Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing

AbstractTendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation. S100a4-Cre; EP4flox/flox (EP4cKOS100a4) repairs healed with improved gliding function at day 14, followed by impaired gliding at day 28, relative to wild type. Interestingly, EP4cKOS100a4 resulted in only transient deletion of EP4, suggesting up-regulation of EP4 in an alternative cell population in these mice. Loss of EP4 in Scleraxis-lineage cells did not alter gliding function, suggesting that Scx-lineage cells are not the predominant EP4 expressing population. In contrast, a dramatic increase in α-SMA+, EP4+ double-positive cells were observed in EP4cKOS100a4 suggesting that EP4cKOS100a4 repairs heal with increased infiltration of EP4 expressing α-SMA myofibroblasts, identifying a potential mechanism of late up-regulation of EP4 and impaired gliding function in EP4cKOS100a4 tendon repairs.</jats:p

Metabolic response during high-intensity interval exercise and resting vascular and mitochondrial function in CrossFit participants

High-intensity functional training (HIFT) can play a major role in preventing cardiometabolic disease. The majority of HIFT interventions incorporate CrossFit (CF) training. We measured aerobic capacity, metabolic response during high-intensity interval exercise (HIIE), resting mitochondrial oxidative capacity, and resting vascular function in adults who participated in CF training (> one year) vs. a sedentary group completing one year (SED). Twenty-one participants were recruited (CF n = 13 vs. SED n = 8). CF participants had a 33.0% greater relative VO2 peak (p.200). CF participants had greater mitochondrial oxidative capacity (p=.014). There were no differences in large artery function, but CF participants had greater baseline arterial diameter (p=.004) and faster reperfusion following arterial occlusion (p<.05). These data support HIFT programs’ effectiveness in improving fitness, weight status, and metabolic, mitochondrial, and vascular function

How do you know it is true? integrity in research and publications: AOA critical issue

High-quality medical care is the result of clinical decisions based upon scientific principles garnered from basic, translational, and clinical research. Information regarding the natural history of diseases and their responses to various treatments is introduced into the medical literature through the approximately one million PubMed journal articles published each year. Pharmaceutical and device companies, universities, departments, and researchers all stand to gain from research publication. Basic and translational research is highly competitive. Success in obtaining research funding and career advancement requires scientific publication in the medical literature. Clinical research findings can lead to changes in the pattern of orthopaedic practice and have implications for the utilization of pharmaceuticals and orthopaedic devices. Research findings can be biased by ownership of patents and materials, funding sources, and consulting arrangements. The current high-stakes research environment has been characterized by an increase in plagiarism, falsification or manipulation of data, selected presentation of results, research bias, and inappropriate statistical analyses. It is the responsibility of the orthopaedic community to work collaboratively with industry, universities, departments, and medical researchers and educators to ensure the integrity of the content of the orthopaedic literature and to enable the incorporation of best practices in the care of orthopaedic patients

The Isotropic Radio Background and Annihilating Dark Matter

Observations by ARCADE-2 and other telescopes sensitive to low frequency radiation have revealed the presence of an isotropic radio background with a hard spectral index. The intensity of this observed background is found to exceed the flux predicted from astrophysical sources by a factor of approximately 5-6. In this article, we consider the possibility that annihilating dark matter particles provide the primary contribution to the observed isotropic radio background through the emission of synchrotron radiation from electron and positron annihilation products. For reasonable estimates of the magnetic fields present in clusters and galaxies, we find that dark matter could potentially account for the observed radio excess, but only if it annihilates mostly to electrons and/or muons, and only if it possesses a mass in the range of approximately 5-50 GeV. For such models, the annihilation cross section required to normalize the synchrotron signal to the observed excess is sigma v ~ (0.4-30) x 10^-26 cm^3/s, similar to the value predicted for a simple thermal relic (sigma v ~ 3 x 10^-26 cm^3/s). We find that in any scenario in which dark matter annihilations are responsible for the observed excess radio emission, a significant fraction of the isotropic gamma ray background observed by Fermi must result from dark matter as well.Comment: 11 pages, 6 figure

The Cosmic Microwave Background in an Inhomogeneous Universe - why void models of dark energy are only weakly constrained by the CMB

The dimming of Type Ia supernovae could be the result of Hubble-scale inhomogeneity in the matter and spatial curvature, rather than signaling the presence of a dark energy component. A key challenge for such models is to fit the detailed spectrum of the cosmic microwave background (CMB). We present a detailed discussion of the small-scale CMB in an inhomogeneous universe, focusing on spherically symmetric `void' models. We allow for the dynamical effects of radiation while analyzing the problem, in contrast to other work which inadvertently fine tunes its spatial profile. This is a surprisingly important effect and we reach substantially different conclusions. Models which are open at CMB distances fit the CMB power spectrum without fine tuning; these models also fit the supernovae and local Hubble rate data which favours a high expansion rate. Asymptotically flat models may fit the CMB, but require some extra assumptions. We argue that a full treatment of the radiation in these models is necessary if we are to understand the correct constraints from the CMB, as well as other observations which rely on it, such as spectral distortions of the black body spectrum, the kinematic Sunyaev-Zeldovich effect or the Baryon Acoustic Oscillations.Comment: 23 pages with 14 figures. v2 has considerably extended discussion and analysis, but the basic results are unchanged. v3 is the final versio

A Vicious Cycle of Fear of Falling Avoidance Behavior in Parkinson’s Disease: A Path Analysis

Background: Postural instability (PI) in Parkinson\u27s disease (PD) is associated with several negative downstream consequences. Objective: The purpose was to explore the validity of a theoretical model of these downstream consequences arranged in a vicious cycle wherein PI leads to decreased balance confidence, which in turn leads to increased fear of falling (FOF) avoidance behavior, which in turn leads to decreased physical conditioning, which then feeds back and negatively affects PI. Methods: A path analysis of cross-sectional data from 55 participants with PD was conducted. The four constructs in the model connected in succession were: 1. PI (principal components analysis (PCA) composite of the Unified Parkinson\u27s Disease Rating Scale PI and Gait Difficulty score, Timed Up and Go test, and Berg Balance Scale); 2. balance confidence (Activities-Specific Balance Confidence Scale); 3. FOF avoidance behavior (PCA composite of the FOF Avoidance Behavior Questionnaire and average number of steps per day); and, 4. physical conditioning (2-Minute Step Test). Results: The path model was an excellent fit to the data, χ2 (7) = 7.910, p =.341, CFI = 0.985, TLI = 0.968, RMSEA = 0.049 (90% CI: 0.000 to 0.179). The moderate to strong and uniformly significant parameter estimates were −0.519, −0.651, −0.653, and −0.570, respectively (ps \u3c 0.01). Conclusions: PI directly and inversely predicted balance confidence, which in turn directly and inversely predicted FOF avoidance behavior. Furthermore, FOF avoidance behavior directly and inversely predicted physical conditioning, which directly and inversely predicted PI, thereby closing the cycle. These findings highlight the downstream consequences of PI in PD and support the notion of a vicious cycle of FOF avoidance behavior

Exploitation of Business Models for Deep Renovation

In this workshop, we discussed the exploitation experiences gathered in some relevant H2020 projects on deep renovation: TripleA-reno, ProGETonE, P2Endure, 4rinEU, STUNNING, and TURNkey Retrofit. Directives and practical insights that support the experimentation with exploitation strategies in EU-funded projects will be elaborated as outcome of the workshop. The ability to envision user needs and integrate them into a project value proposition is a vehicle towards more effective and sustainable business models for deep renovation practices. However, many projects still struggle to involve the user in their business model design method. In spite of the clarified potential for business models underpinning energy efficiency measures to generate profit in the clean energy market, the uptake of deep renovation practices is not flourishing to its full potential. Several barriers have been highlighted that still distress the market uptake of energy efficiency measures, among which the need for long-term capital for often comparatively small investments, the strain of measuring and distributing the energy savings due to deep renovation practices, as well as general lack of familiarity among consumers with renovation concepts. The dispute here, with even the economically sound business models, is that, for the user, there is an apparent lack of attractiveness for deep renovations, that goes beyond the mere financial savings or economical profitability offered by the investment. A conceivable resolution to upsurge the market uptake of renovation practices, is therefore the design of business models, which focus on the multiple environmental, social and financial benefits deep renovation practices might deliver for the different stakeholders involved in the process. Benefits, that are sometimes hard to monetise and generalize among the involved user groups, as they do not always resonate to the provider/receiver of these values equally, but on the contrary can develop contrasting interests. Therefore, in this report, we are summarizing the contributions of several H2020 projects on deep renovation, including: TripleA-reno [1], ProGETonE [2], P2Endure [3], 4rinEU [4], STUNNING [5], and TURNkey Retrofit [6]. This, in a way to explore what type of deep renovation business models exist in practice, and how they actually are impacting the EU market uptake of deep renovation practices

Do primordial Lithium abundances imply there's no Dark Energy?

Explaining the well established observation that the expansion rate of the universe is apparently accelerating is one of the defining scientific problems of our age. Within the standard model of cosmology, the repulsive 'dark energy' supposedly responsible has no explanation at a fundamental level, despite many varied attempts. A further important dilemma in the standard model is the Lithium problem, which is the substantial mismatch between the theoretical prediction for 7-Li from Big Bang Nucleosynthesis and the value that we observe today. This observation is one of the very few we have from along our past worldline as opposed to our past lightcone. By releasing the untested assumption that the universe is homogeneous on very large scales, both apparent acceleration and the Lithium problem can be easily accounted for as different aspects of cosmic inhomogeneity, without causing problems for other cosmological phenomena such as the cosmic microwave background. We illustrate this in the context of a void model.Comment: 14 pages, 4 figures. v2: minor rearrangements in the text, comments and references expanded, results unchange