Genetic Susceptibility to Periodontal Disease in Down Syndrome: A Case-Control Study

Severe periodontitis is prevalent in Down syndrome (DS). This study aimed to identify genetic variations associated with periodontitis in individuals with DS. The study group was distributed into DS patients with periodontitis (n = 50) and DS patients with healthy periodontium (n = 36). All samples were genotyped with the “Axiom Spanish Biobank” array, which contains 757,836 markers. An association analysis at the individual marker level using logistic regression, as well as at the gene level applying the sequence kernel association test (SKAT) was performed. The most significant genes were included in a pathway analysis using the free DAVID software. C12orf74 (rs4315121, p = 9.85 × 10⁻⁵, OR = 8.84), LOC101930064 (rs4814890, p = 9.61 × 10⁻⁵, OR = 0.13), KBTBD12 (rs1549874, p = 8.27 × 10⁻⁵, OR = 0.08), PIWIL1 (rs11060842, p = 7.82 × 10⁻⁵, OR = 9.05) and C16orf82 (rs62030877, p = 8.92 × 10⁻⁵, OR = 0.14) showed a higher probability in the individual analysis. The analysis at the gene level highlighted PIWIL, MIR9-2, LHCGR, TPR and BCR. At the signaling pathway level, PI3K-Akt, long-term depression and FoxO achieved nominal significance (p = 1.3 × 10⁻², p = 5.1 × 10⁻³, p = 1.2 × 10⁻², respectively). In summary, various metabolic pathways are involved in the pathogenesis of periodontitis in DS, including PI3K-Akt, which regulates cell proliferation and inflammatory response.     

Bridging challenges of clinical decision support systems with a semantic approach. A case study on breast cancer

The integration of Clinical Decision Support Systems (CDSS) in nowadays clinical environments has not been fully achieved yet. Although numerous approaches and technologies have been proposed since 1960, there are still open gaps that need to be bridged. In this work we present advances from the established state of the art, overcoming some of the most notorious reported difficulties in: (i) automating CDSS, (ii) clinical workflow integration, (iii) maintainability and extensibility of the system, (iv) timely advice, (v) evaluation of the costs and effects of clinical decision support, and (vi) the need of architectures that allow the sharing and reusing of CDSS modules and services. In order to do so, we introduce a new clinical task model oriented to clinical workflow integration, which follows a federated approach. Our work makes use of the reported benefits of semantics in order to fully take advantage of the knowledge present in every stage of clinical tasks and the experience acquired by physicians. In order to introduce a feasible extension of classical CDSS, we present a generic architecture that permits a semantic enhancement, namely Semantic CDSS (S-CDSS). A case study of the proposed architecture in the domain of breast cancer is also presented, pointing some highlights of our methodology.     

Towards an efficient training of university faculty on ICTs

This article presents the results of a research study that took place during the 2007–2008 academic year at the University of the Basque Country³. (UPV/EHU in its Spanish and Basque acronyms). The research’s goal was to establish the guidelines for training opportunities in information and communication technologies (ICTs) that could better address the needs of the faculty at the aforementioned university. The conclusive results provide a picture of the necessary training in ICTs that the faculty requires for their teaching as well as for conducting research. This led us to develop some suggestions that are related to the modular organization of past and present training courses as well as improved guidelines that would help us to restructure the design of the training currently being offered. This restructuring is fundamental in order to include ICTs in the new European space of higher education (ESHE)⁴.     

A highly variable STR at the D12S391 locus

A total of 103 fragments in the STR D12S391 locus were sequenced. 24 different alleles were found which can be grouped into 12 allelic classes based on the total number of repeats. The structure of this compound STR consists of blocks of (AGAT) and (AGAC) repeats with a consensus structure (AGAT)8-17 (AGAC)6-10 (AGAT)0-1. Whereas shorter alleles only have (AGAT) repeats, > 225 bp alleles are more complex, having two motifs (AGAT) and (AGAC). Population data showed that this to be a highly polymorphic STR with a heterozygosity of 0.9. This fact together with its simple structure make this STR very suitable for forensic and genetic purposes.     

Normal and anomalous electrophoretic behavior of polymerase chain reaction-based DNA polymorphisms in polyacrylamide gels

The electrophoretic mobility of five single tandem repeats (STRs) and four amplified fragment length polymorphisms (AFLPs) in polyacrylamide gels was tested under denaturing and nondenaturing conditions. Relative anomalous mobility in nondenaturing conditions was found in one AT-rich AFLP (3'ApoB) and in two AT-rich STRs (HUMACTBP2 and HUMF13A1). In these cases, highly anomalous electrophoretic behavior was found even when changes were made in the %T value alone. In such cases typing results were affected by the gel composition. The mobility of these systems was nevertheless normal under denaturing conditions. As a consequence of this study, we recommended that the typing of these systems should only be performed under denaturing conditions and we also recommend the further study of the electrophoretic behavior of repetitive DNA polymorphisms, especially AT-rich systems, before they are used in forensic or genetic applications.     

Design and Development of a Mobile Cardiac Rehabilitation System

In this article we present the design and implementation of a mobile cardiac monitoring system oriented to patients in Phase II and III of cardiac rehabilitation. The complete monitoring system involves both hardware and software design perspectives. At the hardware level, we present a T-shirt with a 12-lead ECG system and an embedded inertial sensor for the monitoring of activity and energy expenditure. At the software level, a modular cloud platform performs data processing to detect relevant cardiac events and to provide advanced visualization capabilities. As a case study, we have implemented our system at the Cardiac Rehabilitation program at Donostia University Hospital (Spain). Finally, the validation of the 12-lead ECG recording system is also presented and discussed.     

Minisatellite variant repeat (MVR) analysis of the HRAS1 minisatellite locus

Two alternative electrophoretic strategies were used to study the internal variation of the HRAS1 minisatellite after minisatellite variant repeat mapping (MVR-PCR) was carried out. While the use of automated sequencers with fluorescent based technology is ideal for analyzing fragment size, and therefore, for analyzing the repeat number, the use of polyacrylamide gels and silver staining is more appropriate for the analysis of internal variation. Thirteen different fragments ranging from 27 to 80 repeats were found in a sample from 80 healthy Caucasian individuals. By using MVR mapping we were able to detect heterozygotes which appear as homozygotes when fragment length analysis was used. As a result of this, the 13 alleles, which we had detected, increased to 16 alleles when MVR sequences were analyzed. The extremely conservative arrays of repeats allow us to infer the theoretical origin of rare alleles from a major group of specific alleles. The HRAS1 minisatellite has been extensively studied due to its association with cancer. However, the methodology used up to now has limited the scope of previous research. Our approach permits the identification of alleles in a fast and reliable way using their MVR codes, thus allowing association studies with cancer.     

Sequence variation of a variable short tandem repeat at the D18S535 locus

A short tandem repeat in the D18S535 locus was sequenced in 25 selected alleles. A total of 8 different alleles were found which can be designated according to the total number of repeats. This STR is a simple hypervariable STR consisting of blocks of (GATA) repeats with a basic sequence structure (GATA)1(GACA)1(GATA)1 (GAT)1(GATA)9-16. Population data showed that this is a highly polymorphic STR with a heterozygosity of more than 0.80, a simple structure and small size (130-158 bp) which makes this an interesting DNA polymorphism for forensic and genetic purposes.     

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims

The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated.

Material and Methods

One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot^® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan^® Real-time PCR.

Results

Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05).

Conclusion

SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.