Consumption of ultra-processed food products and its effects on children's lipid profiles: a longitudinal study.

BACKGROUND AND AIMS: Cardiovascular disease development is related to known risk factors (such as diet and blood lipids) that begin in childhood. Among dietary factors, the consumption of ultra-processing products has received attention. This study investigated whether children's consumption of processed and ultra-processing products at preschool age predicted an increase in lipid concentrations from preschool to school age. METHODS AND RESULTS: Cohort study conducted with 345 children of low socioeconomic status from São Leopoldo, Brazil, aged 3-4 years and 7-8 years. Blood tests were done to measure lipid profile. Dietary data were collected through 24-h recalls and the children's processed and ultra-processing product intake was assessed. Linear regression analysis was used to assess the relationship between processed and ultra-processed product intake at 3-4 years on changes in lipid concentrations from preschool to school age. The percentage of daily energy provided by processed and ultra-processed products was 42.6 ± 8.5 at preschool age and 49.2 ± 9.5 at school age, on average. In terms of energy intake, the main products consumed were breads, savoury snacks, cookies, candy and other sweets in both age groups. Ultra-processed product consumption at preschool age was a predictor of a higher increase in total cholesterol (ß = 0.430; P = 0.046) and LDL cholesterol (ß = 0.369; P = 0.047) from preschool to school age. CONCLUSION: Our data suggest that early ultra-processed product consumption played a role in altering lipoprotein profiles in children from a low-income community in Brazil. These results are important to understanding the role of food processing and the early dietary determinants of cardiovascular disease.

Attosecond-pump attosecond-probe x-ray spectroscopy of liquid water.

Attosecond-pump/attosecond-probe experiments have long been sought as the most straightforward method for observing electron dynamics in real time. Although there has been much success with overlapped near-infrared femtosecond and extreme ultraviolet attosecond pulses combined with theory, true attosecond-pump/attosecond-probe experiments have been limited. We used a synchronized attosecond x-ray pulse pair from an x-ray free-electron laser to study the electronic response to valence ionization in liquid water through all x-ray attosecond transient absorption spectroscopy (AX-ATAS). Our analysis showed that the AX-ATAS response is confined to the subfemtosecond timescale, eliminating any hydrogen atom motion and demonstrating experimentally that the 1b1 splitting in the x-ray emission spectrum is related to dynamics and is not evidence of two structural motifs in ambient liquid water.

Metal mutagens and carcinogens affect RNA synthesis rates in a distinct manner.

Five metal salts (lead, cadmium, cobalt, copper, and manganese),which are mutagenic or carcinogenic, decreasing the fidelity of DNA synthesis in vitro, stimulated chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis. In contrast, other metal salts (zinc, magnesium, lithium, sodium,and potassium) not in this category inhibited chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis.

Early-onset sepsis with Staphylococcus auricularis in an extremely low-birth weight infant - an uncommon pathogen.

Coagulase-negative staphylococci (CoNS) are often dismissed as a contaminant of blood cultures and are rarely considered as an etiology of perinatally acquired infections. We describe a case of early-onset sepsis with Staphylococcus auricularis in an extremely low-birth weight infant.

Effects of Phos-Chek G75-F and Silv-Ex on red-winged blackbird (Agelaius phoeniceus) embryos.

Effects of field application levels of wildfire control chemicals, Phos-Chek G75-F (PC) and Silv-Ex (SE), were examined on red-winged blackbird (Agelaius phoeniceus) embryos. Embryos were more sensitive to PC and SE when eggs were immersed for 10s at an early developmental stage (days 3-5 of incubation) than at a later stage (days 6-9 of incubation). The LC(50) (concentration causing 50% mortality) for early stage embryos exposed to PC was 213.3g/L (slope=1.6; 95% confidence interval [CI]=129.1-326.1). The no observed effect concentration (NOEC) was below 135g PC/L, which caused a significant increase in embryonic mortality and represents the lowest field coverage level of 1gal/100feet(2). The LC(50) for early stage embryos exposed to SE was 19.8g/L (slope=1.5; 95% CI=11.7-52.2). Significant mortality was observed at 10g SE/L and marginal at 7.5g SE/L with an apparent NOEC around 5g SE/L. Neither chemical resulted in apparent developmental malformations.

Misreport of energy intake assessed with food records and 24-h recalls compared with total energy expenditure estimated with DLW.

BACKGROUND/OBJECTIVES: The accuracy of dietary assessment methods has rarely been validated using precise techniques. The objective of this work was to evaluate the validity of energy intake (EI) estimated with food records (FRs) and 24-h recalls (24hRs) against total energy expenditure (EE) estimated by the doubly labeled water (DLW) method. In addition, the magnitude of EI under-reporting was assessed along with its associated characteristics. SUBJECTS/METHODS: The studied group included 83 adults between 20 and 60 years of age who were recruited from a population-based sample. Within-person variation-adjusted means of EI estimated from two FRs and three 24hRs were compared with EE estimated using the DLW method multiple-point protocol. The Wilcoxon signed-rank test was used to assess the differences between EI and EE, whereas Bland-Altman and survival-agreement plots assessed the agreement between the estimates. RESULTS: The mean EE (2540 kcal) was greater than the mean reported EI for both dietary assessment methods (FR: 1774 kcal; 24hR: 1658 kcal, P<0.01). The frequency of under-reporting was lower (20%) for EI estimated with the 24hR than that estimated with the FR (32%). Men presented lower magnitude of under-reported EI than women did. For women, differences between EI and EE were lower with FR than with 24hR. Overall, FR and 24hR showed similar performance. The mean under-reported EI was ~30% for both methods. CONCLUSIONS: Irregular meal habits, smoking and low education were associated with the under-report of EI. Both FR and 24hR are subjected to bias suggesting the need of refining the procedures applied in dietary assessment methods.

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Growth retardation at early life and metabolic adaptation among North Korean children.

The high prevalence of obesity is a major public health issue and contributes to the 'double burden' of disease in developing countries. Early exposure to poor nutrition may cause metabolic adaptations that, when accompanied by exposure to 'affluent' nutrition, may increase the risk for obesity and other metabolic disorders. The aim of this study was to determine differences in energy metabolism and nutritional status between normal-height and growth-retarded North Korean children living in South Korea. A total of 29 children were recruited and underwent measurements of resting energy expenditure (REE), respiratory quotient (RQ), anthropometrics and dietary intake. There was no difference in REE or any assessment of obesity between the growth-retarded and normal-height children. Children who were classified as growth retarded (HAZ<-1.0) or stunted (HAZ<-2.0) had a significantly higher RQ (ß=0.036 or 0.060, respectively, P=0.018 or 0.016), independent of sex, age, fat-free mass, fat mass and food quotient, compared with children with normal height. The results from this study, the first from an Asian population, add to the growing body of literature suggesting that undernutrition early in life results in adaptations in energy metabolism that favor fat deposition, increasing the risk of stunted children becoming overweight or obese later in life. Continued research on this topic is warranted, given the continued rise in the prevalence of the double burden in transitional countries.

Effect of antacids on absorption of clorazepate.

The effect of a magnesia and alumina antacid suspension on the absorption of clorazepate dipotassium was studied in 15 normal healthy adult subjects who ingested a 15-mg dose of clorazepate alone or with single or multiple doses of antacid. The results of this three-period randomized complete crossover study showed a trend of initially slower absorption and lower peak nordiazepam plasma levels when administered with the antacid suspension. However, there were no significant differences among treatments in the extent of absorption as measured by the area under the plasma level-time curves. Clorazepate plasma levels were of relatively short duration and similar for all treatments. The urinary excretion pattern was likewise comparable with conjugated oxazepam, the major species measured. Plasma elimination half-lives of nordiazepam and clorazepate were not affected by the antacid treatments.

Why are nutritionally stunted children at increased risk of obesity? Studies of metabolic rate and fat oxidation in shantytown children from São Paulo, Brazil.

BACKGROUND: Previous research suggested that nutritionally stunted children may have increased risk of obesity, but little is known about potential underlying mechanisms. OBJECTIVE: We sought to test the hypothesis that stunted children have a low metabolic rate and impaired fat oxidation relative to nonstunted children. DESIGN: The subjects were 58 prepubertal boys and girls aged 8-11 y from the shantytowns of São Paulo, Brazil. Twenty-eight were stunted (height-for-age z score <-1.5) and 30 had similar weight-for-height but normal height (height-for-age z score >-1.5). Parents of children in the 2 groups had equivalent height and body mass index values. Fasting and postprandial energy expenditure, respiratory quotient (RQ), and substrate oxidation were measured with indirect calorimetry in a 3-d resident study in which all food was provided and body composition was measured with dual-energy X-ray absorptiometry. RESULTS: Stunted children had normal resting energy expenditure relative to body composition compared with control children (4559 +/- 90 and 4755 +/- 86 kJ/d, respectively; P: = 0.14) and had normal postprandial thermogenesis (2.4 +/- 0.3% and 2.0 +/- 0.3% of meal load, respectively; P: = 0.42). However, fasting RQ was significantly higher in the stunted group (0.92 +/- 0.009 compared with 0.89 +/- 0.007; P: = 0.04) and consequently, fasting fat oxidation was significantly lower (25 +/- 2% compared with 34 +/- 2% of energy expenditure; P: < 0.01). CONCLUSIONS: Childhood nutritional stunting is associated with impaired fat oxidation, a factor that predicted obesity in other at-risk populations. This finding may help explain recent increases in body fatness and the prevalence of obesity among stunted adults and adolescents in developing countries.

Energy expenditure of stunted and nonstunted boys and girls living in the shantytowns of São Paulo, Brazil.

BACKGROUND: Stunting increases the risk of obesity in developing countries, particularly in girls and women, but the underlying reason is not known. OBJECTIVE: Our objective was to test the hypothesis that stunted children have lower energy expenditure than do nonstunted children, a factor that has predicted an increased risk of obesity in other high-risk populations. DESIGN: A cross-sectional study was conducted in shantytown children from São Paulo, Brazil. Twenty-eight stunted children aged 8-11 y were compared with 30 nonstunted children with similar weight-for-height. Free-living total energy expenditure (TEE) was measured over 7 d by using the doubly labeled water method. In addition, resting energy expenditure (REE) was measured by indirect calorimetry and body composition was measured by dual-energy X-ray absorptiometry. RESULTS: There were no significant associations between stunting and any measured energy expenditure parameter, including REE adjusted for weight (f1.gif" BORDER="0"> +/- SEM: 4575 +/- 95 compared with 4742 +/- 91 kJ/d, in stunted and nonstunted children, respectively) and TEE adjusted for weight (8424 +/- 239 compared with 8009 +/- 221 kJ/d, in stunted and nonstunted children, respectively). In multiple regression models that included fat-free mass and fat mass, girls had significantly lower TEE than did boys (P: < 0.05) but not significantly lower REE (P: = 0.17). CONCLUSIONS: There was no association between stunting and energy expenditure after differences between groups in body size and composition were accounted for. However, the girls had lower TEE than did boys, which may help to explain the particularly high risk of obesity in stunted adolescent girls and women in urban areas of developing countries.

New inhibitors of renin that contain novel phosphostatine Leu-Val replacements.

A novel series of renin inhibitors based on the Phe8-His9-Leu10-Val11 substructure of renin's natural substrate, angiotensinogen, is reported. These inhibitors retain the Phe8-His9 portion of the native substructure and employ novel phosphostatine Leu10-Val11 replacements (LVRs). The phosphostatine LVRs were prepared by condensing a dialkyl phosphonate ester stabilized anion with either N-t-Boc-amino aldehydes or N-tritylamino aldehydes (derived from the corresponding amino acid). Structure-activity relationships at the Leu10 side chain revealed that the LVR derived from L-cyclohexylalanine provided a 130-fold boost in potency over the LVR derived from L-leucine. The dialkyl ester moiety was varied and a loss in potency was incurred when the alkyl ester was chain extended or alpha-branched; dimethyl esters provided optimum potency. The phosphonate moiety was replaced by a half-acid half-ester phosphonate and dimethylphosphinate; both replacements lead to a loss in potency. The more potent inhibitors (IC50 = 20-50 nM) were found to be selective inhibitors for renin over porcine pepsin and bovine cathepsin D (little or no inhibition was observed at 10(-5) M).

Stabilization of the N-terminal residues of luteinizing hormone-releasing hormone agonists and the effect on pharmacokinetics.

To stabilize leuprolide (1) against chymotrypsin and intestinal degradation several agonists of LHRH (2-12), modified at position 1, 2, or 3 and/or containing N-alpha-methyl at positions 1, 2, or 4, were synthesized by SPPS. These agonists were tested in vitro for (a) rat pituitary LHRH receptor binding, (b) LH release from rat pituitary cells, (c) stability against chymotrypsin, and (d) stability against rat intestinal degradation. The clearances of the compounds in the rat were determined using a RIA. Complete stabilization against chymotrypsin (t1/2) and lumenal degradation (T1/2) was achieved with substitution of NMe-Ser4 in leuprolide; however, with an increase in clearance. Substitution with 1-Nal3 increased both t1/2 and T1/2, while substitution with NAc-Sar1 increased only T1/2. [NAcSar1,NMeSer4,D-Trp6,Pro9NHEt]LHRH (12), the doubly stabilized analogue, was tested in the rat by both iv and id administrations, and its bioavailabilities were measured. No significant improvement in id absorption over leuprolide was observed.

Azido glycols: potent, low molecular weight renin inhibitors containing an unusual post scissile site residue.

Azidomethyl-substituted 1,2- and 1,3-diols were prepared from Boc-cyclohexylalanal and evaluated as transition state analogue renin inhibitors, leading to the development of a small (MW less than 600), nanomolar inhibitor. Remarkable aqueous solubility enhancement followed the incorporation of an N-terminal urea functionality. Evaluation of selected compounds both in vivo and in vitro demonstrated that while transport across the intestine occurred upon id administration, extensive liver extraction resulted in low systemic levels.

Azole endothelin antagonists. 3. Using delta log P as a tool to improve absorption.

The oral absorption profile of a family of azole-based ET(A)-selective antagonists has been improved through a rational series of structural modifications which were suggested by analysis of the physicochemical parameter delta log P. Comparison of urea 2 with a series of well-absorbed compounds using delta log P analysis suggested that 2 has an excess capacity for forming hydrogen bonds with solvent. A series of urea modifications were explored as a means of reducing H-bonding capacity while maintaining affinity for the ET(A)-receptor. The correlation between delta log P values and absorption in an intraduodenal (id) bioavailability model was good; this strategy uncovered replacements for each of the urea NH groups which simultaneously improve both potency and drug absorption. A combination of these optimized modifications produces carbamate 16h, a highly-selective ET(A) antagonist with a potency/bioavailability profile consistent with an oral route of administration.

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Effects of polychlorinated dibenzo-p-dioxins and dibenzofurans on nesting wood ducks (Aix sponsa) at Bayou Meto, Arkansas.

Wood ducks (Aix sponsa) nesting along Bayou Meto downstream from a hazardous waste site in central Arkansas were contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Residues in eggs, based on 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQ), ranged up to 611 parts per trillion (ppt), and egg arithmetic means were 90-fold higher at the site nearest the point source compared with a reference site. We monitored productivity of wood ducks in artificial nest boxes at three sites on the bayou and at a reference site on a separate drainage during 1988-1990. Productivity was suppressed (p < 0.05) at the bayou sites compared with the reference site, and egg TCDD-EQs were inversely correlated (p < 0.001) with productivity in corresponding nests. The threshold range of toxicity, where reduced productivity was evident in wood ducks (based on TCDD-EQs), was > 20 to 50 ppt. Oxidative stress and teratogenic effects occurred in ducklings at the more contaminated nesting sites nearest the point source. These findings suggest that wood ducks may be more sensitive to PCDD and PCDF contamination than some other aquatic birds and could serve as an indicator species for monitoring biological impacts from these contaminants.

Bioavailability of valproic acid under fasting/nonfasting regimens.

Valporic acid absorption was faster from a syrup than from a capsule form. Peak serum levels occurred with an hour with the syrup formulation. The drug was absorbed more rapidly when administered fasting and immediately before meal compared with immediately after meal. The extent of absorption from each formulation and for each meal regimen was similar. Pharmacokinetic evaluation of the data indicate a serum half-life of 12 hours.

Steady-state bioavailability of two clorazepate dipotassium dosage forms.

A specially designed tablet dosage form of the benzodiazepine clorazepate dipotassium (Tranxene) was developed for once-a-day administration. The drug was administered at a dose of 22.5 mg as (1) the tablet, (2) three 7.5 mg capsules, or (3) one 7.5-mg capsule given every 6 hours. Peak serum levels from the tablet were intermediate between those of the single- and divided-dose capsule regimens. The desired decrease in magnitude of peak levels was obtained without affecting the extent of absorption. Pharmacokinetic analysis of the data according to a two-compartment open model with first-order absorption indicated that the serum half-life (t0.5beta) of nordiazepam, the major biotransformation product present in serum, was about 48 hours and served as a basis for the design of a multiple-dose steady-state study. Multiple-dose administration of the tablet and divided-capsule regimen to two groups of subjects for ten days indicated each dosage form yielded similar minimum steady-state serum levels of about 0.6 micrograms/ml which plateaued following seven days of drug administration. The dosage forms were crossed over between the groups on day 11 and administered for an additional four days. The minimum serum levels obtained with the tablet and capsule were not statistically different. Additionally, the peak serum level and area under the curve (pi=24 hours) at steady state were equivalent between the dosage forms. Good agreement was obtained between model-predicted and observed serum levels during multiple-dose administration for both the tablet and capsule regimens. The serum half-life of nordiazepam following 14 days of clorazepate dipotassium administration was similar to that found after a single dose. These results indicate that a single daily dose of drug as the tablet produced serum levels equivalent to a divided-capsule regimen.

Protective effect of MgSO4 infusion on nmda receptor binding characteristics during cerebral cortical hypoxia in the newborn piglet.

This study tests the hypothesis that magnesium, a selective non-competitive antagonist of the NMDA receptor, will attenuate hypoxia-induced alteration in NMDA receptors and preserve MK-801 binding characteristics during cerebral hypoxia in vivo. Anesthetized, ventilated and instrumented newborn piglets were divided into three groups: normoxic controls were compared to untreated hypoxic and Mg(2+)-treated hypoxic piglets. Cerebral hypoxia was induced by lowering the FiO2 to 5-7% and confirmed biochemically by a decrease in the levels of phosphocreatine (82% lower than control). The Mg(2+)-treated group received MgSO4 600 mg/kg over 30 min followed by 300 mg/kg administered during 60 min of hypoxia. Plasma Mg2+ concentrations increased from 1.6 +/- 0.1 mg/dl to 17.7 +/- 3.3 mg/dl. 3H-MK-801 binding was used as an index of NMDA receptor modification. The Bmax in control, hypoxic and Mg(2+)-treated hypoxic piglets was 1.09 +/- 0.17, 0.70 +/- 0.25 and 0.96 +/- 0.14 pmoles/mg protein, respectively. The Kd for the same groups were 10.02 +/- 2.04, 4.88 +/- 1.43 and 8.71 +/- 2.23 nM, respectively. The Bmax and Kd in the hypoxic group were significantly lower compared to the control and Mg(2+)-treated hypoxic groups, indicating a preservation of NMDA receptor number and affinity for MK-801 during hypoxia with Mg2+. The activity of Na+, K+ ATPase, a marker of neuronal membrane function, was lower in the hypoxic group compared to the control and Mg(2+)-treated hypoxic groups. These findings show that MgSO4 prevents the hypoxia-induced modification of the NMDA receptor and attenuates neuronal membrane dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)