Wellbeing in Children and Adolescents with Fontan Physiology.

OBJECTIVE: To assess health-related quality of life (HRQOL) and global quality of life (QOL) in children and adolescents with Fontan physiology and identify key predictors influencing these outcomes. STUDY DESIGN: Cross-sectional analysis of 73 children and adolescents enrolled in the Australia and New Zealand Fontan Registry (ANZFR) aged 6-17 years, at least 12 months post-Fontan operation. Assessments included the Pediatric Quality of Life Inventory 4.0 (PedsQL) for HRQOL and a developmentally-tailored visual analogue scale (0-10) for global QOL, along with validated sociodemographic, clinical, psychological, relational, and parental measures. Clinical data were provided by the ANZFR. RESULTS: Participants (mean age: 11.5±2.6 years, 62% male) reported lower overall HRQOL (p<0.001), and lower scores across all HRQOL domains (all p<0.0001), compared with normative data. Median global QOL score was 7.0 (IQR 2.2), with most participants (79%) rating their global QOL ≥6. Anxiety and depressive symptoms requiring clinical assessment were reported by 21% and 26% of participants, respectively. Age, sex, and perceived seriousness of CHD explained 15% of the variation in HRQOL scores, while depressive symptoms and treatment-related anxiety explained an additional 37% (final model: 52% of variance explained). For global QOL, sociodemographic and clinical factors explained 13% of the variance in scores, while depressive symptoms explained a further 25% (final model: 38% of variance explained). Parental factors were not associated with child QOL outcomes. CONCLUSIONS: Children and adolescents with Fontan physiology experience lower HRQOL than community-based norms, despite reporting fair overall QOL. Psychological factors predominantly influenced QOL outcomes, indicating strategies to bolster psychological health could improve QOL in this population.

Syntheses and studies of deuterated Imdiazo[1,2-a]pyridine-3-carboxamides with potent anti-tuberculosis activity and improved metabolic properties.

The imidazo[1,2-a]pyridine-3-carboxyamides (IAPs) are a unique class of compounds endowed with impressive nanomolar in vitro potency against Mycobacterium tuberculosis (Mtb) as exemplified by clinical candidate Telacebec (Q203). These compounds target mycobacterial respiration through inhibition of the QcrB subunit of cytochrome bc1:aa3 super complex resulting in bacteriostatic efficacy in vivo. Our labs have had a long-standing interest in the design and development of IAPs. However, some of these compounds suffer from short in vivo half-lives, requiring multiple daily dosing or the addition of a cytochrome P450 inhibitor for murine efficacy evaluations. Deuteration has been shown to decrease metabolism as the C-D bond is stronger than the CH bond. Herein we describe our efforts on design and synthesis of potent deuterated IAPs and the effect that deuteration has upon metabolism through microsomal stability studies.

Shoot-level flammability across the Dracophyllum (Ericaceae) phylogeny: evidence for flammability being an emergent property in a land with little fire.

Plant flammability varies across species, but the evolutionary basis for this variation is not well understood. Phylogenetic analysis of interspecific variation in flammability can provide insights into the evolution of plant flammability. We measured four components of flammability (ignitability, sustainability, combustibility and consumability) to assess the shoot-level flammability of 21 species of Dracophyllum (Ericaceae). Using a macroevolutionary approach, we explored phylogenetic patterns of variation in shoot-level flammability. Shoot-level flammability varied widely in Dracophyllum. Species in the subgenus Oreothamnus had higher flammability and smaller leaves than those in the subgenus Dracophyllum. Shoot flammability (ignitability, combustibility and consumability) and leaf length showed phylogenetic conservatism across genus Dracophyllum, but exhibited lability among some closely related species, such as D. menziesii and D. fiordense. Shoot flammability of Dracophyllum species was negatively correlated with leaf length and shoot moisture content, but had no relationship with the geographic distribution of Dracophyllum species. Shoot-level flammability varied widely in the genus Dracophyllum, but showed phylogenetic conservatism. The higher flammability of the subgenus Oreothamnus may be an incidental or emergent property as a result of the evolution of flammability-related traits, such as smaller leaves, which were selected for other functions and incidentally changed flammability.

Outbreak Characteristics and Epidemic Curves for Multistate Outbreaks of Salmonella Infections Associated with Produce: United States, 2009-2015.

Produce is recognized as a source of Salmonella-related foodborne outbreaks in the United States. Identifying produce as a source of foodborne outbreaks is challenging given short product shelf lives and durations of many produce-associated outbreaks. Investigators consider produce a plausible source when illnesses occur over a short time period and disproportionately affect middle-aged or female individuals. We reviewed characteristics of past Salmonella produce outbreaks and their consistency with principles used by epidemiologists when generating hypotheses about an outbreak source. We queried the Foodborne Disease Outbreak Surveillance System for multistate, produce-associated Salmonella outbreaks reported to the Centers for Disease Control and Prevention from 2009 to 2015. All produce-associated outbreaks were classified as fruit outbreaks or vegetable outbreaks using an established classification scheme. We then compared fruit and vegetable outbreaks by characteristics of size, gender, age, age groups, geographic spread, duration, and velocity measures using Wilcoxon rank-sum tests. Epidemic curves were created to display visual representations of outbreak duration and velocity. We identified 14 fruit outbreaks and 24 vegetable outbreaks. The median number of illnesses for all produce-associated outbreaks was 30 and a high median percentage of illnesses were in females (61.9%). Median age was 34 years, with a median of 53.2% of illnesses affecting the 18-59 age group. For all outbreaks, median duration was 77 d and median time to the 50th percentile of illnesses was 32.5 d. Fruit and vegetable outbreaks differed only in the age groups affected. We used outbreak data to verify common indicators of produce-associated Salmonella outbreaks. Outbreaks affected females and middle-aged individuals more commonly, while fruit and vegetable outbreaks impacted different age groups. Although median outbreak duration was less than 12 weeks for both fruit and vegetable outbreaks, there was considerable variation, decreasing its utility as an indicator of produce as a source of the outbreak.

Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position statement.

The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.

Evidence for sex differences in fetal programming of physiological stress reactivity in infancy.

Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.

Feasibility and Acceptability of Facilitated Advance Care Planning in Outpatient Clinics: A Qualitative Study of Patient and Caregivers Experiences.

Guidelines recommend advance care planning (ACP) for people with advanced illness; however, evidence supporting ACP as a component of outpatient care is lacking. We sought to establish the feasibility and acceptability of a facilitated ACP intervention for people attending tertiary outpatient clinics. Data from 20 semi-structured interviews with patient (M = 79.3 ± 7.7, 60% male) and caregiver (M = 68.1 ± 11.0, 60% female) participants recruited as part of a pragmatic, randomized controlled trial (RCT) were analyzed using qualitative descriptive methodology. Patients were randomized to intervention (e.g., facilitated support) or control (e.g., standard care). Intervention patients expressed high satisfaction, reporting the facilitated ACP session was clear, straightforward, and suited to their needs. Intervention caregivers did not report any significant concerns with the facilitated ACP process. Control participants reported greater difficulty completing ACP compared to intervention participants. Embedding facilitated ACP into tertiary outpatient care appears feasible and acceptable for people with advanced illnesses.

Feasibility and acceptability of facilitated advance care planning in outpatient clinics: A qualitative study of health-care professionals experience.

OBJECTIVE: This study sought to determine the feasibility and acceptability of a facilitated advance care planning (ACP) intervention implemented in outpatient clinics, as perceived by health-care professionals (HCPs). METHODS: Data from seven focus groups (n = 27) and nine semi-structured interviews with HCPs recruited as part of a pragmatic, randomised controlled trial (RCT) were analysed using qualitative descriptive methodology. Components of the intervention included HCP education and training, tools to assist HCPs with patient selection, hardcopy information, and ACP documentation, and specialised nurse-facilitators to support HCPs to complete ACP conversations and documentation with patients and caregivers. RESULTS: Health-care professionals working in tertiary outpatient clinics perceived the facilitated ACP intervention as feasible and acceptable. Health-care professionals reported a high level of satisfaction with key elements of the intervention, including the specialised education and training, screening and assessment procedures and ongoing support from the nurse-facilitators. Health-care professionals reported this training and support increased their confidence and ACP knowledge, leading to more frequent ACP discussions with patients and their families. Health-care professionals noted their ability to conduct ACP screening and assessment in clinic was impeded by large clinical caseloads and patient-related factors (e.g., dementia diagnoses, and emotional distress). Additional barriers to ACP implementation identified by HCPs included poor collaboration, constrained time and clinical space, undefined roles and standardised recording procedures for HCPs. CONCLUSIONS: Facilitated ACP intervention in outpatient clinics is perceived by HCPs as feasible and acceptable. Addressing barriers and tailoring implementation strategies may improve the delivery of ACP as part of tertiary outpatient care.

What Influences the Prevalence and Intensity of Haemoparasites and Ectoparasites in an Insular Lizard?

Island biogeography theories predict that characteristics such as island size, age, and isolation interplay in host-parasite dynamics. In this study, we analyzed haemogregarines of the Aegean wall lizard, Podarcis erhardii, to investigate how island characteristics relate to parasite prevalence and intensity. A previous assessment of 19 Greek island populations suggested that isolation time and host population density were key predictors of haemogregarines. Here, by combining microscopy and genetic techniques, we extend this previous study to four additional islands: Syros, Folegandros, Santorini and Nea Kameni. We also recorded the prevalence of ticks and mites, definitive hosts for these parasites. The genetically identified haemogregarines are part of a clade with parasites from other lizard species, including some considered as Karyolysus, but others assigned to Hepatozoon. The prevalence of these parasites differed significantly between islands, while their intensity did not. The presence of ticks was associated with endoparasite prevalence, and males were more frequently infected by haemogregarines than females. Combining our data with that of the previous study, we found no significant impact of the island age and area on parasite prevalence. We also confirmed the presence of the unrelated parasite genus Schellackia through microscopy and DNA sequencing, which is the first record of this genus in this host species. Our results further highlight the complexity of host-parasite systems.

JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family.

We report the clinical, neuropsychological, genetic, and radiological features of a large five-generation African-American kindred from the southern USA presenting with a progressive akinetic-rigid syndrome and severe dementia, but clinically insignificant chorea, due to mutations in junctophillin 3 (JPH3). Overt disease onset was in the mid-20s to late 30s with cognitive decline, REM sleep disturbance, or psychiatric features, followed by development of a levodopa-unresponsive akinetic-rigid motor syndrome. Dystonia and myoclonus were present in some subjects. A bedridden, nonverbal severely akinetic-rigid state developed within 10 to 15 years after onset. CTG repeat expansions ranged from 47 to 53. Imaging revealed generalized cerebral atrophy with severe striatal involvement and putaminal rim hyperintensity. Analysis of our kindred indicates that JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. Moreover, chorea may not be overtly manifest at presentation or during significant parts of the disease course.

Motion dazzle and camouflage as distinct anti-predator defenses.

BACKGROUND: Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms. RESULTS: Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected. CONCLUSIONS: Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage.

Application of Enzyme Indicators in Hydrogen Peroxide Biodecontamination Cycle Development: A Critical Evaluation of Indicator Variability and Correlation to Biological Indicator Results.

An important prerequisite for aseptic production of pharmaceuticals is the appropriate reduction of microbiological contamination. Hydrogen peroxide is commonly applied as decontamination agent for such processes in barrier systems. The development and validation of the barrier decontamination cycles is usually performed with the use of biological indicators (Geobacillus stearothermophilus). However, these indicators inherit certain drawbacks. A new type of indicators became available lately, based on the use of enzyme as a substance decomposed by hydrogen peroxide. There is no broad experience on the practical application of these enzyme indicators yet. Therefore, we investigated the practical use of enzyme indicators in comparison with biological indicators. To broaden the understanding on how these indicators might be used in practice, we provided an evaluation of indicator response variability and the correlation of enzyme indicator results to biological indicator results. In this study, we found the variability of the quantitative enzyme indicator reading to be < 30%, which is much smaller than the variability for spore enumeration of biological indicators (-50% to +300%). Further, we introduced a universal normalization approach to enable convenient comparison and evaluation of different enzyme indicator results. Finally, we discussed a new approach to establish a quantitative correlation between enzyme indicators and biological indicators with the use of threshold values to extrapolate theoretical biological indicator group results. We take the findings of this study as a basis for a suggestion on the practical application of enzyme indicators. We expect that the discussed possibilities of correlating enzyme indicator results to biological indicator results will allow the combined practical use of both indicator types. This would enable the continued application of proven approaches in new ways. Beyond this, the fast reading of enzyme indicators with the gain of significant quantitative information might result in faster and safer qualification and validation of pharmaceutical production equipment in the future.

Integrated psychological care in pediatric hospital settings for children with complex chronic illness and their families: a systematic review.

OBJECTIVE: To synthesize and critically evaluate evidence on the effectiveness of integrated psychological care models for children with complex chronic illness within pediatric hospital settings and provide recommendations for successful implementation. DESIGN: Six electronic databases (Medline, Cochrane, Embase, PsycINFO, Scopus, CINAHL) were systematically searched for English language studies including families of children aged 0-17 years with complex chronic illness. Eligible studies reported on psychology or neuropsychology screening, assessment, intervention, or services provided within a pediatric hospital setting. RESULTS: Fifteen studies were identified for review; nine assessed a psychological service, five examined psychosocial screening, and one examined a neuropsychology service. Three studies demonstrated the effectiveness of integrated psychological services in improving child or parent physical, psychological, or behavioral health outcomes. Uptake of psychosocial screening was high (84-96%), but only 25-37% of children or families identified as 'at-risk' engaged with on-site psychology services. Integrated psychological services offering consultations at the same time and location as the child's medical visit reported the highest rates of uptake (77-100%). CONCLUSIONS: The available evidence supports co-location of child medical and psychological services. A more consistent and comprehensive approach to the assessment of patient- and caregiver-reported outcomes and implementation effectiveness is recommended.

Parent-child bonding and attachment during pregnancy and early childhood following congenital heart disease diagnosis.

Diagnosis and treatment of congenital heart disease (CHD) can present challenges to the developing parent-child relationship due to periods of infant hospitalization and intensive medical care, parent-infant separations, child neurodevelopmental delay and feeding problems, and significant parent and child distress and trauma. Yet, the ways in which CHD may affect the parent-child relationship are not well-understood. We systematically reviewed the evidence on parental bonding, parent-child interaction, and child attachment following CHD diagnosis, according to a pre-registered protocol (CRD42019135687). Six electronic databases were searched for English-language studies comparing a cardiac sample (i.e., expectant parents or parents and their child aged 0-5 years with CHD) with a healthy comparison group on relational outcomes. Of 22 unique studies, most used parent-report measures (73%) and yielded mixed results for parental bonding and parent-child interaction quality. Observational results also varied, although most studies (4 of 6) found difficulties in parent-child interaction on one or more affective or behavioural domains (e.g., lower maternal sensitivity, lower infant responsiveness). Research on parental-fetal bonding, father-child relationships, and child attachment behaviour was lacking. Stronger evidence is needed to determine the nature, prevalence, and predictors of relational disruptions following CHD diagnosis, and to inform targeted screening, prevention, and early intervention programs for at-risk dyads.

The Australian and New Zealand Fontan Registry Quality of Life Study: Protocol for a population-based assessment of quality of life among people with a Fontan circulation, their parents, and siblings.

INTRODUCTION: Advances in the care of patients with single-ventricle congenital heart disease have led to a new generation of individuals living with a Fontan circulation. For people with Fontan physiology, physical, psychological and neurodevelopmental challenges are common. The objective of this study is to describe and develop a deeper understanding of the factors that contribute to quality of life (QOL) among children, adolescents and adults living with a Fontan circulation across Australia and New Zealand, their parents and siblings. METHODS AND ANALYSIS: This article presents the protocol for the Australian and New Zealand Fontan Registry (ANZFR) QOL Study, a cross-sectional, population-based study designed to examine QOL among people of all ages with a Fontan circulation, their parents and siblings. Study eligibility criteria includes (1) individuals with a Fontan circulation aged ≥6 years, at least 12 months post-Fontan procedure and enrolled in the ANZFR; (2) parents of individuals enrolled in the ANZFR; and (3) siblings aged ≥6 years of an individual enrolled in the ANZFR. A novel, online research platform is used to distribute personalised assessments tailored to participant age and developmental stage. A suite of validated psychometric self-report and parent-proxy report instruments capture potential correlates and predictors of QOL, including symptoms of psychological distress, personality attributes, coping and cognitive appraisals, family functioning, healthcare experiences and costs, access to emotional support and socioeconomic factors. Clinical characteristics are captured via self-report and parent-proxy report, as well as the ANZFR. Descriptive analyses and multilevel models will be used to examine QOL across groups and to investigate potential explanatory variables. ETHICS AND DISSEMINATION: Approval has been obtained from all relevant Human Research Ethics Committees (HRECs), including the Sydney Children's Hospitals Network and the Royal Children's Hospital Melbourne HRECs. Study findings will be published in peer-reviewed journals and presented at national and international meetings and seminars.

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings.

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion.

Postprandial oxidative stress in response to dextrose and lipid meals of differing size.

UNLABELLED: We have recently noted that ingestion of dietary lipid (in the form of heavy whipping cream) leads to greater oxidative stress than dietary carbohydrate (in the form of dextrose), when consumed in isocaloric amounts. OBJECTIVE: In the present investigation we attempted to replicate our work and also to determine the oxidative stress response to dextrose and lipid meals of two different kilocalorie (kcal) amounts. DESIGN: Nine young (22 +/- 2 years), healthy men consumed in a random order, cross-over design one of four meals/drinks: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 30 min, 60 min, 120 min, and 180 min post meal. Samples were assayed for glucose, triglycerides (TAG), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Area under the curve (AUC) was calculated for each variable, and a 4 x 5 ANOVA was utilized to further analyze data. RESULTS: A meal x time effect (p = 0.0002) and a time effect was noted for glucose (p < 0.0001; 30 min > Pre, 1 hr, 2 hr, and 3 hr). The dextrose meals primarily contributed to this time effect. No other effects were noted for glucose (p > 0.05). A meal effect was noted for TAG (p = 0.01; 66 g lipid meal > 75 g and 150 g dextrose meals). No other effects were noted for TAG (p > 0.05). An AUC effect was noted for MDA (p = 0.04; 66 g lipid meal > 75 g and 150 g dextrose meals). A meal x time effect (p = 0.02) and a meal effect was noted for MDA (p = 0.004; 66 g lipid meal > 75 g and 150 g dextrose meals). No time effect was noted for MDA (p = 0.72). An AUC effect was noted for H2O2 (p = 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals). A meal x time effect (p = 0.0002), a meal effect (p < 0.0001; 66 g lipid meal > 33 g lipid meal and 75 g and 150 g dextrose meals), and a time effect was noted for H2O2 (p < 0.0001; 2 hr > Pre, 30 min, and 1 hr; 3 hr > Pre). The time effect for H2O2 was primarily influenced by the 66 g lipid meal. CONCLUSIONS: These data indicate that 1) minimal oxidative stress is observed following ingestion of dextrose loads of either 75 g or 150 g, or a lipid load of 33 g and 2) lipid ingestion at 66 g leads to greater oxidative stress than lipid at 33 g or dextrose at either 75 g or 150 g. Hence, in a sample of young and healthy men, only 66 g of lipid (taken in the form of heavy whipping cream) leads to a significant increase in blood oxidative stress, as measured by MDA and H2O2.

Effect of a 21 day Daniel Fast on metabolic and cardiovascular disease risk factors in men and women.

BACKGROUND: Dietary modification via caloric restriction is associated with multiple effects related to improved metabolic and cardiovascular health. However, a mandated reduction in kilocalories is not well-tolerated by many individuals, limiting the long-term application of such a plan. The Daniel Fast is a widely utilized fast based on the Biblical book of Daniel. It involves a 21 day ad libitum food intake period, devoid of animal products and preservatives, and inclusive of fruits, vegetables, whole grains, legumes, nuts, and seeds. The purpose of the present study was to determine the efficacy of the Daniel Fast to improve markers of metabolic and cardiovascular disease risk. METHODS: 43 subjects (13 men; 30 women; 35 ± 1 yrs; range: 20-62 yrs) completed a 21 day period of modified food intake in accordance with detailed guidelines provided by investigators. All subjects purchased and prepared their own food. Following initial screening, subjects were given one week to prepare for the fast, after which time they reported to the lab for their pre-intervention assessment (day 1). After the 21 day fast, subjects reported to the lab for their post-intervention assessment (day 22). For both visits, subjects reported in a 12 hr fasted state, performing no strenuous physical activity during the preceding 24-48 hrs. At each visit, mental and physical health (SF-12 form), resting heart rate and blood pressure, and anthropometric variables were measured. Blood was collected for determination of complete blood count, metabolic panel, lipid panel, insulin, HOMA-IR, and C-reactive protein (CRP). Subjects' self-reported compliance, mood, and satiety in relation to the fast were also recorded. Diet records were maintained by all subjects during the 7 day period immediately prior to the fast (usual intake) and during the final 7 days of the fast. RESULTS: Subjects' compliance to the fast was 98.7 ± 0.2% (mean ± SEM). Using a 10 point scale, subjects' mood and satiety were both 7.9 ± 0.2. The following variables were significantly (p < 0.05) lower following the fast as compared to before the fast: white blood cell count (5.68 ± 0.24 vs. 4.99 ± 0.19 103.µL-1), blood urea nitrogen (13.07 ± 0.58 vs. 10.14 ± 0.59 mg.dL-1), blood urea nitrogen/creatinine (14.74 ± 0.59 vs. 11.67 ± 0.68), protein (6.95 ± 0.07 vs. 6.77 ± 0.06 g.dL-1), total cholesterol (171.07 ± 4.57 vs. 138.69 ± 4.39 mg.dL-1), LDL-C (98.38 ± 3.89 vs. 76.07 ± 3.53 mg.dL-1), HDL-C (55.65 ± 2.50 vs. 47.58 ± 2.19 mg.dL-1), SBP (114.65 ± 2.34 vs. 105.93 ± 2.12 mmHg), and DBP (72.23 ± 1.59 vs. 67.00 ± 1.43 mmHg). Insulin (4.42 ± 0.52 vs. 3.37 ± 0.35 µU.mL-1; p = 0.10), HOMA-IR (0.97 ± 0.13 vs.0.72 ± 0.08; p = 0.10), and CRP (3.15 ± 0.91 vs. 1.60 ± 0.42 mg.L-1; p = 0.13), were lowered to a clinically meaningful, albeit statistically insignificant extent. No significant difference was noted for any anthropometric variable (p > 0.05). As expected, multiple differences in dietary intake were noted (p < 0.05), including a reduction in total kilocalorie intake (2185 ± 94 vs. 1722 ± 85). CONCLUSION: A 21 day period of modified dietary intake in accordance with the Daniel Fast is 1) well-tolerated by men and women and 2) improves several risk factors for metabolic and cardiovascular disease. Larger scale, randomized studies, inclusive of a longer time period and possibly a slight modification in food choice in an attempt to maintain HDL cholesterol, are needed to extend these findings.

Health-Related Quality of Life in Children, Adolescents, and Adults With a Fontan Circulation: A Meta-Analysis.

Background People with a Fontan circulation experience a range of physical, psychosocial and neurodevelopmental challenges alongside, or caused by, their cardiac condition, with significant consequences for health-related quality of life (HRQOL). We meta-analyzed HRQOL outcomes reported by people with a Fontan circulation or their proxies and evaluated predictors of poorer HRQOL. Methods and Results Six electronic databases were searched for peer-reviewed, English-language articles published before March 2019. Standardized mean differences (SMD) were calculated using fixed and random-effects models. Fifty articles reporting on 29 unique studies capturing HRQOL outcomes for 2793 people with a Fontan circulation and 1437 parent-proxies were analyzed. HRQOL was lower in individuals with a Fontan circulation compared with healthy referents or normative samples (SMD, -0.92; 95% CI, -1.36 to -0.48; P<0.001). Lower scores were reported across all HRQOL domains, with the largest differences found for physical (SMD, -0.90; 95% CI, -1.13 to -0.67; P<0.001) and school/work functioning (SMD, -0.71; 95% CI, -0.90 to -0.52; P<0.001). Meta-regression analyses found no significant predictors of self-reported physical functioning, but older age at Fontan operation was associated with poorer emotional functioning (ß=-0.124; P=0.004), and diagnosis of hypoplastic left heart was associated with poorer social functioning (ß=-0.007; P=0.048). Sensitivity analyses showed use of the PedsQL Core Module was associated with lower HRQOL scores compared with the Short-Form Health Survey-36. Conclusions HRQOL outcomes for people with a Fontan circulation are lower than the general population. Optimal care acknowledges the lifelong impact of the Fontan circulation on HRQOL and offers targeted strategies to improve outcomes for this growing population.