Efficacy of a technology-based client-centred training system in neurological rehabilitation: a randomised controlled trial

Background

Maintaining upright posture is an unstable task that requires sophisticated neuro-muscular control. Humans use foot–ground interaction forces, characterized by point of application, magnitude, and direction to manage body accelerations. When analyzing the directions of the ground reaction forces of standing humans in the frequency domain, previous work found a consistent pattern in different frequency bands. To test whether this frequency-dependent behavior provided a distinctive signature of neural control or was a necessary consequence of biomechanics, this study simulated quiet standing and compared the results with human subject data.

Methods

Aiming to develop the simplest competent and neuromechanically justifiable dynamic model that could account for the pattern observed across multiple subjects, we first explored the minimum number of degrees of freedom required for the model. Then, we applied a well-established optimal control method that was parameterized to maximize physiologically-relevant insight to stabilize the balancing model.

Results

If a standing human was modeled as a single inverted pendulum, no controller could reproduce the experimentally observed pattern. The simplest competent model that approximated a standing human was a double inverted pendulum with torque-actuated ankle and hip joints. A range of controller parameters could stabilize this model and reproduce the general trend observed in experimental data; this result seems to indicate a biomechanical constraint and not a consequence of control. However, details of the frequency-dependent pattern varied substantially across tested control parameter values. The set of parameters that best reproduced the human experimental results suggests that the control strategy employed by human subjects to maintain quiet standing was best described by minimal control effort with an emphasis on ankle torque.

Conclusions

The findings suggest that the frequency-dependent pattern of ground reaction forces observed in quiet standing conveys quantitative information about human control strategies. This study’s method might be extended to investigate human neural control strategies in different contexts of balance, such as with an assistive device or in neurologically impaired subjects.

     

αE‐catenin is a candidate tumor suppressor for the development of E‐cadherin‐expressing lobular‐type breast cancer

Although mutational inactivation of E‐cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), approximately 10–15% of all ILCs retain membrane‐localized E‐cadherin despite the presence of an apparent non‐cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α‐catenin (CTNNA1) loss in the regulation of anchorage independence of non‐invasive breast carcinoma. We found that inactivating somatic CTNNA1 mutations in human breast cancer correlated with lobular and mixed ducto‐lobular phenotypes. Further, inducible loss of α‐catenin in mouse and human E‐cadherin‐expressing breast cancer cells led to atypical localization of E‐cadherin, a rounded cell morphology, and anoikis resistance. Pharmacological inhibition experiments subsequently revealed that, similar to E‐cadherin‐mutant ILC, anoikis resistance induced by α‐catenin loss was dependent on Rho/Rock‐dependent actomyosin contractility. Finally, using a transplantation‐based conditional mouse model, we demonstrate that inducible inactivation of α‐catenin instigates acquisition of lobular features and invasive behavior. We therefore suggest that α‐catenin represents a bona fide tumor suppressor for the development of lobular‐type breast cancer and as such provides an alternative event to E‐cadherin inactivation, adherens junction (AJ) dysfunction, and subsequent constitutive actomyosin contraction. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Photochemical damage to skin fibroblasts caused by protoporphyrin and violet light

Summary Foreskin fibroblasts cultured in a medium containing protoporphyrin and exposed to violet light lose the capacity to proliferate. This phenomenon can be assessed on the basis of the ability of the irradiated cells to form colonies. Potentially lethal injuries can, however, be repaired during post-irradiation incubation under optimal growth conditions. We investigated the photodynamically induced transformations of certain molecular targets in the irradiated cells. Biochemical analysis showed that only traces of unsaturated fatty acids were oxidized, but SH groups of both the membranes and the cytosol appeared to be very sensitive targets. Of the tryptophan content, 20% was damaged during irradiation. Recovery was observed during post-irradiation incubation. The tryptophan content and the SH groups recovered to some extent, and these results showed a good correlation with the regeneration of surviving cells.     

The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry

Breast Cancer Research and Treatment - The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer,...     

The Nef-infectivity enigma: mechanisms of enhanced lentiviral infection

The Nef protein is an essential factor for lentiviral pathogenesis in humans and other simians. Despite a multitude of functions attributed to this protein, the exact role of Nef in disease progression remains unclear. One of its most intriguing functions is the ability of Nef to enhance the infectivity of viral particles. In this review we will discuss current insights in the mechanism of this well-known, yet poorly understood Nef effect. We will elaborate on effects of Nef, on both virion biogenesis and the early stage of the cellular infection, that might be involved in infectivity enhancement. In addition, we provide an overview of different HIV-1 Nef domains important for optimal infectivity and briefly discuss some possible sources of the frequent discrepancies in the field. Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function.     

Successful upper airway stimulation therapy in an adult Down syndrome patient with severe obstructive sleep apnea

Sleep and Breathing - The aim of this study was to report on the successful application of upper airway stimulation (UAS) therapy in an adult Down syndrome (DS) patient with severe obstructive...