Adaptational phenomena and mechanical responses during running: effect of surface, aging and task experience

The goals of the study were to identify adaptational phenomena in running mechanics over a variety of surfaces due to age related changes in the muscle-tendon units (MTUs) capacities, to examine whether running experience is associated with adaptational effects on running mechanics over a variety of surfaces even at old age, and to investigate whether surface condition affects running mechanics. The investigation was executed on 30 old and 19 young including 29 runners and 20 non-active subjects. In a previous study we documented that the older had lower MTUs capacities. In the present study running mechanics were analysed as the same subjects ran at 2.7 m/s over three surfaces having different compliance. Surface condition did not affect centre of mass trajectory, duty factor or joint kinetics (P > 0.01). Older react to the reduced MTUs capacity by increasing duty factor and benefiting from a mechanical advantage for the triceps surae MTU and a lower rate of force generation on all surfaces (P < 0.01). Runners displayed lower average horizontal forces and a higher mechanical advantage for the quadriceps femoris MTU for all surfaces (P < 0.01). The results provided strong evidence on that running strategy remained essentially unchanged over a variety of surfaces. Adaptive improvements in running mechanics due to task experience were present for all surfaces and did not depend on age. We further concluded that older adults were able to recalibrate their running strategy to adjust the task effort to the reduced MTUs capacities in a feedforward control manner for a variety of mechanical environments.     

Regulated complement deposition on the surface of human endothelial cells: effect of tobacco smoke and shear stress

Cigarette smoke and hemodynamic stress both contribute to vascular inflammation and associated atherosclerosis. We recently demonstrated direct activation of complement components C4 and C3 on human endothelial cells (EC). The present study was designed to explore complement activation on bone marrow microvascular endothelial cells (BMEC) and human umbilical vein endothelial cells (HUVEC) in response to endothelial cell injury by tobacco smoke extract, shear stress, or other known inflammatory and atherogenic mediators, lipopolysaccharide (LPS) and INF-gamma. Following treatment, confluent EC monolayers were exposed to plasma (60 min, 37 degrees C), and cell surface deposition of stable complement derivatives C4d, iC3b and SC5b-9 was measured in situ using an ELISA approach. Consistent with previous results, moderate levels of C4d, iC3b and SC5b-9 deposition were observed on native EC monolayers exposed to human plasma. Tobacco smoke and shear stress enhanced EC C4d deposition. In contrast, LPS and INF-gamma failed to affect EC mediated complement activation, despite evidence of EC activation illustrated by ICAM-1 expression. The combination of tobacco smoke and shear stress nearly doubled EC C4d expression. No increases in iC3b or SC5b-9 were noted, suggesting inhibition of classical and alternative pathway C3 convertase assembly or activity. Indeed, concomitantly increased surface expression of complement regulatory proteins CD35 (CR1) and CD55 was observed following EC exposure to tobacco smoke and shear stress. These results suggest that a balance between complement activation and regulation exists at the EC surface, and may impact vascular injury leading to thrombosis, arteriosclerosis, and atherogenesis.     

Association between gallstone-evoked pain, inflammation and proliferation of nerves in the gallbladder: a possible explanation for clinical differences

OBJECTIVE: To investigate whether enhanced neuroproliferation could be involved in the pathogenesis of gallstone pain. MATERIAL AND METHODS: Gallbladders from 117 patients with gallstones and 43 controls were examined. The gallbladder samples were immunostained against the pan-neuronal marker PGP 9.5 and the number of nerves and nerve area per tissue area estimated. RESULTS: More nerves and an increased nerve area per tissue area were found in uncomplicated symptomatic gallstone disease. In comparison, acute cholecystitis displayed a significantly (p=0.01) decreased number of nerves and nerve area per tissue area. In both categories, the gallbladder neck contained more nerves (p=0.06 and 0.04, respectively) and an increased nerve area per tissue area (p=0.034 and 0.008, respectively) than the body. CONCLUSIONS: Uncomplicated disease showed enhanced neuroproliferation, significantly more in the gallbladder neck, whereas significantly fewer nerves were observed in acute cholecystitis. Nerve growth alteration may play a role in uncomplicated gallstone pain but the pathology may be different in inflammation.     

Production and diagnostic application of monoclonal antibodies against influenza virus H5

Nine monoclonal antibodies (mAbs) against avian influenza virus (AI) H5 subtype from mice immunized with inactivated virus H5N1 (A/Turkey/ON/6213/66) were produced. Upon testing, the results indicated that the binding epitopes of eight out of the nine mAbs were conformational, while one mAb (#7) reacted with denatured H5N1 only. Two mAbs #10 and #11 reacted with all of the thirteen H5 strains tested indicating that the binding epitopes of these mAbs were conserved among these H5 subtypes.Possible applications of these mAbs in rapid tests for H5 antigen were explored. Double antibody sandwich (DAS) ELISAs were developed using two selected mAbs #10 and #11. This DAS ELISA detects specific H5 viruses and is able to identify all thirteen H5 strains tested. Three mAbs showed reactivity with AI H5 antigen for both immunofluorescence (IF) and immunohistochemistry. A cELISA used to screen chickens that had been infected with an H5 virus was developed with mAb #9 and recombinant H5 antigen. The sera from chickens that have been infected with an H5N1 virus were examined using the cELISA. 80% of the sera from H5 infected chickens showed a positive H5 specific antibody response at 7 days post-infection (dpi) and remained positive until the end of the experiment on day 30 (>40% inhibition). This panel of the AI H5 specific mAbs is valuable for the development of various immunoassays.     

Refining a probabilistic model for interpreting verbal autopsy data

OBJECTIVE: To build on the previously reported development of a Bayesian probabilistic model for interpreting verbal autopsy (VA) data, attempting to improve the model's performance in determining cause of death and to reassess it. DESIGN: An expert group of clinicians, coming from a wide range geographically and in terms of specialization, was convened. Over a four-day period the content of the previous probabilistic model was reviewed in detail and adjusted as necessary to reflect the group consensus. The revised model was tested with the same 189 VA cases from Vietnam, assessed by two local clinicians, that were used to test the preliminary model. RESULTS: The revised model contained a total of 104 indicators that could be derived from VA data and 34 possible causes of death. When applied to the 189 Vietnamese cases, 142 (75.1%) achieved concordance between the model's output and the previous clinical consensus. The remaining 47 cases (24.9%) were presented to a further independent clinician for reassessment. As a result, consensus between clinical reassessment and the model's output was achieved in 28 cases (14.8%); clinical reassessment and the original clinical opinion agreed in 8 cases (4.2%), and in the remaining 11 cases (5.8%) clinical reassessment, the model, and the original clinical opinion all differed. Thus overall the model was considered to have performed well in 170 cases (89.9%). CONCLUSIONS: This approach to interpreting VA data continues to show promise. The next steps will be to evaluate it against other sources of VA data. The expert group approach to determining the required probability base seems to have been a productive one in improving the performance of the model.     

Traffic, susceptibility, and childhood asthma

Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5-7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child's history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR)=1.29; 95% confidence interval (CI), 1.01-1.86], prevalent asthma (OR=1.50; 95% CI, 1.16-1.95), and wheeze (OR=1.40; 95% CI, 1.09-1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR=1.85; 95% CI, 1.11-3.09), prevalent asthma (OR=2.46; 95% CI, 0.48-4.09), and recent wheeze (OR=2.74; 95% CI, 1.71-4.39). The higher risk of asthma near a major road decreased to background rates at 150-200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.