From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase.

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website ( http://www.uniprot.org/ ). It also evokes precautions that are necessary for successful predictions and extrapolations.

Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins.

An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure alpha-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb.

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

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

Evaluation of the compliance with recommended procedures in newborns exposed to HBsAg-positive mothers: a multicenter collaborative study.

BACKGROUND: Maternal-infant transmission of hepatitis B virus (HBV) during birth carries a high risk for chronic HBV infection in infants with frequent subsequent development of chronic disease. This can be efficiently prevented by early immunization of exposed newborns. The purpose of this study was to determine the compliance with official recommendations for prevention of perinatal HBV transmission in hepatitis B surface antigen (HBsAg) exposed infants. METHODS: Records of pregnant women at 4 sites in Switzerland, admitted for delivery in 2005 and 2006, were screened for maternal HBsAg testing. In HBsAg-exposed infants, recommended procedures (postnatal active and passive immunization, completion of immunization series, and serological success control) were checked. RESULTS: Of 27,131 women tested for HBsAg, 194 (0.73%) were positive with 196 exposed neonates. Of these neonates, 143 (73%) were enrolled and 141 (99%) received simultaneous active and passive HBV immunization within 24 hours of birth. After discharge, the HBV immunization series was completed in 83%. Only 38% of children were tested for anti-HBs afterwards and protective antibody values (>100 U/L) were documented in 27% of the study cohort. No chronically infected child was identified. Analysis of hospital discharge letters revealed significant quality problems. CONCLUSIONS: Intensified efforts are needed to improve the currently suboptimal medical care in HBsAg-exposed infants. We propose standardized discharge letters, as well as reminders to primary care physicians with precise instructions on the need to complete the immunization series in HBsAg-exposed infants and to evaluate success by determination of anti-HBs antibodies after the last dose.

Qui utilise les crèches en Suisse ? : logiques sociales du recours aux structures d'accueil collectif pour la petite enfance

Depuis quelque temps, de plus en plus de spécialistes de la politique sociale préconisent une stratégie d'investissement social dans laquelle les crèches joueraient un rôle majeur. Cette stratégie vise à prévenir les exclusions sociales par la promotion de l'égalité des chances et de l'accès à l'emploi en vue d'un allègement des dépenses de protection sociale passive. Outre qu'elles permettent aux familles d'avoir deux revenus, les crèches ont en effet l'avantage de réduire les écarts au niveau des compétences cognitives et linguistiques entre les enfants venant de différents milieux sociaux. Mais le succès d'une telle stratégie présuppose que certains publics cibles recourent effectivement aux crèches, à savoir les ménages disposant d'un faible revenu ou/et de niveau de formation, ainsi que les familles issues de l'immigration. Or, des analyses statistiques sur la base de l'Enquête suisse sur la population active (ESPA) de 2008 montrent que, pour les familles en Suisse, les chances d'utiliser une crèche augmentent avec le niveau de formation des parents. Concernant plus particulièrement le niveau de formation des mères, ce phénomène n'est d'ailleurs que partiellement conditionné par le taux d'activité supérieur de celles ayant accompli une formation de degré tertiaire. En outre, certaines populations d'immigrés dont l'intégration dans la société suisse est réputée difficile sont peu disposées à recourir aux crèches. Les immigrés de première génération de quasiment toutes les origines fortement représentées en Suisse ont en revanche plus de chances que les parents d'origine suisse de faire appel au service d'une crèche à raison d'au moins 4 jours/semaine, ce qui peut influer négativement sur le comportement de l'enfant. Ce dernier résultat semble paradoxal mais montre qu'une migration rend plus difficile l'organisation d'une garde informelle comme solution complémentaire à la crèche. En synthèse, la présente étude attire l'attention sur le fait que les atouts pédagogiques et socialisants des crèches reviennent avant tout aux enfants de parents d'origine suisse ou venant de pays culturellement proches et ayant un niveau de formation supérieur. Telle que conçue actuellement, l'offre de crèches en Suisse ne semble guère opérer comme un instrument efficace de l'investissement social. Immer mehr Experten der Sozialpolitik empfehlen eine ,,Strategie der sozialen Investitionen", die den Kindertagesstätten (bzw. Kinderkrippen) eine wichtige Rolle zuschreibt. Ziel dieser Strategie ist es, durch Förderung von Chancengleichheit und Arbeitsmarktpartizipation sozialen Ausgrenzungen vorzubeugen, um Einsparungen im Bereich der passiven Sozialleistungen zu ermöglichen. Krippen haben einerseits den Vorteil, dass sie es den Familien ermöglichen, zwei Einkommen zu erzielen. Andererseits tragen sie zur Minderung von kognitiven und sprachlichen Fähigkeitsunterschieden zwischen Vorschulkindern aus verschiedenen sozialen Milieus bei. Der Erfolg dieser Strategie setzt jedoch voraus, dass gewisse Zielgruppen tatsächlich Krippen nutzen, nämlich bezüglich Einkommen und/oder Bildung benachteiligte Haushalte sowie Familien mit Migrationshintergrund. Die vorliegenden statistischen Analysen aufgrund der SAKE-Daten von 2008 (Schweizerische Arbeitskräfteerhebung) ergeben jedoch für die Schweiz, dass die Wahrscheinlichkeit, eine Krippe zu nutzen, mit dem Bildungsniveau der Eltern steigt. Was das Bildungsniveau der Mütter im Besonderen anbelangt, ist dieses Phänomen nur teilweise bedingt durch den tendenziell höheren Beschäftigungsgrad der besser Ausgebildeten. Zudem haben einige Migrantengruppen, deren Integration in die Schweizer Gesellschaft als besonders schwierig betrachtet wird, eine bedeutend tiefere Benützungswahrscheinlichkeit als Eltern Schweizer Herkunft. Für fast alle in der Schweiz stark vertretenen Migranten erster Generation ist dennoch das statistische Risiko grösser, die Krippe während mindestens 4 Tagen/Woche zu nutzen, was einen negativen Einfluss auf das Verhalten des Kindes haben kann. Dieses scheinbar paradoxe Ergebnis ist darauf zurückzuführen, dass ein Migrationshintergrund das Organisieren von krippenergänzenden Betreuungslösungen informeller Art meist erschwert. Gesamthaft zeigt die vorliegende Studie auf, dass die positiven pädagogischen und sozialisierenden Effekte der Krippen in erster Linie Kindern zugutekommen, deren Eltern eine höhere Ausbildung haben, Schweizer Herkunft sind oder aus einem kulturell nahestehenden Land kommen. So wie es gegenwärtig eingerichtet ist, scheint das Krippenangebot in der Schweiz kaum als effizientes Instrument sozialer Investitionen zu wirken.

Collaborative quality improvement to manage pain in acute care hospitals.

Objective. Collaborative quality improvement programs have been successfully used to manage chronic diseases in adults and acute lung complications in premature infants. Their effectiveness to improve pain management in acute care hospitals is currently unknown. The purpose of this study was to determine whether a collaborative quality improvement program implemented at hospital level could improve pain management and overall pain relief. Design.To assess the effectiveness of the program, we performed a before-after trial comparing patient's self-reported pain management and experience before and after program implementation. We included all adult patients hospitalized for more than 24 hours and discharged either to their home or to a nursing facility, between March 1, 2001 and March 31, 2001 (before program implementation) and between September 15, 2005 and October 15, 2005 (after program implementation). Setting.A teaching hospital of 2,096 beds in Geneva, Switzerland. Patients.All adult patients hospitalized for more than 24 hours and discharged between 1 to 31 March 2001 (before program) and 15 September to 15 October 2005 (after program implementation). Interventions.Implementation of a collaborative quality improvement program using multifaceted interventions (staff education, opinion leaders, patient education, audit, and feedback) to improve pain management at hospital level. Outcome Measures.Patient-reported pain experience, pain management, and overall hospital experience based on the Picker Patient Experience questionnaire, perceived health (SF-36 Health survey). Results.After implementation of the program only 2.3% of the patients reported having no pain relief during their hospital stay (vs 4.5% in 2001, P = 0.05). Among nonsurgical patients, improvements were observed for pain assessment (42.3% vs 27.9% of the patients had pain intensity measured with a visual analog scale, P = 0.012), pain management (staff did everything they could to help in 78.9% vs 67.9% of cases P = 0.003), and pain relief (70.4% vs 57.3% of patients reported full pain relief P = 0.008). In surgical patients, pain assessment also improved (53.7.3% vs 37.6%) as well as pain treatment. More patients received treatments to relieve pain regularly or intermittently after program implementation (95.1% vs 91.9% P = 0.046). Conclusion.Implementation of a collaborative quality improvement program at hospital level improved both pain management and pain relief in patients. Further studies are needed to determine the overall cost-effectiveness of such programs.