Musculoskeletal modelling deconstructs the paradoxical effects of elastic ankle exoskeletons on plantar-flexor mechanics and energetics during hopping

This is the final version. Available from Company of Biologists via the DOI in this record.Experiments have shown that elastic ankle exoskeletons can be used to reduce ankle joint and plantar-flexor muscle loading when hopping in place and, in turn, reduce metabolic energy consumption. However, recent experimental work has shown that such exoskeletons cause less favourable soleus (SO) muscle-tendon mechanics than is observed during normal hopping, which might limit the capacity of the exoskeleton to reduce energy consumption. To directly link plantar-flexor mechanics and energy consumption when hopping in exoskeletons, we used a musculoskeletal model of the human leg and a model of muscle energetics in simulations of muscle-tendon dynamics during hopping with and without elastic ankle exoskeletons. Simulations were driven by experimental electromyograms, joint kinematics and exoskeleton torque taken from previously published data. The data were from seven males who hopped at 2.5 Hz with and without elastic ankle exoskeletons. The energetics model showed that the total rate of metabolic energy consumption by ankle muscles was not significantly reduced by an ankle exoskeleton. This was despite large reductions in plantar-flexor force production (40-50%). The lack of larger metabolic reductions with exoskeletons was attributed to increases in plantar-flexor muscle fibre velocities and a shift to less favourable muscle fibre lengths during active force production. This limited the capacity for plantar-flexors to reduce activation and energy consumption when hopping with exoskeleton assistance.This work was supported by the Visiting Scholars Program of The National Center for Simulation in Rehabilitation Research (NCSRR). The NCSRR is a National Center for Medical Rehabilitation Research supported by National Institutes of Health (NIH) research infrastructure grant [R24 HD065690]. This study was in part funded by US Israel Binational Science Foundation Start Up Grant [2011152] awarded to G.S.S

Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome

Background Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome. Aim To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome. Methods Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy. Results Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing. Conclusions Bowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea

Seismic slip on an upper-plate normal fault during a large subduction megathrust rupture

Quantification of stress accumulation and release during subduction zone seismic cycles requires an understanding of the distribution of fault slip during earthquakes. Reconstructions of slip are typically constrained to a single, known fault plane. Yet, slip has been shown to occur on multiple faults within the subducting plate1 owing to stress triggering2, resulting in phenomena such as earthquake doublets3. However, rapid stress triggering from the plate interface to faults in the overriding plate has not been documented. Here we analyse seismic data from the magnitude 7.1 Araucania earthquake that occurred in the Chilean subduction zone in 2011. We find that the earthquake, which was reported as a single event in global moment tensor solutions4, 5, was instead composed of two ruptures on two separate faults. Within 12?s a thrust earthquake on the plate interface triggered a second large rupture on a normal fault 30?km away in the overriding plate. This configuration of partitioned rupture is consistent with normal-faulting mechanisms in the ensuing aftershock sequence. We conclude that plate interface rupture can trigger almost instantaneous slip in the overriding plate of a subduction zone. This shallow upper-plate rupture may be masked from teleseismic data, posing a challenge for real-time tsunami warning systems

Predicting the location of the hip joint centres, impact of age group and sex

Clinical gait analysis incorporating three-dimensional motion analysis plays a key role in planning surgical treatments in people with gait disability. The position of the Hip Joint Centre (HJC) within the pelvis is thus critical to ensure accurate data interpretation. The position of the HJC is determined from regression equations based on anthropometric measurements derived from relatively small datasets. Current equations do not take sex or age into account, even though pelvis shape is known to differ between sex, and gait analysis is performed in populations with wide range of age. Three dimensional images of 157 deceased individuals (37 children, 120 skeletally matured) were collected with computed tomography. The location of the HJC within the pelvis was determined and regression equations to locate the HJC were developed using various anthropometrics predictors. We determined if accuracy improved when age and sex were introduced as variables. Statistical analysis did not support differentiating the equations according to sex. We found that age only modestly improved accuracy. We propose a range of new regression equations, derived from the largest dataset collected for this purpose to date

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The ‘SGLT2i Prescribing Tool for T2DM Management’, previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care

Information system for monitoring and assessing stress among medical students

Author ProofThe severe or prolonged exposure to stress-inducing factors in occupational and academic settings is a growing concern. The literature describes several potentially stressful moments experienced by medical students throughout the course, affecting cognitive functioning and learning. In this paper, we introduce the EUSTRESS Solution, that aims to create an Information System to monitor and assess, continuously and in real-time, the stress levels of the individuals in order to predict chronic stress. The Information System will use a measuring instrument based on wearable devices and machine learning techniques to collect and process stress-related data from the individual without his/her explicit interaction. A big database has been built through physiological, psychological, and behavioral assessments of medical students. In this paper, we focus on heart rate and heart rate variability indices, by comparing baseline and stress condition. In order to develop a predictive model of stress, we performed different statistical tests. Preliminary results showed the neural network had the better model fit. As future work, we will integrate salivary samples and self-report questionnaires in order to develop a more complex and intelligent model.QVida+ project (Estimação Contínua de Qualidade de Vida para Auxílio Eficaz à Decisão Clínica), funded by European Structural funds (FEDER-003446), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

The conventional gait model - success and limitations

The Conventional Gait Model (CGM) is a generic name for a family of closely related and very widely used biomechanical models for gait analysis. After describing its history, the core attributes of the model are described followed by evaluation of its strengths and weaknesses. An analysis of the current and future requirements for practical biomechanical models for clinical and other gait analysis purposes which have been rigorously calibrated suggests that the CGM is better suited for this purpose than any other currently available model. Modifications are required, however, and a number are proposed