Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial

This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.     

Size-specific information channels and selective attention: visual evoked potential and behavioral measures.

Subjects were shown a stimulus (diffuse light or a checkerboard pattern with checks subtending 12' or 35' of arc) and were instructed to remember and attend (give a reaction time response to or count) that stimulus during the course of an approximately 6-min trial. A trial consisted of the random presentation of 8 stimulus flashes (diffuse light and checkerboards with 9, 12, 18, 24, 35, 45, 94 and 95 min checks) at a rate of 1/555--930 msec. Visual evoked potentials and reaction times were averaged to each of the 8 stimuli. The purpose of the experiment was to assess how specifically the relevant stimulus could be attended, as indicated by VEPs and behavioral responses to the relevant and 7 irrelevant stimuli. Attention to one check size resulted in greater amplitude VEP components to that size than to other sizes: the greater the discrepancy between the flashed and attended check size, the smaller the VEP amplitude. Such size tuning was first evident in the VEP 160 msec after stimulation and most evident at 260 msec. The bandwidth of the VEP amplitude size-tuning functions became progressively narrower from 160 up to 260 msec, that point in time when the RT response was initiated. The width at 260 msec was similar to that indicated by the behavioral RT data (modal latency of 322 msec). The functional components of the VEP appeared to reflect the effects of attention on the activity of cortical size channels or detectors.     

Post-transfusion purpura: a heterogeneous syndrome

Three new patients with post-transfusion purpura (PTP) are described. As the manifestations in two differ significantly from those of previously reported cases, they serve to expand the definition of this syndrome. Although all 14 previously reported cases have occurred in Pl- A1-negative females, one of our patients was a Pl-A-negative male. Moreover, a female whose postrecovery platelets possessed the Pl-A1 antigen is described. Antiplatelet antibody activity was detected in all three patients by the 51Cr release test; in contrast, only one reacted in the complement (C) fixation assay. Serum obtained during the acute episode from the PlA1-positive patient reacted against platelets from four of 11 normals by C fixation and against platelets from 48 of 53 normals by 51Cr release, including five of nine Pl-A1-negative platelet samples. This case represents the first instance of PTP in which the platelet isoantibody was not specifically directed against the Pl-A1 antigen. These observations suggest that PTP may be a more heterogeneous disorder than previously realized.     

Effect of "inside-out" and "outside-in" attitude displays on off-axis tracking in pilots and nonpilots

BACKGROUND: Pilots employing helmet-mounted displays spend sustained periods of time looking off-axis, necessitating the inclusion of attitude symbology on the helmet to maintain spatial awareness. We examined how fundamentally different attitude references, a moving-horizon ("inside-out") or a moving-aircraft ("outside-in"), affected pilot and nonpilot attitude control when looking on- or off-axis. Both a rear-view and a side-view outside-in perspective were depicted to investigate the effect of control-display compatibility. METHODS: Subjects performed a compensatory pitch-roll tracking task either looking on-axis or 90 degrees off-axis using three symbologies: 1) a compressed pitch ladder with horizon line; 2) a 3-D aircraft representation viewed from the rear; and 3) a 3-D aircraft representation viewed from the side. Tracking error in roll and pitch, control bias, and subjective ratings were collected and analyzed. RESULTS: There was no significant difference in the tracking performance of U.S. Air Force pilots in pitch and roll using the inside-out or outside-in rear-view formats on- and off-axis, although they preferred the inside-out format. Nonpilots tracked significantly better using the outside-in rear-view format, which they also preferred. Both groups tracked poorly using the outside-in side-view format and control-display compatibility had no important effect. CONCLUSIONS: Pilots are equally adept using outside-in and inside-out displays. Given that an outside-in display may better reflect a person's inherent frame of reference for orientation (as evidenced by the nonpilots' superior performance with it), the results seem to indicate that pilots, through experience, have adapted to an inside-out frame of reference.     

Characterization of human skeletal stem and bone cell populations using dielectrophoresis

Dielectrophoresis (DEP) is a non‐invasive cell analysis method that uses differences in electrical properties between particles and surrounding medium to determine a unique set of cellular properties that can be used as a basis for cell separation. Cell‐based therapies using skeletal stem cells are currently one of the most promising areas for treating a variety of skeletal and muscular disorders. However, identifying and sorting these cells remains a challenge in the absence of unique skeletal stem cell markers. DEP provides an ideal method for identifying subsets of cells without the need for markers by using their dielectric properties. This study used a 3D dielectrophoretic well chip device to determine the dielectric characteristics of two osteosarcoma cell lines (MG‐63 and SAOS‐2) and an immunoselected enriched skeletal stem cell fraction (STRO‐1 positive cell) of human bone marrow. Skeletal cells were exposed to a series of different frequencies to induce dielectrophoretic cell movement, and a model was developed to generate the membrane and cytoplasmic properties of the cell populations. Differences were observed in the dielectric properties of MG‐63, SAOS‐2 and STRO‐1 enriched skeletal populations, which could potentially be used to sort cells in mixed populations. This study provide evidence of the ability to characterize different human skeletal stem and mature cell populations, and acts as a proof‐of‐concept that dielectrophoresis can be exploited to detect, isolate and separate skeletal cell populations from heterogeneous bone marrow cell populations. Copyright © 2012 John Wiley & Sons, Ltd.     

甲基莲心碱对豚鼠心房生理特性及异丙肾上腺素和Ca2+量—效反应的影响

甲基莲心碱1～100μmol/L浓度依赖性地抑制豚鼠左心房收缩性,延长功能性不应期,降低兴奋性;30μmol/L甲基莲心碱能明显提高肾上腺素诱发左心房自律性的阈浓度。对异丙肾上腺素量—效反应的影响,不同于β-受体阻滞剂普萘洛尔,表现为非竞争性拮抗作用,对Ca²⁺量—效反应的影响,与抗钙剂维拉帕米类似,呈竞争性和非竞争性双重拮抗作用。