Effects of half-dose spiomet treatment in girls with early puberty and accelerated bone maturation: a multicenter, randomized, placebo-controlled study protocol.

BACKGROUND: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. METHODS: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0-9.3 years; birthweight (BW) for gestational age in lower tertile (-1.96< Z-score <-0.44), body mass index (BMI) in upper tertile (+0.44< Z-score < +1.96) and early progressive puberty (Tanner B2 at 7.7-9.0 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. INTERVENTIONS: randomization (1:1) for placebo vs mini-spiomet. PRIMARY OUTCOME: annualized bone age advancement (0-1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. DISCUSSION: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. TRIAL REGISTRATION: EudraCT 2021-006766-21. Registered on May 30, 2022.

Applying Entropy to Human Center of Foot Pressure Data to Assess Attention Investment in Balance Control.

Assessing the amount of attention invested in the control of balance is crucial when evaluating balance abilities. The purpose of the present study was to examine the relevance of applying entropy to human center of foot pressure data to assess attention investment in balance control. To achieve this goal, young healthy adults were tested in a static postural task consisting in standing as immobile as possible with their eyes closed under normal, altered (foam) and improved (ankle-foot orthosis). The center of foot pressure displacements were recorded using a force platform. Three dependent variables were computed. Results showed decreased values of velocity and displacement of Center of Pressure (CoP), indicating a less important amount of postural sway, and increased values of Sample Entropy of CoP, suggesting a less amount of attention invested in the control of bipedal posture than when the somatosensation from the foot and the ankle was normal.

Assessment of attention demand for balance control using a Smartphone: implementation and evaluation.

Dual-task paradigm studies strongly highlights the importance of considering attention demand when assessing the ability of an individual to control balance. This paper introduces the implementation of a Smartphone application for quantitative and independent assessment of attention demand for balance control. A proof-of-concept study was designed to evaluate the effectiveness of the iBalance system in assessing the attention demand for balance control. Eight young healthy adults voluntarily performed a dual-task paradigm procedure, in which they were asked to respond vocally as rapidly as possible to an unpredictable auditory stimulus while maintaining a stable seated posture and two standing postures of increasing difficulty: bipedal and unipedal. Trunk sway measurements were used as an index of postural performance, whereas reaction time measurements were used as an index of the attention demand allocated for executing the postural tasks. In line with the existing literature, results showed that, as the postural task increased in difficulty, trunk sway and attention demand used for controlling balance increased. Taken together, these results are promising, suggesting that the iBalance system could constitute a wireless, portable, lightweight, pervasive, low-cost, user-friendly Smartphone-based system for quantitative and independent assessment of attention demand for balance control suitable for home use.

Mobile Phone-Based Joint Angle Measurement for Functional Assessment and Rehabilitation of Proprioception.

Assessment of joint functional and proprioceptive abilities is essential for balance, posture, and motor control rehabilitation. Joint functional ability refers to the capacity of movement of the joint. It may be evaluated thereby measuring the joint range of motion (ROM). Proprioception can be defined as the perception of the position and of the movement of various body parts in space. Its role is essential in sensorimotor control for movement acuity, joint stability, coordination, and balance. Its clinical evaluation is commonly based on the assessment of the joint position sense (JPS). Both ROM and JPS measurements require estimating angles through goniometer, scoliometer, laser-pointer, and bubble or digital inclinometer. With the arrival of Smartphones, these costly clinical tools tend to be replaced. Beyond evaluation, maintaining and/or improving joint functional and proprioceptive abilities by training with physical therapy is important for long-term management. This review aims to report Smartphone applications used for measuring and improving functional and proprioceptive abilities. It identifies that Smartphone applications are reliable for clinical measurements and are mainly used to assess ROM and JPS. However, there is lack of studies on Smartphone applications which can be used in an autonomous way to provide physical therapy exercises at home.

Performance Evaluation of Smartphone Inertial Sensors Measurement for Range of Motion.

Over the years, smartphones have become tools for scientific and clinical research. They can, for instance, be used to assess range of motion and joint angle measurement. In this paper, our aim was to determine if smartphones are reliable and accurate enough for clinical motion research. This work proposes an evaluation of different smartphone sensors performance and different manufacturer algorithm performances with the comparison to the gold standard, an industrial robotic arm with an actual standard use inertial motion unit in clinical measurement, an Xsens product. Both dynamic and static protocols were used to perform these comparisons. Root Mean Square (RMS) mean values results for static protocol are under 0.3° for the different smartphones. RMS mean values results for dynamic protocol are more prone to bias induced by Euler angle representation. Statistical results prove that there are no filter effect on results for both protocols and no hardware effect. Smartphones performance can be compared to the Xsens gold standard for clinical research.

Dynalets: a new method for modelling and compressing biological signals. Applications to physiological and molecular signals.

The biological information coming from electrophysiologic sensors like ECG, pulse sensor or from molecular signal devices like NMR spectrometry has to be visualized and manipulated in a compressed way for an efficient medical use by clinicians, if stored in scientific data bases or in personalized patient records repositories. Here, we define a new transform called Dynalet based on Liénard ordinary differential equations susceptible to model the mechanism at the source of the studied signal, and we propose to apply this new technique first to the modelling and compression of real biological periodic signals like ECG and pulse rhythm. We consider that the cardiovascular activity results from the summation of cellular oscillators located in the cardiac sinus node and we show that, as a result, the van der Pol oscillator (a particular Liénard system) fits well the ECG signal and the pulse signal. The reconstruction of the original signal (pulse or ECG) using Dynalet transform is then compared with that of Fourier, counting the number of parameters to be set for obtaining an expected signal-to-noise ratio. Then, we apply the Dynalet transform to the modelling and compression of molecular spectra obtained by protein NMR spectroscopy. The reconstruction of the original signal (peak) using Dynalet transform is again compared with that of Fourier. After reconstructing visually the peak, we propose to periodize the signal and give it to hear, the whole process being called the protein "stethoscope".

Contribution of each leg to the control of unperturbed bipedal stance in lower limb amputees: new insights using entropy.

The present study was designed to assess the relative contribution of each leg to unperturbed bipedal posture in lower limb amputees. To achieve this goal, eight unilateral traumatic trans-femoral amputees (TFA) were asked to stand as still as possible on a plantar pressure data acquisition system with their eyes closed. Four dependent variables were computed to describe the subject's postural behavior: (1) body weight distribution, (2) amplitude, (3) velocity and (4) regularity of centre of foot pressure (CoP) trajectories under the amputated (A) leg and the non-amputated (NA) leg. Results showed a larger body weight distribution applied to the NA leg than to the A leg and a more regular CoP profiles (lower sample entropy values) with greater amplitude and velocity under the NA leg than under the A leg. Taken together, these findings suggest that the NA leg and the A leg do not equally contribute to the control of unperturbed bipedal posture in TFA. The observation that TFA do actively control unperturbed bipedal posture with their NA leg could be viewed as an adaptive process to the loss of the lower leg afferents and efferents because of the unilateral lower-limb amputation. From a methodological point of view, these results demonstrate the suitability of computing bilateral CoP trajectories regularity for the assessment of lateralized postural control under pathological conditions.