Microbiological Lessons Learned from the Space Shuttle

After 30 years of being the centerpiece of NASA s human spacecraft, the Space Shuttle will retire. This highly successful program provided many valuable lessons for the International Space Station (ISS) and future spacecraft. Major microbiological risks to crewmembers include food, water, air, surfaces, payloads, animals, other crewmembers, and ground support personnel. Adverse effects of microorganisms are varied and can jeopardize crew health and safety, spacecraft systems, and mission objectives. Engineering practices and operational procedures can minimize the negative effects of microorganisms. To minimize problems associated with microorganisms, appropriate steps must begin in the design phase of new spacecraft or space habitats. Spacecraft design must include requirements to control accumulation of water including humidity, leaks, and condensate on surfaces. Materials used in habitable volumes must not contribute to microbial growth. Use of appropriate materials and the implementation of robust housekeeping that utilizes periodic cleaning and disinfection will prevent high levels of microbial growth on surfaces. Air filtration can ensure low levels of bioaerosols and particulates in the breathing air. The use of physical and chemical steps to disinfect drinking water coupled with filtration can provide safe drinking water. Thorough preflight examination of flight crews, consumables, and the environment can greatly reduce pathogens in spacecraft. The advances in knowledge of living and working onboard the Space Shuttle formed the foundation for environmental microbiology requirements and operations for the International Space Station (ISS) and future spacecraft. Research conducted during the Space Shuttle Program resulted in an improved understanding of the effects of spaceflight on human physiology, microbial properties, and specifically the host-microbe interactions. Host-microbe interactions are substantially affected by spaceflight. Astronaut immune functions were found to be altered. Selected microorganisms were found to become more virulent during spaceflight. The increased knowledge gained on the Space Shuttle resulted in further studies of the host-microbe interactions on the ISS to determine if countermeasures were necessary. Lessons learned from the Space Shuttle Program were integrated into the ISS resulting in the safest space habitat to date

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Burkholderia pseudomallei Is Spatially Distributed in Soil in Northeast Thailand

Melioidosis is a severe infection caused by the environmental bacterium Burkholderia pseudomallei. Soil sampling is important to identify geographic regions where humans and animals are at risk of exposure. The purpose of this study was to examine a factor that has a major bearing on the accuracy of soil sampling: the spatial distribution of B. pseudomallei in soil of a specified sampling site. Soil sampling was performed using a fixed-interval grid of 100 sampling points in each of two sites (disused land and rice field) in northeast Thailand, and the presence and amount of B. pseudomallei determined using culture. Mapping of the presence and B. pseudomallei count demonstrated that samples taken from areas adjacent to sampling points that were culture positive (negative) for B. pseudomallei were also likely to be culture positive (negative), and samples taken from areas adjacent to sampling points with a high (low) B. pseudomallei count were also likely to yield a high (low) count (spatial autocorrelation). These data were used as the basis for highlighting several pitfalls in current approaches to soil sampling, together with a discussion of the suitability of a range of sampling strategies in different geographical locations and for different study objectives

A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus

Neutralizing antibodies are a significant component of the host's protective response against flavivirus infection. Neutralization of flaviviruses occurs when individual virions are engaged by antibodies with a stoichiometry that exceeds a required threshold. From this “multiple-hit” perspective, the neutralizing activity of antibodies is governed by the affinity with which it binds its epitope and the number of times this determinant is displayed on the surface of the virion. In this study, we investigated time-dependent changes in the fate of West Nile virus (WNV) decorated with antibody in solution. Experiments with the well-characterized neutralizing monoclonal antibody (MAb) E16 revealed a significant increase in neutralization activity over time that could not be explained by the kinetics of antibody binding, virion aggregation, or the action of complement. Additional kinetic experiments using the fusion-loop specific MAb E53, which has limited neutralizing activity because it recognizes a relatively inaccessible epitope on mature virions, identified a role of virus “breathing” in regulating neutralization activity. Remarkably, MAb E53 neutralized mature WNV in a time- and temperature-dependent manner. This phenomenon was confirmed in studies with a large panel of MAbs specific for epitopes in each domain of the WNV envelope protein, with sera from recipients of a live attenuated WNV vaccine, and in experiments with dengue virus. Given enough time, significant inhibition of infection was observed even for antibodies with very limited, or no neutralizing activity in standard neutralization assays. Together, our data suggests that the structural dynamics of flaviviruses impacts antibody-mediated neutralization via exposure of otherwise inaccessible epitopes, allowing for antibodies to dock on the virion with a stoichiometry sufficient for neutralization

Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe

Short Lag Times for Invasive Tropical Plants: Evidence from Experimental Plantings in Hawai'i

Background: The lag time of an invasion is the delay between arrival of an introduced species and its successful spread in a new area. To date, most estimates of lag times for plants have been indirect or anecdotal, and these estimates suggest that plant invasions are often characterized by lag times of 50 years or more. No general estimates are available of lag times for tropical plant invasions. Historical plantings and documentation were used to directly estimate lag times for tropical plant invasions in Hawai’i. Methodology/Principal Findings: Historical planting records for the Lyon Arboretum dating back to 1920 were examined to identify plants that have since become invasive pests in the Hawaiian Islands. Annual reports describing escape from plantings were then used to determine the lag times between initial plantings and earliest recorded spread of the successful invaders. Among 23 species that eventually became invasive pests, the average lag time between introduction and first evidence of spread was 14 years for woody plants and 5 years for herbaceous plants. Conclusions/Significance: These direct estimates of lag times are as much as an order of magnitude shorter than previous, indirect estimates, which were mainly based on temperate plants. Tropical invaders may have much shorter lag times than temperate species. A lack of direct and deliberate observations may have also inflated many previous lag time estimates. Although there have been documented cases of long lag times due to delayed arrival of a mutualist or environmenta

Effects of climate and snow depth on Bromus tectorum population dynamics at high elevation

Invasive plants are thought to be especially capable of range shifts or expansion in response to climate change due to high dispersal and colonization abilities. Although highly invasive throughout the Intermountain West, the presence and impact of the grass Bromus tectorum has been limited at higher elevations in the eastern Sierra Nevada, potentially due to extreme wintertime conditions. However, climate models project an upward elevational shift of climate regimes in the Sierra Nevada that could favor B. tectorum expansion. This research specifically examined the effects of experimental snow depth manipulations and interannual climate variability over 5 years on B. tectorum populations at high elevation (2,175 m). Experimentally-increased snow depth had an effect on phenology and biomass, but no effect on individual fecundity. Instead an experimentally-increased snowpack inhibited population growth in 1 year by reducing seedling emergence and early survival. A similar negative effect of increased snow was observed 2 years later. However, a strong negative effect on B. tectorum was also associated with a naturally low-snow winter, when seedling emergence was reduced by 86%. Across 5 years, winters with greater snow cover and a slower accumulation of degree-days coincided with higher B. tectorum seedling density and population growth. Thus, we observed negative effects associated with both experimentally-increased and naturally-decreased snowpacks. It is likely that the effect of snow at high elevation is nonlinear and differs from lower elevations where wintertime germination can be favorable. Additionally, we observed a doubling of population size in 1 year, which is alarming at this elevation

Enhancing legacy in palliative care: study protocol for a randomized controlled trial of Dignity Therapy focused on positive outcomes

BACKGROUND: Dignity Therapy is a brief psychotherapy that can enhance a sense of legacy while addressing the emotional and existential needs of patients receiving hospice or palliative care. In Dignity Therapy, patients create a formalized “legacy” document that records their most cherished memories, their lessons learned in life, as well as their hopes and dreams for loved ones in the future. To date, this treatment has been studied for its impact on mitigating distress within hospice and palliative care populations and has provided mixed results. This study will instead focus on whether Dignity Therapy enhances positive outcomes in this population. METHODS/DESIGN: In this study, 90 patients with cancer receiving hospice or palliative care will complete a mixed-methods randomized controlled trial of Dignity Therapy (n = 45) versus Supportive Attention (n = 45). The patients will be enrolled in the study for 3 weeks, receiving a total of six study visits. The primary outcomes examine whether the treatment will quantitatively increase levels of positive affect and a sense of life closure. Secondary outcomes focus on gratitude, hope, life satisfaction, meaning in life, resilience, and self-efficacy. Using a fixed, embedded dataset design, this study will additionally use qualitative interviews to explore patients’ perceptions regarding the use of positive outcome measures and whether these outcomes are appropriately matched to their experiences in therapy. DISCUSSION: Dignity Therapy has shown mixed results when evaluating its impact on distress, although no other study to date has solely focused on the potential positive aspects of this treatment. This study is novel in its use of mixed methods assessments to focus on positive outcomes, and will provide valuable information about patients’ direct experiences in this area. TRIAL REGISTRATION: ISRCTN9138919

What "best practice" could be in Palliative Care: an analysis of statements on practice and ethics expressed by the main Health Organizations

<p>Abstract</p> <p>Background</p> <p>In palliative care it would be necessary to refer to a model. Nevertheless it seems that there are no official statements which state and describe that model. We carried out an analysis of the statements on practice and ethics of palliative care expressed by the main health organizations to show which dimensions of end-of-life care are taken into consideration.</p> <p>Methods</p> <p>The official documents by the most representative health organisations committed to the definition of policies and guidelines for palliative and end-of-life care had been considered. The documents were analysed through a framework of the components of end-of-life care derived from literature, which was composed of 4 main "areas" and of 12 "sub-areas".</p> <p>Results</p> <p>Overall, 34 organizations were identified, 7 international organisations, and 27 organisations operating on the national level in four different countries (Australia, Canada, UK and United States). Up to 56 documents were selected and analysed. Most of them (38) are position statements. Relevant quotations from the documents were presented by "areas" and "sub-areas". In general, the "sub-areas" of symptoms control as well as those referring to relational and social issues are more widely covered by the documents than the "sub-areas" related to "preparation" and to "existential condition". Indeed, the consistency of end-of-life choices with the patient's wishes, as well as completion and meaningfulness at the end of life is given only a minor relevance.</p> <p>Conclusions</p> <p>An integrated model of the best palliative care practice is generally lacking in the documents. It might be argued that the lack of a fixed and coherent model is due to the relevance of unavoidable context issues in palliative care, such as specific cultural settings, patient-centred variables, and family specificity. The implication is that palliative care staff have continuously to adapt their model of caring to the specific needs and values of each patient, more than applying a fixed, although maybe comprehensive, care model.</p

Stem cells from human extracted deciduous teeth expanded in foetal bovine and human sera express different paracrine factors after exposure to freshly prepared human serum

Background: The response of stem cells to paracrine factors within the host’s body plays an important role in the regeneration process after transplantation. The aim of this study was to determine the viability and paracrine factor profile of stem cells from human extracted deciduous teeth (SHED) pre-cultivated in media supplemented with either foetal bovine serum (FBS) or pooled human serum (pHS) in the presence of individual human sera (iHS). Methods: SHED (n=3) from passage 4 were expanded in FBS (FBS-SHED) or pHS (pHS-SHED) supplemented media until passage 7. During expansion, the proliferation of SHED was determined. Cells at passage 7 were further expanded in human serum from four individual donors (iHS) for 120 hours followed by assessment of cell viability and profiling of the secreted paracrine factors. Results: Proliferation of SHED was significantly higher (p<0.05) in pHS supplemented media compared to FBS supplemented media. pHS-SHED also maintained their higher proliferation rate compared to FBS-SHED in the presence of iHS. In iHS supplemented media, FBS-SHED expressed significantly higher levels of SDF-1A (p<0.05) after 24 hours compared to pHS-SHED. Similar results were found for HGF (p<0.01), LIF (p<0.05), PDGF-BB (p<0.05), SDF-1A (p<0.01), and IL-10 (p<0.05) when cell culture supernatants from FBS-SHED was profiled 120 hours post-incubation. Conclusion: SHED expanded in pHS instead of FBS have higher proliferative capacity and show an altered secretion profile. Further studies are needed to determine whether these differences could result in better engraftment and regeneration following transplantation