Postnatal neurodevelopment is profoundly influenced by environmental experiences. Environmental enrichment is a commonly used experimental paradigm that has uncovered numerous examples of experience-dependent plasticity in health and disease. However, the role of environmental enrichment in normal development, especially glial development, is largely unexplored. Oligodendrocytes, the myelin-forming glia in the central nervous system, provide metabolic support to axons and establish efficient saltatory conduction by producing myelin. Indeed, alterations in myelin are strongly correlated with sensory, cognitive, and motor function. The timing of developmental myelination is uniquely positioned to be influenced by environmental stimuli, as peak myelination occurs postnatally and continues into adulthood. To determine if developmental myelination is impacted by environmental experience, mice were housed in an enriched environment during peak myelination through early adulthood. Using translating ribosome affinity purification, oligodendrocyte-specific RNAs were isolated from subcortical white matter at various postnatal ages. RNA-sequencing revealed that differences in the oligodendrocyte translatome were predominantly evident after prolonged and continuous environmental enrichment. These translational changes corresponded with altered oligodendrocyte lineage cell dynamics and enhanced myelination. Furthermore, consistent with increased developmental myelination, enriched mice displayed enhanced motor coordination on a beam walking task. These findings indicate that protracted environmental stimulation is sufficient to modulate developmental myelination and to promote behavioral function.
Background
Patients admitted to the pediatric intensive care unit (PICU) are frequently evaluated for bacterial infections and initiated on antibiotic regimens that include a MRSA-active agent even though invasive MRSA infections are rare in this population. The MRSA PCR nasal swab (MRSA-PCR) is a non-invasive test for MRSA colonization that has been shown within adult ICUs to have a high negative predictive value (NPV), making it a potentially valuable tool for antimicrobial stewardship. This study evaluated the performance of the MRSA-PCR in predicting invasive MRSA infection in critically ill pediatric patients.
Methods
A retrospective cohort study was performed in a 44-bed PICU from January 2013 to December 2018 when it was protocol for all admissions to be screened with a MRSA-PCR. Patients who had both a MRSA-PCR and cultures obtained to evaluate for invasive infection within seven days were included in the study. Invasive MRSA infection was defined by the isolation of MRSA from clinical cultures along with infectious signs and symptoms. A random sample comprising 55% of the patient population was evaluated. We calculated sensitivity, specificity, positive predictive value (PPV) and NPV of the MRSA-PCR for confirmed invasive MRSA infection.
Results
Of the 4,410 patients reviewed, 1,961 patients met inclusion criteria (45% female, mean age 7.4 yrs. [birth-19.9 yrs.]). MRSA-PCR was positive in 13.5% of patients. Invasive MRSA infection was identified in 25 patients (2 blood, 19 respiratory, 2 soft tissue, 1 pleural fluid, and 1 urine culture) equaling 1.2% of encounters and an incidence rate of 1.1 case per 1,000 patient days. The MRSA-PCR demonstrated a PPV of 8.7% and a NPV of 99.8% (see table).
Conclusion
The MRSA-PCR has a poor PPV but a very high NPV for invasive MRSA infection in critically ill pediatric patients, a result that is congruent with what has been reported in the adult literature. The high NPV of the MRSA-PCR in this vulnerable patient population makes it a potentially powerful tool for antimicrobial stewardship. Creation of protocols to guide antimicrobial selection based on MRSA-PCR results may lead to a significant reduction in unnecessary antibiotic exposure, drug level monitoring, and patient risk of renal injury or adverse reactions.
Disclosures
All Authors: No reported disclosures.
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