Are head-down tilt bedrest studies capturing the true nature of spaceflight-induced cognitive changes? A review

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions

Testing the Impact of Prebiotics on Anxiety-like Behaviors in Aged Male Rats

The composition of gut microbiota has direct impacts on neural structure, neurochemistry, and behavior. Specifically, the gut microbiota has been shown to modulate anxiety-like behaviors. In addition, administering prebiotics, compounds that promote the growth of commensal bacteria, has been demonstrated to reduce anxiety and anxiety-related behaviors. However, this effect has yet to be tested in older animals despite anxiety being implicated as a most common disorder in adult populations. Therefore, this study seeks to fill this knowledge gap by investigating the link between prebiotic interventions and anxiety-like behaviors in aged populations. It was hypothesized that older rats treated with the prebiotic fructooligosaccharide (FOS) would display an increase in exploratory behaviors, correlating to a decrease in anxiety, compared to the controls. Behavioral assays such as the open field test (OFT), elevated plus maze (EPM), and a social anxiety (SA) test were conducted. Results demonstrate moderate evidence that rats administered FOS had increased exploration in the center zone of the OFT. This finding suggests that FOS helps to modulate behavior in aged animals. With moderate evidence for increased exploration as evidence for decreased anxiety in FOS treated animals, this study provides a platform for further investigation of the role of modulating gut microbiota in older animals. Investigating the effects of senescence versus prebiotic treatment of the rats in this cohort was dampened by the limitations of the precedent of behavioral assays utilized on smaller, younger animals. As a result, this study calls for a widening of behavioral assay parameters to allow for effective data collection in an aging population

Platelets kill circulating parasites of all major Plasmodium species in human malaria

Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet–erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi. Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet–erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.This work was supported by the Australian National Health and Medical Research Council (Grants #1037304, #1045156, #490037, #605524, #1047082, #1047090, and #1066502, and Fellowships to N.M.A. [#1042072, #1135820], B.E.B. [#1088738], and M.J.G. [#1138860]), the Australian Research Council (grant #120100061), the Wellcome Trust (Fellowships to R.N.P. [#200909] and J.R.P. [#099875]), the Singapore National Medical Research Council (Award to T.W.Y. [CSA INV 15nov007]), and the Australian Department of Foreign Affairs and Trade

Host Porphobilinogen Deaminase Deficiency Confers Malaria Resistance in Plasmodium chabaudi but Not in Plasmodium berghei or Plasmodium falciparum During Intraerythrocytic Growth

An important component in host resistance to malaria infection are inherited mutations that give rise to abnormalities and deficiencies in erythrocyte proteins and enzymes. Understanding how such mutations confer protection against the disease may be useful for developing new treatment strategies. A mouse ENU-induced mutagenesis screen for novel malaria resistance-conferring mutations identified a novel non-sense mutation in the gene encoding porphobilinogen deaminase (PBGD) in mice, denoted here as PbgdMRI58155. Heterozygote PbgdMRI58155 mice exhibited ~50% reduction in cellular PBGD activity in both mature erythrocytes and reticulocytes, although enzyme activity was ~10 times higher in reticulocytes than erythrocytes. When challenged with blood-stage P. chabaudi, which preferentially infects erythrocytes, heterozygote mice showed a modest but significant resistance to infection, including reduced parasite growth. A series of assays conducted to investigate the mechanism of resistance indicated that mutant erythrocyte invasion by P. chabaudi was normal, but that following intraerythrocytic establishment a significantly greater proportions of parasites died and therefore, affected their ability to propagate. The Plasmodium resistance phenotype was not recapitulated in Pbgd-deficient mice infected with P. berghei, which prefers reticulocytes, or when P. falciparum was cultured in erythrocytes from patients with acute intermittent porphyria (AIP), which had modest (20-50%) reduced levels of PBGD. Furthermore, the growth of Pbgd-null P. falciparum and Pbgd-null P. berghei parasites, which grew at the same rate as their wild-type counterparts in normal cells, were not affected by the PBGD-deficient background of the AIP erythrocytes or Pbgd-deficient mice. Our results confirm the dispensability of parasite PBGD for P. berghei infection and intraerythrocytic growth of P. falciparum, but for the first time identify a requirement for host erythrocyte PBGD by P. chabaudi during in vivo blood stage infection.The authors were supported by an International Macquarie University Research Excellence Scholarship (CS), the NHMRC (490037, 605524, APP1047090, and APP1066502), the Australian Research Council (DP120100061) and the National Collaborative Research Infrastructure (NCRIS) via the Australian Phenomics Network (APN)

Assay platform for clinically relevant metallo-beta-lactamases

Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors

Addressing future work ability of employees in GP consultations: results of a cross-sectional study

Objectives!#!In this study we examined to what extent members of a best-practice integrated healthcare model in Germany discussed their subjective future work ability with their general practitioner (GP); furthermore, we examined independent variables which explain whether future work ability is discussed.!##!Methods!#!In a cross-sectional survey, 1168 (out of 3218 invited) integrated healthcare members responded to a standardized questionnaire. This study includes n = 475 employed respondents who were at most 65 years old. We determined the (relative) frequency of employed members up to 65 years who had already discussed their subjective future work ability with their GP. By means of logistic regression analysis, explanatory variables were identified which statistically explained the discussion of future work ability with their GP.!##!Results!#!N = 80 (16.8%) respondents stated they had discussed their future work ability with their GP. A multiple logistic regression analysis showed the following results: The odds ratio for discussing future work ability is increased the more satisfied respondents are with their general practitioner, the worse they assess their current work ability in relation to the physical demands of the job, and when respondents suffer from one or more chronic diseases (Nagelkerke's pseudo-R!##!Conclusions!#!Even in this healthcare setting, employees up to the age of 65 rarely discussed their subjective future work ability with their GP. This suggests that the issue 'future work ability' is even less commonly discussed in other community-based care settings in Germany. It seems that health care providers involved in acute care only sporadically take this issue into consideration - despite the great importance of maintaining work ability

The Relationship between Health Literacy, Quality of Life, and Subjective Health: Results of a Cross-Sectional Study in a Rural Region in Germany

Low health literacy is associated with poorer health and quality of life. An open question is whether a regional integrated healthcare system whose management strives to enable and empower its members with regard to health issues can contribute to a higher level of health literacy in the population. Against this background, in a cross-sectional study we surveyed a random selection of members of an integrated healthcare system in southwestern Germany (n = 180). The standardized questionnaire included, inter alia, questions on health literacy and subjective health. In this sample we wanted to (1) determine the proportion of respondents with sufficient health literacy and (2) investigate whether the association between health literacy and quality of life and subjective health status—as found in other studies—can be replicated. In our sample a health literacy score could be calculated in 126 subjects (70%). A sufficient level of health literacy was detected in 62% of respondents. Confirming the findings of a meta-analysis based on international studies, we found moderate correlations between health literacy and quality of life (r = 0.41) and health literacy and subjective health status (r = 0.40); these correlations hardly decreased when we controlled for various sociodemographic characteristics. As the proportion of respondents with sufficient health literacy was higher in our sample than in comparable studies conducted in Germany, we may hypothesize that an integrated healthcare system like the one we surveyed could have contributed to increased health literacy in the population. Thus, it could be worthwhile to investigate this research question with a more rigorous study design and a larger sample