To date, Healthy Eating Index 2015 (HEI-2015) scores have not been published in the peer-reviewed literature for nationally representative samples of American children.
The aim of this study was to ...use the HEI-2015 to describe the diet quality of American children overall and within various sociodemographic populations.
We used 3 cycles of NHANES dietary data sets (2009–2010, 2011–2012, and 2013–2014) to calculate HEI-2015 total and component scores by use of the population ratio method for children aged 2–18 y (n = 9000). Diet-quality scores were computed overall and by age (2–5, 6–11, and 12–18 y), gender, race or ethnicity (non-Hispanic black, non-Hispanic white, Mexican American, other Hispanic, and other race), and family poverty-to-income ratio (below or at or above the poverty threshold). HEI-2015 mean total and component scores were computed along with 95% CIs.
The HEI-2015 total mean score for children overall was 54.9 (range: 0–100). As the age group increased, the total scores decreased; the total mean score was significantly higher for children in the youngest age group compared with the 2 older age groups (60.1 compared with 53.9 compared with 52.0, respectively). The total mean score was significantly lower for non-Hispanic black children compared with Mexican American children, other Hispanic children, and children of other races (52.6 compared with 57.0, 56.8, and 57.1, respectively). The total mean score was significantly lower for non-Hispanic white children compared with Mexican-American children (54.2 compared with 57.0). No differences in total mean scores were apparent between boys and girls or between poverty threshold classes. The total mean scores for cross-classified sociodemographic characteristics generally followed the same patterns observed for single characteristics, with notable differences occurring within age and race or ethnicity classes.
The diet quality of American children remains low overall, with continued disparities across some sociodemographic populations, notably age and race or ethnicity. The results of these analyses can help guide the efforts of child nutrition researchers, practitioners, and other stakeholders.
Efforts to model pancreatic cancer in mice have focused on mimicking genetic changes found in the human disease, particularly the activating KRAS mutations that occur in pancreatic tumors and their ...putative precursors, pancreatic intraepithelial neoplasia (PanIN). Although activated mouse Kras mutations induce PanIN lesions similar to those of human, only a small minority of cells that express mutant Kras go on to form PanINs. The basis for this selective response is unknown, and it is similarly unknown what cell types in the mature pancreas actually contribute to PanINs. One clue comes from the fact that PanINs, unlike most cells in the adult pancreas, exhibit active Notch signaling. We hypothesize that Notch, which inhibits differentiation in the embryonic pancreas, contributes to PanIN formation by abrogating the normal differentiation program of tumor-initiating cells. Through conditional expression in the mouse pancreas, we find dramatic synergy between activated Notch and Kras in inducing PanIN formation. Furthermore, we find that Kras activation in mature acinar cells induces PanIN lesions identical to those seen upon ubiquitous Kras activation, and that Notch promotes both initiation and dysplastic progression of these acinar-derived PanINs, albeit short of invasive adenocarcinoma. At the cellular level, Notch/Kras coactivation promotes rapid reprogramming of acinar cells to a duct-like phenotype, providing an explanation for how a characteristically ductal tumor can arise from nonductal acinar cells.
Some amyloid-forming polypeptides are associated with devastating human diseases and others provide important biological functions. For both, oligomeric intermediates appear during amyloid assembly. ...Currently we have few tools for characterizing these conformationally labile intermediates and discerning what governs their benign versus toxic states. Here, we examine intermediates in the assembly of a normal, functional amyloid, the prion-determining region of yeast Sup35 (NM). During assembly, NM formed a variety of oligomers with different sizes and conformation-specific antibody reactivities. Earlier oligomers were less compact and reacted with the conformational antibody A11. More mature oligomers were more compact and reacted with conformational antibody OC. We found we could arrest NM in either of these two distinct oligomeric states with small molecules or crosslinking. The A11-reactive oligomers were more hydrophobic (as measured by Nile Red binding) and were highly toxic to neuronal cells, while OC-reactive oligomers were less hydrophobic and were not toxic. The A11 and OC antibodies were originally raised against oligomers of Aβ, an amyloidogenic peptide implicated in Alzheimer’s disease (AD) that is completely unrelated to NM in sequence. Thus, this natural yeast prion samples two conformational states similar to those sampled by Aβ, and when assembly stalls at one of these two states, but not the other, it becomes extremely toxic. Our results have implications for selective pressures operating on the evolution of amyloid folds across a billion years of evolution. Understanding the features that govern such conformational transitions will shed light on human disease and evolution alike.
Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants ...with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.
In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 normal to 5 most impaired), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.
Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval CI, 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).
The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).
Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity ...modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.
Children's food preference and intake patterns are affected by parental child feeding practices. The objective was to determine patterns of food parenting practices regarding junk food and sugary ...drinks (JS) and investigate their associations with demographic characteristics and dietary intake in a large cohort of parents and their children (12-17 years). Dyadic survey data from the cross-sectional, internet-based Family Life, Activity, Sun, Health, and Eating Study, conducted in 2014, were analyzed using latent class analysis to identify patterns of use for six JS parenting practices - negative emotions, restriction, monitoring, availability, modeling, and child involvement - based on parent and child report. Model covariates included self-reported parent and child sex, age (child only), body mass index category (based on height and weight), added sugars intake, and legitimacy of parental authority. Based on 1657 parent-child dyads, five parenting practice patterns were identified representing different levels of practice use - Complete Influencers (28%; reference class), Indifferent Influencers (21%), Negative Influencers (20%), Minimal Influencers (18%), and Disagreeing Influencers (13%). Compared to older child dyads, younger child dyads were less likely to belong to Indifferent and Minimal Influencers (79 and 63% lower odds, respectively). Greater parent added sugars intake increased the odds of belonging to Indifferent and Negative Influencers (4 and 5% higher for every teaspoon increase, respectively) while greater child added sugars intake decreased the odds of belonging to Minimal Influencers (6% lower for every teaspoon increase). Compared to dyads with high scores, dyads with low child scores for legitimacy of parental authority regarding JS were 18 times as likely to belong to Disagreeing Influencers. The study findings suggest that parents utilize distinct patterns of feeding practices regarding JS ranging from use of many practices, use of some practices, to low use of any practice, with differential associations with parent and child intakes of added sugars. Counseling or intervening with parents to use a mix of structure practices, such as availability and modeling, to positively influence their child's and possibly their own intake of sugary snacks and drinks may prove more efficacious than use of coercive control practices, such as negative emotions.
Soil microorganisms mediate many processes such as nitrification, denitrification, and methanogenesis that regulate ecosystem functioning and also feed back to influence atmospheric chemistry. These ...processes are of particular interest in freshwater wetland ecosystems where nutrient cycling is highly responsive to fluctuating hydrology and nutrients and soil gas releases may be sensitive to climate warming. In this review we briefly summarize research from process and taxonomic approaches to the study of wetland biogeochemistry and microbial ecology, and highlight areas where further research is needed to increase our mechanistic understanding of wetland system functioning. Research in wetland biogeochemistry has most often been focused on processes (e.g., methanogenesis), and less often on microbial communities or on populations of specific microorganisms of interest. Research on process has focused on controls over, and rates of, denitrification, methanogenesis, and methanotrophy. There has been some work on sulfate and iron transformations and wetland enzyme activities. Work to date indicates an important process level role for hydrology and soil nutrient status. The impact of plant species composition on processes is potentially critical, but is as yet poorly understood. Research on microbial communities in wetland soils has primarily focused on bacteria responsible for methanogenesis, denitrification, and sulfate reduction. There has been less work on taxonomic groups such as those responsible for nitrogen fixation, or aerobic processes such as nitrification. Work on general community composition and on wetland mycorrhizal fungi is particularly sparse. The general goal of microbial research has been to understand how microbial groups respond to the environment. There has been relatively little work done on the interactions among environmental controls over process rates, environmental constraints on microbial activities and community composition, and changes in processes at the ecosystem level. Finding ways to link process-based and biochemical or gene-based assays is becoming increasingly important as we seek a mechanistic understanding of the response of wetland ecosystems to current and future anthropogenic perturbations. We discuss the potential of new approaches, and highlight areas for further research.
Formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as Alzheimer's disease or prion diseases. Moreover, increasing evidence ...indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease‐associated proteins may share common structural features. Previous studies revealed that toxic effects of the scrapie prion protein (PrPSc), a β‐sheet‐rich isoform of the cellular PrP (PrPC), are dependent on neuronal expression of PrPC. In this study, we demonstrate that PrPC has a more general effect in mediating neurotoxic signalling by sensitizing cells to toxic effects of various β‐sheet‐rich (β) conformers of completely different origins, formed by (i) heterologous PrP, (ii) amyloid β‐peptide, (iii) yeast prion proteins or (iv) designed β‐peptides. Toxic signalling via PrPC requires the intrinsically disordered N‐terminal domain (N‐PrP) and the GPI anchor of PrP. We found that the N‐terminal domain is important for mediating the interaction of PrPC with β‐conformers. Interestingly, a secreted version of N‐PrP associated with β‐conformers and antagonized their toxic signalling via PrPC. Moreover, PrPC‐mediated toxic signalling could be blocked by an NMDA receptor antagonist or an oligomer‐specific antibody. Our study indicates that PrPC can mediate toxic signalling of various β‐sheet‐rich conformers independent of infectious prion propagation, suggesting a pathophysiological role of the prion protein beyond of prion diseases.
PrPC can interact with and mediate toxic signalling of misfolded β‐sheet‐rich oligomers of different origin.
Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially ...leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions.
Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators.
Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges.
Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.
The Lower Mississippi Delta is characterized by several factors associated with poor diet quality. Our objective was to measure local nutrition environments of pregnant women and their infants who ...participated in a nutrition and physical activity intervention to assess environmental exposures potentially influencing their dietary habits.
We measured the nutrition environments of 5 towns in which participants resided by using the Nutrition Environment Measures Survey for grocery stores, convenience stores, full-service restaurants, and fast food restaurants. We used general linear models to test for differences in ratio scores, calculated by dividing each food outlet score by the maximum score possible, among food outlet classes and subclasses.
Mean total ratio scores (expressed as percentages) for the Nutrition Environment Measures Survey among 4 classes of food outlets were significantly different from one another except for convenience stores and full-service restaurants. On average, grocery stores (n = 11) had 54% of maximum points possible, followed by full-service restaurants (21%; n = 50), convenience stores (16%; n = 86), and fast food restaurants (8%; n = 119). We found no significant differences in mean total ratio scores among convenience store subclasses. For fast food restaurant subclasses, stand-alone restaurants (n = 81) had 19% of maximum points possible, significantly higher than grocery store delicatessens (6%; n = 8), corner stores that sold fast food (3%; n = 5), and gas stations that sold fast food (4%; n = 25).
These 5 Lower Mississippi Delta towns scored low on nutrition environment measures associated with healthful eating. Behavioral interventions designed to bring about positive changes in dietary habits of rural residents are needed; however, effects may be minimal if environmental factors supportive of healthful eating are not available.