Simulated hypergravity induces changes in human tendon-derived cells: from cell morphology to gene expression

Gravity influences physical and biological processes, having an impact on development, as well as homeostasis of living systems. The musculoskeletal system is comprised of several mechano- responsive tissues and altered gravitational forces are known to influence distinct properties, including bone mineral density and skeletal muscle mass. This is particularly relevant in a near- weightlessness (microgravity) environment, which is found during spaceflight and, not less importantly, during bed resting. Over the years, several studies have been conducted under simulated conditions of altered gravity owing to the advances on ground-based facilities, such as bioreactors for microgravity / hypo-gravity (1g) studies. Interestingly, microgravity-induced alterations are comparable to tissue degeneration caused by disuse and ageing. In turn, exposing musculoskeletal tissues to hypergravity may constitute a way of simulating (over)loading or, eventually, to be used as a measure to rescue cell phenotype after exposure to near-weightlessness conditions. Different studies have focused on bone, cartilage and skeletal muscle, but effects on tendons and ligaments have been underappreciated. Therefore, we evaluated the influence of increasing g-levels (5g, 10g, 15g and 20g) and different hypergravity exposure periods (4 and 16 h) on the behaviour of human tendon- derived cells (hTDCs). For this purpose, hTDCs were exposed to simulated hypergravity conditions using the Large Diameter Centrifuge (LDC) from the European Space Research and Technology Centre (ESTEC, ESA, The Netherlands). Human TDCs cultured under standard conditions (1g, normogravity, Earth gravity force) were used as controls. The effects of hypergravity on the viability of hTDCs, as well as on the expression of tendon related markers at the gene level were evaluated. Simulated hypergravity resulted in a reduced cell content after 16 h independently of g-level, as determined by DNA quantification. Additionally, the different g-levels studied led to changes in cell and cytoskeleton morphology. Strikingly, a 16-hour period of exposure resulted in alterations of gene expression profiles. Overall, gene expression of tendon-related markers, including collagen types I (col1a1) and III (col3a1), scleraxis (scx), tenomodulin (tnmd), decorin (dcn) and tenascin (tnc), seemed to be increased upon hypergravity stimulation and in comparison to cells cultured under control conditions. Altogether, these results highlight that altered gravity, particularly simulated hypergravity, has an influence on the phenotype of tendon cells, opening new avenues for research focused on using altered gravity as a model for overloading-induced tendon tissue injury or as measure to rescue the phenotype of degenerated tendon cells. Acknowledgements The authors would like to thank ESA Education Office for Spin Your Thesis! 2016 programme. R.C-A acknowledges the PhD grant SFRH/BD/96593/2013 from FCT â Fundação para a Ciência e a Tecnologia. SFRH/BD/96593/2013 from FCT –Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Harnessing Wicked Problems in Multi-stakeholder Partnerships

Despite the burgeoning literature on the governance and impact of cross-sector partnerships in the past two decades, the debate on how and when these collaborative arrangements address globally relevant problems and contribute to systemic change remains open. Building upon the notion of wicked problems and the literature on governing such wicked problems, this paper defines harnessing problems in multi-stakeholder partnerships (MSPs) as the approach of taking into account the nature of the problem and of organizing governance processes accordingly. The paper develops an innovative analytical framework that conceptualizes MSPs in terms of three governance processes (deliberation, decision-making and enforce-ment) harnessing three key dimensions of wicked problems (knowledge uncertainty, value conflict and dynamic complexity). The Roundtable on Sustainable Palm Oil provides an illustrative case study on how this analytical framework describes and explains organizational change in partnerships from a problem-based perspective. The framework can be used to better understand and predict the complex relationships between MSP governance processes, systemic change and societal problems, but also as a guiding tool in (re-)organizing governance processes to continuously re-assess the problems over time and address them accordingly

State of emergency medicine in Spain

Spain has universal public health care coverage. Emergency care provisions are offered to patients in different modalities and levels according to the characteristics of the medical complaint: at primary care centers (PCC), in an extrahospital setting by emergency medical services (EMS) and at hospital emergency departments (ED). We have more than 3,000 PCCs, which are run by family doctors (general practitioners) and pediatricians. On average, there is 1 PCC for every 15,000 to 20,000 inhabitants, and every family doctor is in charge of 1,500 to 2,000 citizens, although less populated zones tend to have lower ratios. Doctors spend part of their duty time in providing emergency care to their own patients. While not fully devoted to emergency medicine (EM) practice, they do manage minor emergencies. However, Spanish EMSs contribute hugely to guarantee population coverage in all situations. These EMS are run by EM technicians (EMT), nurses and doctors, who usually work exclusively in the emergency arena. EDs dealt with more than 25 million consultations in 2008, which implies, on average, that one out of two Spaniards visited an ED during this time. They are usually equipped with a wide range of diagnostic tools, most including ultrasonography and computerized tomography scans. The academic and training background of doctors working in the ED varies: nearly half lack any structured specialty residence training, but many have done specific master or postgraduate studies within the EM field. The demand for emergency care has grown at an annual rate of over 4% during the last decade. This percentage, which was greater than the 2% population increase during the same period, has outpaced the growth in ED capacity. Therefore, Spanish EDs become overcrowded when the system exerts minimal stress. Despite the high EM caseload and the potential severity of the conditions, training in EM is still unregulated in Spain. However, in April 2009 the Spanish Minister of Health announced the imminent approval of an EM specialty, allowing the first EM resident to officially start in 2011. Spanish emergency physicians look forward to the final approval, which will complete the modernization of emergency health care provision in Spain

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

In vitro and in vivo assessment of magnetically actuated biomaterials for tendon regeneration

Tendon regeneration can be undermined by the formation of fibrous adhesions (scar tissue) between the healing tendon and the surrounding tissues. Scarring is associated with the recruitment of inflammatory cells such as macrophages and mast cells[1]. To tackle this issue we advocate the implementation of postoperative rehabilitation programmes to control inflammation levels and scarring, ensuring this way better clinical outcomes. In this study we propose the insertion of a magnetic responsive biomaterial between the healing tendon and the surrounding tissues. We hypothesise this material in combination with a magnetic field will modulate inflammation and reduce fibrous adhesion. Here we present the results from the first stage of our study, where magnetic biomaterials were tested subcutaneously to evaluate the inflammatory response and the ability of this material to control the presence of fibrous tissue.info:eu-repo/semantics/publishedVersio

Continuous exposure to simulated hypergravity induced changes in proliferation, morphology and gene expression of human tendon cells

Gravity influences physical and biological processes, especially during development and homeostasis of several tissues in the human body. Studies under altered gravity have been receiving great attention towards a better understanding of microgravity, hypogravity (1g) induced alterations. In the present work, the influence of simulated hypergravity over human tendon-derived cells (hTDCs) was studied at 5, 10, 15 and 20g for 4 or 16 h, using a large diameter centrifuge (LDC). Main results showed that 16 h of simulated hypergravity limited cell proliferation. Cell area was higher in hTDCs cultured at 5, 10 and 15g for 16 h, in comparison to 1g control. Actin filaments were more pronounced in hTDCs cultured at 5 and 10g for 16 h. Focal adhesion kinase (FAK) was mainly expressed in focal adhesion sites upon hypergravity stimulation, in comparison to perinuclear localization in control cells after 16 h; and FAK number/cell increased with increasing g-levels. A tendency towards an up-regulation of tenogenic markers was observed; SCX, TNC, COL3A1 and DCN were significantly up-regulated in hTDCs cultured at 15g and COL3A1 and DCN were significantly up-regulated in hTDCs cultured at 20g. Overall, simulated hypergravity affected the behavior of hTDCs, with more pronounced effects in the long-term period (16 h) of stimulation.The experiments reported here were performed in the framework of the Spin Your Thesis!  2016 programme, organized by ESA Education Office. Authors are grateful to the staff of  ESA Education Office, Nigel Savage and Lukas Pfeiffer, for the insightful discussion and  support; and to Alan Dowson and Elsa Silva for the technical support before and during the  campaign.  The authors would like to thank to Hospital da Prelada (Porto, Portugal) for providing  tendon  tissue  samples.  Authors  also  acknowledge  Portuguese  funds  through  FCT  –  Fundação para a Ciência e a Tecnologia in the framework of FCT‐POPH‐FSE, the PhD grant  SFRH/BD/96593/2013 of R.C‐A and the consolidator grant IF/00593/2015 of M.E.G.; to the  project RL3‐TECT‐NORTE‐07‐0124‐FEDER‐000020 cofinanced by ON.2 under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund  (ERDF). info:eu-repo/semantics/publishedVersio

2-dimensional carbon nanostructures obtained by laser ablation in liquid: effect of an ultrasonic field

COLA 2017, Marseille (France) from 3 to 8 september 2017. -- https://cola2017.sciencesconf.org/The ablation of carbon targets immersed in deionized water, in absence and in presence of ultrasonic waves is reported, and the differences investigated. The lasers used were an excimer laser emitting 20 ns pulses at 193 nm and a Nd:YAG laser at 355 nm..The obtained nanostructures were characterized by Transmission Electron Microscopy (TEM) and Raman spectroscopy. Transmission electron images reveal that the produced carbon nanostructures obtained at 193 nm, with and without ultrasound, are graphene-like sheets. The samples prepared without ultrasound have larger sizes of several microns and more regular shapes whereas those prepared with ultrasound have sizes of less than a micrometer and irregular shapes; additionally, in this last case, some quasi-spherical particles with sizes around 10 nm are observed. Irradiating at 355 nm results in the production of small nanoparticles in both cases. Figure 1 a, and 1b, show the graphene-like structures obtained without and with ultrasound respectively. In figure 1c the crystalline character of the graphene-like structures is shown. Additionally, the targets were analyzed in the irradiated zone by Raman spectroscopy in both cases (with and without ultrasound). Some differences were found indicating local structural changes in the case of ultrasound presence.Peer Reviewe