Down-regulation of the two-component system and cell-wall biosynthesis-related genes was associated with the reversion to daptomycin susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus.

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

[Obstetrical complications of genital mutilation in Malian rural environment]. / Complications obstétricales des mutilations génitales en milieu rural malien.

OBJECTIVE: To describe maternal and fetal complications during delivery of mutilated women. MATERIALS AND METHODS: It was a case study, witnesses with matching going from February 1st, 2008 till January 31st, 2009 which took place in Mopti's region. We compared maternal and fetal complications of mutilated and non-mutilated women. Using statistical tests were Chi(2) (P<0.05), Odd-Ratio (OR) and its 95% confident interval (CI95%). RESULTS: We recorded 410 deliveries among which 280 mutilated women (68%). One hundred and forty excised women were included. There is a significant difference between duration of eviction>30 mm (RC=8.27 [4.66-14.76], P<0.001); simple perennials lacerations (RC=14.54 [4.79-49.56], P<0.001) and full perennials lacerations (RC=8.90 [1.91-57.23], P<0.001) in the two groups. The scores of morbid Apgar (RC=9.70 [4.35-22,29], P<0.001) were more important in groups of cases. Moreover, we recorded 3 neonatal deaths and 4 complicated perennials lacerations in the group of cases only. CONCLUSION: Maternal and fetal complications are significantly more important for the excised woman's than for the not excised women.

[Reasons for hospitalisation of hiv-infected children in pediatric service of the Gabriel Toure teaching hospital, Bamako]. / Causes d'hospitalisation des enfants infectes par le vih dans le service de pediatrie du CHU Gabriel Toure de Bamako.

PURPOSE: The aim of our study was to determine the reasons of hospitalization of HIV-infected children in our context and to identify factors associated with mortality in the course of hospitalization. PATIENTS AND METHOD: Our study took place in the department of pediatrics of the Gabriel Touré Teaching Hospital. It involved all the children hospitalized between March 1st and August 31st, 2010 to whom an infection with HIV was diagnosed before or during the hospitalization. RESULTS: Thirty seven HIV-infected children were hospitalized. The average age at admission was 46,9 months and the sex ratio was 0,76. HIV infection was discovered during the hospitalization for 29 children (78,4%). Fifteen children were orphan of at least a parent. The medical pathological history include sickle cell disease (2 cases) and tuberculosis (1 case). The great majority (91,9%) were at WHO stage 3 or 4. The main AIDS-defining events were severe malnutrition (73%) and pneumonia (45,9%). They were followed by bacterial infections (21,6%) and malaria (13,5%). An anemia was found at 85,7 % of the children. CONCLUSION: Efforts must be made for early diagnosis and management of pediatric's HIV infection.

BUT: L'objectif de notre étude était de déterminer les raisons d'hospitalisation des enfants infectés par le VIH dans notre contexte et d'identifier les facteurs associés à la mortalité en cours d'hospitalisation. MATÉRIELS ET MÉTHODE: Elle s'est déroulée dans le service de pédiatrie du CHU Gabriel Touré. Elle a concerné tous les enfants hospitalisés entre le 1er mars et le 31 août 2010 chez lesquels une infection à VIH a été diagnostiquée avant ou pendant l'hospitalisation. RÉSULTATS: Trente sept enfants infectés par le VIH ont été hospitalisés. L'âge moyen à l'admission était de 46,9 mois avec un sexe ratio de 0,76. L'infection au VIH a été découverte pendant l'hospitalisation pour 29 enfants (78,4%). Quinze enfants étaient orphelins d'au moins un parent. Les antécédents pathologiques médicaux retrouvés étaient la drépanocytose (2 cas) et la tuberculose (1 cas). La grande majorité (91,9%) était à un stade 3 ou 4 de l'OMS. Les principales affections classant SIDA retrouvées ont été la dénutrition (73%) et la pneumonie (45,9%) sévères. Elles ont été suivies des infections bactériennes (21,6%) et du paludisme (13,5%). Une anémie a été retrouvée chez 85,7% des enfants. CONCLUSION: Des efforts doivent être fournis pour le diagnostic et la prise en charge précoces de l'infection à VIH pédiatrique.

Development of a non-radioactive, 384-well format assay to detect inhibitors of the mitogen-activated protein kinase kinase 4.

Mitogen-activated protein kinase (MAPK) kinases (MKKs, also called MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK]) are constituents of numerous signal transduction pathways involved in growth, differentiation, and stress response. One of its members, MKK4, directly phosphorylates and activates the c-Jun terminal kinases (also called stress-activated protein kinase [SAPK]) in response to stress and pro-inflammatory cytokines. Recent evidence suggest that control of MKK4 activity may provide a novel approach for the treatment of cancer or as anti-inflammatory therapy. To screen for novel low-molecular-weight inhibitors of MKK4, we established a quantitative, non-radioactive in vitro kinase assay. Human MKK4 was expressed as fusion protein with glutathione S-transferase (GST) in Escherichia coli. Co-expression of a constitutive active fragment of the MAPK/ERK kinase kinase-1 yielded active GST-MKK4 using GST-SAPK alpha-kinase-negative (KN) mutant as substrate. We determined the kinetic constants for ATP and GST-SAPK alpha-KN. The apparent Km value for GST-SAPKalpha-KN was 3.7 microM, while the apparent Km value for ATP was 0.17 microM. Staurosporine inhibited GST-MKK4 with an IC50 of 70 nM. The kinase assay was adapted to a 384-well non-radioactive format. After the kinase reaction the phosphorylated product was captured onto a streptavidin-coated microtiter plate, and phosphorylation was detected with a europium-labeled anti-phosphotyrosine antibody, which allowed time-resolved fluorescence measurement.

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.