Systematic comparison of sea urchin and sea star developmental gene regulatory networks explains how novelty is incorporated in early development.

The extensive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN for endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages. Comparison of the GRNs identifies how novelty is incorporated in early development. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study. Their primary role was to provide remotely delivered weight-loss services (via the Healthy Weight for Life program) to eligible participants in the intervention group. These services were partly provided as in-kind and partly funded through the study. We have received ethical approval from the University of Sydney to replace the Healthy Weight for Life program with the Commonwealth Scientific and Industrial Research Organisation's (CSIRO) Total Wellbeing Diet. The amended weight loss advice and support paragraph of the manuscript is outlined below. All changes to the protocol were made and approved before starting the trial and were prospectively changed on our trial registration (ACT RN12617001595303). Amended weight loss advice and support paragraph: If the patient has a BMI =27 kg/m2, the patient will be offered the option of participating in the remotelydelivered weight loss program. The Australian Commonwealth Scientific and Industrial Research Organisation's (CSIRO) "Total Wellbeing Diet" is based on an evidence-based weight management strategy that utilises a structured, nutritionally balanced eating plan designed to be incorporated into a balanced lifestyle program [2, 3]. The program is a 12- week, low glycaemic index, high protein, healthy eating program with online support and tracking tools, meal plans and educational resources on a healthy diet. It is delivered by SP Health (http://www.sphealth.com/) on behalf of the CSIRO. After completion of the 12-week program, patients may elect to continue the basic program for an additional 12-weeks. Patients who elect to undertake the online weight-loss program will continue to be supported by the PARTNER Care Support Team throughout their time on the weight-loss program. This program will be undertaken in conjunction with the PARTNER exercise program and educational resources on healthy lifestyle change.

Targeted physiotherapy for patellofemoral joint osteoarthritis: A protocol for a randomised, single-blind controlled trial

<p>Abstract</p> <p>Background</p> <p>The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA.</p> <p>Methods</p> <p>90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction.</p> <p>Conclusion</p> <p>This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce the personal and societal burden of this increasing public health problem.</p> <p>Trial Registration</p> <p>Australia New Zealand Clinical Trials Registry ACTRN12608000288325</p

Bi-fluorescent Staphylococcus aureus infection enables single-cell analysis of intracellular killing in vivo

Techniques for studying the clearance of bacterial infections are critical for advances in understanding disease states, immune cell effector functions, and novel antimicrobial therapeutics. Intracellular killing of Staphylococcus aureus by neutrophils can be monitored using a S. aureus strain stably expressing GFP, a fluorophore that is quenched when exposed to the reactive oxygen species (ROS) present in the phagolysosome. Here, we expand upon this method by developing a bi-fluorescent S. aureus killing assay for use in vivo. Conjugating S. aureus with a stable secondary fluorescent marker enables the separation of infected cell samples into three populations: cells that have not engaged in phagocytosis, cells that have engulfed and killed S. aureus, and cells that have viable internalized S. aureus. We identified ATTO647N-NHS Ester as a favorable dye conjugate for generating bi-fluorescent S. aureus due to its stability over time and invariant signal within the neutrophil phagolysosome. To resolve the in vivo utility of ATTO647N/GFP bi-fluorescent S. aureus, we evaluated neutrophil function in a murine model of chronic granulomatous disease (CGD) known to have impaired clearance of S. aureus infection. Analysis of bronchoalveolar lavage (BAL) from animals subjected to pulmonary infection with bi-fluorescent S. aureus demonstrated differences in neutrophil antimicrobial function consistent with the established phenotype of CGD

Patient-Facing Mobile Apps to Support Physiotherapy Care: Protocol for a Systematic Review of Apps Within App Stores

BACKGROUND: Care delivered by physiotherapists aims to facilitate engagement in positive health behaviors by patients (eg, adherence to exercise). However, research suggests that behavioral interventions are frequently omitted from care. Hence, better understanding of strategies that can be used by physiotherapists to support patients to engage in positive behaviors is important and likely to optimize outcomes. Digital health interventions delivered via mobile apps are garnering attention for their ability to support behavior change. They have potential to incorporate numerous behavior change techniques (BCTs) to support goals of physiotherapy care, including but not limited to self-monitoring, goal setting, and prompts/alerts. Despite their potential to support physiotherapy care, much is still unknown about what apps are available to consumers, the BCTs they use, their quality, and their potential to change behaviors. OBJECTIVE: The primary aim of this study is to systematically review the mobile apps available in app stores that are intended for use by patients to support physiotherapy care, including the BCTs within these apps. The secondary aims are to evaluate the quality and behavior change potential of these apps. METHODS: A systematic review of mobile apps in app stores will be undertaken. This will be guided by recommendations for systematic reviews in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement but adapted to suit our app store search, consistent with similar systematic reviews of apps published in the Journal of Medical Internet Research. Apple Store and Google Play will be searched with a two-step search strategy, using terms relevant to physiotherapy, physiotherapists, and common physiotherapy care. Key eligibility criteria will include apps that are intended for use by patients and are self-contained or stand-alone without the need of additional wearable devices or other add-ons. Included apps will be coded for BCTs and rated for quality using the Mobile Application Rating Scale (MARS) and for potential to change behavior using the App Behavior Change Scale (ABACUS). RESULTS: App store search and screening are expected to be completed in 2021. Data extraction and quality appraisal are expected to commence by November 2021. The study results are expected to be published in a subsequent paper in 2022. CONCLUSIONS: Knowledge gained from this review will support clinical practice and inform research by providing a greater understanding of the quality of currently available mobile apps and their potential to support patient behavior change goals of physiotherapy care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/29047

Correction to: Effectiveness of a new model of primary care management on knee pain and function in patients with knee osteoarthritis: Protocol for THE PARTNER STUDY

After the publication of this protocol [1], our collaborator Prima Health solutions advised us of their intent to withdraw from the study. Their primary role was to provide remotely delivered weight-loss services (via the Healthy Weight for Life program) to eligible participants in the intervention group. These services were partly provided as in-kind and partly funded through the study. We have received ethical approval from the University of Sydney to replace the Healthy Weight for Life program with the Commonwealth Scientific and Industrial Research Organisation's (CSIRO) Total Wellbeing Diet. The amended weight loss advice and support paragraph of the manuscript is outlined below. All changes to the protocol were made and approved before starting the trial and were prospectively changed on our trial registration (ACT RN12617001595303). Amended weight loss advice and support paragraph: If the patient has a BMI =27 kg/m2, the patient will be offered the option of participating in the remotelydelivered weight loss program. The Australian Commonwealth Scientific and Industrial Research Organisation's (CSIRO) "Total Wellbeing Diet" is based on an evidence-based weight management strategy that utilises a structured, nutritionally balanced eating plan designed to be incorporated into a balanced lifestyle program [2, 3]. The program is a 12- week, low glycaemic index, high protein, healthy eating program with online support and tracking tools, meal plans and educational resources on a healthy diet. It is delivered by SP Health (http://www.sphealth.com/) on behalf of the CSIRO. After completion of the 12-week program, patients may elect to continue the basic program for an additional 12-weeks. Patients who elect to undertake the online weight-loss program will continue to be supported by the PARTNER Care Support Team throughout their time on the weight-loss program. This program will be undertaken in conjunction with the PARTNER exercise program and educational resources on healthy lifestyle change.

Exercise, education, manual-therapy and taping compared to education for patellofemoral osteoarthritis: a blinded, randomised clinical trial

Objective: Patellofemoral joint osteoarthritis (PFJ OA) contributes considerably to knee OA symptoms. This study aimed to determine the efficacy of a PFJ-targeted exercise, education manual-therapy and taping program compared to OA education alone, in participants with PFJ OA. Methods: A randomised, participant-blinded and assessor-blinded clinical trial was conducted in primary-care physiotherapy. 92 people aged ≥40 years with symptomatic and radiographic PFJ OA participated. Physiotherapists delivered the PFJ-targeted exercise, education, manual-therapy and taping program, or the OA-education (control condition) in eight sessions over 12 weeks.Primary outcomes at 3-month (primary) and 9-month follow-up: (1) patient-perceived global rating of change (2) pain visual analogue scale (VAS) (100 mm); and (3) activities of daily living (ADL) subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS). Results: 81 people (88%) completed the 3-month follow-up and data analysed on an intention-to-treat basis. Between-group baseline similarity for participant characteristics was observed. The exercise, education, manual-therapy and taping program resulted in more people reporting much improvement (20/44) than the OA-education group (5/48) (number needed to treat 3 (95% confidence interval (CI) 2 to 5)) and greater pain reduction (mean difference: -15.2 mm, 95% CI -27.0 to -3.4). No significant effects on ADL were observed (5.8; 95% CI -0.6 to 12.1). At 9 months there were no significant effects for self-report of improvement, pain (-10.5 mm, 95% CI -22.7 to 1.8) or ADL (3.0, 95% CI -3.7 to 9.7). Conclusion: Exercise, education, manual-therapy and taping can be recommended to improve short-term patient rating of change and pain severity. However over 9-months, both options were equivalent. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12608000288325): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=82878

Foot posture in people with medial compartment knee osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Foot posture has long been considered to contribute to the development of lower limb musculoskeletal conditions as it may alter the mechanical alignment and dynamic function of the lower limb. This study compared foot posture in people with and without medial compartment knee osteoarthritis (OA) using a range of clinical foot measures. The reliability of the foot measures was also assessed.</p> <p>Methods</p> <p>The foot posture of 32 patients with clinically and radiographically-confirmed OA predominantly in the medial compartment of the knee and 28 asymptomatic age-matched healthy controls was investigated using the foot posture index (FPI), vertical navicular height and drop, and the arch index. Independent t tests and effect size (Cohen's d) were used to investigate the differences between the groups in the foot posture measurements.</p> <p>Results</p> <p>Significant differences were found between the control and the knee OA groups in relation to the FPI (1.35 ± 1.43 vs. 2.46 ± 2.18, p = 0.02; <it>d </it>= 0.61, medium effect size), navicular drop (0.02 ± 0.01 vs. 0.03 ± 0.01, p = 0.01; <it>d </it>= 1.02, large effect size) and the arch index (0.22 ± 0.04 vs. 0.26 ± 0.04, p = 0.04; <it>d </it>= 1.02, large effect size). No significant difference was found for vertical navicular height (0.24 ± 0.03 vs. 0.23 ± 0.03, p = 0.54; <it>d </it>= 0.04, negligible effect size).</p> <p>Conclusion</p> <p>People with medial compartment knee OA exhibit a more pronated foot type compared to controls. It is therefore recommended that the assessment of patients with knee OA in clinical practice should include simple foot measures, and that the potential influence of foot structure and function on the efficacy of foot orthoses in the management of medial compartment knee OA be further investigated.</p

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30