Heat Shock Protein 40 and Immune Function in Altered Gravity

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role of HSP40 during stress-induced altered gravity conditions, wild-type and Hsp40 mutant Drosophila melanogaster were exposed to ground-based chronic hypergravity conditions, followed by quantitative PCR (qPCR) analysis of immune gene expression. In addition, larval hemocytes were collected to determine the functional output in response to E. coli bioparticle phagocytosis. Preliminary data indicates a required role for Hsp40 in strengthening immune function during stress-induced spaceflight in flies. In short, a critical need to evaluate the relationship between HSPs and immune suppression during space flight is necessary. Since space travel may become available to the general public in the not too distant future, and for the possibility of long-term space missions, a more comprehensive evaluation of the molecules responsible for immune dysfunction observed during space flight is required

Stress-Induced Heat Shock Protein 40 and Immune Function in Altered Gravity

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role of HSP40 during stress-induced altered gravity conditions, wild-type and Hsp40 mutant Drosophila melanogaster were exposed to ground-based chronic hypergravity conditions, followed by quantitative PCR (qPCR) analysis of immune gene expression. In addition, larval hemocytes were collected to determine the functional output in response to E. coli bioparticle phagocytosis. Preliminary data indicates a required role for Hsp40 in strengthening immune function during stress-induced spaceflight in flies. In short, a critical need to evaluate the relationship between HSPs and immune suppression during space flight is necessary. Since space travel may become available to the general public in the not too distant future, and for the possibility of long-term space missions, a more comprehensive evaluation of the molecules responsible for immune dysfunction observed during space flight is required

Pay-for-performance as a cost-effective implementation strategy: results from a cluster randomized trial

Abstract Background Pay-for-performance (P4P) has been recommended as a promising strategy to improve implementation of high-quality care. This study examined the incremental cost-effectiveness of a P4P strategy found to be highly effective in improving the implementation and effectiveness of the Adolescent Community Reinforcement Approach (A-CRA), an evidence-based treatment (EBT) for adolescent substance use disorders (SUDs). Methods Building on a $30 million national initiative to implement A-CRA in SUD treatment settings, urn randomization was used to assign 29 organizations and their 105 therapists and 1173 patients to one of two conditions (implementation-as-usual (IAU) control condition or IAU+P4P experimental condition). It was not possible to blind organizations, therapists, or all research staff to condition assignment. All treatment organizations and their therapists received a multifaceted implementation strategy. In addition to those IAU strategies, therapists in the IAU+P4P condition received US$50 for each month that they demonstrated competence in treatment delivery (A-CRA competence) and US $200 for each patient who received a specified number of treatment procedures and sessions found to be associated with significantly improved patient outcomes (target A-CRA). Incremental cost-effectiveness ratios (ICERs), which represent the difference between the two conditions in average cost per treatment organization divided by the corresponding average difference in effectiveness per organization, and quality-adjusted life years (QALYs) were the primary outcomes. Results At trial completion, 15 organizations were randomized to the IAU condition and 14 organizations were randomized to the IAU+P4P condition. Data from all 29 organizations were analyzed. Cluster-level analyses suggested the P4P strategy led to significantly higher average total costs compared to the IAU control condition, yet this average increase of 5$333), a 325% increase in the average number of patients who received the targeted dosage of treatment (ICER = $453), and a 325$8.134). Further supporting P4P as a cost-effective implementation strategy, the cost per QALY was only $8681 (95$1191–$16,171). Conclusion This study provides experimental evidence supporting P4P as a cost-effective implementation strategy. Trial registration NCT01016704

Morphology of <i>Penicillium rubens</i> Biofilms Formed in Space

Fungi biofilms have been found growing on spacecraft surfaces such as windows, piping, cables, etc. The contamination of these surfaces with fungi, although undesirable, is highly difficult to avoid. While several biofilm forming species, including Penicillium rubens, have been identified in spacecraft, the effect of microgravity on fungal biofilm formation is unknown. This study sent seven material surfaces (Stainless Steel 316, Aluminum Alloy, Titanium Alloy, Carbon Fiber, Quartz, Silicone, and Nanograss) inoculated with spores of P. rubens to the International Space Station and allowed biofilms to form for 10, 15, and 20 days to understand the effects of microgravity on biofilm morphology and growth. In general, microgravity did not induce changes in the shape of biofilms, nor did it affect growth in terms of biomass, thickness, and surface area coverage. However, microgravity increased or decreased biofilm formation in some cases, and this was incubation-time- and material-dependent. Nanograss was the material with significantly less biofilm formation, both in microgravity and on Earth, and it could potentially be interfering with hyphal adhesion and/or spore germination. Additionally, a decrease in biofilm formation at 20 days, potentially due to nutrient depletion, was seen in some space and Earth samples and was material-dependent

Evaluating the demographic history of the Seychelles kestrel (Falco araea): genetic evidence for recovery from a population bottleneck following minimal conservation management.

An important requirement for biologists conserving vulnerable species of wildlife and managing genetic problems associated with small population size is to evaluate existing evidence regarding what is known of a species’ recent population history. For endemic island species in particular, current genetic impoverishment could be due to either a recent population crash or a consequence of an evolutionary history of sustained isolation and small effective population size. Interpreting any given case can often be further complicated by incomplete or contradictory evidence from historical field surveys that might suggest a very different demographic history. Here, we use the case of the Seychelles kestrel (Falco araea), an island endemic previously listed as critically-endangered but now relatively common, to illustrate how genetic data from microsatellite genotypes of 100–150-year-old museum specimens reveals a recent and severe population crash since the 1940s to approximately eight individuals, before the population recovered. We re-interpret the historical population trajectory of the Seychelles kestrel in the light of the minimal intervention required for this species to recover. We examine different ecological explanations for the decline and apparently unassisted recovery of the Seychelles kestrel, review the evidence for similarly unaided recoveries elsewhere and discuss the implications of unaided population recoveries for future species conservation programmes. Demographic profiles from historical genetic signatures can provide highly informative evidence when evaluating past and future recovery efforts for endangered species

Lessons learned from the implementation of a video health coaching technology intervention to improve self-care of family caregivers of adults with heart failure

Individuals with heart failure (HF) typically live in the community and are cared for at home by family caregivers. These caregivers often lack supportive services and the time to access those services when available. Technology can play a role in conveniently bringing needed support to these caregivers. The purpose of this article is to describe the implementation of a virtual health coaching intervention with caregivers of HF patients (“Virtual Caregiver Coach for You”—ViCCY). A randomized controlled trial is currently in progress to test the efficacy of the intervention to improve self-care. In this trial, 250 caregivers will be randomly assigned to receive health information via a tablet computer (hereafter, tablet) plus 10 live health coaching sessions delivered virtually (intervention group; n = 125) or health information via a tablet only (control group; n = 125). Each tablet has specific health information websites preloaded. To inform others embarking on similar technology projects, here we highlight the technology challenges encountered with the first 15 caregivers who received the ViCCY intervention and the solutions used to overcome those challenges. Several adaptations to the implementation of ViCCY were needed to address hardware, software, and network connectivity challenges. Even with a well-designed research implementation plan, it is important to re-examine strategies at every step to solve implementation barriers and maximize fidelity to the intervention. Researcher and interventionist flexibility in adapting to new strategies is essential when implementing a technology-based virtual health coaching intervention

Colonic Inhibition of Phosphatase and Tensin Homolog Increases Colitogenic Bacteria, Causing Development of Colitis in Il10-/- Mice

BackgroundPhosphatase and tensin homolog (Pten) is capable of mediating microbe-induced immune responses in the gut. Thus, Pten deficiency in the intestine accelerates colitis development in Il10-/- mice. As some ambient pollutants inhibit Pten function and exposure to ambient pollutants may increase inflammatory bowel disease (IBD) incidence, it is of interest to examine how Pten inhibition could affect colitis development in genetically susceptible hosts.MethodsWith human colonic mucosa biopsies from pediatric ulcerative colitis and non-IBD control subjects, we assessed the mRNA levels of the PTEN gene and the gene involved in IL10 responses. The data from the human tissues were corroborated by treating Il10-/-, Il10rb-/-, and wild-type C57BL/6 mice with Pten-specific inhibitor VO-OHpic. We evaluated the severity of mouse colitis by investigating the tissue histology and cytokine production. The gut microbiome was investigated by analyzing the 16S ribosomal RNA gene sequence with mouse fecal samples.ResultsPTEN and IL10RB mRNA levels were reduced in the human colonic mucosa of pediatric ulcerative colitis compared with non-IBD subjects. Intracolonic treatment of the Pten inhibitor induced colitis in Il10-/- mice, characterized by reduced body weight, marked colonic damage, and increased production of inflammatory cytokines, whereas Il10rb-/- and wild-type C57BL/6 mice treated with the inhibitor did not develop colitis. Pten inhibitor treatment changed the fecal microbiome, with increased abundance of colitogenic bacteria Bacteroides and Akkermansia in Il10-/- mice.ConclusionsLoss of Pten function increases the levels of colitogenic bacteria in the gut, thereby inducing deleterious colitis in an Il10-deficient condition