Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets with less β-cells, and impaired pancreatic vascularity. To test whether supplemental amino acids infused into the IUGR fetus could improve these complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino acid infusions into a sheep model of placental insufficiency and IUGR near the end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin secretion compared with control fetuses. These results were confirmed in isolated IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal glucose-stimulated insulin secretion and islet size were restored to control values. These changes were associated with normalization of fetal pancreatic vascularity and higher fetal pancreatic vascular endothelial growth factor A protein concentrations. These results demonstrate that decreased fetal amino acid supply contributes to the pathogenesis of pancreatic islet defects in IUGR. Moreover, the results show that pancreatic islets in IUGR fetuses retain their ability to respond to increased amino acids near the end of gestation after chronic fetal growth restriction.

Objectives To evaluate the precision of aligner (Invisalign®) treatment with the current material (SmartTrack®) in achieving expansion or contraction of the maxilla and occlusal contacts as simulated in the proprietary planning software (ClinCheck®, CC). Materials and methods Thirty patients thus treated were retrospectively evaluated. Four maxillary models were analyzed per patient: a pretreatment model, a scan-based CC model, a posttreatment clinical model, and a CC model reflecting the treatment outcome as initially simulated. Thirteen transverse parameters were measured on each model separately by two investigators. Occlusal contacts were also analyzed. Results The measuring method was validated by both investigators arriving at similar results for the effectiveness by which the simulated treatment goals had been clinically achieved. Significant differences (p < 0.05; Wilcoxon signed-rank test) were observed for transfer precision from the casts to the planning software and between the simulated and clinical outcomes. Intense occlusal contacts in the simulations materialized less common (≈ 2%) than ideal contacts (≈ 60%) in the clinical outcomes. Conclusions The effectiveness of achieving the simulated transverse goals was 45% and was generally not found to be better with SmartTrack® than with the previously used Ex30® material. Out of 100 simulated occlusal contacts, 40 will never materialize, and achieving around 60 will adequately ensure a clinically favorable contact pattern. Clinical relevance With the caveat that any overcorrection will to some extent reduce the precision, it seems perfectly possible to make deliberate use of overcorrection in current aligner therapies for transverse maxillary expansion or contraction.

Overcoming impaired growth in an intrauterine growth restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We tested whether prolonged amino acid infusion would increase protein accretion in the IUGR fetus produced from chronic placental insufficiency. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg·day (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in IUGR-AA vs. IUGR-Sal (P<0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were 4-fold higher in IUGR-AA (P<0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus, the total amino acid delivery rate (net umbilical amino acid uptake plus infusion rate) was higher in IUGR-AA (IUGR-AA 30 ± 4, IUGR-Sal 19 ± 1 μmol·kg·min, P<0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate measured using a leucine tracer was higher in IUGR-AA (IUGR-AA 2.5 ± 0.3, IUGR-Sal 1.7 ± 0.3 μmol·kg·min, P<0.05). Fetal protein accretion rate was not statistically different between the IUGR groups due to variability in response to amino acids (IUGR-AA 1.6 ± 0.4, IUGR-Sal 0.8 ± 0.3 μmol·kg-1·min). Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.