Indications, perspectives et limites de la stimulation électrique épidurale en cas d'artériopathie périphérique ou coronarienne [Indications, limits and future of epidural spinal cord electrical stimulation for coronary and peripheral artery disease]

The electrical stimulation of the dorsal columns of the spinal cord exerts a dual analgesic and vasodilatory effect on ischemic tissues. It is increasingly considered a valuable method to treat severe and otherwise intractable coronary and peripheral artery disease. The quality of the results depends from both a strict selection of the patients by vascular specialists and the frequency and quality of the follow-up controls. However the indications, limits, mode of action and results of spinal cord stimulation are still poorly understood. This article, based on a personal experience of 164 implantations for peripheral and coronary artery disease, aims to draw attention to this technique and to provide information on recent and future developments.

NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module.

MHC class II (MHCII) genes are transactivated by the NOD-like receptor (NLR) family member CIITA, which is recruited to SXY enhancers of MHCII promoters via a DNA-binding "enhanceosome" complex. NLRC5, another NLR protein, was recently found to control transcription of MHC class I (MHCI) genes. However, detailed understanding of NLRC5's target gene specificity and mechanism of action remained lacking. We performed ChIP-sequencing experiments to gain comprehensive information on NLRC5-regulated genes. In addition to classical MHCI genes, we exclusively identified novel targets encoding non-classical MHCI molecules having important functions in immunity and tolerance. ChIP-sequencing performed with Rfx5(-/-) cells, which lack the pivotal enhanceosome factor RFX5, demonstrated its strict requirement for NLRC5 recruitment. Accordingly, Rfx5-knockout mice phenocopy Nlrc5 deficiency with respect to defective MHCI expression. Analysis of B cell lines lacking RFX5, RFXAP, or RFXANK further corroborated the importance of the enhanceosome for MHCI expression. Although recruited by common DNA-binding factors, CIITA and NLRC5 exhibit non-redundant functions, shown here using double-deficient Nlrc5(-/-)CIIta(-/-) mice. These paradoxical findings were resolved by using a "de novo" motif-discovery approach showing that the SXY consensus sequence occupied by NLRC5 in vivo diverges significantly from that occupied by CIITA. These sequence differences were sufficient to determine preferential occupation and transactivation by NLRC5 or CIITA, respectively, and the S box was found to be the essential feature conferring NLRC5 specificity. These results broaden our knowledge on the transcriptional activities of NLRC5 and CIITA, revealing their dependence on shared enhanceosome factors but their recruitment to distinct enhancer motifs in vivo. Furthermore, we demonstrated selectivity of NLRC5 for genes encoding MHCI or related proteins, rendering it an attractive target for therapeutic intervention. NLRC5 and CIITA thus emerge as paradigms for a novel class of transcriptional regulators dedicated for transactivating extremely few, phylogenetically related genes.

Fièvres virales d'ailleurs [Viral fevers from elsewhere].

Some viruses are transmitted only in specific parts of the world and do not exist in Switzerland. However, the increase in intercontinental travels, the tendency of travelers to have activities in remote rural areas, the transportation (sometimes forbidden) of exotic animals, the climatic warming and the adaptation of viruses to new vectors produce an extension of viral diseases towards Northern countries. To improve the identification of these infections in travelers, but also in European autochthonous populations, it is necessary to know the clinical characteristics and the websites announcing the epidemics. Neurological or hemorrhagic signs should incite the clinician to suspect a viral hemorrhagic fever, diagnosis to be considered if the destination and chronology are compatible, strict isolation measures being necessary.

The burnout syndrome and associated personality disturbances. The study in three graduate programs in Dentistry at the University of Barcelona

Objective: Determine the presence of"burnout" syndrome and characteristic personality patterns in the students and faculty of three graduate programs in Dentistry at the University of Barcelona: Department of Oral Surgery and Implantology, Department of Orthodontics and Department of Integrated Dentistry. Materials and Methods: The study was carried out in 78 dentists. The level of"burnout" was evaluated using the Maslach Burnout Inventory, socio-demographic variables and, finally, the personality test. Results: Oral surgeons constituted the group of highlevel"burnout". The profile of an individual with a propensity to"burn out" is a single man, with a median age of 27, that is in the first years of the graduate program and that combines studies with 30 hours of clinical practice and/or other work (p<0,05). Narcissistic and borderline are the types of personality most frequently found in the individuals that present"burnout" syndrome (p<0,05). Conclusions: In general, no high levels of"burnout" were registered in the studied population, only 2-3%, if applying strict definition of"burnout", and 10% if these criteria were amplified. We believe it is necessary to identify the individuals with a tendency towards"burnout", in order to establish preventive measures and avoid future negative behaviour at work as well as at the personal level.

Dénervation rénale pour le traitement de l'hypertension artérielle résistante: proposition pour une attitude multidisciplinaire commune [Renal denervation in resistant hypertension: proposal for a common multidisciplinary attitude].

The prevalence of resistant hypertension ranges between 5-30%. Patients with resistant hypertension are at increased risk of cardiovascular events. Radiofrequency renal denervation is a recent and promising technique that can be used in the setting of resistant hypertension. However, long-term safety and efficacy data are lacking and evidence to use this procedure outside the strict setting of resistant hypertension is missing. The aim of the article is to propose a common work-up for nephrologists, hypertensiologists, cardiologists and interventional radiologists in order to avoid inappropriate selection of patients and a possible misuse of this procedure.

Developing psychosis and its risk States through the lens of schizotypy.

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorders.

First detection of Waddlia chondrophila in Africa using SYBR Green real-time PCR on veterinary samples.

Waddlia chondrophila is a strict intracellular microorganism belonging to the order Chlamydiales that has been isolated twice from aborted bovine fetuses, once in USA and once in Germany. This bacterium is now considered as an abortigenic agent in cattle. However, no information is available regarding the presence of this bacterium in Africa. Given the low sensitivity of cell culture to recover such an obligate intracellular bacterium, molecular-based diagnostic approaches are warranted. This report describes the development of a quantitative SYBR Green real-time PCR assay targeting the recA gene of W. chondrophila. Analytical sensitivity was 10 copies of control plasmid DNA per reaction. No cross-amplification was observed when testing pathogens that can cause abortion in cattle. The PCR exhibited a good intra-run and inter-run reproducibility. This real-time PCR was then applied to 150 vaginal swabs taken from Tunisian cows that have aborted. Twelve samples revealed to be Waddlia positive, suggesting a possible role of this bacterium in this setting. This new real-time PCR assay represents a diagnostic tool that may be used to further study the prevalence of Waddlia infection.

Scale Effects in Hydraulic Model Tests of Rock Protected Structures, HR-119, 1970

A laboratory investigation was undertaken to determine the limiting model Reynolds number above which the scour behavior of rock protected structures can be reproduced in hydraulic models scaled according to the Froude criterion. A submerged jet was passed over an initially full scour pocket containing uniform glass spheres and the rate of scour was measured as a function of time. The dimensions of the scour pocket and jet and the particle diameters were varied as needed to maintain strict geometric similarity. For each of two different Froude numbers the Reynolds number was varied over a wide range. The normalized scour rate was found to be practically independent of the Reynolds number, R, (based on the jet velocity and particle diameter) at values of R above about 2.5 x 10^3, and to decrease with Rat smaller values. A grid placed in the jet was found to have a very strong effect on the scour rate. In an attempt to explain the effect of R on the scour behavior, turbulent pressure and velocity fluctuations were measured in air flows and water flows, respectively, over rigid scour pockets having the same geometry as those formed in the scour experiments. The normalized spectra of the fluctuations were found to be nearly independent of R, but the flow pattern was found to be very sensitive to the inlet condition, the jet deflecting upward or downward in a not wholly explainable manner. This indicates that scour behavior can be modeled only if the approach flow is also accurately modeled.

A developmental framework for endodermal differentiation and polarity.

The endodermis is a root cell layer common to higher plants and of fundamental importance for root function and nutrient uptake. The endodermis separates outer (peripheral) from inner (central) cell layers by virtue of its Casparian strips, precisely aligned bands of specialized wall material. Here we reveal that the membrane at the Casparian strip is a diffusional barrier between the central and peripheral regions of the plasma membrane and that it mediates attachment to the extracellular matrix. This membrane region thus functions like a tight junction in animal epithelia, although plants lack the molecular modules that establish tight junction in animals. We have also identified a pair of influx and efflux transporters that mark both central and peripheral domains of the plasma membrane. These transporters show opposite polar distributions already in meristems, but their localization becomes refined and restricted upon differentiation. This "central-peripheral" polarity coexists with the apical-basal polarity defined by PIN proteins within the same cells, but utilizes different polarity determinants. Central-peripheral polarity can be already observed in early embryogenesis, where it reveals a cellular polarity within the quiescent center precursor cell. A strict diffusion block between polar domains is common in animals, but had never been described in plants. Yet, its relevance to endodermal function is evident, as central and peripheral membranes of the endodermis face fundamentally different root compartments. Further analysis of endodermal transporter polarity and manipulation of its barrier function will greatly promote our understanding of plant nutrition and stress tolerance in roots.

Capturing epidermal stemness for regenerative medicine.

The skin is privileged because several skin-derived stem cells (epithelial stem cells from epidermis and its appendages, mesenchymal stem cells from dermis and subcutis, melanocyte stem cells) can be efficiently captured for therapeutic use. Main indications remain the permanent coverage of extensive third degree burns and healing of chronic cutaneous wounds, but recent advances in gene therapy technology open the door to the treatment of disabling inherited skin diseases with genetically corrected keratinocyte stem cells. Therapeutic skin stem cells that were initially cultured in research or hospital laboratories must be produced according strict regulatory guidelines, which ensure patients and medical teams that the medicinal cell products are safe, of constant quality and manufactured according to state-of-the art technology. Nonetheless, it does not warrant clinical efficacy and permanent engraftment of autologous stem cells remains variable. There are many challenges ahead to improve efficacy among which to keep telomere-dependent senescence and telomere-independent senescence (clonal conversion) to a minimum in cell culture and to understand the cellular and molecular mechanisms implicated in engraftment. Finally, medicinal stem cells are expansive to produce and reimbursement of costs by health insurances is a major concern in many countries.

Functional genomics of intracellular bacteria.

During the genomic era, a large amount of whole-genome sequences accumulated, which identified many hypothetical proteins of unknown function. Rapidly, functional genomics, which is the research domain that assign a function to a given gene product, has thus been developed. Functional genomics of intracellular pathogenic bacteria exhibit specific peculiarities due to the fastidious growth of most of these intracellular micro-organisms, due to the close interaction with the host cell, due to the risk of contamination of experiments with host cell proteins and, for some strict intracellular bacteria such as Chlamydia, due to the absence of simple genetic system to manipulate the bacterial genome. To identify virulence factors of intracellular pathogenic bacteria, functional genomics often rely on bioinformatic analyses compared with model organisms such as Escherichia coli and Bacillus subtilis. The use of heterologous expression is another common approach. Given the intracellular lifestyle and the many effectors that are used by the intracellular bacteria to corrupt host cell functions, functional genomics is also often targeting the identification of new effectors such as those of the T4SS of Brucella and Legionella.

Between manualized treatments and principle-guided psychotherapy: illustration in the case of Caroline

My case study of "Caroline"-a 26 year old presenting with depression, PTSD symptoms, and a history of sexual abuse as a teenager-represents a "third way" between (1) a strict adherence to a manualized treatment, and (2) a principle-guided therapy, in which the therapy follows particular theoretical concepts, but depends on the therapist's clinical judgement to flexibly apply them to the individual case. Specifically, in my therapy with Caroline (Kramer, 2009), I employed Foa and Rothbaum's (1998) cognitive-behavioral, "Prolonged Exposure" (PE) manual for PTSD, but deviated from it in certain ways based upon my evaluation of Caroline's individualized goals and reactions using Grawe and Caspar's "Plan Analysis," which is a cross-theoretical model for assessment and treatment planning. In their commentaries on my case study of Caroline, Caspar (2009) and Haldimann-Balli (see Appendix in Kramer, 2009) support my use of this third way. On the other hand, the other commentators-Muller (2009) and Hembree and Brinen (2009)-critique my handling of the case, arguing that strict adherence to the Foa and Rothbaum manual would have resulted in a more cost-effective therapy. In this article, I respond to the important issues raised by the four commentators.

L'autre du même : emprunts et répétitions dans le "Roman de Perceforest"

Issu de la fin du Moyen Âge, le Roman de Perceforest est le plus long texte que le Moyen Âge nous ait laissé. Il entend décrire la vie des ancêtres préchrétiens d'Arthur et de ses chevaliers en les faisant descendre d'Alexandre le Grand. Au fil de son récit, l'auteur met en place une véritable poétique de la reprise, tant externe qu'interne. Il multiplie les références à des textes préexistants issus de différentes matières et va même jusqu'à en intégrer des morceaux entiers. Il reprend par ailleurs des parties de sa propre oeuvre, n'hésitant pas à reproduire des schémas, voire des séquences narratives précises. Cette esthétique répétitive a plusieurs conséquences, tant sur l'appartenance générique du texte, sur sa construction, que sur sa réception par le lecteur. Elle est au coeur de notre étude. Nous nous intéressons plus spécifiquement à un phénomène particulier de reprise qui montre l'intégration d'une séquence préexistante dans un contexte distinct de son apparition d'origine et que nous qualifions d'emprunt. Notre travail s'organise autour d'un examen successif des différents types d'emprunts qui apparaissent au sein du texte, tant intertextuels qu'intratextuels. À terme, c'est la cohérence et l'individualité du Perceforest, ainsi que la conception de l'écriture qui anime son auteur que nous mettons en avant, tout en proposant des jalons pour une théorie générale de l'emprunt. - The Roman de Perceforest, the longest known text from the Middle Ages, aims to describe the life of Arthur's pre-christian ancestors and knights, presenting them as descendants of Alexander the Great. Along the storytelling, a genuine poetics of external and internal repetition takes place: the Perceforest s authors multiply the references to previous texts belonging to several materials, integrating sometimes entire parts of other texts. Furthermore the narrative reproduces its own patterns and particular sequences in different places of the text. Throughout this research, we consider the influence of such repetition aesthetics on the literary genre definition, on its construction as well as on the reader's reception. In this dissertation, we explore a specific category of repetitions where pre-existing sequences are embedded in a narrative context that differs from the original context of occurrence, which we called emprunt (s). Reviewing the species of inter- and intra-textual recurrences occurring within the text, we reveal some overlooked aspects of the consistency, the specificity of the Perceforest and its author's idea of writing, striving to groundwork on general theory of «emprunts» that shall thereby be laid.

Statistical properties of population differentiation estimators under stepwise mutation in a finite island model.

Microsatellite loci mutate at an extremely high rate and are generally thought to evolve through a stepwise mutation model. Several differentiation statistics taking into account the particular mutation scheme of the microsatellite have been proposed. The most commonly used is R(ST) which is independent of the mutation rate under a generalized stepwise mutation model. F(ST) and R(ST) are commonly reported in the literature, but often differ widely. Here we compare their statistical performances using individual-based simulations of a finite island model. The simulations were run under different levels of gene flow, mutation rates, population number and sizes. In addition to the per locus statistical properties, we compare two ways of combining R(ST) over loci. Our simulations show that even under a strict stepwise mutation model, no statistic is best overall. All estimators suffer to different extents from large bias and variance. While R(ST) better reflects population differentiation in populations characterized by very low gene-exchange, F(ST) gives better estimates in cases of high levels of gene flow. The number of loci sampled (12, 24, or 96) has only a minor effect on the relative performance of the estimators under study. For all estimators there is a striking effect of the number of samples, with the differentiation estimates showing very odd distributions for two samples.

Human papilloma virus type and recurrence rate after surgical clearance of anal condylomata acuminata

Résumé : Le condylome acuminé anal (CAA), transmis par contact sexuel, résulte d'une infection par Human Papilloma Virus (HPV). Son traitement chirurgical est grevé d'un taux de récidive de 4-29%. Le but de cette étude était d'identifier une éventuelle corrélation entre type d'HPV présent dans les CAA excisés chirurgicalement et taux de récidive de la maladie, Cette étude rétrospective porte sur 140 patients opérés au Centre Hospitalier Universitaire Vaudois de CAA, entre 1990 et 2005. Le diagnostic lésionnel a été confirmé par un examen histomorphologique. Le(s) type(s) d'HPV présent(s) dans ces lésions a été déterminé par Polymerase Chain Reaction (PCR). Les patients ont donné leur accord à cette analyse et complété un questionnaire. Une éventuelle corrélation entre récidive de CAA, type d'HPV et status HIV a été recherchée. HPV 6 et 11 sont les virus les plus fréquemment découverts (51% et 28%, respectivement) chez les 140 patients (123H/17F). Trente-cinq (25%) d'entre eux ont présenté une récidive. HPV 11 était present chez 19 (41%) sujets. Ceci est statistiquement significatif (P<0.05), en comparaison aux autres HPVs. Il n'y a par contre pas de différence significative entre la fréquence de récidive des 33 (24%) patients HIV-positifs et le reste du collectif. HPV 11 est donc associé à un taux de récidive de CAA significativement élevé. Un suivi strict des patients atteints est nécessaire pour identifier une récidive et la traiter sans délai, notamment lorsque HPV 11 est present. Ces résultats innovateurs soulèvent la question de la nécessité de pratiquer une typisation virale systématique sur les lésions excisées. La justification d'une telle attitude demande toutefois encore d'être confirmée.