Biomechanical Loading as an Alternative Treatment for Tremor: A Review of Two Approaches

Background: Tremor is the most common movement disorder and strongly increases in incidence and prevalence with aging. Although not life threatening, upper-limb tremors hamper the independence of 65% of people suffering from them affected persons, greatly impacting their quality of life. Current treatments include pharmacotherapy and surgery (thalamotomy and deep brain stimulation). However, these options are not sufficient for approximately 25% of patients. Therefore, further research and new therapeutic options are required to effectively manage pathological tremor. Methods: This paper presents findings of two research projects in which two different wearable robots for tremor management were developed based on force loading and validated. The first consisted of a robotic exoskeleton that applied forces to tremulous limbs and consistently attenuated mild and severe tremors. The second was a neuroprosthesis based on transcutaneous neurostimulation. A total of 22 patients suffering from parkinsonian or essential tremor (ET) of different severities were recruited for experimental validation, and both systems were evaluated using standard tasks employed for neurological examination. The inclusion criterion was a postural and/or kinetic pathological upper-limb tremor resistant to medication. Results: The results demonstrate that both approaches effectively suppressed tremor in most patients, although further research is required. The work presented here is based on clinical evidence from a small number of patients (n = 10 for robotic exoskeleton and n = 12 for the neuroprosthesis), but most had a positive response to the approaches. In summary, biomechanical loading is non-invasive and painless. It may be effective in patients who are insufficiently responsive (or have adverse reactions) to drugs or in whom surgery is contraindicated. Discussion: This paper identifies and evaluates biomechanical loading approaches to tremor management and discusses their potential

During gait with crutches

The goal of this study was to develop a three-dimensional kinematic and kinetic model of the right upper extremity and a Lofstrand crutch in order to analyze joint displacements and loads during crutch-assisted gait. A Lofstrand crutch was instrumented with a six-component load cell to measure forces and moments at the crutch tip. The crutch and the right upper extremity of a subject were instrumented with markers to obtain kinematic data. A biomechanical model based on rigid bodies was implemented in biomechanical analysis software. To demonstrate the functionality of the model, a pilot test was conducted on one healthy individual during Lofstrand crutch-assisted gait. The shoulder extended during the support phase and flexed in the swing phase, the elbow flexed during the swing, and the wrist remained in extension throughout the cycle. In the shoulder and elbow joints, the predominant reaction forces were upward, whereas the internal force moments were flexion and extension, respectively. This tool will be useful when it comes to identifying risk factors for joint pathology associated with pattern gait, aid design or crutch overuse.Peer Reviewe

Instrumentation and biomechanical model for kinematic and kinetic analysis of upper limbs during gait with crutches

[EN] The goal of this study was to develop a three-dimensional kinematic and kinetic model of the right upper extremity and a Lofstrand crutch in order to analyze joint displacements and loads during crutch-assisted gait. A Lofstrand crutch was instrumented with a six-component load cell to measure forces and moments at the crutch tip. The crutch and the right upper extremity of a subject were instrumented with markers to obtain kinematic data. A biomechanical model based on rigid bodies was implemented in biomechanical analysis software. To demonstrate the functionality of the model, a pilot test was conducted on one healthy individual during Lofstrand crutch-assisted gait. The shoulder extended during the support phase and flexed in the swing phase, the elbow flexed during the swing, and the wrist remained in extension throughout the cycle. In the shoulder and elbow joints, the predominant reaction forces were upward, whereas the internal force moments were flexion and extension, respectively. This tool will be useful when it comes to identifying risk factors for joint pathology associated with pattern gait, aid design or crutch overuse.This work was supported by a grant from the Castile-La Mancha Social & Health Foundation (Fundación Sociosanitaria de Castilla la Mancha) (PI2010/50). The research for this manuscript was partially funded by a CONSOLIDER INGENIO grant from the Spanish Ministry of Science and Innovation under its HYPER project (Hybrid NeuroProsthetic and NeuroRobotic Devices for Functional Compensation and Rehabilitation of Motor Disorders, CSD2009- 00067). We should like to thank Ana de los Reyes, Antonio del Ama, Beatriz Crespo, Fernando Trincado, Iris Dimbwadyo, Vicente Lozano, and Soraya Pérez for their contributions to this study.Pérez-Rizo, E.; Solís-Mozos, M.; Belda Lois, JM.; Page Del Pozo, AF.; Taylor, J.; Pons, JL.; Gil-Agudo, Á. (2013). Instrumentation and biomechanical model for kinematic and kinetic analysis of upper limbs during gait with crutches. Journal of Accessibility and Design for All. 3(2):135-156. https://doi.org/10.17411/jacces.v3i2.16S1351563

Rehabilitation of gait after stroke: a review towards a top-down approach

This document provides a review of the techniques and therapies used in gait rehabilitation after stroke. It also examines the possible benefits of including assistive robotic devices and brain-computer interfaces in this field, according to a top-down approach, in which rehabilitation is driven by neural plasticity

Considerations for future modification of The Association for the Study of Reproductive Biology embryo grading system incorporating time-lapse observations

10 Pág.The Association for the Study of Reproductive Biology (ASEBIR) Interest Group in Embryology (in Spanish 'Grupo de Interés de Embriología') reviewed key morphokinetic parameters to assess the contribution of time-lapse technology (TLT) to the ASEBIR grading system. Embryo grading based on morphological characteristics is the most widely used method in human assisted reproduction laboratories. The introduction and implementation of TLT has provided a large amount of information that can be used as a complementary tool for morphological embryo evaluation and selection. As part of IVF treatments, embryologists grade embryos to decide which embryos to transfer or freeze. At the present, the embryo grading system developed by ASEBIR does not consider dynamic events observed through TLT. Laboratories that are using TLT consider those parameters as complementary data for embryo selection. The aim of this review was to evaluate review time-specific morphological changes during embryo development that are not included in the ASEBIR scoring system, and to consider them as candidates to add to the scoring system.Peer reviewe

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome\u27s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism