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Neural tube defects (NTDs) are serious congenital malformations. In this study, we aimed to identify more specific and sensitive maternal serum biomarkers for noninvasive NTD screenings. We collected serum from 37 pregnant women carrying fetuses with NTDs and 38 pregnant women carrying normal fetuses. Isobaric tags for relative and absolute quantitation were conducted for differential proteomic analysis, and an enzyme‐linked immunosorbent assay was used to validate the results. We then used a support vector machine (SVM) classifier to establish a disease prediction model for NTD diagnosis. We identified 113 differentially expressed proteins; of these, 23 were either up‐ or downregulated 1.5‐fold or more, including five complement proteins (C1QA, C1S, C1R, C9, and C3); C3 and C9 were downregulated significantly in NTD groups. The accuracy rate of the SVM model of the complement factors (including C1QA, C1S, and C3) was 62.5%, with 60% sensitivity and 67% specificity, while the accuracy rate of the SVM model of alpha‐fetoprotein (AFP, an established biomarker for NTDs) was 62.5%, with 75% sensitivity and 50% specificity. Combination of the complement factor and AFP data resulted in the SVM model accuracy of 75%, and receiver operating characteristic curve analysis showed 75% sensitivity and 75% specificity. These data suggest that a disease prediction model based on combined complement factor and AFP data could serve as a more accurate method of noninvasive prenatal NTD diagnosis. [ABSTRACT FROM AUTHOR]

This paper aimed to examine the effect of breastfeeding on longitudinal patterns of common infections up to 2 years and respiratory symptoms up to 8 years. To assess the incidence and reoccurrence of infections and allergic symptoms in the first years of life among 1,603 children from the EDEN mother–child cohort, distinct longitudinal patterns of infectious diseases as well as skin rash and respiratory symptoms were identified by group‐based trajectory modelling. To characterize infections, we considered the parent‐reported number of cold/nasopharyngitis and diarrhoea from birth to 12 months and otitis and bronchitis/bronchiolitis from birth to 2 years. To characterize allergy‐related symptoms, we considered the parent‐reported occurrence of wheezing and skin rash from 8 months to 8 years and asthma from 2 to 8 years. Then associations between breastfeeding and these longitudinal patterns were assessed through adjusted multinomial logistic regression. Compared with never‐breastfed infants, ever‐breastfed infants were at a lower risk of diarrhoea events in early infancy as well as infrequent events of bronchitis/bronchiolitis throughout infancy. Only predominant breastfeeding duration was related to frequent events of bronchitis/bronchiolitis and infrequent events of otitis. We found no significant protective effect of breastfeeding on longitudinal patterns of cold/nasopharyngitis, skin rash, or respiratory symptoms. For an infant population with a short breastfeeding duration, on average, our study confirmed a protective effect of breastfeeding on diarrhoea events in early infancy, infrequent bronchitis/bronchiolitis and, to a lesser extent, infrequent otitis events up to 2 years but not on other infections, skin rash, or respiratory symptoms4. In an infant population with a short breastfeeding duration and using longitudinal patterns of infection, skin rash and respiratory symptoms, on average, our study confirmed a protective effect of breastfeeding on diarrhea events in early infancy, infrequent bronchitis/bronchiolitis and, to a lesser extent,infrequent otitis events up to 2 years but not on cold/ nasopharyngitis, skin rash or respiratory symptoms. [ABSTRACT FROM AUTHOR]

Natural-based polyols are seen by polyurethane industries as an alternative to the petroleum-based polyols because of increasing challenges due to the oil crisis and global warming. In this research, four different derivatives of bio-polyols are examined, which include the precursor Jatropha curcas oil (JC) that was extracted from Jatropha curcas seeds, as well as the derivatives epoxidated-polyol (EJ), hydroxylated epoxy-polyol (JP) and epoxy-polyurethane (JU). The computational studies provide more insight into their experimentally observed properties and can be useful in further customized design of this type of bio-polyols for industrial application. Results show that the JU monomer is more stable in terms of potential energy, level of atomic fluctuation, diffusion, radial distribution function, and with properties indicating the possibility of forming the best crystal solid. Monomer JU is also found to have the best resistance to acidic attack, using the results from the interaction energy, radial distribution function (RDF) and level of diffusion. [ABSTRACT FROM AUTHOR]

By using quasi-Banach techniques as key ingredient we prove Poincaré- and Sobolev- type inequalities for m-subharmonic functions with finite (p, m)-energy. A consequence of the Sobolev type inequality is a partial confirmation of Błocki’s integrability conjecture for m-subharmonic functions. [ABSTRACT FROM AUTHOR]

The possibility of plutonium (Pu) intake by radiation workers can not be ruled out. Transportation of Pu(IV) to various organs/cells is mainly carried through iron-carrying protein, serum transferrin (sTf), by receptor-mediated endocytosis. Understanding the Pu–sTf interaction is a primary step toward future design of its decorporating agents. We report MD simulations of Pu(IV) binding with sTf and look out for its decorporation at extracellular pH using suitable ligands. MD simulations were carried out in polarizable water environment at different protonation states of the protein. Results unravel the binding motif of Pu(IV): (1) sTf binds the ion in closed conformation at extracellular serum pH with carbonate as synergistic anions, (2) change in protonation state of dilysine (K206 and K296)-trigger and that of the carbonate ion at acidic endosomal pH is found to cause conformational changes of protein, conducive for the heavy ion to be released, although; (3) strong electrostatic interaction between D63 in the binding-cleft and Pu(IV) is found not to ever set free the ion. In an endeavour to decorporate Pu(IV), fragmented molecular form of hydroxypyridinone (HOPO) and catechol (CAM)-based ligands are docked at the binding site (BS) of the protein and metadynamics simulations are conducted. Pu(IV) binding at BS is found to be so strong that it was not detached from BS with the docked HOPO. However, for the identical set of simulation parameters, CAM is found to facilitate dislodging the heavy ion from the protein's binding influence. Differential behaviour of the two chelators is further explored. Fragmented molecular form of hydroxy-pyridinone (HOPO) and catecholamide (CAM) ligands were docked at the binding-site (BS) of human serum transferrin (sTf) to explore their feasibility as plausible Pu(IV) decorporating agents by employing metadynamics method. CAM was found to dislodge Pu from the sTf BS, while HOPO could not. [ABSTRACT FROM AUTHOR]

Although relatively uncommon, the incidence of fetal echogenic lung lesions - a heterogeneous group of anomalies that includes congenital pulmonary airway malformations (CPAM) and bronchopulmonary sequestrations (BPS) - has increased recently. Two decades ago, the CPAM-volume ratio (CVR) was first described as a tool to predict the development of hydrops, with this outcome found to be unlikely in fetuses with CVRs of ≤1.6 cm2. Since then, no clear international consensus has evolved as to the optimal CVR thresholds for the prediction of fetal/neonatal outcomes. This systematic review aimed to assess all original research studies that reported on the predictive utility of the CVR. Potentially relevant papers were identified through searching for citations of the paper that originally described the CVR, in addition to keyword searches of electronic databases. Fifty-two original research papers were included in the final review. Of these, 34 used the CVR for descriptive purposes only, 5 assessed the validity of established thresholds in different populations, and 13 proposed new thresholds. The evidence identified in this review would suggest that a threshold much lower than 1.6 cm2 is likely to be of greater utility in most populations for many outcomes of perinatal relevance. For neonatal outcomes (mostly respiratory compromise at birth), a CVR on the initial ultrasound scan ranging from 0.5 to 1.0 cm2 appears to have the greatest predictive value. Although a number of studies concurred that 1.6 cm2 was a useful threshold for the prediction of hydrops, many others were unable to assess this due to the rarity of this complication. For this reason, thresholds as low as 0.4 cm2 may be more useful for the prediction of a broader range of fetal concerns, including mediastinal shift and fluid collections. Further large-scale studies are required to determine the true utility of this well-established index. [ABSTRACT FROM AUTHOR]

Background: Despite the growing interest in the relation between adiposity in children and different lifestyle clusters, few studies used a longitudinal design to examine a large range of behaviors in various contexts, in particular eating- and sleep-related routines, and few studies have examined these factors in young children. The objectives of this study were to identify clusters of boys and girls based on diet, sleep and activity-related behaviors and their family environment at 2 and 5 years of age, and to assess whether the clusters identified varied across maternal education levels and were associated with body fat at age 5. Methods: At 2 and 5 years, respectively, 1436 and 1195 parents from the EDEN mother-child cohort completed a questionnaire including behavioral data. A latent class analysis aimed to uncover gender-specific behavioral clusters. Body fat percentage was estimated by anthropometric and bioelectrical impedance measurements. Association between cluster membership and body fat was assessed with mutivariable linear regression models. Results: At 2 years, two clusters emerged that were essentially characterized by opposite eating habits. At 5 years, TV exposure was the most distinguishing feature, but the numbers and types of clusters differed by gender. An association between cluster membership and body fat was found only in girls at 5 years of age, with girls in the cluster defined by very high TV exposure and unfavorable mealtime habits (despite high outdoor playing and walking time) having the highest body fat. Girls whose mother had low educational attainment were more likely to be in this high-risk cluster. Girls who were on a cluster evolution path corresponding to the highest TV viewing time and the least favorable mealtime habits from 2 to 5 years of age had higher body fat at 5 years. Conclusions: Efforts to decrease TV time and improve mealtime routines may hold promise for preventing overweight in young children, especially girls growing up in disadvantaged families. These preventive efforts should start as early in life as possible, ideally before the age of two, and should be sustained over the preschool years. [ABSTRACT FROM AUTHOR]

Here, we provide mechanistic insight to the photocleavage of a compound in the folate family, namely pteroic acid. A bis-decyl chain derivative of pteroic acid was synthesized, structurally characterized and photochemically investigated. We showed that, like folic acid, pteroic acid and the decylated derivative undergo a photocleavage reaction in the presence of H 2 O, while no reaction was observed in methanol solution. Furthermore, density functional theory calculations were carried out to predict relative stabilities of hypothetical mono-, bis- and tris-decylated pteroic acid derivatives to help rationalize the regioselectivity of the bis-decyl pteroic acid product. Additionally, the lipophilicity of the bis-decyl pteroic acid appears to confer a hydrophobic property enabling an interaction with biomembranes., (© 2022 American Society for Photobiology.)

Background: Assisted reproductive techniques (ART) are associated with a higher risk of tetralogy of Fallot (TOF) and multiple pregnancies may be associated with a higher risk of congenital anomalies. We assessed the extent to which the association between ART and risk of TOF may be mediated by the higher risk of multiple pregnancies associated with ART., Methods: We conducted a case-control study using population-based data from the Paris Registry of Congenital Malformations for the period 1987-2009 and a cohort study of congenital heart defects (EPICARD). The study population included 395 cases of TOF and 4104 malformed controls with no known associations with ART. The analysis was based on a path-analysis model using a counterfactual approach, which allows decomposition of the total effect of ART into an indirect effect (that mediated by the association between ART and multiple pregnancies) and a direct effect., Results: ART (all methods combined) were associated with a 2.6-fold higher odds of TOF after adjustment for maternal and paternal characteristics and year of birth (adjusted OR 2.6, 95% CI, 1.5-4.5). Most (79%) of the effect associated with ART was a direct effect (i.e., not mediated by multiple pregnancies), whereas 21% of the effect of ART was due to its association with multiple pregnancies (i.e., the indirect effect). In vitro fertilization with intracytoplasmic sperm injection was associated with a 3.5-fold higher odds of TOF (adjusted OR 3.5, 95% CI, 1.1-11.2); 11% of this effect was mediated through the association of ICSI with multiple pregnancies., Conclusions: By far, most of the higher risk of TOF associated with ART is a direct effect and only a small proportion of the effect may be mediated by multiple pregnancies.

Objective: To report results of the 2021 French National Perinatal Survey (ENP) in metropolitan France and assess trends in the main indicators of perinatal health, medical practices, and risk factors in France since 1995., Population and Method: All the samples included all women giving birth at a gestational age of at least 22 weeks of gestation and/or to an infant weighing at least 500 grams in all maternity units in metropolitan France during one week in 1995 (N=13 048), 2003 (N=14 324), 2010 (N=14 546), 2016 (N=12 553), and 2021 (N=12 088). The data came from postpartum interviews of the women at the hospital and their medical records. Comparisons between surveys showed trends over time., Results: Between 1995 and 2021, maternal characteristics changed. Maternal age and the frequency of women with obesity rose: in 2021, 24.6% of women were 35 years or older (21.1% in 2016, 19.2% in 2010, 15.9% in 2003 and 12.4% in 1995) and 14.4% were obese (11.8% in 2016, 9.9% in 2010 and 7.4% in 2003). Some antenatal prevention behaviors that improved in 2021 were not smoking during the third trimester, acid folic administration before pregnancy, and vaccination against influenza. The percentage of women with an early prenatal appointment ("4 th month appointment"), implemented to facilitate screening of maternal vulnerability during pregnancy, has continued to rise. The percentage of women receiving prenatal care by midwives has risen markedly (39.0% in 2021 versus 11.7% in 2016). Serum screening for Down syndrome continues to increase (91.8% of women in 2021). The rate of induction of labor has risen significantly (20.2% in 1995 and 25.8% in 2021). The mode of delivery has not varied significantly since 2003; in 2021, the cesarean rate was 21.4% and the instrumental vaginal delivery rate 12.4%. Episiotomy was increasingly rare, among both primiparous and multiparous women (16.5% and 2.9% in 2021, respectively). The prevalence of coronavirus (SARS-CoV2) infection during pregnancy was 5.7%. Preterm live births increased regularly, slightly but significantly over the 1995-2016 period and then remained stable between 2016 and 2021 (7.0%). In 2021, 56.3% of women exclusively breastfed during their hospital stay, a modest increase in comparison with 2016 (54.6%)., Conclusion: Routine national perinatal surveys highlight positive trends over time in some preventive practices, decreases in some medical interventions consistent with national guidelines, and the increasing role of midwives in prenatal care. Nonetheless, some indicators remain less than optimal and require more detailed analyses., Competing Interests: Disclosure or interest The authors have no conflict of interest to declare, (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Structural significance of conformational preferences and ribose ring puckering of newly discovered hyper modified nucleotide, 5'-monophosphate 2-methylthio cyclic N 6 -threonylcarbamoyladenosine (p-ms 2 ct 6 A) have been investigated using quantum chemical semi-empirical RM1 and molecular dynamics simulation techniques. Automated geometry optimization of most stable structure of p-ms 2 ct 6 A has also been carried out with the help of abinitio (HF SCF, DFT) as well as semi empirical quantum chemical (RM1, AM1, PM3, and PM6) methods. Most stable structure of p-ms 2 ct 6 A is stabilized by intramolecular interactions between N(3)…HC(2'), N(1)…HC(16), O(13)…HC(15), and O(13)…HO(14). The torsion angles alpha (α) and beta (β) show the significant characteristic patterns with the involvement of intramolecular hydrogen bonding to provide stability to the p-ms 2 ct 6 A. Further, molecular dynamics simulations of p-ms 2 ct 6 A revealed the role of ribose sugar ring puckering i.e. C2'-endo and C3'-endo on the structural dynamics of ms 2 ct 6 A side chain. The modified nucleotide p-ms 2 ct 6 A periodically prefers both the C2'-endo and C3'-endo sugar with 'anti' and 'syn' conformations. This property of p-ms 2 ct 6 A could be useful to recognize the starting ANN codons. All atom explicit MD simulation of anticodon loop (ACL) of tRNA Lys of Bacillus subtilis containing ms 2 ct 6 A at 37th position showed the U-turn feature, base stacking ability with other adjacent bases and hydrogen bonding interactions similar to the isolated base p-ms 2 ct 6 A. The ribose sugar puckering contributes to the orientation of the side chain conformation of p-ms 2 ct 6 A. Thus, the present study could be helpful to understand the structure-function relationship of the hypermodified nucleoside, ms 2 ct 6 A in recognition of the proper codons AAA/AAG during protein biosynthesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The congenital lung malformation volume ratio (CVR) is a prenatal ultrasound measurement that parameterizes congenital lung malformation (CLM) size. The aims of this study were to use serial measurements to create estimated growth curves of fetal CVR for asymptomatic and symptomatic neonates with CLM and to investigate whether a discriminant prognostic model based on these measurements could predict accurately which fetuses with CLM will require invasive respiratory support at delivery and should therefore be delivered at a tertiary-care facility.Methods: This was a retrospective study of fetuses diagnosed prenatally with CLM at three tertiary-care children's hospitals between 2009 and 2016. Those with two or more sonographic measurements of CVR were included. Serial fetal CVR measurements were used to create estimated growth curves for neonates with and those without respiratory symptoms at delivery, defined as requiring invasive respiratory support for the first 24 h after delivery. A discriminant model based on serial CVR measurements was used to calculate the dynamic probability of the need for invasive respiratory support. The performance of this model overall and in preterm and term neonates was compared with those using maximum CVR thresholds of 1.0 and 1.6.Results: Of the 147 neonates meeting the inclusion criteria, 16 (10.9%) required postnatal invasive respiratory support. The estimated CVR growth curve models showed different growth trajectories for asymptomatic and symptomatic neonates, with significantly higher CVR in symptomatic neonates, and values peaking late in the second trimester at around 25 weeks' gestation in asymptomatic neonates. All prognostic methods had high accuracy for the prediction of the need for invasive respiratory support in term neonates, but the discriminant model had the best performance overall (area under the receiver-operating characteristics curve (AUC) = 0.88) and in the preterm population (AUC = 0.85).Conclusions: The estimated CVR growth curves showed different growth patterns in asymptomatic and symptomatic neonates with CLM. The dynamic discriminant model performed well overall and particularly in neonates that were carried to term. Development of an externally validated clinical tool based on this analysis could be useful in determining the site of delivery for fetuses with CLM. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Coffee is a composite mixture of more than a thousand diverse phytochemicals like alkaloids, phenolic compounds, vitamins, carbohydrates, lipids, minerals and nitrogenous compounds. Coffee has multifunctional properties as a food additive and nutraceutical. As a nutraceutical, coffee has anti-inflammatory, anti-oxidant, antidyslipidemic, anti-obesity, type-2 diabetes mellitus (DM), and cardiovascular diseases (CVD), which can serve for the treatment and prevention of metabolic syndrome and associated disorders. On the other hand, as a food additive, coffee has antimicrobial activity against a wide range of microorganisms, inhibits lipid peroxidation (LPO), and can function as a prebiotic. The outcomes of different studies also revealed that coffee intake may reduce the incidence of numerous chronic diseases, like liver disease, mental health, and it also overcomes the all-cause mortality, and suicidal risks. In some studies, high intake of coffee is linked to increase CVD risk factors, like cholesterol, plasma homocysteine and blood pressure (BP). There is also a little evidence that associated the coffee consumption with increased risk of lung tumors in smokers. Among adults who consume the moderate amount of coffee, there is slight indication of health hazards with strong indicators of health benefits. Moreover, existing literature suggests that it may be cautious for pregnant women to eliminate the chances of miscarriages and impaired fetal growth. The primary purpose of this narrative review is to provide an overview of the findings of the positive impacts and risks of coffee consumption on human health. In conclusion, to date, the best available evidence from research indicates that drinking coffee up to 3-4 cups/day provides health benefits for most people. [ABSTRACT FROM AUTHOR]

Children with developmental coordination disorder also manifest difficulties in non-motor domains (attentional, emotional, behavioral and socialization skills). Longitudinal studies can help disentangle the complex relationships between the development of motor skills and other cognitive domains. This study aims to examine the contribution of early cognitive factors to changes in motor skills during the preschool period. Children (N = 1144) from the EDEN mother–child cohort were assessed for motor skills with the Copy Design task (NEPSY battery) and the parent-rated Ages and Stages Questionnaire (fine and gross motor skills scores) at ages 3 and 5–6 years. At 3 years, language skills were evaluated using tests from the NEPSY and ELOLA batteries. Emotional problems, conduct problems, inattention and hyperactivity symptoms, peer relationships and pro-social behavior were assessed with the Strengths and Difficulties Questionnaire (SDQ) also at 3 years. Linear and logistic regression models were performed to examine whether positive and negative changes in motor skills between 3 and 5–6 years are associated with specific cognitive skills at 3 years, while adjusting for a broad range of pre- and postnatal environmental factors. In the linear regression model, the SDQ Inattention symptoms score at 3 years was associated with negative changes in motor skills (standardized β = − 0.09, SD = 0.03, p value = 0.007) and language skills at 3 years were associated with positive changes in motor skills (standardized β = 0.05, SD = 0.02, p value = 0.041) during the preschool period. In logistic regression models, the SDQ Inattention symptoms score at 3 years was associated with a higher likelihood of a declining trajectory of motor skills (OR [95% CI] = 1.37 [1.02–1.84]). A higher language skills score at 3 years was associated with an increased likelihood of a resilient trajectory (1.67 [1.17–2.39]). This study provides a better understanding of the natural history of developmental coordination delays by identifying cognitive factors that predict changes in motor skills between the ages of 3 and 5–6 years. [ABSTRACT FROM AUTHOR]

Although several studies have shown a positive association between socio‐economic position and size at birth, not enough is known about the modifiable factors that may be involved. We aimed to investigate whether maternal prepregnancy body mass index (BMI), smoking, diet, and depression during pregnancy mediate the positive association between maternal education and birth size. Weight and length z‐scores specific for gestational age and sex were calculated for 1,500 children from the EDEN mother–child cohort. A mediation analysis of the associations between maternal education and birth size was conducted with a counterfactual method, adjusted for recruitment centre, parity, maternal height, and age. In the comparison of children of mothers with low versus intermediate education levels, maternal smoking during pregnancy explained 52% of the total effect of education on birth weight. Similar findings were observed with birth length z‐score (37%). The comparison of children of mothers with high versus intermediate education levels yielded a non‐significant total effect, which masked opposite mediating effects by maternal BMI and smoking during pregnancy on both birth weight and length. Prepregnancy BMI and maternal smoking during pregnancy mediate the positive association between maternal education and birth weight and length z‐scores. These mediators, however, act in opposite directions, thereby masking the extent to which healthy prenatal growth is socially differentiated. [ABSTRACT FROM AUTHOR]

Objectives: To assess prenatal changes in the volume of congenital pulmonary malformations (CPM) and examine whether these changes differ in lesions that appear cystic on ultrasound compared with hyperechoic lesions, and to study the relationship between CPM volume and risk of fetal compression.Methods: We conducted a nationally representative, multicenter, prospective cohort study, which included 579 ultrasound examinations in 176 pregnant women with a diagnosis of fetal CPM, between March 2015 and November 2016. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume. We modeled changes in CPM volume ratio (CVR) as a function of gestational age, overall and for cystic/mixed vs hyperechoic malformations, and examined the association between CVR and signs of compression during pregnancy.Results: When modeling CVR changes over time, there was a statistically significant decrease in CVR with increasing gestational age (P < 0.001), but the pattern of change differed according to CPM phenotype at first ultrasound examination: cystic/mixed CPM were characterized by a monotonic decrease in CVR with increasing gestational age (P = 0.002), whereas hyperechoic CPM showed an initial increase in CVR up to 27 weeks of gestation, followed by a decrease thereafter (P < 0.001). Peak CVR values were predicted as early as 21-22 weeks for cystic/mixed CPMs compared with 25-26 weeks for hyperechoic malformations. Regardless of CPM phenotype, fetuses that showed no sign of compression at any point had substantially lower CVR at first CVR measurement, and the CVR remained relatively constant thereafter. Among the subpopulation of fetuses with no sign of compression at first CVR measurement, the odds of a subsequent compression was 7-fold higher (adjusted odds ratio, 7.0; 95% CI, 1.6-29.9) if initial CVR was > 0.4 vs CVR ≤ 0.4 cm2 .Conclusions: Predicted changes in CVR during pregnancy differ between cystic and hyperechoic malformations. This may be the result of different pathophysiological mechanisms or differences in the timing of occurrence of these different types of CPM. CVR measured at the initial diagnostic ultrasound examination was strongly associated with the odds of subsequent compression. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. OBJECTIVES: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter <10 (PM10) or <2.5µm (PM2.5) and DNA methylation in newborns and children. METHODS: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. RESULTS: Six CpGs were significantly associated [false discovery rate (FDR) <0.05] with prenatal PM10 and 14 with PM2.5 exposure. Two of the PM10-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p<0.05) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM10 exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM10 and or PM2.5 exposure, of which two PM10-related DMRs, including H19 and MARCH11, replicated in newborns. CONCLUSIONS: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. [ABSTRACT FROM AUTHOR]

Metaproteomics, the study of protein expression in microbial communities, is a versatile tool for environmental microbiology. Achieving sufficiently high metaproteome coverage to obtain a comprehensive picture of the activities and interactions in microbial communities is one of the current challenges in metaproteomics. An essential step to maximize the number of identified proteins is peptide separation via liquid chromatography (LC) prior to mass spectrometry (MS). Thorough optimization and comparison of LC methods for metaproteomics are, however, currently lacking. Here, we present an extensive development and test of different 1D and 2D-LC approaches for metaproteomic peptide separations. We used fully characterized mock community samples to evaluate metaproteomic approaches with very long analytical columns (50 and 75 cm) and long gradients (up to 12 h). We assessed a total of over 20 different 1D and 2D-LC approaches in terms of number of protein groups and unique peptides identified, peptide spectrum matches (PSMs) generated, the ability to detect proteins of low-abundance species, the effect of technical replicate runs on protein identifications and method reproducibility. We show here that, while 1D-LC approaches are faster and easier to set up and lead to more identifications per minute of runtime, 2D-LC approaches allow for a higher overall number of identifications with up to >10,000 protein groups identified. We also compared the 1D and 2D-LC approaches to a standard GeLC workflow, in which proteins are pre-fractionated via gel electrophoresis. This method yielded results comparable to the 2D-LC approaches, however with the drawback of a much increased sample preparation time. Based on our results, we provide recommendations on how to choose the best LC approach for metaproteomics experiments, depending on the study aims. [ABSTRACT FROM AUTHOR]

BACKGROUND: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols. OBJECTIVE: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental-to-birth weight ratio (PFR). METHODS: Placental weight and birth weight were available for 473 mother-son pairs in the EDEN (Etude des Déterminants pré et postnatals du développement et de la santé de l'Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders. RESULTS: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome. DISCUSSION: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother-child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. [ABSTRACT FROM AUTHOR]

The use of folic acid supplements before and during the first three months of pregnancy significantly reduces the risk of fetal neural tube defects (NTDs). This study assessed knowledge and factors that influence the use of folic acid, the actual use of folic acid and its relationship with socio-demographic factors among women of childbearing age in the Ife Central Local Government, Ile-Ife, Osun State, Nigeria. A cross-sectional descriptive design was adopted to select 400 women of childbearing age who participated in the study using a self-structured questionnaire. Results from this study showed that 39.8 per cent of the study participants had good knowledge about the benefits of folic acid, 64.6 per cent of the participants reported to have used folic acid at one time in their lives, while 55.5 per cent of them reported not to have taken folic acid before their pregnancy. This study also revealed a significant association between the respondents’ socio-demographic factors and the use of folic acid with a p-value of .000 (p-value < 0.05). The study concluded that knowledge about the use of folic acid for the prevention of NTDs among women of childbearing age is not adequate and that very few of them used folic acid at the appropriate time. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence, timing of diagnosis and infant mortality of congenital heart defects (CHD) with population-based data and using a classification that allows regrouping of the International Paediatric and Congenital Cardiac Code into a manageable number of categories based on anatomic and clinical criteria (ACC-CHD)., Design: Population-based cohort study., Setting: Greater Paris., Patients: All cases (live births, terminations of pregnancy for foetal anomaly (TOPFA), foetal deaths) diagnosed prenatally, or up to 1 year of age in the birth cohorts, May 2005-April 2008, for women in Greater Paris (n=317 538 births). Diagnoses were confirmed in specialised centres and subsequently coded and classified into the categories of ACC-CHD by paediatric cardiologists in the study group., Results: The total number of CHD was 2867, including 2348 live births (82%), 466 TOPFA (16.2%) and 53 foetal deaths (1.8%). The total prevalence of CHD was 90 per 10 000. After exclusion of ventricular septal defects (VSD), 40% of 'isolated' CHD was diagnosed prenatally with about one half of the remaining diagnosed before 7 days of age. Nevertheless, one in five cases of these major CHD was diagnosed after the fourth week. Infant mortality of 'isolated' CHD-VSD excluded was 8.5% with 40% of deaths occurring after the fourth week of life. These outcomes varied substantially across categories of ACC-CHD., Conclusions: Timing of diagnosis, TOPFA, risk and timing of infant mortality were highly variable across the categories of CHD in ACC-CHD, suggesting that it may be a useful measure of severity, and hence, predictor of outcomes of CHD.

Background and Objectives: Preterm birth (PTB) and congenital heart defect (CHD) are 2 major causes of mortality and disability of perinatal origin. There are limited data on the relation between CHD and PTB. Our objective was to use population-based data to estimate the risk of PTB in newborns with CHD and to study specific associations between categories of CHD and PTB., Methods: We used data from a population-based cohort study of CHD (EPIdémiologique sur le devenir des enfants porteurs de CARDiopathies congénitales study), including 2189 live births with CHD (excluding isolated atrial septal defects) born between 2005 and 2008. We categorized CHD by using an anatomic and clinical classification. Data from the French National Perinatal Survey of 2003 were used to compare PTB in the EPIdémiologique sur le devenir des enfants porteurs de CARDiopathies congénitales study to that of the general population., Results: Of the newborns with CHD, 13.5% were preterm. The odds of PTB were twofold higher than for the general population (odds ratio 2.0, 95% confidence interval 1.6-2.5), essentially due to an increase in spontaneous PTB for newborns with CHD. The risk of PTB associated with CHD persisted after exclusion of chromosomal or other anomalies. There were significant variations in risk of PTB across the categories of CHD after adjustment for known risk factors of PTB and factors related to medical management of pregnancy and delivery., Conclusions: We found a higher risk of PTB in newborns with CHD, which was essentially due to spontaneous PTB. Risk of PTB varied for categories of CHD. Our finding may be helpful for generating hypotheses about the developmental links between CHD and PTB.

Neuraminidase A (NanA) from the pathogenic bacteria Streptococcus pneumoniae catalyzes the cleavage of terminal sialic acid residues from oligosaccharide receptors on the surface of human respiratory epithelium cells and is considered to be the key virulence factor. The search for new regulatory ligand-binding sites in the structure of this enzyme is of fundamental interest and can reveal new targets to design drugs for treating pneumonia, meningitis, and other human infectious diseases. The low molecular weight compound optactin has been recently shown to inhibit the activity of the homologous Neuraminidase B (NanB). Furthermore, optactin binds at a separate site of the protein structure, which is topologically different from the catalytic center. The bioinformatic and structural analysis using the pocketZebra method was used to annotate a new, previously unknown site in the NanA structure. This new site is analogous to the optactin binding site in NanB and characterized by the high content of subfamily-specific positions, what indicates the importance of this site for the enzyme function. Molecular modeling was used to study optactin binding at the allosteric sites of the homologous neuraminidases NanA and NanB. Tyr250, Thr251, Lys334, Gln494, Lys499, Lys597, Thr657, and Glu658 residues were shown to stabilize the optactin molecule in the NanB structure, with water molecules playing an important role in the coordination of the ligand. Molecular modeling has shown that optactin binding by NanA is complicated due to substitutions in the subfamily-specific positions of the allosteric center. The peculiarities of the structural organization of the new NanA binding site facilitate the targeted search for complementary ligands that can selectively regulate the activity of this enzyme. [ABSTRACT FROM AUTHOR]

Abortion is a behavior that is stigmatized and difficult to measure. To improve reporting of abortion and other sensitive behaviors in the United States, the National Survey of Family Growth (NSFG) supplements the interviewer administered face-to-face (FTF) interview with audio computer-assisted self-interviewing (ACASI). This paper estimates differential reporting of abortion and other pregnancy outcomes (miscarriage, live birth) in the NSFG (2002, 2006-2010, 2011-2015) between women's ACASI and FTF interviews. Examining reporting of less stigmatized pregnancy outcomes can help understand the relative contributions of stigma and survey-level factors in reporting of abortions. More women reported abortions, miscarriages and births in the ACASI than the FTF interview. Differences in reporting were moderated by the length of recall. The ACASI elicited relatively more reporting of abortions and miscarriages among non-white and low-income women. Reporting ratios increased over time. ACASI is a tool that may work differently across time, for different measures, and with varying survey contexts. [ABSTRACT FROM AUTHOR]

Objective: Maternal thyroid dysfunction during pregnancy is associated with neurodevelopmental impairment in the offspring. No data are currently available for the offspring of patients treated early for congenital hypothyroidism (CH). The aim of this study was to investigate motor and language milestones at one year of age in a populationbased registry of children born to young women with CH. Design and methods: We assessed 110 children born to mothers with CH, and 1367 children from the EDEN French population-based birth cohort study prospectively, at the age of one year, with identical questionnaires. Outcomes were assessed in terms of scores for childhood developmental milestones relating to mobility, motor coordination, communication, motricity and language skills. Results: After adjustment for confounding factors, children born to mothers with CH were found to have a higher risk of poor motor coordination than those of the EDEN cohort (OR: 4.18, 95% CI: 2.52-6.93). No differences were identified for the other four domains investigated. Children born to mothers with gestational diabetes have a higher risk of low motor coordination score than their peers (OR: 2.10, 95% CI: 1.21-3.66). Children born to mothers with TSH = 10 IU/L during the first six months of pregnancy were more likely to have low motricity or communication skills scores than those born to mothers with lower TSH concentrations (56% vs 21% for each score, P < 0.04). Conclusions: Maternal CH may have slight adverse effects on some developmental milestones in the child at one year of age, particularly for children born to mothers with uncontrolled hypothyroidism. However, it remains unclear whether these adverse effects modify subsequent neurodevelopment. [ABSTRACT FROM AUTHOR]

The C-alkylpyrogallol[4]arene macrocycles are known to form self-assembled dimeric and hexameric nanocapsules. Several conformations of alkyl-substituted pyrogallol[4]arenes have been found to be thermodynamically stable, with the most stable structures typically being a chair and cone. However, experimental evidence suggests that aryl-substituted pyrogallol[4]arenes exist in the chair conformation, implying that because for nanocapsule formation the cone is the necessary conformer of the subunits of these capsules, the chair must undergo some transition to the cone. To benchmark the intrinsic behavior of these systems, we here use quantum chemical calculations and molecular dynamics simulations to (1) investigate conformers of the R=H system and their solvent interactions to understand the structures and their relative stabilities, (2) explore interconversions between conformers, and (3) gain preliminary insight into the mechanism by which self-assembly of the nanocapsule occurs. [ABSTRACT FROM AUTHOR]

The mass production of graphene and graphene oxide (GO) is essential for its use in commercial products. To improve its processing in the solution, dispersion behavior of graphene-based materials and their colloidal stability must be further understood. This study used all-atom molecular dynamics simulations to understand how electrostatics, van der Waals interactions, and hydrogen bonding affect the exfoliation and stability of three-layered graphene as a function of oxidation and solvent. Water, methanol, and ethanol were chosen as solvents due to their various dispersion behaviors. Our study indicated that (1) both surface oxidation level and solvent type can heavily influence the stability and (2) a decrease in interlayer vdW interactions, an increase in GO–solvent electrostatic interactions, and an increase in GO–solvent hydrogen bonding are important factors that can facilitate the dissolution of GO. [ABSTRACT FROM AUTHOR]

Amyloid peptide fibrillogenesis induced by Cu(II) ions is a key event in the pathogenesis of Alzheimer's disease. Dendrimers have been found to be active in preventing fibril formation. Therefore, they hold promise for the treatment of Alzheimer's disease. In this study, the fibrillation mechanism of amyloid peptide Aβ 1-40 was studied by adding Cu(II) in the absence and presence of 4 generation poly(propyleneimine) glycodendrimer functionalized with sulfate groups, using dynamic light scattering (DLS), circular dichroism (CD), fluorescence, electron paramagnetic resonance (EPR) and molecular modeling (MD). The glycodendrimer was non-toxic to mHippoE-18 embryonic mouse hippocampal cells, selected as a nerve cell model, and decreased the toxicity of peptide aggregates formed after the addition of Cu(II). The binary systems of Cu(II)-glycodendrimer, Cu(II)-peptide, and glycodendrimer-peptide were first characterized. At the lowest Cu(II)/glycodendrimer molar ratios, Cu(II) was complexed by the internal-dendrimer nitrogen sites. After saturation of these sites, Cu(II) binding with sulfate groups occurred. Stable Cu(II)-peptide complexes formed within 5 min and were responsible for a transition from an α helix to a β-sheet conformation of Aβ 1-40. Glycodendrimer-peptide interactions provoked the stabilization of the α-helix, as demonstrated in the absence of Cu(II) by the Thioflavin T assay, and in the presence of Cu(II) by CD, EPR, and MD. Formation of fibrils is differentially modulated by glycodendrimer and Cu(II) concentrations for a fixed amount of Aβ 1-40. Therefore, this multidisciplinary study facilitated the recognition of optimal experimental conditions that allow the glycodendrimer to avoid the fibril formation induced by Cu(II). [ABSTRACT FROM AUTHOR]

BACKGROUND: Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. OBJECTIVES: We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. METHODS: Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. RESULTS: At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR) = 1.67 [95% confidence interval (CI): 1.10, 2.54], p = 0.01 and HR = 1.87 (95% CI: 1.01, 3.48), p = 0.04, respectively}. CONCLUSIONS: Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. [ABSTRACT FROM AUTHOR]

The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic glutamine provided in cis by the GTPase and an arginine supplied in trans by a GTPase activating protein ( GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis. As the cis-Gln encounters a steric clash, the Rab GTPases employ the so-called dual finger mechanism where the interacting GAP supplies a trans-Gln for catalysis. Using experimental and computational methods, we demonstrate how the cis-Gln of Rab33 overcomes the steric clash when it is stabilized by a residue in the vicinity. In effect, this demonstrates how both cis-Gln- and trans-Gln-mediated mechanisms could operate in the same GTPase in different contexts, i.e. depending on the GAP that regulates its action. Interestingly, in the case of Rab5, which possesses a higher intrinsic GTP hydrolysis rate, a similar stabilization of the cis-Gln appears to overcome the steric clash. Taken together with the mechanisms seen for Rab1, it is evident that the observed variations in Rab and their GAP partners allow structural plasticity, or in other words, the choice of different catalytic mechanisms. [ABSTRACT FROM AUTHOR]

Sulfated quercetin derivatives are important authentic standards for metabolic studies. Quercetin-3'-O-sulfate, quercetin-4'-O-sulfate, and quercetin-3-O-sulfate as well as quercetin-di-O-sulfate mixture (quercetin-7,3'-di-O-sulfate, quercetin-7,4'-di-O-sulfate, and quercetin- 3',4'-di-O-sulfate) were synthetized by arylsulfotransferase from Desulfitobacterium hafniense. Purified monosulfates and disulfates were fully characterized using MS and NMR and tested for their 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) and N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging, Folin-Ciocalteau reduction (FCR), ferric reducing antioxidant power (FRAP), and anti-lipoperoxidant activities in rat liver microsomes damaged by tert-butylhydroperoxide. Although, as expected, the sulfated metabolites were usually less active than quercetin, they remained still effective antiradical and reducing agents. Quercetin-3'-O-sulfate was more efficient than quercetin-4'-O-sulfate in DPPH and FCR assays. In contrast, quercetin-4'-O-sulfate was the best ferric reductant and lipoperoxidation inhibitor. The capacity to scavenge ABTS+• and DMPD was comparable for all substances, except for disulfates, which were the most efficient. Quantum calculations and molecular dynamics simulations on membrane models supported rationalization of free radical scavenging and lipid peroxidation inhibition. These results clearly showed that individual metabolites of food bioactives can markedly differ in their biological activity. Therefore, a systematic and thorough investigation of all bioavailable metabolites with respect to native compounds is needed when evaluating food health benefits. [ABSTRACT FROM AUTHOR]

The present study aims to determine to which extent social withdrawal at 1 year is associated with the child's IQ at the end of the preschool period. Children ( N = 1045) from the EDEN mother-child cohort were assessed for social withdrawal behaviours at 1 year by trained midwives using the Alarm Distress BaBy (ADBB) scale. Midwives also examined infants' language and motor development at 1 year. At the age 5-6 years, IQ scores were based on the WPPSI-III. Linear regression models were used to determine the association between IQ and ADBB, adjusted for a broad range of pre- and postnatal environmental factors and for language and motor skills scores at 1 year. After adjusting for environmental factors, children with social withdrawal at 1 years (ADBB ≥5; N = 195) had significantly lower IQ scores at 5-6 years (−2.81 IQ points; p value 0.007) compared to children without social withdrawal (ADBB <5; N = 847). When motor and language skills at 1 year were included in the previous model, no association between social withdrawal and IQ at 5-6 years was found. Being socially withdrawn at 1 year is associated with lower IQ scores at 5-6 years. The potential influence of these developmental aspects on each other (withdrawal behaviour and language/motor skills) may occur early in development. Our results improve our understanding of the outcomes of early social withdrawal behaviour and call for early detection of delay in acquisition of language/motor skills among socially withdrawn young children. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health. OBJECTIVE: We estimated the associations between gestational exposure to select phthalates and phenols and respiratory health in boys. METHODS: Among 587 pregnant women from the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l’Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s (FEV1) was measured by spirometry. Adjusted associations of urinary metabolites log–transformed concentrations with respiratory outcomes and FEV1 in percent predicted (FEV1%) were estimated by survival and linear regression models, respectively. RESULTS: No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate [hazard rate (HR)=1.10; 95% confidence interval (CI): 1.00, 1.21] and tended to be negatively associated with FEV1% (beta=−0.59; 95% CI: −1.24, 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (HR=1.23; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (HR=1.13; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing. CONCLUSION: Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. OBJECTIVES: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. METHODS: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. RESULTS: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity-inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. CONCLUSIONS: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose-response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. [ABSTRACT FROM AUTHOR]

ABSTRACT Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet dual inhibitors are challenging to design due to differences in the conformations of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99. Analysis of crystal structures and molecular dynamics (MD) simulations of complexes of Mdm2 and MdmX resulted in the identification of a water molecule with a long residence time that appears to be modulated by the conformation of Y100/99. These observations lead us to speculate that dual inhibitors either (i) stabilize both Mdm2 and MdmX with Y100/99 in the open conformation typically seen in complexes of Mdm2 with p53, or (ii) the dual inhibitors are agnostic to the conformation of Y100/99. The recently developed potent dual inhibitory stapled peptide Atsp7041 appears to be agnostic to the conformation of the gatekeeper residue. Proteins 2017; 85:1493-1506. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives As early-life feeding experiences may influence later health, we aimed to examine relations between feeding patterns over the first year of life and child's growth in the first 5 years of life. Methods Our analysis included 1022 children from the EDEN mother-child cohort. Three feeding patterns were previously identified, i.e. 'Later dairy products introduction and use of ready-prepared baby foods' (pattern-1), 'Long breastfeeding, later main meal food introduction and use of home-made foods' (pattern-2) and 'Use of ready-prepared adult foods' (pattern-3). Associations between the feeding patterns and growth [weight, height and body mass index {BMI}] were analysed by multivariable linear regressions. Anthropometric changes were assessed by the final value adjusted for the initial value. Results Even though infant feeding patterns were not related to anthropometric measurements at 1, 3 and 5 years, high scores on pattern-1 were associated with higher 1-3 years weight and height changes. High scores on pattern-2 were related to lower 0-1 year weight and height changes, higher 1-5 years weight and height changes but not to BMI changes, after controlling for a wide range of potential confounding variables including parental BMI. Scores on pattern-3 were not significantly related to growth. Additional adjustment for breastfeeding duration reduced the strength of the associations between pattern-2 and growth but not those between pattern-1 and height growth. Conclusion Our findings emphasize the relevance of considering infant feeding patterns including breastfeeding duration, age of complementary foods introduction as well as type of foods used when examining effects of early infant feeding practices on later health. © 2017 World Obesity Federation [ABSTRACT FROM AUTHOR]