Survey of T-2 and HT-2 toxins by LC–MS/MS in oats and oat products from European oat mills in 2005–2009

T-2 and HT-2 toxins were analysed in oats (n = 243), oat flakes (n = 529), oat meal (n = 105) and oat by-products (n = 209) from 11 European mills during 2005–2009 by high-performance liquid chromatography with a triple quadrupole mass spectrometer. Limits of quantification were 5 μg kg−1 for both T-2 and HT-2 toxins in oats. The incidence of T-2 + HT-2 (> 5 μg kg−1) in oats, oat flakes, oat meal and oat by-products was 93, 77, 34 and 99%, respectively. The mean values of T-2 + HT-2 were 94, 17, 11 and 293 μg kg−1 for oats, oat flakes, oat meal and oat by-products, respectively. T-2 and HT-2 occurred together and the T-2 level was 52% of HT-2 in oats. Maximal T-2 and HT-2 concentration in oat flakes and oat meal were 197 and 118 μg kg−1. The toxins were reduced by 82–88% during processing, but increased 3.1 times in oat by-products

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Interactions between HIV-1 Reverse Transcriptase and the Downstream Template Strand in Stable Complexes with Primer-Template

Background: Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) forms stable ternary complexes in which RT is bound tightly at fixed positions on the primer-template (P/T). We have probed downstream interactions between RT and the template strand in the complex containing the incoming dNTP (+1 dNTPNRTNP/T complex) and in the complex containing the pyrophosphate analog, foscarnet (foscarnetNRTNP/T complex). Methods and Results: UV-induced cross-linking between RT and the DNA template strand was most efficient when a bromodeoxyuridine residue was placed in the +2 position (the first template position downstream from the incoming dNTP). Furthermore, formation of the +1 dNTPNRTNP/T complex on a biotin-containing template inhibited binding of streptavidin when biotin was in the +2 position on the template but not when the biotin was in the +3 position. Streptavidin pre-bound to a biotin residue in the template caused RT to stall two to three nucleotides upstream from the biotin residue. The downstream border of the complex formed by the stalled RT was mapped by digestion with exonuclease RecJF. UV-induced cross-linking of the complex formed by the pyrophosphate analog, foscarnet, with RT and P/T occurred preferentially with bromodeoxyuridine in the +1 position on the template in keeping with the location of RT one base upstream in the foscarnetNRTNP/T complex (i.e., in the pre-translocation position). Conclusions: For +1 dNTPNRTNP/T and foscarnetNRTNP/T stable complexes, tight interactions were observed between RT an

Exploring the barriers and facilitators of psychological safety in primary care teams: a qualitative study

Background Psychological safety is the concept by which individuals feel comfortable expressing themselves in a work environment, without fear of embarrassment or criticism from others. Psychological safety in healthcare is associated with improved patient safety outcomes, enhanced physician engagement and fostering a creative learning environment. Therefore, it is important to establish the key levers which can act as facilitators or barriers to establishing psychological safety. Existing literature on psychological safety in healthcare teams has focused on secondary care, primarily from an individual profession perspective. In light of the increased focus on multidisciplinary work in primary care and the need for team-based studies, given that psychological safety is a team-based construct, this study sought to investigate the facilitators and barriers to psychological safety in primary care multidisciplinary teams. Methods A mono-method qualitative research design was chosen for this study. Healthcare professionals from four primary care teams (n = 20) were recruited using snowball sampling. Data collection was through semi-structured interviews. Thematic analysis was used to generate findings. Results Three meta themes surfaced: shared beliefs, facilitators and barriers to psychological safety. The shared beliefs offered insights into the teams’ background functioning, providing important context to the facilitators and barriers of psychological safety specific to each team. Four barriers to psychological safety were identified: hierarchy, perceived lack of knowledge, personality and authoritarian leadership. Eight facilitators surfaced: leader and leader inclusiveness, open culture, vocal personality, support in silos, boundary spanner, chairing meetings, strong interpersonal relationships and small groups. Conclusion This study emphasises that factors influencing psychological safety can be individualistic, team-based or organisational. Although previous literature has largely focused on the role of leaders in promoting psychological safety, safe environments can be created by all team members. Members can facilitate psychological safety in instances where positive leadership behaviours are lacking - for example, strengthening interpersonal relationships, finding support in silos or rotating the chairperson in team meetings. It is anticipated that these findings will encourage practices to reflect on their team dynamics and adopt strategies to ensure every member’s voice is heard

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Gorlin syndrome associated with small bowel carcinoma and mesenchymal proliferation of the gastrointestinal tract: case report and review of literature

<p>Abstract</p> <p>Background and Case Presentation</p> <p>A patient with nevoid basal cell carcinoma syndrome (Gorlin syndrome) presented with two unusual clinical features, i.e. adenocarcinoma of the small bowel and extensive mesenchymal proliferation of the lower gastrointestinal tract.</p> <p>Conclusions</p> <p>We discuss the possibility that these two features are pathogenetically linked to the formerly undescribed patient's <it>PTCH </it>germ line mutation.</p

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

K70Q Adds High-Level Tenofovir Resistance to “Q151M Complex” HIV Reverse Transcriptase through the Enhanced Discrimination Mechanism

HIV-1 carrying the “Q151M complex” reverse transcriptase (RT) mutations (A62V/V75I/F77L/F116Y/Q151M, or Q151Mc) is resistant to many FDA-approved nucleoside RT inhibitors (NRTIs), but has been considered susceptible to tenofovir disoproxil fumarate (TFV-DF or TDF). We have isolated from a TFV-DF-treated HIV patient a Q151Mc-containing clinical isolate with high phenotypic resistance to TFV-DF. Analysis of the genotypic and phenotypic testing over the course of this patient's therapy lead us to hypothesize that TFV-DF resistance emerged upon appearance of the previously unreported K70Q mutation in the Q151Mc background. Virological analysis showed that HIV with only K70Q was not significantly resistant to TFV-DF. However, addition of K70Q to the Q151Mc background significantly enhanced resistance to several approved NRTIs, and also resulted in high-level (10-fold) resistance to TFV-DF. Biochemical experiments established that the increased resistance to tenofovir is not the result of enhanced excision, as K70Q/Q151Mc RT exhibited diminished, rather than enhanced ATP-based primer unblocking activity. Pre-steady state kinetic analysis of the recombinant enzymes demonstrated that addition of the K70Q mutation selectively decreases the binding of tenofovir-diphosphate (TFV-DP), resulting in reduced incorporation of TFV into the nascent DNA chain. Molecular dynamics simulations suggest that changes in the hydrogen bonding pattern in the polymerase active site of K70Q/Q151Mc RT may contribute to the observed changes in binding and incorporation of TFV-DP. The novel pattern of TFV-resistance may help adjust therapeutic strategies for NRTI-experienced patients with multi-drug resistant (MDR) mutations