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ct on precision and accuracy before the test is deployed in research studies or clinical practice.BACKGROUND To define the role of topical timolol maleate (TTM) in the treatment of infantile haemangiomata (IH). METHODS In this single-centre randomised controlled trial, we included all less then 1-year-old infants within a 13-month period presenting with small ( less then 2 cm) superficial IH located at high-risk areas (i.e. tip of ears, tip of nose, eyelids, acral areas, facial areas, scalp, neck, buttocks, perineum and axilla). Patients either received 12 months of 0.5% TTM solution (study group) or watchful waiting (control group). The primary outcome was IH with development of complications that required additional interventions. The secondary outcomes included side effects of TTM and change in IH size. RESULTS Forty-two children were eligible to the study. Patients who received TTM were noted to have significantly fewer complications than the control group (4.2% versus 29%, odds ratio 9.58 [95% confidence interval 1.01-91.62], p = 0.04). Mean IH volume percentage reduction was significantly more for the TTM group and no-TTM group at 3, 6 and 12 months. CONCLUSIONS TTM is an effective and safe treatment option to reduce complications, IH volume and the need for further intervention for infants with small superficial IH located at high-risk areas. IMPACT There is a lack of reliable signs to predict ulceration, disfigurement and other complications for high-risk IH.Treatment options range from watchful waiting to early systemic treatment, with TTM a novel and promising treatment.The exact role of TTM remains unanswered due to a lack of evidence-based research.TTM is effective and safe for infants with superficial IH of less then 2 cm in high-risk areas.Early TTM use on IH can reduce complications, IH volume and the need for further treatment.BACKGROUND Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. METHODS To determine whether increasing fecal cholesterol excretion could ameliorate unconjugated hyperbilirubinemia, we treated hyperbilirubinemic Gunn rats with ezetimibe (EZE), an intestinal cholesterol absorption inhibitor, and/or a liver X receptor (LXR) and farnesoid X receptor (FXR) agonist (T0901317 (T09) and obeticholic acid (OCA), respectively), known to stimulate TICE. RESULTS We found that EZE treatment alone or in combination with T09 or OCA increased fecal cholesterol disposal but did not lower plasma UCB levels. CONCLUSIONS These findings do not support a link between the regulation of transintestinal excretion of cholesterol and bilirubin. Furthermore, induction of fecal cholesterol excretion is not a potential therapy for unconjugated hyperbilirubinemia. IMPACT Increasing fecal cholesterol excretion is not effective to treat unconjugated hyperbilirubinemia.This is the first time a potential relation between transintestinal excretion of cholesterol and unconjugated bilirubin is investigated.Transintestinal excretion of cholesterol and unconjugated bilirubin do not seem to be quantitatively linked.Unlike intestinal fatty acids, cholesterol cannot “capture” unconjugated bilirubin to increase its excretion.These results add to our understanding of ways to improve and factors regulating unconjugated bilirubin disposal in hyperbilirubinemic conditions.BACKGROUND Although it is commonly accepted that upper airway obstruction (UAO) increases gastroesophageal reflux (GER), the link is poorly understood and insufficiently documented. learn more In addition, while hypoxia is often encountered in infants with UAO, its consequences on GER are virtually unknown. The two aims of the present study were to characterize the effects of (1) UAO and (2) hypoxia on GER. METHODS Seventeen lambs underwent polysomnographic and esophageal impedance/pH-metry monitoring during UAO vs. a control condition (6 h, ten lambs) or 10% hypoxia vs. normoxic condition (3 h, seven other lambs). RESULTS Moderate-to-severe UAO was maintained throughout monitoring (inspiratory tracheal pressure of -13 (-15, -12) cm H2O vs. -1 (-1, -1) cm H2O in control condition, p = 0.005). While the number of GERs increased with UAO (2 (1, 4) vs. 0 (0, 3) in the control condition, p = 0.03), the increase was less than anticipated and inconsistent among the lambs. Also, sustained 10% hypoxia did not alter the number of GERs (2 (1, 3) vs. 0 (0, 5) in the control condition, p = 0.9). CONCLUSIONS The presence of an UAO for 6 h mildly increased the number of GERs, whereas hypoxia for 3 h had no significant effect. IMPACT The effect of upper airway obstruction and hypoxia on gastroesophageal reflux is poorly documented in the neonatal period. A moderate-to-severe upper airway obstruction for 6 h results in a mild, inconsistent increase in the number of gastroesophageal refluxes. Overall, a hypoxia of 10% for 3 h had no significant impact on gastroesophageal reflux. The prescription of an antireflux medication in infants with upper airway obstruction must not be systematic but rely on objective signs of a pathologic gastroesophageal reflux.Previous studies have shown the presence of several subunits of the inhibitory glycine receptor (GlyR) in the reward system, specifically in medium spiny neurons (MSNs) of the nucleus Accumbens (nAc). It was suggested that GlyR α1 subunits regulate nAc excitability and ethanol consumption. However, little is known about the role of the α2 subunit in the adult brain since it is a subunit highly expressed during early brain development. In this study, we used genetically modified mice with a mutation (KR389-390AA) in the intracellular loop of the GlyR α2 subunit which results in a heteromeric α2β receptor that is insensitive to ethanol. Using this mouse model denoted knock-in α2 (KI α2), our electrophysiological studies showed that neurons in the adult nAc expressed functional KI GlyRs that were rather insensitive to ethanol when compared with WT GlyRs. In behavioral tests, the KI α2 mice did not show any difference in basal motor coordination, locomotor activity, or conditioned place preference compared with WT littermate controls.