Contribution a l'etude des especes africaines du genre Acioa Aubl.

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Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Approximation algorithms and hardness results for the joint replenishment Problepm with constant demands

19th Annual European Symposium, Saarbrücken, Germany, September 5-9, 2011. ProceedingsIn the Joint Replenishment Problem (JRP), the goal is to coordinate the replenishments of a collection of goods over time so that continuous demands are satisfied with minimum overall ordering and holding costs. We consider the case when demand rates are constant. Our main contribution is the first hardness result for any variant of JRP with constant demands. When replenishments per commodity are required to be periodic and the time horizon is infinite (which corresponds to the so-called general integer model with correction factor), we show that finding an optimal replenishment policy is at least as hard as integer factorization. This result provides the first theoretical evidence that the JRP with constant demands may have no polynomial-time algorithm and that relaxations and heuristics are called for. We then show that a simple modification of an algorithm by Wildeman et al. (1997) for the JRP gives a fully polynomial-time approximation scheme for the general integer model (without correction factor). We also extend their algorithm to the finite horizon case, achieving an approximation guarantee asymptotically equal to √9/8

Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes

View full abstracthttps://openworks.mdanderson.org/leading-edge/1002/thumbnail.jp

Can an online clinical data management service help in improving data collection and data quality in a developing country setting?

Background: Data collection by Electronic Medical Record (EMR) systems have been proven to be helpful in data collection for scientific research and in improving healthcare. For a multi-centre trial in Indonesia and the Netherlands a web based system was selected to enable all participating centres to easily access data. This study assesses whether the introduction of a Clinical Trial Data Management service (CTDMS) composed of electronic Case Report Forms (eCRF) can result in effective data collection and treatment monitoring. Methods: Data items entered were checked for inconsistencies automatically when submitted online. The data were divided into primary and secondary data items. We analysed both the total number of errors and the change in error rate, for both Primary and Secondary items, over the first five month of the trial. Results: In the first five months 51 patients were entered. The Primary data error rate was 1.6%, whilst that for Secondary data was 2.7% against acceptable error rates for analysis of 1% and 2.5% respectively. Conclusion: The presented analysis shows that after five months since the introduction of the CTDMS the Primary and Secondary data error rates reflect acceptable levels of data quality. Furthermore, these error rates were decreasing over time. The digital nature of the CTDMS, as well as the online availability of that data, gives fast and easy insight in adherence to treatment protocols. As such, the CTDMS can serve as a tool to train and educate medical doctors and can improve treatment protocols.Maarten A Wildeman, Jeroen Zandbergen, Andrew Vincent, Camelia Herdini, Jaap M Middeldorp, Renske Fles, Otilia Dalesio, Emile van der Donk, I Bing Ta

Short-Term Effect of Different Teaching Methods on Nasopharyngeal Carcinoma for General Practitioners in Jakarta, Indonesia

In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period

Children of Prisoners: Their Situation and Role in Long-Term Crime Prevention

Studies suggest that maintaining family ties can help reduce the likelihood of reoffending, and that while parental imprisonment can increase a child’s likelihood to offend, positive responses to the situation can aid the children’s well-being, attitude and attainment. Drawing on findings from the recently completed EU-funded COPING Project on the mental health of children of prisoners, this chapter explores the factors that aid a child’s ability to cope with parental imprisonment and the actions that different stakeholders can take to support them. It identifies some of the mental health impacts at different stages of parental imprisonment, the roles played by non-imprisoned parents/carers and by schools, and suggests options for further clarifying the factors that help and hinder children of prisoners in the short and long term

The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

The original publication is available at http://www.jnrbm.com/content/10/1/12Includes bibliographyAbstract Background The gene family KCNE1-5, which encode modulating β-subunits of several repolarising K+-ion channels, has been associated with genetic cardiac diseases such as long QT syndrome, atrial fibrillation and Brugada syndrome. The minK peptide, encoded by KCNE1, is attached to the Z-disc of the sarcomere as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic disease associated with an improper hypertrophic response. Results The coding regions of KCNE1, KCNE2, KCNE3, KCNE4, and KCNE5 were examined, by direct DNA sequencing, in a cohort of 93 unrelated HCM probands and 188 blood donor controls. Fifteen genetic variants, four previously unknown, were identified in the HCM probands. Eight variants were non-synonymous and one was located in the 3'UTR-region of KCNE4. No disease-causing mutations were found and no significant difference in the frequency of genetic variants was found between HCM probands and controls. Two variants of likely functional significance were found in controls only. Conclusions Mutations in KCNE genes are not a common cause of HCM and polymorphisms in these genes do not seem to be associated with a propensity to develop arrhythmiaPeer Reviewe