Background Maternal breast milk (MBM) is enriched in microRNAs, factors that regulate protein translation throughout the human body. MBM from mothers of term and preterm infants differ in nutrient, hormone, and bioactive factor composition, but the microRNA differences between these groups have not been compared. We hypothesized that gestational age at delivery influences microRNA in MBM, particularly microRNAs involved in immunologic and metabolic regulation. Methods MBM from mothers of premature infants (pMBM) obtained 3–4 weeks post-delivery was compared with MBM from mothers of term infants obtained at birth (tColostrum) and 3–4 weeks post-delivery (tMBM). The microRNA profile in lipid and skim fractions of each sample was evaluated with high-throughput sequencing. Results The expression profiles of nine microRNAs in lipid and skim pMBM differed from tMBM. Gene targets of these microRNAs were functionally related to elemental metabolism and lipid biosynthesis. The microRNA profile of tColostrum was also distinct from pMBM, but clustered closely with tMBM. Twenty-one microRNAs correlated with gestational age demonstrated limited relationships with method of delivery, but not other maternal infant factors. Conclusion Premature delivery results in a unique MBM microRNA profile with metabolic targets. This suggests preterm milk may have adaptive functions for growth in premature infants.

To assess the accuracy and physiological relevance of circulating microRNA (miRNA) as a biomarker of pediatric concussion, we compared changes in salivary miRNA and cerebrospinal fluid (CSF) miRNA concentrations after childhood traumatic brain injury (TBI). A case-cohort design was used to compare longitudinal miRNA concentrations in CSF of seven children with severe TBI against three controls without TBI. The miRNAs "altered" in CSF were interrogated in saliva of 60 children with mild TBI and compared with 18 age- and sex-matched controls. The miRNAs with parallel changes (Wilcoxon rank sum test) in CSF and saliva were interrogated for predictive accuracy of TBI status using a multivariate regression technique. Spearman rank correlation identified relationships between miRNAs of interest and clinical features. Functional analysis with DIANA mirPath identified related mRNA pathways. There were 214 miRNAs detected in CSF, and 135 (63%) were also present in saliva. Six miRNAs had parallel changes in both CSF and saliva (miR-182-5p, miR-221-3p, mir-26b-5p, miR-320c, miR-29c-3p, miR-30e-5p). These miRNAs demonstrated an area under the curve of 0.852 for identifying mild TBI status. Three of the miRNAs exhibited longitudinal trends in CSF and/or saliva after TBI, and all three targeted mRNAs related to neuronal development. Concentrations of miR-320c were directly correlated with child and parent reports of attention difficulty. Salivary miRNA represents an easily measured, physiologically relevant, and accurate potential biomarker for TBI. Further studies assessing the influence of orthopedic injury and exercise on peripheral miRNA patterns are needed.

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Background: Methadone is effective treatment for opioid addiction, but regulations restrict its use. Methadone medical maintenance treats stabilized methadone patients in a medical setting, but only experimental programs have been studied. Objective: To evaluate the implementation of the first methadone medical maintenance program established outside a reseach setting. Design: One‐year program evaluation. Setting: A public hospital and a community opioid treatment program. Participants: Methadone patients with >1 year of clinical stability. Eleven generalist physicians and 4 hospital pharmacists. Interventions: Regulatory exemptions were requested. Physicians and pharmacists were trained. Patients were transferred to the medical setting and permitted 1‐month supplies of methadone. Measurements: Patient eligibility and willingness to enroll, treatment retention, urine toxicology results, change in addiction severity and functional status, medical services provided, patient and physician satisfaction, and physician attitudes toward methadone maintenance. Results: Regulatory exemptions were obtained after a 14‐month process, and the program was cited in federal policy as acceptable for widespread implementation. Forty‐nine of 684 patients (7.2%) met stability criteria, and 30 enrolled. Twenty‐eight were retained for 1 year, and 2 transferred to other programs. Two patients had opioid‐positive urine tests and were managed in the medical setting. Previously unmet medical needs were addressed, and the Addiction Severity Index (ASI) medical composite score improved over time (P=.02). Patient and physician satisfaction were high, and physician attitudes toward methadone maintenance treatment became more positive (P=.007). Conclusions: Methadone medical maintenance is complex to arrange but feasible outside a research setting, and can result in good clinical outcomes.

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Examining community views on genetic/epigenetic research allows collaborative technology development. Parent perspectives toward genetic/epigenetic testing for autism spectrum disorder (ASD) are not well-studied. Parents of children with ASD (n = 131), non-ASD developmental delay (n = 39), and typical development (n = 74) completed surveys assessing genetic/epigenetic knowledge, genetic/epigenetic concerns, motives for research participation, and attitudes/preferences toward ASD testing. Most parents (96%) were interested in saliva-based molecular testing for ASD. Some had concerns about privacy (14%) and insurance-status (10%). None (0%) doubted scientific evidence behind genetic/epigenetic testing. Most reported familiarity with genetics (88%), but few understood differences from epigenetics (19%). Child developmental status impacted insurance concerns (p = 0.01). There is broad parent interest in a genetic/epigenetic test for ASD. It will be crucial to carefully consider and address bioethical issues surrounding this sensitive topic while developing such technology.

Studies in humans and pre-clinical animal models show milk-derived miRNAs reflect mammary gland function during lactation. The zinc transporter SLC30A2 /ZnT2 plays a critical role in mammary gland function; ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and secretion, resulting in sub-optimal lactation. Non-synonymous genetic variation in SLC30A2 is common in humans, and several common ZnT2 variants are associated with changes in milk components that suggest breast dysfunction in women. To identify novel mechanisms through which dysfunction might occur, milk-derived miRNA profiles were characterized in women harboring three common genetic variants in SLC30A2 (D 103 E, T 288 S, and Exon 7). Expression of ten miRNAs differed between genotypes, and contributed to distinct spatial separation. Studies in breast milk and cultured MECs confirmed expression of ZnT2 variants alters abundance of protein levels of several predicted mRNA targets critical for breast function (PRLR, VAMP7, and SOX4). Moreover, bioinformatic analysis identified two novel gene networks that may underlie normal MEC function. Thus, we propose that genetic variation in genes critical for normal breast function such as SLC30A2 has important implications for lactation performance in women, and that milk-derived miRNAs can be used to identify novel mechanisms and for diagnostic potential.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.