Improving Inverse Dynamics Accuracy in a Planar Walking Model Based on Stable Reference Point

Physiologically and biomechanically, the human body represents a complicated system with an abundance of degrees of freedom (DOF). When developing mathematical representations of the body, a researcher has to decide on how many of those DOF to include in the model. Though accuracy can be enhanced at the cost of complexity by including more DOF, their necessity must be rigorously examined. In this study a planar seven-segment human body walking model with single DOF joints was developed. A reference point was added to the model to track the body’s global position while moving. Due to the kinematic instability of the pelvis, the top of the head was selected as the reference point, which also assimilates the vestibular sensor position. Inverse dynamics methods were used to formulate and solve the equations of motion based on Newton-Euler formulae. The torques and ground reaction forces generated by the planar model during a regular gait cycle were compared with similar results from a more complex three-dimensional OpenSim model with muscles, which resulted in correlation errors in the range of 0.9–0.98. The close comparison between the two torque outputs supports the use of planar models in gait studies

A New Technique to Improve the Operation of Prosthetic Limbs during Muscle Fatigue

Prosthetic limbs hold a promise to renew the quality of life for the amputee. Neural commands are decoded via a classifier to generate control signals for the prosthetic devices. In the literature, many challenges and limitations have been identified that affect the prosthesis operation. One such drawback is muscle fatigue which degrades the surface electromyogram (sEMG) signals, and consequently, the performance of the deployed classification algorithm declines from 90% to 50% of average accuracy. We used a new technique using the Linear Discrimination Analysis (LDA) algorithm and the muscle synergy-based task discrimination (MSD) algorithm to improve the classification accuracy. In this technique, during muscles contraction/fatigue, we used the LDA algorithms in the beginning and the MSD algorithms later. The applied technique exhibited better movement classification performance during normal and muscle fatigue conditions. However, more work needs to be done to effectively solve the muscle fatigue problem in prosthesis design

A Review of EMG Techniques for Detection of Gait Disorders

Electromyography (EMG) is a commonly used technique to record myoelectric signals, i.e., motor neuron signals that originate from the central nervous system (CNS) and synergistically activate groups of muscles resulting in movement. EMG patterns underlying movement, recorded using surface or needle electrodes, can be used to detect movement and gait abnormalities. In this review article, we examine EMG signal processing techniques that have been applied for diagnosing gait disorders. These techniques span from traditional statistical tests to complex machine learning algorithms. We particularly emphasize those techniques are promising for clinical applications. This study is pertinent to both medical and engineering research communities and is potentially helpful in advancing diagnostics and designing rehabilitation devices

Effect of Novel Dietary Supplement on Metabolism in \u3cem\u3evitro\u3c/em\u3e and \u3cem\u3ein vivo\u3c/em\u3e

Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF) in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were measured hourly for 3 h post-ingestion. To investigate molecular effects, human rhabdomyosarcoma cells (RD) and mouse myocytes (C2C12) were treated with various doses of RF for various durations. RF enhanced energy expenditure and systolic blood pressure in human males without altering substrate utilization. In myocytes, RF enhanced metabolism, metabolic gene expression, and mitochondrial content suggesting RF may target common energetic pathways which control mitochondrial biogenesis. RF appears to increase metabolism immediately following ingestion, although it is unclear if RF provides benefits beyond those provided by caffeine alone. Additional research is needed to examine safety and efficacy for human weight loss

James Lind Alliance research priorities: What role do carbohydrates, fats and proteins have in the management of type 2 diabetes, and are there risks and benefits associated with particular approaches?

Aims To assess the role played by carbohydrates, fat and proteins in the management of Type 2 diabetes. Background Diabetes research tends to reflect the interests of academics or the pharmaceutical industry, rather than those of people living with Type 2 diabetes. The James Lind Alliance and Diabetes UK addressed this issue by defining the research priorities of people living with Type 2 diabetes. Three of the top 10 research priority questions focused on lifestyle. Methods A narrative review was undertaken with a structured search strategy using three databases. Search terms included the three macronutrients and Type 2 diabetes. No restrictions were placed on macronutrient quantity or length of study follow‐up. Outcomes included changes in HbA1c, body weight, insulin sensitivity and cardiovascular risk. Results There is no strong evidence that there is an optimal ratio of macronutrients for improving glycaemic control or reducing cardiovascular risk. Challenges included defining the independent effect of macronutrient manipulation and identifying the effects of macronutrients, independent of foods and dietary patterns. Extreme intakes of macronutrients may be associated with health risks. Conclusions It is challenging to formulate food‐based guidelines from studies based on macronutrient manipulation. Structured education should be offered to support individuals in discovering their optimal, individual dietary approach. Recommendations for dietary guidelines should be expressed in terms of foods and not macronutrients

Exploration of T cell immune responses by expression of a dominant-negative SHP1 and SHP2

SHP1 and SHP2 are SH2 domain-containing proteins which have inhibitory phosphatase activity when recruited to phosphorylated ITIMs and ITSMs on inhibitory immune receptors. Consequently, SHP1 and SHP2 are key proteins in the transmission of inhibitory signals within T cells, constituting an important point of convergence for diverse inhibitory receptors. Therefore, SHP1 and SHP2 inhibition may represent a strategy for preventing immunosuppression of T cells mediated by cancers hence improving immunotherapies directed against these malignancies. Both SHP1 and SHP2 contain dual SH2 domains responsible for localization to the endodomain of inhibitory receptors and a protein tyrosine phosphatase domain which dephosphorylates and thus inhibits key mediators of T cell activation. We explored the interaction of the isolated SH2 domains of SHP1 and SHP2 to inhibitory motifs from PD1 and identified strong binding of both SH2 domains from SHP2 and more moderate binding in the case of SHP1. We next explored whether a truncated form of SHP1/2 comprising only of SH2 domains (dSHP1/2) could act in a dominant negative fashion by preventing docking of the wild type proteins. When co-expressed with CARs we found that dSHP2 but not dSHP1 could alleviate immunosuppression mediated by PD1. We next explored the capacity of dSHP2 to bind with other inhibitory receptors and observed several potential interactions. In vivo we observed that the expression of PDL1 on tumor cells impaired the ability of CAR T cells to mediate tumor rejection and this effect was partially reversed by the co-expression of dSHP2 albeit at the cost of reduced CAR T cell proliferation. Modulation of SHP1 and SHP2 activity in engineered T cells through the expression of these truncated variants may enhance T cell activity and hence efficacy in the context of cancer immunotherapy

In Vitro and In Vivo Characterization of the Alkaloid Nuciferine

RationaleThe sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.MethodsNuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.ResultsNuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.ConclusionsThe molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions

Aggregation of nontuberculous mycobacteria is regulated by carbon-nitrogen balance

Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens that colonize household water systems and cause chronic lung infections in susceptible patients. The ability of NTM to form surface-attached biofilms in the nonhost environment and corded aggregates in vivo is important to their ability to persist in both contexts. Underlying the development of these multicellular structures is the capacity of mycobacterial cells to adhere to one another. Unlike most other bacteria, NTM spontaneously and constitutively aggregate in vitro, hindering our ability to understand the transition between planktonic and aggregated cells. While culturing a model NTM, Mycobacterium smegmatis, in rich medium, we fortuitously discovered that planktonic cells accumulate after ∼3 days of growth. By providing selective pressure for bacteria that disperse earlier, we isolated a strain with two mutations in the oligopeptide permease operon (opp). A mutant lacking the opp operon (Δopp) disperses earlier than wild type (WT) due to a defect in nutrient uptake. Experiments with WT M. smegmatis revealed that growth as aggregates is favored when carbon is replete, but under conditions of low available carbon relative to available nitrogen, M. smegmatis grows as planktonic cells. By adjusting carbon and nitrogen sources in defined medium, we tuned the cellular C/N ratio such that M. smegmatis grows either as aggregates or as planktonic cells. C/N-mediated aggregation regulation is widespread among NTM with the possible exception of rough-colony Mycobacterium abscessus isolates. Altogether, we show that NTM aggregation is a controlled process that is governed by the relative availability of carbon and nitrogen for metabolism