Computer intuition: guiding scientific research in imaging and oral implantology

As the costs associated with clinical research and new drug development increase, it is incumbent upon us to develop alternative research methodologies. A new Computer Intuition (CI) program identifies literature-based evidence with the potential to generate a hypothesis that is most likely to be clinically confirmed regarding the cause of a disease or the questions being posed. The objective of this study was to demonstrate whether computer intuition can be used to guide scientific research in solving important biomedical questions. The establishment of CI as an alternative research methodology has the potential to accelerate the translation of basic science findings into clinical practice. The specific aim of this study was to develop a CI-driven hypothesis related to the controversial issue debating which radiographic imaging technology is most suitable for diagnostic purposes prior to the placement of oral implants. This hypothesis was then compared, in retrospect, with a known opinion established following a recent literature review on this issue. In his review of the literature, Frederiksen (1995) suggests that multiplanar reformatted computed tomography (CT) is the diagnostic imaging modality of choice prior to implant placement. To compare the CI hypothesis with Frederiksen's (1995) opinion, we subjected 34 relevant papers to CI analysis. The output consisted of clusters of important statements, phrases, and thought processes from the given dataset rated with the greatest potential to generate testable hypotheses. Both CI's output and Frederiksen (1995) indicated that CT scanning is the diagnostic imaging modality of choice prior to implant placement. Although the ultimate utility of CI is dependent on the successful testing of its derived hypothesis, this preliminary retrospective study suggests that CI might be useful in guiding scientific research.     

The characteristics of bone injuries in childhood

All aboard for an imaginary journey to the village of Health Care Chaos where the different actors and issues involved in the very real state of health care come alive. The author incorporates an interview with Virginia Trotter Betts, President of the American Nurses Association, to highlight the controversy surrounding the involvement and role of advanced practice nurses.     

Role of lipids in the permeabilization of membranes by class L amphipathic helical peptides

We studied the mechanism of membrane permeabilization by the 18L model peptide (GIKKFLGSIWKFIKAFVG), which features the consensus class L sequence averaged from the number of naturally occurring lytic peptides. Two aspects of membrane lipid composition significantly affected peptide-membrane interactions: the presence of acidic lipids and, in zwitterionic membranes, and the presence of nonbilayer forming lipids. In zwitterionic membranes, 18L peptide destabilizes the membrane, leading to a transient formation of large defects in the membrane which result generally in contents leakage, but in the presence of bilayer-bilayer contact can alternatively lead to vesicle fusion. In membranes containing acidic lipids (DOPC:DOPG, DOPG), 18L caused leakage but not fusion, probably due to mutual repulsion of acidic vesicles. While the extent of contents leakage was approximately the same as for zwitterionic membranes, the kinetics of leakage could be resolved only by using stopped-flow, leakage being essentially complete within the first minute. Previously, we reported that apolipoprotein (class A) and lytic (class L) peptide analogs have opposing effects on some properties of biological membranes. This reciprocal effect of 18L and Ac-18A-NH2, class A model peptide, is restricted to membranes with a high propensity for nonbilayer phase formation (DOPE, Me-DOPE, DOPC:DOPE, DOPC:Me-DOPE). The decrease in the content of nonbilayer phase forming lipid or the addition of acidic lipids reduces or eliminates the reciprocal effects. This suggests the importance of nonbilayer phase propensity for certain functions of biological membranes.     

Improved method for studying skin lipid samples from cyanoacrylate strips by high-performance thin-layer chromatography

A non-invasive method for sampling skin surface lipids is cyanoacrylate stripping (CAC-TS). It was the purpose of our study to improve the method for sampling of skin surface lipids and the separation of epidermal lipid fractions by a modification of the methods described by Melnik and by Imokawa et al. Briefly, lipids on the glass slide sampled by CAC-TS from the forearm of 75 volunteers and from the forehead of 60 volunteers were eluted in hexane/ethanol under ultrasonication. Identification of the diluted total superficial sebaceous and epidermal skin lipids was performed by sequential high-performance thin-layer chromatography. For quantification of the lipids we used densitometric methods. By this modified method we were able to show a clear and complete separation of all relevant lipids from a cyanoacrylate strip that represented 1-2 mg stratum corneum only.     

Experimental evaluation of theoretical contact forces in the cat patellofemoral joint

The purpose of this study was to evaluate the accuracy of patellofemoral contact forces predicted from a planar model of the patella by comparison with experimentally determined in situ contact forces. Patellofemoral contact pressures and areas were measured experimentally in an animal preparation with pressure sensitive film. Patellar tendon forces and lines of action used as input to the model were measured in the intact joint of the same preparation. Predicted and measured contact forces at different joint loads were compared at three different joint angles using linear regression analysis. r2-coefficients ranged from 0.94 to 0.95, and the slopes of the regression lines ranged from 1.64 to 2.11 for the three joint angles. The high r2-coefficients for all comparisons indicate that both methods were able to quantify the relative changes in the cat patellofemoral contact forces under different loading conditions accurately. However, the consistent finding of slopes greater than 1.0 indicates that the measured contact forces were systematically larger than the corresponding predicted forces. Analysis of the possible sources for the observed discrepancies between predicted and measured contact forces suggested that the directly measured patellar tendon forces were the most likely candidate causing the systematic differences. The results of this study suggest that a relatively simple model of the patellofemoral joint appears to be valid to quantify joint contact forces if appropriate patellar tendon force values can be provided as input to the model.     

Platelet alpha-granules

Platelets contain a vast number of biologically active molecules within cytoplasmic granules which are classified according to their respective distinct ultrastructures, densities and content. The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and (2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen (Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin (TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit membrane has been demonstrated to contain a number of physiologically important receptors including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate from small precursor granules which can be observed budding from the trans-Golgi network within the platelet precursor cell the MK. During MK maturation the alpha-granules become very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-granular contents are destined for release during platelet activation at sites of vessel wall injury and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the pathogenesis of atherosclerosis.