Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.

Wound infection following stoma takedown: primary skin closure versus subcuticular purse-string suture.

Abstract: Background Stoma closure has been associated with a high rate of surgical site infection (SSI) and the ideal stoma-site skin closure technique is still debated. The aim of this study was to compare the rate of SSI following primary skin closure (PC) versus a skin-approximating, subcuticular purse-string closure (APS). Methods All consecutive patients undergoing stoma closure between 2002 and 2007 by two surgeons at a single tertiary-care institution were retrospectively assessed. Patients who had a new stoma created at the same site or those without wound closure were excluded. The end point was SSI, determined according to current CDC guidelines, at the stoma closure site and/or the midline laparotomy incision. Results There were 61 patients in the PC group (surgeon A: 58 of 61) and 17 in the APS group (surgeon B: 16 of 17). The two groups were similar in baseline and intraoperative characteristics, except that patients in the PC group were more often diagnosed with benign disease (p = 0.0156) and more often had a stapled anastomosis (p = 0.002). The overall SSI rate was 14 of 78 (18%). All SSIs occurred in the PC group (14 of 61 vs. 0 of 17, p = 0.03). Conclusions Our study suggests that a skin-approximating closure with a subcuticular purse-string of the stoma site leads to less SSI than a primary closure. Randomized studies are needed to confirm our findings and assess additional end points such as healing time, cost, and patient satisfaction.

Diagnostic potential of neutrophil elastase inhibitor complex in the routine care of critically ill newborn infants.

It has been suggested that determination of the neutrophil elastase alpha1-proteinase inhibitor complex (E-alpha1PI) improves the diagnosis of bacterial infection in newborns. We evaluated the use of E-alpha1PI measurements in 143 newborns, consecutively admitted to a tertiary intensive care unit, employing a new random access assay and a sampling procedure that minimises post-collection artefacts. The 95% range for noninfected newborns was 20-110 microg/l up to the 5th day of life and 20-85 microg/l thereafter. The sensitivity as to the diagnosis of culture-proven bloodstream infection was 80% for E-alpha1PI, 86% for the immature to total neutrophil ratio, 64% for C-reactive protein and 37% for the total white blood cell count. The corresponding specificity amounted to 97%, 85%, 85% and 86%, respectively. E-alpha1PI increases preceded elevations of C-reactive protein by 18 h. Like C-reactive protein, E-alpha1PI levels did not distinguish between bloodstream infection and non-bacterial inflammatory responses. Results of E-alpha1PI became available within 1 h of collection and usually 2-3 h before manual leucocyte counts. CONCLUSION: Determination of neutrophil elastase alpha1-proteinase inhibitor levels yields diagnostic advantages comparable to those of manual differential counts but provide faster turnaround times.

A randomised controlled pilot study comparing Mepitel(®) and SurfaSoft(®) on paediatric donor sites treated with Recell(®).

This randomized controlled pilot study examined the effects of a silicone net dressing (Mepitel(®)) and a monofilament polyamide woven dressing (SurfaSoft(®)) on the rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal on paediatric donor sites treated with epithelial cell suspension (ReCell(®)). Fifteen children (1-15 years) admitted for acute or reconstructive burns procedures in a tertiary referral hospital in Australia were randomly assigned to the experimental group, Mepitel(®) (n=8) and to the control group, SurfaSoft(®) (n=7). All donor sites were treated with ReCell(®) and covered with the assigned dressing. Measurements of rate of epithelialisation and epidermal maturation, pain, and ease of dressing removal were recorded every two days until the wound was healed. Results showed that there was no difference in the rate of epidermal maturation between the two groups. Less pain and force to remove the dressing was shown in the Mepitel(®) group when compared to SurfaSoft(®). The rate of epithelialisation was found to be an unreliable measure. Although additional research is required to support the results of this study, these results suggest that Mepitel's(®) pliable, self-adhesive and atraumatic properties may improve healing of ReCell(®) treated donor sites with less pain at dressing changes. This pilot study provides a strong base for further research in this area.

The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis.

The ability of pollutants to affect human health is a major concern, justified by the wide demonstration that reproductive functions are altered by endocrine disrupting chemicals. The definition of endocrine disruption is today extended to broader endocrine regulations, and includes activation of metabolic sensors, such as the peroxisome proliferator-activated receptors (PPARs). Toxicology approaches have demonstrated that phthalate plasticizers can directly influence PPAR activity. What is now missing is a detailed molecular understanding of the fundamental basis of endocrine disrupting chemical interference with PPAR signaling. We thus performed structural and functional analyses that demonstrate how monoethyl-hexyl-phthalate (MEHP) directly activates PPARgamma and promotes adipogenesis, albeit to a lower extent than the full agonist rosiglitazone. Importantly, we demonstrate that MEHP induces a selective activation of different PPARgamma target genes. Chromatin immunoprecipitation and fluorescence microscopy in living cells reveal that this selective activity correlates with the recruitment of a specific subset of PPARgamma coregulators that includes Med1 and PGC-1alpha, but not p300 and SRC-1. These results highlight some key mechanisms in metabolic disruption but are also instrumental in the context of selective PPAR modulation, a promising field for new therapeutic development based on PPAR modulation.

Une carte des zones de cisaillement ductiles des Alpes Centrales

The main deformation structures due to the Tertiary continental collision in the Western Swiss Alps are ductile shear zones. Four main shear zones can be recognized on the structural map, each characterised by a different shear direction. The first D I shear zone with a X I, SE (transverse) stretching direction has been created during the under-thrusting towards the SE of the European plate under the Adriatic plate. This took place mainly by ductile deformation of the upper part of the European continental basement with the formation of the external massifs basement folds and the Penninic foldnappes. The second D II shear zone (Simplon ductile shear zone) is characterized by a XII stretching, dipping from 0 to 30-degrees to the SW (longitudinal stretching). It is approximately 10 km wide, and crosses the Alpine nappes in an oblique direction. It corresponds to a relative SW transport direction of the upper units together with the Adriatic plate. This dextral transpression zone is also responsible for the stretching parallel to the elongation of the Alpine belt. The third D III shear zone is made of mylonites with a steep stretching direction and corresponds to the hanging wall of the Canavese reverse fault. The D IV shear zones, dextral wrench zones combined with underthrusting movement, are characterised by a W and SW stretching direction. They were formed during and after the S facing backfolding which for instance made the Mischabel fold and the Boggioleto fold. Actually it occupies two narrow areas of more ductile rocks between the Mischabel backfold to the N and the Monte Rosa nappe to the S and allong the Canavese Line. These dextral shear zones represent probably the western continuation of the Tonale Line dextral wrench fault. The D I to IV ductile shear zone were formed under greenschist and amphibolite facies conditions during the Tertiary orogenic metamorphism. Their regional distribution is limited to the metamorphic ductile zone representing the deep part of the Alpine belt, between 10 and 30 km depth. The emplacement and orientation of the shear zones was also directed by the geometry of the boundaries of the European and Adriatic plates. The analysis of the superposed Central Alpine shear zones permits thus to propose a model of the history of the relative convergent and wrench movements which took place between the European and Adriatic plates during the Alpine Tertiary continental collision.

The gendering of excellence through quality criteria: the case of the SNSF Professorships in Switzerland

The Swiss National Science Foundation Professorships Programme is presented as a scientific programme that aims to promote outstanding young scholars to professorial positions. Academic excellence is presented as the main selection criterion. The emphasis put on the research portfolio and on the age of the candidates means that the beneficiaries of these professorships put forward an image of excellence that is more embedded in data-based sciences than in the humanities and social sciences, thus strengthening the domination of a sector scientific activity essentially occupied by men over the sector that has opened up more widely to women. This paper aims to deconstruct the criteria of academic excellence as they appear in this programme and to show that what seem quality criteria are in fact inspired by a specific androcentric model. These biases tend to undermine the gender equality aims of the programme.

Multislice CT for assessing in-stent dimensions after left main coronary artery stenting: a comparison with three dimensional intravascular ultrasound

Objective: To evaluate the agreement between multislice CT (MSCT) and intravascular ultrasound (IVUS) to assess the in-stent lumen diameters and lumen areas of left main coronary artery (LMCA) stents. Design: Prospective, observational single centre study. Setting: A single tertiary referral centre. Patients: Consecutive patients with LMCA stenting excluding patients with atrial fibrillation and chronic renal failure. Interventions: MSCT and IVUS imaging at 912 months follow-up were performed for all patients. Main outcome measures: Agreement between MSCT and IVUS minimum luminal area (MLA) and minimum luminal diameter (MLD). A receiver operating characteristic (ROC) curve was plotted to find the MSCT cut-off point to diagnose binary restenosis equivalent to 6 mm2 by IVUS. Results: 52 patients were analysed. PassingBablok regression analysis obtained a β coefficient of 0.786 (0.586 to 1.071) for MLA and 1.250 (0.936 to 1.667) for MLD, ruling out proportional bias. The α coefficient was −3.588 (−8.686 to −0.178) for MLA and −1.713 (−3.583 to −0.257) for MLD, indicating an underestimation trend of MSCT. The ROC curve identified an MLA ≤4.7 mm2 as the best threshold to assess in-stent restenosis by MSCT. Conclusions: Agreement between MSCT and IVUS to assess in-stent MLA and MLD for LMCA stenting is good. An MLA of 4.7 mm2 by MSCT is the best threshold to assess binary restenosis. MSCT imaging can be considered in selected patients to assess LMCA in-stent restenosis

Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

Late Cretaceous to Eocene geology of the South Central American forearc area (southern Costa Rica and western Panama) : initiation and evolution of an intra-oceanic convergent margin

Résumé : L'arc volcanique du sud de l'Amérique Centrale se situe sur la marge SW de la Plaque Caraïbe, au-dessus des plaques subduites de Cocos et Nazca. Il s'agit de l'un des arcs intra-océaniques les plus étudiés au monde, qui est généralement considéré comme s'étant développé à la fin du Crétacé le long d'un plateau océanique (le Plateau Caraïbe ou CLIP) et se trouvant actuellement dans un régime de subduction érosive. Au cours des dernières décennies, des efforts particuliers ont été faits pour comprendre les processus liés à la subduction sur la base d'études géophysiques et géochimiques. Au sud du Costa Rica et à l'ouest du Panama, des complexes d'accrétions et structures à la base de l'arc volcanique ont été exposés grâce à la subduction de rides asismiques et de failles transformantes. Des affleurements, situés jusqu'à seulement 15 km de la fosse, offrent une possibilité unique de mieux comprendre quelques uns des processus ayant lieu le long de la zone de subduction. Nous présentons de nouvelles contraintes sur l'origine de ces affleurements en alliant une étude de terrain poussée, de nouvelles données géochimiques, sédimentaires et paléontologiques, ainsi que des observations structurales effectuées en télédétection. Une nouvelle stratigraphie tectonique entre le Campanien et l'Éocène est définie pour la région d'avant-arc située entre la Péninsule d'Osa (Costa Rica) et la Péninsule d'Azuero (Panama). Nos résultats montrent que la partie externe de la marge est composée d'un arrangement complexe de roches ignées et de séquences sédimentaires de recouvrement qui comprennent principalement le socle de l'arc, des roches d'arc primitif, des fragments de monts sous-marins accrétés et des mélanges d'accrétion. Des preuves sont données pour le développement de l'arc volcanique du sud de l'Amérique Centrale sur un plateau océanique. Le début de la subduction le long de la marge SW de la Plaque Caraïbe a eu lieu au Campanien et a généré des roches d'arc primitif caractérisées par des affinités géochimiques particulières, globalement intermédiaires entre des affinités de plateau et d'arc insulaire. L'arc était mature au Maastrichtien et formait un isthme essentiellement continu entre l'Amérique du Nord et l'Amérique du Sud. Ceci a permis la migration de faunes terrestres entre les Amériques et pourrait avoir contribué à la crise fin Crétacé -Tertiaire en réduisant les courants océaniques subéquatoriaux entre le Pacifique et l'Atlantique. Plusieurs unités composées de fragments de monts sous-marins accrétés sont définies. La nature et l'arrangement structural de ces unités définissent de nouvelles contraintes sur les modes d'accrétion des monts sous-marins/îles océaniques et sur l'évolution de la marge depuis la formation de la zone de subduction. Entre la fin du Crétacé et l'Éocène moyen, la marge a enregistré plusieurs épisodes ponctuels d'accrétion de monts sous-marins alternant avec de la subduction érosive. A l'Éocène moyen, un événement tectonique régional pourrait avoir causé un fort couplage entre les plaques supérieure et inférieure, menant à des taux plus important d'accrétion de monts sous-marins. Durant cette période, la situation le long de la marge était très semblable à la situation actuelle et caractérisée par la présence de monts sous-marins subductants et l'absence d'accrétion de sédiments. L'enregistrement géologique montre qu'il n'est pas possible d'attribuer une nature érosive ou accrétionnaire à la marge dans le passé ou -par analogie- aujourd'hui, parce que (1) les processus d'accrétion et érosifs varient fortement spatialement et temporellement et (2) il est impossible d'évaluer la quantité exacte de matériel tectoniquement enlevé à la marge depuis le début de la subduction. Au sud du Costa Rica, certains fragments de monts sous-marins accrétés sont représentatifs d'une interaction entre une ride et un point chaud dans le Pacifique au Crétacé terminal/Paléocène. L'existence de ces fragments de monts sous-marins et la morphologie du fond de l'Océan Pacifique indiquent que la formation de la ride de Cocos-Nazca s'est formée au moins ~40 Ma avant l'âge proposé par les modèles tectoniques actuels. Au Panama, nous avons identifié une île océanique d'âge début Éocène qui a été accrétée à l'Éocène moyen. L'accrétion a eu lieu à très faible profondeur par détachement de l'île dans la fosse, et a mené à une exceptionnelle préservation des structures volcaniques. Des affleurement comprenant aussi bien des parties basses et hautes de l'édifice volcanique on été étudiées, depuis la phase sous-marine bouclier jusqu'à la phase subaérienne post-bouclier. La stratigraphie nous a permis de différencier les laves de la phase sous-marine de celles de la phase subaérienne. La composition des laves indique une diminution progressive de l'intensité de la fusion partielle de la source et une diminution de la température des laves produites durant les derniers stades de l'activité volcanique. Nous interprétons ces changements comme étant liés à l'éloignement progressif de l'île océanique de la zone de fusion ou point chaud. Abstract The southern Central American volcanic front lies on the SW edge of the Caribbean Plate, inboard of the subducting Cocos and Nazca Plates. It is one of the most studied intra-oceanic convergent margins around the world, which is generally interpreted to have developed in the late Cretaceous along an oceanic plateau (the Caribbean Large Igneous Province or CLIP) and to be currently undergoing a regime of subduction erosion. In the last decades a particular effort has been made to understand subduction-related processes on the basis of geophysical and geochemical studies. In southern Costa Rica and western Panama accretionary complexes and structures at the base of the volcanic front have been exposed in response to subduction of aseismic ridges and transforms. Onland exposures are located as close as to 15 km from the trench and provide a unique opportunity to better understand some of the processes occurring along the subduction zone. We provide new constraints on the origins of these exposures by integrating a comprehensive field work, new geochemical, sedimentary and paleontological data, as well as structural observations based on remote imaging. A new Campanian to Eocene tectonostratigraphy is defined for the forearc area located between the Osa Peninsula (Costa Rica) and the Azuero Peninsula (Panama). Our results show that the outer margin is composed of a complicated arrangement of igneous complexes and overlapping sedimentary sequences that essentially comprise an arc basement, primitive island-arc rocks, accreted seamount fragments and accretionary mélanges. Evidences are provided for the development of the southern Central American arc on the top an oceanic plateau. The subduction initiation along the SW edge of the Caribbean Plate occurred in the Campanian and led to formation of primitive island-arc rocks characterized by unusual geochemical affinities broadly intermediate between plateau and arc affinities. The arc was mature in the Maastrichtian and was forming a predominantly continuous landbridge between the North and South Americas. This allowed migration of terrestrial fauna between the Americas and may have contributed to the Cretaceous-Tertiary crisis by limiting trans-equatorial oceanic currents between the Pacific and the Atlantic. Several units composed of accreted seamount fragments are defined. The nature of the units and their structural arrangement provide new constraints on the modes of accretion of seamounts/oceanic islands and on the evolution of the margin since subduction initiation. Between the late Cretaceous and the middle Eocene, the margin recorded several local episodes of seamount accretion alternating with tectonic erosion. In the middle Eocene a regional tectonic event may have triggered strong coupling between the overriding and subducting plates, leading to higher rates of seamount accretion. During this period the situation along the margin was very similar to the present and characterized by subducting seamounts and absence of sediment accretion. The geological record shows that it is not possible to ascribe an overall erosive or accretionary nature to the margin in the past and, by analogy, today, because (1) accretionary and erosive processes exhibit significant lateral and temporal variations and (2) it is impossible to estimate the exact amount of material tectonically eroded from the margin since subduction initiation. In southern Costa Rica, accreted seamount fragments point toward a plume-ridge interaction in the Pacific in the late Cretaceous/Paleocene. This occurrence of accreted seamount fragments and morphology of the Pacific Ocean floor is indicative of the formation of the Cocos-Nazca spreading system at least ~40 Ma prior to the age proposed in current tectonic models. In Panama, we identified a remarkably-well preserved early Eocene oceanic island that accreted in the middle Eocene. The accretion probably occurred at very shallow depth by detachment of the island in the trench and led to an exceptional preservation of the volcanic structures. Exposures of both deep and superficial parts of the volcanic edifice have been studied, from the submarine-shield to subaerial-postshield stages. The stratigraphy allowed us to distinguish lavas produced during the submarine and subaerial stages. The lava compositions likely define a progressive diminution of source melting and a decrease in the temperature of erupted melts in the latest stages of volcanic activity. We interpret these changes to primarily reflect the progressive migration of the oceanic island out of the melting region or hotspot.

Transcriptional repression of peroxisome proliferator-activated receptor beta/delta in murine keratinocytes by CCAAT/enhancer-binding proteins.

The roles of peroxisome proliferator-activated receptors (PPARs) and CCAAT/enhancer-binding proteins (C/EBPs) in keratinocyte and sebocyte differentiation suggest that both families of transcription factors closely interact in the skin. Initial characterization of the mouse PPARbeta promoter revealed an AP-1 site that is crucial for the regulation of PPARbeta expression in response to inflammatory cytokines in the skin. We now present evidence for a novel regulatory mechanism of the expression of the PPARbeta gene by which two members of the C/EBP family of transcription factors inhibit its basal promoter activity in mouse keratinocytes. We first demonstrate that C/EBPalpha and C/EBPbeta, but not C/EBPdelta, inhibit the expression of PPARbeta through the recruitment of a transcriptional repressor complex containing HDAC-1 to a specific C/EBP binding site on the PPARbeta promoter. Consistent with this repression, the expression patterns of PPARbeta and C/EBPs are mutually exclusive in keratinocytes of the interfollicular epidermis and hair follicles in mouse developing skin. This work reveals the importance of the regulatory interplay between PPARbeta and C/EBP transcription factors in the control of proliferation and differentiation in this organ. Such insights are crucial for the understanding of the molecular control regulating the balance between proliferation and differentiation in many cell types including keratinocytes.

Contribution of electrostatic interactions, compactness and quaternary structure to protein thermostability: lessons from structural genomics of Thermotoga maritima.

Studies of the structural basis of protein thermostability have produced a confusing picture. Small sets of proteins have been analyzed from a variety of thermophilic species, suggesting different structural features as responsible for protein thermostability. Taking advantage of the recent advances in structural genomics, we have compiled a relatively large protein structure dataset, which was constructed very carefully and selectively; that is, the dataset contains only experimentally determined structures of proteins from one specific organism, the hyperthermophilic bacterium Thermotoga maritima, and those of close homologs from mesophilic bacteria. In contrast to the conclusions of previous studies, our analyses show that oligomerization order, hydrogen bonds, and secondary structure play minor roles in adaptation to hyperthermophily in bacteria. On the other hand, the data exhibit very significant increases in the density of salt-bridges and in compactness for proteins from T.maritima. The latter effect can be measured by contact order or solvent accessibility, and network analysis shows a specific increase in highly connected residues in this thermophile. These features account for changes in 96% of the protein pairs studied. Our results provide a clear picture of protein thermostability in one species, and a framework for future studies of thermal adaptation.

Experience and endocrine stress responses in neonatal and pediatric critical care nurses and physicians.

OBJECTIVE: Critical care is a working environment with frequent exposure to stressful events. High levels of psychological stress have been associated with increased prevalence of burnout. Psychological distress acts as a potent trigger of cortisol secretions. We attempted to objectify endocrine stress reactivity. DESIGN: Observational cohort study during two 12-day periods in successive years. SETTING: A tertiary multidisciplinary neonatal and pediatric intensive care unit (33 beds). SUBJECTS: One hundred and twelve nurses and 27 physicians (94% accrual rate). INTERVENTIONS AND MEASUREMENTS: Cortisol determined from salivary samples collected every 2 hrs and after stressful events. Participants recorded the subjective perception of stress with every sample. Endocrine reactions were defined as transient surges in cortisol of >50% and 2.5 nmol/L over the baseline. MAIN RESULTS: During 7,145 working hours, we observed 474 (12.5%) endocrine reactions from 3,781 samples. The mean cortisol increase amounted to 10.6 nmol/L (219%). The mean occurrence rate of endocrine reactions per subject and sample was 0.159 (range, 0-0.43). Although the mean raw cortisol levels were lower in experienced team members (>3 yrs of intensive care vs. <3 yrs, 4.1 vs. 4.95 nmol/L, p < .001), professional experience failed to attenuate the frequency and magnitude of endocrine reactions, except for the subgroup of nurses and physicians with >8 yrs of intensive care experience. A high proportion (71.3%) of endocrine reactions occurred without conscious perception of stress. Unawareness of stress was higher in intensive care nurses (75.1%) than in intermediate care nurses (51.8%, p < .01). CONCLUSIONS: Stress-related cortisol surges occur frequently in neonatal and pediatric critical care staff. Cortisol increases are independent of subjective stress perception. Professional experience does not abate the endocrine stress reactivity.

Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB.

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.

La douleur prolongée chez le nouveau-né: étude de cas [Prolonged pain in neonates: retrospective analysis].

INTRODUCTION: infants hospitalised in neonatology are inevitably exposed to pain repeatedly. Premature infants are particularly vulnerable, because they are hypersensitive to pain and demonstrate diminished behavioural responses to pain. They are therefore at risk of developing short and long-term complications if pain remains untreated. CONTEXT: compared to acute pain, there is limited evidence in the literature on prolonged pain in infants. However, the prevalence is reported between 20 and 40 %. OBJECTIVE : this single case study aimed to identify the bio-contextual characteristics of neonates who experienced prolonged pain. METHODS : this study was carried out in the neonatal unit of a tertiary referral centre in Western Switzerland. A retrospective data analysis of seven infants' profile, who experienced prolonged pain ,was performed using five different data sources. RESULTS : the mean gestational age of the seven infants was 32weeks. The main diagnosis included prematurity and respiratory distress syndrome. The total observations (N=55) showed that the participants had in average 21.8 (SD 6.9) painful procedures that were estimated to be of moderate to severe intensity each day. Out of the 164 recorded pain scores (2.9 pain assessment/day/infant), 14.6 % confirmed acute pain. Out of those experiencing acute pain, analgesia was given in 16.6 % of them and 79.1 % received no analgesia. CONCLUSION: this study highlighted the difficulty in managing pain in neonates who are exposed to numerous painful procedures. Pain in this population remains underevaluated and as a result undertreated.Results of this study showed that nursing documentation related to pain assessment is not systematic.Regular assessment and documentation of acute and prolonged pain are recommended. This could be achieved with clear guidelines on the Assessment Intervention Reassessment (AIR) cyclewith validated measures adapted to neonates. The adequacy of pain assessment is a pre-requisite for appropriate pain relief in neonates.