[Suffering at work among medical students: qualitative study using semi-structured interviews]. / Souffrance au travail des étudiants en médecine : étude qualitative par entretiens semi-dirigés.

INTRODUCTION: Suffering at work among health professionals is a hot topic. Medical students, doctors of tomorrow, are far from being spared. Prevalence of anxiety and mood disorders range from 20.3 to 69 % for the former and from 12 to 30 % for the latter. The purpose of this article is to determine these factors by qualitative research, according to medical students' points of view. METHODS: It is a qualitative study using semistructured interviews. The analysis is done according to the Grounded Theory. RESULTS: 12 medical students are interviewed. They expressed difficulties at work and positive factors. Three major themes are identified in selective coding: occupational factors, " study " factors and individual factors. All themes are both a source of well-being and ill-being according to the situations specified in the results. CONCLUSION: Studying medicine includes positive and negative aspects. Abandonment issues, lack of recognition and insufficient coaching emerge from our study. Screening of suffering at work should be systematic for medical students.

INTRODUCTION: La souffrance au travail chez les professionnels de santé est un sujet d'actualité. Les étudiants en médecine, médecins de demain, sont loin d'être épargnés. Ils présentent notamment des troubles anxieux et de l'humeur dont les prévalences s'échelonnent de 20,3 à 69 % pour les premiers et de 12 à 30 % pour les seconds. Cette étude a pour objectif de déterminer ce qui est ressenti comme positif ou négatif au travail du point de vue des étudiants hospitaliers. Matériel et méthode : Il s'agit d'une étude qualitative par entretiens semi-dirigés. L'analyse se fait selon une thématisation progressive en suivant la Grounded Theory, ou théorisation ancrée, méthode issue des sciences sociales, visant à élaborer une théorie des représentations, non à partir d'hypothèses prédéterminées, mais à partir de données de terrain recueillies par entretiens. Résultats : La variation est maximale. La saturation des données a été atteinte avec 12 sujets. Ceux-ci ont exprimé des difficultés au travail mais aussi des facteurs de ressenti positif. Trois grands thèmes ont été définis en codage sélectif : les facteurs professionnels, les facteurs " étude " et les facteurs individuels. Quelle que soit la thématique abordée, les relations avec le ressenti du travail sont à la fois source d'épanouissement et de souffrance selon les situations précisées dans les résultats. CONCLUSION: Le vécu des études médicales comprend des aspects positifs et négatifs. Les problématiques de délaissement, de manque de reconnaissance ou encore d'accompagnement insuffisant ressortent de notre étude. Ceci ouvre des pistes de prévention. Le dépistage d'un malêtre au travail devrait être systématique chez ces étudiants.

Biased relevance filtering in the auditory system: A test of confidence-weighted first-impressions.

Although first-impressions are known to impact decision-making and to have prolonged effects on reasoning, it is less well known that the same type of rapidly formed assumptions can explain biases in automatic relevance filtering outside of deliberate behavior. This paper features two studies in which participants have been asked to ignore sequences of sound while focusing attention on a silent movie. The sequences consisted of blocks, each with a high-probability repetition interrupted by rare acoustic deviations (i.e., a sound of different pitch or duration). The probabilities of the two different sounds alternated across the concatenated blocks within the sequence (i.e., short-to-long and long-to-short). The sound probabilities are rapidly and automatically learned for each block and a perceptual inference is formed predicting the most likely characteristics of the upcoming sound. Deviations elicit a prediction-error signal known as mismatch negativity (MMN). Computational models of MMN generally assume that its elicitation is governed by transition statistics that define what sound attributes are most likely to follow the current sound. MMN amplitude reflects prediction confidence, which is derived from the stability of the current transition statistics. However, our prior research showed that MMN amplitude is modulated by a strong first-impression bias that outweighs transition statistics. Here we test the hypothesis that this bias can be attributed to assumptions about predictable vs. unpredictable nature of each tone within the first encountered context, which is weighted by the stability of that context. The results of Study 1 show that this bias is initially prevented if there is no 1:1 mapping between sound attributes and probability, but it returns once the auditory system determines which properties provide the highest predictive value. The results of Study 2 show that confidence in the first-impression bias drops if assumptions about the temporal stability of the transition-statistics are violated. Both studies provide compelling evidence that the auditory system extrapolates patterns on multiple timescales to adjust its response to prediction-errors, while profoundly distorting the effects of transition-statistics by the assumptions formed on the basis of first-impressions.

The retinal pigment epithelium undergoes massive apoptosis during early differentiation and pigmentation of the optic cup.

PURPOSE: The aim of our work was to study apoptosis during the development of the retinal pigment epithelium (RPE) in mice between embryonic day (E) 10.5 and E12.5 and to examine a possible link between apoptosis and pigmentation. METHODS: We collected mouse embryos at E10.5, E11.5, and E12.5 and labeled apoptotic cells in 5-µm paraffin sections, using the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. We counted the total number of cells and the number of apoptotic cells in the early developing RPE and calculated the percentage of apoptosis at each stage. RESULTS: In the C57BL/6J mouse, 17% of the RPE cells were apoptotic at E10.5 compared to 0.9% at E12.5. At E11.5, three-quarters of the RPE cells began to pigment, and apoptotic cells were located mostly in the nonpigmented part. In contrast, in the BALB/c mouse (tyrosinase-deficient) and pJ mouse (carrying mutations in the p gene) hypopigmented strains, the RPE contained significantly fewer apoptotic cells (7.5% and 10.1%, respectively) at E10.5 than controls. Subsequently at E11.5 and E12.5, the two hypopigmented strains displayed different apoptotic patterns; the BALB/c RPE had a similar percentage of apoptotic cells to controls (1.5% and 1.1%, respectively, for BALB/c versus 3.0% and 0.9%, respectively, for C57BL/6J), whereas the pJ RPE contained significantly more apoptosis (7.5% and 3.5%, respectively). Overall we observed differences in the evolution of the relative total number of RPE cells between the three strains. CONCLUSIONS: Apoptosis is a main event during the first stages of normal RPE development, indicating an essential role during RPE differentiation. Moreover, the early apoptotic pattern and possibly the whole early development of the RPE is different between hypopigmented and pigmented strains, as well as between BALB/c and pJ mice. This suggests the existence of regulatory and developmental differences with a more complex origin than just differing pigmentation levels.

Metabolic design of macroscopic bioreaction models: application to Chinese hamster ovary cells.

The aim of this paper is to present a systematic methodology to design macroscopic bioreaction models for cell cultures based upon metabolic networks. The cell culture is seen as a succession of phases. During each phase, a metabolic network represents the set of reactions occurring in the cell. Then, through the use of the elementary flux modes, these metabolic networks are used to derive macroscopic bioreactions linking the extracellular substrates and products. On this basis, as many separate models are obtained as there are phases. Then, a complete model is obtained by smoothly switching from model to model. This is illustrated with batch cultures of Chinese hamster ovary cells.

Contagious bovine pleuropneumonia vaccines, historic highlights, present situation and hopes.

Contagious bovine pleuropneumonia (CBPP) is a contagious infection of cattle caused by a mycoplasma, M. mycoides subsp. mycoides SC (MmmSC). It induces lesions of pleuropneumonia in acute cases and the formation of pulmonary "sequestra" in chronic cases. The disease is prevalent mostly in Africa, where it is responsible for high losses, but it has also been sporadically present in Southern Europe until 1999. Vaccination is now prohibited in most countries except in Africa. An empirical "inoculation" procedure was developed as early as 1852 in Europe but it may have been used even earlier in Africa. The inoculation of pleural fluid was performed at the tip of the tail in Europe and on the bridge of the nose in Africa. It conferred good protection but induced a high number of fatal cases. Various inactivated preparations have been tested in the past with inconclusive results leading sometime to some protection and some other time to a sensitisation of the immunised animals. Such preparations have never been used in the field. Attenuated MmmSC strains have been developed in the 1950s and used extensively in the field both in Africa and Australia. The best known vaccine strains are KH3J, T1/44 and T1sr. Vaccination campaigns have succeeded in reducing considerably the CBPP prevalence in these two continents but eradication was achieved in Australia only by switching to strict measures of animal movement control and a stamping-out policy. The search for new CBPP vaccines has become a major issue for African countries that are facing an increase in outbreaks. The rationale for this search is based on a better understanding of the mycoplasma virulence mechanisms that could lead to a targeted attenuation of MmmSC strains. It is also based on a better understanding of the bovine immune response that may be driven to a pathogenic inflammatory response or conversely to a better balanced response leading to protection.

In vivo adenovirus-mediated delivery of a uPA/uPAR antagonist reduces retinal neovascularization in a mouse model of retinopathy.

Diabetic retinopathy and retinopathy of prematurity are among the leading causes of vision impairment throughout the world. Both diseases are characterized by pathological angiogenesis, which severely impairs vision. Extracellular proteinases play important roles in endothelial cell migration during angiogenesis. Amino-terminal fragment (ATF) is an angiostatic molecule that targets the uPA/uPAR system and inhibits endothelial cell migration. The angiostatic effect of ATF has been demonstrated in models of cancer, but has never been assessed in pathological retinal neovascularization. Endostatin also has angiostatic effects on tumor growth and retinal neovascularization. We used an adenoviral vector carrying the murine ATF (AdATFHSA) or endostatin gene coupled to human serum albumin (HSA) (AdEndoHSA) to increase the half-life of the therapeutic protein in the circulation. We induced retinopathy by exposing 7-day-old mice to high levels of oxygen. They were intravitreally injected with the vectors. Local injection of AdATFHSA or AdEndoHSA reduced retinal neovascularization by 78.1 and 79.2%, respectively. Thus, the adenovirus-mediated delivery of ATFHSA or EndoHSA reduces retinal neovascularization in a mouse model of hypoxia-induced neovascularization.

Major role of BAX in apoptosis during retinal development and in establishment of a functional postnatal retina.

Apoptosis plays a major role in the development of the central nervous system. Previous studies of apoptosis induction during retinal development are difficult to interpret, however, because they explored different mouse strains, different developmental periods, and used different assays. Here, we first established a comprehensive sequential pattern of cell death during the whole development of the C57BL/6J mouse retina, from E10.5 to postnatal day (P) 21 by using the terminal deoxynucleotidyl transferase (TdT) -mediated deoxyuridine triphosphate (dUTP)-biotinylated nick end labeling (TUNEL) assay. We confirmed the existence of three previously described apoptotic peaks and identified another, later peak at P15, in both the outer nuclear layer, in which the photoreceptors differentiate, and the ganglion cell layer. Comparison of wild-type C57BL/6 mice, gld mice, defective in the death ligand fasL, and bax-/- mice, defective in the pro-apoptotic BAX protein, revealed a minor role for FAS ligand but a crucial role for BAX in both apoptosis and normal retinal development. The lack of BAX resulted in thicker than normal inner neuroblastic and ganglion cell layers in adults, with larger numbers of cells and an impaired electroretinogram response related to a decreased number of responsive cells. Our findings indicate that cell death during normal retinal development is important for the modeling of a functional vision organ and showed that the pro-apoptotic BAX protein plays a crucial role in this process.

Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis.

The RCS rat presents an autosomal recessive retinal pigment epithelium dystrophy characterized by the outer segments of photoreceptors being phagocytosis-deficient. A systematic genetic study allowed us to restrict the interval containing the rdy locus to that between the markers D3Mit13 and D3Rat256. We report the chromosomal localization of the rat c-mer gene in the cytogenetic bands 3q35-36, based on genetic analysis and radiation hybrid mapping. Using a systematic biocomputing analysis, we identified two strong related candidate genes encoding protein tyrosine kinase receptors of the AXL subfamily. The comparison of their expression patterns in human and mice tissues suggested that the c-mer gene was the best gene to screen for mutations. RCS rdy- and RCS rdy+ cDNAs were sequenced. The RCS rdy- cDNAs carried a significant deletion in the 5' part of the coding sequence of the c-mer gene resulting in a shortened aberrant transcript encoding a 20 amino acid peptide. The c-mer gene contains characteristic motifs of neural cell adhesion. A ligand of the c-mer receptor, Gas6, exhibits antiapoptotic properties.

Contagious bovine pleuropneumonia. A reassessment of the efficacy of vaccines used in Africa.

Contagious bovine pleuropneumonia is a major threat for cattle in Africa. Since 1956 the T1/44 strain has been used as a vaccine, and later on, T1sr, a streptomycin-resistant variant that gives fewer post-vaccinal reactions had been developed. These vaccines are known not to be very efficient but they normally should provide protection for about eight months. However, recent emergency vaccinations, performed in various countries in the southern part of the continent apparently met with failure, casting doubts on the identity as well as the protection afforded by the T1sr strain. A vaccine trial has been designed to reassess the real protection afforded by these vaccines in face of recently isolated pathogenic strains. Great care has been taken to test the original vaccinal strains at a dose corresponding to the minimum requirement by international standards. The test was performed in Cameroon, Kenya, and Namibia as to take into account the genetic diversity that exists among the pathogenic strains. In those conditions, the protection rate at three months varied from 33 to 67%, whatever the strain used, T1/44 or T1sr. These results call for additional research for vaccine development and careful planning of strategies in the fight against CBPP.

[Strategies for prevention and eradication of contagious bovine pleuropneumonia with or without vaccination]. / Stratégies de prophylaxie et d'éradication de la péripneumonie contagieuse bovine avec ou sans vaccination.

Contagious bovine pleuropneumonia (CBPP) offers, like rinderpest, the paradox of having been eradicated from some countries (north-western Europe, the United States of America) before the nature of the pathogenic agent was known. As a preventive measure, inoculation of pathogenic material was used but success varies due to strategic inadequacies. The same applies to vaccination with more or less attenuated live strains of Mycoplasma mycoides subsp. mycoides. Many ideas for prophylaxis have been suggested. Disease-free countries must apply the recommendations of the International Animal Health Code of the Office International des Epizooties (OIE), including those concerning the operation of epidemiological surveillance systems. Infected countries (or regions) select one of the following courses of action, depending on epidemiological, geographic, economic and social circumstances: Slaughter of affected and in-contact animals. This radical, simple and effective solution cannot be applied everywhere, particularly in a number of developing countries which have pastoral economies. Slaughter of affected animals and vaccination of those in contact. This method, which actually perpetuates the infection, is unfortunately still used widely. Preventive vaccination of healthy animals, coupled with the slaughter of affected animals and/or revaccination of those exposed to infection. This method controls the situation if outbreaks are detected efficiently and combated energetically. The tactical approach for disease-free and infected areas should continue to be that of large-scale and repeated vaccination, recommended since 1970 and the efficiency of which has been proved. This approach can lead to eradication when maintained for at least three years and applied to an entire infected region or country. A country is recognised as free from infection under rules adopted by the OIE in 1995.

[Practical aspects of leukotriene E4 determination in urine]. / Aspects pratiques du dosage du leucotriène E4 dans les urines.

Leukotrienes constitute a class of potent biological mediators of inflammation and anaphylaxis. However, their routine assay in various biological fluids is restricted by the complexity of the methodology. Previously this could only be performed by research laboratories with high pressure liquid chromatography and radioimmunological capabilities. The recent availability of kits for immunoenzymatic assay of leukotrienes offers a new tool for clinical laboratories provided the limitations of the method are understood. We suggest a simplified methodology for direct urinary LTE4 detection and outline a number of areas of concern encountered with this method.

Measuring recovery from general anaesthesia using critical flicker frequency: a comparison of two methods.

Critical flicker frequency (CFF) is the frequency at which a flickering light appears steady. It is a sensitive measure for assessing recovery from anaesthesia. The CFF is almost always determined with the method of limits by which the flickering frequency is progressively decreased (or increased) until the patient reports a change from fusion to flicker (or flicker to fusion). This method has two disadvantages: it is influenced by the response bias (i.e., the subjective criterion used by the subject to decide that flicker is present or absent) and by the response delay (i.e., the interval between the perceptual change and the response). To avoid these problems, the method of forced choice is recommended. For each trial, the subject observes the light during two short successive periods. The light flickers during only one period, according to chance. The patient must indicate the period during which flickers occur. If uncertain, the patient has to make a guess. The aim of this study was to compare the two methods for assessing recovery from general anaesthesia. Two induction agents were used to obtain different recovery profiles. Twenty patients undergoing uncomplicated surgery lasting less than two hours were tested. They received either thiopentone or midazolam for induction, according to a randomized design. Vecuronium was used to facilitate tracheal intubation and anaesthesia was maintained with fentanyl, isoflurane and nitrous oxide. The CFF was measured before induction and at 60, 120 and 180 minutes after arrival in the recovery room. The person measuring CFF was unaware of the induction agent used.(ABSTRACT TRUNCATED AT 250 WORDS)

[Attenuation of a strain of rinderpest virus: potential homologous live vaccine]. / Atténuation d'une souche de virus de la peste des petits ruminants: candidat pour un vaccin homologue vivant.

Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants frequently associated with severe mortality in these hosts. In countries where it occurs, PPR represents an important constraint to the improved productivity of sheep and goats. Until now the only way to combat this plague has been the use of heterologous rinderpest vaccine; all attempts to develop a homologous vaccine have ended in failure. The present communication describes the attenuation of the Nigerian strain PPRV Nig 75/1 by serial passage in Vero cells. The avirulent virus obtained has the same characteristics as Plowright and Ferris' rinderpest vaccine. The virus is advanced as a potential homologous vaccine against PPR.

The historical background and global importance of heartwater.

The first written record of what probably could have been heartwater originates from South Africa and dates back to 1838. Since then, the disease was described from almost all the African countries south of the Sahara as well as from Madagascar, São Tome, Reunion, Mauritius and a number of islands in the Caribbean. Most research on the disease, at least until recently, was conducted in South Africa. Progress in research was slow but a few outstanding findings are mentioned in this paper. Despite inadequate information on its actual economic impact on livestock production, it is generally accepted that heartwater is either the most or second most important tick-borne disease in Africa. Depending on the area, heartwater ranks either second or third amongst diseases such as East Coast fever, tsetse-transmitted trypanosomiasis, rinderpest and perhaps also schistosomiasis. Heartwater is a major obstacle with regard to the introduction of highly producing animals intended for the upgrading of local breeds. Furthermore, it remains a major threat to areas such as the American mainland, where potential vectors are present but where the disease does not occur.