Adherence of Abiotrophia defectiva and Granulicatella species to fibronectin: is there a link with endovascular infections?

During a 6-year period, we isolated three Abiotrophia defectiva, six Granulicatella adiacens and two G. 'para-adiacens' strains from clinical specimens. All A. defectiva strains were isolated from immunocompetent patients with endovascular infections, whereas the Granulicatella spp. strains were isolated from immunosuppressed patients with primary bacteremia. As the capacity of bacteria to adhere to the host extracellular matrix (ECM) has been implicated in the pathogenesis of endovascular infection, we investigated the ability of A. defectiva and Granulicatella spp. isolates to bind different ECM components immobilized in microtiter plates. Adherence tests showed a strong attachment of A. defectiva strains to fibronectin, whereas Granulicatella spp. strains were not adherent. The poor adherence of Granulicatella spp. strains to the ECM could be correlated with a lower propensity to induce endocarditis.

Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures.

To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.

From the Cover: Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination.

The ability of vaccines to induce memory cytotoxic T-cell responses in the lung is crucial in stemming and treating pulmonary diseases caused by viruses and bacteria. However, most approaches to subunit vaccines produce primarily humoral and only to a lesser extent cellular immune responses. We developed a nanoparticle (NP)-based carrier that, upon delivery to the lung, specifically targets pulmonary dendritic cells, thus enhancing antigen uptake and transport to the draining lymph node; antigen coupling via a disulfide link promotes highly efficient cross-presentation after uptake, inducing potent protective mucosal and systemic CD8(+) T-cell immunity. Pulmonary immunization with NP-conjugated ovalbumin (NP-ova) with CpG induced a threefold enhancement of splenic antigen-specific CD8(+) T cells displaying increased CD107a expression and IFN-γ production compared with immunization with soluble (i.e., unconjugated) ova with CpG. This enhanced response was accompanied by a potent Th17 cytokine profile in CD4(+) T cells. After 50 d, NP-ova and CpG also led to substantial enhancements in memory CD8(+) T-cell effector functions. Importantly, pulmonary vaccination with NP-ova and CpG induced as much as 10-fold increased frequencies of antigen-specific effector CD8(+) T cells to the lung and completely protected mice from morbidity following influenza-ova infection. Here, we highlight recruitment to the lung of a long-lasting pool of protective effector memory cytotoxic T-cells by our disulfide-linked antigen-conjugated NP formulation. These results suggest the reduction-reversible NP system is a highly promising platform for vaccines specifically targeting intracellular pathogens infecting the lung.

Psychometric evaluation of the French version of the questionnaire attitudes towards morphine use; a cross-sectional study in Valais, Switzerland.

BACKGROUND: In Switzerland, nurses are allowed to prescribe and administer morphine in emergency situations without a doctor. Still, nurses and other health professionals are often reluctant to prescribe and administer morphine for pain management in patients. No valid French-speaking instrument is available in Switzerland to assess the attitudes of nurses and other health professionals towards the prescription and administration of morphine. In this study, we evaluated the psychometric properties of the French version of the questionnaire "Attitudes towards morphine use". METHODS: The instrument was derived from an Italian version. Forward and back translations of the questionnaire were performed. Item analysis and construct validity were assessed between April and December 2010 in a cross sectional study including five Swiss hospitals in a sample of 588 health professionals (533 nurses, mean age 38.3 ± 10.2 years). Thirty subjects participated in test-retest reliability. RESULTS: The time to complete the instrument ranged between 12 and 15 minutes and neither floor nor ceiling effect were found. The initial 24-item instrument showed an intraclass correlation (ICC) of 0.69 (95% CI: 0.64 to 0.73, P < 0.001), and a Cronbach's α of 0.700. Factor analysis led to a six-component solution explaining 52.4% of the total variance. After excluding five items, the shortened version showed an ICC of 0.74 (95% CI, 0.70 to 0.77, P < 0.001) and a Cronbach's α of 0.741. Factor analysis led to a five-component solution explaining 54.3% of the total variance. The five components were named "risk of addiction/dependence"; "operational reasons for not using morphine"; "risk of escalation"; "other (non-dependence) risks" and "external (non-operational) reasons". In test-retest, the shortened instrument showed an ICC of 0.797 (95% CI, 0.630 to 0.911, P < 0.001) and a Cronbach's α of 0.797. CONCLUSIONS: The 19-item shortened instrument assessing attitudes towards the prescription and administration of morphine showed adequate content and construct validity.

Le taux de détresse respiratoire du nouveau-né augmente, celui des césariennes aussi: et si ce n'était pas un hasard? [Respiratory distress of the neonate and the rate of caesarean section have increased over the last 30 years. Is there a link?]

Ces trente dernières années, on note en Suisse une augmentation significative de l'incidence du syndrome de détresse respiratoire (SDR) chez le nouveau-né (NN), touchant particulièrement les enfants avec un poids de naissance >2500 g. En même temps, le taux des césariennes (CS) s'est aussi accru. Une explication pour une éventuelle corrélation entre les deux évolutions est une augmentation en particulier des CS électives qui ont tendance à être planifiées à un terme précoce pour éviter la mise en travail spontanée. Suite à cela, le foetus est privé de différents mécanismes qui favorisent l'adaptation pulmonaire périnatale. Les bénéfices réels de la CS sur la morbidité tant foetale que maternelle ne doivent pas faire oublier que la CS est un facteur de risque pour le SDR du NN. Ce risque peut être diminué efficacement en planifiant une CS élective après 39 semaines révolues. In Switzerland, the rate of respiratory distress in neonates needing hospitalization has doubled over the last thirty years, concerning in particular babies weighing more than 2500 g. In the same time, the rate of Caesarean section (CS) has also multiplied. We suppose that a link between the two evolutions might be the increase of elective CS. They tend to be planned early at term to avoid the onset of spontaneous labour As a consequence, the foetus is deprived of different mechanisms helping pulmonary transition around birth. The potential benefits of CS regarding morbidity of foetus and mother should not overshadow that CS is a significant risk factor for respiratory problems of the neonate. This risk could be dramatically decreased by planning elective CS only after completed 39 weeks of gestation

Determinants and burden of chronic kidney disease in the population-based CoLaus study: a cross-sectional analysis.

BACKGROUND: Chronic kidney disease (CKD) represents an increasing health burden. We present the population-based prevalence of CKD and compare the CKD Epidemiology collaboration (CKD-EPI) and modification of diet in renal disease (MDRD) equations to estimate the glomerular filtration rate, using the revised CKD classification with three albuminuria classes. We also explore factors associated with CKD. METHODS: The Swiss population-based, cross-sectional CoLaus study conducted in Lausanne (2003-2006) included 2810 men and 3111 women aged 35-75. CKD prevalence was assessed using CKD-EPI and MDRD equations and albuminuria estimated by the albumin-to-creatinine ratio in spot morning urine. Multivariate logistic regression was used to analyse determinants of CKD. RESULTS: Prevalence [95% confidence interval (CI)] of all stages CKD was 10.0% (9.2-10.8%) with CKD-EPI and 13.8% (12.9-14.6%) with MDRD. Using the revised CKD classification, the prevalence of low-, medium-, high- and very high-risk groups was 90.0, 8.46, 1.18 and 0.35% with CKD-EPI, respectively. With MDRD, the corresponding values were 86.24, 11.86, 1.55 and 0.35%. Using the revised classification, CKD-EPI systematically reclassified people in a lower risk category than MDRD. Age and obesity were more strongly associated with CKD in men [odds ratio (95% CI): 2.23(1.95; 2.56) per 10 years and 3.05(2.08;4.47), respectively] than in women [1.46 (1.29; 1.65) and 1.78 (1.30;2.44), respectively]. Hypertension, type 2 diabetes, serum homocysteine and uric acid were positively independently associated with CKD in men and women. CONCLUSIONS: One in 10 adults suffers from CKD in the population of Lausanne. CKD-EPI systematically reclassifies people in a lower CKD risk category than MDRD. Serum homocysteine and uric acid levels are associated with CKD independently of classical risk factors such as age, hypertension and diabetes.

Freedom of choice of specialist physicians is important to Swiss resident: a cross-sectional study.

QUESTION UNDER STUDY: To assess how important the possibility to choose specialist physicians is for Swiss residents and to determine which variables are associated with this opinion. METHODS: This cross-sectional study used data from the 2007 Swiss population-based health survey and included 13,642 non-institutionalised adults who responded to the telephone and paper questionnaires. The dependent variable included answers to the question "How important is it for you to be able to choose the specialist you would like to visit?" Independent variables included socio-demographics, health and past year healthcare use measures. Crude and adjusted logistic regressions for the importance of being able to choose specialist physicians were performed, accounting for the survey design. RESULTS: 45% of participants found it very important to be able to choose the specialist physician they wanted to visit. The answers "rather important", "rather not important" and "not important" were reported by 28%, 20% and 7% of respondents. Women, individuals in middle/high executive position, those with an ordinary insurance scheme, those reporting ≥2 chronic conditions or poorer subjective health, or those who had had ≥2 outpatient visits in the preceding year were more likely to find this choice very important. CONCLUSIONS: In 2007, almost half of all Swiss residents found it very important to be able to choose his/her specialist physician. The further development of physician networks or other chronic disease management initiatives in Switzerland, towards integrated care, need to pay attention to the freedom of choice of specialist physicians that Swiss residents value. Future surveys should provide information on access and consultations with specialist physicians.

Assessing the link between coping patterns and interpersonal behaviors in depressed women

Aim. Stressful life events are an important contributor to the onset and course of depression. Coping strategies and interpersonal patterns have been found to mediate the effects of stress [1]. Methods. This study examined the relationship between coping patterns and interpersonal interactions in early psychotherapy sessions of 25 female patients with major depression. Transcripts were rated for coping patterns using the Coping Patterns Rating Scale (CPRS; [2]). Interpersonal patterns were assessed using the Structural Analysis of Social Behavior (SASB; [3]). Results. Significant correlations were found between coping patterns and markers of interpersonal functioning in selected contexts. Discussion. The implications of these findings in understanding an important aspect of vulnerability to depression and enhancing treatment outcome are discussed.