Parental perceptions of body weight and appetite in infants and toddlers with cystic fibrosis.

Nutritional status has clinical relevance and is a target of guidance to parents of children with cystic fibrosis (CF). Growth is routinely monitored in CF clinics but there is no standardized way of assessing appetitive behaviors or parents' perceptions of their children's appetite. Greater understanding of these factors could improve clinical guidance regarding parent feeding behaviors. We therefore aimed to assess parent perceptions of child weight, and parent reports of child appetite using the Baby Eating Behavior Questionnaire (BEBQ), in a sample of infants and toddlers with CF, compared with a community sample. We additionally assessed relationships of parent perceptions of child weight with parent feeding behaviors in the sample with CF. Anthropometric and questionnaire data were collected for 32 infants and toddlers with CF, as well as 193 infants and toddlers drawn from RESONANCE, a community cohort study. Parents perceived children with CF to be lower in weight than their actual weight, to a greater extent than was evident in the community sample. Parents who perceived their children with CF to be underweight vs. right weight reported greater slowness in eating on the BEBQ. Parents perceived children with CF to have greater slowness in eating and lower enjoyment of food, compared to parents of children in the community sample, independent of sample differences in child weight, age, and sex. Our results demonstrate the potential utility of the BEBQ in a clinical sample and suggest it may be helpful for clinicians to assess parents' perceptions of their child's weight and appetite to promote a fuller understanding of the child's nutritional status, facilitate appropriate feeding behaviors and alleviate unnecessary concerns.

Eating disorder symptom non-endorsers in hospitalised patients with anorexia nervosa: Who are they?

OBJECTIVE: Impaired insight and illness denial are common in anorexia nervosa (AN). Missing an AN diagnosis may delay treatment and negatively impact outcomes. METHOD: The current retrospective study examined the prevalence and characteristics of AN symptom non-endorsement (i.e., scoring within the normal range on the Eating Disorder Examination Questionnaire [EDE-Q] or the Eating Disorder Examination [EDE] interview) in three independent samples of hospitalised patients with AN (N1 = 154; N2 = 300; N3 = 194). A qualitative chart review of a subsample of non-endorsers (N4 = 32) extracted reports of disordered eating behaviours observed by the treatment team. RESULTS: The prevalence of non-endorsement ranged from 11% to 34% across sites. Non-endorsers were more likely to be diagnosed with AN restricting type (AN-R) and reported fewer symptoms of co-occurring psychopathology than endorsers. Groups benefitted equally from treatment. The qualitative chart review indicated that objective symptoms of AN were recorded by staff in over 90% of non-endorsers. CONCLUSIONS: Eating disorder symptom assessments using the EDE-Q or EDE may miss symptomatology in up to a third of individuals hospitalised with AN. This study highlights the potential utility of multi-modal assessment including patient interviews, collateral informants, and behavioural observation to circumvent non-endorsement.

Unbiased Quantitative Single-Cell Morphometric Analysis to Identify Microglia Reactivity in Developmental Brain Injury.

Microglia morphological studies have been limited to the process of reviewing the most common characteristics of a group of cells to conclude the likelihood of a "pathological" milieu. We have developed an Imaris-software-based analytical pipeline to address selection and operator biases, enabling use of highly reproducible machine-learning algorithms to quantify at single-cell resolution differences between groups. We hypothesized that this analytical pipeline improved our ability to detect subtle yet important differences between groups. Thus, we studied the temporal changes in Iba1+ microglia-like cell (MCL) populations in the CA1 between P10-P11 and P18-P19 in response to intrauterine growth restriction (IUGR) at E12.5 in mice, chorioamnionitis (chorio) at E18 in rats and neonatal hypoxia-ischemia (HI) at P10 in mice. Sholl and convex hull analyses differentiate stages of maturation of Iba1+ MLCs. At P10-P11, IUGR or HI MLCs were more prominently 'ameboid', while chorio MLCs were hyper-ramified compared to sham. At P18-P19, HI MLCs remained persistently 'ameboid' to 'transitional'. Thus, we conclude that this unbiased analytical pipeline, which can be adjusted to other brain cells (i.e., astrocytes), improves sensitivity to detect previously elusive morphological changes known to promote specific inflammatory milieu and lead to worse outcomes and therapeutic responses.

Sexual Dimorphism in the Closure of the Hippocampal Postnatal Critical Period of Synaptic Plasticity after Intrauterine Growth Restriction: Link to Oligodendrocyte and Glial Dysregulation.

Intrauterine growth restriction (IUGR) resulting from hypertensive disease of pregnancy (HDP) leads to sexually dimorphic hippocampal-dependent cognitive and memory impairment in humans. In our translationally relevant mouse model of IUGR incited by HDP, we have previously shown that the synaptic development in the dorsal hippocampus including GABAergic development, NPTX2+ excitatory synaptic formation, axonal myelination, and perineural net (PNN) formation were perturbed by IUGR at adolescent equivalence in humans (P40). The persistence of these disturbances through early adulthood and the potential upstream mechanisms are currently unknown. Thus, we hypothesized that NPTX2+ expression, PNN formation, axonal myelination, all events closing synaptic development in the hippocampus, will be persistently perturbed, particularly affecting IUGR female mice through P60 given the fact that they had worse short-term recognition memory in this model. We additionally hypothesized that such sexual dimorphism is linked to persistent glial dysregulation. We induced IUGR by a micro-osmotic pump infusion of a potent vasoconstrictor U-46619, a thromboxane A2-analog, in the last week of the C57BL/6 mouse gestation to precipitate HDP. Sham-operated mice were used as controls. At P60, we assessed hippocampal and hemispheric volumes, NPTX2 expression, PNN formation, as well as myelin basic protein (MBP), Olig2, APC/CC1, and M-NF expression. We also evaluated P60 astrocytic (GFAP) reactivity and microglial (Iba1 and TMEM119) activation using immunofluorescent-immunohistochemistry and Imaris morphological analysis plus cytokine profiling using Meso Scale Discovery platform. IUGR offspring continued to have smaller hippocampal volumes at P60 not related to changes in hemisphere volume. NPTX2+ puncta counts and volumes were decreased in IUGR hippocampal CA subregions of female mice compared to sex-matched shams. Intriguingly, NPTX2+ counts and volumes were concurrently increased in the dentate gyrus (DG) subregion. PNN volumes were smaller in CA1 and CA3 of IUGR female mice along with PNN intensity in CA3 but they had larger volumes in the CA3 of IUGR male mice. The myelinated axon (MBP+) areas, volumes, and lengths were all decreased in the CA1 of IUGR female mice compared to sex-matched shams, which correlated with a decrease in Olig2 nuclear expression. No decrease in the number of APC/CC1+ mature oligodendrocytes was identified. We noted an increase in M-NF expression in the mossy fibers connecting DG to CA3 only in IUGR female mice. Reactive astrocytes denoted by GFAP areas, volumes, lengths, and numbers of branching were increased in IUGR female CA1 but not in IUGR male CA3 compared to sex-matched shams. Lastly, activated microglia were only detected in IUGR female CA1 and CA3 subregions. We detected no difference in the cytokine profile between sham and IUGR adult mice of either sex. Collectively, our data support a sexually dimorphic impaired closure of postnatal critical period of synaptic plasticity in the hippocampus of young adult IUGR mice with greater effects on females. A potential mechanism supporting such dimorphism may include oligodendrocyte dysfunction in IUGR females limiting myelination, allowing axonal overgrowth followed by a reactive glial-mediated synaptic pruning.

Parental dieting impacts inpatient treatment outcomes for adolescents with restrictive eating disorders.

OBJECTIVE: Parental feeding practices and disordered eating are potential risk factors for the development of disordered eating in children and adolescents. This study measured the relationship between parental dieting behaviours and inpatient treatment outcomes for adolescents with restrictive eating disorders (EDs). METHOD: Parents of adolescents with restrictive EDs (N = 45) admitted to a specialty integrated inpatient-partial hospital meal-based ED treatment programme completed questionnaires assessing parental eating and exercise behaviours. Adolescent clinical data, including percentage median body mass index (%mBMI) at admission and discharge and rate of weight gain, were abstracted from the electronic medical record. RESULTS: Adolescents whose parents reported dieting had a slower rate of weight gain (3.47 lbs./week) compared to participants whose parents were not dieting (4.54 lbs./week; p = 0.017). Additionally, participants whose parents reported dieting had a lower %mBMI at programme discharge (M = 93.56) than participants whose parents did not report dieting (M = 95.99; p = 0.033). CONCLUSION: Parental dieting behaviours may impact an adolescent's response to inpatient ED treatment. Findings suggest a need to assess parental dieting behaviour, and when appropriate, provide additional psychoeducation regarding the potential risks of weight or shape-focussed dialogue and the benefits of modelling adaptive meal behaviours.

Greater dietary variety is associated with lower food anxiety at discharge from intensive eating disorder treatment.

OBJECTIVE: Food anxiety and limited dietary variety often persist after intensive treatment for eating disorders (EDs) and may contribute to relapse. Prior studies demonstrate decreased meal-related anxiety with residential or inpatient treatment, but less is known about changes in dietary variety and anxiety associated with specific foods. The current study assessed change in food anxiety and dietary variety in inpatients with EDs (anorexia nervosa and bulimia nervosa) in relation to discharge outcomes from meal-based behavioral treatment. METHOD: Patients (N = 128) admitted to a specialized, hospital-based behavioral treatment program completed measures of food anxiety, dietary variety, and ED symptoms at admission and discharge. Demographic and clinical data were abstracted from electronic medical records. A novel network community analysis identified three food anxiety groups: fruit-veg, animal-based, and carb-based foods. RESULTS: High-energy density combination foods were most anxiety-provoking and most avoided. Food anxiety decreased, and dietary variety increased from admission to discharge. Reduction in food anxiety was associated with lower ED symptom scores and higher normative eating self-efficacy at discharge. For animal-based foods, increased dietary variety was associated with lower food anxiety at discharge. Neither variety nor anxiety was associated with weight restoration. DISCUSSION: Findings highlight the importance of broadening dietary variety and targeting food anxiety during the nutritional rehabilitation and weight restoration phase of ED treatment. Increasing dietary variety may contribute to reduced food anxiety, which, in turn, may increase normative eating self-efficacy. These results may help inform nutritional guidelines for meal-based treatment programs. PUBLIC SIGNIFICANCE: Consuming a greater variety of foods during meal-based intensive treatment may help alleviate food anxiety in patients with eating disorders.

Dysregulation of ErbB4 Signaling Pathway in the Dorsal Hippocampus after Neonatal Hypoxia-Ischemia and Late Deficits in PV+ Interneurons, Synaptic Plasticity and Working Memory.

Neonatal hypoxic-ischemic (HI) injury leads to deficits in hippocampal parvalbumin (PV)+ interneurons (INs) and working memory. Therapeutic hypothermia (TH) does not prevent these deficits. ErbB4 supports maturation and maintenance of PV+ IN. Thus, we hypothesized that neonatal HI leads to persistent deficits in PV+ INs, working memory and synaptic plasticity associated with ErbB4 dysregulation despite TH. P10 HI-injured mice were randomized to normothermia (NT, 36 °C) or TH (31 °C) for 4 h and compared to sham. Hippocampi were studied for α-fodrin, glial fibrillary acidic protein (GFAP), and neuroregulin (Nrg) 1 levels; erb-b2 receptor tyrosine kinase 4 (ErbB4)/ Ak strain transforming (Akt) activation; and PV, synaptotagmin (Syt) 2, vesicular-glutamate transporter (VGlut) 2, Nrg1, and ErbB4 expression in coronal sections. Extracellular field potentials and behavioral testing were performed. At P40, deficits in PV+ INs correlated with impaired memory and coincided with blunted long-term depression (LTD), heightened long-term potentiation (LTP) and increased Vglut2/Syt2 ratio, supporting excitatory-inhibitory (E/I) imbalance. Hippocampal Nrg1 levels were increased in the hippocampus 24 h after neonatal HI, delaying the decline documented in shams. Paradoxically ErbB4 activation decreased 24 h and again 30 days after HI. Neonatal HI leads to persistent deficits in hippocampal PV+ INs, memory, and synaptic plasticity. While acute decreased ErbB4 activation supports impaired maturation and survival after HI, late deficit reemergence may impair PV+ INs maintenance after HI.