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Objectives: To develop a brief teamwork measure and determine how teamwork relates to provider experience, burnout, and work intentions., Study Design: Survey of clinicians., Methods: We analyzed data from Optum's 2019 biannual clinician survey, including a validated burnout measure and measures of provider experience and intent to stay. A 6-item measure of team effectiveness (TEAM) focused on efficiency, communication, continuous improvement, and leadership. Construct validity was assessed with content, reliability, and correlation with burnout. Generalized estimating equations with robust SEs determined relationships among TEAM score, provider experience, and intent to stay, controlling for demographics, clustering, and practice factors., Results: Of 1500 physicians and advanced practice clinicians (1387 with complete data; response rate 56%), there were 58% in primary care; 57% were women, and 38% identified as Asian, Black/Hispanic, or another race/ethnicity other than White non-Hispanic. Burnout was present in 30%. The Cronbach α was excellent (0.86), and TEAM correlated with the validated burnout measure (adjusted odds ratio [OR] of lower burnout with high TEAM score, 0.28; 95% CI, 0.19-0.40; P < .0001). Clinicians with TEAM scores of at least 4 were more likely to have positive provider experiences (79% favorable vs 24% with low TEAM score; P < .001), had lower burnout rates (17% vs 44%%; P < .001), and more often intended to stay (93% vs 65%; P < .001). TEAM index score was strongly associated with provider experience (adjusted OR, 11.72; 95% CI, 8.11-16.95; P < .001) and intent to stay (adjusted OR, 7.24; 95% CI, 5.34-9.83; P < .001)., Conclusions: The TEAM index is related to provider experience, burnout, and intent to stay, and it may help organizations optimize clinical work environments.

The phylogenetic relationships of the new dryosaurid genus Iyuku are explored using parsimony analysis. As all known specimens are juvenile, each character of the data matrix was examined across all included taxa for morphological changes through ontogeny in the phylogenetic characters. Any character that changed in any taxon was considered an ontogenetically sensitive character (OSC) and coded as unknown for juvenile specimens, including all specimens of Iyuku. This method was tested with three other genera in the data set that are known from juvenile and adult specimens: Orodromeus, Dryosaurus, and Hypacrosaurus. Four separate analyses were performed: (1) standard phylogenetic coding, (2) coding OSCs as unknown for juveniles, with both juvenile and adult OTUs present, (3) removal of adult specimens from second analysis, (4) adult specimens where known, taxa known only from juveniles coded as unknown for OSCs. In all taxa, congeneric juvenile and adult specimens were recovered as sister taxa (analysis 2), and juveniles in analysis 3 were found at a congruent node to the congeneric adult in analyses 1 and 4, though with a loss of resolution in the tree. Consideration of the changes in morphology through ontogeny across a given set of taxa can allow some confidence in the phylogenetic affinities of juvenile specimens. In all analyses, Iyuku is recovered as the sister taxon to Dysalotosaurus within Dryosauridae., (© 2022 American Association for Anatomy.)

Autologous chimeric antigen receptor-modified T-cells (CAR-T) provide meaningful benefit for otherwise refractory malignancies. As clinical indications for CAR-T cells are expanding, hospitals hitherto not active in the field of immune effector cell therapy will need to build capacity and expertise. The GoCART Coalition seeks to disseminate knowledge and skills to facilitate the introduction of CAR-T cells and to standardize management and documentation of CAR-T cell recipients, in order to optimize outcomes and to be able to benchmark clinical results against other centers. Apheresis generates the starting material for CAR-T cell manufacturing. This guide provides some initial suggestions for patient's apheresis readiness and performance to collect starting material and should thus facilitate the implementation of a CAR-T-starting material apheresis facility. It cannot replace, of course, the extensive training needed to perform qualitative apheresis collections in compliance with national and international regulations and assess their cellular composition and biological safety., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

In patients with an end-stage renal disease, dialysis a or kidney transplant are required to prolong live. For survival of the transplanted kidney, besides the HLA-system, the ABO blood type of donor and patient is also of importance. When the donor organ is derived from a living donor, time can be available prior to the transplant to reduce blood type AB antibodies in case of ABO major incompatibility between organ donor and recipient by double filtration apheresis., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions., (© 2023. The Author(s).)

Objectives: There is a global increase in the number of women diagnosed with cancer during their pregnancy and a nascent evidence base to guide their supportive care. The purposes of this study were to (1) map research on the psychosocial issues affecting women and their partners on diagnosis and treatment for cancer during pregnancy; (2) determine available supportive care or educational interventions; and (3) identify knowledge gaps for future research and development., Design: Scoping review., Search Strategy: Six databases were searched (Scopus, CINAHL, PsycINFO, Medline, Intermid, Maternal and Infant Health) to retrieve primary research (January 1995 to November 2021) investigating women and/or their partner's decision-making and their psychosocial outcomes during and after pregnancy., Data Extraction and Synthesis: Sociodemographic, gestational and disease characteristics of participants and psychosocial issues identified were extracted. Leventhal's self-regulatory model of illness provided a framework for mapping study findings enabling evidence synthesis and gap analysis., Results: Twelve studies were included, conducted in eight countries in six continents. Most women (70% of 217) were diagnosed with breast cancer during pregnancy. Reporting of sociodemographic, psychiatric, obstetric and oncological characteristics that are important in assessing psychosocial outcomes was inconsistent. None of the studies had a longitudinal design and no supportive care or educational interventions were identified. The gap analysis highlighted the lack of evidence about pathways to diagnosis, impact of late effects and how internal/social resources may affect outcomes., Conclusions: Research has focused on women with gestational breast cancer. Little is known about those diagnosed with other cancers. We encourage future study designs to capture data on sociodemographic, obstetric, oncological and psychiatric characteristics and adopt a longitudinal approach to explore the longer term psychosocial impact on women and their families. Future research should include outcomes that are meaningful for women (and their partners) and draw on international collaboration to accelerate progress in this field., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus ( S. aureus ) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study's results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth's gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.

The precise study of mechanically activated ion channels requires a combination of electrophysiology to directly measure channel-mediated ionic flux and a means to apply meaningful mechanical stimuli to activate the channel. In metazoans, individual cells in vivo experience mechanical inputs at the cell-substrate interface where cells form connections to the local microenvironment. To study such processes in vitro, a technique is required where mechanical stimuli can be applied to cells via connections with an underlying substrate. Here, we outline the methodology for combining whole-cell patch-clamp electrophysiology (to monitor transmembrane currents) with elastomer pillar arrays that can be deflected (to apply stimuli to cells). This quantitative technique can be used to assess changes in sensitivity and kinetics of mechanically evoked currents when cell intrinsic or cell extrinsic factors are manipulated., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

In Australia, mental illness has been recognised as a National Health Priority area, with the coronavirus pandemic adding a layer of urgency to the need to address the multiple health problems faced by clients with mental illnesses. Whilst much has been done in efforts to support these clients, little is known about their medication knowledge and experience with health professionals. The aim of the study was to explore the knowledge and beliefs of clients on the use of psychotropic medications and study their experiences with healthcare providers. Adult participants at a not-for-profit community-managed specialist mental health service provider in Adelaide, South Australia were recruited. Four focus group sessions were conducted between February 2020 and March 2021. All sessions were co-facilitated by a peer practitioner with lived experience. Sessions were audio recorded and transcribed verbatim. Participants (n = 27) reported that provision of medication education was inadequate and, in some cases, non-existent. There was an apparent lack of support for monitoring and managing common side effects, such as weight gain. Participants described not being involved in any decision-making processes and that establishing and maintaining a therapeutic relationship with their healthcare providers was challenging. Perceived stigma remains a barrier in accessing healthcare. Despite participants regularly interacting with a range of healthcare providers, findings highlight key gaps in care, particularly medication education and establishing a therapeutic relationship with their healthcare providers. Future mental health reforms should consider the provision of additional medication education in community settings, such as at not-for-profit organisations. Moreover, healthcare providers should take a proactive approach in establishing therapeutic relationships., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Cytotoxic T lymphocytes (CTLs) lyse target cells by delivering lytic granules that contain the pore former perforin to the cytotoxic immunological synapse. Here, we establish that opposing cytoskeletal forces drive lytic granule polarization and simultaneously shape T cell synapse topography to enhance target perforation. At the cell rear, actomyosin contractility drives the anterograde movement of lytic granules toward the nucleus. At the synapse, dynein-derived forces induce negatively curved membrane pockets to which granules are transported around the nucleus. These highly concave degranulation pockets are located directly opposite positively curved bulges on the target cell membrane. We identify a curvature bias in the action of perforin, which preferentially perforates positively curved tumor cell membrane. Together, these findings demonstrate murine and human T cell-mediated cytotoxicity to be a highly tuned mechano-biochemical system, in which the forces that polarize lytic granules locally bend the synaptic membrane to favor the unidirectional perforation of the target cell., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the association between pre-hospital 12-lead electrocardiogram (PHECG) use in patients presenting to emergency medical services (EMS) with acute stroke, and clinical outcomes and system delays., Methods: Multi-centre linked cohort study. Patients with verified acute stroke admitted to hospital via EMS were identified through routinely collected hospital data and linked to EMS clinical records via EMS unique identifiers. Ordinal and logistic regression analyses were undertaken to analyse the relationship between having a PHECG and modified Rankin Scale (mRS); hospital mortality; pre-hospital time intervals; door-to-scan and door-to-needle times; and rates of thrombolysis., Results: Of 1161 eligible patients admitted between 29 December 2013 and 30 January 2017, PHECG was performed in 558 (48%). PHECG was associated with an increase in mRS (adjusted odds ratio [aOR] 1.30, 95% confidence interval [CI] 1.01-1.66, p = 0.04) and hospital mortality (aOR 1.83, 95% CI 1.26-2.67, p = 0.002). There was no association between PHECG and administration of thrombolytic treatment (aOR 1.06, 95% CI 0.75-1.52, p = 0.73). Patients who had PHECG recorded spent longer under the care of EMS (median 49 vs 43 minutes, p = 0.006). No difference in times to receiving brain scan (median 28 with PHECG vs 29 minutes no PHECG, p = 0.32) or thrombolysis (median 46 vs 48 minutes, p = 0.37) were observed., Conclusion: The PHECG was associated with worse outcomes and longer delays in patients with acute ischaemic stroke., (© 2022 The Author(s).)

The ability of cells to convert mechanical perturbations into biochemical information is an essential aspect of mammalian physiology. The molecules that mediate such mechanotransduction include mechanically activated ion channels, which directly convert mechanical inputs into electrochemical signals. The unifying feature of these channels is that their open probability increases with the application of a mechanical input. However, the structure, activation profile and sensitivity of distinct mechanically activated ion channels vary from channel to channel. In this review, we discuss how ionic currents can be mechanically evoked and monitored in vitro, and describe the distinct activation profiles displayed by a range of mammalian channels. In addition, we discuss the various mechanisms by which the best-characterized mammalian, mechanically activated ion channel, PIEZO1, can be modulated. The diversity of activation and modulation of these mammalian ion channels suggest that these molecules may facilitate a finely controlled and diverse ability to sense mechanical inputs in mammalian cells., (© 2021 Federation of European Biochemical Societies.)

The advancement of microgravity simulators is helping many researchers better understanding the impact of the mechanically unloaded space environment on cellular function and disfunction. However, performing microgravity experiments on Earth, using simulators such as the Random Positioning Machine, introduces some unique practical challenges, including air bubble formation and leakage of growth medium from tissue culture flask and plates, all of which limit research progress. Here, we developed an easy-to-use hybrid biological platform designed with the precision of 3D printing technologies combined with PDMS microfluidic fabrication processes to facilitate reliable and reproducible microgravity cellular experiments. The system has been characterized for applications in the contest of brain cancer research by exposing glioblastoma and endothelial cells to 24 h of simulated microgravity condition to investigate the triggered mechanosensing pathways involved in cellular adaptation to the new environment. The platform demonstrated compatibility with different biological assays, i.e., proliferation, viability, morphology, protein expression and imaging of molecular structures, showing advantages over the conventional usage of culture flask. Our results indicated that both cell types are susceptible when the gravitational vector is disrupted, confirming the impact that microgravity has on both cancer and healthy cells functionality. In particular, we observed deactivation of Yap-1 molecule in glioblastoma cells and the remodeling of VE-Cadherin junctional protein in endothelial cells. The study provides support for the application of the proposed biological platform for advancing space mechanobiology research, also highlighting perspectives and strategies for developing next generation of brain cancer molecular therapies, including targeted drug delivery strategies., (© 2022. The Author(s).)

Objective: This research took a co-design approach to develop a social intervention to support people affected by a cancer diagnosis to be physically active., Methods: We conducted semi-structured interviews with five key stakeholder groups: (1) adults with a recent breast or prostate cancer diagnosis; (2) family and friends of cancer patients; (3) healthcare professionals; (4) physical activity providers; and (5) cancer charity representatives. Inductive content analysis was used to identify themes in the data. We then worked with a subset of participants to co-develop the intervention., Results: Participants welcomed the idea of a social approach to a physical activity intervention. Input was received on the timing and format of delivery, how to communicate about physical activity to cancer patients and their family and friends and the types of physical activity that would be appropriate. Our findings suggest that interventions need to be flexible in terms of timing and delivery and offer a wide range of physical activity options. These findings directly informed the co-development of 'All Together Active'., Conclusion: All Together Active is designed to support cancer patients and their family and friends to be active throughout treatment and beyond, benefiting their physical and mental health., (© 2022 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management., Introduction: The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older., Methods: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence., Results: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement., Conclusion: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases., (© 2022. The Author(s).)

Many aspects of mammalian physiology are mechanically regulated. One set of molecules that can mediate mechanotransduction are the mechanically activated ion channels. These ionotropic force sensors are directly activated by mechanical inputs, resulting in ionic flux across the plasma membrane. While there has been much research focus on the role of mechanically activated ion channels in touch sensation and hearing, recent data have highlighted the broad expression pattern of these molecules in mammalian cells. Disruption of mechanically activated channels has been shown to impact ( a ) the development of mechanoresponsive structures, ( b ) acute mechanical sensing, and ( c ) mechanically driven homeostatic maintenance in multiple tissue types. The diversity of processes impacted by these molecules highlights the importance of mechanically activated ion channels in mammalian physiology.

Purpose: To report patient activation, which is the knowledge, skills, and confidence in self-managing health conditions, and patient-reported outcomes of men after prostate cancer treatment from a community pharmacy lifestyle intervention., Methods: The 3-month lifestyle intervention was delivered to 116 men in nine community pharmacies in the UK. Patient Activation Measure (PAM) was assessed at baseline, 3 and 6 months. Prostate cancer-related function and quality of life were assessed using the European Prostate Cancer Index Composite (EPIC-26) and EuroQOL 5-dimension 5-level (EQ5D-5L) questionnaires at baseline and 6 months. Lifestyle assessments included Mediterranean Diet Adherence Screener (MEDAS) at baseline, 3 and 6 months and Godin Leisure Time Exercise Questionnaire (GLTEQ) at baseline and 3 months., Results: PAM score increased from 62 [95% CI 59-65] at baseline to 66 [64-69] after the intervention (p = 0.001) and remained higher at 6 months (p = 0.008). Scores for all the EPIC-26 domains (urinary, bowel and hormonal) were high at both assessments, indicating good function (between 74 [70-78] and 89 [86-91]), except sexual domain, where scores were much lower (21 [17-25] at baseline, increasing to 24 [20-28] at 6 months (p = 0.012)). In EQ5D-5L, 3% of men [1-9] reported self-care problems, while 50% [41-60] reported pain and discomfort, and no significant changes over time. Men who received androgen deprivation therapy, compared with those who did not, reported higher (better) urinary incontinence scores (p < 0.001), but lower (worse) scores in the urinary irritative/obstructive (p = 0.003), bowel (p < 0.001) and hormonal (p < 0.001) domains. Poor sexual function was common across all age groups irrespective of prostate cancer treatment., Conclusions: The intervention led to significant improvements in patient activation, exercise and diet. Community pharmacy could deliver effective services to address sexual dysfunction, pain and discomfort which are common after prostate cancer., (© 2021. The Author(s).)

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing safe in-person schooling has been a dynamic process balancing evolving community disease burden, scientific information, and local regulatory requirements with the mandate for education. Considerations include the health risks of SARS-CoV-2 infection and its post-acute sequelae, the impact of remote learning or periods of quarantine on education and well-being of children, and the contribution of schools to viral circulation in the community. The risk for infections that may occur within schools is related to the incidence of SARS-CoV-2 infections within the local community. Thus, persistent suppression of viral circulation in the community through effective public health measures including vaccination is critical to in-person schooling. Evidence suggests that the likelihood of transmission of SARS-CoV-2 within schools can be minimized if mitigation strategies are rationally combined. This article reviews evidence-based approaches and practices for the continual operation of in-person schooling., Competing Interests: LA serves on the medical advisory board of the MLD Foundation, CureMLD and “Don't Forget Morgan”. She is a consultant for Orchard Therapeutics, Biogen, and Takeda. She receives compensation and/or research funding for these roles. Additionally, she serves as an uncompensated member of the Board of Trustees and the scientific COVID-19 advisory committee of the Waldorf School of Philadelphia. GF is a chief scientific advisor for the journal Science Translational Medicine and is a senior advisor to Calico Laboratories and receives compensation for both roles. TG serves as an editor for the journal Circulation Genomic and Precision and receives compensation from the American Heart Association for this work. He was an uncompensated member of the Board of Trustees of the Waldorf School of Philadelphia and serves on the school's scientific COVID-19 advisory committee without compensation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lordan, Prior, Hennessy, Naik, Ghosh, Paschos, Skarke, Barekat, Hollingsworth, Juska, Mazaleuskaya, Teegarden, Glascock, Anderson, Meng, Tang, Weljie, Bottalico, Ricciotti, Cherfane, Mrcela, Grant, Poole, Mayer, Waring, Adang, Becker, Fries, FitzGerald and Grosser.)

The purpose of this study was to compare fitness parameters and cardiovascular disease risk of older and younger men with prostate cancer (PCa) and explore how men's fitness scores compared to normative age values. 83 men were recruited post-treatment and undertook a cardiopulmonary exercise test (CPET), sit-to-stand, step-and-grip strength tests and provided blood samples for serum lipids and HbA1c. We calculated waist-to-hip ratio, cardiovascular risk (QRISK2), Charlson comorbidity index (CCI) and Godin leisure-time exercise questionnaire [GLTEQ]. Age-group comparisons were made using normative data. Men > 75 years, had lower cardiopulmonary fitness, as measured by VO 2 Peak (ml/kg/min) 15.8 + 3.8 p < 0.001, and lower grip strength(28.6+5.2 kg p < 0.001) than younger men. BMI ≥30kg/m 2 and higher blood pressure all contributed to a QRisk2 score indicative of 20% chance of cardiovascular risk within 10 years (mean: 36.9-6.1) p < 0.001. Age, BMI and perceived physical activity were significantly associated with lower cardiopulmonary fitness. Men with PCa > 75 years had more cardiovascular risk factors compared to normative standards for men of their age. Although ADT was more frequent in older men, this was not found to be associated with cardiopulmonary fitness, but obesity and low levels of physical activity were. Secondary prevention should be addressed in men with PCa to improve men's overall health., (© 2021 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Basirun, Ferlazzo, Howell, Liu, Middleton, Martinac, Narayanan, Poole, Gentile and Chou.)

Background: The Gaucher Investigative Therapy Evaluation is a national clinical cohort of 250 patients aged 5-87 years with Gaucher disease in the United Kingdom-an ultra-rare genetic disorder. To inform clinical decision-making and improve pathophysiological understanding, we characterized the course of Gaucher disease and explored the influence of costly innovative medication and other interventions. Retrospective and prospective clinical, laboratory and radiological information including molecular analysis of the GBA1 gene and comprising > 2500 variables were collected systematically into a relational database with banking of collated biological samples in a central bioresource. Data for deep phenotyping and life-quality evaluation, including skeletal, visceral, haematological and neurological manifestations were recorded for a median of 17.3 years; the skeletal and neurological manifestations are the main focus of this study., Results: At baseline, 223 of the 250 patients were classified as type 1 Gaucher disease. Skeletal manifestations occurred in most patients in the cohort (131 of 201 specifically reported bone pain). Symptomatic osteonecrosis and fragility fractures occurred respectively in 76 and 37 of all 250 patients and the first osseous events occurred significantly earlier in those with neuronopathic disease. Intensive phenotyping in a subgroup of 40 patients originally considered to have only systemic features, revealed neurological involvement in 18: two had Parkinson disease and 16 had clinical signs compatible with neuronopathic Gaucher disease-indicating a greater than expected prevalence of neurological features. Analysis of longitudinal real-world data enabled Gaucher disease to be stratified with respect to advanced therapies and splenectomy. Splenectomy was associated with an increased hazard of fragility fractures, in addition to osteonecrosis and orthopaedic surgery; there were marked gender differences in fracture risk over time since splenectomy. Skeletal disease was a heavy burden of illness, especially where access to specific therapy was delayed and in patients requiring orthopaedic surgery., Conclusion: Gaucher disease has been explored using real-world data obtained in an era of therapeutic transformation. Introduction of advanced therapies and repeated longitudinal measures enabled this heterogeneous condition to be stratified into obvious clinical endotypes. The study reveals diverse and changing phenotypic manifestations with systemic, skeletal and neurological disease as inter-related sources of disability., (© 2021. The Author(s).)

The tissue microenvironment contains a complex assortment of multiple cell types, matrices, and vessel structures, which is difficult to reconstruct in vitro. Here, we demonstrate model tumor microenvironments formed through direct writing of vasculature channels and tumor cell aggregates, within a cell-laden microgel matrix. Photocrosslinkable microgels provide control over local and global mechanics, while enabling the integration of virtually any cell type. Direct writing of a Pluronic sacrificial ink into a stromal cell-microgel suspension is used to form vessel structures for endothelialization, followed by printing of melanoma aggregates. Tumor cells migrate into the prototype vessels as a function of spatial location, thereby providing a measure of invasive potential. The integration of perfusable channels with multiple spatially defined cell types provides new avenues for modelling development and disease, with scope for both fundamental research and drug development efforts.

Introduction Most medical school applicants use the internet as a source of information when applying for medical school. Previous analyses have evaluated residency and fellowship websites; however, an in-depth analysis of medical school websites is lacking. Methods We evaluated 192 United States (US) medical school websites for presence or absence of 39 items relevant to medical school applicants. Items fell into seven general categories: curriculum, research, demographics of incoming class, admissions information, faculty, financial aid, and social. Results Of the 192 websites evaluated (152 allopathic and 40 osteopathic schools), websites contained a mean of 23 items (59%) with a standard deviation of 4.2 items. Conclusion Our study examining US medical school websites revealed a lack of online information for medical school applicants. As medical school interviews transition to being online during the COVID-19 pandemic, the importance of the medical school website to applicants becomes increasingly crucial. The information contained in our study could be used to improve the functionality and quality of information on medical school websites, which could help both applicants and the medical schools themselves., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Pollock et al.)

Association of body mass index and hip fracture has been controversial. In this study, women with lowest and highest body weight had the highest fracture incidence. A 25-year follow-up indicated that obesity associates with early hip fracture risk and suggested increasing trend in normal-weight women at a later stage., Introduction: Obesity is a pandemic health issue. Its association with hip fracture risk remains controversial. We studied the long-term relationship of body mass index and hip fracture incidence in postmenopausal women., Methods: The cohort of 12,715 Finnish women born in 1932-1941 was followed for 25 years, covering ages from 58 up to 83. Fractures and deaths were obtained from national registries. Women were investigated in deciles of BMI as well as in WHO weight categories (normal, overweight, or obese). The follow-up analysis was carried out in two age strata as "early" (58-70 years) and "late" (> 70 years). Body weight information was updated accordingly. Femoral neck BMD was recorded for a subsample (n = 3163). Altogether, 427 hip fractures were observed., Results: A higher risk of early hip fracture was observed in obese and normal-weight compared with overweight women with hazard ratios (HRs) of 2.3 ((95% CI) 1.4-3.7) and 2.0 (1.3-3.1) while no difference was observed in late hip fracture risk between the three WHO categories (log rank p = 0.14). All-cause mortality during the follow-up was 19.3%. Compared with normal weight women, the obese women had a higher risk of death with an HR of 1.6 (1.4-1.8) and higher baseline BMD (p < 0.001). Faster bone loss was observed in the obese compared with other women (p < 0.001)., Conclusion: Obesity associates with earlier hip fracture and higher postfracture mortality. The obese women with low BMD have clearly the highest risk of hip fracture. This combination increases hip fracture risk more than either of the factors alone. After 75 years of age, risk appears to increase more in normal weight women, but this trend is in need of further confirmation.

The European Resuscitation Council has produced these first aid guidelines, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics include the first aid management of emergency medicine and trauma. For medical emergencies the following content is covered: recovery position, optimal positioning for shock, bronchodilator administration for asthma, recognition of stroke, early aspirin for chest pain, second dose of adrenaline for anaphylaxis, management of hypoglycaemia, oral rehydration solutions for treating exertion-related dehydration, management of heat stroke by cooling, supplemental oxygen in acute stroke, and presyncope. For trauma related emergencies the following topics are covered: control of life-threatening bleeding, management of open chest wounds, cervical spine motion restriction and stabilisation, recognition of concussion, cooling of thermal burns, dental avulsion, compression wrap for closed extremity joint injuries, straightening an angulated fracture, and eye injury from chemical exposure., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients with inflammatory bowel disease (IBD) have an excess burden of axial spondyloarthritis (axSpA), which, if left untreated, may significantly impact on clinical outcomes. We aimed to estimate the prevalence of axSpA, including previously undiagnosed cases, in IBD patients from studies involving cross-sectional imaging and identify the IBD features potentially associated with axSpA., Methods: PubMed, Embase and Cochrane databases were searched systematically between 1990 and 2018. Article reference lists and key conference abstract lists from 2012 to 2018 were also reviewed. All abstracts were reviewed by two authors to determine eligibility for inclusion. The study inclusion criteria were (a) adults aged 18 years or above, (b) a clinical diagnosis of IBD and (c) reporting identification of sacroiliitis using cross-sectional imaging., Results: A total of 20 observational studies were identified: 12 used CT, 6 used MR and 2 utilised both computed tomography (CT) and magnetic resonance (MR) imaging. Sample sizes ranged from 25 to 1247 (a total of 4096 patients); 31 studies were considered to have low selection bias, 13 included two or more radiology readers, and 3 included rheumatological assessments. The prevalence of sacroiliitis, the most commonly reported axSpA feature, ranged from 2.2% to 68.0% with a pooled prevalence of 21.0% [95% confidence interval (CI) 17-26%]. Associated IBD features include increasing IBD duration, increasing age, male sex, IBD location, inflammatory back pain and peripheral arthritis. No significant difference in the prevalence of sacroiliitis between Crohn's disease and ulcerative colitis was identified. Study limitations include variability in the individual study sample sizes and patient demographics., Conclusion: This review highlights the need for larger, well-designed studies using more sensitive imaging modalities and multivariable modelling to better estimate the prevalence of axSpA in IBD. An improved knowledge of the IBD phenotype(s) associated with axSpA and use of cross-sectional imaging intended for IBD assessment to screen for axSpA may help clinicians identify those patients most at risk., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Collaborations between health systems and community-based organizations (CBOs) are increasingly common mechanisms to address the unmet health-related social needs of high-risk populations. However, there is limited evidence on how to develop, manage, and sustain these partnerships, and implementation rarely incorporates perspectives of community social service organizations. To address these gaps, we elicited CBOs' perspectives on service delivery for clients, the impact of the Whole Person Care-Los Angeles (WPC-LA) initiative to integrate health and social care, and their suggestions for improving health system partnerships., Methods: Using stakeholder engaged principles and a qualitative Rapid Assessment Process, we conducted brief surveys and in-depth semi-structured interviews with 65 key informants from 36 CBOs working with WPC-LA., Results: Major themes identified by CBOs included: 1) the importance of a holistic, client-centered, continuously engaged approach that is reliant on regional partnerships; 2) benefits of WPC-LA expanding capacity and networks; 3) concerns about communication and redundancy hindering WPC-LA; and 4) a need for more equitable partnerships incorporating their approaches., Conclusions: CBOs value opportunities for integration with health systems, bring critical expertise to these partnerships, and seek to strengthen cross-sector collaborations. Early, equitable, and inclusive participation in the development and implementation of these partnerships may enhance their effectiveness, but requires policy that prioritizes and incentivizes sustainable and mutually beneficial partnerships.

Background: UK migrants born in intermediate to high prevalence areas for blood borne viruses (BBV) including hepatitis B, hepatitis C and HIV are at increased risk of these infections. National guidance from Public Health England (PHE) and National Institute for Health and Care Excellence (NICE) recommends primary care test this population to increase diagnoses and treatment. We aimed to investigate primary care professionals' knowledge of entitlements, and perceptions of barriers, for migrants accessing healthcare, and their policies, and reported practices and influences on provision of BBV testing in migrants., Methods: A pre-piloted questionnaire was distributed between October 2017 and January 2018 to primary care professionals attending the Royal College of General Practitioners and Best Practice in Primary Care conferences, via a link in PHE Vaccine Updates and through professional networks. Survey results were analysed to give descriptive statistics, and responses by respondent characteristics: profession, region, practice size, and frequency of seeing migrant patients. Responses were considered on a per question basis with response rates for each question presented with the results., Results: Four hundred fourteen questionnaires were returned with responses varying by question, representing an estimated 5.7% of English GP practices overall. Only 14% of respondents' practices systematically identified migrant patients for testing. Universal opt-out testing was offered to newly registering migrant patients by 18% of respondents for hepatitis B, 17% for hepatitis C and 21% for HIV. Knowledge of healthcare entitlements varied; fewer clinical staff knew that general practice consultations were free to all migrants (76%) than for urgent care (88%). Performance payment structure (76%) had the greatest reported influence on testing, followed by PHE and Clinical Commissioning Group recommendations (73% each). Language and culture were perceived to be the biggest barriers to accessing care., Conclusions: BBV testing for migrant patients in primary care is usually ad hoc, which is likely to lead to testing opportunities being missed. Knowledge of migrants' entitlements to healthcare varies and could affect access to care. Interventions to improve professional awareness and identification of migrant patients requiring BBV testing are needed to reduce the undiagnosed and untreated burden of BBVs in this vulnerable population.

Ion channels activated by mechanical inputs are important force sensing molecules in a wide array of mammalian cells and tissues. The transient receptor potential channel, TRPV4, is a polymodal, nonselective cation channel that can be activated by mechanical inputs but only if stimuli are applied directly at the interface between cells and their substrate, making this molecule a context-dependent force sensor. However, it remains unclear how TRPV4 is activated by mechanical inputs at the cell-substrate interface, which cell intrinsic and cell extrinsic parameters might modulate the mechanical activation of the channel and how mechanical activation differs from TRPV4 gating in response to other stimuli. Here we investigated the impact of substrate mechanics and cytoskeletal components on mechanically evoked TRPV4 currents and addressed how point mutations associated with TRPV4 phosphorylation and arthropathy influence mechanical activation of the channel. Our findings reveal distinct regulatory modulation of TRPV4 from the mechanically activated ion channel PIEZO1, suggesting the mechanosensitivity of these two channels is tuned in response to different parameters. Moreover, our data demonstrate that the effect of point mutations in TRPV4 on channel activation are profoundly dependent on the gating stimulus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sianati, Schroeter, Richardson, Tay, Lamandé and Poole.)

Around 200,000 people live with chronic hepatitis B in England. Despite national guidance on identification and management of cases and their close contacts, testing rates of close contacts is as low as 43% in high prevalence areas of London. Our study aimed to determine whether a nurse-led enhanced management and contact tracing of chronically infected individuals improved testing uptake, vaccination and onward referral of close contacts. The study was conducted across Greater Manchester and East of England regions between October 2015 and July 2017. All HBV chronically infected individuals registered with a GP and their close contacts were eligible for recruitment. The proportion of contacts who were tested, vaccinated and referred where appropriate were compared before and after the nurse-led intervention. Baseline and outcome information was collected using questionnaires. The intervention improved case referral rates by an additional 14% (from 86% (88/102 cases) to 99.7%; 648/650 cases). The proportion of contacts tested increased from 34% to 72%-94% with 18 new cases of HBV diagnosed. Amongst close contacts tested, vaccination rates of at least three doses increased from 77% (43/56) to 93% (452/491) during the study. Our study has shown that nurse-led enhanced management greatly improves identification, testing and vaccination of close contacts. The identification of new acute and chronic cases is likely to make the intervention cost effective and local health commissioners should consider providing a nurse-led service as part of hepatitis B care pathways., (© 2020 Crown copyright. Journal of Viral Hepatitis published by John Wiley & Sons Ltd. This article is published with the permission of the Controller of HMSO and the Queen’s Printer for Scotland.)

In a series of human cadaveric experiments, Dr. Paul Segond first described the avulsion injury occurring at the anterolateral tibial plateau that later took his name. The fracture is thought to arise as a consequence of excessive tibia internal rotation which often also elicits damage to other connective tissue of the knee. The exact mechanism behind the avulsion is, however, unclear. A number of ligamentous structures have been proposed in separate studies to insert into the Segond fragment. Suggestions include the iliotibial band (ITB), biceps femoris and the controversial 'anterolateral ligament' (ALL). Despite increasing knowledge of tibial plateau bony microarchitecture in both healthy and disease states, no studies have yet, to our knowledge, considered the role of tibial sub-entheseal bone structure in pathogenesis of the Segond fracture. The goal of this study was thus to elucidate the differences in trabecular properties at regions across the tibial plateau in order to provide an explanation for the susceptibility of the anterolateral region to avulsion injury. Twenty human tibial plateaus from cadaveric donors were dissected and imaged using a Nikon-XTH225-μCT scanner with <80 μm isotropic voxel size. Scans were reconstructed using MicroView 3D Image Viewer and Analysis Tool. Subsequent virtual biopsy at ten anatomically defined regions of interest (ROI) generated estimates of bone volume fraction ('bone volume divided by total volume' (BV/TV)). The overall mean BV/TV value across all 20 tibiae and all 10 ROIs was 0.271. Univariate repeated-measurements ANOVA demonstrated that BV/TV values differed between ROIs. BV/TV values at the Segond site (Sα, Sβ or Sγ) were lower than all other ROIs at 0.195, 0.192 and 0.193, respectively. This suggests that, notwithstanding inter- and intra-specimen variation, the Segond site tends to have a lower trabecular bone volume fraction than entheseal sites elsewhere on the tibia. Since BV/TV correlates with tensile and torsional strength, the lower BV/TV at the Segond site could equate to a region of local weakness in certain individuals which predisposes them to an avulsion injury following the application of force from excessive internal rotation. The low BV/TV recorded at the Segond site also challenges the idea that the fracture occurs due to pull from a discrete 'anterolateral ligament', as the tension exerted focally would be expected to elicit a hypertrophic response in line with Frost's Mechanostat hypothesis. Our data would instead agree with the aforementioned reports of the fibrous band at the Segond site being part of a broader insertion of an 'anterolateral complex'., (© 2020 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

This is the summary publication of the International Liaison Committee on Resuscitation's 2020 International Consensus on First Aid Science With Treatment Recommendations. It addresses the most recent published evidence reviewed by the First Aid Task Force science experts. This summary addresses the topics of first aid methods of glucose administration for hypoglycemia; techniques for cooling of exertional hyperthermia and heatstroke; recognition of acute stroke; the use of supplementary oxygen in acute stroke; early or first aid use of aspirin for chest pain; control of life- threatening bleeding through the use of tourniquets, haemostatic dressings, direct pressure, or pressure devices; the use of a compression wrap for closed extremity joint injuries; and temporary storage of an avulsed tooth. Additional summaries of scoping reviews are presented for the use of a recovery position, recognition of a concussion, and 6 other first aid topics. The First Aid Task Force has assessed, discussed, and debated the certainty of evidence on the basis of Grading of Recommendations, Assessment, Development, and Evaluation criteria and present their consensus treatment recommendations with evidence-to-decision highlights and identified priority knowledge gaps for future research. The 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Science With Treatment Recommendations (CoSTR) is the fourth in a series of annual summary publications from the International Liaison Committee on Resuscitation (ILCOR). This 2020 CoSTR for first aid includes new topics addressed by systematic reviews performed within the past 12 months. It also includes updates of the first aid treatment recommendations published from 2010 through 2019 that are based on additional evidence evaluations and updates. As a result, this 2020 CoSTR for first aid represents the most comprehensive update since 2010., (Copyright © 2020. Published by Elsevier B.V.)

Objective: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant., Design: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering., Results: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation., Conclusions: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The polymodal channel TRPV4 has been shown to regulate development and maintenance of cartilage. Here we investigate whether TRPV4 activity regulates the early deposition and structure of collagen matrix in the femoral head cartilage by comparing the 3D morphology and the sub-micrometer organization of the collagen matrix between wild type and Trpv4 -/- mice pups four to five days old. Two-photon microscopy can be used to conduct label-free imaging of cartilage, as collagen generates a second harmonic signal (second harmonic generation [SHG]) under pulsed infrared excitation. In one set of measurements, we use circularly polarized laser light to reconstruct the 3D morphology of the femoral head cartilage and to measure the tissue thickness. Second, by rotating the direction of the linearly polarized light and using polarized SHG detection, we investigate the sub-micrometer orientation of collagen fibers in the cartilage. At this developmental stage, we cannot detect statistically significant differences between the two mice strains, although a tendency toward a more random orientation of collagen fibers and a higher thickness of the whole cartilage seems to characterize the Trpv4 -/- mice. We discuss possible reasons for these observations. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry., (© 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.)

Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression of this protein in PIEZO1-deficient cells, that exhibit no baseline mechanosensitivity, is sufficient to reconstitute mechanically activated currents. Melanoma cells lacking functional Elkin1 exhibit defective mechanoelectrical transduction, decreased motility and increased dissociation from organotypic spheroids. By analysing cell adhesion properties, we demonstrate that Elkin1 deletion is associated with increased cell-substrate adhesion and decreased homotypic cell-cell adhesion strength. We therefore conclude that Elkin1 supports a PIEZO1-independent mechanoelectrical transduction pathway and modulates cellular adhesions and regulates melanoma cell migration and cell-cell interactions., Competing Interests: AP, JS, MM, LS, JB, JT, CC, CF, OS, MO, RF, ME, CW, BM, MB, GL, KP No competing interests declared, (© 2020, Patkunarajah et al.)

Objective: In this article, we describe how we developed and validated key performance indicators (KPIs) for pre-hospital blood transfusion and offer suggestions for other organisations wishing to develop performance metrics., Background: KPIs are metrics that compare actual care against an ideal structure, process or outcome standard. An increasing number of UK-based pre-hospital critical care services now carry blood components to enable pre-hospital blood transfusion., Methods: A working group of pre-hospital physicians and paramedics was formed to create and validate performance indicators that reflected a high-quality pre-hospital transfusion. This was performed by literature searching and reviewing consensus documents that guide the best practice and then adjusting the indicators as the process evolved., Results: Throughout the year, the performance against the domains was monitored monthly and outputs communicated within the clinical staff of the organisation; at the end of the year, the domains were amended. The final list of performance indicators was as follows: (a) rationale for transfusion documented in the notes; (b) rationale for transfusion in line with Thames Valley Air Ambulance blood transfusion guideline; (c) aggressive management of hypothermia; (d) tranexamic acid administered within an hour of injury; (e) evidence of bleeding in hospital; (f) monitoring of adverse effects of blood transfusion; (g) overall-was the use of blood justified; and (h) no units wasted this month., Conclusions: This study has shown that it is feasible to devise and implement clinical performance indicators for pre-hospital blood transfusion and that their use has increased the focus on this important area., (© 2020 British Blood Transfusion Society.)

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain., Competing Interests: Declaration of Interests R.S.-N. has a patent (US9551718B2) related to this work., (Copyright © 2020. Published by Elsevier Inc.)

While collating contributions and comments from 36 researchers, the coordinating authors accidentally omitted Dr. Suzanne Carrière from the list of contributing co-authors. Dr. Carrière's data are described in Tables 1 and 3, Figure 2 and several places in the narrative.The new author list is thus updated in this article.

The peregrine falcon (Falco peregrinus) and the gyrfalcon (Falco rusticolus) are top avian predators of Arctic ecosystems. Although existing monitoring efforts are well established for both species, collaboration of activities among Arctic scientists actively involved in research of large falcons in the Nearctic and Palearctic has been poorly coordinated. Here we provide the first overview of Arctic falcon monitoring sites, present trends for long-term occupancy and productivity, and summarize information describing abundance, distribution, phenology, and health of the two species. We summarize data for 24 falcon monitoring sites across the Arctic, and identify gaps in coverage for eastern Russia, the Arctic Archipelago of Canada, and East Greenland. Our results indicate that peregrine falcon and gyrfalcon populations are generally stable, and assuming that these patterns hold beyond the temporal and spatial extents of the monitoring sites, it is reasonable to suggest that breeding populations at broader scales are similarly stable. We have highlighted several challenges that preclude direct comparisons of Focal Ecosystem Components (FEC) attributes among monitoring sites, and we acknowledge that methodological problems cannot be corrected retrospectively, but could be accounted for in future monitoring. Despite these drawbacks, ample opportunity exists to establish a coordinated monitoring program for Arctic-nesting raptor species that supports CBMP goals.

A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease., (Copyright © 2020 Bradbury, Wu, Choi, Rowan, Zhang, Poole, Lauko and Chou.)

Mechanomics represents the natural progression of knowledge at the intersection of mechanics and biology with the aim to codify the role of mechanical environment on biological adaptation. Compared to the mapping of the human genome, the challenge of mapping the mechanome remains unsolved. Solving this grand challenge will require both top down and bottom up R&D approaches using experimental and computational tools to visualize and measure adaptation as it occurs. Akin to a mechanical test of a smart material that changes its mechanical properties and local environment under load, stem cells adapt their shape, cytoskeletal architecture, intrinsic mechanical properties, as well as their own niche, through cytoskeletal adaptation as well as up- and down-regulation of structural proteins that modulate their mechanical milieux . Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, reconfiguring of cytoskeletal machinery (nucleus, cytoskeleton), in response to controlled mechanical forces and stresses applied at cellular boundaries. Coupled with multiphysics computational and virtual power theoretical approaches, these novel experimental approaches enable mechanical testing of stem cells, multicellular templates, and tissues inhabited by stem cells, while the stem cells themselves evolve over time . The novel approach is paving the way to decipher mechanisms of structural and functional adaptation of stem cells in response to controlled mechanical cues. This mini-review outlines integrated approaches and methodologies implemented to date in a series of studies carried out by our consortium. The consortium's body of work is described in context of current roadblocks in the field and innovative, breakthrough solutions and is designed to encourage discourse and cross disciplinary collaboration in the scientific community., (Copyright © 2020 Putra, Song, McBride-Gagyi, Chang, Poole, Whan, Dean, Sansalone and Knothe Tate.)

Mechanomics, the mechanics equivalent of genomics, is a burgeoning field studying mechanical modulation of stem cell behavior and lineage commitment. Analogous to mechanical testing of a living material as it adapts and evolves, mapping of the mechanome necessitates the development of new protocols to assess changes in structure and function in live stem cells as they adapt and differentiate. Previous techniques have relied on imaging of cellular structures in fixed cells and/or live cell imaging of single cells with separate studies of changes in mechanical and biological properties. Here we present two complementary protocols to study mechanobiology and mechanoadaptation of live stem cells in adherent and motile contexts. First, we developed and tested live imaging protocols for simultaneous visualization and tracking of actin and tubulin mechanoadaptation as well as shape and volume of cells and their nuclei in adherent model embryonic murine mesenchymal stem cells (C3H/10T1/2) and in a neuroblastoma cell line. Then we applied the protocol to enable quantitative study of primary human mesenchymal stem cells in a motile state, e.g. , ingression in a three-dimensional, in vitro cell culture model. Together, these protocols enable study of emergent structural mechanoadaptation of the cell's own cytoskeletal machinery while tracking lineage commitment using phenotypic (quantitative morphology measures) and genotypic ( e.g. , reverse transcription Polymerase Chain Reaction, rtPCR) methods. These tools are expected to facilitate the mapping of the mechanome and incipient mechanistic understanding of stem cell mechanobiology, from the cellular to the tissue and organ length scales., Competing Interests: Competing interests In context of full disclosure, the live imaging studies of nucleus shape and volume changes and cytoskeletal adaptation were carried out using an imaging and perfusion chamber developed by Professor Knothe Tate's MechBio Team and later commercialized through a nonexclusive license agreement with Harvard Apparatus, Warner Instruments (https://www.warneronline.com/proflow-shear-flow-chamber-pfc-1). The study design and outcomes were conducted without consultation or involvement by Warner Instruments and other perfusion chamber and/or microfluidics-based platforms could be implemented with these protocols ( Shemesh et al., 2015 ). The studies were made possible through the generous support of the U.S. National Institutes of Health (DD and MLKT), U.S. National Institutes of Health Training Grant (recipients: SM-G, MJS), U.S. National Science Foundation (MLKT), Australian National Health and Medical Research Council (MLKT), the Paul Trainor Foundation (MLKT), and Gold and Silver Star grants from UNSW for "near miss funding" of Australian Research Council grant proposals., (Copyright © 2019 The Authors; exclusive licensee Bio-protocol LLC.)

PIEZO1 is a bona fide mammalian mechanically activated channel that has recently been shown to provide instructive cues during neuronal specification, texture sensing, and cell migration where mechanical inputs arise at the interface between the cells and their substrate. Here, we have investigated whether the mechanical properties of the substrate alone can modulate PIEZO1 activity, in response to exogenously applied stimuli, using elastomeric pillar arrays as force transducers. This methodology enables application of mechanical stimuli at cell-substrate contact points by deflecting individual pili. We found that PIEZO1 is more sensitive to substrate deflections with increased spacing between pili (reducing surface roughness) but not on more stiff substrates. Cellular contractility was required for the sensitization of PIEZO1 but was not essential for PIEZO1 activation. Computational modeling suggested that the membrane tension changes generated by pillar deflections were below the membrane tension changes that arise from cellular indentation or high-speed pressure clamp assays. We conclude that the mechanics of the microenvironment can modulate PIEZO1 signaling, highlighting the importance of studying channel activation directly at the cell-substrate interface. We propose that forces arising from actin-mediated contractility and within the lipid bilayer act synergistically to regulate PIEZO1 activation by stimuli applied at contacts between cells and their surroundings.