Impact on Renal Function and Hospital Outcomes of an Individualized Management of Cardiopulmonary Bypass in Congenital Heart Surgery: A Pilot Study

During cardiopulmonary bypass (CPB), high flows can allow an adequate perfusion to kidneys, but, on the other hand, they could cause emboli production, increased vascular pressure, and a more intense inflammatory response, which are in turn causes of renal damage. Along with demographic variables, other intra-operative management and post-operative events, this might lead to Acute kidney injury (AKI) in infants undergoing cardiac surgery. The aim of our study was to investigate if a CPB strategy with flow requirements based on monitoring of continuous metabolic and hemodynamic parameters could have an impact on outcomes, with a focus on renal damage. Thirty-four consecutive infants and young children undergoing surgery requiring CPB, comparable as for demographic and patho-physiological profile, were included. In Group A, 16 patients underwent, for a variable period of 20 min, CPB aiming for the minimal flow that could maintain values of MVO2 > 70% and frontal NIRS (both left and right) > 45%, and renal NIRS > 65%. In Group B, 18 patients underwent nominal flows CPB. Tapered CPB allowed for a mean reduction of flows of 34%. No difference in terms of blood-gas analysis, spectroscopy trend, laboratory analyses, and hospital outcome were recorded. In patients developing AKI (20%), renal damage was correlated with demographic characteristics and with renal NIRS during the first 6 h in the ICU. A safe individualized strategy for conduction of CPB, which allows significant flow reduction while maintaining normal hemodynamic and metabolic parameters, does not impact on renal function and hospital outcomes

LUVMI: an innovative payload for the sampling of volatiles at the Lunar poles

The ISECG identifies one of the first exploration steps as in situ investigations of the moon or asteroids. Europe is developing payload concepts for drilling and sample analysis, a contribution to a 250kg rover as well as for sample return. To achieve these missions, ESA depends on international partnerships. Such missions will be seldom, expensive and the drill/sample site selected will be based on observations from orbit not calibrated with ground truth data. Many of the international science community’s objectives can be met at lower cost, or the chances of mission success improved and the quality of the science increased by making use of an innovative, low mass, mobile robotic payload following the LEAG recommendations. LUVMI provides a smart, low mass, innovative, modular mobile payload comprising surface and subsurface sensing with an in-situ sampling technology capable of depth-resolved extraction of volatiles, combined with a volatile analyser (mass spectrometer) capable of identifying the chemical composition of the most important volatiles. This will allow LUVMI to: traverse the lunar surface prospecting for volatiles; sample subsurface up to a depth of 10 cm (with a goal of 20 cm); extract water and other loosely bound volatiles; identify the chemical species extracted; access and sample permanently shadowed regions (PSR). The main innovation of LUVMI is to develop an in situ sampling technology capable of depth-resolved extraction of volatiles, and then to package within this tool, the analyser itself, so as to maximise transfer efficiency and minimise sample handling and its attendant mass requirements and risk of sample alteration. By building on national, EC and ESA funded research and developments, this project will develop to TRL6 instruments that together form a smart modular mobile payload that could be flight ready in 2020. The LUVMI sampling instrument will be tested in a highly representative environment including thermal, vacuum and regolith simulant and the integrated payload demonstrated in a representative environment

Cardiac hypertrophy is inhibited by a local pool of cAMP regulated by phosphodiesterase 2

Rationale: Chronic elevation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels has been associated with cardiac remodelling and cardiac hypertrophy. However, enhancement of particular aspects of cAMP/protein kinase A (PKA) signalling appears to be beneficial for the failing heart. cAMP is a pleiotropic second messenger with the ability to generate multiple functional outcomes in response to different extracellular stimuli with strict fidelity, a feature that relies on the spatial segregation of the cAMP pathway components in signalling microdomains. Objective: How individual cAMP microdomains impact on cardiac pathophysiology remains largely to be established. The cAMP-degrading enzymes phosphodiesterases (PDEs) play a key role in shaping local changes in cAMP. Here we investigated the effect of specific inhibition of selected PDEs on cardiac myocyte hypertrophic growth. Methods and Results: Using pharmacological and genetic manipulation of PDE activity we found that the rise in cAMP resulting from inhibition of PDE3 and PDE4 induces hypertrophy whereas increasing cAMP levels via PDE2 inhibition is anti-hypertrophic. By real-time imaging of cAMP levels in intact myocytes and selective displacement of PKA isoforms we demonstrate that the anti-hypertrophic effect of PDE2 inhibition involves the generation of a local pool of cAMP and activation of a PKA type II subset leading to phosphorylation of the nuclear factor of activated T cells (NFAT). Conclusions: Different cAMP pools have opposing effects on cardiac myocyte cell size. PDE2 emerges as a novel key regulator of cardiac hypertrophy in vitro and in vivo and its inhibition may have therapeutic applications

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

As human spaceflight progresses with extended mission durations, the demand for effective and safe drugs will necessarily increase. To date, the accepted medications used during missions (for space motion sickness, sleep disturbances, allergies, pain, and sinus congestion) are administered under the assumption that they act as safely and efficaciously as on Earth. However, physiological changes have been documented in human subjects in spaceflight involving fluid shifts, muscle and bone loss, immune system dysregulation, and adjustments in the gastrointestinal tract and metabolism. These alterations may change the pharmacokinetics (PK) and pharmacodynamics of commonly used medications. Frustratingly, the information gained from bed rest studies and from in‐flight observations is incomplete and also demonstrates a high variability in drug PK. Therefore, the objectives of this review are to report (i) the impact of the space environmental stressors on human physiology in relation to PK; (ii) the state‐of‐the‐art on experimental data in space and/or in ground‐based models; (iii) the validation of ground‐based models for PK studies; and (iv) the identification of research gaps

3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

: 3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future

3D Bioprinting in Microgravity: Opportunities, Challenges, and Possible Applications in Space

3D bioprinting has developed tremendously in the last couple of years and enables the fabrication of simple, as well as complex, tissue models. The international space agencies have recognized the unique opportunities of these technologies for manufacturing cell and tissue models for basic research in space, in particular for investigating the effects of microgravity and cosmic radiation on different types of human tissues. In addition, bioprinting is capable of producing clinically applicable tissue grafts, and its implementation in space therefore can support the autonomous medical treatment options for astronauts in future long term and far-distant space missions. The article discusses opportunities but also challenges of operating different types of bioprinters under space conditions, mainly in microgravity. While some process steps, most of which involving the handling of liquids, are challenging under microgravity, this environment can help overcome problems such as cell sedimentation in low viscous bioinks. Hopefully, this publication will motivate more researchers to engage in the topic, with publicly available bioprinting opportunities becoming available at the International Space Station (ISS) in the imminent future

LUVMI – Volatile Extraction and Measurements in Lunar Polar Regions

The low inclination of the lunar orbit allows areas in high latitudes to remain in eternal darkness.   These Permanently Shadowed Regions (PSR) are never illuminated by heating sunlight and are some of the coldest places in the Solar System which are thought to contain vast deposits of water and other volatiles.  In‐situ measurements are required as a definite proof of the existence of water and other volatiles in and around a PSR. The LUnar Volatiles Mobile Instrumentation (LUVMI) is an autonomous, low mass, modular rover consisting of surface and subsurface sensing instruments with an in‐situ sampling and analysis technology capable of depth resolved volatile extraction and characterisation.  With a total mass of less than 20 kg LUVMI is intended as an additional mobile payload for a lunar polar lander mission that will add the capability of allowing access to a PSR.  Volatile extraction from the lunar regolith will be carried out by the Volatiles Sampler (VS), which will sample the subsurface up to a depth of 10 cm, extract water and other loosely bound volatiles through heating.  The design of the VS provides efficient volatile sample transfer and minimizes sample handling requirements.  Evolved volatile characterisation will be performed by the Volatiles Analyser (VA) which is a miniature mass spectrometer based on the Ptolemy mass spectrometer instrument on‐board Philae, the ESA Rosetta Lander. We will discuss the LUVMI rover concept, the current concept of operations and the design of the mass spectrometer extraction systems

LUVMI Rover to Characterise Volatile Content in Lunar Polar Regions

The low inclination of the lunar orbit allows areas in high and low latitudes to remain in eternal darkness. These Permanently Shadowed Regions (PSR) are never illuminated by sunlight and are some of the coldest places in the Solar System and could contain vast deposits of water and other volatiles. In-situ measurements are required as a ‘ground-truth’ measurement to determine the existence volatiles in these regions. The LUnar Volatiles Mobile Instrumentation (LUVMI) is an autonomous, low mass, modular rover concept consisting of surface and subsurface sensing instruments with an in-situ sampling and analysis technology capable of depth resolved volatile extraction and characterisation. Volatile extraction from the lunar regolith will be carried out by the Volatiles Sampler (VS), which will sample the subsurface up to a depth of 20 cm, extract water and other loosely bound volatiles through heating. The design of the VS provides efficient volatile sample transfer and minimizes sample handling requirements. Evolved volatile characterisation will be performed by the Volatiles Analyser (VA) which is a miniature ion trap mass spectrometer based on the Ptolemy mass spectrometer instrument on-board Philae, the ESA Rosetta Lander. LUVMI-X (eXtended) will add the capability of allowing direct access to a PSR(s) via a miniature instrumented low velocity projectile that will be launched from the rover platform into areas of interest that are inaccessible to the rover. We will discuss the LUVMI test campaign conducted in December 2018, the current LUVMI-X configuration, the design of the mass spectrometer extraction systems and recent laboratory results obtained with volatile doped regolith simulant

Suture in Space: Preparation of an Experiment on the Healing of Sutured Wounds on Board the ISS

Wound healing (WH) is a process strictly regulated and highly conserved throughout evolution because it is indispensable for surviving injuries. On Earth WH has been studied in depth, nevertheless the role of mechanical factors in regulating the process and the mechanisms that, in adult mammals, lead to scarring instead of tissue regeneration are not well understood. In weightlessness WH has been poorly studied, and the effect of loading/unloading on the healing mechanisms is quite completely unknown. Preliminary studies showed microgravity-induced alterations in mechanisms underlying tissue repair. The implementation of procedures and tools to manage emergency surgery, trauma, serious burns, wounds and sutures is mandatory for future human deep space exploration missions at distances which are incompatible with medical evacuation to Earth. Therefore, studies on WH in weightlessness are needed and they are also an unique opportunity for understanding healing mechanisms still not completely known. The Suture in Space experiment, which will be performed on board the International Space Station (ISS), was selected by ESA (ESA-AO-ILSRA-2014) and supported by ASI in its development phase. It aims to study in weightlessness the behavior and healing of ex vivo sutured wound models prepared from skin and blood vessels biopsies derived from plastic and vascular surgery in healthy subjects. The experiment preparation required intense research activity on ground in order to: i) standardize procedures for collection of biopsies, model preparation, tissue culturing and monitoring, postflight analysis of samples; ii) define the requirements for hardware development. To ensure tissue viability throughout the in-flight experiment (4 weeks), we studied and developed a new tissue culture technique based on enriched culture media and a device able to model the physiological mechanical tension in the tissues and monitor its changes during WH, thus enabling the study of suture mechanical properties. The culture technique and WH models developed for the Suture in Space experiment can be applied to study: i) mechanical properties of tissues, tissue constructs, wounds and sutures in different loading conditions; ii) the role of gravity in tissue repair; iii) the relationship between biochemical and mechanical factors in repair mechanisms; iv) the influence of mechanical factors on scar quality; v) the effectiveness of treatments promoting WH, when applied in different loading conditions. The results of the experiment are expected to help in defining: i) strategies to manage wounds and promote healing in Space and on Earth; ii) suture techniques and materials to be used in space environment