[From symptom to diagnosis-symptom checkers re-evaluated : Are symptom checkers finally sufficient and accurate to use? An update from the ENT perspective]. / Vom Symptom zur Diagnose ­ Tauglichkeit von Symptom-Checkern : Update aus Sicht der HNO.

BACKGROUND: Every seventh diagnosis is a misdiagnosis. Each year, 1.5 million lives could be saved worldwide with the correct diagnosis. Physicians have to consider over 20,000 diseases. A study from Harvard University published in 2015 tested 19 symptom checkers and found them to be insufficient, with only 29-71% accuracy in diagnosis. OBJECTIVE: The current study investigates the diagnostic accuracy of new symptom checkers from an ENT perspective. MATERIALS AND METHODS: The authors update the abovenamed diagnostic accuracy comparison by (1) including the five new symptom checkers Symptoma, Ada, FindZebra, Mediktor, and Babylon; and (2) normalizing results of the previously tested symptom checkers as to reflect each diagnostic accuracy based on the same set of patient vignettes. The winner is then compared to the two symptom checkers with the most scientific evidence, namely Isabel and FindZebra, on the basis of an ENT-specific test with patient vignettes sourced from the British Medical Journal. RESULTS: Most of the new symptom checkers demonstrated diagnostic accuracy rates within the previously established range, with the exception of Symptoma, which scored the right diagnosis in 82.2% of cases at the top of the list (+38% points), and in 100% of cases in the top 3 (+29% points) and the top 10 (+16% points), thus raising the bar in this field. The cross-validation with ENT cases resulted in a diagnostic accuracy of 64.3 vs. 21.4 vs. 26.2% (top 1), 92.9 vs. 40.5 vs. 42.9% (top 3), and 100 vs. 61.9 vs. 54.8% (top 10) for Symptoma vs. Isabel vs. FindZebra, respectively. CONCLUSIONS: Symptoma is the first and only viable solution in this market. Large-scale studies should be conducted to further validate these results as well as to assess the actual practical performance of the symptom checkers and their ability to diagnose rare diseases.

Robustness of atomistic Go models in predicting native-like folding intermediates.

Go models are exceedingly popular tools in computer simulations of protein folding. These models are native-centric, i.e., they are directly constructed from the protein's native structure. Therefore, it is important to understand up to which extent the atomistic details of the native structure dictate the folding behavior exhibited by Go models. Here we address this challenge by performing exhaustive discrete molecular dynamics simulations of a Go potential combined with a full atomistic protein representation. In particular, we investigate the robustness of this particular type of Go models in predicting the existence of intermediate states in protein folding. We focus on the N47G mutational form of the Spc-SH3 folding domain (x-ray structure) and compare its folding pathway with that of alternative native structures produced in silico. Our methodological strategy comprises equilibrium folding simulations, structural clustering, and principal component analysis.

Effects of physical exercise on peripheral vision and learning in children with spina bifida manifesta.

The purpose of this research was to investigate the effects of active exercise of the arms on various physiological, perceptual, and cognitive parameters of children with spina bifida manifesta who were aged 9 to 12 yr. Following a 5-min. rest interval, subjects were either not exercised (control days) for a 6-min. period or were exercised (experimental days) for a 6-min. period. Cardiac measures, respiratory function, peripheral vision, and figural learning trials were recorded after exercise. Wilcoxon matched-pairs signed rank tests were computed on the means of the exercise and no-exercise conditions for each measure. Six minutes of active exercise resulted in significant increases in peripheral vision, respiratory and cardiac measures and significant decreases in figural learning trials for these children. A floor effect was noted for the figural learning test. It was concluded that exercise increased blood flow through the lungs allowing for greater oxygen diffusion in the brain and other facilitatory effects resulting in more effective cerebral activity. Curriculum revisions for such children seem to indicate the importance of activity in facilitating subsequent learning.

Identification of a conserved aggregation-prone intermediate state in the folding pathways of Spc-SH3 amyloidogenic variants.

We compared the folding pathways of selected mutational variants of the α-spectrin SH3 domain (Spc-SH3) by using a continuum model that combines a full atomistic protein representation with the Go potential. Experimental data show that the N47G mutant shows very little tendency to aggregate while the N47A and triple mutant D48G(2Y) are both amyloidogenic, with the latter being clearly more aggregation prone. We identified a strikingly similar native-like folding intermediate across the three mutants, in which strand ß(1) is totally unstructured and more than half of the major hydrophobic core residues are highly solvent exposed. Results from extensive docking simulations show that the ability of the intermediates to dimerize is largely driven by strand ß(1) and is consistent with the in vitro aggregation behavior reported for the corresponding mutants. They further suggest that residues 44 and 53, which are key players in the nucleation-condensation mechanism of folding, are also important triggers of the aggregation process.