A comparison of sequential total and activated white cell count in patients undergoing coronary artery bypass grafting, using cardiopulmonary bypass, with and without a white cell filter

Introduction Cardiopulmonary bypass (CPB) has been shown to induce a systemic inflammatory response similar to the local reaction seen after tissue damage [1]. This leads to the release of toxic substances, such as elastase, which cause endothelial damage and may adversely affect outcome [2]. Use of a leucocyte depleting arterial line filter is one of many anti-inflammatory strategies that are undergoing evaluation. Leucocyte depleting filters may be capable of selectively removing activated white cells [3], but this has not been proved in vivo. The aim of the present study was to compare sequential total and activated white cells during CPB, using either a leucocyte depleting or standard arterial line filter. Materials and methods After local ethical committee approval, 20 patients undergoing coronary artery bypass grafting using CPB were prospectively randomly allocated to have either a Leukogard LG–6 (Pall Biomedical, Portsmouth, UK) or a nonleucocyte depleting filter inserted into the arterial line of the CPB circuit. Arterial limb blood samples were taken immediately after institution of CPB (0min) and at 10–min intervals throughout the bypass period. Activated white cells were identified using nitroblue tetrazolium, then both total and activated white cell numbers counted after staining with Leucoplate.Results Table 1 shows the number of white cells counted/1.25 ? l (volume of a single channel of Nageotte counting chamber) using light microscopy (× 25).Conclusion The LG6 leucocyte filter reduces the total white cell count and is capable of selectively removing activated white cells during CPB. The exact relationship between leucocyte depletion and improved patient outcome still remains unclear

Structurally similar allosteric modulators of α7 nicotinic acetylcholine receptors exhibit five distinct pharmacological effects.

Activation of nicotinic acetylcholine receptors (nAChRs) is associated with the binding of agonists such as acetylcholine to an extracellular site that is located at the interface between two adjacent receptor subunits. More recently, there has been considerable interest in compounds, such as positive and negative allosteric modulators (PAMs and NAMs), that are able to modulate nAChR function by binding to distinct allosteric sites. Here we examined a series of compounds differing only in methyl substitution of a single aromatic ring. This series of compounds includes a previously described α7-selective allosteric agonist, cis-cis-4-p-tolyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4MP-TQS), together with all other possible combinations of methyl substitution at a phenyl ring (18 additional compounds). Studies conducted with this series of compounds have revealed five distinct pharmacological effects on α7 nAChRs. These five effects can be summarized as: 1) nondesensitizing activation (allosteric agonists), 2) potentiation associated with minimal effects on receptor desensitization (type I PAMs), 3) potentiation associated with reduced desensitization (type II PAMs), 4) noncompetitive antagonism (NAMs), and 5) compounds that have no effect on orthosteric agonist responses but block allosteric modulation (silent allosteric modulators (SAMs)). Several lines of experimental evidence are consistent with all of these compounds acting at a common, transmembrane allosteric site. Notably, all of these chemically similar compounds that have been classified as nondesensitizing allosteric agonists or as nondesensitizing (type II) PAMs are cis-cis-diastereoisomers, whereas all of the NAMs, SAMs, and type I PAMs are cis-trans-diastereoisomers. Our data illustrate the remarkable pharmacological diversity of allosteric modulators acting on nAChRs

An Artificial Light Source Influences Mating and Oviposition of Black Soldier Flies, Hermetia illucens

Current methods for mass-rearing black soldier flies, Hermetia illucens (L.) (Diptera: Stratiomyidae), in the laboratory are dependent on sunlight. Quartz-iodine lamps and rare earth lamps were examined as artificial light sources for stimulating H. illucens to mate and lay eggs. Sunlight was used as the control. Adults in the quartz-iodine lamp treatment had a mating rate of 61% of those in the sunlight control. No mating occurred when the rare earth lamp was used as a substitute. Egg hatch for the quartz-iodine lamp and sunlight treatments occurred in approximately 4 days, and the hatch rate was similar between these two treatments. Larval and pupal development under these treatments required approximately 18 and 15 days at 28°° C, respectively. Development of methods for mass rearing of H. illucens using artificial light will enable production of this fly throughout the year without investing in greenhouse space or requiring sunlight

The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.

Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9' position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22' position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties

Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Using sequence data to identify alternative routes and risk of infection: a case-study of campylobacter in Scotland

<b>Background:</b> Genetic typing data are a potentially powerful resource for determining how infection is acquired. In this paper MLST typing was used to distinguish the routes and risks of infection of humans with Campylobacter jejuni from poultry and ruminant sources.<p></p> <b>Methods:</b> C. jejuni samples from animal and environmental sources and from reported human cases confirmed between June 2005 and September 2006 were typed using MLST. The STRUCTURE software was used to assign the specific sequence types of the sporadic human cases to a particular source. We then used mixed case-case logistic regression analysis to compare the risk factors for being infected with C. jejuni from different sources.<p></p> <b>Results:</b> A total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a source that could be assigned with a probability of greater than 0.95. Compared to ruminant sources, cases attributed to poultry sources were typically among adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852), not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population density of greater than 500 people/km(2) (OR = 1.213, 95% CIs = 1.030, 1.431), reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned strains had a similar epidemiology to the unassigned strains, with the exception of a significantly higher likelihood of reporting overseas travel in unassigned strains.<p></p> <b>Conclusions:</b> Rather than estimate relative risks for acquiring infection, our analyses show that individuals acquire C. jejuni infection from different sources have different associated risk factors. By enhancing our ability to identify at-risk groups and the times at which these groups are likely to be at risk, this work allows public health messages to be targeted more effectively. The rapidly increasing capacity to conduct genetic typing of pathogens makes such traced epidemiological analysis more accessible and has the potential to substantially enhance epidemiological risk factor studies

Natural enemies from South Africa for biological control of Lagarosiphon major (Ridl.) Moss ex Wager (Hydrocharitaceae) in Europe

The non-native invasive plant, Lagarosiphon major (Hydrocharitaceae) is a submersed aquatic macrophyte that poses a significant threat to water bodies in Europe. Dense infestations prove difficult to manage using traditional methods. In order to initiate a biocontrol programme, a survey for natural enemies of Lagarosiphon was conducted in South Africa. Several phytophagous species were recorded for the first time, with at least three showing notable promise as candidate agents. Amongst these, a leaf-mining fly, Hydrellia sp. (Ephydridae) that occurred over a wide distribution causes significant leaf damage despite high levels of parasitism by braconid wasps. Another yet unidentified fly was recorded mining the stem of L. major. Two leaf-feeding and shoot boring weevils, cf. Bagous sp. (Curculionidae) were recorded damaging the shoot tips and stunting the growth of the stem. Several leaf-feeding lepidopteran species (Nymphulinae) were frequently recorded, but are expected to feed on a wide range of plant species and are not considered for importation before other candidates are assessed. The discovery of several natural enemies in the country of origin improves the biological control prospects of L. major in Europe

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Why Do Situational Interviews Predict Performance? Is it Saying How You Would Behave or Knowing How You Should Behave?

Purpose: The present study examined two theoretical explanations for why situational interviews predict work-related performance, namely (a) that they are measures of interviewees’ behavioral intentions or (b) that they are measures of interviewees’ ability to correctly decipher situational demands. Design/Methodology/Approach: We tested these explanations with 101 students, who participated in a 2-day selection simulation. Findings: In line with the first explanation, there was considerable similarity between what participants said they would do and their actual behavior in corresponding work-related situations. However, the underlying postulated mechanism was not supported by the data. In line with the second explanation, participants’ ability to correctly decipher situational demands was related to performance in both the interview and work-related situations. Furthermore, the relationship between the interview and performance in the work-related situations was partially explained by this ability to decipher situational demands. Implications: Assessing interviewees’ ability to identify criteria might be of additional value for making selection decisions, particularly for jobs where it is essential to assess situational demands. Originality/Value: The present study made an effort to open the ‘black box’ of situational interview validity by examining two explanations for their validity. The results provided only moderate support for the first explanation. However, the second explanation was fully supported by these results