Primary Immune Deficiency Treatment Consortium (PIDTC) report.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

The YaaA protein of the Escherichia coli OxyR regulon lessens hydrogen peroxide toxicity by diminishing the amount of intracellular unincorporated iron.

Hydrogen peroxide (H(2)O(2)) is commonly formed in microbial habitats by either chemical oxidation processes or host defense responses. H(2)O(2) can penetrate membranes and damage key intracellular biomolecules, including DNA and iron-dependent enzymes. Bacteria defend themselves against this H(2)O(2) by inducing a regulon that engages multiple defensive strategies. A previous microarray study suggested that yaaA, an uncharacterized gene found in many bacteria, was induced by H(2)O(2) in Escherichia coli as part of its OxyR regulon. Here we confirm that yaaA is a key element of the stress response to H(2)O(2). In a catalase/peroxidase-deficient (Hpx(-)) background, yaaA deletion mutants grew poorly, filamented extensively, and lost substantial viability when they were cultured in aerobic LB medium. The results from a thyA forward mutagenesis assay and the growth defect of the yaaA deletion in a recombination-deficient (recA56) background indicated that yaaA mutants accumulated high levels of DNA damage. The growth defect of yaaA mutants could be suppressed by either the addition of iron chelators or mutations that slowed iron import, indicating that the DNA damage was caused by the Fenton reaction. Spin-trapping experiments confirmed that Hpx(-) yaaA cells had a higher hydroxyl radical (HO(•)) level. Electron paramagnetic resonance spectroscopy analysis showed that the proximate cause was an unusually high level of intracellular unincorporated iron. These results demonstrate that during periods of H(2)O(2) stress the induction of YaaA is a critical device to suppress intracellular iron levels; it thereby attenuates the Fenton reaction and the DNA damage that would otherwise result. The molecular mechanism of YaaA action remains unknown.

Identifying characteristics and outcomes in youth with obesity and developmental disabilities.

BACKGROUND: Youth with developmental disability are at increased risk of obesity; literature focusing on the two is rare. OBJECTIVE: To identify characteristics and outcomes of youth presenting for obesity care having a disability as compared to without. METHODS: A medical record review of youth aged 2-18 years initiating obesity care 2013-2015 at a tertiary care obesity management program. Youth were grouped by disability status to identify differences in presenting characteristics and factors associated with a reduction in body mass index (BMI) percent of the 95th BMI percentile (BMIp95) over 12 months. Logistic regression (LR) models examined associations with BMIp95 drop (<5-points versus ≥5-points) for each disability group. RESULTS: Of 887 subjects, 253 (28.5%) had a disability. At presentation, youth with disability were more often (p < 0.01) male (58.5% versus 47.9%), had birth weight <2500 g (14.1% versus 8.4%), had a father who was not obese (61.6% versus 47.4%), and were on weight influencing medications. Overall, 182 subjects (20.5%) completed 12-month follow-up. At follow-up, the with disability group (n = 63) had mean -2.3 (SD 10.7) BMIp95 change (p = 0.679); youth having a motor disability less often had ≥5-point BMIp95 drop (odds ratio 0.15, 95% confidence interval 0.04-0.59). At follow-up, the no disability group (n = 119) had mean -2.9 (SD 8.5) BMIp95 change; youth identified as having initial severe obesity status and not having a parent with diabetes more often had ≥5-point BMIp95 drop. CONCLUSION: Youth with developmental disabilities were as successful in obesity care as those without disabilities. Predictors of success differed between the groups.

Primary Care-Based Interventions to Promote Positive Parenting Behaviors: A Meta-analysis.

CONTEXT: Utilization of primary care settings offers a promising approach to enhance parenting practices that are critical for promoting early childhood development. Determining the impact of existing primary care interventions on key parenting behaviors will aid providers and policy makers as they seek strategies to improve early child outcomes. OBJECTIVE: To evaluate the efficacy of primary care-based interventions on parenting practices that promote early child development among children younger than 36 months. DATA SOURCES: PubMed, Excerpta Medica dataBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature databases were searched electronically. STUDY SELECTION: English-language articles that were quasi-randomized or randomized controlled trials, included parents of children <36 months of age, and reported outcomes related to parenting behaviors that promote early child development. DATA EXTRACTION: Two reviewers independently extracted data regarding participants, interventions, and outcomes. Quantitative meta-analyses were conducted with random effects for study and fitted with restricted maximum likelihood methods. RESULTS: The review included 13 studies reporting parenting outcomes in 2 categories: participation in cognitively stimulating activities and positive parent-child interactions. We found a statistically significant positive effect of primary care-delivered interventions and parent-child interactions (summary standardized mean difference 0.29, 95% confidence interval [CI] 0.06-0.52, P < .0001) and participation in cognitively stimulating activities (summary standardized mean difference 0.34, 95% CI 0.03-0.54; summary odds ratio 0.13, 95% CI 0.01-0.25, P < .0001). LIMITATIONS: Limitations included heterogeneity in measures used, outcomes, and timing of assessments. CONCLUSIONS: Primary care-based interventions modestly affect positive parenting behaviors important for early childhood development. Randomized controlled trials with comparable outcome measures using standardized assessments are needed to assess further beneficial impacts.

Genetic testing for autism spectrum disorders.

Children with autism spectrum disorders (ASD) have unique developmental and behavioral phenotypes, and they have specific challenges with communication, social skills, and repetitive behaviors. At this time, no single etiology for ASD has been identified. However, evidence from family studies and linkage analyses suggests that genetic factors play a pivotal role in the etiology of ASD. However, ASD appear to be influenced by complex genetic and environmental factors, and evidence suggests that this is not a single gene disorder. In particular, ASD has a complex behavioral phenotype, and this variation reflects complex genotypes under the influence of external factors. With these considerations in mind, it is important to recognize that genetic testing is a vital component of the diagnostic evaluation of children with ASD. For example, children with ASD who have definitive etiologies may be able to access more specific resources, they may be spared long, emotionally and financially exhausting diagnostic journeys, and associated medical conditions and comorbidities can be managed proactively. Most importantly, children with disabilities of unknown origin should have an ongoing evaluation of potential etiologies for their symptoms (Crocker, 1987). Our purpose is to describe current trends in genetic testing for ASD, potential genetic etiologies of ASD, known genetic disorders associated with ASD, and recommendations for genetic testing in ASD. We will also emphasize the importance of access to informed health professionals, especially in the contexts of stigma and community supports.

Kindergarten readiness after prematurity: Integrating health, development, and behavioral functioning to optimize educational outcomes of vulnerable children.

In the past 20 years, many advances (e.g., maternal steroids and surfactant) have changed the course of neonatal medicine. As a result, extremely preterm infants survive medical complications that were previously fatal. Once they are discharged from the neonatal intensive care unit, preterm infants may continue to experience a spectrum of medical and developmental challenges, and their families are faced with the potentially daunting task of nurturing a vulnerable child. Families may be referred to multiple systems of care, including primary care physicians, pediatric subspecialists, and early intervention services. The ultimate goal for preterm infants is to optimize their motor, communicative, social-emotional, and adaptive development as well as to promote their learning at home, at school, and in the community. As children transition to school, key indicators of their functional status include the amount of developmental, educational, habilitative, and behavioral supports they require to participate in learning activities with their peers. Success may be measured by whether preterm infants are ready for large-group learning with peers and the extent of supports required to make this important transition. The purpose of this review is to describe what is known about certain indicators of school readiness in preterm infants, including neurodevelopmental impairments, social-emotional skills, and social factors. We conclude with guidelines for using this transition as an important indicator of developmental trajectories that may help us to better understand risk and resilience in this vulnerable population of children.