Colonization of the oral cavity by Candida species: risk factors in long-term geriatric care

The population of elderly people in hospitals for long-term geriatric care presents many risk factors for nosocomial infection by Candida species. The aim of this work was to reduce the risk of C. albicans nosocomial infections starting from colonization of the oral cavity. The population of concern was the patients in long-stay geriatrics units; a sample of 110 people was selected by drawing lots. The clinical and biological parameters of each patient included in the study were recorded. The oral cavity was colonized by Candida spp in 67% of cases. The distribution of the strains showed that C. albicans was the most frequently identified strain, followed by C. glabrata; of the 73 patients with at least one strain of Candida spp., 47 had a clinically diagnosed candidiasis (64.4%). The wearing of dentures was not statistically linked with the development of oral candidiasis. Detecting which patients have been colonized, identifying the risk factors and applying preventive measures should reduce the probability of elderly people falling into the vicious circle of infection-malnutrition-immune-depression.     

CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells

We analyzed herein whether members of the tetraspanin superfamily are involved in human immature dendritic cell (DC) functions such as foreign antigen internalization, phagocytosis, and cell migration. We show that CD63, CD9, CD81, CD82, and CD151 are present in immature DCs. Whereas CD9 and CD81 are mostly expressed at the cell surface, CD63 and CD82 are also located in intracellular organelles. Complexes of monoclonal antibody (Mab) FC-5.01-CD63 or Fab-5.01-CD63 were rapidly translocated "outside-in" and followed the endocytic pathway through early endosomes and lysosomes, reaching major histocompatibility complex (MHC) class II-enriched compartments (MIICs) in less than one hour. Internalization of CD63 was also observed during Saccharomyces cerevisiae phagocytosis. Moreover, an association of CD63 with the beta-glycan receptor dectin-1 was observed. Mabs against CD9, CD63, CD81, and CD82 enhanced by 50% the migration induced by the chemokines macrophage inflammatory protein-5 (MIP-5) and MIP-1alpha. Concomitantly, Mabs against CD63 and CD82 diminished the surface expression of CD29, CD11b, CD18, and alpha5 integrins. By immunoprecipitation experiments we found that CD63 associated with integrins CD11b and CD18. These results suggest that CD9, CD63, CD81, and CD82 could play a role in modulating the interactions between immature DCs and their environment, slowing their migratory ability. However, only CD63 would intervene in the internalization of complex antigens.     

Toll-like receptor 4 is not involved in host defense against pulmonary Legionella pneumophila infection in a mouse model

Legionella pneumophila is a gram-negative microorganism that causes a severe pneumonia known as "legionnaires disease." Toll-like receptor 4 (TLR4) transduces the lipopolysaccharide signal and is therefore considered to play a role in host defense against gram-negative bacterial infection. To determine the role of TLR4 in L. pneumophila pneumonia, C3H/HeJ mice, which display a nonfunctional gene encoding TLR4 (TLR4), and wild-type (wt) C3H/HeN mice were intranasally inoculated with L. pneumophila serogroup 1. Infection proceeded in an identical way in TLR4 mutant and wt mice, as reflected by similar bacterial outgrowth in the lungs. In addition, the inflammatory responses to L. pneumophila infection-as assessed by histopathologic analysis, cell influx in bronchoalveolar lavage fluid, myeloperoxidase activity in lungs, and lung cytokine concentrations-were indistinguishable in TLR4 mutant and wt mice. These data suggest that, in this mouse model, TLR4 does not play a role in resistance to L. pneumophila.     

Effect of supplementation with antioxidants upon long-term risk of hypertension in the SU.VI.MAX study: association with plasma antioxidant levels

OBJECTIVE: To assess the effects of supplementation with a combination of antioxidant vitamins and trace elements, at nutritional doses, upon the 6.5-year risk of hypertension in the SU.VI.MAX trial. To describe the association between baseline plasma antioxidant levels and the same long-term risk using observational data from the study. SETTING: A total of 5086 adults from the SU.VI.MAX trial, a randomized primary prevention trial. RESULTS: Compared with the placebo group, no effect of supplementation upon the 6.5-year risk of hypertension could be detected (odds ratio, 1.04 and 95% confidence interval, 0.87-1.23 in men; and odds ratio, 1.10 and 95% confidence interval, 0.95-1.29 in women). Furthermore, compared with men in the first tertile, those in the second and third tertiles of serum baseline levels of beta-carotene presented a lower risk of hypertension in both the placebo and supplementation groups. Multivariate-adjusted odds ratios (95% confidence interval) were 0.70 (0.44-1.12) and 0.53 (0.33-0.86) in the placebo group, and were 0.59 (0.37-0.94) and 0.67 (0.42-1.07) in the supplementation group. In women, a decreasing trend was observed with vitamin C levels and risk of hypertension in the intervention group. No association could be shown between vitamin E and trace element plasma levels and the risk of hypertension. CONCLUSIONS: Despite an inverse association between baseline plasma levels of beta-carotene in men and the risk of developing hypertension, we could not demonstrate any beneficial effect of low-dose antioxidant supplementation upon the 6.5-year risk of hypertension in the randomized analysis.     

High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n = 23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p < 0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.     

Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey

Background

Chronic insomnia has a recognized impact on health-related quality-of-life (HRQoL) but data on utility scores across countries are lacking. The objective of the present study was to assess health related quality of life (HRQoL) and utility scores in individuals from three different countries (USA, France, and Japan), comparing sufferers of chronic insomnia to good sleepers.

Methods

A cross-sectional survey (SLEEPI-i) of 4067 persons in the US (n = 1298; 478 good sleepers and 820 patients with insomnia), France (n = 1858; 998 good sleepers and 860 patients with insomnia) and Japan (n = 911; 506 good sleepers and 405 patients with insomnia). Enrollment and data collection using consumer panels were web-based in the US and France, and gathered via a postal survey in Japan. People with chronic insomnia (>6 months) were selected based on Insomnia Severity Index scores (ISI). Severity of insomnia was assessed using the ISI score and HRQoL was assessed using the self-administered Short-Form SF-36 Health Survey. Utility scores were derived using the algorithm developed by Brazier et al. Multivariate analyses were used to adjust for potential confounding factors.

Results

In all countries, people with chronic insomnia (40% treated) reported lower SF-36 scores in each of eight domains compared with good sleepers (P < .0001). Chronic insomnia was associated with significantly lower utility scores compared with good sleepers (mean scores 0.63 versus 0.72 in the US, 0.57 versus 0.67 in France, and 0.67 versus 0.77 in Japan, P < .0001).

Conclusions

This survey suggests that chronic insomnia is associated with significant impairment of HRQoL and decreased utilities across the different geographical regions studied.