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bioRxiv2022

Sensing Echoes: Temporal misalignment as the Earliest Marker of Neurodevelopmental Derail

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3-4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy. Significance StatementAutism is currently detected on average after 4.5 years of age, based on differences in social interactions. Yet basic building blocks that develop to scaffold social interactions are present at birth and quantifiable at clinics. Auditory Brainstem Response tests, routinely given to neonates, infants, and young children, contain information about delays in signal transmission important for sensory integration. Although currently discarded as gross data under traditional statistical approaches, new analytics reveal unambiguous differences in ABR signals fluctuations between typically developing neonates and those who received an autism diagnosis. With very little effort and cost, these new analytics could be added to the clinical routine testing of neonates to create a universal screening tool for neurodevelopmental derailment and prodrome of autism.

neuroscience↗

bioRxiv2019

Short-, medium- and long-term metabolic responses of adult ewes submitted to nutritional and β-adrenergic challenges

BackgroundIn order to maintain homeostasis, ruminants submitted to alternating shortage and refeeding situations manifest switches in metabolic pathways induced by undernutrition and body reserves (BR) replenishment cycles. The objective of this experiment was to study adaptive regulatory mechanisms present during subsequent feeding transition periods and the inherent lipolytic activity of the adipose tissue in individuals with contrasted BR. Three diets containing different levels of energy were offered to 36 mature, dry, non-pregnant Merinos dArles ewes in an experiment lasting 122 days. Ewes were selected with similar body weight (BW), body condition score (BCS) and were allocated into three equivalent treatments according to the plane of nutrition: normally fed (Control); underfed (Under) or overfed (Over). The BW, BCS and individual energy metabolism were monitored. At the end of the experiment, lipolytic activity of adipose tissue was studied through a {beta}-adrenergic challenge to the same ewes, with body conditions according to the offered diet (Normal, Leans and Fat, respectively).\n\nResultsAnabolic or catabolic responses to energy dietary manipulation were accompanied by synchronised metabolic regulation, leading to contrasting metabolic and BR profiles. Average BW and BCS were higher and lower in Over and Under ewes, respectively. The higher and lower BR variations were observed for Under and Over ewes. Higher plasma non-esterified fatty acids (NEFA) concentrations were accompanied by lower insulin, leptin and glucose. Differences in leptin were consistent with the dietary energy load (Over > Control > Under). After refeeding, a rebound in BW and BCS was observed for the three groups whereas NEFA was drastically reduced in Under ewes. No differences among treatments were detected in NEFA profiles at the end of the study but lipolytic activity responses to the {beta} - adrenergic challenge were different and coherent with the adipose tissue mass (Fat > Normal > Lean) and, importantly, was also different between ewes from the same group or BR status, thus evidencing diversity among individual adaptive capacities.\n\nConclusionsThe ability of ewes to quickly overcome undernutrition situations by efficiently using their BR was confirmed. There is potential for a simplified {beta}-adrenergic challenge protocol helping to identify differences in adaptive capacity among individuals.

physiology↗