Objective To improve, with the aid of psychometric analysis, the Balance Evaluation System’s Test (BESTest), a tool designed to analyse several postural control systems that may contribute to poor functional balance in adults. Methods We examined performance of the BESTest in a convenience sample of 115 consecutive adult patients with diverse neurological diagnoses and disease severity, referred to rehabilitation for balance disorders. Factor (both explorative and confirmatory) and Rasch analysis were used to process the data in order to produce a new, reduced and coherent balance measurement tool. Results Factor analysis selected 24 out of the 36 original BESTest items likely to represent the unidimensional construct of ‘dynamic balance’. Rasch analysis was then used to: 1) improve the rating categories, and 2) delete 10 items (misfitting or showing local dependency). The model consisting of the remaining 14 tasks was verified with confirmatory factor analysis to meet the stringent requirements of modern measurement. Conclusion The new 14-item scale (dubbed mini-BESTest) focuses on dynamic balance, can be conducted in 10-15 minutes, and contains items belonging evenly to four of the six sections from the original BESTest. Further studies are needed to confirm the usefulness of the mini-BESTest in clinical settings.

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The 2 scales behave similarly, but the Mini-BESTest appears to have a lower ceiling effect, slightly higher reliability levels, and greater accuracy in classifying individual patients who show significant improvement in balance function.

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The ALSFRS-R fails to satisfy rigorous measurement standards and should be, at least in part, revised. At present, ALSFRS-R should be considered as a profile of mean scores from three different domains (bulbar, motor and respiratory functions) more than a global total score. Further studies on ALSFRS-R using modern psychometric methods are warranted to confirm our findings and refine the metric quality of this scale, through a step by step process.

SUMMARY The mitochondrial calcium uniporter complex is essential for calcium (Ca2+) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca2+ signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate-and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU. We validate mitoxantrone in orthogonal mammalian cell-based assays, demonstrating that our screening approach is an effective and robust tool for MCU-specific drug discovery and, more generally, for the identification of compounds that target mitochondrial functions.

We describe the characteristics of displacement of the head and hip in normal young subjects standing on a moving platform undergoing continuous sinusoidal horizontal translation in the antero-posterior direction, at frequencies ranging from 0.1-1 Hz. The head, hip and malleolus were marked by light-emitting diodes (LEDs), and the displacement of each LED was quantified by (1) the measure of the shift during each cycle of translation, (2) the standard deviation (SD) of the path travelled during the whole trial, (3) the power spectrum (PS) of the signal and (4) the cross-correlation (CC) between pairs of LED signals. At each frequency of translation, with eyes open (EO), the displacement of head was smaller than that of hip, and the displacement of hip was smaller than that of malleolus. With eyes closed (EC), this order was reversed. The peak value of the CC functions of the pairs malleolus/head, malleolus/hip and hip/head decreased by passing from low to high frequency of translation, under both visual conditions, and decreased more for the pair malleolus/head than malleolus/hip. The lags between body segment displacements ranged between 30 ms and 150 ms, on average, the former segment of each pair preceding the latter. The fast Fourier transformation of hip and head displacement showed a power spectrum peak at the frequency imposed by the platform translation. The peak was larger with EC than EO. With EC, another peak appeared at 0.2 Hz, possibly corresponding to the respiratory frequency. We conclude that, when vision was allowed, subjects behaved as a non-rigid, noninverted pendulum, and stabilised head in space. When vision was denied, head oscillated more than the platform, especially at low translation frequencies. Therefore, the strategy of balance control shifted from a pendulum to an inverted-pendulum behaviour, passing from active head-and-trunk control to maximal body compliance to the perturbation.