Despite extensive research, the understanding of human health changes that result from long-duration space-flight remains limited, in part due to the wide range of study types and designs, lack of independent experiment replication and data dispersal in many articles. We have compiled a database from 37 health studies that re-ported data for 517 parameters from missions of longer than 3-month duration on the International Space Station. We found an abundance of physiological and biochemical parameters and limited psychological/ behavioral in-flight data. When we compared in-flight to pre-flight data, 14 out of 40 studied measurement type categories changed significantly, whereas only 3 categories changed significantly post-flight. Collagen break-down biomarkers in urine showed the greatest effect, a 2-fold increase in-flight, but no data in this category was reported post-flight. Eye movements related to the vestibular system function had the greatest in-flight effect that was sustained post-flight, with a decrease of 81% in-flight and a 32% decrease remained post-flight. Analysis of the in-flight compared to post-flight biochemical and physiological changes revealed overall low correlations (R2 = 0.03 & R2 = 0.23, respectively), as parameters tend to return to baseline post-flight. As we look to longer duration space missions, this review provides an opportunity to identify and highlight salient results that have been reported to date for long duration spaceflight, to enhance our understanding of space health and to develop effective countermeasures. We believe that the compiled data could be explored for medical interpretation of the observed changes, in-flight timeline of changes for natural history studies, correlation analysis for parameters across different body systems, and comparison of in-flight responses to ground-based studies.

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind's efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion.

For centuries, fermented soy foods have been dietary staples in Asia and, now, in response to consumer demand, they are available throughout the world. Fermentation bestows unique flavors, boosts nutritional values and increases or adds new functional properties. In this review, we describe the functional properties and underlying action mechanisms of soy-based fermented foods such as Natto, fermented soy milk, Tempeh and soy sauce. When possible, the contribution of specific bioactive components is highlighted. While numerous studies with in vitro and animal models have hinted at the functionality of fermented soy foods, ascribing health benefits requires well-designed, often complex human studies with analysis of diet, lifestyle, family and medical history combined with long-term follow-ups for each subject. In addition, the contribution of the microbiome to the bioactivities of fermented soy foods, possibly mediated through direct action or bioactive metabolites, needs to be studied. Potential synergy or other interactions among the microorganisms carrying out the fermentation and the host's microbial community may also contribute to food functionality, but the details still require elucidation. Finally, safety evaluation of fermented soy foods has been limited, but is essential in order to provide guidelines for consumption and confirm lack of toxicity.

The effect of soy ferments on gene expression induced by the proinflammatory cytokine tumour necrosis factor α (TNFα) at the intestinal epithelial cell (IEC) level was evaluated. Microarray-based transcriptional analysis revealed that soy fermented with Lactobacillus helveticus R0052 and Streptococcus thermophilus R0083 (SF-Lh) down-regulated 33 of 40 proinflammatory genes up-regulated by TNFα in HT-29 IEC, attenuating expression of genes encoding several proinflammatory cytokines and cell adhesion molecules. TNFα-mediated activation of gene expression associated with the NF-κB pathway was also repressed, as was Interleukin-8 (IL-8) production. In contrast, soy fermented with Bifidobacterium longum R0175 and S. thermophilus R0083 (SF-Bl) up-regulated expression of three proinflammatory genes induced by TNFα. Increased intracellular levels of hydrogen peroxide (H2O2) were detected in HT-29 IEC following incubation with SF-Lh. These results indicate that SF-Lh has immunomodulatory activity through reduction of proinflammatory gene expression at the IEC level.

In 2012, the International Space Station (ISS) (Fig. 1) partnership published the updated International Space Station Benefits for Humanity [1], a compilation of stories about the many benefits being realized in the areas of human health, Earth observations and disaster response, and global education. This compilation has recently been revised to include updated statistics on the impacts of the benefits, and new benefits that have developed since the first publication. Two new sections have also been added to the book, economic development of space and innovative technology. This paper will summarize the updates on behalf of the ISS Program Science Forum, made up of senior science representatives across the international partnership.The new section on "Economic Development of Space" highlights case studies from public-private partnerships that are leading to a new economy in low earth orbit (LEO). Businesses provide both transportation to the ISS as well as some research facilities and services. These relationships promote a paradigm shift of government-funded, contractor-provided goods and services to commercially-provided goods purchased by government agencies. Other examples include commercial firms spending research and development dollars to conduct investigations on ISS and commercial service providers selling services directly to ISS users. This section provides examples of ISS as a test bed for new business relationships, and illustrates successful partnerships.The second new section, "Innovative Technology," merges technology demonstration and physical science findings that promise to return Earth benefits through continued research. Robotic refueling concepts for life extensions of costly satellites in geo-synchronous orbit have applications to robotics in industry on Earth. Flame behavior experiments reveal insight into how fuel burns in microgravity leading to the possibility of improving engine efficiency on Earth. Nanostructures and smart fluids are examples of materials improvements that are being developed using data from ISS.The publication also expands the benefits of research results in human health, environmental change and disaster response and in education activities developed to capture student imaginations in support of science, technology, engineering and mathematics, or STEM, education internationally. Applications to human health of the knowledge gained on ISS continue to grow and improve healthcare technologies and our understanding of human physiology. Distinct benefits return to Earth from the only orbiting multi-disciplinary laboratory of its kind. The ISS is a stepping stone for future space exploration by providing findings that develop LEO and improve life on our planet. (C) 2016 Published by Elsevier Ltd. on behalf of IAA.

Throughout the history of the International Space Station (ISS), crews on board have conducted a variety of scientific research and educational activities. Well into the second year of full utilization of the ISS laboratory, the trend of scientific accomplishments and educational opportunities continues to grow. More than 1500 investigations have been conducted on the ISS since the first module launched in 1998, with over 700 scientific publications. The ISS provides a unique environment for research, international collaboration and educational activities that benefit humankind. This paper will provide an up to date summary of key investigations, facilities, publications, and benefits from ISS research that have developed over the past year. Discoveries in human physiology and nutrition have enabled astronauts to return from ISS with little bone loss, even as scientists seek to better understand the new puzzle of “ocular syndrome” affecting the vision of up to half of astronauts. The geneLAB campaign will unify life sciences investigations to seek genomic, proteomic and metabolomics of the effect of microgravity on life as a whole. Combustion scientists identified a new “cold flame” phenomenon that has the potential to improve models of efficient combustion back on Earth. A significant number of instruments in Earth remote sensing and astrophysics are providing new access to data or nearing completion for launch, making ISS a significant platform for understanding of the Earth system and the universe. In addition to multidisciplinary research, the ISS partnership conducts a myriad of student led research investigations and educational activities aimed at increasing student interest in science, technology, engineering and mathematics (STEM). Over the past year, the ISS partnership compiled new statistics of the educational impact of the ISS on students around the world. More than 43 million students, from kindergarten to graduate school, with more than 28 million teachers located in 49 countries have participated in some aspect of ISS educational activities. These activities include student-developed investigations, education competitions and classroom versions of ISS investigations, participating in ISS investigator experiments, ISS hardware development, educational demonstrations and cultural activities. Through the many inquiry-based educational activities, students and teachers are encouraged to participate in the ISS program thus motivating the next generation of students to pursue careers in STEM.

The ISS partnership has seen a substantial increase in research accomplished, crew efforts devoted to research, and results of ongoing research and technology development. The ISS laboratory is providing a unique environment for research and international collaboration that benefits humankind. Benefits come from the engineering development, the international partnership, and from the research results. Benefits can be of three different types: scientific discovery, applications to life on Earth, and applications to future exploration. Working across all ISS partners, we identified key themes where the activities on the ISS improve the lives of people on Earth--not only within the partner nations, but also in other nations of the world. Three major themes of benefits to life on earth emerged from our review: benefits to human health, education, and Earth observation and disaster response. Other themes are growing as use of the ISS continues. Benefits to human health range from advancements in surgical technology, improved telemedicine, and new treatments for disease. Earth observations from the ISS provide a wide range of observations that include: marine vessel tracking, disaster monitoring and climate change. The ISS participates in a number of educational activities aimed to inspire students of all ages to learn about science, technology, engineering and mathematics. To date over 63 countries have directly participated in some aspect of ISS research or education. In summarizing these benefits and accomplishments, ISS partners are also identifying ways to further extend the benefits to people in developing countries for the benefits of humankind.

During 2011, the International Space Station reached an important milestone in the completion of assembly and the shift to the focus on a full and continuous utilization mission in space. The ISS partnership itself has also met a milestone in the coordination and cooperation of utilization activities including research, technology development and education. We plan and track all ISS utilization activities jointly and have structures in place to cooperate on common goals by sharing ISS assets and resources, and extend the impacts and efficiency of utilization activities. The basic utilization areas on the ISS include research, technology development and testing, and education/outreach. Research can be categorized as applied research for future exploration, basic research taking advantage of the microgravity and open space environment, and Industrial R&D / commercial research focused at industrial product development and improvement. Technology development activities range from testing of new spacecraft systems and materials to the use of ISS as an analogue for future exploration missions to destinations beyond Earth orbit. This presentation, made jointly by all ISS international partners, will highlight the ways that international cooperation in all of these areas is achieved, and the overall accomplishments that have come as well as future perspectives from the cooperation. Recently, the partnership has made special efforts to increase the coordination and impact of ISS utilization that has humanitarian benefits. In this context the paper will highlight tentative ISS utilization developments in the areas of Earth remote sensing, medical technology transfer, and education/outreach.

Enhancement of nutritional or vitamin content of foods is commonly touted as a major benefit of probiotics. In this paper, we examined the ability of three probiotic bacteria either alone or in combination to enhance nutritional content. Pure and mixed cultures of Streptococcus thermophilus ST5 and Lactobacillus helveticus R0052 or Bifidobacterium longum R0175 were used to prepare fermented soy beverages. The effects of strain, acidification and mixed cultures on the deconjugation of soy isoflavones were examined. Acidification to pH 4.7 alone resulted in a 7% drop in isoflavone levels. Deconjugation levels varied between the different glucosides. Fermentation by L. helveticus R0052 resulted in the 50% reduction in total glucosides with O-malonyl glucosides being reduced 64%. Fermentation by S. thermophilus ST5 or B. longum R0175 had no significant effect on isoflavone levels. Combining a S. thermophilus strain with a L. helveticus culture reduced the effectiveness of the latter. Fermentation did not significantly modify vitamin B1 or B6 levels.

Astronauts face numerous health challenges during long-duration space missions, including diminished immunity, bone loss and increased risk of radiation-induced carcinogenesis. Changes in the intestinal flora of astronauts may contribute to these problems. Soy-based fermented food products could provide a nutritional strategy to help alleviate these challenges by incorporating beneficial lactic acid bacteria, while reaping the benefits of soy isoflavones. We carried out strain selection for the development of soy ferments, selecting strains of lactic acid bacteria showing the most effective growth and fermentation ability in soy milk (Streptococcus thermophilus ST5, Bifidobacterium longum R0175 and Lactobacillus helveticus R0052). Immunomodulatory bioactivity of selected ferments was assessed using an in vitro challenge system with human intestinal epithelial and macrophage cell lines, and selected ferments show the ability to down-regulate production of the pro-inflammatory cytokine interleukin-8 following challenge with tumour necrosis factor-alpha. The impact of fermentation on vitamin B1 and B6 levels and on isoflavone biotransformation to agluconic forms was also assessed, with strain variation-dependent biotransformation ability detected. Overall this suggests that probiotic bacteria can be successfully utilized to develop soy-based fermented products targeted against health problems associated with long-term space travel.

Abstract Immunomodulatory effects of lactic acid bacteria vary with strain and may vary with growth phase and medium. The ability of different lactobacilli strains (Lactobacillus helveticus R0052, L. rhamnosus R0011, L. rhamnosus GG) at different growth phases to modulate macrophage and intestinal epithelial cell cytokine production following a proinflammatory challenge was examined. Soy and milk ferments were also prepared with strains shown to grow well in soy milk (Bifidobacteria longum R0175 and Lactobacillus helveticus R0052). Modulation of cytokine production by human macrophage cell lines (U937 and THP-1) and intestinal epithelial cells (HT-29) induced by Tumor Necrosis Factor αwas assayed by ELISA for interleukin-8 (IL-8) production. Strain-dependent differences were observed in the ability of spent MRS broths from log versus stationary growth phase, and of soy and milk ferments to down-regulate IL-8 production by challenged U937 cells. Overall, variation in immunomodulatory activity of these lactic acid bacteria reflects not only strain variation but potentially also differences in growth phase and substrate. Funded by NSERC, Lallemand Inc. and the Canadian Space Agency.

As the pace of human exploration of space is accelerated, the need to address the challenges of long-duration human missions becomes imperative. Working with limited resources, we must determine the most effective way to meet this challenge. A great deal of science management centres on “applied” versus “basic” research as the cornerstone of a program. We have chosen to largely ignore such a labeling of science and concentrate on quality, as determined by peer review, as the primary criterion for science selection. Space Life Sciences is a very young science and access to space continues to be difficult. Because we have few opportunities for conducting science, and space life science is very challenging, we are comfortable maintaining a very high bar for selection. In order to ensure adequate depth to our community we have elected to concentrate our efforts. Working in concert with members of the community, we have identified specific areas of focus that are chosen by their importance in space, but also according to Canada's strength in the terrestrial counterpart of the research. It is hoped that through a balanced but highly competitive program with the emphasis on quality, Canadian scientists can contribute to making space a safer, more welcoming place for our astronauts.

The Canadian Space Agency (CSA) has a strong history of supporting microgravity research in space. Canada is an International Space Station (ISS) Partner and has played a key role in construction of the ISS, through provision and operation of the ISS robotic arm. The CSA also plans to contribute to microgravity research onboard ISS, through the support of Canadian scientists and the development of microgravity payloads. The CSA is particularly committed to manifesting payloads on ISS that allow scientists to address fundamental questions and problems that also have important application to human society. With regard to the development of facilities for microgravity research, the CSA is currently identifying and assessing gaps in the capabilities of extant, manifested, and planned facilities of the other ISS partners. In order to avoid duplication of effort, CSA development of facilities for ISS will only occur if significant gaps in capability are identified that are linked to important microgravity research endeavors. The CSA is also developing a program of ISS utilization that includes regular solicitation of the best scientific proposals from the Canadian microgravity research community, with focus on the fields of material science, fluid dynamics, combustion, and biotechnology. Payload development and manifesting will then allow Canadian scientists to regularly utilize the ISS. The Canadian microgravity research community is also supported by regular announcements of opportunity that give Canadian scientists the opportunity to test new ideas and concepts for microgravity research, for example by using microgravity analog systems.

It is generally agreed that space science benefits from an international collaboration. There are different mechanisms to make this happen but to recognize opportunities requires a keen awareness of the activities, people and respective strengths. Apex- Cambium is a joint Canadian Space Agency (CSA)-National Aeronautics and Space Administration (NASA) initiative. It was made possible in large part through the good relations and shared willingness to meet a common objective, that of doing exciting science in space. The actual mechanics of bringing an international project together can be divided into two perspectives: programmatic and implementation. The programmatic component includes recognizing complementarities, bringing science together, and the need to have Agencies approve and accept joint responsibility for the mission. The implementation component involves working to define science requirements, available resources and assigning individual responsibilities while keeping the overall success criteria as a collective objective. The APEX-CAMB11.JM mission will be described from the point of view of both CSA and NASA. Suggestions on how to facilitate these types of initiatives will be provided and highlights of the APEX-Cambium collaboration will be provided.

Space agencies of countries such as Canada experience particular challenges with respect to the establishment and maintenance of a flourishing space physical sciences community. The Canadian Space Agency has developed a long-term plan that will allow a relatively large number of Canadian scientists and industry partners to contribute to space physical science, and that will also provide a continual flow of flight experiments. This plan has inherent flexibility, allowing it to be adapted and used by space agencies of countries with a similar population base and resource capability as Canada. The plan can be visualized as a pyramid, with conceptual studies forming the base, and flight experiments the peak. Conceptual studies are solicited through a yearly Announcement of Opportunity (AO) that supplies grants to top-ranked proposals. Feasibility studies, which follow naturally from successfully completed conceptual studies, are solicited in the same AO. Depending on the maturity and complexity of the scientific and technical requirements for a flight experiment, a research team can submit proposals for flight experiment AOs de novo (i.e. without previous CSA funding) or after a successful feasibility study. Announcements of Opportunity for flight experiment will be offered every two years, depending on the number of successful proposals undergoing implementation. Applicants to these AOs will be able to tailor proposals to appropriate categories; i.e. proposals that have low resource (e.g. upmass, crewtime) requirements will be assessed separately from proposals that have significant resource requirements. It is expected that this AO scheme, combined with strategic support of workshops and a strong network of collaboration among international partner agencies, will allow CSA to develop and sustain a vigorous space physical science community.