Occupational Performance Coaching for parents of picky eaters: A mixed methods study.

BACKGROUND/AIM: Picky eating is a common childhood phenomenon that impacts many families' occupations surrounding mealtimes. Evidence of the effectiveness of Occupational Performance Coaching (OPC) for caregivers of children suggests it may represent a useful occupation-focused intervention for parents of picky eaters. Using an OPC-targeted intervention, this study aims to report preliminary effectiveness, explore the experience of parents' participation, and investigate factors that influence the OPC intervention. METHODS: This study used an explanatory mixed-method design. Parent participants (n = 8) were recruited via purposive sampling and engaged in three sessions of OPC delivered via an online platform between October and December 2022. Standardised assessments were completed before and after OPC and a qualitative semi-structured interview two weeks after the final OPC session. Variables were analysed descriptively, and independent t tests were performed to compare scores on each standardised assessment pre- and post-intervention. Pearson's correlation analyses were conducted to consider associations between resistance to change and the extent of change in each outcome measure. Reflexive thematic analysis was conducted on postintervention interview transcripts. CONSUMER AND COMMUNITY INVOLVEMENT: Consumer invovlement was limited to parents feedback on their experiences of the intervention. RESULTS: Improvements in occupational performance as measured by the COPM change score were statistically significant (p = <0.001). Child eating behaviours, as measured by the CEBQ Food Fussiness subscale change score (p = 0.01) and BPFAS change score (p = 0.02), demonstrated significant improvements. The extent to which parents viewed these behaviours as problematic as measured by the BPFAS problem change score, showed a significant reduction (p = <0.001). Three themes emerged from interviews with parents: small changes beyond nutrition, parents supported as the experts, and what parents value within an intervention. CONCLUSION: Targeted OPC intervention delivered online by an occupational therapist may be an effective intervention for parents of picky eaters. Future studies using randomised controls are required before OPC can be routinely recommended in a clinical setting for the management of picky eating in children.

A qualitative inquiry of parents of extremely picky eaters: Experiences, strategies and future directions.

BACKGROUND/AIM: Picky eating is a common childhood phenomenon in younger children, impacting family relationships and mealtimes. Limited qualitative studies have explored parents' experiences of parenting an extremely picky eater. This study aimed to address this gap. METHODS: This exploratory qualitative research design included participants who were Australian-based parents (n = 10) of children aged 2-6 years with a minimum picky eating score of 3.33, indicating extreme picky eating, on the Food Fussiness subscale of the Child Eating Behavior Questionnaire (CEBQ). Parents were interviewed online via Zoom using semi-structured interviews focused on their experiences of having a child who is a picky eater. Reflexive thematic analysis was used to analyze the data. RESULTS: Five themes were identified: 1: The picky eating journey for parents. 2: Picky eating impacts families and mealtimes. 3: Parents have attempted multiple strategies to manage picky eating. 4: Emotions associated with parenting an extremely picky eater. 5: Parents of extremely picky eaters have a positive outlook for the future. CONCLUSION: This qualitative study demonstrates that parents' experiences of parenting an extremely picky eater are varied. Parents desire health professionals who listen to their concerns and provide evidence-based knowledge around parent feeding practices to positively impact picky eating.

The Link between Suicidality and Electroencephalography Asymmetry: A Systematic Review and Meta-analysis.

As one of the leading causes of death globally, suicide has been researched extensively to better understand factors that confer risk or resilience for suicidality. Promising areas of the literature have focused on brain-based factors that might indicate susceptibility to suicide. Some studies have investigated the link between electroencephalography (EEG) asymmetry, referring to differences in electrical activity in the brain from the left to right hemisphere, and suicidality. The present study is a comprehensive review and meta-analysis of the literature to see if certain patterns in EEG asymmetry serve as a diathesis for suicidal thoughts and behaviors. The results of the current investigation found that EEG asymmetry was not systematically related to suicide based on the literature reviewed. While the present review does not rule out all brain-based factors, the findings suggest that EEG asymmetry may not be a biomarker for suicidality.

Picky eating in children: Current clinical trends, practices, and observations within the Australian health-care context.

BACKGROUND/AIM: Childhood picky eating occurs when there is limited intake or variety of food and/or unwillingness to try new foods. Within research settings, standardised assessments are used to describe picky eating behaviours in children. However, little is known about assessment practices of occupational therapists. Similarly, occupational therapy interventions for picky eating in the literature focus on; providing strategies for parents, and working with the child on self-feeding skills. Despite this, interventions and strategies utilised by occupational therapists in clinical practice within an Australian health-care context are unknown. This study examines Australian health professionals' observations of picky eating behaviours, the use of childhood picky eating assessments and interventions, and differences between occupational therapists and other professionals. METHODS: Health professionals (n = 179) were recruited through professional organisations, such as Occupational Therapy Australia. Participants completed an online survey between March and May 2021. Independent variables were reported using descriptive statistics, with logistic regression used to consider differences between occupational therapists and other health professionals. Conventional content analysis was used to analyse responses to open-ended questions. RESULTS: The final sample included 109 eligible participants, with an average of 8.5 years working with picky eaters. Results indicated picky eating behaviours aligned with those reported in the literature. Participants relied on clinical observations and workplace designed assessments. The most common interventions were education, coaching, and the sequential oral sensory approach to feeding. Occupational therapy participants were significantly more likely than other health professional participants to report always using coaching and education. CONCLUSION: Although few health professionals used standardised or validated assessments, the use of education and coaching by occupational therapists aligned with the literature. Results highlight the need for more rigorous investigation to determine the sensitivity of current assessments to differentiate between clinical and typical picky eating, and the effectiveness of interventions for childhood picky eating.

Changes in Electroencephalography Alpha Associated With Childhood Neglect and Adolescent Alcohol Use.

The present pilot study is interested in the relationship between childhood neglect, brain function, and alcohol use in adolescence. The goal is to guide future prevention and intervention efforts related to alcohol use following childhood neglect. This pilot study comprised 53 adolescents (12-14 years at baseline) recruited from the Department of Social Services (DSS). Self- and DSS-reported neglect, electroencephalography (EEG) alpha power, and alcohol use behaviors were measured over 1 year. Higher DSS neglect severity in year 1 was related to lower self-efficacy to alcohol use temptation in year 2. Lower EEG alpha power in the parietal region in year 1 was linked to lower self-efficacy to the temptation of alcohol use in year 2. This pilot project has value for using tools, such as EEG, in child maltreatment and alcohol use studies, including with underrepresented adolescents, to better understand brain-related mechanisms in home-based research.

The Link between Suicidality and Electroencephalography Asymmetry: A Systematic Review and Meta-analysis

As one of the leading causes of death globally, suicide has been researched extensively to better understand factors that confer risk or resilience for suicidality. Promising areas of the literature have focused on brain-based factors that might indicate susceptibility to suicide. Some studies have investigated the link between electroencephalography (EEG) asymmetry, referring to differences in electrical activity in the brain from the left to right hemisphere, and suicidality.The present study is a comprehensive review and meta-analysis of the literature to see if certain patterns in EEG asymmetry serve as a diathesis for suicidal thoughts and behaviors. The results of the current investigation found that EEG asymmetry was not systematically related to suicide based on the literature reviewed. While the present review does not rule out all brain-based factors, the findings suggest that EEG asymmetry may not be a biomarker for suicidality.

Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1.

The orphan nuclear receptor HNF4alpha and the LIM homeodomain factor Isl1 are co-expressed in pancreatic beta-cells and are required for the differentiation and function of these endocrine cells. HNF4alpha activates numerous genes and mutations in its gene are associated with maturity onset diabetes of the young. Cofactors and transcription factors that interact with HNF4alpha are crucial to modulate its transcriptional activity, since the latter is not regulated by conventional ligands. These transcriptional partners interact mainly through the HNF4alpha AF-1 module and the ligand binding domain, which contains the AF-2 module. Here, we showed that Isl1 could enhance the HNF4alpha-mediated activation of transcription of the HNF1alpha, PPARalpha and insulin I promoters. Isl1 interacted with the HNF4alpha AF-2 but also required the HNF4alpha carboxy-terminal F domain for optimal interaction and transcriptional synergy. More specifically, we found that naturally occurring HNF4alpha isoforms, differing only in their F domain, exhibited different abilities to interact and synergize with Isl1, extending the crucial transcriptional modulatory role of the HNF4alpha F domain. HNF4alpha interacted with both the homeodomain and the first LIM domain of Isl1. We found that the transcriptional synergy between HNF4alpha and Isl1 involved an increase in HNF4alpha loading on promoter. The effect was more pronounced on the rat insulin I promoter containing binding sites for both HNF4alpha and Isl1 than on the human HNF1alpha promoter lacking an Isl1 binding site. Moreover, Isl1 could mediate the recruitment of the cofactor CLIM2 resulting in a further transcriptional enhancement of the HNF1alpha promoter activity.

Hepatocyte nuclear factor 4alpha enhances the hepatocyte nuclear factor 1alpha-mediated activation of transcription.

Hepatocyte Nuclear Factor 1alpha (HNF1alpha) and Hepatocyte Nuclear Factor 4alpha (HNF4alpha) are two liver-enriched transcription factors coexpressed in specific tissues where they play a crucial role through their involvement in a complex cross-regulatory network. HNF1alpha down regulates HNF4alpha-mediated activation of transcription via a direct protein-protein interaction. Here we show that HNF4alpha enhances the transcriptional activity of HNF1alpha in a DNA binding independent manner, thus indicating that it behaves as a HNF1alpha coactivator. Using mutations in the ligand binding domain (LBD) of HNF4alpha, we confirmed the involvement of the Activation Function 2 module and demonstrated the requirement of the integrity of the LBD for the interaction with HNF1alpha. Moreover, we show that HNF4alpha cooperates with p300 to achieve the highest HNF1alpha-mediated transcription rates. Our findings highlight a new way by which HNF4alpha can regulate gene expression and extend our knowledge of the complexity of the transcriptional network involving HNF4alpha and HNF1alpha.

Hepatocyte nuclear factor 4 alpha isoforms originated from the P1 promoter are expressed in human pancreatic beta-cells and exhibit stronger transcriptional potentials than P2 promoter-driven isoforms.

The nuclear receptor hepatocyte nuclear factor (HNF) 4 alpha is involved in a transcriptional network and plays an important role in pancreatic beta-cells. Mutations in the HNF4 alpha gene are correlated with maturity-onset diabetes of the young 1. HNF4 alpha isoforms result from both alternative splicing and alternate usage of promoters P1 and P2. It has recently been reported that HNF4 alpha transcription is driven almost exclusively by the P2 promoter in pancreatic islets. We observed that transcripts from both P1 and P2 promoters were expressed in human pancreatic beta-cells and in the pancreatic beta-cell lines RIN m5F and HIT-T15. Expression of HNF4 alpha proteins originating from the P1 promoter was confirmed by immunodetection. Due to the presence of the activation function module AF-1, HNF4 alpha isoforms originating from the P1 promoter exhibit stronger transcriptional activities and recruit coactivators more efficiently than isoforms driven by the P2 promoter. Conversely, activities of isoforms produced by both promoters were similarly repressed by the corepressor small heterodimer partner. These behaviors were observed on the promoter of HNF1 alpha that is required for beta-cell function. Our results highlight that expression of P1 promoter-driven isoforms is important in the control of pancreatic beta-cell function.

Maturity-onset diabetes of the young Type 1 (MODY1)-associated mutations R154X and E276Q in hepatocyte nuclear factor 4alpha (HNF4alpha) gene impair recruitment of p300, a key transcriptional co-activator.

Hepatocyte nuclear factor 4alpha (HNF4alpha) is a nuclear receptor involved in glucose homeostasis and is required for normal beta-cell function. Mutations in the HNF4alpha gene are associated with maturity-onset diabetes of the young type 1. E276Q and R154X mutations were previously shown to impair intrinsic transcriptional activity (without exogenously supplied co-activators) of HNF4alpha. Given that transcriptional partners of HNF4alpha modulate its intrinsic transcriptional activity and play crucial roles in HNF4alpha function, we investigated the effects of these mutations on potentiation of HNF4alpha activity by p300, a key co-activator for HNF4alpha. We show here that loss of HNF4alpha function by both mutations is increased through impaired physical interaction and functional cooperation between HNF4alpha and p300. Impairment of p300-mediated potentiation of HNF4alpha transcriptional activity is of particular importance for the E276Q mutant since its intrinsic transcriptional activity is moderately affected. Together with previous results obtained with chicken ovalbumin upstream promoter-transcription factor II, our results highlight that impairment of recruitment of transcriptional partners represents an important mechanism leading to abnormal HNF4alpha function resulting from the MODY1 E276Q mutation. The impaired potentiations of HNF4alpha activity were observed on the promoter of HNF1alpha, a transcription factor involved in a transcriptional network and required for beta-cell function. Given its involvement in a regulatory signaling cascade, loss of HNF4alpha function may cause reduced beta-cell function secondary to defective HNF1alpha expression. Our results also shed light on a better structure-function relationship of HNF4alpha and on p300 sequences involved in the interaction with HNF4alpha.

Negative regulation of human fibrinogen gene expression by peroxisome proliferator-activated receptor alpha agonists via inhibition of CCAAT box/enhancer-binding protein beta.

Fibrinogen is a coagulation factor and an acute phase reactant up-regulated by inflammatory cytokines, such as interleukin 6 (IL-6). Elevated plasma fibrinogen levels are associated with coronary heart diseases. Fibrates are clinically used hypolipidemic drugs that act via the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR alpha). In addition, most fibrates also reduce plasma fibrinogen levels, but the molecular mechanism is unknown. In this study, we demonstrate that fibrates decrease basal and IL-6-stimulated expression of the human fibrinogen-beta gene in human primary hepatocytes and hepatoma HepG2 cells. Fibrates diminish basal and IL-6-induced fibrinogen-beta promoter activity, and this effect is enhanced in the presence of co-transfected PPAR alpha. Site-directed mutagenesis experiments demonstrate that PPAR alpha activators decrease human fibrinogen-beta promoter activity via the CCAAT box/enhancer-binding protein (C/EBP) response element. Co-transfection of the transcriptional intermediary factor glucocorticoid receptor-interacting protein 1/transcriptional intermediary factor 2 (GRIP1/TIF2) enhances fibrinogen-beta gene transcription and alleviates the repressive effect of PPAR alpha. Co-immunoprecipitation experiments demonstrate that PPAR alpha and GRIP1/TIF2 physically interact in vivo in human liver. These data demonstrate that PPAR alpha agonists repress human fibrinogen gene expression by interference with the C/EBP beta pathway through titration of the coactivator GRIP1/TIF2. We observed that the anti-inflammatory action of PPAR alpha is not restricted to fibrinogen but also applies to other acute phase genes containing a C/EBP response element; it also occurs under conditions in which the stimulating action of IL-6 is potentiated by dexamethasone. These findings identify a novel molecular mechanism of negative gene regulation by PPAR alpha and reveal the direct implication of PPAR alpha in the modulation of the inflammatory gene response in the liver.

Functional properties of the R154X HNF-4alpha protein generated by a mutation associated with maturity-onset diabetes of the young, type 1.

Mutations in the hepatocyte nuclear factor 4alpha (HNF-4alpha) gene are associated with one form of maturity-onset diabetes of the young (MODY1). The R154X mutation generates a protein lacking the E-domain which is required for normal HNF-4alpha functions. Since pancreatic beta-cell dysfunction is a feature of MODY1 patients, we compared the functional properties of the R154X mutant in insulin-secreting pancreatic beta-cells and non-beta-cells. The R154X mutation did not affect nuclear localisation in beta-cells and non-beta-cells. However, it did lead to a greater impairment of HNF-4a function in beta-cells compared to non-beta-cells, including a complete loss of transactivation activity and a dominant-negative behaviour. .

Functional study of the E276Q mutant hepatocyte nuclear factor-4alpha found in type 1 maturity-onset diabetes of the young: impaired synergy with chicken ovalbumin upstream promoter transcription factor II on the hepatocyte nuclear factor-1 promoter.

Seven mutations in the hepatocyte nuclear factor (HNF)-4alpha gene have been shown to correlate with type 1 maturity-onset diabetes of the young (MODY 1), a monogenic form of type 2 diabetes. Up to now, only the functional properties of two MODY 1 HNF-4alpha mutants, Q268X and V393I, have been investigated to address how the mutations in the HNF-4alpha gene, found by genetic studies, can give rise to impaired activities of mutated HNF-4alpha proteins and can cause this disease. The E276Q mutation results in a nonconservative substitution occurring in the HNF-4alpha E domain, which is involved in dimerization and transactivation activities as well as in protein-protein interactions with other transcription factors or coactivators. Using the mutated human HNF-4alpha2, we have found that, in the absence of chicken ovalbumin upstream promoter transcription factor II (COUP TFII), the E276Q substitution does not significantly affect the dimerization and transactivating activities of HNF-4alpha, at least on the promoters studied herein. On the other hand, in the presence of COUP TFII, the substitution impairs the enhancement of HNF-4-mediated activation of HNF-1 promoter. The impaired synergy between COUP TFII and HNF-4 on the HNF-1 promoter results from an alteration of their interaction. HNF-1 expression plays a crucial role in transactivation of insulin promoter and of numerous genes coding for enzymes involved in glucose homeostasis. Therefore, its downregulation resulting from the E276Q mutation in HNF-4alpha gene most probably impairs the function of pancreatic beta-cells.

The activity of the activation function 2 of the human hepatocyte nuclear factor 4 (HNF-4alpha) is differently modulated by F domains from various origins.

Hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear hormone-receptor superfamily, which plays an important role in the regulation of several genes involved in numerous metabolic pathways. HNF-4 contains a DNA-binding domain located in domain C and two activation-function domains, designated AF-1 and AF-2, located in domains A/B and E, respectively. The seven isoforms of human HNF-4, termed alpha1-alpha6 and gamma, differ mainly by their A/B and F domains. The high sequence variability of the F domain led us to investigate whether this domain modulates the transcriptional activity of HNF-4. Using constructs having the same core receptor and different F domains, we observed that the F domains of HNF-4 modulate the transactivating activity of the full-length HNF-4. A more precise analysis using HNF-4alpha AF-2 fused to GAL4 protein and various F domains demonstrated that F domains of isoforms alpha3 and gamma exhibited inhibitory effects on the activation function AF-2 but that their inhibition behaviours were weaker than that of HNF-4alpha2 F domain, which has been reported previously. The presence of domain F results in a decreased interaction with the co-activator glucocorticoid receptor-interacting protein 1. For a given F domain, the modulating effects on the full-length HNF-4 as well as on the AF-2 depended on the target promoters. Our results suggest that the presence of domain F results in conformation changes in HNF-4 AF-2 or in its spatial environment, which probably modify the interaction of the AF-2 activation domain with co-factors and transcription factors bound to cis-elements of the target promoters.

The DNA-binding protein II from Zymomonas mobilis. Complete amino acid sequence and interaction with DNA.

The primary structure of the DNA-binding protein II from Zymomonas mobilis has been determined from data provided by automated Edman degradation of the intact protein and of peptides derived from cleavage at aspartic acid and arginine residues. When compared with the homologous protein isolated from other bacteria, the DNA-binding protein II from Z mobilis shows many substitutions. Several non-conservative substitutions at positions usually highly conserved in this type of protein probably account for the weaker DNA-binding activity of this protein compared to that of the E coli protein.

A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. During the course of our search for susceptibility genes contributing to the more common late-onset NIDDM forms, we observed nominal evidence for linkage between NIDDM and markers in the region of the HNF-4alpha/MODY1 locus in a subset of French families with NIDDM diagnosed before 45 yr of age. Thus, we screened these families for mutations in the HNF-4alpha gene. We found a missense mutation, resulting in a valine-to-isoleucine substitution at codon 393 in a single family. This mutation cosegregated with diabetes and impaired insulin secretion, and was not present in 119 control subjects. Expression studies showed that this conservative substitution is associated with a marked reduction of transactivation activity, a result consistent with this mutation contributing to the insulin secretory defect observed in this family.

mRNA expression of HNF-4 isoforms and of HNF-1alpha/HNF-1beta variants and differentiation of human cell lines that mimic highly specialized phenotypes of intestinal epithelium.

The mRNA expression of HNF-4 isoforms and the ratio of HNF-1alpha/HNF-1beta variants in cell lines representing highly specialized phenotypes of human intestinal epithelium were studied by RT-PCR. A strong rise in expression of HNF-4 isoforms alpha2, alpha4 and gamma correlates with commitment into highly differentiated enterocyte-like phenotype of Caco-2 cells which best mimic enterocytes, whereas only isoform alpha4 expression is high in the less differentiated HT-29 G- cells. These increased expressions are not encountered in the highly differentiated mucous-secreting HT-29 MTX cells. Differentiation into highly specialized enterocyte-like Caco-2 cells and mucous-secreting HT-29 MTX cells is accompanied by a moderate rise in HNF-1 without change in the ratio of its variants. Our data corroborate those of Spath et al. (Mol. Cell. Biol., 1997, 17, 1913) in hepatoma cells and suggest that HNF-4 isoforms alpha2, alpha4 and gamma play a major role in the differentiation of enterocytes.

Transgenic rabbits expressing human apolipoprotein A-I in the liver.

Human apolipoprotein A-I (apo A-I) transgenic rabbits were created by use of an 11-kb genomic human apo A-I construct containing a liver-specific promoter. Five independent transgenic lines were obtained in which human apo A-I gene had integrated and was expressed. Plasma levels of human apo A-I ranged from 8 to 100 mg/dL for the founder and up to 175 mg/dL for the progeny. Rabbit apo A-I levels were substantially decreased in the transgenic rabbits. HDL cholesterol (HDL-C) levels were higher in two of the five transgenic rabbit lines than in controls (line 20 versus nontransgenic littermate, HDL-C = 80 +/- 7 versus 37 +/- 6 mg/dL; line 8 versus nontransgenic littermate, HDL-C = 54 +/- 16 versus 35 +/- 6 mg/dL). This resulted in less atherogenic lipoprotein profiles, with very low (VLDL + LDL-C)/HDL-C ratios. HDL size and protein and lipid compositions were similar between transgenic and littermate nontransgenic rabbits. However, a large amount of pre-beta apo A-I-containing lipoproteins was observed in the plasma of the highest human apo A-I expressor. Cell cholesterol efflux was evaluated with the incubation of whole serum from transgenic and control rabbits. Cell cholesterol efflux was highly correlated with HDL cholesterol, with apo A-I, and with the presence of pre-beta apo A-I-containing lipoproteins. These rabbits will be an extremely useful model for the evaluation of the effect of increased hepatic apo A-I expression on atherosclerosis.

Two regulatory elements of similar structure and placed in tandem account for the repressive activity of the first intron of the human apolipoprotein A-II gene.

Recent reports indicate that apolipoprotein (apo) A-II, the second most abundant protein of high-density lipoproteins, plays a crucial role in counteracting the beneficial effect of apo A-I against atherogenesis. Transcription of the human apo A-II gene is controlled by an enhancer comprising 14 regulatory elements located upstream of its promoter whereas the first intron of this gene behaves as a silencer. Here we show that two sequence elements account for the repressive activity of this intron and correspond to negative regulatory elements termed NRE I and NRE II. The activity of intron I and the nuclear proteins binding to NRE I and II are encountered in hepatic cells but not in non-hepatic cells studied here. Both NREs form nucleoprotein complexes of very similar physicochemical characteristics and bind the same or closely related proteins. Site-directed mutagenesis, transient transfection and gel-shift analysis experiments indicate that both NREs exhibit similar structures, being composed of two sites required for maximal activity and optimal binding of transcription factors. Therefore two negative regulatory elements of similar structure and function, placed in tandem, account for the repressive activity of the first intron of the human apo A-II gene. These NREs do not exhibit structural similarity with known NREs of other genes.