Functionalisation of terpenoids at C-4 via organopalladium dimers: cyclopropane formation during oxidation of homoallylic sigma-organopalladium intermediates with lead tetraacetate

The synthesis of new potential adjuvant saponin aglycons was investigated by selective palladium mediated C-H functionalisation of appropriately functionalised derivatives of lanosterol, cholesterol, and friedelin. The desired equatorial aldehyde functionality was successfully introduced into the lanosterol skeleton as expected. Cyclopalladation of a cholesterol derivative proceeded as expected, but during oxidation of the organopalladium intermediate, participation of the adjacent alkene functionality led to stereoselective formation of a cyclopropane and introduction of an acetate group into the steroid backbone at C-6. Further investigation of this unusual cyclopropane formation on a model decalin system confirmed the result, but C-H activation on a related open chain system was prevented by complexation of the alkene functionality to the palladium. (c) 2007 Elsevier Ltd. All rights reserved

Genome Sequence of Corynebacterium pseudotuberculosis MB20 bv. equi Isolated from a Pectoral Abscess of an Oldenburg Horse in California.

The genome of Corynebacterium pseudotuberculosis MB20 bv. equi was sequenced using the Ion Personal Genome Machine (PGM) platform, and showed a size of 2,363,089 bp, with 2,365 coding sequences and a GC content of 52.1%. These results will serve as a basis for further studies on the pathogenicity of C. pseudotuberculosis bv. equi

Selection Bias in a Study of Implantable Defibrillator Patients: The Role of Type D Personality

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Selection bias constitutes a major issue in research using volunteers as study participants. Purpose We examined whether research in partners may affect participation rates of implantable cardioverterdefibrillator (ICD) patients with a Type D personality (joint presence of negative affectivity and social inhibition). Method Patients who underwent ICD implantation between May 2003 and November 2007, and who had a partner, were included (n=440). In September 2005, a substudy on partners of ICD patients was added (n=276 patients). Results The proportion Type D patients after the start of the partner substudy was significantly lower as compared to the proportion before this substudy (17.5 % versus 28.8%; p= 0.006). Patients who participated following the start of the partner substudy were less likely to have a Type D personality (OR=0.44; p=0.002), adjusting for possible confounders. In the partner substudy, nonparticipation was more prevalent among partners of Type D patients as compared to partners of non-Type D patients (20.4 % versus 10.1%; p=0.044). Partner nonparticipation was marginally significantly associated with Type D personality of the patient (OR=2.13; p=0.083), adjusting for confounders. Conclusions The addition of a partner substudy may be related to a decreased proportion of participants with a Type D personality. Nonparticipation was more prevalent among partners of Type D patients. These observations may influence results of studies, as Type Ds tend to be less healthy

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome

Chiral dynamics in systems with strangeness

In this talk a brief review of several problems involving systems with strangeness is made. In the first place one shows how the Λ(1405), Λ(1670) and Σ(1620) states, for S=−1, and the Ξ(1620) for S=−2 are generated dynamically in the context of unitarized chiral perturbation theory. The results for the K¯N interaction are then used to evaluate the K−d scattering length. Results obtained for the kaon selfenergy in a nuclear medium within this approach, with application to K− atoms, are also mentioned. Finally a few words are said about recent developments in the weak decay of Λ hypernuclei and the puzzle of the Γn/Γp ratio

Nuclear matter to strange matter transition in holographic QCD

We construct a simple holographic QCD model to study nuclear matter to strange matter transition. The interaction of dense medium and hadrons is taken care of by imposing the force balancing condition for stable D4/D6/D6 configuration. By considering the intermediate and light flavor branes interacting with baryon vertex homogeneously distributed along R^3 space and requesting the energy minimization, we find that there is a well defined transition density as a function of current quark mass. We also find that as density goes up very high, intermediate (or heavy) and light quarks populate equally as expected from the Pauli principle. In this sense, the effect of the Pauli principle is realized as dynamics of D-branes.Comment: 13 pages, 14 figure

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating

A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

<p>Abstract</p> <p>Background</p> <p>Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk.</p> <p>Methods</p> <p>We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System.</p> <p>Results</p> <p>Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; <it>P </it>= .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; <it>P </it>= .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy.</p> <p>Conclusions</p> <p>Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.</p