Invited Mini Review Metabolic Bone Disease of Prematurity: Overview and Practice Recommendations.

Metabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex-utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum calcium, phosphorus, and alkaline phosphatase to identify infants at risk. If these labs are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of phosphate can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines.

Neighborhood adversity, child health, and the role for community development.

Despite medical advances, childhood health and well-being have not been broadly achieved due to rising chronic diseases and conditions related to child poverty. Family and neighborhood living conditions can have lasting consequences for health, with community adversity affecting health outcomes in significant part through stress response and increased allostatic load. Exposure to this "toxic stress" influences gene expression and brain development with direct and indirect negative consequences for health. Ensuring healthy child development requires improving conditions in distressed, high-poverty neighborhoods by reducing children's exposure to neighborhood stressors and supporting good family and caregiver functioning. The community development industry invests more than $200 billion annually in low-income neighborhoods, with the goal of improving living conditions for residents. The most impactful investments have transformed neighborhoods by integrating across sectors to address both the built environment and the social and service environment. By addressing many facets of the social determinants of health at once, these efforts suggest substantial results for children, but health outcomes generally have not been considered or evaluated. Increased partnership between the health sector and community development can bring health outcomes explicitly into focus for community development investments, help optimize intervention strategies for health, and provide natural experiments to build the evidence base for holistic interventions for disadvantaged children. The problems and potential solutions are beyond the scope of practicing pediatricians, but the community development sector stands ready to engage in shared efforts to improve the health and development of our most at-risk children.

Correlates of complementary and alternative medicine (CAM) use in Chicago area children with diabetes (DM).

AIMS: To correlate complementary and alternative medicine (CAM) use in children with diabetes mellitus (DM) with DM control and other family or disease characteristics. METHODS: Parents/guardians of children with DM were interviewed about demographics, clinical characteristics, CAM use, health care beliefs, psychosocial variables, and religious beliefs. The child's hemoglobin A1c (HgbA1c) value from the visit was collected. Statistical analyses included chi(2), Fisher's exact test, and 2-sample t-tests. RESULTS: 106 families with type 1 DM were interviewed. 33% of children tried CAM in the last year; 75% of parents had ever tried CAM. Children most commonly tried faith healing or prayer; parents most commonly tried faith healing or prayer, chiropractic, massage, and herbal teas. Children were more likely to have used CAM if their parents or siblings used CAM or their family was more religious. They were more likely to have discussed CAM with their providers if they used CAM. Parents of child CAM users reported more problems with DM treatment adherence. CONCLUSIONS: Children with DM used CAM. There were no differences in DM control, demographics, healthcare beliefs, stress, or quality of life between CAM users and non-users. Practitioners should inquire about CAM use to improve DM care for children.

Complementary and alternative medicine use in children with type 1 diabetes: a pilot survey of parents.

OBJECTIVE: The aim of this study was to examine the prevalence and characteristics of complementary and alternative medicine (CAM) use among children with diabetes. DESIGN: Anonymous surveys were completed by guardians of children with diabetes attending an urban diabetes clinic over three months. The survey included demographics, parent and child CAM use (excluding vitamins), and perceived opinions of health providers about CAM use. The representativeness of the surveyed sample was evaluated and analyses examined associations with child CAM use. RESULTS: Children in the analysis (N = 86, 33% response rate) were similar to the potential population for age, gender, insurance type, and age at diabetes diagnosis. Children analyzed were mean 10.9 years of age (SD 3.9), 56% male, 71% Caucasian, 83% privately insured, and 90% spoke English at home. Parents were 22% foreign born and 45% college graduates; 19% of children and 45% of parents had tried CAM. There were 30 CAM use occurrences among 16 children; 60% were CAM activities (ie, faith healing, chiropractic treatments, relaxation techniques) and 40% were CAM supplements (ie, herbs, nutritional supplements, herbal teas). Child CAM use was more common if a parent had used CAM (33% vs 6%; P = .002) and among children with foreign-born parents (37% vs 13%; P = .04). CAM was used to decrease diabetes complications and improve overall health. Parents were comfortable discussing CAM with the diabetes team and their child's primary care provider. CONCLUSIONS: Children with diabetes were using CAM as an adjunctive therapy for diabetes. The diabetes healthcare team needs an increased awareness about CAM.

Discovery of highly selective inhibitors of p38alpha.

The p38 MAP kinases are a family of serine/threonine protein kinases that play a key role in cellular pathways leading to pro-inflammatory responses. We have developed and implemented a method for rapidly identifying and optimizing potent and selective p38alpha inhibitors, which is amenable to other targets and target classes. A diverse library of druggable, purified and quantitated molecules was assembled and standardized enzymatic assays were performed in a microfluidic format that provided very accurate and precise inhibition data allowing for development of SAR directly from the primary HTS. All compounds were screened against a collection of more than 60 enzymes (kinases, proteases and phosphatases), allowing for removal of promiscuous and non-selective inhibitors very early in the discovery process. Follow-up enzymological studies included measurement of concentration of compound in buffer, yielding accurate determination of K(i) and IC50 values, as well as mechanism of action. In addition, active compounds were screened against less desirable properties such as inhibition of the enzyme activity by aggregation, irreversible binding, and time-dependence. Screening of an 88,634-compound library through the above-described process led to the rapid identification of multiple scaffolds (>5 active compounds per scaffold) of potential drug leads for p38alpha that are highly selective against all other enzymes tested, including the three other p38 isoforms. Potency and selectivity data allowed prioritization of the identified scaffolds for optimization. Herein we present results around our 3-thio-1,2,4-triazole lead series of p38- selective inhibitors, including identification, SAR, synthesis, selectivity profile, enzymatic and cellular data in their progression towards drug candidates.