Latino Caregiver Psychosocial Factors and Health Care Services for Children Involved in the Child Welfare System.

Children in the child welfare system have a high prevalence of health problems, making pediatric health service use critical. Latino children represent a growing proportion of the child welfare system, and are at increased risk for health problems. Many have argued that Latino caregivers can provide Latino children with the least disruptive out-of-home placement, but little is known about how caregiver factors might relate to health services utilization or child health status within this population. This study assessed relationships between caregiver psychosocial factors, health care service utilization, and health status for children in the child welfare system. This sample featured 48 Latino caregivers involved in child welfare. Logistic regression models were used to test for relationships between caregiver psychosocial factors and appointment adherence and child health status. Problem-focused coping was positively related to well-child status. No psychosocial factors were related to medical appointment adherence. Case workers may help improve child health outcomes by promoting problem-focused coping skills among Latino caregivers.

Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.

Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91(phox). We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD.

IL-2-activated haploidentical NK cells restore NKG2D-mediated NK-cell cytotoxicity in neuroblastoma patients by scavenging of plasma MICA.

NK group 2D (NKG2D)-expressing NK cells exhibit cytolytic activity against various tumors after recognition of the cellular ligand MHC class I chain-related gene A (MICA). However, release of soluble MICA (sMICA) compromises NKG2D-dependent NK-cell cytotoxicity leading to tumor escape from immunosurveillance. Although some molecular details of the NKG2D-MICA interaction have been elucidated, its impact for donor NK (dNK) cell-based therapy of solid tumors has not been studied. Within an ongoing phase I/II trial, we used allogeneic IL-2 activated dNK cells after haploidentical stem cell transplantation for immunotherapy of patients with high-risk stage IV neuroblastoma. NKG2D levels on activated dNK cells increased strongly when compared with freshly isolated dNK cells and correlated with enhanced NK-cell cytotoxicity. Most importantly, elevated sMICA levels in patients plasma correlated significantly with impaired dNK-cell-mediated cytotoxicity. This effect could be reversed by high-dose infusion of activated dNK cells, which display high levels of surface NKG2D. Our data suggest that the provided excess of NKG2D leads to clearance of sMICA and preserves cytotoxicity of dNK cells via non-occupied NKG2D. In conclusion, our results identify this tumor immune escape mechanism as a target to improve immunotherapy of neuroblastoma and presumably other tumors.

The whole picture: Child maltreatment experiences of youths who were physically abused.

The purpose of the current study was to describe the maltreatment experiences of a sample of urban youths identified as physically abused using the Maltreatment Case Record Abstraction Instrument (MCRAI). The sample (n=303) of 9-12 year old youths was recruited from active child protective services (CPS) cases in 2002-2005, and five years of child protective service records were reviewed. The demographic and maltreatment experiences of MCRAI-identified youths with physical abuse were compared to maltreated youths who were not physically abused and youths who were identified as physically abused by CPS when they entered this longitudinal study. T-tests and chi-square tests were used to compare the demographics and maltreatment experiences of the sample MCRAI-identified physically abused to the sample MCRAI-identified as nonphysically abused maltreated by gender. Of the total sample, 156 (51%) were identified by MCRAI as physically abused and 96.8% of these youth also experienced other types of maltreatment. Whereas youth with the initial CPS identification of physical abuse showed little co-occurrence (37.7%) with other forms of maltreatment. The MCRAI-identified physically abused youths had a significantly higher mean number of CPS reports and higher mean number of incidents of maltreatment than MCRAI-identified nonphysically maltreated youths. Lifeline plots of case record history from the time of first report to CPS to entry into the study found substantial individual variability in maltreatment experiences for both boys and girls. Thus, obtaining maltreatment information from a single report vastly underestimates the prevalence of physical abuse and the co-occurrence of other maltreatment types.

IL-2-driven regulation of NK cell receptors with regard to the distribution of CD16+ and CD16- subpopulations and in vivo influence after haploidentical NK cell infusion.

To characterize natural killer (NK) cell subpopulations during activation, we analyzed the NK cell receptor repertoire and functionality of purified clinical scale CD56CD3 donor NK cells during stimulation with 1000 U/mL interleukin (IL)-2 for up to 14 days. In a phase I/II trial, we investigated the efficacy and feasibility of nonidentical NK cell infusion in patients with neuroblastoma after haploidentical stem cell transplantation. After IL-2 stimulation, large differences in the distribution of CD16 and CD16 subpopulations were found in 12 donors. Thereby, surface expression for all natural cytotoxicity receptors (NCRs) and NKG2D increased. In addition, killer cell immunoglobulin-like receptor (KIR) NK cells were overgrown by KIR proportion and the homing receptor CD62L was lost during stimulation. NK cell cytotoxicity against K562 and neuroblastoma cells increased and significantly higher cytokine secretion (eg, interferon-gamma, tumor necrosis factor-beta, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta) was observed after IL-2 stimulation compared with freshly isolated NK cells. However, NK cells of donors showing an initially enhanced cytotoxicity combined with NCR and CD69 expression, seemed to be exhausted and did not favor a stimulation period over 9 days. When IL-2-stimulated NK cells were given to transplant recipients, they induced a decrease of peripheral blood NK, in particular of CD56-NK cells. Our data indicate that IL-2 stimulation increases the expression of activating receptors and emphasizes mechanisms beside KIR/human leukocyte antigen. Furthermore, the results suggest that the expansion period of purified NK cells has to be individualized to optimize NK cell immunotherapy.