Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice

The study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days were also studied. Snca mRNA levels were increased in the raphe nuclei in the losers and in the VTA of the winners. After fighting deprivation Snca mRNA levels were decreased to the control level in both groups. Snca mRNA levels were similar to the control level in the VTA of the losers and in the raphe nuclei of the winners. However Snca gene expression was increased in these areas after no-fight period in the winners and losers in comparison with respective mRNA levels in the undeprived animals. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei. It was concluded, that social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice

Are Individuals Fickle-Minded?

Game theory has been used to model large-scale social events — such as constitutional law, democratic stability, standard setting, gender roles, social movements, communication, markets, the selection of officials by means of elections, coalition formation, resource allocation, distribution of goods, and war — as the aggregate result of individual choices in interdependent decision-making. Game theory in this way assumes methodological individualism. The widespread observation that game theory predictions do not in general match observation has led to many attempts to repair game theory by creating behavioral game theory, which adds corrective terms to the game theoretic predictions in the hope of making predictions that better match observations. But for game theory to be useful in making predictions, we must be able to generalize from an individual’s behavior in one situation to that individual’s behavior in very closely similar situations. In other words, behavioral game theory needs individuals to be reasonably consistent in action if the theory is to have predictive power. We argue on the basis of experimental evidence that the assumption of such consistency is unwarranted. More realistic models of individual agents must be developed that acknowledge the variance in behavior for a given individual

Evidence of immunometabolic dysregulation and airway dysbiosis in athletes susceptible to respiratory illness

Background Respiratory tract infection (RTI) is a leading cause of training and in-competition time-loss in athlete health. The immune factors associated with RTI susceptibility remain unclear. In this study, we prospectively characterise host immune factors in elite athletes exhibiting RTI susceptibility. Methods Peripheral blood lymphocyte flow cytometry phenotyping and 16S rRNA microbial sequencing of oropharyngeal swabs was performed in a prospective elite athlete cohort study (n = 121). Mass cytometry, peripheral blood mononuclear cell (PBMC) stimulation and plasma metabolic profiling was performed in age-matched highly-susceptible (HS) athletes (≥4RTI in last 18 months) (n = 22) compared to non-susceptible (NS) (≤1RTI in last 18 months) (n = 23) athletes. Findings were compared to non-athletic healthy controls (HC) (n = 19). Findings Athletes (n = 121) had a reduced peripheral blood memory T regulatory cell compartment compared to HC (p = 0.02 (95%CI:0.1,1.0)) and reduced upper airway bacterial biomass compared to HC (p = 0.032, effect size r = 0.19). HS athletes (n = 22) had lower circulating memory T regulatory cells compared to NS (n = 23) athletes (p = 0.005 (95%CI:-1.5,-0.15)) and HC (p = 0.002 (95%CI:-1.9,-0.3) with PBMC microbial stimulation assays revealing a T-helper 2 skewed immune response compared to HC. Plasma metabolomic profiling showed differences in sphingolipid pathway metabolites (a class of lipids important in infection and inflammation regulation) in HS compared to NS athletes and HC, with sphingomyelin predictive of RTI infection susceptibility (p = 0.005). Interpretation Athletes susceptible to RTI have reduced circulating memory T regulatory cells, metabolic dysregulation of the sphingolipid pathway and evidence of upper airway bacterial dysbiosis. Funding This study was funded by the English Institute of Sport (UK)

Comparison of the airway microbiota in children with chronic suppurative lung disease

Rationale: The airway microbiota is important in chronic suppurative lung diseases (CSLD), such as primary ciliary dyskinesia (PCD) and cystic fibrosis (CF). This comparison has not previously been described but is important because difference between the two diseases may relate to the differing prognoses and lead to pathological insights and potentially, new treatments. Objectives: To compare the longitudinal development of the airway microbiota in children with PCD to that of CF and relate this to age and clinical status. Methods: Sixty-two age-matched children (age range 0.5–17 years) with PCD or CF (n=31 in each group) were recruited prospectively and followed for 1.1 years. Throat swabs or sputum as well as clinical information were collected at routine clinical appointments. 16S rRNA gene sequencing was performed. Measurements and Main Results: The microbiota was highly individual and more diverse in PCD and differed in community composition when compared with CF. Whilst Streptococcus was the most abundant genus in both conditions, Pseudomonas was more abundant in CF with Haemophilus more abundant in PCD (Padj=0.0005). In PCD only, an inverse relationship was seen in the relative abundance of Streptococcus and Haemophilus with age. Conclusions: Bacterial community composition differs between children with PCD and those with CF. Pseudomonas is more prevalent in CF and Haemophilus in PCD, at least until infection with Pseudomonas supervenes. Interactions between organisms, particularly members of Haemophilus, Streptococcus, and Pseudomonas genera appear important. Study of the interactions between these organisms may lead to new therapies or risk stratification

National observational study to evaluate the "cleanyourhands" campaign (NOSEC): a questionnaire based study of national implementation

INTRODUCTION: The number of national hand-hygiene campaigns has increased recently, following the World Health Organisation's (WHO) "Save Lives: clean your hands" initiative (2009), which offers hospitals a multi-component hand-hygiene intervention. The number of campaigns to be evaluated remains small. Most evaluations focus on consumption of alcohol hand rub (AHR). We are not aware of any evaluation reporting implementation of all campaign components. In a previously published report, we evaluated the effects of the English and Welsh cleanyourhands campaign (2004-8) on procurement of AHR and soap, and on selected healthcare associated infections. We now report on the implementation of each individual campaign component: provision of bedside AHR, ward posters, patient empowerment materials, audit and feedback, and guidance to secure institutional engagement. METHOD: SETTING: all 189 acute National Health Service (NHS) hospitals in England and Wales (December 2005-June 2008). Six postal questionnaires (five voluntary, one mandatory) were distributed to infection control teams six-monthly from 6 to 36 months post roll-out. Selection and attrition bias were measured. RESULTS: Response rates fell from 134 (71 %) at 6 months to 82 (44 %) at 30 months, rising to 167 (90 %) for the final mandatory one (36 months). There was no evidence of attrition or selection bias. Hospitals reported widespread early implementation of bedside AHR and posters and a gradual rise in audit. At 36 months, 90 % of respondents reported the campaign to be a top hospital priority, with implementation of AHR, posters and audit reported by 96 %, 97 % and 91 % respectively. Patient empowerment was less successful. CONCLUSIONS: The study suggests that all campaign components, apart from patient empowerment, were widely implemented and sustained. It supports previous work suggesting that adequate piloting, strong governmental support, refreshment of campaigns, and sufficient time to engage institutions help secure sustained implementation of a campaign's key components. The results should encourage countries wishing to launch coordinated national campaigns for hospitals to participate in the WHO's "Save Lives" initiative, which offers hospitals a similar multi-component intervention

Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field still needs to rely on a 50-y-old laborious and time-consuming method to assess the lifespan of yeast cells and to isolate differentially aged cells for microscopic snapshots via manual dissection of daughter cells from the larger mother cell. Here, we are unique in achieving continuous and high-resolution microscopic imaging of the entire replicative lifespan of single yeast cells. Our microfluidic dissection platform features an optically prealigned single focal plane and an integrated array of soft elastomer-based micropads, used together to allow for trapping of mother cells, removal of daughter cells, monitoring gradual changes in aging, and unprecedented microscopic imaging of the whole aging process. Using the platform, we found remarkable age-associated changes in phenotypes (e.g., that cells can show strikingly differential cell and vacuole morphologies at the moment of their deaths), indicating substantial heterogeneity in cell aging and death. We envision the microfluidic dissection platform to become a major tool in aging research.

A Proline-Rich Structural Protein of the Surface Sheath of Larval Brugia Filarial Nematode Parasites

Both cDNA and genomic DNA sequences have been isolated which encode a proline-rich precursor protein of the sheath from microfilariae, the first stage larvae of the filarial nematode parasites Brugia pahangi andBrugia malayi. This 22-kDa protein is soluble only under reducing conditions and is extensively cross- linked by both disulfide and nonreducible bonds. Immunogold electron microscopy shows that the protein is localized exclusively in the sheath, a vestigial remnant of the eggshell, which is retained by and encloses the mature microfilaria. Analysis by Western blotting confirms that the protein is expressed only in microfilariae and adult female worms, although transcripts are detectable only in adult females. The deduced amino acid sequence contains a short N-terminal hydrophobic putative leader sequence, a central repetitive domain that contains 14 copies of a degenerate 5-amino acid repeat with the consensus sequence Met- Pro-Pro-Gln-Gly, and a C-terminal prolinerich do- main flanked by clusters of cysteine residues. These clusters can be aligned with cysteine residues implicated in cross-linking of a family of cuticular collagens originally identified in Caenorhabditiselegans but which extends to other nematodes

Exploring what lies behind public preferences for avoiding health losses caused by lapses in healthcare safety and patient lifestyle choices

© 2013 Singh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Although many studies have identified public preferences for prioritising health care interventions based on characteristics of recipient or care, very few of them have examined the reasons for the stated preferences. We conducted an on-line person trade-off (PTO) study (N=1030) to investigate whether the public attach a premium to the avoidance of ill health associated with alternative types of responsibilities: lapses in healthcare safety, those caused by individual action or lifestyle choice; or genetic conditions. We found that the public gave higher priority to prevention of harm in a hospital setting such as preventing hospital associated infections than genetic disorder but drug administration errors were valued similar to genetic disorders. Prevention of staff injuries, lifestyle diseases and sports injuries, were given lower priority. In this paper we aim to understand the reasoning behind the responses by analysing comments provided by respondents to the PTO questions. Method: A majority of the respondents who participated in the survey provided brief comments explaining preferences in free text responses following PTO questions. This qualitative data was transformed into explicit codes conveying similar meanings. An overall coding framework was developed and a reliability test was carried out. Recurrent patterns were identified in each preference group. Comments which challenged the assumptions of hypothetical scenarios were also investigated. Results: NHS causation of illness and a duty of care were the most cited reasons to prioritise lapses in healthcare safety. Personal responsibility dominated responses for lifestyle related contexts, and many respondents mentioned that health loss was the result of the individual’s choice to engage in risky behaviour. A small proportion of responses questioned the assumptions underlying the PTO questions. However excluding these from the main analysis did not affect the conclusions. Conclusion: Although some responses indicated misunderstanding or rejection of assumptions we put forward, the results were still robust. The reasons put forward for responses differed between comparisons but responsibility was the most frequently cited. Most preference elicitation studies only focus on eliciting numerical valuations but allowing for qualitative data can augment understanding of preferences as well as verifying results.EPSRC through the MATCH programme(EP/F063822/1 and EP/G012393/1) and HERG within Brunel University