Analysis of nanomaterial biocoronas in biological and environmental surroundings.

A biomolecular coating, or biocorona, forms on the surface of engineered nanomaterials (ENMs) immediately as they enter biological or environmental systems, defining their biological and environmental identity and influencing their fate and performance. This biomolecular layer includes proteins (the protein corona) and other biomolecules, such as nucleic acids and metabolites. To ensure a meaningful and reproducible analysis of the ENMs-associated biocorona, it is essential to streamline procedures for its preparation, separation, identification and characterization, so that studies in different labs can be easily compared, and the information collected can be used to predict the composition, dynamics and properties of biocoronas acquired by other ENMs. Most studies focus on the protein corona as proteins are easier to monitor and characterize than other biomolecules and play crucial roles in receptor engagement and signaling; however, metabolites play equally critical roles in signaling. Here we describe how to reproducibly prepare and characterize biomolecule-coated ENMs, noting especially the steps that need optimization for different types of ENMs. The structure and composition of the biocoronas are characterized using general methods (transmission electron microscopy, dynamic light scattering, capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry) as well as advanced techniques, such as transmission electron cryomicroscopy, synchrotron-based X-ray absorption near edge structure and circular dichroism. We also discuss how to use molecular dynamic simulation to study and predict the interaction between ENMs and biomolecules and the resulting biocorona composition. The application of this protocol can provide mechanistic insights into the formation, composition and evolution of the ENM biocorona, ultimately facilitating the biomedical and agricultural application of ENMs and a better understanding of their impact in the environment.

Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements.

Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.

Food Insecurity and Changes in Diet Quality and Body Mass Index z-Scores Among Elementary School Students.

Background: Previous research has identified food insecurity as a risk factor for obesity but those studies employed cross-sectional designs and were largely focused on adults and young children. In addition, there is a paucity of studies examining the association between food insecurity and changes in children's overall diet quality. This study aimed to assess whether food insecurity is associated with subsequent changes in diet quality and BMI z-scores over 2 years among 7- to 12-year-old children. Methods: We used 2011-2019 secondary data (n = 404) from three randomized controlled trials in Minnesota. Food insecurity was identified using the U.S. Household Food Security Survey Module at baseline (Time 0). Diet quality was determined using the Healthy Eating Index (HEI)-2015 from 24-hour recalls, and BMI z-scores were calculated using measured height and weight. These two outcomes were measured at Time 0, Time 1 (10-12 months from Time 0), and Time 2 (15-24 months from Time 0). Results: Compared with children from food-secure households, those from food-insecure households experienced a 0.13 greater increase in BMI z-scores from Time 0 to Time 2 [95% confidence interval (CI): 0.04 to 0.21] and a 4.5 point increase in HEI-2015 from Time 0 to Time 1 (95% CI: 0.99 to 8.01). Conclusion: Household food insecurity may widen weight disparities among elementary school-aged children. Further studies are needed to identify the role of diet quality in weight changes among children with food insecurity. Clinical Trial Registration Number: NCT01538615, NCT02029976, NCT02973815.

Sequential extraction of anthocyanins and pectin from jabuticaba (Plinia cauliflora) peel: Peel pretreatment effect and ultrasound-assisted extraction.

The jabuticaba bark is rich in anthocyanins and fibers, and its use may be of industrial interest. In the food sector, its used as an ingredient in the production of fermented products, liqueurs or enriched flours. It also has pharmaceutical and cosmetic applications. The objective was to evaluate the effect of pretreatment and fresh use of jabuticaba peels in the extraction of total phenolic compound (TPC) and total anthocyanin (TA) contents with and without ultrasound assistance and in the sequential extraction of pectin from the residue. In the TPC and TA extraction, a 3x2 factorial design was used. For conventional anthocyanin extraction (CAE), occurred in an incubator under agitation. For ultrasound-assisted anthocyanin extraction (UAE) was utilized an ultrasonic homogenizer with probe (20 kHz, 160 W). The extracts were quantified (TPC, TA, antioxidant activity and color). The residues were characterized and used for sequential pectin extraction, which was quantified and characterized. The results were subjected to analysis of variance. Fresh jabuticaba peel is a residue that can be used to sequentially extract phenolic compounds, particularly anthocyanins and pectin. The use of ultrasound (UAE) was less efficient than CAE for extracting TPC and TA or performing sequential extraction on all pretreatment peels.

Associations between cooking skills, cooking with processed foods, and health: a cross-sectional study.

To improve health outcomes, home cooking has been suggested as a solution to reduce intakes of processed foods. However, little is known about how cooking skills or cooking with processed foods influence health. This cross-sectional study examined associations between diet and health outcomes with cooking skills and cooking with processed foods. The dataset included a nationally representative sample of 18 460 adults from Canadian Community Health Survey (CCHS) annual component rapid response modules on food skills. In the CCHS rapid response modules, diet and health outcomes (fruit and vegetable intake, general health, mental health, and obesity) and data related to cooking skills and cooking with processed foods were collected through self-report. Separate logistic regression models were fitted for each outcome, controlling for age, income, and education, and stratified by sex. Adults with poor cooking skills were less likely to have adequate fruit and vegetable intake (≥5 servings per day) (p < 0.001), very good general health (p < 0.001) or mental health (p < 0.001), and obesity (p = 0.02) compared to advanced cooking skills. Adults who cooked with highly processed foods were less likely to have adequate fruit and vegetable intake (p < 0.001), very good general health (p = 0.002) or mental health (p < 0.001), but more likely to have obesity (p = 0.03) compared to cooking with minimally processed foods. Cooking skills alone appear insufficient to protect against obesity. Results suggest that not only are cooking skills important, but the quality of ingredients also matter. Limiting the use of processed foods in addition to improving cooking skills are potential intervention targets to promote better health and diet outcomes.

SIRT2 transgenic over-expression does not impact lifespan in mice.

The NAD+ -dependent deacylase family of sirtuin enzymes have been implicated in biological ageing, late-life health and overall lifespan, though of these members, a role for sirtuin-2 (SIRT2) is less clear. Transgenic overexpression of SIRT2 in the BubR1 hypomorph model of progeria can rescue many aspects of health and increase overall lifespan, due to a specific interaction between SIRT2 and BubR1 that improves the stability of this protein. It is less clear whether SIRT2 is relevant to biological ageing outside of a model where BubR1 is under-expressed. Here, we sought to test whether SIRT2 over-expression would impact the overall health and lifespan of mice on a nonprogeroid, wild-type background. While we previously found that SIRT2 transgenic overexpression prolonged female fertility, here, we did not observe any additional impact on health or lifespan, which was measured in both male and female mice on standard chow diets, and in males challenged with a high-fat diet. At the biochemical level, NMR studies revealed an increase in total levels of a number of metabolites in the brain of SIRT2-Tg animals, pointing to a potential impact in cell composition; however, this did not translate into functional differences. Overall, we conclude that strategies to enhance SIRT2 protein levels may not lead to increased longevity.

Parent meal self-efficacy and practices in households with healthy home food environments in the face of economic hardship.

Some families who experience economic hardship demonstrate remarkable strength and resourcefulness to sustain a healthy home food environment. This ability to navigate economic barriers could be associated with parent meal practices that promote children's healthful dietary intake. Therefore, this study aimed to examine 1) whether parent meal self-efficacy and practices were associated with economic assistance status and home fruit and vegetable (FV) availability and 2) how parent meal self-efficacy and practices differed by home FV availability and economic assistance status. Analyses utilized baseline data from 274 parent/child dyads from two childhood obesity prevention trials: HOME Plus (urban) and NU-HOME (rural). Parents in households with high FV availability (regardless of economic assistance) had significantly higher self-efficacy in preparing healthy foods, family dinner routines, frequency of child's plate being half filled with FV, frequency of family dinner and breakfast, and lower frequency of purchasing dinner from fast food restaurants. Economic assistance was not associated with parent meal self-efficacy and practices. Four family groups were created and defined by economic assistance (yes/no) and home FV availability (high/low). About 31% of families that received economic assistance and had high home FV availability were food insecure. Families (n = 39) receiving economic assistance and having high home FV availability had greater frequency of family dinners compared to those in households with economic assistance and low home FV availability (n = 47) (p = 0.001); no other parent meal self-efficacy or practices differed between groups. Our findings suggest some families can maintain healthy home food environments despite economic hardship and frequent family dinners may be an important strength for these families. More research is needed to investigate asset-based models to understand the family strengths that enable them to thrive during difficult times.

Phenotypic Drug Resistance Pattern and Mutation Characteristics of Mycobacterium tuberculosis from Different Body Fluids Among Extra Pulmonary Patients Presented in Selected Hospitals in Addis Ababa, Ethiopia.

Background: Drug resistance in tuberculosis poses challenges to both the control and prevention of the disease. The extent of resistance is not well known in developing countries, including Ethiopia. This study was conducted to determine the drug resistance patterns and mutation characteristics of Mycobacterium tuberculosis among extra pulmonary tuberculosis patients in selected health facilities in Addis Ababa. Material and Methods: A cross-sectional study was conducted from February 2022 to August 2022 in selected hospitals in Addis Ababa. Socio-demographic and clinical data were collected using structured questionnaire. Mycobacterium tuberculosis complex (MTBC) isolates were tested for phenotypic drug susceptibility patterns using the Mycobacterium growth indicator tube (MGIT) method for first-line drugs and mutation characteristics using the Line Probe Assay (LPA) method. The data were analyzed using: SPSS version 23, and a P-value ≤ 0.05 was considered statistically significant. Results: From a total of 308 patient samples from presumptive extra pulmonary patients, 44 (14.3%) were positive for MTBC. Any drug resistance was discovered in 25% of 44 MTBC isolates evaluated for five first-line drugs phenotypically, with isoniazid (INH) and pyrazinamide (PZA) resistance accounting for a greater proportion with 13.6% and 11.4% of the isolates, respectively. Two (4.5%) of the isolates were MDR-TB. Out of 44 isolates tested using the Geno Type MTBDRplus assay, 5 (11.4%) showed mutations at katG and 2 (4.5%) showed mutations in the rpoB genes. Conclusion: Both the phenotypic and genotypic drug susceptibility test results showed a high proportion of INH resistance. All INH resistance-conferring mutations were identified from katG gene. The overall prevalence of MDR-TB was also high. For early case detection and treatment, expanding diagnostic capacity for first-line DST is a vital step to limit further spread of drug resistant TB strains in the study area.

Human Milk Feeding and Direct Breastfeeding Improve Outcomes for Infants With Single Ventricle Congenital Heart Disease: Propensity Score-Matched Analysis of the NPC-QIC Registry.

Background Infants with single ventricle congenital heart disease undergo 3 staged surgeries/interventions, with risk for morbidity and mortality. We estimated the effect of human milk (HM) and direct breastfeeding on outcomes including necrotizing enterocolitis, infection-related complications, length of stay, and mortality. Methods and Results We analyzed the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry (2016-2021), examining HM/breastfeeding groups during stage 1 and stage 2 palliations. We calculated propensity scores for feeding exposures, then fitted Poisson and logistic regression models to compare outcomes between propensity-matched cohorts. Participants included 2491 infants (68 sites). Estimates for all outcomes were better in HM/breastfeeding groups. Infants fed exclusive HM before stage 1 palliation (S1P) had lower odds of preoperative necrotizing enterocolitis (odds ratio [OR], 0.37 [95% CI, 0.17-0.84]; P=0.017) and shorter S1P length of stay (rate ratio [RR], 0.87 [95% CI, 0.78-0.98]; P=0.027). During the S1P hospitalization, infants with high HM had lower odds of postoperative necrotizing enterocolitis (OR, 0.28 [95% CI, 0.15-0.50]; P<0.001) and sepsis (OR, 0.29 [95% CI, 0.13-0.65]; P=0.003), and shorter S1P length of stay (RR, 0.75 [95% CI, 0.66-0.86]; P<0.001). At stage 2 palliation, infants with any HM (RR, 0.82 [95% CI, 0.69-0.97]; P=0.018) and any breastfeeding (RR, 0.71 [95% CI, 0.57-0.89]; P=0.003) experienced shorter length of stay. Conclusions Infants with single ventricle congenital heart disease in high-HM and breastfeeding groups experienced multiple significantly better outcomes. Given our findings of improved health, strategies to increase the rates of HM/breastfeeding in these patients should be implemented. Future research should replicate these findings with granular feeding data and in broader congenital heart disease populations, and should examine mechanisms (eg, HM components, microbiome) by which HM/breastfeeding benefits these infants.

Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing.

AIMS/HYPOTHESIS: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management. METHODS: We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021. RESULTS: In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks. CONCLUSIONS/INTERPRETATION: Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.

Predictors of Human Milk Feeding and Direct Breastfeeding for Infants with Single Ventricle Congenital Heart Disease: Machine Learning Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Registry.

OBJECTIVE: To identify factors that support or limit human milk (HM) feeding and direct breastfeeding (BF) for infants with single ventricle congenital heart disease at neonatal stage 1 palliation (S1P) discharge and at stage 2 palliation (S2P) (∼4-6 months old). STUDY DESIGN: Analysis of the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry (2016-2021; 67 sites). Primary outcomes were any HM, exclusive HM, and any direct BF at S1P discharge and at S2P. The main analysis involved multiple phases of elastic net logistic regression on imputed data to identify important predictors. RESULTS: For 1944 infants, the strongest predictor domain areas included preoperative feeding, demographics/social determinants of health, feeding route, clinical course, and site. Significant findings included: preoperative BF was associated with any HM at S1P discharge (OR = 2.02, 95% CI = 1.74-3.44) and any BF at S2P (OR = 2.29, 95% CI = 1.38-3.80); private/self-insurance was associated with any HM at S1P discharge (OR = 1.91, 95% CI = 1.58-2.47); and Black/African-American infants had lower odds of any HM at S1P discharge (OR = 0.54, 95% CI = 0.38-0.65) and at S2P (0.57, 0.30-0.86). Adjusted odds of HM/BF practices varied among NPC-QIC sites. CONCLUSIONS: Preoperative feeding practices predict later HM and BF for infants with single ventricle congenital heart disease; therefore, family-centered interventions focused on HM/BF during the S1P preoperative time are needed. These interventions should include evidence-based strategies to address implicit bias and seek to minimize disparities related to social determinants of health. Future research is needed to identify supportive practices common to high-performing NPC-QIC sites.

Daphnia as a model organism to probe biological responses to nanomaterials-from individual to population effects via adverse outcome pathways.

The importance of the cladoceran Daphnia as a model organism for ecotoxicity testing has been well-established since the 1980s. Daphnia have been increasingly used in standardised testing of chemicals as they are well characterised and show sensitivity to pollutants, making them an essential indicator species for environmental stress. The mapping of the genomes of D. pulex in 2012 and D. magna in 2017 further consolidated their utility for ecotoxicity testing, including demonstrating the responsiveness of the Daphnia genome to environmental stressors. The short lifecycle and parthenogenetic reproduction make Daphnia useful for assessment of developmental toxicity and adaption to stress. The emergence of nanomaterials (NMs) and their safety assessment has introduced some challenges to the use of standard toxicity tests which were developed for soluble chemicals. NMs have enormous reactive surface areas resulting in dynamic interactions with dissolved organic carbon, proteins and other biomolecules in their surroundings leading to a myriad of physical, chemical, biological, and macromolecular transformations of the NMs and thus changes in their bioavailability to, and impacts on, daphnids. However, NM safety assessments are also driving innovations in our approaches to toxicity testing, for both chemicals and other emerging contaminants such as microplastics (MPs). These advances include establishing more realistic environmental exposures via medium composition tuning including pre-conditioning by the organisms to provide relevant biomolecules as background, development of microfluidics approaches to mimic environmental flow conditions typical in streams, utilisation of field daphnids cultured in the lab to assess adaption and impacts of pre-exposure to pollution gradients, and of course development of mechanistic insights to connect the first encounter with NMs or MPs to an adverse outcome, via the key events in an adverse outcome pathway. Insights into these developments are presented below to inspire further advances and utilisation of these important organisms as part of an overall environmental risk assessment of NMs and MPs impacts, including in mixture exposure scenarios.

Human milk feeding and direct breastfeeding improve outcomes for infants with single ventricle congenital heart disease: Propensity score matched analysis of the NPC-QIC registry.

Background: Infants with single ventricle (SV) congenital heart disease (CHD) undergo three staged surgeries/interventions, with risk for morbidity and mortality. We estimated the effect of human milk (HM) and direct breastfeeding (BF) on outcomes including necrotizing enterocolitis (NEC), infection-related complications, length of stay (LOS), and mortality. Methods: We analyzed the National Pediatric Cardiology Quality Improvement Collaborative registry (2016-2021), examining HM/BF groups during stage 1 (S1P) and stage 2 (S2P) palliations. We calculated propensity scores for feeding exposures, then fitted Poisson and logistic regression models to compare outcomes between propensity-matched cohorts. Results: Participants included 2491 infants (68 sites). Estimates for all outcomes were better in HM/BF groups. Infants fed exclusive HM before S1P had lower odds of preoperative NEC (OR=0.37, 95% CI=0.17-0.84, p=0.017) and shorter S1P LOS (RR=0.87, 0.78-0.98, p=0.027). During the S1P hospitalization, infants with high HM had lower odds of postoperative NEC (OR=0.28, 0.15-0.50, p<0.001) and sepsis (0.29, 0.13-0.65, p=0.003), and shorter S1P LOS (RR=0.75, 0.66-0.86, p<0.001). At S2P, infants with any HM (0.82, 0.69-0.97, p=0.018) and any BF (0.71, 0.57-0.89, p=0.003) experienced shorter LOS. Conclusions: Infants with SV CHD in high HM and BF groups experienced multiple significantly better outcomes. Given our findings of improved health, strategies to increase the rates of HM/BF in these patients should be implemented. Future research should replicate these findings with granular feeding data and in broader CHD populations, and should examine mechanisms (eg, HM components; microbiome) by which HM/BF benefits these infants. Clinical Perspective: What is new?: This is the first large, multisite study examining the impact of human milk and breastfeeding on outcomes for infants with single ventricle congenital heart disease.All outcome estimates were better in high human milk and breastfeeding groups, with significantly lower odds of necrotizing enterocolitis, sepsis, and infection-related complications; and significantly shorter length of stay at both the neonatal stage 1 palliation and the subsequent stage 2 palliation.All estimates of all-cause mortality were substantially lower in human milk and breastfeeding groups, with clinically important estimates of 75%-100% lower odds of mortality in direct breastfeeding groups.What are the clinical implications?: There is a critical need for improved, condition-specific lactation support to address the low prevalence of human milk and breastfeeding for infants with single ventricle congenital heart disease.Increasing the dose and duration of human milk and direct breastfeeding has strong potential to substantially improve the health outcomes of these vulnerable infants.

Patterns of Breastfeeding and Human Milk Feeding in Infants with Single-Ventricle Congenital Heart Disease: A Population Study of the National Pediatric Cardiology Quality Improvement Collaborative Registry.

Introduction: Infants with single-ventricle (SV) congenital heart disease (CHD) undergo staged surgical and/or catheter-based palliation and commonly experience feeding challenges and poor growth. Little is known about human milk (HM) feeding or direct breastfeeding (BF) in this population. Aim: To determine (1) HM and BF prevalence for infants with SV CHD, and (2) whether BF at neonatal stage 1 palliation (S1P) discharge is associated with any HM at stage 2 palliation (S2P; ∼4-6 months old). Materials and Methods: Analysis of the National Pediatric Cardiology Quality Improvement Collaborative registry (2016-2021) using (1) descriptive statistics for prevalence, and (2) logistic regression adjusted for multiple variables (e.g., prematurity, insurance, length of stay) to examine early BF/later HM feeding. Results: Participants included 2,491 infants from 68 sites. HM prevalence ranged from 49.3% any/41.5% exclusive before S1P to 37.1% any/7.0% exclusive at S2P. Direct BF ranged from 16.1% any/7.9% exclusive before S1P to 9.2% any/3.2% exclusive at S2P discharge. Prevalence varied among sites; for example, 0-100% any HM before S1P. Infants BF at S1P discharge had greater odds of any HM (odds ratio = 4.11, 95% confidence interval [CI] = 2.79-6.07, p < 0.001) and exclusive HM (1.85, 95% CI 1.03-3.30, p = 0.039) at S2P. Conclusions: The prevalence of HM and BF for infants with SV CHD was low and declined over time. Direct BF at S1P discharge was associated with increased odds of any HM at S2P. Wide variation suggests that site-specific practices impact feeding outcomes. HM and BF prevalence are suboptimal in this population, and identification of supportive institutional practices is needed.

Food Insecurity and Parent Feeding Practices in Urban and Rural Children Ages 7-12 years.

Objective: To examine associations between food insecurity and parent feeding practices for children ages 7-12 years; to determine differences between cohorts in urban and rural communities. Design: Secondary analysis using baseline data from 2 randomized controlled trials: HOME Plus (urban) and NU-HOME (rural). Participants: Convenience sample of 264 parent-child dyads. Children were 51.5% female, 9.28 ± 1.45 years. Variables Measured: Dependent variables included the Child Feeding Questionnaire (CFQ) restrictive feeding subscale, parent modeling of fruits and vegetables score, and family meal frequency (FMF) at breakfast and the evening meal. Food insecurity was the primary independent variable. Analysis: Multivariable linear or Poisson regression for each outcome. Results: Food insecurity was associated with a 26% lower weekly rate of FMF at breakfast (95% CI 6%-42%; p=0.02). In stratified analysis, this association was only in the rural NU-HOME study (44% lower weekly rate; 95% CI 19%-63%; p=0.003). Food insecurity was not associated with CFQ restrictive score, parent modeling score, or FMF at the evening meal. Conclusions and Implications: Food insecurity was associated with less frequent family breakfast, but not with other parent feeding practices. Future studies could investigate supportive mechanisms for positive feeding practices in households experiencing food insecurity.

Parent Weight, Diet, Active Living, and Food-Related Outcomes of the Family-Focused:NU-HOME Randomized Controlled Trial: NU-HOME Randomized Controlled Trial.

BACKGROUND: Little is known about parent outcomes of rural, family-focused childhood obesity prevention trials. OBJECTIVE: Our aim was to evaluate parent outcomes of the rural, family-focused NU-HOME (New Ulm at HOME [Healthy Offerings via the Mealtime Environment]) randomized controlled trial designed to prevent obesity in children aged 7 through 10 years. DESIGN: Families were randomized to the intervention or wait-list control group after baseline data collection. Staff measured parent height, weight, and percent body fat. Surveys measured parent cognitive and behavioral outcomes (eg, portion-size confidence, dietary intake, total and moderate-to-vigorous physical activity, and screen time). Post-intervention data were collected 8 to 10 months after baseline. PARTICIPANTS/SETTING: The randomized controlled trial took place in rural, south central Minnesota, and enrolled parent and child dyads (N = 114; 2017-2018); 98 parents provided data at post intervention (2018-2019) and comprise the analytic sample. Parent inclusion criteria were being the primary meal preparer, living with the child most of the time, and being willing to attend intervention sessions. Exclusion criteria were planning to move or having a medical condition that would contraindicate participation. INTERVENTION: The theory-guided intervention (7 sessions and 4 goal-setting calls) focused on family eating and active living behaviors. MAIN OUTCOME MEASURES: Height, weight, and percent body fat were measured and the survey assessed diet, active living, and food-related outcomes. STATISTICAL ANALYSES PERFORMED: Multiple linear regression models tested change in parent outcomes from baseline to post intervention by treatment group adjusted for demographic characteristics and baseline values. RESULTS: In the intervention group vs control group, parent total weekly hours of physical activity was 1.73 hours higher (95% CI 0.11 to 3.35 hours) and portion-size confidence was 1.49 points higher (95% CI 0.78 to 2.19). No other statistically significant changes were observed by treatment group. CONCLUSIONS: Findings indicate that parent cognitive and behavioral outcomes are amenable to change in family-focused childhood obesity prevention programs. Parent increases in portion-size confidence and total physical activity hours may support long-term parent health and provide positive context for child health.

Hyperinsulinemic Hypoglycemia Diagnosed in Childhood Can Be Monogenic.

CONTEXT: Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood. OBJECTIVE: We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to later age at presentation of disease. METHODS: We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (diagnosed with HI < 12 months of age) or childhood-onset (diagnosed at age 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children. RESULTS: We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort; this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% [n = 1248/1675], P < 0.00001). Most (75%) individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years, suggesting these cases represent the tail end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy. CONCLUSION: We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.

Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1.

Background: Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism caused by an activating GLUD1 mutation. Objective: The aim of this study was to determine the clinical profile and long-term neurological outcomes in children with HI/HA syndrome. Method: This study is a retrospective review of patients with GLUD1 mutation, treated at two centers in the UK and Russia, over a 15-year period. Different risk factors for neuro-developmental disorders were analysed by Mann-Whitney U test and Fisher's exact P test. Results: We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 h-18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. Twenty four cases responded to diazoxide and protein restriction whilst one patient underwent partial pancreatectomy. In total, 13 cases (52%) developed neurodevelopmental manifestations. Epilepsy (n = 9/25, 36%), learning difficulties (n = 8/25, 32%) and speech delay (n = 8/25, 32%) were the most common neurological manifestation. Median age of presentation for epilepsy was 12 months with generalised tonic-clonic seizures being the most common (n = 4/9, 44.4%) followed by absence seizures (n = 3/9, 33.3%). Early age of presentation (P = 0.02), diazoxide dose (P = 0.04) and a mutation in exon 11 or 12 (P = 0.01) were associated with neurological disorder. Conclusion: HI/HA syndrome is associated with wide spectrum of neurological disorders. These neurological manifestations were more frequent in cases with mutations affecting the GTP-binding site of GLUD1 in our cohort.

Weight Status Among Minnesota Hispanic or Latino/a Youth: An Exploration of Protective Factors.

PURPOSE: Pediatric obesity disproportionately impacts Hispanic or Latino/a adolescents. Culturally appropriate family-based behavioral initiatives to improve weight status are warranted. The purpose of this research was to determine prevalence rates and identify protective factors associated with having overweight/obesity (body mass index ≥ 85th percentile) to inform Hispanic or Latino/a-targeted behavioral intervention development. DESIGN: Secondary data analyses of a population-based statewide survey. SETTING: Minnesota public high schools. PARTICIPANTS: Male (n = 2,644) and female (n = 2,798) Hispanic or Latino/a 9th and 11th graders (N = 5,442). MEASURES: Obesity-related behaviors (meeting fruit and vegetable [F&V] and physical activity [PA] recommendations), family caring, family country/region of origin, and weight status. ANALYSIS: Stepwise logistic regression models (F&V, PA), stratified by biological sex, were used to identify protective factors of overweight/obesity. RESULTS: The overall prevalence of meeting F&V and PA recommendations was 11.0% and 11.8%, respectively. Meeting F&V recommendations was not protective against overweight/obesity in either sex. Yet, males and females who met PA recommendations had significantly lower odds of having overweight/obesity (p < .05). In F&V and PA models, family caring was protective against overweight/obesity in females (p < .05), and family country/region of origin was protective against overweight/obesity in both sexes (p < .05). CONCLUSION: Findings illustrate a need for obesity prevention initiatives for Hispanic or Latino/a youth. More research is needed to understand the protective nature of family caring and country/region of origin.

A novel method to map community- and neighborhood-level access to rural physical activity built environments in the United States.

Physical activity (PA) built environments may support PA among rural youth and families. In the United States (U.S.), differences between rural and urban PA built environments are assessed using coarse scale, county-level methods. However, this method insufficiently examines environmental differences within rural counties. The present study uses rural-specific geospatial mapping techniques and a fine scale, within-rural grouping strategy to identify differing levels of access to the PA built environment among a rural sample. First, PA infrastructure variables (parks, sidewalks) within a rural region of the Midwest U.S. were mapped. Then, households (N = 112) of participants in the NU-HOME study, a childhood obesity prevention trial, were categorized to community-level and neighborhood-level PA built environment groups using two access indicators; Rural-Urban Commuting Area (RUCA) codes and Walk Scores®, respectively. Finally, households were categorized to new groups that combined community-level RUCA codes and neighborhood-level Walk Scores® to indicate the diverse ways in which rural families might access PA built environments, including by vehicle travel and pedestrian commuting. Household access to PA infrastructure (per geospatial proximity and density analyses), parent perceptions of the PA environment, and child PA were examined across the new combined access groups. All measures of household access to PA infrastructure significantly differed by group (p <.0001). Several parent PA perceptions differed by group; child PA did not. The present study provides future researchers with innovative strategies to map and examine how access to the PA built environment differs within a rural area. Due to the public availability of the access indicators used (RUCA codes, Walk Scores®), study methods can be replicated.