Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology’s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC’s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.     

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease

IntroductionThe inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established.ObjectivesThe study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group.ResultsIn the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= −0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= −0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= −0.41, p=.003).ConclusionsCRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.     

Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation

Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS.     

Predicting transmitted irradiance through CAD/CAM resin composite crowns in a simulated clinical model

ObjectiveTo predict the clinically relevant transmitted irradiance that is available for luting when a CAD/CAM restoration is inserted. The influence of irradiance, exposure distance, light curing unit (LCU) angulation and direction of polymerization is analyzed when curing through crowns of different thicknesses.MethodsThree modern CAD/CAM resin-based composites (RBCs) were used to produce 45 crown-shaped specimens. The distance between fissure and crown base was set at 1.0, 1.5 and 2.0 mm (n = 5). Transmitted irradiance, while using a violet-blue LCU, was measured with a photo-spectrometer. 180 exposure conditions per specimen were investigated by variation in LCU curing mode, angulation, exposure distance and direction. Data was analyzed using univariate ANOVA followed by Tukey HSD (α = 0.05) and comparison of 95% confidence intervals.ResultsThe CAD/CAM-RBC’s decadic absorption coefficient ranges from 0.317 mm^?1 to 0.387 mm^?1 and the reflection correcting factor for crowns ranges from 0.305 to 0.337. Transmitted irradiance decreases significantly with increasing exposure distance and decreasing incident irradiance. For tilt angles greater than 10°, transmitted irradiances are significantly reduced (?11% for 20°, ?23% for 30°). Significantly lowest transmitted irradiances were measured for vestibular curing direction (up to ?15%).SignificanceA calculation model can predict the transmitted irradiance through a CAD/CAM restoration in dependence of restoration thickness and radiant emittance. The practitioner can be supported by this model to adapt material choice of dental restoration and adhesive system to the individual situation. Variation in exposure conditions shows negative effect on the transmission of light and should be limited.     

FindZebra: A search engine for rare diseases

BackgroundThe web has become a primary information resource about illnesses and treatments for both medical and non-medical users. Standard web search is by far the most common interface to this information. It is therefore of interest to find out how well web search engines work for diagnostic queries and what factors contribute to successes and failures. Among diseases, rare (or orphan) diseases represent an especially challenging and thus interesting class to diagnose as each is rare, diverse in symptoms and usually has scattered resources associated with it.MethodsWe design an evaluation approach for web search engines for rare disease diagnosis which includes 56 real life diagnostic cases, performance measures, information resources and guidelines for customising Google Search to this task. In addition, we introduce FindZebra, a specialized (vertical) rare disease search engine. FindZebra is powered by open source search technology and uses curated freely available online medical information.ResultsFindZebra outperforms Google Search in both default set-up and customised to the resources used by FindZebra. We extend FindZebra with specialized functionalities exploiting medical ontological information and UMLS medical concepts to demonstrate different ways of displaying the retrieved results to medical experts.ConclusionsOur results indicate that a specialized search engine can improve the diagnostic quality without compromising the ease of use of the currently widely popular standard web search. The proposed evaluation approach can be valuable for future development and benchmarking. The FindZebra search engine is available at http://www.findzebra.com/.     

The long-term consequence of salivary contamination at various stages of adhesive application and clinically feasible remedies to decontaminate

Clinical Oral Investigations - To analyse the bond quality in dentine post-ageing after salivary contamination and decontamination at different stages of dental adhesive application. A total of...     

The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm.

We have carried out partial amino acid sequenceanalysis of a putative nuclear pore complex protein (nucleoporin) of rat thatreacts with wheat germ agglutinin and with the polyspecific monoclonal antibody414. Surprisingly, these partial amino acid sequence data revealed a high degreeof similarity with the human CAN protein, the complete cDNA-derived primarystructure of which was reported by Von Lindern et al. [Von Lindern, M.,Fornerod, M., van Baal, S., Jaegle, M., de Wit, T., Buijs, A. & Grosveld, G.(1992) Mol. Cell. Biol. 12, 1687-1697]. The CAN protein has been proposed to bea putative oncogene product associated with myeloid leukemogenesis. Itssubcellular localization was not established. To confirm that the putative ratnucleoporin is indeed a homolog of the human CAN protein and to determine itssubcellular localization, we expressed a 39-kDa internal segment of the213,790-Da human CAN protein in Escherichia coli and raised monospecificantibodies, which reacted with the putative rat nucleoporin. Immunofluorescencemicroscopy of HeLa cells gave a punctate nuclear surface staining patterncharacteristic of nucleoporins, and immunoelectron microscopy yielded specificdecoration of the cytoplasmic side of the nuclear pore complex. This suggeststhat the protein is part of the short fibers that emanate from the cytoplasmicaspect of the nuclear pore complex. In agreement with previously proposednomenclature for nucleoporins, we propose the alternative term nup214(nucleoporin of 214 kDa) for the CAN protein.