Exploring the influence of context on social norms around Australian parents' food provision using story completion.

OBJECTIVE: To explore the differences in social norms around parents' food provision in different provision contexts and by demographics. DESIGN: Qualitative study using story completion methodology via an online survey in September 2021. Adults 18+ with or without children were randomised to one of three story stems focusing on food provision in different contexts; food provision at home (non-visitor), with visitors present and with the involvement of sport. Stories were coded and themed using thematic analysis. A content analysis was performed to determine count and frequency of codes in stories by participant demographics and story assumptions. SETTING: Australia. PARTICIPANTS: Adults (n 196). RESULTS: Nine themes were identified from the data resulting in four social norms around providing healthy foods and justifying non-adherence to healthy eating guidelines, evolution of family life and mealtime values, the presence of others influencing how we engage with food provision and unhealthy foods used as incentives/rewards in sport. Following content analysis, no differences of themes or norms by participant demographics or story assumptions were found. CONCLUSIONS: We identified pervasive social norms around family food provision and further identified how contextual factors resulted in variations or distinct norms. This highlights the impact context may have on the social norms parents face when providing food to their children and the opportunities and risks of leveraging these social norms to influence food choice in these contexts. Public health interventions and practitioners should understand the influence of context and social environments when promoting behaviour change and providing individualised advice. Future research could explore parents' experiences of these norms and to what extent they impact food choice.

Evaluation of a long day care intervention targeting the mealtime environment and curriculum to increase children's vegetable intake: a cluster randomised controlled trial using the multiphase optimisation strategy framework.

OBJECTIVE: To determine the reach, adoption, implementation and effectiveness of an intervention to increase children's vegetable intake in long day care (LDC). DESIGN: A 12-week pragmatic cluster randomised controlled trial, informed by the multiphase optimisation strategy (MOST), targeting the mealtime environment and curriculum. Children's vegetable intake and variety was measured at follow-up using a modified Short Food Survey for early childhood education and care and analysed using a two-part mixed model for non-vegetable and vegetable consumers. Outcome measures were based on the RE-AIM framework. SETTING: Australian LDC centres. PARTICIPANTS: Thirty-nine centres, 120 educators and 719 children at follow-up. RESULTS: There was no difference between intervention and waitlist control groups in the likelihood of consuming any vegetables when compared with non-vegetable consumers for intake (OR = 0·70, (95 % CI 0·34-1·43), P = 0·32) or variety (OR = 0·73 (95 % CI 0·40-1·32), P = 0·29). Among vegetable consumers (n 652), there was no difference between groups in vegetable variety (exp(b): 1·07 (95 % CI:0·88-1·32, P = 0·49) or vegetable intake (exp(b): 1·06 (95 % CI: 0·78, 1·43)), P = 0·71) with an average of 1·51 (95 % CI 1·20-1·82) and 1·40 (95 % CI 1·08-1·72) serves of vegetables per day in the intervention and control group, respectively. Intervention educators reported higher skills for promoting vegetables at mealtimes, and knowledge and skills for teaching the curriculum, than control (all P < 0·001). Intervention fidelity was moderate (n 16/20 and n 15/16 centres used the Mealtime environment and Curriculum, respectively) with good acceptability among educators. The intervention reached 307/8556 centres nationally and was adopted by 22 % eligible centres. CONCLUSIONS: The pragmatic self-delivered online intervention positively impacted educator's knowledge and skills and was considered acceptable and feasible. Intervention adaptations, using the MOST cyclic approach, could improve intervention impact on children' vegetable intake.

A great way to bring up health behaviour topics at playgroup: a qualitative evaluation of the Healthy Conversations @ Playgroup program.

BACKGROUND: The early years is a critical stage to establish optimal nutrition and movement behaviours. Community playgroups are a relaxed environment for parents with a focus on social connection and supporting parents in their role as 'First Teachers'. Playgroups are therefore an opportunistic setting to promote health behaviours in the early years. To support parents with young children around healthy lifestyle behaviours, the Healthy Conversations @ Playgroup program was delivered in urban and regional areas, across three Australian jurisdictions between 2021-2023. OBJECTIVE: This qualitative evaluation aimed to understand how the Healthy Conversations @ Playgroup program was experienced by parents, playgroup coordinators and peer facilitators. DESIGN: Semi-structured virtual interviews and focus groups were conducted with parents, playgroup coordinators (i.e., person responsible for coordinating the playgroup) and peer facilitators (i.e., trained facilitator for the program) that participated in the Healthy Conversations @ Playgroup study. Transcripts were analysed following a thematic analysis approach. RESULTS: Twenty-eight playgroup parents, coordinators or peer facilitators participated in one of 8 focus groups or 5 interviews. Four themes were developed: Program strengths and challenges; Setting strengths and challenges; Factors that impact program delivery; Participant's suggestions for future program delivery. CONCLUSIONS: The Healthy Conversations @ Playgroup program was valued by parents, providing validation and normalisation of parenting practices, and fostering a shared experience of parenting. Playgroups are a convenient setting for families to attend. The dynamic and distracting nature of the playgroup setting were carefully considered when designing the program. Strategies to further enhance program engagement could include use of coordinator or parent champions, tailored delivery, and extending the reach to other family members. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000055808, registered 22 January 2021, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380890.

Unpacking the cost of the lunchbox for Australian families: a secondary analysis.

Ninety per cent of Australian school children bring a home-packed lunch to school, with 44% of the food consumed during school hours being unhealthy. Among other factors, cost is a key consideration for food provision; however, the costs to Australian families are not well understood. Therefore, we aimed to determine what families are currently paying for school lunchboxes in Australian primary schools and to examine associations between food costs and socio-demographic factors with dietary quality. An audit of local retail outlets was used to determine the food costs of lunchbox contents. Costs (AUD) were adjusted for inflation as of early 2023. The lunchboxes of 1026 children aged 4-12 years at 12 Catholic primary schools in New South Wales, Australia, were assessed at the start of the day, using photography assessment methods and a validated School Food Checklist. The mean cost of lunchbox contents was $4.48 AUD (SD 1.53), containing a mean energy of 2699 kJ (SD 859), with 37.3% (SD 23.9) of energy sourced from unhealthy foods. Multiple linear regression analyses found that the strongest predictors of higher lunchbox cost (P < 0.05) were a higher proportion of energy from unhealthy foods (B = 0.016) and lower Socio-Economic Indexes for Areas (B = -0.178), when controlling for child socio-demographics. The results indicated that lunchbox food costs to Australian families are comparable to alternative school food service models in Australia and internationally. Results demonstrate the cost of food is not the only barrier to providing a healthy school lunchbox. Demonstrating a need for cost-considerate systematic interventions addressing food provision challenges and socio-economic disparities faced by families.

Eating Disorders In weight-related Therapy (EDIT) Collaboration: rationale and study design.

The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.

Mapping the behaviour change potential of meal kits to positively influence parental food literacy.

OBJECTIVE: This study aimed to examine the theoretical potential of meal kit subscription services in Australia to promote parental food literacy using the retrospective application of behaviour change frameworks. DESIGN: A one-week subscription was purchased for all Australian-based meal kit subscription services (n 9) to access content and features available to subscribers. Behaviour change techniques (BCTs) identified in the subscription and meal planning features, meal kit delivery (i.e. ingredients and recipes) and website were coded using the behaviour change technique taxonomy (BCTTv1) and associated behaviour change frameworks. Identified BCTs were mapped to the theoretical domains framework to identify potential mechanisms of action for influencing parental food literacy development. SETTING: Australia. RESULTS: Thirty-five BCTs were identified across the nine meal kit services reviewed, ranging from nineteen to twenty-nine BCTs per company. Sixteen BCTs were common to all meal kits services, from the hierarchical clusters of 'goals and planning', 'shaping knowledge', 'social support', 'natural consequences', 'comparison of behaviour', 'repetitions and substitution', 'associations', 'reward and threat', 'antecedents' and 'regulation'. Across the meal kit services, the most frequently identified mechanisms of action were motivation (n 27) and capability (n 19). CONCLUSION: These findings support the applicability of behaviour change frameworks to commercial meal kit subscription services and provide a theory-informed process for identifying BCTs that may be relevant for promoting parental food literacy within this context. Further research is required to explore how families engage with meal kit subscription services to determine the exposure and delivery of identified BCT content and to evaluate the potential influence on food literacy development.

Exploring Australian children's perceptions of a school-provided lunch model using a story completion method.

Children in Australia currently bring a packed lunch to school from home. Many children are not consuming a healthy diet at school. There is interest from key stakeholders (e.g. education and the non-government sector, food service and parents/caregivers) to transform the Australian system to a school-provided model to improve children's diets, reduce parental burden and address food insecurity. To facilitate a successful transition to this system, it is important to consider the views of the children. We aimed to explore Australian primary school children's perceptions of a hypothetical school-provided lunch model. To achieve this aim, we undertook a qualitative study using the story completion method. Twenty-one grade-five children, from one public primary school in South Australia, participated in a once-off data collection session. Children were given a brief story stem and asked to complete a story about a hypothetical school-provided lunch scenario. The story data were analysed using thematic analysis. Four main themes were generated: the eating environment, the food provided, processes of the mealtime and time. The desire for choice was an additional overarching theme that cut across all themes. Our study provides the first exploration of South Australian children's perceptions of hypothetical school-provided meals. These insights can be used to co-design an acceptable school food system with children to create a positive eating environment that supports healthy eating habits they can carry forward into adulthood.

Exploring the social norms regarding parents' food provision in Australia using story completion methodology.

Children's diets are not aligned with dietary guidelines, with the social context including social norms being one factor influencing parents' food provision. Little is known about social norms in broad society that parents face when providing food to children. We aimed to determine the social norms surrounding family food provision from the perspectives of Australian adults. This qualitative study used story completion methodology via an online survey to gather hypothetical stories from adults (≥18 years). Participants were presented with a story stem focusing on home food provision. Stories (i.e. data) were coded and analysed using thematic analysis. Five themes were identified from the data (N = 75); 1. Providing a healthy snack, 2. Providing justification for the provision of unhealthy convenience foods, 3. Increasing child autonomy in food provision, 4. Mealtimes are a social occasion, and 5. Contextual factors influencing food provision and social norms. From these themes, social norms were identified around providing healthy foods and justifying non-adherence to healthy eating guidelines and evolution of family life and mealtime values. This study provides new knowledge that there are social norms around parents providing healthy foods and needing to justify non-adherence to healthy eating guidelines, as well as the norm that family life and mealtime values are evolving. This highlights the need to consider the broader context that influences food choices. Furthermore, this study highlights the utility of novel methods in this field.

The food and nutrient intake of 5- to 12-year-old Australian children during school hours: a secondary analysis of the 2011-2012 National Nutrition and Physical Activity Survey.

OBJECTIVE: School food intake of Australian children is not comprehensively described in literature, with limited temporal, nationally representative data. Greater understanding of intake at school can inform school-based nutrition promotion. This study aimed to describe the dietary intake of primary-aged children during school hours and its contribution to daily intake. DESIGN: This secondary analysis used nationally representative, cross-sectional data from the 2011 to 2012 National Nutrition and Physical Activity Survey. Dietary intake was assessed using validated 24-h dietary recalls on school days. Descriptive statistics were undertaken to determine energy, nutrients, food groups and food products consumed during school hours, as well as their contributions to total daily intake. Associations between school food intake and socio-demographic characteristics were explored. SETTING: Australia. PARTICIPANTS: Seven hundred and ninety-five children aged 5-12 years. RESULTS: Children consumed 37 % of their daily energy and 31-43 % of select nutrient intake during school hours, with discretionary choices contributing 44 % of school energy intake. Most children consumed less than one serve of vegetables, meat and alternatives or milk and alternatives during school hours. Commonly consumed products were discretionary choices (34 %, including biscuits, processed meat), bread (17 %) and fruit (12 %). There were limited associations with socio-economic position variables, apart from child age. CONCLUSIONS: Children's diets were not aligned with national recommendations, with school food characterised by high intake of discretionary choices. These findings are consistent with previous Australian evidence and support transformation of the Australian school food system to better align school food consumption with recommendations.

Identifying opportunities for strengthening advice to enhance vegetable liking in the early years of life: qualitative consensus and triangulation methods.

OBJECTIVE: To prioritise and refine a set of evidence-informed statements into advice messages to promote vegetable liking in early childhood, and to determine applicability for dissemination of advice to relevant audiences. DESIGN: A nominal group technique (NGT) workshop and a Delphi survey were conducted to prioritise and achieve consensus (≥70 % agreement) on thirty evidence-informed maternal (perinatal and lactation stage), infant (complementary feeding stage) and early years (family diet stage) vegetable-related advice messages. Messages were validated via triangulation analysis against the strength of evidence from an Umbrella review of strategies to increase children's vegetable liking, and gaps in advice from a Desktop review of vegetable feeding advice. SETTING: Australia. PARTICIPANTS: A purposeful sample of key stakeholders (NGT workshop, n 8 experts; Delphi survey, n 23 end users). RESULTS: Participant consensus identified the most highly ranked priority messages associated with the strategies of: 'in-utero exposure' (perinatal and lactation, n 56 points) and 'vegetable variety' (complementary feeding, n 97 points; family diet, n 139 points). Triangulation revealed two strategies ('repeated exposure' and 'variety') and their associated advice messages suitable for policy and practice, twelve for research and four for food industry. CONCLUSIONS: Supported by national and state feeding guideline documents and resources, the advice messages relating to 'repeated exposure' and 'variety' to increase vegetable liking can be communicated to families and caregivers by healthcare practitioners. The food industry provides a vehicle for advice promotion and product development. Further research, where stronger evidence is needed, could further inform strategies for policy and practice, and food industry application.

Study protocol for Healthy Conversations @ Playgroup: a multi-site cluster randomized controlled trial of an intervention to promote healthy lifestyle behaviours in young children attending community playgroups.

BACKGROUND: Early childhood is a critical window for preventing obesity and chronic disease. Yet, 1 in 4 Australian children aged 5 years and under are affected by overweight or obesity; and significant proportions of children under 5 years fail to meet guidelines for diet quality, physical activity (PA), screen time, and sleep. Consequently, effective interventions to promote healthy lifestyle behaviors and prevent obesity during early childhood are needed. Community playgroups provide an opportunity for parents, carers, and children to meet in a safe and relaxed environment to play and share information. The structure, low cost and reach of playgroups provide a unique platform to engage parents in a scalable program to promote healthful lifestyle behaviors and prevent childhood obesity. However, the evidence base for the effectiveness of health promotion programs delivered in community playgroup settings is limited and lacking credible evidence from rigorously conducted randomized controlled trials. METHODS: The Healthy Conversations @ Playgroup randomized controlled trial (RCT) aims to address the underlying behavioral risk factors for obesity by helping parents take effective steps to improve their child's dietary, PA, screen time, and sleep behaviors. The intervention program comprises 10 "healthy conversations" led by a trained peer facilitator, designed to increase parents' behavioral capability and self-efficacy to implement autonomy-supportive parenting practices. The program will be delivered biweekly during regularly scheduled playgroup sessions over 10-weeks. Effectiveness will be tested in a 2-arm cluster RCT involving 60 community playgroups in three states across Australia. After baseline assessments, participating playgroups will be randomly allocated to either intervention or wait-list control conditions. Primary outcomes (vegetable intake, discretionary foods, daily PA, screen time, sleep duration, and body mass index [BMI] z-score) will be assessed at baseline, immediately post-intervention (10-weeks; T2) and 6-months post-intervention (T3). Outcomes will be assessed for differential change at T2 and T3. DISCUSSION: The Healthy Conversations @ Playgroup trial will rigorously evaluate a novel peer-led intervention program to promote healthful lifestyle behaviors and prevent obesity in children and families attending community playgroups. If effective, the program could be immediately scaled-up and delivered in community playgroups across Australia. TRIAL REGISTRATION: Trial registered 22nd January 2021 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12621000055808 ).

Pediatric Providers' Knowledge, Attitudes, Practice, and Barriers to Firearms Safety Counseling.

OBJECTIVES: Firearms-related injuries and deaths are a leading cause of death in children and young adults ages 5 to 24 years. This study evaluated the counseling practices and barriers to providing safe firearms storage education by pediatricians and advance practice providers. METHODS: An online survey was sent to 296 pediatric outpatient providers in Houston, Texas. Pediatric providers were asked about demographics, knowledge, attitudes, and current practices regarding firearms safety counseling. Descriptive and comparative analyses were performed. RESULTS: Survey respondents (N = 76) were 86% women and 87% physicians. Most (86%) agree that they should discuss firearms safety with parents, whereas only 32% report routine counseling. The most frequent barrier to providing education was insufficient time (63%), followed by unfamiliarity with guns (26%). CONCLUSIONS: Pediatric providers are interested in firearms safety counseling, but few incorporate it into their practice. Addressing barriers of time and comfort level around firearms are potential first steps to curbing a leading cause of injury death among children. Further research is needed to develop counseling methods that are time efficient and culturally competent for the pediatric office.

Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase.

Accelerated ubiquitination and subsequent endoplasmic reticulum (ER)-associated degradation (ERAD) constitute one of several mechanisms for feedback control of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids. This ERAD is initiated by the accumulation of certain sterols in ER membranes, which trigger binding of reductase to ER membrane proteins called Insigs. Insig-associated ubiquitin ligases facilitate ubiquitination of reductase, marking the enzyme for extraction across the ER membrane through a reaction that is augmented by nonsterol isoprenoids. Once extracted, ubiquitinated reductase becomes dislocated into the cytosol for degradation by 26S proteasomes. In this review, we will highlight several advances in the understanding of reductase ERAD, which includes the discovery for a role of the vitamin K2 synthetic enzyme UBIAD1 in the reaction and demonstration that sterol-accelerated ERAD significantly contributes to feedback regulation of reductase and cholesterol metabolism in livers of whole animals.

Understanding the influence of physical resources and social supports on primary food providers' snack food provision: a discrete choice experiment.

BACKGROUND: Snack eating occasions contribute approximately a third of children's energy intake, with approximately half of all unhealthy foods consumed during snack times. Therefore, it is critical to understand the drivers of primary food providers' snack provision. The study aims were to determine the relative importance of physical resources and social supports when primary food providers are choosing snacks to provide to their child, and to investigate how these attributes differ in social versus non-social occasions, and between subgroups of primary food providers based on socio-economic position. METHODS: Primary food providers of three to seven-year olds completed an online discrete choice experiment, by making trade-offs when completing repeated, hypothetical choice tasks on the choice of snacks to provide to their child in: 1) non-social and 2) social condition. Choice tasks included two alternatives consisting of varying attribute (i.e. factor) levels, and an opt-out option. The order of conditions shown were randomized across participants. Multinomial logit model analyses were used to determine utility weights for each attribute. RESULTS: Two-hundred and twenty-five primary food providers completed the study, providing 1125 choice decisions per condition. In the non-social condition, the top three ranked attributes were type of food (utility weight 1.94, p < 0.001), child resistance (- 1.62, p < 0.001) and co-parent support (0.99, p < 0.001). In the social condition, top ranking attributes were child resistance (utility weight - 1.50, p < 0.001), type of food (1.38, p < 0.001) and co-parent support (1.07, p < 0.001). In both conditions, time was not a significant influence and cost was of lowest relative importance. Subgroup analyses revealed cost was not a significant influence for families from higher socio-economic backgrounds. CONCLUSIONS: Type of food, child resistance and co-parent support were of greatest relative importance in primary food providers' snack provision decision-making, regardless of social condition or socio-economic position. In designing future interventions to reduce unhealthy snacks, researchers should prioritize these influences, to better support primary food providers in changing their physical and social opportunity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry no. ACTR N12618001173280.

Impact of Electronic and Steric Changes of Ligands on the Assembly, Stability, and Redox Activity of Cu4(µ4-S) Model Compounds of the CuZ Active Site of Nitrous Oxide Reductase (N2OR).

Model compounds have been widely utilized in understanding the structure and function of the unusual Cu4(µ4-S) active site (CuZ) of nitrous oxide reductase (N2OR). However, only a limited number of model compounds that mimic both structural and functional features of CuZ are available, limiting insights about CuZ that can be gained from model studies. Our aim has been to construct Cu4(µ4-S) clusters with tailored redox activity and chemical reactivity via modulating the ligand environment. Our synthetic approach uses dicopper(I) precursor complexes (Cu2L2) that assemble into a Cu4(µ4-S)L4 cluster with the addition of an appropriate sulfur source. Here, we summarize the features of the ligands L that stabilize precursor and Cu4(µ4-S) clusters, along with the alternative products that form with inappropriate ligands. The precursors are more likely to rearrange to Cu4(µ4-S) clusters when the Cu(I) ions are supported by bidentate ligands with 3-atom bridges, but steric and electronic features of the ligand also play crucial roles. Neutral phosphine donors have been found to stabilize Cu4(µ4-S) clusters in the 4Cu(I) oxidation state, while neutral nitrogen donors could not stabilize Cu4(µ4-S) clusters. Anionic formamidinate ligands have been found to stabilize Cu4(µ4-S) clusters in the 2Cu(I):2Cu(II) and 3Cu(I):1Cu(II) states, with both the formation of the dicopper(I) precursors and subsequent assembly of clusters being governed by the steric factor at the ortho positions of the N-aryl substituents. Phosphaamidinates, which combine a neutral phosphine donor and an anionic nitrogen donor in the same ligand, form multinuclear Cu(I) clusters unless the negative charge is valence-trapped on nitrogen, in which case the resulting dicopper precursor is unable to rearrange to a multinuclear cluster. Taken together, the results presented in this study provide design criteria for successful assembly of synthetic model clusters for the CuZ active site of N2OR, which should enable future insights into the chemical behavior of CuZ.

Primary Renal Ewing Sarcoma in Children and Young Adults.

The Ewing sarcoma family of tumors (ESFT) are high-grade small round blue cell malignancies traditionally presenting in children and adolescents. The most common site of primary disease is bone, though extraskeletal primary sites are well-recognized. We present 6 cases of primary ESFT of the kidney and 1 case of the adrenal gland. Patients were 11 to 18 years of age at diagnosis. Metastases at diagnosis were present in most cases (n=6). All patients underwent surgery, and most received radiation (n=5). Five patients relapsed after initial remission. Comprehensive review of the primary renal ESFT literature was used to analyze various factors, including age, sex, disease metrics, metastases at diagnoses, and overall survival in a total of 362 cases. Notably, while the general ESFT population has reported rates of metastasis at diagnosis of 20% to 25%, this rate in the renal ESFT population was 53% with a rate of 59% in adolescent and young-adult patients (11 to 24 y). Nodal disease at diagnosis was present in 24% of renal ESFT cases compared with 3.2% in patients with primary skeletal ESFT. While this malignant process may share histologic and molecular features with its bone and soft tissue counterparts, primary renal ESFT presentations seem to be more aggressive and have worse outcomes.

UbiA prenyltransferase domain-containing protein-1 modulates HMG-CoA reductase degradation to coordinate synthesis of sterol and nonsterol isoprenoids.

UBIAD1 (UbiA prenyltransferase domain-containing protein-1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2 We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized 3-hydroxy-3-methylglutaryl (HMG) CoA reductase. UBIAD1 binding inhibits sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several mechanisms for feedback control of this rate-limiting enzyme in the branched pathway that produces cholesterol and nonsterol isoprenoids such as GGpp. Accumulation of GGpp in ER membranes triggers release of UBIAD1 from reductase, permitting its maximal ERAD and ER-to-Golgi transport of UBIAD1. Mutant UBIAD1 variants associated with Schnyder corneal dystrophy (SCD), a human disorder characterized by corneal accumulation of cholesterol, resist GGpp-induced release from reductase and remain sequestered in the ER to block reductase ERAD. Using lines of genetically manipulated cells, we now examine consequences of UBIAD1 deficiency and SCD-associated UBIAD1 on reductase ERAD and cholesterol synthesis. Our results indicated that reductase becomes destabilized in the absence of UBIAD1, resulting in reduced cholesterol synthesis and intracellular accumulation. In contrast, an SCD-associated UBIAD1 variant inhibited reductase ERAD, thereby stabilizing the enzyme and contributing to enhanced synthesis and intracellular accumulation of cholesterol. Finally, we present evidence that GGpp-regulated, ER-to-Golgi transport enables UBIAD1 to modulate reductase ERAD such that synthesis of nonsterol isoprenoids is maintained in sterol-replete cells. These findings further establish UBIAD1 as a central player in the reductase ERAD pathway and regulation of isoprenoid synthesis. They also indicate that UBIAD1-mediated inhibition of reductase ERAD underlies cholesterol accumulation associated with SCD.

Management of Pediatric Adhesive Small Bowel Obstruction: Do Timing of Surgery and Age Matter?

BACKGROUND: Adhesive small bowel obstruction (ASBO) in children is generally managed with initial observation. However, no clear guidelines exist regarding indications to operate. Our purpose was to compare outcomes of ASBO management to determine whether timing of surgery and patient age should affect management. MATERIALS AND METHODS: A retrospective review of children admitted to a tertiary care children's hospital for ASBO between 2011 and 2015 was performed. Data included demographics, imaging, operative findings, and clinical management, which were analyzed using χ2 test, Fischer's exact test, t-test, analysis of variance, or logistic regression when appropriate. RESULTS: We identified 258 admissions for 202 patients. Urgent operation was performed in 12% and the rest had nonoperative management (NOM), which was successful in 54%. Patients younger than 1 y of age were more likely to require operation (odds ratio 3.71, 95% confidence interval [CI] 1.69-8.15; P < 0.01), and patients with prior ASBO were less likely to require operation (odds ratio 0.51, 95% CI 0.31-0.84; P < 0.01). At presentation, fever was most common in patients who had urgent operation (22.3% versus failure of NOM 7.6% versus successful NOM 6.6%; P = 0.02), but there were no differences in leukocytosis or abdominal pain. Excluding urgent operations, bowel resection was more common when operation was delayed more than 48 h (32.6% versus 15.3%; P = 0.04). CONCLUSIONS: In children with adhesive small bowel obstruction, NOM can be successful, but when failure is suspected, early operation before 48 h should be considered to avoid bowel loss, especially in children younger than 1 y of age.

Intravenous Acetaminophen-Induced Hypotension: A Review of the Current Literature.

Objective: Recent literature suggests that intravenous (IV) administration may cause hypotension in hospitalized patients; data further suggest that this effect is most pronounced in the critically ill. The purpose of this review is to identify and evaluate current literature that addresses the incidence and implications of IV acetaminophen-induced hypotension. Data Sources: A literature search of MEDLINE, Cochrane, and EMBASE databases was performed (2002-2019) using the following terms: acetaminophen, paracetamol, intravenous, and hypotension. Abstracts and peer-reviewed publications were reviewed. Study Selection and Data Extraction: Relevant English-language studies conducted in humans evaluating the hemodynamic effects of IV acetaminophen were considered. Data Synthesis: A majority of the 19 studies included in this review identified a statistically significant drop in hemodynamic variables after the administration of 500 to 1000 mg IV acetaminophen as measured by changes in systolic blood pressure, diastolic blood pressure, or mean arterial pressure. Of the trials reporting vasopressor use, the authors found a significant increase in vasopressor requirements following IV acetaminophen administration. Relevance to Patient Care and Clinical Practice: This review represents the first comprehensive review of IV acetaminophen-induced hypotension. The findings raise the question of whether IV acetaminophen is an appropriate choice for inpatient pain or temperature management in the critically ill. Conclusions: Available evidence indicates that the administration of IV acetaminophen may be harmful in the critically ill. Additional monitoring is likely required when using IV acetaminophen in this specific population, particularly if a patient is hemodynamically unstable prior to administration.

Evaluation of Simulation Models that Estimate the Effect of Dietary Strategies on Nutritional Intake: A Systematic Review.

Background: Dietary simulation modeling can predict dietary strategies that may improve nutritional or health outcomes.Objectives: The study aims were to undertake a systematic review of simulation studies that model dietary strategies aiming to improve nutritional intake, body weight, and related chronic disease, and to assess the methodologic and reporting quality of these models.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guided the search strategy with studies located through electronic searches [Cochrane Library, Ovid (MEDLINE and Embase), EBSCOhost (CINAHL), and Scopus]. Study findings were described and dietary modeling methodology and reporting quality were critiqued by using a set of quality criteria adapted for dietary modeling from general modeling guidelines.Results: Forty-five studies were included and categorized as modeling moderation, substitution, reformulation, or promotion dietary strategies. Moderation and reformulation strategies targeted individual nutrients or foods to theoretically improve one particular nutrient or health outcome, estimating small to modest improvements. Substituting unhealthy foods with healthier choices was estimated to be effective across a range of nutrients, including an estimated reduction in intake of saturated fatty acids, sodium, and added sugar. Promotion of fruits and vegetables predicted marginal changes in intake. Overall, the quality of the studies was moderate to high, with certain features of the quality criteria consistently reported.Conclusions: Based on the results of reviewed simulation dietary modeling studies, targeting a variety of foods rather than individual foods or nutrients theoretically appears most effective in estimating improvements in nutritional intake, particularly reducing intake of nutrients commonly consumed in excess. A combination of strategies could theoretically be used to deliver the best improvement in outcomes. Study quality was moderate to high. However, given the lack of dietary simulation reporting guidelines, future work could refine the quality tool to harmonize consistency in the reporting of subsequent dietary modeling studies.