Structure-function specialisation of the interfascicular matrix in the human achilles tendon

Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency, but such tendons commonly obtain debilitating injuries. In equine tendons, energy storing is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the human positional anterior tibial tendon and energy storing Achilles tendons, testing the hypothesis that the Achilles tendon IFM has specialised composition and mechanical properties, which are lost with ageing. Data demonstrate IFM specialisation in the energy storing Achilles, with greater elasticity and fatigue resistance than in the positional anterior tibial tendon. With ageing, alterations occur predominantly to the proteome of the Achilles IFM, which are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments for tendinopathy

A randomized comparison of retrograde left-sided versus anterograde right-sided ablation of the atrioventricular junction

Background: Catheter ablation of the atrioventricular node (AVN) is an effective treatment for patients with symptomatic atrial fibrillation. This study compares the success rate, procedure time, radiation time, and complication rates of retrograde left-sided (LSA) and anterograde right-sided (RSA) AVN ablation in a randomised controlled trial. / Methods: Thirty-one patients undergoing AVN ablation were randomized to either LSA (15 patients) or RSA (16 patients). Crossover occurred after six unsuccessful radiofrequency (RF) applications. / Results: The LSA cohort had a mean age of 77.00 ± 5.17 and the RSA cohort was 79.44 ± 6.08 (p =.0240). There were five crossovers from LSA to RSA and there was one crossover from RSA to LSA. There was no significant difference in ablation time between LSA and RSA (210.40 ± 179.77 vs. 192.19 ± 130.29 seconds, p =.748). There was no significant difference in procedure time, fluoroscopy time, radiation dose, or number of RF applications between the two groups. There was 1 (6.67%) serious adverse event in the LSA group and 1 (6.25%) in the RSA group due to femoral hematomas requiring blood transfusion or intervention. There was no significant difference in patient-reported discomfort between LSA and RSA (16.43 ± 20.67 vs. 17.87 ± 28.08, p =.877). The study was stopped before full recruitment due to futility. / Conclusions: Retrograde LSA of the AVN does not reduce RF applications, procedure time, or radiation exposure compared with conventional RSA and cannot be recommended as a first-line clinical approach

Inhibition of vascular smooth muscle cell calcification by ATP analogues

Arterial medial calcification (AMC) has been associated with phenotypic changes in vascular smooth muscle cells (VSMCs) that reportedly makes them more osteoblast-like. Previous work has shown that ATP/UTP can inhibit AMC directly via P2 receptors and indirectly by NPP1-mediated hydrolysis to produce the mineralisation inhibitor, pyrophosphate (PPi). This study investigated the role of P2X receptors in the inhibitory effects of extracellular nucleotides on VSMC calcification. We found that Bz-ATP, α,β-meATP and β,γ-meATP, inhibited calcification by up to 100%. Culture in a high phosphate medium (2mM) was associated with increased VSMC death and apoptosis; treatment with Bz-ATP, α,β-meATP and β,γ-meATP reduced apoptosis to levels seen in non-calcifying cells. Calcification was also associated with alterations in the protein levels of VSMC (e.g. SM22α, SMA) and osteoblast-associated (e.g. Runx2, osteopontin) markers; Bz-ATP, α,β-meATP and β,γ-meATP attenuated these changes in protein expression. Long-term culture with Bz-ATP, α,β-meATP and β,γ-meATP resulted in lower extracellular ATP levels and an increased rate of ATP breakdown. P2X receptor antagonists failed to prevent the inhibitory effects of these analogues suggesting that they act via P2X receptor-independent mechanisms. In agreement, the breakdown products of α,β-meATP and β,γ-meATP (α,β-meADP and methylene diphosphonate, respectively) also dose dependently inhibited VSMC calcification. Furthermore, the actions of Bz-ATP, α,β-meATP and β,γ-meATP were unchanged in VSMCs isolated from NPP1 knockout mice, suggesting that the functional effects of these compounds do not involve NPP1-mediated generation of PPi. Together, these results indicate that the inhibitory effects of ATP analogues on VSMC calcification and apoptosis in vitro may be mediated, at least in part, by mechanisms that are independent of purinergic signalling and PPi

Rapid induction of autoantibodies during ARDS and septic shock

<p>Abstract</p> <p>Background</p> <p>Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.</p> <p>Methods</p> <p>Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.</p> <p>Results</p> <p>From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.</p> <p>Conclusion</p> <p>The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.</p

A randomized sham-controlled study of pulmonary vein isolation in symptomatic atrial fibrillation (The SHAM-PVI study): Study design and rationale

INTRODUCTION: Pulmonary vein (PV) isolation has been shown to reduce atrial fibrillation (AF) burden and symptoms in patients. However, to date previous studies have been unblinded raising the possibility of a placebo effect to account for differences in outcomes. HYPOTHESIS & METHODS: The objective of this study is to compare PV isolation to a sham procedure in patients with symptomatic AF. The SHAM-PVI study is a double blind randomized controlled clinical trial. 140 patients with symptomatic paroxysmal or persistent AF will be randomized to either PV isolation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing). All patients will receive an implantable loop recorder. The primary outcome is total AF burden at 6 months postrandomisation (excluding the 3 month blanking period). Key secondary outcomes include (1) time to symptomatic and asymptomatic atrial tachyarrhythmia (2) total atrial tachyarrhythmia episodes and (3) patient reported outcome measures. RESULTS: Enrollment was initiated in January 2020. Through April 2023 119 patients have been recruited. Results are expected to be disseminated in 2024. CONCLUSION: This study compares PV isolation using cryoablation to a sham procedure. The study will estimate the effect of PV isolation on AF burden

UK survey of occupational therapist’s and physiotherapist’s experiences and attitudes towards hip replacement precautions and equipment

Background: Total hip replacement (THR) is one of the most common orthopaedic procedures in the United Kingdom (UK). Historically, people following THR have been provided with hip precautions and equipment such as: raised toilet seats and furniture rises, in order to reduce the risks of dislocation post-operation. The purpose of this study was to determine current practices in the provision of these interventions in the UK for people following primary THR. Methods: A 27-question, self-administered online survey was developed and distributed to UK physiotherapists and occupational therapists involved in the management of people following primary THR (target respondents). The survey included questions regarding the current practices in the provision of equipment and hip precautions for THR patients, and physiotherapist’s and occupational therapist’s attitudes towards these practices. The survey was disseminated through print and web-based/social media channels. Results: 170 health professionals (87 physiotherapists and 83 occupational therapists), responded to the survey. Commonly prescribed equipment in respondent’s health trusts were raised toilet seats (95%), toilet frames and rails (88%), furniture raises (79%), helping hands/grabbers (77%), perching stools (75%) and long-handled shoe horns (75%). Hip precautions were routinely prescribed by 97% of respondents. Hip precautions were most frequently taught in a pre-operative group (52% of respondents). Similarly equipment was most frequently provided pre-operatively (61% respondents), and most commonly by occupational therapists (74% respondents). There was variability in the advice provided on the duration of hip precautions and equipment from up to six weeks post-operatively to life-time usage. Conclusions: Current practice on hip precautions and provision of equipment is not full representative of clinician’s perceptions of best care after THR. Future research is warranted to determine whether and to whom hip precautions and equipment should be prescribed post-THR as opposed to the current ‘blanket’ provision of equipment and movement restriction provided in UK practice

Heart rate recovery in patients with hypertrophic cardiomyopathy

Recovery in heart rate (HR) after exercise is a measure of autonomic function and a prognostic indicator in cardiovascular disease. The aim of this study was to characterize heart rate recovery (HRR) and to determine its relation to cardiac function and morphology in patients with hypertrophic cardiomyopathy (HC). We studied 18 healthy volunteers and 41 individuals with HC. All patients underwent clinical assessment and transthoracic echocardiography. Continuous beat-by-beat assessment of HR was obtained during and after cardiopulmonary exercise testing using finger plethysmography. HRR and power spectral densities were calculated on 3 minutes of continuous RR recordings. Absolute HRR was lower in patients than that in controls at 1, 2, and 3 minutes (25.7 ± 8.4 vs 35.3 ± 11.0 beats/min, p <0.001; 36.8 ± 9.4 vs 53.6 ± 13.2 beats/min, p <0.001; 41.2 ± 12.2 vs 62.1 ± 14.5 beats/min, p <0.001, respectively). HRR remained lower in patients at 2 and 3 minutes after normalization to peak HR. After normalization to the difference in HR between peak exercise and rest, HRR was significantly impaired in individuals with obstructive HC at 3 minutes compared with controls. HR at 3 minutes correlated with peak left ventricular outflow tract gradient (B 0.154 beats/min/mm Hg, confidence interval 0.010 to 0.299, p = 0.037) and remained a significant predictor of HRR after multivariable analysis. Spectral analysis showed a trend toward an increased low-frequency to high-frequency ratio in patients (p = 0.08) suggesting sympathetic predominance. In conclusion, HRR is impaired in HC and correlates with the severity of left ventricular outflow tract gradient. Prospective studies of the prognostic implications of impaired HRR in HC are warranted. © 2014 Elsevier Inc. All rights reserved

Ultra-high bandwidth quantum secured data transmission

Quantum key distribution (QKD) provides an attractive means for securing communications in optical fibre networks. However, deployment of the technology has been hampered by the frequent need for dedicated dark fibres to segregate the very weak quantum signals from conventional traffic. Up until now the coexistence of QKD with data has been limited to bandwidths that are orders of magnitude below those commonly employed in fibre optic communication networks. Using an optimised wavelength divisional multiplexing scheme, we transport QKD and the prevalent 100 Gb/s data format in the forward direction over the same fibre for the first time. We show a full quantum encryption system operating with a bandwidth of 200 Gb/s over a 100 km fibre. Exploring the ultimate limits of the technology by experimental measurements of the Raman noise, we demonstrate it is feasible to combine QKD with 10 Tb/s of data over a 50 km link. These results suggest it will be possible to integrate QKD and other quantum photonic technologies into high bandwidth data communication infrastructures, thereby allowing their widespread deployment