Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection, and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms toward infected cells.

The effect of parental loss on cognitive and affective interference in adolescent boys from a post-conflict region.

Little is known about the impact of early-life stressors such as parental loss on cognitive-affective processing during adolescence, especially in regions chronically affected by war and armed conflict. Here, we tested 72 male adolescents living in Northern Uganda (ages 14-19), 52 of whom still had both of their parents and 20 participants who had experienced parental loss. Participants completed a classic color-naming Stroop task as well as an affective interference task, the opposite emotions test (OET). Adolescents with parental loss showed a decrease in performance over time, especially on the Stroop task. Critically, this decrement in performance was positively associated with reported symptoms of trauma, but only in the parental loss group. The current data suggest a difficulty in maintaining cognitive control performance in youths with experience of parental loss. The findings are discussed in relation to traumatic stress and mental health in post-conflict regions.

The mediating role of stigmatization in the mental health of adolescent victims of sexual violence in Eastern Congo.

This study aims to explore the factors that explain the mental sequelae of war-related sexual violence and focuses in particular on the role of stigmatization. Drawing on a large-scale quantitative survey undertaken in the war-affected region of eastern Democratic Republic of the Congo, we analyze how stigmatization mediates the mental health impact of sexual violence on adolescent girls who were victims of rape. Twenty-two secondary schools were randomly selected out of a stratified sample in Bunia, Eastern Congo. In a cross-sectional, population-based survey, 1,305 school-going adolescent girls aged 11-23 completed self-report measures assessing war-related traumatic events, experiences of sexual violence, stigmatization, and mental health symptoms. Of the 1,305 participants, 38.2% (n=499) reported experiences of sexual violence. Victims of sexual violence reported more war-related traumatic events and more stigmatization experiences. Several hierarchical regression analyses examined the mediating impact of stigmatization on the relationship between sexual violence and mental health outcomes, thereby controlling for sociodemographics (age, parental availability, and socioeconomic status) and war-related traumatic exposure. Our findings show that this stigmatization largely explains the mental health impact of sexual violence, in particular, on adolescent girls' reported symptoms of depression (full mediation) and posttraumatic stress (avoidance and total PTSD: full mediation; hyperarousal: partial (40%) mediation). No evidence of mediation by stigmatization was found for symptoms of anxiety and intrusion. Stigmatization plays thus an important role in shaping the mental sequelae of sexual violence, a finding with major consequences for clinical practice.

Prospective evaluation of clinical voiding reeducation or voiding school for lower urinary tract conditions in children.

PURPOSE: We conducted a prospective controlled study evaluating the results of a clinical voiding reeducation program (voiding school) for treatment of lower urinary tract conditions in children compared to no treatment. MATERIALS AND METHODS: A total of 38 children with nonneurogenic lower urinary tract conditions were included in the study. Controls, consisting of 15 children on the waiting list for the same program, received no treatment. The clinical voiding reeducation program consisted of instruction on voiding and drinking, individualized voiding diaries, pelvic floor biofeedback training, uroflowmetry, alarm therapy, cognitive therapy and psychological support. Data on voiding, drinking, pelvic floor control, voided volume, uroflow, incontinence and stool habits were gathered before the program, during the program and 6 months after the program. In the control group the same data were gathered. RESULTS: In the study group a positive effect of voiding school was observed in 92% of children, with 42% becoming completely dry, 24% improving from incontinence during the day and night to incontinence during the day or night only, and 26% remaining incontinent. In all patients the number and amount of incontinence episodes decreased. In the control group no differences were observed between the start of study and 6 months later. The study group did significantly better on voided volume and incontinence compared to controls. CONCLUSIONS: In this prospective controlled study a positive effect was noted on voided volume and incontinence with a clinical voiding reeducation program (voiding school).

The Inter-regional Belgian Bank Employee Nutrition Study (IBBENS).

OBJECTIVE: This study compares the dietary intake in different geographical areas in Belgium. DESIGN: Food habits were examined by the 3-day food record with additional intervieW. SETTING: The study was performed in the head offices of one bank situated in seven Dutch-speaking cities (spread over two districts) in the north and one French-speaking city in the south of Belgium. SUBJECTS: 371 male and 192 female healthy employees participated in the survey. RESULTS: The results show a difference in fat consumption between north and south. Men in the French-speaking district consumed on average 18.8 E% (SD = 3.2) of saturated fat, compared to 16.2 (2.8) and 16.7 (2.9) E% for the two Dutch-speaking districts (P < 0.001). For women the respective data are 18.9 (3.2), 16.4 (3.0) and 17.1 (3.1) E% (P < 0.01). The E% of polyunsaturated fat in the three districts equals respectively 5.2 (1.8), 7.2 (2.4) and 6.7 (2.5) (P < 0.001) for men; 4.9 (1.8), 7.2 (2.7) and 6.6 (2.2) (P < 0.001) for women. A significantly lower P/S ratio (P < 0.001, for both sexes) and U/S ratio (P < 0.001, for both sexes) was found in the south. The intake of cholesterol (mg per 4.18 MJ) was significantly higher in the south (P = 0.01, for both sexes). The differences between the Dutch-speaking centres were relatively small. For men significant differences in P/S ratio, 0.48 (0.22) in the east versus 0.43 (0.20) in the west (P < 0.001), and in E% of monounsaturated fat, 15.2 (2.7) versus 16.3 (3.1) (P < 0.01), could be established. CONCLUSION: Differences in fat intake exist between the north and the south of Belgium. Within the north significant differences exist in P/S ratio and in intake of monounsaturated fat.