ESCMID postgraduate technical workshop on intracellular bacteria: from biology to clinic.

Infection by intracellular bacteria can lead to several diseases in both veterinary and human medicine. Unfortunately, the biology of these intracellular bacteria is highly complex due to their interactions with their host cells. Thus, it is very important to develop several tools in order to better understand the complex intracellular life of these pathogens, so allowing to improve the diagnosis options and the treatments of infectious diseases that they are causing. The workshop organised in Villars-sur-Ollon (Switzerland) by the ESCMID Study group on intracellular bacteria was a good opportunity to enhance our knowledge on these fastidious pathogens. During 5 days, 15 speakers gave 41 talks, covering all fields, from biology to clinic of different intracellular bacteria such as Bartonella, Chlamydia, Coxiella, Ehrlichia, Listeria, Parachlamydia, Rickettsia, and Waddlia. The format of this postgraduate course, which took place in the Swiss mountains, allowed interactive sessions and living discussions between the participants coming from all around the world. One of the major strength was to gather epidemiologists, clinical microbiologists, infectious diseases specialists, entomologists, veterinarians as well as bioinformaticians, biochemists and biologists to deliver a unique "one-health science" on intracellular bacteria. Here, we summarise the main take-home messages delivered during this meeting.

The European Board of Physical and Rehabilitation Medicine : the past, the present and the future [Europejska Rada Medycyny Fizykalnej i Rehabilitacji: przeszłość, teraźniejszość i perspektywy]

Right from the beginning of the development of the medical specialty of Physical and Rehabilitation Medicine (PRM) the harmonization of the fields of competence and the specialist training across Europe was always an important issue. The initially informal European collaboration was formalized in 1963 under the umbrella of the European Federation of PRM. The European Academy of PRM and the UEMS section of PRM started to contribute in 1969 and 1974 respectively. In 1991 the European Board of Physical and Rehabilitation Medicine (EBPRM) was founded with the specific task of harmonizing education and training in PRM in Europe. The EBPRM has progressively defined curricula for the teaching of medical students and for the postgraduate education and training of PRM specialists. It also created a harmonized European certification system for medical PRM specialists, PRM trainers and PRM training sites. European teaching initiatives for PRM trainees (European PRM Schools) were promoted and learning material for PRM trainees and PRM specialists (e-learning, books and e-books, etc.) was created. For the future the Board will have to ensure that a minimal specific undergraduate curriculum on PRM based on a detailed European catalogue of learning objectives will be taught in all medical schools in Europe as a basis for the general medical practice. To stimulate the harmonization of national curricula, the existing postgraduate curriculum will be expanded by a syllabus of competencies related to PRM and a catalogue of learning objectives to be reached by all European PRM trainees. The integration of the certifying examination of the PRM Board into the national assessment procedures for PRM specialists will also have to be promoted.

Prevalência da incontinência urinária em adultos e idosos hospitalizados

Este estudo objetivou verificar a prevalência da incontinência urinária em pacientes hospitalizados e identificar as associações estatísticas existentes entre os índices obtidos e algumas variáveis demográficas e clínicas da clientela. Os dados foram colhidos no Hospital Universitário da USP, junto a 77 pacientes internados em três diferentes clínicas. Os resultados indicaram prevalências total de 35% e parciais de 48%, 37% e 22% nas Clínicas Cirúrgica, Obstétrica e Médica, respectivamente. Correlações estatisticamente significativas foram verificadas entre a prevalência e disúria (r=0,19 e p=0,046), infecções urinárias (r=0,24 e p=0,019), tempo de internação (r=-0,32 e p=0,002) e sexo masculino (r=-0,27 e p=0,008).

A hierarchical approach to model parameter optimization for developmental systems.

In the context of Systems Biology, computer simulations of gene regulatory networks provide a powerful tool to validate hypotheses and to explore possible system behaviors. Nevertheless, modeling a system poses some challenges of its own: especially the step of model calibration is often difficult due to insufficient data. For example when considering developmental systems, mostly qualitative data describing the developmental trajectory is available while common calibration techniques rely on high-resolution quantitative data. Focusing on the calibration of differential equation models for developmental systems, this study investigates different approaches to utilize the available data to overcome these difficulties. More specifically, the fact that developmental processes are hierarchically organized is exploited to increase convergence rates of the calibration process as well as to save computation time. Using a gene regulatory network model for stem cell homeostasis in Arabidopsis thaliana the performance of the different investigated approaches is evaluated, documenting considerable gains provided by the proposed hierarchical approach.

Les carcinomes adénosquameux de la sphère ORL : à propos de 20 cas et revue de la littérature

Le but de cette étude rétrospective et descriptive était de déterminer les aspects cliniques et anatomopathologiques ainsi que les modes de presentation et de récidive des carcinomes adénosquameux de la sphere ORL, traités de manière curative, et recensés entre le 1er janvier 1989 et le 31 décembre 2010 au sein des Institutions du Rare Cancer Network. Nous avons retenu 20 cas de patients traités par chirurgie (S), et/ou radiothérapie (RT), avec ou sans chimiothérapie (CT) concomitante. L'âge médian était de 59.5 ans au moment du diagnostic (étendue, 48-73). La classification selon le TNM montrait des stades avancés pour la majorité des patients, avec un, deux, cinq et 11 patients présentant respectivement une Uimeur de stade I, II, III, et IVa. Les sites anatomiques incriminés étaient la cavité orale (n=4), l'oropharynx (n=5), Phypopharynx (n=2), le larynx (n2), les glandes salivaires (n=2), le vestibule nasal (n=2), les sinus maxillaires (n=2) et enfin le nasopharynx (n=l). Seize patients ont bénéficié d'une chirurgie, et 17 d'un traitement combiné (S+RT chez 13, RT+CT chez deux, et les trois modalités chez les deux derniers patients). Apres un suivi médian de 16 mois (étendue, 9-62), 3, 1, 1, 1,2 and 4 patients ont développé une récidive à distance, régionale, locale, locorégionale, locorégionale + à distance, et régionale + à distance. Toutes les récidives locales sont survenues dans le champ d'irradiation. Au dernier suivi, neuf patients étaient vivants sans maladie. La survie globale, la survie sans maladie, et le contrôle locorégional médians et à 3 ans étaient respectivement de 39 mois et 52% (95%[CI]:28-75%), 12 mois et 32% (95%[CI]: 11-54%) et enfin 33 mois et 47% (95%[CI]:20-74%). L'analyse multivariée a montré que la survie sans maladie était inversement corrélée à la présence d'effractions capsulaires (p=0.01) et aux stades avancés (IV versus I-III, p=0.002). D'une manière générale, nous avons confirmé que le pronostic global des carcinomes adénosquameux de la sphère ORL est sombre, ceci étant majoritairement dû à la survenue précoce de métastases ganglionnaires et à distance, lesquelles surviennent chez plus de la moitié des patients. En revanche, nous avons pu montrer que le contrôle local obtenu par un traitement combiné de radio-chimiothérapie permet aux patients diagnostiqués à un stade précoce de bénéficier d'une survie sans maladie tout à fait favorable.

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial.

BACKGROUND: The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue. METHODS: We performed a multicentre, parallel, randomized controlled, closed-label, observer-blinded trial. We recruited from the practices of 44 primary care physicians in France from March to July 2006. We randomly assigned 198 women aged 18-53 years who complained of fatigue and who had a ferritin level of less than 50 ug/L and hemoglobin greater than 12.0 g/dL to receive either oral ferrous sulfate (80 mg of elemental iron daily; n = 102) or placebo (n = 96) for 12 weeks. The primary outcome was fatigue as measured on the Current and Past Psychological Scale. Biological markers were measured at 6 and 12 weeks. RESULTS: The mean score on the Current and Past Psychological Scale for fatigue decreased by 47.7% in the iron group and by 28.8% in the placebo group (difference -18.9%, 95% CI -34.5 to -3.2; p = 0.02), but there were no significant effects on quality of life (p = 0.2), depression (p = 0.97) or anxiety (p = 0.5). Compared with placebo, iron supplementation increased hemoglobin (0.32 g/dL; p = 0.002) and ferritin (11.4 μg/L; p < 0.001) and decreased soluble transferrin receptor (-0.54 mg/L; p < 0.001) at 12 weeks. INTERPRETATION: Iron supplementation should be considered for women with unexplained fatigue who have ferritin levels below 50 μg/L. We suggest assessing the efficiency using blood markers after six weeks of treatment. Trial registration no. EudraCT 2006-000478-56.

Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis.

OBJECTIVES: Gender differences in psychotic disorder have been observed in terms of illness onset and course; however, past research has been limited by inconsistencies between studies and the lack of epidemiological representative of samples assessed. Thus, the aim of this study was to elucidate gender differences in a treated epidemiological sample of patients with first episode psychosis (FEP). METHODS: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics of 661 FEP consecutive patients treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. RESULTS: Prior to onset of psychosis, females were more likely to have a history of suicide attempts (p=.011) and depression (p=.001). At service entry, females were more likely to have depressive symptoms (p=.007). Conversely, males had marked substance use problems that were evident prior to admission (p<.001) and persisted through treatment (p<.001). At service entry, males also experienced more severe psychopathology (p<.001) and lower levels of functioning (GAF, p=.008; unemployment/not studying p=.004; living with family, p=.003). Treatment non-compliance (p<.001) and frequent hospitalisations (p=.047) were also common for males with FEP. At service discharge males had significantly lower levels of functioning (GAF, p=.008; unemployment/not studying p=.040; living with family, p=.001) compared to females with FEP. CONCLUSIONS: Gender differences are evident in illness course of patients with FEP, particularly with respect to past history of psychopathology and functioning at presentation and at service discharge. Strategies to deal with these gender differences need to be considered in early intervention programs.

Is a pre-anaesthetic information form really useful ?

Background: All patients should be fully informed about the risks and benefits of anaesthetic procedures before giving a written consent. Moreover, the satisfaction level may vary in proportion to the information given. We aimed to determine, in a single-blind randomized-controlled study, whether an information form given before the pre-anaesthetic consultation could improve perceived information, information gain and satisfaction level. Methods: Two hundred patients ASA 1-3 scheduled for an elective orthopaedic surgery were randomized into two groups: a group that received an information form before the pre-anaesthetic consultation (IF group) and a control group (no information form). A standardized questionnaire was submitted after the pre-anaesthetic consultation and after the operation. This 17-item questionnaire explored perceived information (five items), information gain (three items) and satisfaction level (nine items). The items of each topic were pooled and compared between groups. Results: One hundred and eighty-five patients (92.5%) completed the study. The IF group had better perceived information (IF group 73% vs. control group 63%, P=0.002), higher information gain (IF group 75% vs. control group 62%, P=0.001) and a higher satisfaction level (IF group 95% vs. control group 92%, P=0.048). Conclusions: Our study suggests that an information form given before the pre-anaesthetic consultation enhances perceived information, information gain and satisfaction level. Méthode Cette étude prospective randomisée en simple aveugle a été conduite à l'hôpital Orthopédique du Centre Hospitalier Universitaire Vaudois. Deux cents patients prévus pour une chirurgie élective orthopédique ont été recrutés entre avril et juin 2008 et repartis en deux groupes selon une table de randomisation : un groupe recevait une feuille d'information 30 minutes avant la consultation préanesthésique, et l'autre pas. Les patients des deux groupes étaient ensuite examinés à la consultation preoperatoire par un anesthésiste indépendant de l'étude, puis recevaient un questionnaire standardisé. Ce questionnaire, issu de questionnaires existants, et validé préalablement sur un échantillon de 50 patients, comportait 17 questions qui exploraient la perception- de l'information (5 questions), le gain d'information (3 questions) et le niveau de satisfaction (9 questions) Parmi ces 17 questions, 3 étaient posées 24 h après l'intervention chirurgicale lors d'une visite dans la chambre ou lors d'un contact téléphonique. Les réponses étaient analysées et comparées entre les deux groupes. Résultats Cent huitante-cinq patients ont terminé l'étude. Le groupe qui a reçu la feuille d'information avait une meilleure perception de l'information (73% vs 63% dans le groupe de contrôle, ρ = 0 002) un gain d'information plus élevé (75% vs. 62% dans le groupe de contrôle, ρ = 0.001) et un niveau de satisfaction plus élevé (95% vs. 92% dans le groupe de contrôle, ρ= 0.048). Discussion et conclusion Cette étude a permis de démontrer que la remise d'une feuille d'information explicative avant la consultation préanesthésique était un moyen simple et bon marché pour améliorer la perception de l'information et le niveau de satisfaction.

Molecular phylogenetics of shrews (Mammalia: Soricidae) reveal timing of transcontinental colonizations.

We sequenced 2167 base pairs (bp) of mitochondrial DNA cytochrome b and 16S, and 1390 bp of nuclear genes BRCA1 and ApoB in shrews taxa (Eulipotyphla, family Soricidae). The aim was to study the relationships at higher taxonomic levels within this family, and in particular the position of difficult clades such as Anourosorex and Myosorex. The data confirmed two monophyletic subfamilies, Soricinae and Crocidurinae. In the former, the tribes Anourosoricini, Blarinini, Nectogalini, Notiosoricini, and Soricini were supported. The latter was formed by the tribes Myosoricini and Crocidurini. The genus Suncus appeared to be paraphyletic and included Sylvisorex. We further suggest a biogeographical hypothesis, which shows that North America was colonized by three independent lineages of Soricinae during middle Miocene. Our hypothesis is congruent with the first fossil records for these taxa. Using molecular dating, the first exchanges between Africa and Eurasia occurred during the middle Miocene. The last one took place in the Late Miocene, with the dispersion of the genus Crocidura through the old world.

PPARdelta/beta: the lobbyist switching macrophage allegiance in favor of metabolism.

Macrophages, which belong to the immune system, are increasingly being recognized for their contribution to metabolic regulation. In two studies by Kang et al. (2008) and Odegaard et al. (2008) in this issue of Cell Metabolism, we learn that alternative activation (M2a) of resident macrophages in liver and adipose tissue depends highly on PPARdelta/beta activity, leading to improved fatty acid metabolism and insulin sensitivity.

Prenatal ultrasonographic detection of gastrointestinal obstruction: results from 18 European congenital anomaly registries.

OBJECTIVES: We evaluated the prenatal detection of gastrointestinal obstruction (GIO, including atresia, stenosis, absence or fistula) by routine ultrasonographic examination in an unselected population all over Europe. METHODS: Data from 18 congenital malformation registries in 11 European countries were analysed. These multisource registries used the same methodology. All fetuses/neonates with GIO confirmed within 1 week after birth who had prenatal sonography and were born during the study period (1 July 1996 to 31 December 1998) were included. RESULTS: There were 670 793 births in the area covered and 349 fetuses/neonates had GIO. The prenatal detection rate of GIO was 34%; of these 40% were detected < or = 24 weeks of gestation (WG). A total of 31% (60/192) of the isolated GIO were detected prenatally, as were 38% (59/157) of the associated GIO (p=0.26). The detection rate was 25% for esophageal obstruction (31/122), 52% for duodenal obstruction (33/64), 40% for small intestine obstruction (27/68) and 29% for large intestine obstruction (28/95) (p=0.002). The detection rate was higher in countries with a policy of routine obstetric ultrasound. Fifteen percent of pregnancies were terminated (51/349). Eleven of these had chromosomal anomalies, 31 multiple malformations, eight non-chromosomal recognized syndromes, and one isolated GIO. The participating registries reflect the various national policies for termination of pregnancy (TOP), but TOPs after 24 WG (11/51) do not appear to be performed more frequently in countries with a liberal TOP policy. CONCLUSION: This European study shows that the detection rate of GIO depends on the screening policy and on the sonographic detectability of GIO subgroups.

Anachronistic facies from a drowned Lower Triassic carbonate platform: Lower member of the Alwa Formation (Ba'id Exotic), Oman Mountains

- The lower member of the Alwa Formation (Lower Olenekian), found within the Ba'id Exotic in the Oman Mountains (Sultanate of Oman), consists of ammonoid-bearing, pelagic limestones that were deposited on an isolated, drowned carbonate platform on the Neotethyan Gondwana margin. The strata contain a variety of unusual carbonate textures and features, including thrombolites, Frutexites-bearing microbialites that contain synsedimentary cements, matrix-free breccias surrounded by isopachous calcite cement, and fissures and cavities filled with large botryoidal cements. Thrombolites are found throughout the study interval, and occur as 0.5-1.0 m thick lenses or beds that contain laterally laterally-linked stromatactis cavities. The Frutexites-bearing microbialites occur less frequently, and also form lenses or beds, up to 30 cm thick; the microbialites may be laminated, and often developed on hardgrounds. In addition, the Frutexites-bearing microbialites also contain synsedimentary calcite cement crusts and botryoids (typically <1 cm thick) that harbour layers or pockets of what appear to be bacterial sheaths and coccoids, and are indicative of biologically mediated precipitation of the cement bodies. Slumping following lithification led to fracturing of the limestone and the precipitation of large, botryoidal aragonite cements in fissures that cut across the primary fabric. Environmental conditions, specifically palaeoxygenation and the degree of calcium carbonate supersaturation, likely controlled whether the thrombolites (high level of calcium carbonate supersaturation associated with vertical mixing of water masses and dysoxic conditions) or Frutexites-bearing microbialites (low level of calcium carbonate supersaturation associated with anoxic conditions and deposition below a stable chemocline) formed. The results of this study point to continued environmental stress in the region during the Early Triassic that likely contributed to the uneven recovery from the Permian-Triassic mass extinction.

Increased EBV Reactivation in the Cerebrospinal Fluid of Patients with Early Multiple Sclerosis

Epstein-Barr virus (EBV) has been consistently associated with multiple sclerosis (MS), but whether this virus is a trigger of MS remains undetermined. Recently, EBV-infected B cells recognized by activated CD8_ T cells have been detected in the meninges of autopsied MS patients. In addition, a strong EBV-specific CD8_ T cell response in the blood of patients with MS of recent onset was reported. Here, to further explore the putative relationship between MS and EBV, we assessed the EBV-specific cellular and humoral immune responses in the blood and the cerebrospinal fluid (CSF) of patients with early MS or other neurological diseases, separated into inflammatory (IOND) and non-inflammatory (NIOND) groups. The MS non-associated neurotropic herpesvirus cytomegalovirus (CMV) served as a control. Fifty-eight study subjects were enrolled, including 44 patients (13 with early MS (onset of MS less than one year prior to the assay), 15 with IOND and 16 with NIOND) in the immunological arm of the study. The cellular immune response was investigated using a functional CFSE cytotoxic T lymphocyte (CTL) assay performed with short-term cultured EBV- or CMVspecific effector T cells from the CSF and the blood. The humoral immune response specific for these two viruses was also examined in both the blood and the CSF. The recruitment of a given virusspecific antibody in the CSF as compared to the blood was expressed as antibody indexes (AI). We found that, in the CSF of early MS patients, there was an enrichment in EBV-, but not CMV-specific, CD8_ CTL as compared to the CSF of IOND (P_ 0.003) and NIOND patients (P_0.0009), as well as compared to paired blood samples (P_0.005). Additionally, relative viral capsid antigen (VCA)-, but not EBV encoded nuclear antigen 1 (EBNA1)- or CMV-specific, AI were increased in the CSF of early MS as compared to IOND (P_0.002) or NIOND patients (P_0.008) and correlated with the EBVspecific CD8_ CTL responses in the CSF (rs_0.54, P_0.001). Fourteen additional patients were enrolled in the virological arm of the study: using semi-nested PCR, EBV-encoded nuclear RNA1 (EBER1)-a transcript expressed during all stages of EBV infection-was detected in the CSF of 2/4 early MS, but only 1/6 IOND and 0/4 NIOND patients. Altogether, our data suggest that a reactivation of EBV, but not CMV, is taking place in the central nervous system of patients with MS of recent onset. These data significantly strengthen the link between EBV and MS and may indicate a triggering role of EBV in this disease. This work was supported by grants from the Swiss National Foundation and from the Swiss Society for Multiple Sclerosis.

Decision-support tools to manage drug incompatibilities: evaluation by nurses

Introduction Preventing drug incompatibilities has a high impact onthe safety of drug therapy. Although there are no internationalguidelines to manage drug incompatibilities, different decision-supporttools such as handbooks, cross-tables and databases are available.In a previous study, two decision-support tools have been pre-selectedby pharmacists as fitting nurses' needs on the wards1. The objective ofthis study was to have these both tools evaluated by nurses todetermine which would be the most suitable for their daily practice.Materials & Methods Evaluated tools were:1. Cross-table of drug pairs (http://files.chuv.ch/internet-docs/pha/medicaments/pha_phatab_compatibilitessip.pdf)2. Colour-table (a colour for each drug according to the pH: red =acid; blue = basic; yellow = neutral; black = to be infused alone)2Tools were assessed by 48 nurses in 5 units (PICU, adult andgeriatric intensive care, surgery, onco-hematology) using a standardizedform1. The scientific accuracy of the tools was evaluated bydetermining the compatibility of five drugs pairs (rate of correctanswers according to the Trissel's Handbook on Injectable Drugs,chi-square test). Their ergonomics, design, reliability and applicabilitywere estimated using visual analogue scales (VAS 0-10; 0 =null, 10 = excellent). Results are expressed as the median and interquartilerange (IQR) for 25% and 75% (Wilcoxon rank sum test).Results The rate of correct answers was above 90% for both tools(cross-table 96.2% vs colour-table 92.5%, p[0.05).The ergonomics and the applicability were higher for the crosstable[7.1 (IQR25 4.0, IQR75 8.0) vs 5.0 (IQR25 2.7, IQR75 7.0), p =0.025 resp. 8.3 (IQR25 7.4, IQR75 9.2) vs 7.6 (IQR25 5.9, IQR75 8.8)p = 0.047].The design of the colour-table was judged better [4.6 (IQR25 2.9,IQR75 7.1) vs 7.1 (IQR25 5.4, IQR75 8.4) p = 0.002].No difference was observed in terms of reliability [7.3 (IQR25 6.5,IQR75 8.4) vs 6.7 (IQR25 5.0, IQR758.6) p[0.05].The cross-table was globally preferred by 65% of the nurses (27%colour-table, 8% undetermined) and 68% would like to have thisdecision-support tool available for their daily practice.Discussion & Conclusion Both tools showed the same accuracy toassess drug compatibility. In terms of ergonomics and applicabilitythe cross-table was better than the colour-table, and was preferred bythe nurses for their daily practice. The cross-table will be implementedin our hospital as decision-support tool to help nurses tomanage drug incompatibilities.

Usefulness of intra-articular bupivacain and lidocain adjunction in MR or CT arthrography: a prospective study in 148 patients.

PURPOSE: To evaluate the influence of shorter- and longer-acting intra-articular anaesthetics on post-arthrographic pain. MATERIALS AND METHODS: 154 consecutive patients investigated by MR or CT arthrographies were randomly assigned to one of the following groups: 1--intra-articular contrast injection only; 2--lidocain 1% adjunction; or 3--bupivacain 0.25% adjunction. Pain was assessed before injection, at 15 min, 4 h, 1 day and 1 week after injection by visual analogue scale (VAS). RESULTS: At 15 min, early mean pain score increased by 0.96, 0.24 and 0 in groups 1, 2 and 3, respectively. Differences between groups 1 & 3 and 1 & 2 were statistically significant (p=0.003 and 0.03, respectively), but not between groups 2 & 3 (p=0.54). Delayed mean pain score increase was maximal at 4 h, reaching 1.60, 1.22 and 0.29 in groups 1, 2 and 3, respectively. Differences between groups 1 & 2 and 2 & 3 were statistically significant (p=0.002 and 0.02, respectively), but not between groups 1 & 2 (p=0.46). At 24 h and 1 week, the interaction of local anaesthetics with increase in pain score was no longer significant. Results were independent of age, gender and baseline VAS. CONCLUSION: Intra-articular anaesthesia may significantly reduce post-arthrographic pain. Bupivacain seems to be more effective than lidocain to reduce both early and delayed pain.