the design of the PHR system was to create a clean non-redundant interface that would reassure and communicate calm and serenity to users and guide them through a user-friendly navigation throughout the PHR. A second, but not less important, requirement is that a user interface based on visual elements would be portable and usable in a touch-screen paradigm on mobile devices (i.e. palm top) with minor modifications. This chapter will describe the use of interaction methods, particularly usability testing, for exploring and testing usability and user experience of a PHR user interface based on visual elements. This paper is organized as follows. Section 1 introduces basic concepts on interaction design. Section 2 briefly illustrates visual design and section 3 describes how we taken into account visual design recommendations in ..

STUDIES ON THE ANTIOXIDANT AND FREE-RADICAL SCAVENGING PROPERTIES OF IDB-1016 A NEW FLAVANOLIGNAN COMPLEX

Silybin has been complexed in 1:1 ratio with phosphatidyl choline to give IdB 1016 in order to increase its bioavailability. The antioxidant and free radical scavenger action of this new form of silybin has been evaluated. One hour after the intragastric administration to rats of IdB 1016 (1.5 g/kg b.wt.) the concentration of silybin in the liver microsomes was estimated to be around 2.5 micrograms/mg protein corresponding to a final concentration in the microsomal suspension used of about 10 microM. At these levels IdB decreased by about 40% the lipid peroxidation induced in microsomes by NADPH, CCl4 and cumene hydroperoxide, probably by acting on lipid derived radicals. Spin trapping experiments showed, in fact, that the complexed form of silybin was able to scavenge lipid dienyl radicals generated in the microsomal membranes. In addition, IdB 1016 was also found to interact with free radical intermediates produced during the metabolic activation of carbon tetrachloride and methylhydrazine. These effects indicate IdB 1016 as a potentially protective agent against free radical-mediated toxic damage

Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal dominant lateral temporal epilepsy

Purpose: To describe the clinical and genetic findings of four families with autosomal dominant lateral temporal epilepsy. Methods: A personal and family history was obtained from each affected and unaffected subject along with a physical and neurologic examination. Routine electroen-cephalography and magnetic resonance imaging (MRI) studies were performed in almost all patients. DNAs from family members were screened for LGI1 mutations. The effects of mutations on Lgi1 protein secretion were determined in transfected culture cells. Key Findings: The four families included a total of 11 patients (two deceased), six of whom had lateral temporal epilepsy with auditory aura. Age at onset was in the second decade of life; seizures were well controlled by antiepileptic treatment and MRI studies were normal. We found two pathogenic LGI1 mutations with uncommonly low penetrance: the R136W mutation, previously detected in a sporadic case with telephone-induced partial seizures, gave rise to the epileptic phenotype in three of nine mutation carriers in one family; the novel C179R mutation caused epilepsy in an isolated patient from a family where the mutation segregated. Another novel pathogenic mutation, I122T, and a nonsynonymous variant, I359V, were found in the two other families. Protein secretion tests showed that the R136W and I122T mutations inhibited secretion of the mutant proteins, whereas I359V had no effect on protein secretion; C179R was not tested, because of its predictable effect on protein folding. Significance: These findings suggest that some LGI1 mutations may have a weak penetrance in families with complex inheritance pattern, or isolated patients, and that the protein secretion test, together with other predictive criteria, may help recognize pathogenic LGI1 mutations

Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal dominant lateral temporal epilepsy.

PURPOSE: To describe the clinical and genetic findings of four families with autosomal dominant lateral temporal epilepsy. METHODS: A personal and family history was obtained from each affected and unaffected subject along with a physical and neurologic examination. Routine electroencephalography and magnetic resonance imaging (MRI) studies were performed in almost all patients. DNAs from family members were screened for LGI1 mutations. The effects of mutations on Lgi1 protein secretion were determined in transfected culture cells. KEY FINDINGS: The four families included a total of 11 patients (two deceased), six of whom had lateral temporal epilepsy with auditory aura. Age at onset was in the second decade of life; seizures were well controlled by antiepileptic treatment and MRI studies were normal. We found two pathogenic LGI1 mutations with uncommonly low penetrance: the R136W mutation, previously detected in a sporadic case with telephone-induced partial seizures, gave rise to the epileptic phenotype in three of nine mutation carriers in one family; the novel C179R mutation caused epilepsy in an isolated patient from a family where the mutation segregated. Another novel pathogenic mutation, I122T, and a nonsynonymous variant, I359V, were found in the two other families. Protein secretion tests showed that the R136W and I122T mutations inhibited secretion of the mutant proteins, whereas I359V had no effect on protein secretion; C179R was not tested, because of its predictable effect on protein folding. SIGNIFICANCE: These findings suggest that some LGI1 mutations may have a weak penetrance in families with complex inheritance pattern, or isolated patients, and that the protein secretion test, together with other predictive criteria, may help recognize pathogenic LGI1 mutations. Wiley Periodicals, Inc. \ua9 2011 International League Against Epilepsy