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.
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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