Protease signaling regulates apical cell extrusion, cell contacts, and proliferation in epithelia.

Mechanisms that sense and regulate epithelial morphogenesis, integrity, and homeostasis are incompletely understood. Protease-activated receptor 2 (Par2), the Par2-activating membrane-tethered protease matriptase, and its inhibitor, hepatocyte activator inhibitor 1 (Hai1), are coexpressed in most epithelia and may make up a local signaling system that regulates epithelial behavior. We explored the role of Par2b in matriptase-dependent skin abnormalities in Hai1a-deficient zebrafish embryos. We show an unexpected role for Par2b in regulation of epithelial apical cell extrusion, roles in regulating proliferation that were opposite in distinct but adjacent epithelial monolayers, and roles in regulating cell-cell junctions, mobility, survival, and expression of genes involved in tissue remodeling and inflammation. The epidermal growth factor receptor Erbb2 and matrix metalloproteinases, the latter induced by Par2b, may contribute to some matriptase- and Par2b-dependent phenotypes and be permissive for others. Our results suggest that local protease-activated receptor signaling can coordinate cell behaviors known to contribute to epithelial morphogenesis and homeostasis

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

Seamless Short Video Consumption Via a Web Browser or Application

The present disclosure describes computer-implemented systems and methods for assisting a user to navigate and consume videos hosted on third-party platforms. In response to a user query, a plurality of video results responsive to the user query are displayed and upon selection of one of the plurality of video results, a web browser retrieves and renders a webpage including the video from the respective video hosting platform. The system can playback the video and generate similar video results from a plurality of video hosting platforms pertaining to a given user query

Pathways curriculum and family interventions to promote healthful eating and physical activity in American Indian schoolchildren

Pathways, a multisite school-based study aimed at promoting healthful eating and increasing physical activity, was a randomized field trial including 1704 American Indian third to fifth grade students from 41 schools (21 intervention, 20 controls) in seven American Indian communities

Emergency Department Pediatric Readiness Among US Trauma Centers: A Machine Learning Analysis of Components Associated With Survival.

OBJECTIVE: We used machine learning to identify the highest impact components of emergency department (ED) pediatric readiness for predicting in-hospital survival among children cared for in US trauma centers. BACKGROUND: ED pediatric readiness is associated with improved short-term and long-term survival among injured children and part of the national verification criteria for US trauma centers. However, the components of ED pediatric readiness most predictive of survival are unknown. METHODS: This was a retrospective cohort study of injured children below 18 years treated in 458 trauma centers from January 1, 2012, through December 31, 2017, matched to the 2013 National ED Pediatric Readiness Assessment and the American Hospital Association survey. We used machine learning to analyze 265 potential predictors of survival, including 152 ED readiness variables, 29 patient variables, and 84 ED-level and hospital-level variables. The primary outcome was in-hospital survival. RESULTS: There were 274,756 injured children, including 4585 (1.7%) who died. Nine ED pediatric readiness components were associated with the greatest increase in survival: policy for mental health care (+8.8% change in survival), policy for patient assessment (+7.5%), specific respiratory equipment (+7.2%), policy for reduced-dose radiation imaging (+7.0%), physician competency evaluations (+4.9%), recording weight in kilograms (+3.2%), life support courses for nursing (+1.0%-2.5%), and policy on pediatric triage (+2.5%). There was a 268% improvement in survival when the 5 highest impact components were present. CONCLUSIONS: ED pediatric readiness components related to specific policies, personnel, and equipment were the strongest predictors of pediatric survival and worked synergistically when combined

Tricks and treats: designing technology to support mobility assistance dogs

Assistance dogs are a key intervention to support the autonomy of people with tetraplegia. Previous research on assistive technologies have investigated ways to, ultimately, replace their labour using technology, for instance through the design of smart home environments. However, both the disability studies literature and our interviews suggest there is an immediate need to support these relationships, both in terms of training and bonding. Through a case study of an accessible dog treats dispenser, we investigate a technological intervention responding to these needs, detailing an appropriate design methodology and contributing insights into user requirements and preferences

Upscaling marine forest restoration: challenges, solutions and recommendations from the Green Gravel Action Group

IntroductionTo counteract the rapid loss of marine forests globally and meet international commitments of the UN Decade on Ecosystem Restoration and the Convention on Biological Diversity ‘30 by 30’ targets, there is an urgent need to enhance our capacity for macroalgal restoration. The Green Gravel Action Group (GGAG) is a global network of 67 members that are working on the restoration of a diverse range of macroalgal forests and it aims to facilitate knowledge exchange to fast-track innovation and implementation of outplanting approaches worldwide. MethodsHere, we overview 25 projects conducted by members of the group that are focused on testing and developing techniques for macroalgal restoration. Based on these projects, we summarise the major challenges associated with scaling up the area of marine forests restored. ResultsWe identify several critical challenges that currently impede more widespread rollout of effective large-scale macroalgal restoration worldwide: 1) funding and capacity limitations, 2) difficulties arising from conditions at restoration sites, 3) technical barriers, and 4) challenges at the restoration-policy interface. DiscussionDespite these challenges, there has been substantial progress, with an increasing number of efforts, community engagement and momentum towards scaling up activities in recent years. Drawing on the collective expertise of the GGAG, we outline key recommendations for the scaling up of restoration efforts to match the goals of international commitments. These include the establishment of novel pathways to fund macroalgal restoration activities, building skills and capacity, harnessing emerging innovations in mobile hatchery and seeding technologies, and the development of the scientific and governance frameworks necessary to implement and monitor macroalgal restoration projects at scale

The Effects of Lipopolysaccharide-induced Fever on Maze Performance in the Djungarian Hamster

Fever can be spontaneously induced in mammals by exposure to a novel environment. This stress fever is a true fever which can be blocked by the addition of NSAIDs such as acetylsalicylic acid (aspirin). In this experiment we sought to determine whether or not this fever could have a beneficial effect on learning ability in the Djungarian hamster, Phodopus sungorus. Learning ability was assessed through the use of a T-maze in which accessible food was available on one side of the maze. The percentage of correct turns out of the first 10 was used as the indication of maze performance. Results were analyzed using ANOVA, Fisher' s PLSD, and Student's t-test. In the first experiment we confirm the existence of stress fevers in our model animal by finding the difference in core temperature before and after exposure to a novel environment (p < 0.05). The second experiment looks at maze performance in animals with and without LPS-induced fever and found that animals with LPS-induced fever performed significantly better than controls, as well as those animals administered aspirin and LPS, animals administered LPS alone, or animals run 24 hours after LPS injection (p < 0.05). These results suggest that the fever response has a beneficial effect on maze performance which is downstream of the prostaglandin pathway