Evaluating Impacts of a Multilevel Resilience-Based Psychosocial Intervention on Mental Health of Children Affected by Parental HIV in China

Background: Children affected by parental HIV are commonly exposed to multiple risk factors, including parental illness and death, other traumatic life events, HIV stigma, and poverty, all of which in turn put them at elevated risk of experiencing poor mental health outcomes. Previous research has suggested the promise of psychosocial interventions in improving mental health for children affected by parental HIV through an integrated and multilevel resilience-based approach. However, there are few multilevel resilience-based interventions for this group, and the efficacy of such interventions on mental health outcomes has not been fully examined. Furthermore, very few studies have examined whether resilience-based interventions impact various sub-populations differently or explored the mechanisms through which such intervention effects occur. Therefore, the first aim of this dissertation research was to examine the short-term efficacy (e.g., up to 18 months) of the Child-Caregiver-Advocacy Resilience (ChildCARE) intervention, a multilevel resilience-based psychosocial intervention, on selected mental health outcomes (i.e., depressive symptoms, school anxiety, loneliness) among children affected by parental HIV, as well as testing the potential moderation roles of gender and age in the intervention effects. The second aim of this dissertation research was to examine whether the ChildCARE intervention would yield improvement in mental health beyond 18 months of follow up and whether emotional regulation and coping would act as the potential mechanisms of change through which the ChildCARE intervention improves mental health outcomes for these children. Methods: The ChildCARE intervention is a culturally tailored intervention developed for children affected by parental HIV in China, which consists of intervention components at three levels: child, caregiver, and community. The intervention was evaluated using a 4-arm community-based cluster randomized controlled trial with a sample of 790 children 6-17 years of age (51.6% boys) affected by parental HIV in a rural county in central China from 2012 to 2016. Children and their primary caregivers were randomly assigned by school clusters to a control condition or one of three intervention conditions (i.e., child-only, child + caregiver, child + caregiver + community). Of the three intervention conditions, children and caregivers assigned to the child-only condition were provided child intervention component only, those assigned to the child + caregiver condition were provided both child and caregiver intervention components, and children and caregivers assigned to the child + caregiver + community condition were provided all three intervention components. Data on depressive symptoms, school anxiety, loneliness, emotional regulation, coping, and demographic characteristics were collected from children via self-report at baseline and every six months over 36 months. Results: Overall, the ChildCARE intervention yielded some short-term improvements in depressive symptoms and loneliness, but these improvements were not sustained at 18 months or beyond for children affected by parental HIV. Older children (i.e., ≥ 12 years of age) benefited more from the intervention than their younger counterparts (i.e., \u3c 12 years). Mediation analyses further showed that the ChildCARE intervention yielded significant improvements in positive coping, but not emotional regulation or negative coping at 18 months, whereas changes in emotional regulation, positive coping, and negative coping were consistently associated with depressive symptoms, school anxiety, and loneliness. Conclusions: The findings in this research provide support for the benefits of the ChildCARE intervention on mental health outcomes but highlight the challenges in producing robust, long-term impacts for children affected by parental HIV in central China. This research also suggests the important roles of emotional regulation and coping in influencing mental health outcomes for these children

Pertussis Toxin-sensitive Activation of Phospholipase C by the C5a and fMet-Leu-Phe Receptors

Signal transduction pathways that mediate C5a and fMet-Leu-Phe (fMLP)-induced pertussis toxin (PTx)-sensitive activation of phospholipase C (PLC) have been investigated using a cotransfection assay system in COS-7 cells. The abilities of the receptors for C5a and fMLP to activate PLC beta 2 and PLC beta 3 through the Gbeta gamma subunits of endogenous Gi proteins in COS-7 cells were tested because both PLC beta 2 and PLC beta 3 were shown to be activated by the beta gamma subunits of G proteins in in vitro reconstitution assays. Neither of the receptors can activate endogenous PLC beta 3 or recombinant PLC beta 3 in transfected COS-7 cells. However, both receptors can clearly activate PLC beta 2 in a PTx-sensitive manner, suggesting that the receptors may interact with endogenous PTx-sensitive G proteins and activate PLC beta 2 probably through the Gbeta gamma subunits. These findings were further corroborated by the results that PLC beta 3 could only be slightly activated by Gbeta 1gamma 1 or Gbeta 1gamma 5 in the cotransfection assay, whereas the Gbeta gamma subunits strongly activated PLC beta 2 under the same conditions. PLC beta 3 can be activated by Galpha q, Galpha 11, and Galpha 16 in the cotransfection assay. In addition, the Ggamma 2 and Ggamma 3 mutants with substitution of the C-terminal Cys residue by a Ser residue, which can inhibit wild type Gbeta gamma -mediated activation of PLC beta 2, were able to inhibit C5a or fMLP-mediated activation of PLC beta 2. These Ggamma mutants, however, showed little effect on m1-muscarinic receptor-mediated PLC activation, which is mediated by the Gq class of G proteins. These results all confirm that the Gbeta gamma subunits are involved in PLC beta 2 activation by the two chemoattractant receptors and suggest that in COS-7 cells activation of PLC beta 3 by Gbeta gamma may not be the primary pathway for the receptors

Impact of Adverse Childhood Events on the Psychosocial Functioning of Children Affected by Parental HIV in Rural China

Introduction: Children affected by parental HIV are more likely than unaffected peers to experience trauma and are at-risk for negative psychological and social outcomes. This study aimed to examine the relationship between adverse childhood events and psychosocial functioning among children affected by parental HIV. Methods: A total of 790 children ages 6–17 from Henan, China were enrolled in a longitudinal, randomized controlled trial of a resilience-based psychosocial intervention. At baseline, children reported on numerous psychosocial factors, including trauma exposure, symptoms of anxiety and depression, and peer social functioning. We used linear regression analysis to test the direct effect of trauma exposure on peer social functioning. We then tested whether depression and anxiety symptoms served as two potential parallel mediators in the association between trauma exposure and peer social functioning. Results: Trauma exposure was significantly associated with poor peer social functioning (β = −0.10, p = 0.005) when controlling for key covariates. When depression and anxiety symptoms were added to the model, the association between trauma exposure and peer social functioning became nonsignificant. Instead, there were significant indirect effects from trauma exposure to peer social functioning via depression (β = −0.06, 95%CI[−0.09, −0.03]) and anxiety (β = −0.02, 95%CI[−0.04, −0.00]). Conclusion: This study is among the first to link trauma exposure to peer social functioning deficits for children affected by parental HIV and demonstrates that symptoms of anxiety and depression mediate this relationship. Findings underscore the need for comprehensive psychosocial support for children affected by HIV, including screening for trauma exposure and mental health disorders

Synthesis of novel substituted N-aryl benzamides as hA3G stabilizers and their inhibitory activities against hepatitis C virus replication

AbstractA series of novel amino-substituted N-aryl benzamide analogs were synthesized and evaluated for their ability to inhibit hepatitis C virus (HCV) replication in acutely infected Huh7.5 cells. Most of the substituted N-aryl benzamide compounds showed convincing anti-HCV activities. Compounds 1f, 1g and 4c exhibited potent anti-replicative activity at low micromolar levels (IC50=1.0–2.0μM) with selective indices (SI) greater than 40. Mechanistic analysis indicated that the active compounds increased intracellular hA3G protein levels and inhibited HCV replication in a dose-dependent manner. The results demonstrate that this series of substituted N-aryl benzamide compounds warrant further investigation as inhibitors of HCV replication

Synthesis and antiviral activity of a series of novel N-phenylbenzamide and N-phenylacetophenone compounds as anti-HCV and anti-EV71 agents

AbstractA series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71 (strain SZ-98). The biological results showed that three compounds (23, 25 and 41) exhibited considerable anti-HCV activity (IC50=0.57–7.12μmol/L) and several compounds (23, 28, 29, 30, 31 and 42) displayed potent activity against EV71 with the IC50 values lower than 5.00μmol/L. The potency of compound 23 (IC50=0.57μmol/L) was superior to that of reported compounds IMB-1f (IC50=1.90μmol/L) and IMB-1g (IC50=1.00μmol/L) as anti-HCV agents, and compound 29 possessed the highest anti-EV71 activity, comparable to the comparator drug pirodavir. The efficacy in vivo and antiviral mechanism of these compounds warrant further investigations