Arango, Jorge

Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite–metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

OBJECTIVEThe goal of this study was to determine the functional efficacy of acellular processed nerve allograft (ALG) as compared to sural nerve autograft (AUG) harvested at time of surgery for children with obstetrical brachial plexus injury (OBPI).METHODSA retrospective review of records was performed in patients who underwent surgical repair of OBPI between 2009 and 2015 at Phoenix Children’s Hospital. Patients were grouped based on the type of nerve graft used (AUG using the patient’s own sural nerve or decellularized processed cadaveric nerve ALG) and compared in terms of motor strength, British Medical Research Council score, functionality (Mallet scale score), surgical time, rate of complications, and need for further intervention.RESULTSA total of 52 records were identified meeting study criteria. Sural nerve AUG was used in 22 cases and ALG in 30 cases. Changes from pre- to postsurgical assessment of motor strength were significant for all muscle groups measured except for elbow extension for both groups. All Mallet scores increased significantly. No significant differences were observed in motor strength and functional components between groups. Interventions using ALG had shorter operative times than those performed using AUG. No significant difference was observed in terms of need for further intervention. Two patients (9%) in the AUG group developed stitch abscesses at the harvest site, whereas there were no infectious complications reported in the ALG group.CONCLUSIONSThese findings suggest equivalence in terms of muscle strength and functional outcomes between the use of AUG and ALG for patients with OBPI. However, the less invasive character of ALG repair decreases surgical time and risk of complications.

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA‐containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in‐person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.