Delaying mealtimes reduces fat oxidation: A randomized, crossover, controlled feeding study.

OBJECTIVE: This study investigated the effects of circadian misalignment (CM), induced by delaying mealtimes, independent of sleep timing and duration and eating window duration, on energy expenditure (EE), respiratory quotient (RQ), and substrate oxidation. METHODS: Healthy adults, aged 20 to 49 years, participated in this randomized crossover study under controlled feeding conditions. Eating window duration was identical in both conditions (circadian alignment [CA]: 9:00 am-7:00 pm; CM: 1:00 pm-11:00 pm), and bedtimes were constant (11:30 pm-8:00 am). EE, RQ, and substrate oxidation were obtained over 23 hours in a metabolic chamber on days 3 and 4 and days 14 and 15 in each condition. Twenty-four-hour and post-meal outcomes were analyzed using a linear mixed-effects model including condition, day, and day-by-condition interaction as main predictors and sex as a covariate. RESULTS: Three men and four women (age 37.4 ± 8.8 years, BMI 30.4 ± 3.3 kg/m2 ) completed the study. Twenty-four-hour EE did not differ between conditions. Post-meal RQ for dinner and snack was higher in CM versus CA (both p < 0.001) with correspondingly higher glucose oxidation (both p < 0.01) and lower fat oxidation (dinner only p = 0.0001). CONCLUSIONS: CM, induced by delaying mealtimes by 4 hours relative to CA, independently shifts nutrient metabolism toward greater carbohydrate and lower fat oxidation.

Homelessness in the United States: Implications for Critically Ill Children.

Homelessness is a growing crisis in the United States (U.S.). Across the country, children represent a large proportion of the homeless population. When these children experience critical illness, it poses significant and specific burdens to the child and family, compounded by the social stressors inherent in being housing insecure. Yet research on homelessness in critically ill children remains limited. Here, we provide an overview of the current U.S. homeless population, discuss what is currently known about homelessness and critical illness to inform future research, and close with a proposed homelessness screening and intervention model for use in the pediatric intensive care unit that can further be applied to all pediatric inpatient settings.

Anthropometric models to estimate fat mass at 3 days, 15 and 54 weeks.

BACKGROUND: Currently available infant body composition measurement methods are impractical for routine clinical use. The study developed anthropometric equations (AEs) to estimate fat mass (FM, kg) during the first year using air displacement plethysmography (PEA POD® Infant Body Composition System) and Infant quantitative magnetic resonance (Infant-QMR) as criterion methods. METHODS: Multi-ethnic full-term infants (n = 191) were measured at 3 days, 15 and 54 weeks. Sex, race/ethnicity, gestational age, age (days), weight-kg (W), length-cm (L), head circumferences-cm (HC), skinfold thicknesses mm [triceps (TRI), thigh (THI), subscapular (SCP), and iliac (IL)], and FM by PEA POD® and Infant-QMR were collected. Stepwise linear regression determined the model that best predicted FM. RESULTS: Weight, length, head circumference, and skinfolds of triceps, thigh, and subscapular, but not iliac, significantly predicted FM throughout infancy in both the Infant-QMR and PEA POD models. Sex had an interaction effect at 3 days and 15 weeks for both the models. The coefficient of determination [R2 ] and root mean square error were 0.87 (66 g) at 3 days, 0.92 (153 g) at 15 weeks, and 0.82 (278 g) at 54 weeks for the Infant-QMR models; 0.77 (80 g) at 3 days and 0.82 (195 g) at 15 weeks for the PEA POD models respectively. CONCLUSIONS: Both PEA POD and Infant-QMR derived models predict FM using skinfolds, weight, head circumference, and length with acceptable R2 and residual patterns.

No sustained effects of an intervention to prevent excessive GWG on offspring fat and lean mass at 54 weeks: Yet a greater head circumference persists.

BACKGROUND: LIFT (Lifestyle Intervention for Two) trial found that intervening in women with overweight and obesity through promoting healthy diet and physical activity to control gestational weight gain (GWG) resulted in neonates with greater weight, lean mass and head circumference and similar fat mass at birth. Whether these neonate outcomes are sustained at 1-year was the focus of this investigation. METHODS: Measures included body composition by PEA POD air displacement plethysmography (ADP) and Echo Infant quantitative magnetic resonance (QMR) and head circumference at birth (n = 169), 14 (n = 136) and 54 weeks (n = 137). Differences in fat and lean mass between lifestyle intervention (LI) and Usual care (UC) groups were examined using ANCOVA adjusting for maternal age and BMI, GWG, offspring sex and age. RESULTS: Compared to UC, LI infants had similar weight (112 ± 131 g; P = .40), fat mass (14 ± 80 g; P = .86), lean mass (100 ± 63 g; P = .12) at 14 weeks and similar weight (168 ± 183 g; P = .36), fat mass (148 ± 124 g; P = .24), lean mass (117 ± 92 g; P = .21) at 54 weeks. Head circumference was greater in LI at 54 weeks (0.46 ± 2.1 cm P = .03). CONCLUSIONS: Greater lean mass observed at birth in LI offspring was not sustained at 14 and 54 weeks, whereas the greater head circumference in LI offspring persisted at 54 weeks.

A secondary analysis of maternal ultra-processed food intake in women with overweight or obesity and associations with gestational weight gain and neonatal body composition outcomes.

BACKGROUND: This study is an observational secondary analysis of the Lifestyle Intervention for Two (LIFT) randomised controlled trial data. There is a paucity of data related to mechanisms of health effects and dietary intake of ultra-processed foods (UPF). Earlier studies demonstrate associations between greater UPF intake and weight gain. The purpose of the study was to describe associations among maternal UPF intake with gestational weight gain (GWG) and neonatal body composition. MATERIAL AND METHODS: Women with overweight or obesity (n=156) and offspring (n=126) with complete energy intake, anthropometrics and body composition measures were selected. Maternal weights and diet recalls (Automated Self-Administered 24) were measured at weeks 14 and 35 gestational age (GA). Body composition was assessed by infant quantitative magnetic resonance (infant-QMR) and air displacement plethysmography (ADP) at birth. Dependent variables were GWG and neonatal fat mass, fat-free mass, and lean mass at birth; covariates were dietary, socioeconomic and biological. Stepwise linear regressions were used to test associations. RESULTS: Highest quartile of percentage of energy intake from UPF (PEI-UPF) was not significantly correlated with maternal GWG (p=0.215), infant QMR fat (p=0.816) and lean mass (p=0.423) or ADP fat (p=0.482) or fat-free mass (p=0.835). CONCLUSIONS: While no significant associations with UPF were observed in this smaller size cohort, further investigations would be justified in larger cohorts on the relationships of maternal UPF intake and GWG and offspring outcomes. Clinical Trial NCT01616147.

A New Whole Room Indirect Calorimeter for Measurement of the Energetics of Exercise.

The purpose of this study was to compare the accuracy of exercise energy expenditure (EXEE) measurements from a metabolic cart (HG_MC) to that obtained with a new exercise whole room indirect calorimeter (EX_WRIC). First, the HG_MC and the EX_WRIC were subjected to 10, 30-min ethanol (99.8% purity) and propane (99.5% purity) combustion validations, respectively, for EE, ventilation rates (liters) of oxygen (VO2), carbon dioxide (VCO2), and the respiratory quotient (RQ; VCO2/VO2). Then, 15 healthy adults (13 men and 2 women) cycled at 65% age predicted heart rate max for random determination of their EXEE, VO2, VCO2 and RQ after a 12-hr fast with both the HG-MC and EX_WRIC. Comparing stoichiometry to combustion, the HG_MC underestimated EE (P<0.05), VO2 (P<0.05), VCO2 (P<0.05), and RQ (P<0.05) while no differences were found for the EX_WRIC. The EXEE and VO2 were lower (P<0.05) while RQ was greater (P<0.05) when measured with the HG_MC versus the EX_WRIC. The EX_WRIC was more accurate than the HG_MC without the related tethered connections.

Evaluation of a new whole room indirect calorimeter specific for measurement of resting metabolic rate.

BACKGROUND: The most common methods for obtaining human resting metabolic rate (RMR) use either a ventilated hood connected to a metabolic cart (VH_MC) or calculation by many prediction equations utilizing the person's height and weight. These methods may be inherently inaccurate. The objective of this study is to compare the accuracy for the measurement of RMR by three methods: a new whole room indirect calorimeter specific for this purpose (RMR_WRIC), VH_MC and calculation by the Mifflin equation (ME). First, the VH_MC (Vmax Encore 2900, Carefusion Inc, San Diego, CA) and RMR_WRIC (Promethion GA-6/FG-1, Sable Systems Intl, Las Vegas, NV) were subjected to 10, one-hour ethanol (99.8 % purity) and propane (99.5 % purity) combustion tests, respectively, for simulated metabolic measurements. Thereafter, 40 healthy adults (22 M/18 F, 78.0 ± 24.5 kg, BMI = 25.6 ± 4.8, age 36.6 ± 13.4 years) had one-hour RMR (kcal), ventilation (liters) rates of oxygen (VO2), carbon dioxide (VCO2) and RQ (VCO2/VO2) measured after a 12-h fast with both the VH_ MC and the RMR_WRIC in a randomized fashion. The resting state was documented by heart rate. The RMR was also calculated using the ME, which was compared to both the RMR_WRIC and the VH_MC. All simulated and human metabolic data were extrapolated to 24-h and analyzed (SPSS, Ver. 22). RESULTS: Comparing stoichiometry to actual combustion, the VH_MC underestimated simulated RMR (p < 0.05), VO2 (p < 0.05), VCO2 (p < 0.05) and the RQ. Similarly the RMR_WRIC underestimated simulated RMR (p < 0.05) and VO2 while overestimating VCO2 and the RQ. There was much greater variability in the simulated metabolic data between combustion and the VH_MC as compared to that of the RMR_WRIC. With regards to the volunteers, the RMR, RQ, VO2 and VCO2 determined by the VH_MC tended to be lower in comparison to these measurements determined by the RMR_WRIC. Finally, RMR calculated utilizing the ME was significantly (p < 0.05) less than the RMR_WRIC but similar to that obtained by the VH_MC. CONCLUSION: The RMR_WRIC was more accurate and precise than either the VH_MC or ME, which has implications for determining energy requirements for individuals participating in weight loss or nutrition rehabilitation programs.

An acetylcholinesterase-derived peptide inhibits endocytic membrane activity in a human metastatic breast cancer cell line.

Acetylcholinesterase (AChE) is well established as having non-cholinergic functions and is also expressed in breast tumours where its function(s) is not known. Recently, a candidate peptide sequence towards the C-terminal of the AChE molecule has been identified, as the salient site remote from normal catalysis in neurons, and possibly other cells. The main aim of this study was to explore the possibility that 'AChE-peptide' might also affect human breast cancer cells. Uptake of the non-cytotoxic tracer horseradish peroxidase (HRP) was used as an index of endocytosis, a key component of the metastatic cascade, representing exocytosis/secretory membrane activity and/or plasma membrane protein turnover. AChE-peptide had no affect on the weakly metastatic MCF-7 human breast cancer cell line. By contrast, application of AChE-peptide to the strongly metastatic MDA-MB-231 cells resulted in a dose-dependent inhibition of HRP uptake; treatment with a scrambled variant of the peptide of comparable amino acid length was ineffective. The action of AChE-peptide was suppressed by lowering the extracellular Ca2+ concentration and co-applying a selective antagonist of alpha7, but not alpha4/beta2, nicotinic receptor. The results suggest that AChE-peptide has a novel, selective bioactivity on breast cancer cells and can potentiate metastatic cell behaviour.

Functional maturation of isolated neural progenitor cells from the adult rat hippocampus.

Although neural progenitor cells (NPCs) may provide a source of new neurons to alleviate neural trauma, little is known about their electrical properties as they differentiate. We have previously shown that single NPCs from the adult rat hippocampus can be cloned in the presence of heparan sulphate chains purified from the hippocampus, and that these cells can be pushed into a proliferative phenotype with the mitogen FGF2 [Chipperfield, H., Bedi, K.S., Cool, S.M. & Nurcombe, V. (2002) Int. J. Dev. Biol., 46, 661-670]. In this study, the active and passive electrical properties of both undifferentiated and differentiated adult hippocampal NPCs, from 0 to 12 days in vitro as single-cell preparations, were investigated. Sparsely plated, undifferentiated NPCs had a resting membrane potential of approximately -90 mV and were electrically inexcitable. In > 70%, ATP and benzoylbenzoyl-ATP evoked an inward current and membrane depolarization, whereas acetylcholine, noradrenaline, glutamate and GABA had no detectable effect. In Fura-2-loaded undifferentiated NPCs, ATP and benzoylbenzoyl-ATP evoked a transient increase in the intracellular free Ca(2+) concentration, which was dependent on extracellular Ca(2+) and was inhibited reversibly by pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS), a P2 receptor antagonist. After differentiation, NPC-derived neurons became electrically excitable, expressing voltage-dependent TTX-sensitive Na(+) channels, low- and high-voltage-activated Ca(2+) channels and delayed-rectifier K(+) channels. Differentiated cells also possessed functional glutamate, GABA, glycine and purinergic (P2X) receptors. Appearance of voltage-dependent and ligand-gated ion channels appears to be an important early step in the differentiation of NPCs.

Effects of acetylcholinesterase and butyrylcholinesterase on cell survival, neurite outgrowth, and voltage-dependent calcium currents of embryonic ventral mesencephalic neurons.

The aim of this study was to investigate the effect of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) on cell survival, neurite outgrowth and voltage-dependent calcium currents in developing rat ventral mesencephalic (VM) neurons. Both BuChE and AChE have been shown to promote neurite outgrowth in postnatnal preparations. However, the effect of these substances has never been investigated on rat embryonic VM cells, which are used in animal models of foetal transplantation as a treatment for Parkinson's disease. The effects of incubation with BuChE and tetrameric (G(4))- or monomeric (G(1))-AChE on cell survival and neurite outgrowth were characterised over a 7-day period on dopaminergic cells within embryonic VM cultures. The acute effects of these treatments on voltage-dependent calcium currents from embryonic VM cells were then investigated using whole-cell voltage-clamp recordings. The chronic effect of modulating voltage-dependent calcium channels was subsequently explored using the selective calcium channel antagonists omega-agatoxin IVA, omega-conotoxin GVIA, and nifedipine. The results presented here demonstrate firstly trophic effects of BuChE and G(4)- and G(1)-AChE upon dopaminergic neurite outgrowth, secondly that BuChE and G(4)- and G(1)-AChE have an inhibitory effect on voltage-dependent calcium currents, and finally that selective voltage-dependent calcium channel inhibitors also have trophic effects upon dopaminergic neurite outgrowth.

Expression of voltage-dependent calcium channels in the embryonic rat midbrain.

The diversity of expression of high-voltage activated voltage-dependent calcium channels (VDCC) was investigated with whole-cell voltage-clamp recordings from dissociated embryonic rat ventral mesencephalic cells over a 7-day culture period. Cell phenotype was identified post-recording by fluorescent immunocytochemistry as tyrosine hydroxylase positive (TH+) or glutamic acid decarboxylase positive (GAD+). Both TH+ and GAD+ cells displayed high-threshold calcium (Ca(2+)) currents activated by depolarisations positive to -60 mV. In both cell types, pharmacological dissection using selective VDCC inhibitors, omega-agatoxin IVA (Aga IVA), omega-conotoxin GVIA (GVIA) and nifedipine demonstrated the existence of P/Q-, N- and L-type VDCC, respectively. The remaining residual current could be blocked by cadmium. It was found that the contribution to the whole-cell current by the N-type channel was greater in TH+ cells than GAD+ cells at each time point examined, whilst the contribution to the whole-cell current by the L-type channel was greater in GAD+ cells than TH+ cells. However, over the 7-day culture period, the expression of VDCC types in both cell phenotypes changed in a similar fashion, with the contribution to the whole-cell current from the N-type current decreasing, and the contribution from the R-type current increasing. Our data could provide new insights into a range of neurodevelopmental mechanisms related to Ca(2+) homeostasis in developing mesencephalic neurons.