Objectives Evaluate links between the volume of milk consumed and weight and height status in children age 4 and 5 years. Design We analyzed data from 8950 children followed as part of the Early Childhood Longitudinal Survey–Birth cohort, a nationally-representative cohort of children. We used linear and logistic regression to assess associations of daily servings of milk intake at age 4 years with z-scores of BMI, height and weight-for-height at 4 and 5 years, adjusted for sex, race/ethnicity, socioeconomic status and type of milk consumed. Results Among children who drank milk at age 4 years, higher milk consumption was associated with higher z-scores of BMI, height and weight-for-height at 4 years (all p<0.05). This corresponded to differences between children drinking <1 and ≥4 milk servings daily of approximately 1 cm in height and 0.15 kg in weight. By age 5 years only the association with height remained significant (p<0.001). At 4 years, children drinking ≥3 servings of milk daily were more likely to be overweight/obese (BMI≥85th percentile) than those drinking 0.5–2 servings of milk daily (adjusted odds ratio 1.16 [95% confidence interval 1.02–1.32] p=0.02). Conclusions In a cohort of children at age 4 years, the volume of milk consumed was associated with higher weight status and taller stature, while at 5 years, higher milk consumption continued to be associated with taller stature. Given higher odds of overweight/obesity with milk consumption ≥3 servings daily, this study supports current American Academy of Pediatrics recommendations that pre-school children consume 2 milk servings daily.
Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC50 values of 2.4 μM, 0.26 μM and 5.8 μM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors.
Objective To evaluate children with Crohn’s disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-TNF-α therapy. Study design An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-α therapy, and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2–5) with Crohn’s disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation and DXA whole body fat mass Z-scores over the study interval. Results Sex hormone Z-scores increased significantly over the 10 week induction interval: testosterone Z-scores in males increased from a median of −0.36 to 0.40 (p<0.05) and estradiol Z-scores in females increased from −0.35 to −0.02 (p<0.01). In mixed model regression, the pediatric Crohn’s disease activity index score, cytokine levels and measures of inflammation were significantly and negatively associated with sex hormone Z-scores, and with luteinizing hormone and follicle stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with BMI or fat mass Z-scores. Conclusions Crohn’s disease is associated with delayed maturation, and initiation of anti-TNF-α therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in associated with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation.
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