Transient massive hyperlipidaemia in a type 2 diabetic subject

A 50-year-old man, in apparently good health, was referred to the Lipid Center of San Luigi Gonzaga Hospital, Orbassano (Turin, Italy), by his primary care physician (PCP) because clinical tests at the time of blood donation showed milky plasma with serious hypertriglyceridaemia (>5000 mg/dl) and hyperglycaemia (381 mg/dl), diagnostic for diabetes. It was not possible to perform further blood chemical analyses because hypertriglyceridaemia would have provided abnormal results. The patient entered the hospital to prevent acute pancreatitis, which is often associated with severe hypertriglyceridaemi

Sociomateriality Implications of Software As a Service Adoption on IT-workers’ Roles and Changes in Organizational Routines of IT Systems Support

This paper aims to deepen our understanding on how sociomateriality practices influence IT workers’ roles and skill set requirements and changes to the organizational routines of IT systems support, when an organization migrates an on-premise IT system to a software as a service (SaaS) model. This conceptual paper is part of an ongoing study investigating organizations that migrated on-premise IT email systems to SaaS business models, such as Google Apps for Education (GAE) and Microsoft Office 365 systems, in New Zealand tertiary institutions. We present initial findings from interpretive case studies. The findings are, firstly, technological artifacts are entangled in sociomaterial practices, which change the way humans respond to the performative aspects of the organizational routines. Human and material agencies are interwoven in ways that reinforce or change existing routines. Secondly, materiality, virtual realm and spirit of the technology provide elementary levels at which human and material agencies entangle. Lastly, the elementary levels at which human and material entangle depends on the capabilities or skills set of an individual

Ontology-guided data preparation for discovering genotype-phenotype relationships

International audienceComplexity of post-genomic data and multiplicity of mining strategies are two limits to Knowledge Discovery in Databases (KDD) in life sciences. Because they provide a semantic frame to data and because they benefit from the progress of semantic web technologies, bio-ontologies should be considered for playing a key role in the KDD process. In the frame of a case study relative to the search of genotype-phenotype relationships, we demonstrate the capability of bio-ontologies to guide data selection during the preparation step of the KDD process. We propose three scenarios to illustrate how domain knowledge can be taken into account in order to select or aggregate data to mine, and consequently how it can facilitate result interpretation at the end of the process

Increased High Density Lipoprotein-levels associated with Age-related Macular degeneration. Evidence from the EYE-RISK and E3 Consortia

Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.</p

Hydroimidazolone Modification of the Conserved Arg12 in Small Heat Shock Proteins: Studies on the Structure and Chaperone Function Using Mutant Mimics

Methylglyoxal (MGO) is an α-dicarbonyl compound present ubiquitously in the human body. MGO reacts with arginine residues in proteins and forms adducts such as hydroimidazolone and argpyrimidine in vivo. Previously, we showed that MGO-mediated modification of αA-crystallin increased its chaperone function. We identified MGO-modified arginine residues in αA-crystallin and found that replacing such arginine residues with alanine residues mimicked the effects of MGO on the chaperone function. Arginine 12 (R12) is a conserved amino acid residue in Hsp27 as well as αA- and αB-crystallin. When treated with MGO at or near physiological concentrations (2–10 µM), R12 was modified to hydroimidazolone in all three small heat shock proteins. In this study, we determined the effect of arginine substitution with alanine at position 12 (R12A to mimic MGO modification) on the structure and chaperone function of these proteins. Among the three proteins, the R12A mutation improved the chaperone function of only αA-crystallin. This enhancement in the chaperone function was accompanied by subtle changes in the tertiary structure, which increased the thermodynamic stability of αA-crystallin. This mutation induced the exposure of additional client protein binding sites on αA-crystallin. Altogether, our data suggest that MGO-modification of the conserved R12 in αA-crystallin to hydroimidazolone may play an important role in reducing protein aggregation in the lens during aging and cataract formation

rs5888 Variant of SCARB1 Gene Is a Possible Susceptibility Factor for Age-Related Macular Degeneration

Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including variants in the CFH gene and the ARMS2 LOC387715/HTRA1locus. Our purpose was to perform a case-control study in two populations among individuals who did not carry risk variants for CFHY402H and LOC387715 A69S (ARMS2), called “study” individuals, in order to identify new genetic risk factors. Based on a candidate gene approach, we analyzed SNP rs5888 of the SCARB1 gene, coding for SRBI, which is involved in the lipid and lutein pathways. This study was conducted in a French series of 1241 AMD patients and 297 controls, and in a North American series of 1257 patients with advanced AMD and 1732 controls. Among these individuals, we identified 61 French patients, 77 French controls, 85 North American patients and 338 North American controls who did not carry the CFH nor ARMS2 polymorphisms. An association between AMD and the SCARB1 gene was seen among the study subjects. The genotypic distribution of the rs5888 polymorphism was significantly different between cases and controls in the French population (p<0.006). Heterozygosity at the rs5888 SNP increased risk of AMD compared to the CC genotypes in the French study population (odds ratio (OR) = 3.5, CI95%: 1.4–8.9, p<0.01) and after pooling the 2 populations (OR = 2.9, 95% CI: 1.6–5.3, p<0.002). Subgroup analysis in exudative forms of AMD revealed a pooled OR of 3.6 for individuals heterozygous for rs5888 (95% CI: 1.7–7.6, p<0.0015). These results suggest the possible contribution of SCARB1, a new genetic factor in AMD, and implicate a role for cholesterol and antioxidant micronutrient (lutein and vitamin E) metabolism in AMD

The 18th Annual Meeting of the European Lipoprotein Club

Contains fulltext : 23089.PDF (publisher's version ) (Open Access

The 19th annual meeting of the European Lipoprotein Club

Contains fulltext : 24985.PDF (publisher's version ) (Open Access