Probing the role of point mutations in the cyp51A gene from Aspergillus fumigatus in the model yeast Saccharomyces cerevisiae.

Azole-resistant strains of Aspergillus fumigatus have been detected and the underlying molecular mechanisms of resistance characterized. Point mutations in the cyp51A gene have been proved to be related to azole resistance in A. fumigatus clinical strains and with different resistance profiles depending on the amino acid change (G54E, G54V, G54R, G54W, M220V, M220K, M220T, M220I). The aim of this work was to express A. fumigatus cyp51A genes in the yeast Saccharomyces cerevisiae in order to better assess the contribution of each independent amino acid substitution to resistance. A tetracycline regulatable system allowing repression of the endogenous essential ERG11 gene was used. The expression of Aspergillus cyp51A alleles could efficiently restore the absence of ERG11 in S. cerevisiae. In general, S. cerevisiae clones expressing. A. fumigatus cyp51A alleles from azole-resistant isolates showed higher MICs to all azoles tested than those expressing alleles from susceptible isolates. The azole susceptibility profiles obtained in S. cerevisiae upon expression of specific cyp51A alleles recapitulated susceptibility profiles observed from their A. fumigatus origins. In conclusion this work supports the concept that characteristics of specific A. fumigatus cyp51A alleles could be investigated in the heterologous host S. cerevisiae.

Médecine interne: le point de vue du chef de clinique [Internal medicine: the point of view of the chief resident].

Clinical practice in internal medicine has fundamentely changed over the last decade. Our knowledge has dramatically improved and we are facing new types of patients. Their number is increasing, they are older and suffer from increasingly complex medical conditions. The society has evolved as well therefore transforming our daily practice. This implies important modifications of our role and new challenges. We must also develop new aspects of our practice such as recognizing our errors, quality of care, quality of education, ethics, new strategies for taking care of the patient all this in parallel with continuous education. Our role as (general practitioner) is of utmost importance since it enables us to keep the "big pictures" in a more and more specialized environment.

Increased tender point counts before and after total hip arthroplasty are associated with poorer outcomes but are not individually predictive.

In a prospective study, total hip arthroplasty (THA) patients were assessed preoperatively and postoperatively (n = 95) to determine if tender points (TPs) are associated with poor THA outcomes. Patients with high follow-up TP counts had higher visual analog scale (VAS) for pain and sleep, higher follow-up Western Ontario and McMaster Universities Arthritis Index (pain, stiffness, function), lower Health Assessment Questionnaire, Harris Hip, and Short Form 36 (physical functioning, bodily pain, physical component summary) scores. High follow-up TP were associated with increased pain, pain not relieved by surgery, poor function, and poor sleep. Visual analog scale pain and sleep, Short Form 36 (physical functioning, bodily pain), Western Ontario and McMaster Universities Arthritis Index, Health Assessment Questionnaire, and Harris hip scores improved significantly after THA; TP scores did not. Higher preoperative TP were predictive of higher follow-up TP but were poorly predictive of poor outcome measures after surgery in individual patients, suggesting that preoperative TPs are contraindicative for THA.

Dépistage de l'athérosclérose: point de la situation en 2006. [Screening for atherosclerosis: 2006 update].

In recent years, several screening tests for subclinical atherosclerosis have been developed. The aim of these tests is to be able to better target preventive therapies to patients at high cardiovascular risk. However, the validity of these screening tests has not been well established for wide use in clinical practice. Being aware of these tests results might also enhance patient motivation to change unhealthy behaviors, such as smoking. However, the effectiveness of such strategy has been poorly studied. Early therapy of atherosclerosis has not been shown to improve clinical outcomes yet. Moreover, potential harms of such screening, such as induced anxiety, have been poorly studied. Although promising, such screening should be validated by clinical trials before routine use in clinical practice.

Le projet "SYNAPSY": un point de rencontre entre clinique et neurosciences [The "SYNAPSY" project: where psychiatrists and neuroscientists meet].

The National Center of Competence in Research project "SYNAPSY" aims at identifying certain mechanisms of psychiatric and cognitive disorders, in order to improve the understanding and the genesis of such pathologies, and to promote the development of better diagnostic tools and of new therapeutic approaches. It provides an excellent opportunity for clinical psychiatrists and neuroscientists to develop a synergic mode of collaboration. On the basis of questions stemming from clinical practice and in the frame of patients cohorts, various research projects in neuroscience should lead to progresses that may have a considerable impact on clinical practice.

Evaluation de deux structures à bas seuil de la ville de Lausanne : Le Passage et le Point d'eau

[Table des matières] 1. Méthodes d'évaluation. 2. Le Passage et le Point d'eau. 2.1. Historique et objectifs. 2.2. Etapes de la mise en route. 3.1. Professionnels salariés. 3.2. Bénévoles professionnels. 3.3. Bénévoles d'accueil. 4.1. Activités de la structure. 4.2. Accueil (animations, repas, collations). 4.3. L'offre socio-éducative. 4.4. L'offre sanitaire. 4.5. La distribution du matériel stérile. 5.1. Prestations d'hygiène. 5.2. Soins somatiques. 5.3. Activité sportive. 6.1. Profil des usagers. 6.2. Indicateurs socio-démographiques et d'intégration sociale. 6.3. Etat de santé perçu. 6.4. Fréquentation du réseau (dispositif bas seuil et autre) et de Point d'eau. 7. Consommation de drogues illégales. 8. Fréquentation de la structure. 9.1. Méthodes d'évaluation utilisées. 9.2. Evaluation du Passage et du Point d'eau.

A multimodality vascular imaging phantom with fiducial markers visible in DSA, CTA, MRA, and ultrasound.

The objective was to design a vascular phantom compatible with digital subtraction angiography, computerized tomography angiography, ultrasound and magnetic resonance angiography (MRA). Fiducial markers were implanted at precise known locations in the phantom to facilitate identification and orientation of plane views from three-dimensional (3-D) reconstructed images. A vascular conduit connected to tubing at the extremities of the phantom ran through an agar-based gel filling it. A vessel wall in latex was included around the conduit to avoid diffusion of contrast agents. Using a lost-material casting technique based on a low melting point metal, geometries of pathological vessels were modeled. During the experimental testing, fiducial markers were detectable in all modalities without distortion. No leak of gadolinium through the vascular wall was observed on MRA after 5 hours. Moreover, no significant deformation of the vascular conduit was noted during the fabrication process (confirmed by microtome slicing along the vessel). The potential use of the phantom for calibration, rescaling, and fusion of 3-D images obtained from the different modalities as well as its use for the evaluation of intra- and inter-modality comparative studies of imaging systems are discussed. In conclusion, the vascular phantom can allow accurate calibration of radiological imaging devices based on x-ray, magnetic resonance and ultrasound and quantitative comparisons of the geometric accuracy of the vessel lumen obtained with each of these methods on a given well defined 3-D geometry.

Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood.

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.