An attenuated Listeria monocytogenes vector primes more potent simian immunodeficiency virus-specific mucosal immunity than DNA vaccines in mice.

A human immunodeficiency virus type 1 (HIV-1) vaccine that induces potent immune responses in the gastrointestinal mucosa would be highly desirable. Here we show that attenuated recombinant Listeria monocytogenes, administered orally utilizing its natural route of infection, induces potent mucosal as well as systemic immune responses in mice. Moreover, these responses can be boosted efficiently with replication-incompetent adenoviral vectors. L. monocytogenes elicited more potent simian immunodeficiency virus (SIV) Gag-specific CD8(+) T lymphocyte responses in mucosal compartments than DNA vaccines.

The peer relationships of girls with ASD at school: comparison to boys and girls with and without ASD.

BACKGROUND: This study examines the social relationships of elementary school children with high-functioning autism, focusing on how gender relates to social preferences and acceptance, social connections, reciprocal friendships, and rejection. METHOD: Peer nomination data were analyzed for girls with and without ASD (n = 50) and boys with and without ASD (n = 50). Girls and boys with ASD were matched by age, gender, and IQ. Each child with ASD was matched by age and gender to a typically developing classmate. RESULTS: Consistent with typically developing populations, children with ASD preferred, were accepted by, and primarily socialized with same-gender friends. With fewer nominations and social relationships, girls and boys with ASD appear more socially similar to each other than to the same-gender control group. Additionally, girls and boys with ASD showed higher rates of social exclusion than their typically developing peers. However, boys with ASD were more overtly socially excluded compared to girls with ASD, who seemed to be overlooked, rather than rejected. CONCLUSIONS: Our data suggest a number of interesting findings in the social relationships of children with ASD in schools. Like typically developing populations, children with ASD identify with their own gender when socializing and choosing friends. But given the social differences between genders, it is likely that girls with ASD are experiencing social challenges that are different from boys with ASD. Therefore, gender is an important environmental factor to consider when planning social skills interventions at school.

Prior exposure to an attenuated Listeria vaccine does not reduce immunogenicity: pre-clinical assessment of the efficacy of a Listeria vaccine in the induction of immune responses against HIV.

BACKGROUND: We have evaluated an attenuated Listeria monocytogenes (Lm) candidate vaccine vector in nonhuman primates using a delivery regimen relying solely on oral vaccination. We sought to determine the impact of prior Lm vector exposure on the development of new immune responses against HIV antigens. FINDINGS: Two groups of rhesus macaques one Lm naive, the other having documented prior Lm vector exposures, were evaluated in response to oral inoculations of the same vector expressing recombinant HIV-1 Gag protein. The efficacy of the Lm vector was determined by ELISA to assess the generation of anti-Listerial antibodies; cellular responses were measured by HIV-Gag specific ELISpot assay. Our results show that prior Lm exposures did not diminish the generation of de novo cellular responses against HIV, as compared to Listeria-naïve monkeys. Moreover, empty vector exposures did not elicit potent antibody responses, consistent with the intracellular nature of Lm. CONCLUSIONS: The present study demonstrates in a pre-clinical vaccine model, that prior oral immunization with an empty Lm vector does not diminish immunogenicity to Lm-expressed HIV genes. This work underscores the need for the continued development of attenuated Lm as an orally deliverable vaccine.

Impact of a social skills intervention on the hostile attributions of children with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to a wide array of developmental deficits, including significant impairments in social skills. Given the extensive body of evidence linking social information-processing patterns with social behavior, it is possible that social information-processing may represent one mechanism of behavioral change. The present investigation sought to answer the question of whether a well-established social skills intervention decreased the hostile attributions of children with PAE. Further, was there a differential impact of the intervention on hostile attributions in the context of peer provocation versus group entry scenarios? METHODS: Participants consisted of 100 children (51% male) with PAE between the ages of 6 and 12 years. Participants were randomly assigned to either a social skills intervention, Children's Friendship Training (CFT), or to a Delayed Treatment Control (DTC) condition. RESULTS: Analyses indicated that the social skills intervention resulted in a significantly lower proportion of hostile attributions in peer group entry, but not peer provocation, scenarios. This decrease was maintained over a 3-month follow-up period. CONCLUSIONS: Deficits in social information-processing among individuals with PAE can be improved through social skills intervention, and these changes may lead to more positive developmental outcomes.

A controlled social skills training for children with fetal alcohol spectrum disorders.

Children with fetal alcohol spectrum disorders (FASD) have significant social skills deficits. The efficacy of a child friendship training (CFT) versus a delayed treatment control (DTC) was assessed for 100 children ages 6 to 12 years with FASD. Children in the CFT showed clear evidence of improvement in their knowledge of appropriate social behavior, and according to parent report, CFT resulted in improved social skills and fewer problem behaviors compared with DTC. Gains were maintained at 3-month follow-up. After receiving treatment, the DTC group exhibited similar improvement. Teachers did not report improvement as a function of social skills treatment. The findings suggest that children with FASD benefit from CFT but that these social skills gains may not be observed in the classroom.

Stimulants, neuroleptics, and children's friendship training for children with fetal alcohol spectrum disorders.

BACKGROUND: Peer relationship problems are a significant part of the clinical presentation of children with Fetal Alcohol Spectrum Disorders (FASD). Many of these children have been prescribed psychotropic medications by community practitioners. The present study reports on the interaction between medication status and parent and teacher-reported outcomes for parent-assisted Children's Friendship Training (CFT). METHODS: Seventy seven children (40 boys and 37 girls, age range was 71-139 months) diagnosed with FASD were given 12 sessions of CFT. Parent- and teacher-reported social outcomes were compared across four subgroups of children who were prescribed either stimulant or neuroleptic medication, neither or both types of medications. RESULTS: According to parent and teacher reports, children prescribed neuroleptic medication showed greater improvement on all outcome measures when compared to children not prescribed neuroleptics. In contrast, children prescribed stimulant medication either failed to show improvement or showed poorer outcomes when compared to children not prescribed stimulants. IMPLICATIONS: Children with FASD frequently present with symptoms of inattention and hyperactivity. The present results suggest physicians routinely ask about prenatal alcohol exposure as part of history taking to treat children more effectively who appear to be displaying attention-deficit/hyperactivity disorder symptomatology but who may have FASD.

Executive functioning predicts social skills following prenatal alcohol exposure.

Adverse sequelae of prenatal alcohol exposure include executive function and social skills impairments, although these two domains have not been empirically linked in alcohol-exposed individuals. This study investigated this relationship using the BRIEF and the SSRS in 98 children aged 6 to 11 years. Executive functions explained a significant percentage of variance in parent and teacher rated social skills. No differences were found among children with diagnoses of FAS, partial FAS, or alcohol-related neurodevelopmental disorder. It may be helpful to consider executive functioning in designing social skills interventions for alcohol-exposed children whether or not they have full FAS.

Predictors of stress in parents of children with fetal alcohol spectrum disorders.

This study examined child characteristics and family factors as predictors of stress in the biological or adoptive parents of 6- to 12-year-old children with fetal alcohol spectrum disorders (FASDs). Impaired executive functioning, poorer adaptive functioning, externalizing and internalizing behavior problems, and adoptive parent status all made significant and independent contributions to the prediction of higher levels of child domain stress, as reported by parents on the Parenting Stress Index. Biological parent status and fewer family resources were associated with higher levels of parent domain stress. Teacher ratings of the child"s executive functioning impairments and externalizing and internalizing behavior problems also were associated with parent reports of child domain stress. Findings highlight the need to provide support not only to children with FASDs, but to their caregivers as well.

Long-term outcomes of parent-assisted social skills intervention for high-functioning children with autism spectrum disorders.

This study aims to evaluate the long-term outcome of Children's Friendship Training, a parent-assisted social skills intervention for children. Prior research has shown Children's Friendship Training to be superior to wait-list control with maintenance of gains at 3-month follow-up. Participants were families of children diagnosed with autism spectrum disorder who completed Children's Friendship Training 1-5 years earlier. They were recruited through mail, phone, and email. Information collected included parent and child completed questionnaires and a phone interview. Data were collected on 24 of 52 potential participants (46%). With an average of 35-month follow-up, participants had a mean age of 12.6 years. Results indicated that participants at follow-up were invited on significantly more play dates, showed less play date conflict, improved significantly in parent-reported social skills and problem behaviors, and demonstrated marginally significant decreases in loneliness when compared to pre-Children's Friendship Training.

Predicting treatment success in social skills training for adolescents with autism spectrum disorders: the UCLA Program for the Education and Enrichment of Relational Skills.

This study seeks to examine the predictors of positive social skills outcomes from the University of California, Los Angeles Program for the Education and Enrichment of Relational Skills, an evidence-based parent-assisted social skills program for high-functioning middle school and high school adolescents with autism spectrum disorders. The results revealed that adolescents with higher parent-reported baseline social skills and lower self-reported perceived social functioning demonstrated greater improvement in social skills following the intervention.

Evidence-based social skills training for adolescents with autism spectrum disorders: the UCLA PEERS program.

The present study examines the efficacy and durability of the PEERS Program, a parent-assisted social skills group intervention for high-functioning adolescents with ASD. Results indicate that teens receiving PEERS significantly improved their social skills knowledge, social responsiveness, and overall social skills in the areas of social communication, social cognition, social awareness, social motivation, assertion, cooperation, and responsibility, while decreasing autistic mannerisms and increasing the frequency of peer interactions. Independent teacher ratings revealed significant improvement in social skills and assertion from pre-test to follow-up assessment. Examination of durability of improvement revealed maintenance of gains in nearly all domains with additional treatment gains at a 14-week follow-up assessment.

Pediatric overweight prevention through a parent training program for 2-4 year old Latino children.

BACKGROUND: Latino preschool children in the United States are at high risk for obesity. The objective of this study was to measure over a one-year period whether a parent training based on social learning theory combined with evidence-based interventions to promote optimal nutrition and physical activity will reduce the upward trend of BMI z-scores in groups of 2­4 year old Latino children living in low-income households. METHODS: Seven weekly classes with 2 booster classes were delivered to low-income Latino parents with 2­4 year old children. A randomized controlled pilot study evaluated the effectiveness of the intervention that contrasts 61 children whose parents were randomized to receive Parent Training (PT) with 60 Wait-list (WL) subjects. Forty subjects did not attend the one-year follow up assessment, resulting in 81 subjects who have measurements for both baseline and one-year follow up assessments. To adjust for differential dropout rates and missing observations, imputation of missing data was done using a carefully constructed model that included relevant independent variables. RESULTS: There were no significant subject differences between groups at baseline for family characteristics and BMI categories for child and parent. Children in the intervention group decreased their BMI z-scores significantly on average by .20 (SE= .08) compared to children in the control group who increased z scores on average by .04 (SE=.09) at one year (P<.05). CONCLUSIONS: Parent training is effective to reduce the risk of overweight in preschool Latino children living in low-income households. The findings need to be examined in a larger sample of children.

Parent-assisted group treatment for friendship problems of children with autism spectrum disorders.

Children with Asperger's Disorder or High Functioning Autism are included in regular education classes but find themselves excluded from the social lives of their classmates. This paper briefly reviews studies which attempt to provide them with training to overcome their social difficulties. These interventions have had limited success and have not systematically incorporated the child's parents into the intervention. Children's Friendship Training is a manualized parent-assisted group treatment which teaches social skill through learning and practicing sets of rules of etiquette for key social situations. The treatment approach has been demonstrated to have success in improving friendships of children with autism spectrum disorders. The content of Children's Friendship Training is briefly described and results of controlled studies are reviewed. Limitations of previous research and future directions are also described.

Maternal Reports of Play Dates of Clinic Referred and Community Children.

Recent interventions have focused upon play dates as a means to improve friendships. However, no measures have been published which quantify play date quality. An important characteristic of play dates in this regard may be the amount of conflict. We present the development of such a measure. We compare maternal reports of play dates for 112 community subjects with 48 subjects referred for peer problems (mean age = 8.7 years). We found that clinic-referred subjects had significantly fewer hosted and invited play dates than the community subjects. The mean conflict on play dates was significantly lower for the community subjects than for the clinic-referred subjects. We obtained significant correlations between conflict on play dates and measures of problem behaviors. Our results support the position that conflict on play dates is an important area to target in social skills training programs. The scale may prove useful to clinicians and researchers by facilitating screening and assessing interventions directed towards improving play dates.

A live attenuated Listeria monocytogenes vaccine vector expressing SIV Gag is safe and immunogenic in macaques and can be administered repeatedly.

Listeria monocytogenes (Lm) is known to induce strong cellular immune responses. We constructed a live-attenuated Lm vector, Lmdd-BdopSIVgag, which encodes SIVmac239 gag. Intragastric (i.g.) administration of 3 × 10(12) bacteria to rhesus macaques was safe and induced anti-Gag cellular but no humoral immune responses. Boosting of Gag-specific cellular responses was observed after i.g. administration of Lmdd-BdopSIVgag to previously vaccinated RM despite preexisting anti-Lm immunity shown by lymphoproliferative responses. Surprisingly, anti-Lm cellular responses were also detected in non-vaccinated controls, which may reflect the fact that Lm is a ubiquitous bacterium. The novel, live-attenuated Lmdd-BdopSIVgag may be an attractive platform for oral vaccine delivery.

Prime-boost vaccination with heterologous live vectors encoding SIV gag and multimeric HIV-1 gp160 protein: efficacy against repeated mucosal R5 clade C SHIV challenges.

We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239 gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus > 90%; these RM also had strong SIV Gag-specific proliferation of CD8⁺ T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the α4ß7-expressing CD4⁺ T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection.

A randomized controlled study of parent-assisted Children's Friendship Training with children having autism spectrum disorders.

This study evaluated Children's Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up.

Psychosocial and familial impairment among overweight youth with social problems.

OBJECTIVE: Emerging research indicates that overweight children with social impairments are less responsive to weight control interventions over the long term. A better understanding of the breadth and psychosocial correlates of social problems among overweight youth is needed to optimize long-term weight outcomes. METHODS: A total of 201 overweight children, aged 7-12 years, participated in a randomized controlled trial of two weight maintenance interventions following family-based behavioral weight loss treatment. Children with HIGH (T ≥ 65) versus LOW (T<65) scores on the Child Behavior Checklist Social Problems subscale were compared on their own and their parents' pre-treatment levels of psychosocial impairment using multivariate analysis of variance. Hierarchical regression was used to identify parent and child predictors of social problems in the overall sample. RESULTS: HIGH (n = 71) children evidenced greater eating disorder psychopathology and lower self-worth, as well as a range of interpersonal difficulties, compared with LOW children (n = 130; ps<0.05). Compared with parents of LOW children, parents of HIGH children reported greater levels of their own general psychopathology (p<0.05). Parent psychopathology significantly added to the prediction of social problems in the full sample beyond child sex and z-BMI (ps<0.01). CONCLUSION: A substantial minority of overweight youth experience deficits across the social domain, and such deficits appear to be associated with impairment in a broad range of other psychosocial domains. Augmenting weight loss interventions with specialized treatment components to address child and parent psychosocial problems could enhance socially-impaired children's long-term weight outcomes and decrease risk for later development of psychiatric disturbances.

Parent-assisted social skills training to improve friendships in teens with autism spectrum disorders.

This study examines the efficacy of a manualized parent-assisted social skills intervention in comparison with a matched Delayed Treatment Control group to improve friendship quality and social skills among teens 13-17 years of age with autism spectrum disorders. Targeted skills included conversational skills, peer entry and exiting skills, developing friendship networks, good sportsmanship, good host behavior during get-togethers, changing bad reputations, and handling teasing, bullying, and arguments. Results revealed, in comparison with the control group, that the treatment group significantly improved their knowledge of social skills, increased frequency of hosted get-togethers, and improved overall social skills as reported by parents. Possibly due to poor return rate of questionnaires, social skills improvement reported by teachers was not significant. Future research should provide follow-up data to test the durability of treatment.