Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes.

BACKGROUND: Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. METHODS: Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. RESULTS: A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25. CONCLUSIONS: In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

The proof is in the pudding: children prefer lower fat but higher sugar than do mothers.

OBJECTIVE: Although there are established age-related differences in sweet preferences, it remains unknown whether children differ from mothers in their preference for and perception of fat (creaminess). We examined whether individual differences in sucrose and fat preferences and perception are related to age, genotype and lifestyle. SUBJECTS: Children 5-10 years-old (n=84) and their mothers (n=67) chose the concentration of sucrose and fat most preferred in pudding and sucrose most preferred in water using identical, two-alternative, forced-choice procedures, and ranked pudding samples for intensity of sweetness and creaminess. Subjects were also weighed and measured for height, as well as genotyped for a sweet-receptor gene (TAS1R3). RESULTS: Children preferred higher concentrations of sucrose in water (P=0.03) and in pudding (P=0.05) and lower concentrations of fat in pudding (P<0.01) than did mothers. Children and mothers were equally able to rank the intensity of different concentrations of fat (P=0.12) but not sucrose in pudding (P=0.01). Obese and lean children and mothers did not differ in preferences, but obese mothers were less able to correctly rank the concentration of fat in pudding than were lean mothers (P=0.03). Mothers who smoked preferred a higher concentration of sucrose than did those who never smoked (P<0.01). Individual differences in sweet preference were associated with genetic variation within the TAS1R3 gene in mothers but not children (P=0.04). CONCLUSION: Irrespective of genotype, children prefer higher concentrations of sugar but lower concentrations of fat in puddings than do their mothers. Thus, reduced-fat foods may be better accepted by children than adults.

Early rapid weight gain among formula-fed infants: Impact of formula type and maternal feeding styles.

BACKGROUND: What and how infants are fed are considered important determinants for the risk factor of early rapid gain weight. OBJECTIVES: We conducted secondary analyses on data from a randomized clinical trial, wherein infants randomized to feed cow milk formula had double the incidence of early rapid weight gain than those fed extensively hydrolyzed protein formula, to determine whether maternal feeding styles had independent effects or interactive effects with infant formula type on early rapid weight gain. METHODS: Anthropometry and feeding patterning (number of daily formula feeds) were measured monthly, and maternal feeding styles were measured at 0.5, 3.5, and 4.5 months. Longitudinal models were fitted using generalized estimating equations and separate logistic models conducted. RESULTS: The treatment groups did not differ in formula feeding patterning or in maternal feeding styles, which were stable across the first 4.5 months. Feeding styles had no significant effects on early rapid weight gain and did not interact with formula group. However, type of infant formula had a direct and independent impact on early rapid weight gain (P = 0.003). CONCLUSIONS: The type of infant formula had a differential impact on early rapid weight gain independent of maternal feeding style, highlighting the self-regulatory capabilities of infants.

From biology to behavior: a cross-disciplinary seminar series surrounding added sugar and low-calorie sweetener consumption.

INTRODUCTION: This report presents a synopsis of a three-part, cross-sector, seminar series held at the George Washington University (GWU) in Washington, DC from February-April, 2018. The overarching goal of the seminar series was to provide a neutral forum for diverse stakeholders to discuss and critically evaluate approaches to address added sugar intake, with a key focus on the role of low-calorie sweeteners (LCS). METHODS: During three seminars, twelve speakers from academic institutions, federal agencies, non-profit organizations, and the food and beverage industries participated in six interactive panel discussions to address: 1) Do Farm Bill Policies Impact Population Sugar Intake? 2) What is the Impact of Sugar-sweetened Beverage (SSB) Taxes on Health and Business? 3) Is Sugar Addictive? 4) Product Reformulation Efforts: Progress, Challenges, and Concerns? 5) Low-calorie Sweeteners: Helpful or Harmful, and 6) Are Novel Sweeteners a Plausible Solution? Discussion of each topic involved brief 15-minute presentations from the speakers, which were followed by a 25-minute panel discussion moderated by GWU faculty members and addressed questions generated by the audience. Sessions were designed to represent opposing views and stimulate meaningful debate. Given the provocative nature of the seminar series, attendee questions were gathered anonymously using Pigeonhole™, an interactive, online, question and answer platform. RESULTS: This report summarizes each presentation and recapitulates key perspectives offered by the speakers and moderators. CONCLUSIONS: The seminar series set the foundation for robust cross-sector dialogue necessary to inform meaningful future research, and ultimately, effective policies for lowering added sugar intakes.

Consistency in infants' behavioural signalling of satiation during bottle-feeding.

BACKGROUND: Understanding the dynamics of feeding is essential for preventing accelerated weight gain during infancy, a risk factor for obesity. OBJECTIVES: Because infants satiate on larger volumes of cow milk formula (CMF) than CMF enriched with the free amino acid glutamate (CMF + glu), we used this model system to determine whether infants displayed consistent behaviours despite satiating on lower volumes. METHODS: In this laboratory-based, within-subject experimental study of ≤4-month-old infants (n = 41) and their mothers, infants were videotaped while feeding to satiation CMF on one test day and CMF + glu on the other, in counterbalanced order. Each video-recording was analysed frame-by-frame for frequency and timing of behaviours. RESULTS: Infants' behaviours were consistent in types and frequency but were displayed sooner when feeding CMF + glu compared with CMF. The less responsive the mother's feeding style, the less consistent the infant displayed behaviours across the two formula meals (P = 0.05). Infants who spat up (a possible sign of overfeeding) consumed more formula (P = 0.01) and had less responsive mothers (P = 0.04) compared with the other infants. CONCLUSIONS: Infants are consistent in their behavioural displays during feeding at this developmental age. Regulation of intake and signalling of satiation during bottle-feeding are associated with formula composition and maternal feeding style.

Flavor variety enhances food acceptance in formula-fed infants.

BACKGROUND: Research in humans and animal models suggests that acceptance of solid foods by infants during weaning is enhanced by early experiences with flavor variety. OBJECTIVE: We tested the hypotheses that the acceptance of novel foods by formula-fed infants could be facilitated by providing the infants with a variety of flavors at the time when beikost is first introduced and that, contrary to medical lore, infants who had previously consumed fruit would be less likely to reject vegetables when first introduced than would infants without such an experience. DESIGN: The infants' acceptance of a novel vegetable (puréed carrot) and a novel meat (puréed chicken) was evaluated after a 9-d exposure period in 3 groups of infants, some of whom had previously consumed fruit. During the home-exposure period, one group was fed only carrots, the target vegetable; a second group was fed only potatoes, a vegetable that differed in flavor from carrots; and a third group was fed a variety of vegetables that did not include carrots. RESULTS: Infants fed either carrots or a variety of vegetables, but not those fed potatoes, ate significantly more of the carrots after the exposure period. Exposure to a variety of vegetables also facilitated the acceptance of the novel food, puréed chicken, and daily experience with fruit enhanced the infants' initial acceptance of carrots. CONCLUSION: These findings are the first experimental evidence to indicate that exposure to a variety of flavors enhances acceptance of novel foods in human infants.

Maternal diet alters the sensory qualities of human milk and the nursling's behavior.

Although the majority of human infants are breast-fed for the first few months of life, there is a paucity of information regarding the sensory qualities of human milk and how these qualities are affected by maternal diet. The present study investigated the effects of garlic ingestion by the mother on the odor of her breast milk and the suckling behavior of her infant. Evaluation of the milk samples by a sensory panel revealed garlic ingestion significantly and consistently increased the perceived intensity of the milk odor; this increase in odor intensity was not apparent 1 hour after ingestion, peaked in strength 2 hours after ingestion, and decreased thereafter. That the nursling detected these changes in mother's milk is suggested by the finding that infants were attached to the breast for longer periods of time and sucked more when the milk smelled like garlic. There was a tendency for infants to ingest more milk as well; the lack of a significant effect may be due to the inherent limitations on the total amount of milk available to the infant.

Early flavor experiences: research update.

Anyone who has observed infants for any period of time can testify to the intense activity occurring in and around their mouths--the primary site for learning in the first few months of life. Before they are even able to crawl, infants have learned much about their new sensory world. Though recent research we have begun to explore the impact of these early experiences on infants' acceptance of solid foods and how they explore objects in their environment. We have also begun to focus on the sensory experiences of the formula-fed infant, in particular, how their responses to particular formulas, which are extremely unpalatable to older children and adults, change during infancy. This is a relatively new and exciting area of study, with much research yet to be done. It is clear, however, that infants are not passive receptacles for flavored foods. Parents who offer a variety of foods will provide both a nutritious, well-balanced diet, as well as an opportunity for their children's own personal preferences to develop.

Infanticide in the male rat: the role of the vomeronasal organ.

The present study constitutes the first demonstration that vomeronasal chemoreception plays a role in the response of the virgin male rat to conspecific newborn. Specifically, it shows that virgin males, after removal of the vomeronasal organ, exhibit a decrease in the incidence of infanticidal behavior. This finding is discussed in terms of how responsiveness to young can be affected by changes in the accessory olfactory system.

Pheromonal emission by pregnant rats protects against infanticide by nulliparous conspecifics.

The present studies of experiments focuses on infanticide in the nulliparous rat and asks two questions. First, what do infanticidal nulliparae gain from killing unrelated young? And second, does the recently parturient female have an effective strategy to counter female infanticide? With regard to the first question, we show two benefits from killing unrelated young, namely, that the killer utilizes the young as a food resource and that she occupies the nest site of the mother whose young she has destroyed. With regard to the second question, we show that an extended period of cohabitation with a pregnant female reduces the incidence of infanticidal behavior in nulliparae. Additionally, we demonstrate that the mother emits a pheromone during pregnancy which in itself reduces the incidence of infanticide and, in fact, often makes potentially infanticidal females maternal. The possible endocrine basis of this induced maternal behavior is discussed.

Infanticide in rats: male strategy and female counter-strategy.

The present series of experiments addresses the question of whether mating governs infanticide in the male rat and, in addition, asks whether the female rat has available an effective counter-strategy to male infanticide. With regard to the first question, we found that mating provides a safeguard against the killing of own young. That is, mating induces a general inhibition of infanticide coincident with the birth of the male's young and a recrudescence of infanticide synchronized with their weaning. The particular gain realized in killing alien young depends on the age of young and consequently on whether the mother had reached postpartum estrus. We also found that the pregnant female has an effective strategy to counter male infanticide which she employs before the young are born. The data show that this counter-strategy involves the synthesis of a chemosignal of low volatility emitted during pregnancy. The possible role of the male's vomeronasal system in the reception of this chemosignal is discussed.

Hypothalamic temperature and deep body temperature during copulation in the male rat.

The medial preoptic area (MPOA) of the hypothalamus is involved in both the expression of male sexual behavior and the regulation of physiological temperature. This duality of function led us to ask whether arousal, intromission, and ejaculation are accompanied by a distinctive temperature profile. Using telemetric thermosensors, we monitored MPOA temperature and deep body temperature during copulation in the male rat. Changes in MPOA temperature were highly uniform, more so than changes in body temperature. The MPOA heated prior to ejaculation, cooled rapidly following ejaculation and then began to heat again coincident with the termination of the post-ejaculatory refractory period. These changes could not be related to variations in general activity. The most striking change in MPOA temperature, rapid cooling following ejaculation, was explained in terms of certain behaviorally-induced hemodynamic events.

Sleep disturbances after acute exposure to alcohol in mothers' milk.

The results of previous research in our laboratory revealed that breast-fed infants experience significantly less active sleep after exposure to alcohol in their mothers' milk than do breast-fed infants not exposed to alcohol. The present study tested the hypothesis that infants would compensate for such reductions if their mothers then refrained from drinking alcohol. To this end, 23 breast-fed infants from 3 to 5 months of age and their mothers were tested on 2 days separated by 1 week. A small, computerized movement detector, an actigraph, was placed on the infants' left ankles to monitor sleep and activity patterning after which they were bottle fed mother's milk alone (control condition) on 1 test day and mother's milk containing 32 mg of ethanol per 100 ml--the average concentration detected in human milk after lactating women drank an acute dose (0.3 g/kg) of alcohol--on the other. The infants' behaviors were monitored for the next 24 h; the first 3.5 h of monitoring on each test day took place at the Monell Center. Consistent with previous findings, infants exhibited significantly less active sleep during the 3.5 h immediately after exposure to alcohol in mothers' milk compared with the control condition; the decrease in active sleep was observed in all but 4 of the infants tested. Compensatory increases in active sleep were then observed in the next 20.5 h, when mothers refrained from drinking alcohol. Although the mechanisms underlying the reduction in sleep remain to be elucidated, these findings demonstrate that short-term exposure to small amounts of alcohol in mothers' milk produces distinctive changes in the infants' sleep-wake patterning.

Developmental changes in the acceptance of protein hydrolysate formula.

To investigate the age-related changes in the acceptance of a protein hydrolysate formula, Nutramigen, and to determine whether infants' response to a novel formula is related to their mothers' willingness to try novel foods, healthy infants, who were either 1 to 2 (Group 1) or 7 to 8 (Group 1 retested and Group 2) months of age, were fed their familiar brand of milk- or soy-based formula on one testing day and a casein hydrolysate formula, Nutramigen, on another. The data revealed that infants younger than 2 months detected the difference between Nutramigen and their regular formulas as evidenced by a slight, relative depression in intakes (p = .04). However, these infants drank substantial amounts of the Nutramigen and satiated while feeding it. In marked contrast, virtually all of the 7- to 8-month-old infants rejected the Nutramigen (p = .000002), and this was evident within the 1st minute of the feed. Finally, there was a significant correlation between the mothers' eating habits as determined by the questionnaires and the 1- to 2-month-old infants' response to Nutramigen. Mothers who exhibited a greater willingness to consume novel foods (p = .003) or less food neophobia (p = .04) had infants who consumed relatively more of the Nutramigen.

Developmental changes in nasal airflow patterns.

Airflow through each nasal passage was measured every 10 min throughout a 5-h period in 48 subjects whose ages ranged from 3 to 17 years. The data were subjected to statistical techniques that characterize and quantify periodicities in a time series. Such analyses revealed that for the majority of children younger than 7 years of age, the airflow through the two nostrils changed either randomly (50%) or in parallel (31%). Between the ages of 7 and 10 years, however, the distribution of airflow patterns characteristic of adults emerged, such that the incidence of reciprocity increased to 63%, and the incidence of random and parallel patterns decreased to 31% and 6%, respectively. A similar distribution was evidenced in the 11- to 17-year-old subjects (56% reciprocal, 38% random, 6% parallel). Although the total airflow through the nose also increased with age, the increased inspiratory flow rates could not account for the developmental changes evidenced in airflow patterns.

Mother's milk: a medium for early flavor experiences.

For centuries, many believed that the lactating woman's diet could influence the composition and flavor of her milk and that substances in human milk could be transmitted from the wet nurse or mother and have long-lasting effects on the child. The research described herein focuses on mother's milk as a medium of early sensory experiences for the human infant and establishes several points. First, human milk is not a food of invariant flavor. Rather, like the milk of other mammals, human milk is flavored by ingested compounds such as garlic, mint, vanilla, and alcohol and provides the potential for a rich source of varying chemosensory experiences to the infant. Second, the infants' response to a particular flavor in milk may depend upon the recency and duration of past exposures. That is, the prior diet of mothers, and consequently their infants, may modify the infants' responses to these flavors during breastfeeding.

Organic cleanliness of the Mars Science Laboratory sample transfer chain.

One of the primary science goals of the Mars Science Laboratory (MSL) Rover, Curiosity, is the detection of organics in Mars rock and regolith. To achieve this, the Curiosity rover includes a robotic sampling system that acquires rock and regolith samples and delivers it to the Sample Analysis at Mars (SAM) instrument on board the rover. In order to provide confidence that any significant organics detection result was Martian and not terrestrial in origin, a requirement was levied on the flight system (i.e., all sources minus the SAM instrument) to impart no more than 36 parts per billion (ppb by weight) of total reduced carbon terrestrial contamination to any sample transferred to the SAM instrument. This very clean level was achieved by a combination of a rigorous contamination control program on the project, and then using the first collected samples for a "dilution cleaning" campaign of the sample chain prior to delivering a sample to the SAM instrument. Direct cleanliness assays of the sample-contacting and other Flight System surfaces during pre-launch processing were used as inputs to determine the number of dilution cleaning samples needed once on Mars, to enable delivery of suitably clean samples to the SAM experiment. Taking into account contaminant redistribution during launch thorough landing of the MSL on Mars, the amount of residue present on the sampling hardware prior to the time of first dilution cleaning sample acquisition was estimated to be 60 ng/cm(2) on exposed outer surfaces of the sampling hardware and 20 ng/cm(2) on internal sample contacting surfaces; residues consisting mainly of aliphatic hydrocarbons and esters. After three dilution cleaning samples, estimated in-sample contamination level for the first regolith sample delivered to the SAM instrument at the Gale Crater "Rocknest" site was bounded at ≤10 ppb total organic carbon. A Project decision to forego ejecting the dilution cleaning sample and instead transfer the first drill-acquired sample at the "John Klein" site to SAM resulted in an estimated level of terrestrial contamination of ≤430 ppb. The estimated terrestrial contamination for portions from the second drill-acquired sample, at Cumberland, was ≤69 ppb; the estimate for a future, third, drilled sample is ≤38 ppb. These levels are comparable in magnitude to the SAM instrument blanks at the nanomole level (as chlorohydrocarbon).

In situ cleaning of instruments for the sensitive detection of organics on Mars.

A method is presented for in situ cleaning of spacecraft instruments that analyze planetary soil and rock. We have found that vibrating hardware, used to facilitate powder transport, was also effective at removing contamination. Surfaces can be cleaned below monolayer levels using vibrating surfaces in the presence of mineral powder. Both organic and particulate contamination is efficiently removed. Fine grained regolith from the planetary surface or an organic free reference material may serve as the powder used for cleaning. We present both analytical and experimental results for the contamination transfer fraction and the conditions required to clean the hardware prior to sensitive chemical analysis.

Effects of breast pumping on the pharmacokinetics and pharmacodynamics of ethanol during lactation.

This study tested two hypotheses. First, that breast pumping contributes to the previously observed decrease in ethanol bioavailability in lactating women. Second, that the effects of breast pumping are more pronounced when ethanol is consumed after a meal. The within-subject factor was test condition (fed or fasted) and the between-subject factor was experimental group (pumped before, PB; pumped after, PA). Those randomly assigned to the PB group (N = 8) breast pumped 1 h before drinking, whereas those assigned to the PA group (N = 8) breast pumped 0.6 h after drinking. Pumping before drinking significantly decreased blood ethanol concentration (P < 0.05) and ethanol bioavailability (P = 0.05). Pumping after drinking sped up elimination (P = 0.008), attenuated ethanol-induced hypothermia (P = 0.002), and increased feelings of stimulation (P = 0.03). The effects were more pronounced when ethanol was consumed after a meal. Common neural/hormonal responses to food and suckling may contribute additive effects in altering the pharmacokinetics/pharmacodynamics of ethanol, and perhaps of other drugs, during lactation.