Chronic Ankle Instability Subjects Demonstrate Lower Rate of Torque Development in Ankle Eversion, Hip Abduction Muscles Compared to Healthy, Coper Groups

Chronic ankle instability (CAI) is a pathological condition characterized by repeated lateral ankle sprains. Many ankle sprains are not a singular occurrence and can lead to perpetual disability, with some patients reporting repeated episodes of the ankle “giving way” during activity. CAI is multifactorial in nature, with contributors such as ligamentous laxity, strength deficit, and proprioceptive impairment (1). Each of these contributors negatively affects the muscles of the ankle complex. Rate of torque development (RTD) is a metric demonstrating explosive muscle capability, and is related to measurement of maximal voluntary isometric contraction (MVIC). RTD is a more accurate reflection of functional strength than MVIC because peak torque generally occurs 300ms or more after the onset of torque generation (2) while the time available for torque production in a functional daily movement context is generally between 50-250ms (3). RTD is generally measured within the first 200ms of the trial and therefore better captures the muscle’s ability to generate strength for daily activities. Understanding the relationship between RTD of the ankle evertor/invertor muscles and hip abductor muscles in individuals with CAI against healthy controls will better inform rehabilitation strategies and provide a benchmark of improvement for individuals recovering from CAI. PURPOSE: The purpose of this study was to better understand how CAI affects the force production capabilities of the ankle evertors/invertors, as well as the hip abductors. We hypothesized that individuals with CAI would demonstrate lower RTD in all three muscle groups in comparison to healthy and coper controls. METHODS: A total of 58 males and females participated in this study, and participants were divided into three cohorts. The first was a CAI patient group, a “coper” group, defined as individuals who can return to pre-injury levels of performance after LAS, and a healthy control group. CAI individuals and LAS copers were identified using the guidelines provided by the International Ankle Consortium (4). Subject exclusion criteria included previous history of lower extremity surgery, fracture, neurological disease affecting the lower extremity, or any injury to the lower extremity in the 3 months leading up to the study. Before data was obtained participants were familiarized with experimental procedures and protocols. Signed consent was obtained from each subject prior to data collection. The study was approved by the university institutional review board (Approval number: F2019-338). The study design required two visits from the subjects. The first visit was to familiarize subjects with the ankle eversion, inversion, and hip abduction movements they would be required to perform. On this day patients were also made familiar with the Biodex dynamometer (System Pro 4, Biodex Medical Systems, Inc., Shirley, NY; sampling rate: 100 Hz). On the second day subjects were seated on the dynamometer and performed 3 maximal voluntary isometric contractions (MVIC) of each movement. Patients were instructed to perform the movements as quickly as possible and to hold each trial for 5 seconds. Three trials were collected for each movement, with a minute separating each trial. Subjects were encouraged to give maximal effort through verbal cues. RTD and MVIC were calculated from each torque-time curve using custom code written in MatLab (MathWorks 2021a, Natick, MA). RTD was defined as the rate of change of the first 200ms of each trial; MVIC was defined as the peak value of each trial. RTD and MVIC values were averaged for each subject. RESULTS: No statistically significant differences in sex, age, height, or mass were detected among subjects (Table 1). Table 2 shows mean RTD for each group for the ankle eversion, inversion, and hip abduction movements. Notable results from Table 2 include the finding that CAI patients demonstrated significantly lower RTD than healthy controls (p = .02) and lower RTD than LAS copers (p = .03). Furthermore, CAI patients showed lower hip abductor RTD than healthy controls (p = .04). Table 3 shows MVIC data for each group for each movement and demonstrates that CAI patients showed significantly lower MVIC of the ankle eversion muscles than healthy controls (p = .02). No statistically significant differences in any strength metrics were detected between LAS copers and healthy controls, nor were there differences detected between groups in the ankle inversion movement. DISCUSSION: The primary finding from this study was that CAI ankle eversion RTD was significantly lower than RTD in healthy controls. This is significant because it provides insight on the adverse effects of repeated LAS on the muscles of the ankle complex. One of the factors determining RTD is the force transmission capabilities of the tendinous structures (10), and it is possible that the stretching of the ankle ligaments during LAS negatively affects its ability to efficiently transmit force generated from the muscle. Given the correlation between CAI patients and decreased RTD of ankle eversion muscles, it is possible that focusing on improvement in RTD of this muscle group could improve CAI symptoms. Numerous studies have focused on modalities targeted at improving RTD of the leg extensors muscle groups with generally positive results (5, 9), the majority of which include protocols that would be easily modifiable to the ankle eversion muscle group. Another notable finding from this study was that RTD of the hip abductors in the CAI group was significantly less than that of the healthy group. Although studies exist that have measured maximal hip abduction isometric strength in CAI groups, to our knowledge this is the first study analyzing the RTD of hip abduction. Our findings of deficits in hip abduction strength coincide with those of previous studies (6-8). Whether deficits in hip abduction strength increase potential for LAS or arise as a result of CAI is unclear, but it is becoming evident that the two factors are related. This is a promising area of CAI research and further study is required to fully elucidate the relationship between CAI and hip abductor strength. CONCLUSION: RTD of the ankle evertors in individuals with CAI is significantly lower than in LAS copers and healthy controls. Additionally, CAI patients demonstrated significantly lower RTD in hip abduction than healthy controls. While the need for exploring muscle force production capabilities in individuals with CAI persists, we suggest exploring modalities targeted at improving ankle eversion and hip abduction strength in patients with CAI. It is possible that improving strength in these areas will help return CAI patients to pre-injury levels of function and further our understanding of CAI

The Effects of Chronic Pain Levels on Lower Extremity Muscle Activation During Jump Landing/Cutting in Individuals with Chronic Ankle Instability

Lateral ankle sprains (LASs) are the most common injury in sports. Up to 74% of individuals with an initial LAS develop chronic ankle instability (CAI) with chronic ankle pain being one of the residual symptoms. PURPOSE: To Identify the effects of chronic pain levels on lower extremity muscle activation during a maximal jump landing/cutting in CAI individuals. METHODS: This study was a cross-sectional study. Twenty CAI individuals with high pain (High pain) (9M, 11F; age=22±2year; height= 1.74±0.10m; mass=79.4±14.6kg, pain=67.4±7.7), 20 CAI individuals with low pain (Low pain) (9M, 11F; age=21±3year; height=1.73±0.08m; mass=74.2±12.7kg, pain=91.7±3.9), and 20 healthy controls (Control) (9M, 11F; age=22±1year; height=1.74±0.09m; mass=68.2±10.2kg, pain=100±0). We followed the International Ankle Consortium and Foot and Ankle Outcome Scores for classification of CAI and chronic pain. Electromyography (EMG) data were collected using wireless surface electrodes (2,000 Hz) during 5 trials of maximal jump landing/cutting from initial contact to toe-off (0-100% of stance). Reference EMG data were collected standing position for 3 seconds. EMG data were normalized to the reference EMG data. The electrodes were placed over the tibialis anterior (TA), peroneus longus (PL), medial gastrocnemius (MG), vastus lateralis (VL), gluteus medius (Gmed), and gluteus maximus (Gmax). Functional analyses of variance were used to evaluate between-group differences for kinematics outcomes. RESULTS: The high pain showed 3.3%, 16%, and 14% less activation in TA, PL, and MG, and 16% and 14% more activation in the VL and Gmed than the low pain. The high pain displayed 26%, 11.1%, 15%, 8.2%, 25.4%, and 11.5% less activation in the TA, PL, MG, VL, Gmed, and Gmax than the control. The low pain showed 14.9%, 18.7%, and 11.2% less activation in the TA, VL, and Gmed, and 8.7% more activation in the PL during the landing/cutting than the control. CONCLUSION: Chronic pain levels appear to impact muscle activation in CAI individuals. Both the high and low pain demonstrate altered muscle activation patterns in distal and proximal joints. The high pain prompts a hip-dominant strategy, compensating for deactivated distal muscles. The lower the level of chronic pain, the more active the PL muscles that contribute to ankle stability

Running Biomechanics and Knee Cartilage Health in ACLR Patients

Anterior cruciate ligament reconstruction (ACLR) patients are more likely to subsequently suffer from knee osteoarthritis than non-ACLR counterparts. Exercise is thought to influence articular cartilage, however, it is unclear how running biomechanics are associated with femoral cartilage thickness and composition in ACLR patients. PURPOSE: The purpose of this study was to investigate relationships between running biomechanics and measures of femoral articular cartilage condition (thickness and composition) in ACLR patients and control subjects. METHODS: We used ultrasound and MRI (T2 mapping sequence) to measure articular cartilage thickness and composition, respectively, for 20 ACLR patients (age: 23 ± 3 yrs; mass: 70 ± 10 kg; time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls (age: 22 ± 2 yrs; mass: 67 ± 11 kg). After these measures, all participants completed a 30-minute run on a force-instrumented treadmill. Correlational analyses were used to explore relationships between running biomechanics (vertical ground reaction force (vGRF)) and femoral cartilage thickness and composition (T2 relaxation time). The present procedures were approved by the appropriate institutional board and all subjects provided informed consent before data collection was performed. RESULTS: Significant positive correlations existed for the control subjects only between peak vGRF and overall (r = 0.34; p \u3c 0.01), medial (r = 0.23; p \u3c 0.01), lateral (r = 0.39; p = 0.02), and intercondylar (r = 0.31; p \u3c 0.01) femoral thickness. The ACLR patients showed significant negative correlations between T2 relaxation time for the central-medial region of the femoral condyle, and peak vGRF (r = −0.53; p = 0.01) and vertical impulse due to the vGRF (r = −0.46; p = 0.04). CONCLUSION: These findings offer some limited support for the idea that femoral articular cartilage benefits from increase vGRF during running. This is evidenced by the increased thickness for the control subjects and decreased T2 relaxation time (indicative of increased free-flowing water in the cartilage) for the ACLR patients, as running vGRF increased

Effects of Running on Femoral Articular Cartilage Thickness for Anterior Cruciate Ligament Reconstruction Patients and Non-ACLR Control Subjects

Anterior cruciate ligament reconstruction (ACLR) patients are more likely to develop posttraumatic knee osteoarthritis than non-ACLR counterparts. The effect of running on femoral articular cartilage thickness is unclear. PURPOSE: The purpose of this study was to compare how 30 minutes of running influences femoral articular cartilage thickness for ACLR patients and non-ACLR control subjects. We hypothesized that running would deform the femoral articular cartilage more for the ACLR patients than for the control subjects. METHODS: We recruited 20 individuals with primary unilateral ACLR and 20 matched non-ACLR controls. ACLR patients and control subjects were matched based upon age, gender, BMI, and weekly running mileage. The present procedures were approved by the appropriate institutional board and all subjects provided informed consent before data collection. We used ultrasound imaging to measure femoral articular cartilage thickness before and after 30 minutes of running. The ultrasound images were manually analyzed using ImageJ software by the same investigator. Total femoral articular cartilage cross-sectional area of each image was segmented into three regions: medial, lateral, and intercondylar. Deformation due to the run was compared between the ACLR patients and control subjects for each region using independent t tests (P \u3c 0.05, adjusted for multiple comparisons). RESULTS: The 30-minute run resulted in more deformation for the ACLR patients (0.03 ± 0.01 cm) than the matched controls (0.01 ± 0.01 cm) for the medial region (p \u3c 0.01) of the femoral articular cartilage. Identically, the 30-minute run resulted in more deformation for the ACLR patients (0.03 ± 0.01 cm) than the matched controls (0.01 ± 0.01 cm; p \u3c 0.01) for an average of the entire articular cartilage area (medial, lateral, and intercondylar). No significant differences existed between groups for the lateral or intercondylar regions. CONCLUSION: Thirty minutes of running deformed medial and overall femoral articular cartilage more for ACLR patients than non-ACLR control subjects

Femoral Articular Cartilage Quality, but Not Thickness, Is Decreased for Anterior Cruciate Ligament Reconstruction Patients Relative to Control

Anterior cruciate ligament reconstruction (ACLR) patients are at risk of developing posttraumatic knee osteoarthritis (OA). The etiology of posttraumatic knee OA is complex, potentially involving biomechanical and biochemical factors. Changes in femoral cartilage thickness and composition are associated with knee OA, while current research is ambiguous on cartilage in ACLR patients. PURPOSE: This study aimed to compare femoral cartilage thickness and T2 relaxation time (a compositional measure) between ACLR patients and healthy controls in a resting state. We hypothesized that ACLR patients would exhibit thinner femoral cartilage and increased T2 relaxation times. METHODS: Twenty ACLR patients (6-24 months post-surgery) and 20 matched healthy controls were recruited following institutional board approval. Ultrasound and magnetic resonance imaging data were collected on two separate days, allowing cartilage thickness and composition measurements to be made, respectively. Statistical analyses, including independent t-tests and Holm-Bonferroni corrections, were performed on selected regions of interest. RESULTS: The ACLR group showed increased T2 relaxation times in four of eight femoral regions compared to controls. No significant differences in femoral cartilage thickness were observed between the groups. The primary finding from this study is that ACLR patients did not show differences in femoral cartilage thickness (a morphological measure), but displayed prolonged T2 relaxation times (a compositional measure) compared to controls, at rest. This finding suggests that compositional changes precede morphological shifts in femoral cartilage in early post-ACLR periods (6-24 months). CONCLUSION: These early compositional changes may indicate articular cartilage that is more compressible and subject to increased strain on the solid components of the joint. While ultrasound is a more accessible imaging method, magnetic resonance imaging may provide a more accurate and early evaluation of cartilage quality. Further research is needed to develop practical tools for early detection and monitoring of cartilage degradation in ACLR patients before progression into knee osteoarthritis

Pravastatin Attenuates Acute Radiation-Induced Enteropathy and Improves Epithelial Cell Function

Background and Aim: Radiation-induced enteropathy is frequently observed after radiation therapy for abdominal and pelvic cancer or occurs secondary to accidental radiation exposure. The acute effects of irradiation on the intestine might be attributed to inhibition of mitosis in the crypts, as the loss of proliferative functions impairs development of the small intestinal epithelium and its barrier function. Especially, oxidative damage to intestinal epithelial cells is a key event in the initiation and progression of radiation-induced enteropathy. Pravastatin is widely used clinically to lower serum cholesterol levels and has been reported to have anti-inflammatory effects on endothelial cells. Here, we investigated the therapeutic effects of pravastatin on damaged epithelial cells after radiation-induced enteritis using in vitro and in vivo systems.Materials and Methods: To evaluate the effects of pravastatin on intestinal epithelial cells, we analyzed proliferation and senescence, oxidative damage, and inflammatory cytokine expression in an irradiated human intestinal epithelial cell line (InEpC). In addition, to investigate the therapeutic effects of pravastatin in mice, we performed histological analysis, bacterial translocation assays, and intestinal permeability assays, and also assessed inflammatory cytokine expression, using a radiation-induced enteropathy model.Results: Histological damage such as shortening of villi length and impaired intestinal crypt function was observed in whole abdominal-irradiated mice. However, damage was attenuated in pravastatin-treated animals, in which normalization of intestinal epithelial cell differentiation was also observed. Using in vitro and in vivo systems, we also showed that pravastatin improves the proliferative properties of intestinal epithelial cells and decreases radiation-induced oxidative damage to the intestine. In addition, pravastatin inhibited levels of epithelial-derived inflammatory cytokines including IL-6, IL-1β, and TNF-α in irradiated InEpC cells. We also determined that pravastatin could rescue intestinal barrier dysfunction via anti-inflammatory effects using the mouse model.Conclusion: Pravastatin has a therapeutic effect on intestinal lesions and attenuates radiation-induced epithelial damage by suppressing oxidative stress and the inflammatory response

The AGE-RAGE axis in an Arab population: The United Arab Emirates Healthy Futures (UAEHFS) pilot study

© 2017 The Authors Aims The transformation of the United Arab Emirates (UAE) from a semi-nomadic to a high income society has been accompanied by increasing rates of obesity and Type 2 diabetes mellitus. We examined if the AGE-RAGE (receptor for advanced glycation endproducts) axis is associated with obesity and diabetes mellitus in the pilot phase of the UAE Healthy Futures Study (UAEHFS). Methods 517 Emirati subjects were enrolled and plasma/serum levels of AGE, carboxy methyl lysine (CML)-AGE, soluble (s)RAGE and endogenous secretory (es)RAGE were measured along with weight, height, waist and hip circumference (WC/HC), blood pressure, HbA1c, Vitamin D levels and routine chemistries. The relationship between the AGE-RAGE axis and obesity and diabetes mellitus was tested using proportional odds models and linear regression. Results After covariate adjustment, AGE levels were significantly associated with diabetes status. Levels of sRAGE and esRAGE were associated with BMI and levels of sRAGE were associated with WC/HC. Conclusions The AGE-RAGE axis is associated with diabetes status and obesity in this Arab population. Prospective serial analysis of this axis may identify predictive biomarkers of obesity and cardiometabolic dysfunction in the UAEHFS

A foundation model for atomistic materials chemistry

Machine-learned force fields have transformed the atomistic modelling of materials by enabling simulations of ab initio quality on unprecedented time and length scales. However, they are currently limited by: (i) the significant computational and human effort that must go into development and validation of potentials for each particular system of interest; and (ii) a general lack of transferability from one chemical system to the next. Here, using the state-of-the-art MACE architecture we introduce a single general-purpose ML model, trained on a public database of 150k inorganic crystals, that is capable of running stable molecular dynamics on molecules and materials. We demonstrate the power of the MACE-MP-0 model - and its qualitative and at times quantitative accuracy - on a diverse set problems in the physical sciences, including the properties of solids, liquids, gases, chemical reactions, interfaces and even the dynamics of a small protein. The model can be applied out of the box and as a starting or "foundation model" for any atomistic system of interest and is thus a step towards democratising the revolution of ML force fields by lowering the barriers to entry.Comment: 119 pages, 63 figures, 37MB PD

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded