Ovarian inflammation mediated by Toll-like receptor 4 increased transcripts of maternal effect genes and decreased embryo development

Obese women are subfertile and have reduced assisted reproduction success, which may be due to reduced oocyte competence. We hypothesize that consumption of a high-fat/high-sugar diet induces ovarian inflammation, which is a primary contributor to decreased oocyte quality and pre-implantation embryo development. To test this hypothesis, C57BL/6 (B6) mice with a normal inflammatory response and C3H/HeJ (C3H) mice with a dampened inflammatory response due to dysfunctional Toll-like receptor 4 were fed either normal chow or high-fat/high-sugar diet. In both B6 and C3H females, high-fat/high-sugar diet induced excessive adiposity and hyperglycemia compared to normal chow-fed counterparts. Conversely, ovarian CD68 levels and oocyte expression of oxidative stress markers were increased when collected from B6 high-fat/ high-sugar but not C3H high-fat/high-sugar mice. Following in vitro fertilization of in vivo matured oocytes, blastocyst development was decreased in B6-high-fat/high-sugar but not C3H high-fat/high-sugar mice. Expression of cumulus cell markers of oocyte quality were altered in both B6 high-fat/high-sugar and C3H high-fat/high-sugar. However, there were no diet-dependent differences in spindle abnormalities in either B6 or C3H mice, suggesting potential defects in cytoplasmic maturation. Indeed, there were significant increases in the abundance of maternal effect gene mRNAs in oocytes from only B6 high-fat/high-sugar mice. These differentially expressed genes encode proteins of the subcortical maternal complex and associated with mRNA metabolism and epigenetic modifications. These genes regulate maternal mRNA degradation at oocyte maturation, mRNA clearance at the zygotic genome activation, and methylation of imprinted genes suggesting a mechanism by which inflammation induced oxidative stress impairs embryo development

Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

There is evidence to support the use of supplementation with long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from oily fish or fish oil for the treatment of various inflammatory diseases such as rheumatoid arthritis. Chronic obstructive pulmonary disease (COPD) is a progressive, terminal disease characterized by persistent airflow limitation, lung and systemic inflammation. To date, one randomized controlled trial has been published that assessed the efficacy of LCn-3PUFA in people with this condition. The aim of this article is to discuss the feasibility of conducting a trial to evaluate fish oil supplementation as adjunct therapy in people with COPD.The study is supported by a University of South Australia, Division of Health Sciences grant (DRDG 2011 (round 2))

Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir-Host Populations.

Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host-pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.National Institutes of HealthThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Public Library of Science

Shifting mindsets: a realist synthesis of evidence from self-management support training

Context Accompanying the growing expectation of patient self-management is the need to ensure health care professionals (HCPs) have the required attitudes and skills to provide effective self-management support (SMS). Results from existing training interventions for HCPs in SMS have been mixed and the evidence base is weaker for certain settings, including supporting people with progressive neurological conditions (PNCs). We set out to understand how training operates, and to identify barriers and facilitators to training designed to support shifts in attitudes amongst HCPs. Methods We undertook a realist literature synthesis focused on: (i) the influence of how HCPs, teams and organisations view and adopt self-management; and (ii) how SMS needs to be tailored for people with PNCs. A traditional database search strategy was used alongside citation tracking, grey literature searching and stakeholder recommendations. We supplemented PNC-specific literature with data from other long-term conditions. Key informant interviews and stakeholder advisory group meetings informed the synthesis process. Realist context-mechanism-outcome configurations were generated and mapped onto the stages described in Mezirow's Transformative Learning Theory. Results Forty-four original articles were included (19 relating to PNCs), from which seven refined theories were developed. The theories identified important training elements (evidence provision, building skills and confidence, facilitating reflection and generating empathy). The significant influence of workplace factors as possible barriers or facilitators was highlighted. Embracing SMS often required challenging traditional professional role boundaries. Conclusion The integration of SMS into routine care is not an automatic outcome from training. A transformative learning process is often required to trigger the necessary mindset shift. Training should focus on how individual HCPs define and value SMS and how their work context (patient group and organisational constraints) influences this process. Proactively addressing potential contextual barriers may facilitate implementation. These findings could be applied to other types of training designed to shift attitudes amongst HCPs

An open label pilot trial of low‐dose lithium for young people at ultra‐high risk for psychosis

Aim: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side‐effect profile) of lithium in a sample of young people identified at ultra‐high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). Methods: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side‐effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. Results: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side‐effect assessment indicated that lithium was well‐tolerated. 64% (n = 16) of participants in the lithium group were lithium‐adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. Conclusions: With a side‐effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

Global gene expression analysis of human erythroid progenitors

This article is available open access through the publisher’s website. Copyright @ 2011 American Society of Hematology. This article has an erratum: http://bloodjournal.hematologylibrary.org/content/118/26/6993.3.Understanding the pattern of gene expression during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here, we isolated 4 distinct populations at successive erythropoietin-dependent stages of erythropoiesis, including the terminal, pyknotic stage. The transcriptome was determined using Affymetrix arrays. First, we demonstrated the importance of using defined cell populations to identify lineage and temporally specific patterns of gene expression. Cells sorted by surface expression profile not only express significantly fewer genes than unsorted cells but also demonstrate significantly greater differences in the expression levels of particular genes between stages than unsorted cells. Second, using standard software, we identified more than 1000 transcripts not previously observed to be differentially expressed during erythroid maturation, 13 of which are highly significantly terminally regulated, including RFXAP and SMARCA4. Third, using matched filtering, we identified 12 transcripts not previously reported to be continuously up-regulated in maturing human primary erythroblasts. Finally, using transcription factor binding site analysis, we identified potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts containing many genes with undiscovered functions in erythroblasts are a resource for future functional studies of erythropoiesis. Our Human Erythroid Maturation database is available at https://cellline.molbiol.ox.ac.uk/eryth/index.html.National Health Service Blood and Transplant, National Institute for Health Research Biomedical Research Center Program, and National Institute for Health Research

Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients:Data From the PACE 400 Cohort

Background: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging.Methods: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality—cognition, cortical structure information, and the neuroanatomical measure of brain age gap—to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231).Results: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%–12%, brain age gap 7%, cognition 0%–16%).Conclusions: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis

Penalty Corner Routines in Elite Women’s Indoor Field Hockey: Prediction of Outcomes based on Tactical Decisions

Indoor hockey is a highly competitive international sport, yet no research to date has investigated the key actions within this sport. As with outdoor field hockey, penalty corners represent one of the most likely situations in which goals can be scored. All 36 matches of the round-robin phase of the 2010-2011 England Hockey League Women’s Premier Division ‘Super Sixes’ competition were analysed with the purpose of establishing which factors can predict the scoring of a goal using Binary Logistic Regression analysis. Seventy two (22.6%) of the 319 observed penalty corners resulted in a goal. The strongest predictor of scoring a goal was taking the penalty corner from the goalkeeper’s right. Based on the odds ratio (OR), the odds of the attacking team scoring were 2.27 (CI = 1.41 - 3.65) times higher with penalty corners taken from the goalkeeper’s right as opposed to the left. Additionally, if the goalkeeper decided to rush to the edge of the circle, the odds of the attacking team failing to score were 2.19 (CI = 1.18 - 4.08) times higher compared to when the goalkeeper remained near the goal line. These results suggest that strategic decisions from the players and coaches have an important part to play in the success of penalty corners. Future research should investigate the impact of goalkeepers’ movement and further examine the technical and tactical intricacies of penalty corners

Improving Estimates of Social Contact Patterns for Airborne Transmission of Respiratory Pathogens.

Data on social contact patterns are widely used to parameterize age-mixing matrices in mathematical models of infectious diseases. Most studies focus on close contacts only (i.e., persons spoken with face-to-face). This focus may be appropriate for studies of droplet and short-range aerosol transmission but neglects casual or shared air contacts, who may be at risk from airborne transmission. Using data from 2 provinces in South Africa, we estimated age mixing patterns relevant for droplet transmission, nonsaturating airborne transmission, and Mycobacterium tuberculosis transmission, an airborne infection where saturation of household contacts occurs. Estimated contact patterns by age did not vary greatly between the infection types, indicating that widespread use of close contact data may not be resulting in major inaccuracies. However, contact in persons >50 years of age was lower when we considered casual contacts, and therefore the contribution of older age groups to airborne transmission may be overestimated