[Recurrence of dengue epidemics in Burkina Faso: Community preference for an intervention to prevent the disease]. / Épidémies récurrentes de la dengue au Burkina Faso : préférences communautaires pour une intervention de prévention de la maladie.

BACKGROUND: Community-based interventions have proven effective in several Latin American countries in controlling dengue vector Aedes aegypti and reducing the burden of the disease. However, we did not find any study reporting the assessment or implementation of such interventions in Sub-Saharan Africa. This article presents local communities' preferences for activities as part of the implementation of a community-based intervention for dengue prevention in Ouagadougou (Burkina Faso) where dengue epidemics are recurrent during the rainy season. METHODS: A mixed-method study combining qualitative and quantitative data collection was conducted. Information from 983 households and their preferences for community-based activities for dengue prevention were collected in five neighborhoods of the city using a quantitative questionnaire. Then, 15 qualitative focus groups were organized in one of the neighborhoods that was randomly selected to receive a community-based intervention for dengue prevention. These groups were made up of 216 people representing the different socio-cultural categories: community leaders, men, women, young girls and boys. RESULTS: More than 95% of household respondents to the quantitative questionnaire found community-based interventions acceptable and/or useful: to raise awareness of mosquito-borne disease transmission, to identify and remove the mosquito breeding sites and areas favorable to the development of the adult vectors. Most participants in the focus groups, preferred outreach activities such as video/debate sessions, school and home education sessions, focus groups. They also preferred the implementation of community working groups, responsible for identifying and eliminating mosquito breeding sites in the neighborhood. However, many participants had reservations about sending preventive text messages to residents. They found it feasible but not useful since most people cannot read. CONCLUSION: This study shows that it is important to get the local communities involved in the formulation of health prevention activities in sub-Saharan Africa where some interventions are often implemented using strategies from other continents.

Communication satisfaction and job satisfaction among critical care nurses and their impact on burnout and intention to leave: A questionnaire study.

OBJECTIVES: To investigate the relationship between communication and job satisfaction and their association with intention to leave and burnout among intensive care unit nurses. RESEARCH METHODOLOGY/DESIGN: A multicentre questionnaire study. SETTING/PARTICIPANTS: Intensive care nurses (n = 303) from three Flemish hospitals. MAIN OUTCOME MEASURES: Communication satisfaction assessed by the Communication Satisfaction Questionnaire, intention to leave through the Turnover Intention Scale (from the Questionnaire for the Perception and Assessment of Labour) and burnout by the Maslach Burnout Inventory. Job satisfaction was measured by a visual analogue scale. RESULTS: Average job satisfaction was 7.66 ±â€¯1.34/10. Nurses were most satisfied about 'Communication with supervisor' (68.46%), and most dissatisfied about 'Organisational perspectives' (34.12%). Turnover intention was low among 49.5% (150/290) and high among 6.6% (20/290). Three percent (9/299) of intensive care nurses were at risk for burnout. All dimensions of communication satisfaction were moderately associated with job satisfaction, intention to leave and burnout. CONCLUSION: This study demonstrated high levels of communication and job satisfaction in a sample of nurses in Flanders. Intention to leave and burnout prevalence were low. To a certain extent, communication satisfaction might be associated with job satisfaction, intention to leave and burnout.

Gangliosides in breast cancer: new perspectives.

Gangliosides are essential compounds of the plasma membrane involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly supported by the glycan moiety, and changes in the structure of gangliosides occur under pathological conditions including cancers. With progress in mass spectrometric analysis of gangliosides, the role of gangliosides in breast cancer progression was recently demonstrated. In this review, we summarize current knowledge on the biosynthesis of gangliosides and of the role of disialogangliosides in triple-negative breast cancer progression and metastasis. New perspectives in breast cancer therapy targeting gangliosides are also discussed.

Communication in healthcare: a narrative review of the literature and practical recommendations.

OBJECTIVES: Effective and efficient communication is crucial in healthcare. Written communication remains the most prevalent form of communication between specialised and primary care. We aimed at reviewing the literature on the quality of written communication, the impact of communication inefficiencies and recommendations to improve written communication in healthcare. DESIGN: Narrative literature review. METHODS: A search was carried out on the databases PubMed, Web of Science and The Cochrane Library by means of the (MeSH)terms 'communication', 'primary health care', 'correspondence', 'patient safety', 'patient handoff' and 'continuity of patient care'. Reviewers screened 4609 records and 462 full texts were checked according following inclusion criteria: (1) publication between January 1985 and March 2014, (2) availability as full text in English, (3) categorisation as original research, reviews, meta-analyses or letters to the editor. RESULTS: A total of 69 articles were included in this review. It was found that poor communication can lead to various negative outcomes: discontinuity of care, compromise of patient safety, patient dissatisfaction and inefficient use of valuable resources, both in unnecessary investigations and physician worktime as well as economic consequences. CONCLUSION: There is room for improvement of both content and timeliness of written communication. The delineation of ownership of the communication process should be clear. Peer review, process indicators and follow-up tools are required to measure the impact of quality improvement initiatives. Communication between caregivers should feature more prominently in graduate and postgraduate training, to become engraved as an essential skill and quality characteristic of each caregiver.

Mutual perception of communication between general practitioners and hospital-based specialists.

BACKGROUND: Communication between general practitioners (GPs) and specialists is an important aspect of qualitative care. Efficient communication exchange is essential and key in guaranteeing continuity of care. Inefficient communication is related to several negative outcomes, including patient harm. This study aimed to investigate the perception of GPs and hospital-based specialists in Belgium of the quality of their mutual communication. METHODS: A cross-sectional study was conducted among GPs and specialists. Participants were asked to complete a validated questionnaire on several aspects of their mutual communication. RESULTS: Response rates of 17.9% (343/1.912) for GPs and 17.3% (392/2.263) for specialists were obtained. Both specialists and GPs qualify their mutual telephone accessibility as suboptimal. Specialists think poorly of the GP referral letter, in contrast to GP perception. Eighty per cent of the GPs feel that specialists address their questions appropriately; specialists have a similar perception of their own performance. According to 16.7% of the specialists, GPs not always follow their recommendations. Contrarily, GPs rate their compliance much higher (90.7%). Less than half of the GPs feel that the specialists' letter arrives on time, whereas specialists have a different and a more positive perception. CONCLUSIONS: GPs and specialists disagree on several aspects of their mutual communication. These include the perception of accessibility, in both directions, and of the timeliness of written communication. Feedback is positively appreciated, again in both directions. Nevertheless, specialists feel that uptake of their recommendations is insufficient. Hence, there may remain significant room for improvement, which could contribute significantly to continuity of care and patient safety.

HIV disclosure in the workplace.

OBJECTIVES: As HIV is currently a chronic and manageable disease, an increasing amount of people living with HIV (PLHIV) are (again) active on the labour market. Since research on this topic is scarce, this study aimed to explore experiences of PLHIV in the workplace, especially concerning disclosure and adherence to antiretroviral therapy. METHODS: A questionnaire was developed and validated in collaboration with Sensoa (Flemish expertise centre for sexual health) and participants were recruited using flyers and announcements on websites. RESULTS: A total of 54 PLHIV completed the questionnaire, among whom 50 (92·6%) males. Half of the participants did not disclose their HIV status in the workplace, mostly due to being afraid of social or professional consequences. Those who disclosed, reported no changes in the workplace or even reported receiving more empathy. A minority of participants have to take antiretroviral medication at work and they reported no particular problems related to medication intake. CONCLUSION: Despite improved solidarity and information campaigns, many PLHIV still do not disclose their HIV status in the workplace, most frequently due to fear for discrimination. More actions are warranted, as well as addressing possible self-stigma. Adherence to antiretroviral therapy in the workplace posed little or no problems.

Determinants of adherence in a cohort of Belgian HIV patients: a pilot study.

Since the era of highly active antiretroviral therapy (HAART), HIV is considered a chronic disease. Adherence to HAART is crucial for effectiveness. Non-adherence negatively impacts patient outcome and the larger economy. However, data on adherence among the Belgian HIV cohort are scarce. Therefore, the purpose of this pilot study was to identify determinants of adherence among HIV patients treated in Belgium. The study was conducted at the Aids Reference Centre of Ghent University Hospital between 1 January and 31 December 2012. Sociodemographic data were collected, along with the Simplified Medication Adherence Questionnaire (SMAQ), the Center for Adherence Support Evaluation (CASE) Adherence Index, the EuroQol-6D, the Medical Outcomes Study-HIV (MOS-HIV), the Beck Depression Inventory-II, and three neurocognitive complaints screening questions. To date, 218 patients participated in the study, among whom 173 (79·4%) were male. Mean age was 46·0±10·6 years and 133 patients (63·9%) were homosexual. According to the SMAQ and the CASE, 78·5% and 93·5% of the patients were adherent to antiretroviral therapy. Logistic regression analysis revealed that smoking, neurocognitive complaints, and female sex were independent determinants of non-adherence. In conclusion, there is an elevated risk for non-adherence in smokers, people experiencing neurocognitive problems, and women in our sample. The latter could reflect differences between male and female HIV patients in Belgium. Adherence improving initiatives should be tailored to these three risk groups.

Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex.

Although glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.

Influence of culture conditions on the alpha 1,2-fucosyltransferase and MUC gene expression of a transformed cell line MM-39 derived from human tracheal gland cells.

Human tracheal glands cells (HTGC) in culture are able to respond to adrenergic, cholinergic and purinergic agonists by increasing their serous and mucin secretions. These secretagogues are also able to maintain an optimal responsiveness of serous cells to stimulation when they are regularly and briefly delivered to the cells, making the HTGC a suitable model to study the serous secretion (Merten, in press). Our interest has been focused on the effects of cholinergic and purinergic secretagogues associated to histamine, on the mucous function of the transformed human tracheal gland cell line MM-39, which has a mixed, both serous and mucous, phenotype. When the cells were exposed to short stimulation every 2 days for 3 weeks with 10 or 100 microM carbachol, UTP and histamine, modifications of their mucous phenotype were observed. The expression of MUC genes appeared dependent on the culture conditions. Transcripts of MUC1, MUC4, and MUC5B genes were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 10 microM, in contrast to the unstimulated expression of MUC1 and MUC4 in control cells. MUC1, MUC4, MUC7, MUC6 and MUC11 transcripts were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 100 microM. These culture conditions were also able to induce an alpha 1,2-fucosyltransferase activity absent in the MM-39 cells cultivated with standard conditions. There was no marked effect on the alpha 2,3-sialyltransferase activity although the expression pattern of the sialyltransferase genes was reduced to the unique presence of ST3Gal III. In conclusion, MM-39 cells exposed to repeated stimulation by secretagogues at different concentrations express different sero-mucous phenotypes.

Influence of TNFalpha on the sialylation of mucins produced by a transformed cell line MM-39 derived from human tracheal gland cells.

In order to investigate the influence of inflammation on the peripheral glycosylation of airway mucins, a human respiratory glandular cell line (MM-39) was treated by TNFalpha. The expression and the activity of sialyl- and fucosyl-transferases, involved in the biosynthesis of peripheral carbohydrate determinants like sialyl-Lewis x, were investigated by RT-PCR and by HPAEC respectively. The mRNA steady-state level of sialyl- (ST3Gal III) and of fucosyl- (FUT3) transferases was moderately up-regulated by TNFalpha; a 52% increase of alpha2,3-sialyltransferase activity was also observed in TNFalpha-stimulated MM-39 cells. After metabolic radio-labelling with [(3)H]glucosamine and [(3)H]fucose, the mucins released in the culture supernatant were purified by Sepharose CL-4B, density-gradient centrifugation and treatment with glycosaminoglycans-degrading enzymes. The mucins, released in the culture supernatant from control MM-39 cells, were constituted by two populations of molecules having the same 1.39-1.44 mg/ml density but carrying either high or low amounts of sialic acid residues at their periphery. TNFalpha was able to increase the sialylation of the weakly sialylated mucins. This effect and the enhancement of the alpha2,3-sialyltransferase activity by TNFalpha argue in favour of a regulation of the mucin sialylation by this pro-inflammatory cytokine. Despite the moderate overexpression of FUT3, no fucosylation of mucins produced by MM-39 cells was induced by TNFalpha. In conclusion, the influence of TNFalpha on the sialylation of mucins could explain why the mucins from infected patients suffering either from cystic fibrosis or from chronic bronchitis are more sialylated.

Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis.

Human airway mucins represent a very broad family of polydisperse high molecular mass glycoproteins, which are part of the airway innate immunity. Apomucins, which correspond to their peptide part, are encoded by at least 6 different mucin genes (MUC1, MUC2, MUC4, MUC5B, MUC5AC and MUC7). The expression of some of these genes (at least MUC2 and MUC5AC) is induced by bacterial products, tobacco smoke and different cytokines. Human airway mucins are highly glycosylated (70-80% per weight). They contain from one single to several hundred carbohydrate chains. The carbohydrate chains that cover the apomucins are extremely diverse, adding to the complexity of these molecules. Structural information is available for more than 150 different O-glycan chains corresponding to the shortest chains (less than 12 sugars). The biosynthesis of these carbohydrate chains is a stepwise process involving many glycosyl- or sulfo-transferases. The only structural element shared by all mucin O-glycan chains is a GalNAc residue linked to a serine or threonine residue of the apomucin. There is growing evidence that the apomucin sequences influence the first glycosylation reactions. The elongation of the chains leads to various linear or branched extensions. Their non-reducing end, which corresponds to the termination of the chains, may bear different carbohydrate structures, such as histo-blood groups A or B determinants, H and sulfated H determinants, Lewis a, Lewis b, Lewis x or Lewis y epitopes, as well as sialyl- or sulfo- (sometimes sialyl- and sulfo-) Lewis a or Lewis x determinants. The synthesis of these different terminal determinants involves three different pathways with a whole set of glycosyl- and sulfo-transferases. Due to their wide structural diversity forming a combinatory of carbohydrate determinants as well as their location at the surface of the airways, mucins are involved in multiple interactions with microorganisms and are very important in the protection of the underlying airway mucosa. Airway mucins are oversulfated in cystic fibrosis and this feature has been considered as being linked to a primary defect of the disease. However, a similar pattern is observed in mucins from patients suffering from chronic bronchitis when they are severely infected. Airway mucins from severely infected patients suffering either from cystic fibrosis or from chronic bronchitis are also highly sialylated, and highly express sialylated and sulfated Lewis x determinants, a feature which may reflect severe mucosal inflammation or infection. These determinants are potential sites of attachment for Pseudomonas aeruginosa, the pathogen responsible for most of the morbidity and mortality in cystic fibrosis, and the expression of the sulfo- and glycosyl-transferases involved in their biosynthesis is increased by TNFalpha. In summary, airway inflammation may simultaneously induce the expression of mucin genes (MUC2 and MUC5AC) and the expression of several glycosyl- and sulfo-transferases, therefore modifying the combinatory glycosylation of these molecules.

Sequential biosynthesis of sulfated and/or sialylated Lewis x determinants by transferases of the human bronchial mucosa.

The structural determination of sulfated carbohydrate chains from a cystic fibrosis patient respiratory mucins has shown that sulfation may occur either on the C-3 of the terminal Gal, or on the C-6 of the GlcNAc residue of a terminal N -acetyllactosamine unit. The two enzymes responsible for the transfer of sulfate from PAPS to the C-3 of Gal or to the C-6 of GlcNAc residues have been characterized in human respiratory mucosa. These two enzymes, in conjunction with fucosyl- and sialyltransferases, allow the synthesis of different sulfated epitopes such as 3-sulfo Lewis x (with a 3- O -sulfated Gal), 6-sulfo Lewis x and 6-sulfo-sialyl Lewis x (with a 6- O -sulfated GlcNAc). In the present study, the sequential biosynthesis of these epitopes has been investigated using microsomal fractions from human respiratory mucosa incubated with radiolabeled nucleotide-sugars or PAPS, and oligosaccharide acceptors, mostly prepared from human respiratory mucins. The structures of the radiolabeled products have been determined by their coelution in HPAEC with known oligosaccharidic standards. In the biosynthesis of 6- O -sulfated carbohydrate chains by the human respiratory mucosa, the 6- O -sulfation of a terminal nonreducing GlcNAc residue precedes beta1-4-galactosylation, alpha2-3-sialylation (to generate 6-sulfo-sialyl- N -acetyllactosamine), and alpha1-3-fucosylation (to generate the 6-sulfo-sialyl Lewis x determinant). The 3- O -sulfation of a terminal N -acetyllactosamine may occur if this carbohydrate unit is not substituted. Once an N -acetyllactosamine unit is synthesized, alpha1-3-fucosylation of the GlcNAc residue to generate a Lewis x structure blocks any further substitution. Therefore, the present study defines the pathways for the biosynthesis of Lewis x, sialyl Lewis x, sulfo Lewis x, and 6-sulfo-sialyl Lewis x determinants in the human bronchial mucosa.

Pseudomonas aeruginosa binds to neoglycoconjugates bearing mucin carbohydrate determinants and predominantly to sialyl-Lewis x conjugates.

Pseudomonas aeruginosa plays an important role in the colonization of the airways of patients suffering from cystic fibrosis. It binds to the carbohydrate part of respiratory and salivary mucins and its binding to cystic fibrosis mucins is even higher, suggesting that qualitative or/and quantitative modifications of the carbohydrate chains may be involved in this process. In order to find out the best carbohydrate receptors for P.aeruginosa, a flow cytometry technique using a panel of polyacrylamide based glycoconjugates labeled with fluorescein was developed. The neoglycoconjugates contained neutral, sialylated or sulfated chains analogous to carbohydrate determinants found at the periphery of respiratory mucins (Le(a), Le(y), Le(x), sialyl- and 3'-sulfo-Le(x), and blood group A determinants). We used also neoglycoconjugates containing Gal(alpha1-2)Galbeta and sialyl- N -acetyllactosamine determinants. The interaction of these glycoconjugates with the nonpiliated strain of P.aeruginosa, 1244-NP, was saturable except for the glycoconjugates containing blood group A or sialyl- N -acetyllactosamine epitopes. The measure of Kd indicated that strain 1244-NP had a higher affinity for the glycoconjugate bearing the sialyl-Le(x)determinant than for all the other glycoconjugates studied. The role of sialic acid was confirmed by competition assay using mainly sialylated mucin glycopeptides. In order to find out if this behavior was the same for pathological strains as for the 1244-NP mutant, four mucoid strains of P.aeruginosa isolated from cystic fibrosis patients were analyzed with the Le(x)neoglycoconjugate, its sialylated and its sulfated derivatives. Individual variations in the binding of these strains to the three glycoconjugates were observed. However, three strains out of four had a higher affinity for the sialyl-Le(x)than for the 3'-sulfo-Le(x)derivative.

The sialylation of bronchial mucins secreted by patients suffering from cystic fibrosis or from chronic bronchitis is related to the severity of airway infection.

Bronchial mucins were purified from the sputum of 14 patients suffering from cystic fibrosis and 24 patients suffering from chronic bronchitis, using two CsBr density-gradient centrifugations. The presence of DNA in each secretion was used as an index to estimate the severity of infection and allowed to subdivide the mucins into four groups corresponding to infected or noninfected patients with cystic fibrosis, and to infected or noninfected patients with chronic bronchitis. All infected patients suffering from cystic fibrosis were colonized by Pseudomonas aeruginosa. As already observed, the mucins from the patients with cystic fibrosis had a higher sulfate content than the mucins from the patients with chronic bronchitis. However, there was a striking increase in the sialic acid content of the mucins secreted by severely infected patients as compared to noninfected patients. Thirty-six bronchial mucins out of 38 contained the sialyl-Lewis x epitope which was even expressed by subjects phenotyped as Lewis negative, indicating that at least one alpha1,3 fucosyltransferase different from the Lewis enzyme was involved in the biosynthesis of this epitope. Finally, the sialyl-Lewis x determinant was also overexpressed in the mucins from severely infected patients. Altogether these differences in the glycosylation process of mucins from infected and noninfected patients suggest that bacterial infection influences the expression of sialyltransferases and alpha1,3 fucosyltransferases in the human bronchial mucosa.

Characterization of an N-acetylglucosamine-6-O-sulfotransferase from human respiratory mucosa active on mucin carbohydrate chains.

A microsomal GlcNAc-6-O-sulfotransferase activity from human bronchial mucosa, able to transfer a sulfate group from adenosine 3'-phosphate 5'-phosphosulfate onto methyl-N-acetylglucosaminides or terminal N-acetylglucosamine residues of carbohydrate chains from human respiratory mucins, has been characterized. The reaction products containing a terminal HO3S-6GlcNAc were identified by high performance anion-exchange chromatography. Using methyl-beta-N-acetylglucosaminide as a substrate, the optimal activity was obtained with 0.1% Triton X-100, 30 mM NaF, 20 mM Mn2+, 5 mM AMP in a 30 mM MOPS (3-(N-morpholino) propanesulfonic acid) buffer at pH 6.7. The apparent Km values for adenosine 3'-phosphate 5'-phosphosulfate and methyl-beta-N-acetylglucosaminide were observed at 9.1 x 10(-6) M and 0.54 x 10(-3) M, respectively. The enzyme had more affinity for carbohydrate chains with a terminal GlcNAc residue than for methyl-beta-N-acetylglucosaminide; it was unable to catalyze the transfer of sulfate to position 6 of the GlcNAc residue contained in a terminal Galbeta1-4GlcNAc sequence. However, oligosaccharides with a nonreducing terminal HO3S-6GlcNAc were substrates for a beta1-4 galactosyltransferase from human bronchial mucosa. These data point out that GlcNAc-6-O-sulfotransferase must act before beta1-4 galactosylation in mucin-type oligosaccharide biosynthesis.