Assessment of age-related changes in pediatric gastrointestinal solubility

PurposeCompound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility.MethodsSolubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37°C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media.ResultsFor six of the seven compounds investigated, solubility fell outside an 80–125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II).ConclusionDevelopmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.<br/

Comparative study of preterm infants fed new and existing human milk fortifiers showed favourable markers of gastrointestinal status

AIM: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants. METHODS: We report secondary outcomes from a controlled, double-blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha-1 antitrypsin and calprotectin, and maturity, namely elastase-1. RESULTS: Faecal alpha-1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 +/- 1.32 vs 1.82 +/- 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1-Q3] of 296 [136-565] mug/g stools in both groups combined at study day 21). Faecal elastase-1 was lower in the new fortifier than control fortifier group (202.5 +/- 1.6 vs 257.7 +/- 1.5 mug/g stools, P = .016). CONCLUSION: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised

New insights into the morphology and sedimentary processes along the western slope of Great Bahama Bank.

New high-quality multibeam and seismic data image the western slope of the Great Bahama Bank and the adjacent floor of the Straits of Florida. The extensive survey reveals several unexpected large- and small-scale morphologies. These include bypass areas, channel-leveelobe systems, gullied slopes, and products of slope instabilities at various scales, including long slump scars at the lower slope and mass transport complexes that extend ~30 km into the adjacent basin floor. The toe of the slope is irregularly covered with deep-water carbonate mounds. The abundance of the individual morphological features varies from north to south. From 26°00'N to 25°20'N, the slope is dissected by numerous deep canyons that abruptly end southward, where the slope is characterized by a smooth lower portion and small regularly spaced furrows in its upper part. Further south, two long (25-50 km) scars document instability at the lower slope. One of these scars is the source area of a large mass transport complex. In addition to this large-scale feature, several types of gravity-induced sedimentary processes are revealed. Most of the morphologies and inferred processes of this carbonate system are similar to those observed in siliciclastic systems, including mass transport complexes, gravity currents initiated by density cascading, and overspilling channeled turbidity currents. For the first time, a clear asymmetric channel-levee system has been identified along the slope, suggesting similitude in sorting processes between carbonate and siliciclastic systems and enhancing the reservoir-bearing potential of carbonate slopes. Notable differences with siliciclastic systems include: the lack of connection with the shallow and emerged part of the system (i.e., bank top), and the small size of the sedimentary system. © 2012 Geological Society of America

Mode of Neonatal Delivery Influences the Nutrient Composition of Human Milk: Results From a Multicenter European Cohort of Lactating Women

International audienceBACKGROUND: The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months. OBJECTIVE: This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life. DESIGN: Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother's country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode. RESULTS: Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p \textless 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation. CONCLUSION: Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life

Persistent non-solar forcing of Holocene storm dynamics in coastal sedimentary archives

International audienceConsiderable climatic variability on decadal to millennial timescales has been documented for the past 11,500 years of interglacial climate1, 2, 3. This variability has been particularly pronounced at a frequency of about 1,500 years, with repeated cold intervals in the North Atlantic1, 3. However, there is growing evidence that these oscillations originate from a cluster of different spectral signatures4, ranging from a 2,500-year cycle throughout the period to a 1,000-year cycle during the earliest millennia. Here we present a reappraisal of high-energy estuarine and coastal sedimentary records from the southern coast of the English Channel, and report evidence for five distinct periods during the Holocene when storminess was enhanced during the past 6,500 years. We find that high storm activity occurred periodically with a frequency of about 1,500 years, closely related to cold and windy periods diagnosed earlier1, 2, 3. We show that millennial-scale storm extremes in northern Europe are phase-locked with the period of internal ocean variability in the North Atlantic of about 1,500 years4. However, no consistent correlation emerges between spectral maxima in records of storminess and solar irradiation. We conclude that solar activity changes are unlikely to be a primary forcing mechanism of millennial-scale variability in storminess

Human milk fatty acid composition and its association with maternal blood and adipose tissue fatty acid content in a cohort of women from Europe

International audiencePURPOSE: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. METHODS: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established. RESULTS: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. CONCLUSIONS: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM