Essence of the vacuum quark condensate

We show that the chiral-limit vacuum quark condensate is qualitatively equivalent to the pseudoscalar meson leptonic decay constant in the sense that they are both obtained as the chiral-limit value of well-defined gauge-invariant hadron-to-vacuum transition amplitudes that possess a spectral representation in terms of the current-quark mass. Thus, whereas it might sometimes be convenient to imagine otherwise, neither is essentially a constant mass-scale that fills all spacetime. This means, in particular, that the quark condensate can be understood as a property of hadrons themselves, which is expressed, for example, in their Bethe-Salpeter or light-front wavefunctions.Comment: 5 pages, 1 figur

Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease

The relationship between the halosperm assay and semen analysis performed according to the 4th and 5th Editions of the World Health Organization guidelines

Background: As a standard reference to evaluate male factor infertility, the majority of fertility laboratories use the 4th or 5th Editions of the World Health Organization’s semen analysis guidelines. Following the release of the 5th Edition, debate over its legitimacy has resulted in some laboratories using the 4th and others the 5th Edition. DNA integrity tests have been shown to be a valuable adjunct to semen analysis and have subsequently been adopted by many fertility laboratories. This study explored the prevalence of samples with high DNA fragmentation levels according to semen analysis categories using both the 4th and the 5th Edition reference ranges. Materials and Methods: The study included 905 consecutive semen samples from 863 infertile couples attending a fertility clinic. A semen analysis was conducted according to both the 4th and 5th Edition guidelines published by the World Health Organization. DNA damage was assessed using the Halosperm G2 test kit and expressed as a percentage DNA fragmentation level. Results: Alongside both the World Health Organization 4th and 5th Edition semen analysis criteria abnormal DNA fragmentation levels were more common in abnormal semen samples however elevated DNA fragmentation levels were also found in normal semen samples using the same criteria. Of the samples that were graded as normozoospermic according to the 5th Edition guidelines 16% were deemed to have elevated DNA fragmentation levels compared to 11.7% graded by the 4th Edition guidelines. The number of normozoospermic samples, graded according to the 5th Edition guidelines was significantly higher (n=697) than when the same samples were graded according to 4th Edition guidelines (n=385) (p=0.001). A significant proportion of samples with an abnormal DNA fragmentation level corresponding to the World Health Organisation 4th and 5th Edition criteria were evident in normozoospermic (

The preparation and culture of washed human sperm: a comparison of a suite of protein-free media with media containing human serum albumin

Objective To compare two suites of culture media (one with HSA and one protein-free (PF) supplemented with methylcellulose) for washing human sperm in IVF. Methods Semen samples (n = 41) underwent parallel density gradient preparation using PF or HSA-supplemented culture medium and subsequent yield, survival, morphology and motility were compared. Results The PF medium resulted in a significantly higher sperm yield (P \u3c 0.0001), but similar sperm morphology (P = 0.822) and 24-h survival (P = 0.11). There was, however, a lower percentage of progressively motile sperm (P \u3c 0.0001) and a higher proportion of sperm demonstrating non-progressive motility (P \u3c 0.0001) in the PF medium when observed on a Makler Chamber, apparently an artefact as a similar sperm motility index was measured using a Sperm Quality Analyser (P = 0.83). Attachment of sperm in PF medium to the glass chamber reduced with time and any differences had disappeared after 6 min on the counting chamber. Conclusion These results support the use of PF media supplemented with methylcellulose as an alternative to HSA, although a modification to the manufacturer\u27s protocol of 6-min pre-incubation before assessing sperm motility must be used. Further studies should investigate the function of such sperm prepared in PF medium

Association of maternal tocolysis or antenatal corticosteroids with cerebral palsy: a study protocol

Cerebral palsy (CP) is the most common developmental disorder associated with lifelong motor impairment and disability. Although severe intrapartum hypoxia/ischaemia during birth may be instrumental in the causal pathway leading to cerebral palsy this accounts for only 10% of cases. Antenatal exposures that lead to cerebral palsy are, therefore, important to understand, particularly those that are modifiable. This application seeks to determine whether antenatal exposure to medications to prevent uterine contractions (tocolysis) and assist lung maturation (corticosteroids) have any association with cerebral palsy, particularly in pregnancies presenting moderately preterm. We plan to perform a secondary analysis on two large existing datasets (the ORACLE trials) of pregnancies presenting before term. If an association is found the results could have significant implications for clinical management and the direction of future research.The Research Foundation, Cerebral Palsy Allianc

Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

Background: Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam

Serum concentrations of the biomarkers CA125, CA15-3, CA72-4, tPSA and PAPP-A in natural and stimulated ovarian cycles

Objective: Biomarkers associated with cancer screening (CA125, CA15-3, CA72-4, total prostate specific antigen [tPSA]) and the monitoring of pregnancy (pregnancy associated plasma protein-A [PAPP-A]) were measured during natural and stimulated ovarian cycles in disease-free non-pregnant women to determine if they could reflect normal events relating to ovulation and/or endometrial changes. Methods: A total of 73 blood samples (10 women) collected throughout the natural menstrual cycle, and 64 blood samples (11 women) taken during stimulated ovarian cycles, were analysed on the Roche Cobas e411 automated analyser. Results: Detectable levels of tPSA were measured in at least one point in the cycle in 6/10 of women in the natural cycle and 10/11 of women in stimulated cycles, and CA72-4 was detected in only 12/21 women tested. Concentrations of CA125, tPSA, CA15-3 and CA72-4 showed no significant difference between the natural and stimulated ovarian cycle groups. On average the mean PAPP-A of the natural group was (2.41±0.58) mIU/L higher than the stimulated group (t=4.10, P\u3c 0.001). CA125 and CA15-3 results were both significantly influenced by the stage of the cycle (P\u3c0.0001), whereas tPSA and PAPP-A concentrations revealed no significant changes (P≥0.65). CA72-4 was not affected by the stage of the cycle nor ovarian stimulation. Conclusion: Ovarian stimulation reduced serum PAPP-A levels, CA125 and CA15-3 levels were generally unaffected by ovarian stimulation but displayed cyclical changes throughout both natural and stimulated cycles, whilst tPSA and CA72-4 were not affected by the stage of the cycle or ovarian stimulation

Redox-Linked Domain Movements in the Catalytic Cycle of Cytochrome P450 Reductase

SummaryNADPH-cytochrome P450 reductase is a key component of the P450 mono-oxygenase drug-metabolizing system. There is evidence for a conformational equilibrium involving large-scale domain motions in this enzyme. We now show, using small-angle X-ray scattering (SAXS) and small-angle neutron scattering, that delivery of two electrons to cytochrome P450 reductase leads to a shift in this equilibrium from a compact form, similar to the crystal structure, toward an extended form, while coenzyme binding favors the compact form. We present a model for the extended form of the enzyme based on nuclear magnetic resonance and SAXS data. Using the effects of changes in solution conditions and of site-directed mutagenesis, we demonstrate that the conversion to the extended form leads to an enhanced ability to transfer electrons to cytochrome c. This structural evidence shows that domain motion is linked closely to the individual steps of the catalytic cycle of cytochrome P450 reductase, and we propose a mechanism for this

Verifying the Kugo-Ojima Confinement Criterion in Landau Gauge Yang-Mills Theory

Expanding the Landau gauge gluon and ghost two-point functions in a power series we investigate their infrared behavior. The corresponding powers are constrained through the ghost Dyson-Schwinger equation by exploiting multiplicative renormalizability. Without recourse to any specific truncation we demonstrate that the infrared powers of the gluon and ghost propagators are uniquely related to each other. Constraints for these powers are derived, and the resulting infrared enhancement of the ghost propagator signals that the Kugo-Ojima confinement criterion is fulfilled in Landau gauge Yang-Mills theory.Comment: 4 pages, no figures; version to be published in Physical Review Letter

In vitro evaluation of the interaction of dextrin-colistin conjugates with bacterial lipopolysaccharide.

Dextrin-colistin conjugates have been developed with the aim of reducing clinical toxicity associated with colistin and improving targeting to sites of bacterial infection. This study investigated the in vitro ability of these dextrin-colistin conjugates to bind and modulate bacterial lipopolysaccharide (LPS), and how this binding affects its biological activity. These results showed that colistin, and ‘amylase-activated’ dextrin-colistin conjugate to a lesser extent, bound to LPS and induced significant conformational changes to its structure. In biological studies, both colistin and dextrin-colistin conjugate effectively inhibited LPS-induced hemolysis and TNFα secretion in a concentration-dependent manner, but only dextrin-colistin conjugate did not cause additive toxicity at higher concentrations. This study provides the first direct structural experimental evidence for the binding of dextrin-colistin conjugates and LPS, providing insight into the mode of action of dextrin-colistin conjugates