A 10% increase in step rate improves running kinematics and clinical outcomes in runners with patellofemoral pain at 4 weeks and 3 months

Background: Aberrant frontal plane hip and pelvis kinematics have been frequently observed in runners with patellofemoral pain (PFP). Gait retaining interventions have been shown to improve running kinematics and may therefore be beneficial in runners with PFP. Purpose: the aim of this study was to investigate whether a 10% increase in running step rate influences frontal plane kinematics of the hip and pelvis, as well as clinical outcomes in runners with PFP. Study Design: Case Series Methods: Runners with PFP underwent a 3D gait analysis to confirm the presence of aberrant frontal plane hip and pelvis kinematics at baseline. Twelve participants with frontal plane hip and pelvis kinematics one standard deviation above a reference database, were invited to participate in the gait retraining intervention. Running kinematics along with clinical outcomes of pain and functional measures were recorded at baseline, 4 weeks following retraining and 3-months. Gait retraining consisted of a single session where step rate was increased by 10% using an audible metronome. Participants were asked to continue their normal running while self-monitoring their step rate using a global positioning system watch and audible metronome. Results: Following gait retraining significant improvements in running kinematics and clinical outcomes were observed at 4 week and 3-month follow up. Repeated measures ANOVA with post hoc Bonferroni (p <0.016) showed significant reductions in peak contralateral pelvic drop (Mean Difference [MD], 3.12⁰; 95% Confidence Interval [CI], 1.88⁰, 4.37⁰), hip adduction (MD, 3.99⁰; 95% CI, 2.01⁰, 5.96⁰) and knee flexion (MD, 4.09⁰; 95% CI, 0.04⁰, 8.15⁰), as well as significant increases in self-reported weekly running volume (MD, -13.78km; 95% CI, -22.93km, -4.62km) and longest run pain free (MD, -6.84km; 95% CI, -10.62km, -3.05km). Friedman test with post hoc Wilcoxon signed-rank showed significant improvements in Numerical Rating Scale for worst pain in the past week and Lower Extremity Functional Scale. Conclusion: A single session of gait retraining using a 10% increase in step rate results in significant improvements in running kinematics, pain and function in runners with PFP. These improvements were maintained at 3-month follow up. It is important to assess for aberrant running kinematics at baseline to ensure gait interventions are targeted appropriately. Clinical Relevance: Step rate modification is a simple method of gait retraining that can be easily integrated into clinical practice and running outside of a laboratory setting

Are the arms and head required to accurately estimate centre of mass motion during running?

Accurate measurement of centre of mass (CoM) motion can provide valuable insight into the biomechanics of human running. However, full-body kinematic measurement protocols can be time consuming and difficult to implement. Therefore, this study was performed to understand whether CoM motion during running could be estimated from a model incorporating only lower extremity, pelvic and trunk segments. Full-body kinematic data was collected whilst (n = 12) participants ran on a treadmill at two speeds (3.1 and 3.9 ms−1). CoM trajectories from a full-body model (16-segments) were compared to those estimated from a reduced model (excluding the head and arms). The data showed that, provided an offset was included, it was possible to accurately estimate CoM trajectory in both the anterior-posterior and vertical direction, with root mean square errors of 5 mm in both directions and close matches in waveform similarity (r = 0.975-1.000). However, in the ML direction, there was a considerable difference in the CoM trajectories of the two models (r = 0.774–0.767). This finding suggests that a full-body model is required if CoM motions are to be measured in the ML direction. The mismatch between the reduced and full-body model highlights the important contribution of the arms to CoM motion in the ML direction. We suggest that this control strategy, of using the arms rather than the heavier trunk segments to generate CoM motion, may lead to less variability in CoM motion in the ML direction and subsequently less variability in step width during human running

Is there a pathological gait associated with common soft tissue running injuries?

Background: Previous research has demonstrated clear associations between specific running injuries and patterns of lower limb kinematics. However, there has been minimal research investigating whether the same kinematic patterns could underlie multiple different soft tissue running injuries. If they do, such kinematic patterns could be considered global contributors to running injury. Hypothesis: Injured runners will demonstrate differences in running kinematics when compared to injury free controls. These kinematic patterns will be consistent amongst injury subgroups. Study Design: Case- Control Study Methods: We studied 72 injured runners and 36 healthy controls. The injured group contained four subgroups of runners with either patellofemoral pain, iliotibial band syndrome, medial tibial stress syndrome or Achilles tendinopathy (n = 18 each). Three-dimensional running kinematics were compared between injured and healthy runners and then between the four injured subgroups. A logistic regression model was used to determine which parameters could be used to identify injured runners. Results: The injured runners demonstrated greater contralateral pelvic drop and forward trunk lean at mid-stance and a more extended knee and dorsiflexed ankle at initial contact. The subgroup ANOVA found these kinematic patterns were consistent across each of the four injury subgroups. Contralateral pelvic drop was found to be the most important variable predicting classification of participants as healthy/injured. Importantly, for every 1° increase in pelvic drop there was an 80% increase in the odds of being classified injured. Conclusion: This study identified a number of global kinematic contributors to common running injuries. In particular, we found injured runners to run with greater peak contralateral pelvic drop and trunk forward lean, as well as an extended knee and dorsiflexed ankle at initial contact. Contralateral pelvic drop appears to be the variable most strongly associated with common running related injuries. Clinical Relevance: The identified kinematic patterns may prove beneficial for clinicians when assessing for biomechanical contributors to running injuries

Should physical activity recommendations be ethnicity-specific? Evidence from a cross-sectional study of south Asian and European men

Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1.&lt;p&gt;&lt;/p&gt; Methods Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA.&lt;p&gt;&lt;/p&gt; Findings For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week−1; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week−1.&lt;p&gt;&lt;/p&gt; Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.&lt;p&gt;&lt;/p&gt

Lysyl oxidase-like 2 inhibition ameliorates glomerulosclerosis and albuminuria in diabetic nephropathy

© 2018 The Author(s). Diabetic nephropathy is characterised by the excessive amount of extracellular matrix in glomeruli and tubulointerstitial space. Lysyl oxidase-like 2 (LOXL2) is elevated in renal fibrosis and known to play key roles in ECM stabilisation by facilitating collagen cross-links, epithelial to mesenchymal transition and myofibroblast activation. Thus, targeting LOXL2 may prove to be a useful strategy to prevent diabetic nephropathy. We explored the renoprotective effect of a selective small molecule LOXL2 inhibitor (PXS-S2B) in a streptozotocin-induced diabetes model. Diabetic mice were treated with PXS-S2B for 24 weeks and outcomes compared with untreated diabetic mice and with telmisartan treated animals as comparator of current standard of care. Diabetic mice had albuminuria, higher glomerulosclerosis scores, upregulation of fibrosis markers and increased renal cortical LOXL2 expression. Treatment with PXS-S2B reduced albuminuria and ameliorated glomerulosclerosis. This was associated with reduced expression of glomerular fibronectin and tubulointerstitial collagen I. The renoprotective effects of both PXS-S2B and telmisartan were more marked in the glomerular compartment than in the tubulointerstitial space. The study reveals that LOXL2 inhibition was beneficial in preserving glomerular structure and function. Thus, LOXL2 may be a potential therapeutic target in diabetic nephropathy

Effect of autonomic blocking agents on the respiratory-related oscillations of ventricular action potential duration in humans

Ventricular action potential duration (APD) is an important component of many physiological functions including arrhythmogenesis. APD oscillations have recently been reported in humans at the respiratory frequency. This study investigates the contribution of the autonomic nervous system to these oscillations. In 10 patients undergoing treatment for supraventricular arrhythmias, activation recovery intervals (ARI; a conventional surrogate for APD) were measured from multiple left and right ventricular (RV) endocardial sites, together with femoral artery pressure. Respiration was voluntarily regulated and heart rate clamped by RV pacing. Sympathetic and parasympathetic blockade was achieved using intravenous metoprolol and atropine, respectively. Metroprolol reduced the rate of pressure development (maximal change in pressure over time): 1,271 (± 646) vs. 930 (± 433) mmHg/s; P < 0.01. Systolic blood pressure (SBP) showed a trend to decrease after metoprolol, 133 (± 21) vs. 128 (± 25) mmHg; P = 0.06, and atropine infusion, 122 (± 26) mmHg; P < 0.05. ARI and SBP exhibited significant cyclical variations (P < 0.05) with respiration in all subjects with peak-to-peak amplitudes ranging between 0.7 and 17.0 mmHg and 1 and 16 ms, respectively. Infusion of metoprolol reduced the mean peak-to-peak amplitude [ARI, 6.2 (± 1.4) vs. 4.4 (± 1.0) ms, P = 0.008; SBP, 8.4 (± 1.6) vs. 6.2 (± 2.0) mmHg, P = 0.002]. The addition of atropine had no significant effect. ARI, SBP, and respiration showed significant coupling (P < 0.05) at the breathing frequency in all subjects. Directed coherence from respiration to ARI was high and reduced after metoprolol infusion [0.70 (± 0.17) vs. 0.50 (± 0.23); P < 0.05]. These results suggest a role of respiration in modulating the electrophysiology of ventricular myocardium in humans, which is partly, but not totally, mediated by β-adrenergic mechanisms

Kinematic characteristics of male runners with a history of recurrent calf muscle strain injury

Background: Calf muscle strain injuries are a common running injury affecting male runners and are known to have high reoccurrence rates. Currently, limited evidence exists investigating factors associated with this injury with no previous study investigating the running kinematics of male runners with a history of repeat calf muscle strain injuries. Purpose: To investigate differences in running kinematics between runners with a history of recurrent calf muscle strain injury and injury free controls. Study Design: Case-control investigation Level of Evidence: 4 Methods: Stance phase kinematics were compared between 15 male runners with a history of calf muscle strain injury and 15 male control participants during treadmill running at 3.2m/s. Independent t-tests were used to compare differences in stance phase kinematic parameters between groups and effect sizes were calculated using Cohen’s d. Results: The group with a history of calf muscle strain injury demonstrated a significant 2.1⁰ and 3.1⁰ increase in contralateral pelvic drop and anterior pelvic tilt during mid stance. In addition, this group exhibited longer stance times and a more anterior tilted pelvis, flexed hip and a greater distance between the heel and centre of mass at initial contact. Large effect sizes, greater than 0.8, were observed for all differences. No significant differences were observed for ankle and knee joint kinematics between the groups. Conclusion: This is the first study to identify kinematic characteristics associated with recurrent calf muscle strain injury. While it is not possible to determine causality, the observed kinematic differences may contribute to recurrent nature of this injury. Specifically, it is possible that neuromuscular deficits of the hip and calf muscle complex may lead to increased strain on the calf complex. Rehabilitation interventions which focus on addressing pelvis and hip kinematics may reduce the demands placed upon the calf complex and could prove clinically effective

The between-day repeatability, standard error of measurement and minimal detectable change for discrete kinematic parameters during treadmill running

Background: Kinematic parameters of the trunk, pelvis and lower limbs are frequently associated with both running injuries and performance, and the target of clinical interventions. Currently there is limited evidence reporting the between-day repeatability of discrete kinematic parameters of the trunk, pelvis and lower limbs during treadmill running. Research question: What is the between-day repeatability, standard error of measurement and minimal detectable change of discrete kinematic parameters of the trunk, pelvis and lower limbs during treadmill running? Methods: 16 healthy participants attended two kinematic data collection sessions two weeks apart. Three-dimensional kinematic data were collected while participants ran on a motorised treadmill at 3.2m/s. The interclass correlation coefficient, standard error of measurement and minimal detectable change were calculated for discrete kinematic parameters at initial contact, toe off, peak angles and joint excursions during the stance phase of running. Results: Good to excellent repeatability with low standard error of measurement and minimal detectable change values were observed for sagittal and frontal plane kinematics at initial contact (Range: ICC, 0.829 - 0.941; SEM, 0.6⁰- 2.6⁰; MDC, 1.5⁰- 7.2) and peak angles during stance (Range: ICC, 0.799 – 0.946; SEM, 0.6⁰- 2.6⁰; MDC, 1.7⁰- 7.1⁰). Peak transverse plane kinematics of the hip (ICC, 0.783; SEM, 3.2⁰; MDC, 8.7⁰) and knee (ICC, 0.739; SEM, 3⁰; MDC, 8.4⁰) demonstrated moderate between-day repeatability with large SEM and MDC values. Kinematics at toe off demonstrated the lowest ICC values and largest measurement errors of all parameters (Range: ICC, 0.109 – 0.900; SEM, 0.8⁰- 5.7⁰; MDC, 2.5⁰- 15.7⁰). Significance: This is the first study detailing the measurement error and minimal detectable change for discrete kinematic parameters of the trunk and pelvis during treadmill running. The reported values may provide a useful reference point for future studies investigating between-day differences in running kinematics

Lysyl oxidase inhibitors attenuate cyclosporin A-induced nephropathy in mouse.

Calcineurin inhibitors, such as Cyclosporin (CsA), are the mainstay of anti-rejection therapy in solid organ transplants but can paradoxically induce progressive nephropathy characterised by renal dysfunction and interstitial fibrosis. Lysyl oxidases (LOXs), a group of enzymes that catalyse extracellular matrix (ECM) crosslinking, were shown to implicate in tissue scarring. It is hypothesized that inhibition of these enzymes may render therapeutic effects against CsA-induced nephropathy. In this study, 6-to-8 weeks old C57BL/6 J mice were administered saline or CsA (30 mg/kg/day s.c) for 16 weeks. At 8 weeks, CsA-treated animals were divided into 5 groups respectively treated with: (1) vehicle, (2) PXS-5505 (Pan-LOX inhibitor), (3) PXS-5382 (LOX-like 2 inhibitor), (4) PXS-5505 for 4 weeks then PXS-5382 for 4 weeks (sequential therapy), and (5) Telmisartan (standard therapy). Our results indicate that CsA administration significantly increased the levels of blood urea nitrogen, glomerular and tubular injury, tubulointerstitial fibrosis, inflammation and oxidative stress in mouse kidney. These changes were associated with upregulated mRNA expression of LOX and LOXL2. Administration of Pan-LOX or LOXL2 inhibitors or the sequential therapy suppressed the expression of ECM proteins (α-SMA, FN and COL1A), matrix metalloproteases (MMP)2 and 9, inflammatory markers (TNFα and MCP-1) and TGF-β1-Smad3 signalling. Among all regimens including telmisartan, only Pan-LOX inhibitor PXS-5505 was able to attenuate uraemia. Collectively, our study suggests that Pan-LOX and LOXL2 inhibition can attenuate progressive nephropathy due to CsA administration

Uniform electron gases

We show that the traditional concept of the uniform electron gas (UEG) --- a homogeneous system of finite density, consisting of an infinite number of electrons in an infinite volume --- is inadequate to model the UEGs that arise in finite systems. We argue that, in general, a UEG is characterized by at least two parameters, \textit{viz.} the usual one-electron density parameter $\rho$ and a new two-electron parameter $\eta$. We outline a systematic strategy to determine a new density functional $E(\rho,\eta)$ across the spectrum of possible $\rho$ and $\eta$ values.Comment: 8 pages, 2 figures, 5 table