Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Early life environmental exposure in relation to new onset and remission of allergic diseases in school children: Polish Mother and Child Cohort Study.

Background: This study was based on data from the Polish Mother and Child Cohort Study. Objective: The aim was to study associations between home environment factors and allergic diseases at 1 year of life and new onset and remission of children's allergy diagnosis at ages 7-9 years. Methods: Children's health status was assessed at ∼12 months of age and then at ages between 7-9 years by using a questionnaire administered to the mothers. Children were assessed by pediatrician/allergists. The patients, who were 7-9 years old, underwent skin-prick tests. Exposure to tobacco smoke was evaluated with a questionnaire addressed to parents and/or caregivers and cotinine measurements were taken of mother's saliva during pregnancy and in children's urine at ages 7-9 years. Incidence and remission were calculated by comparing symptoms in the first year of life with symptoms at 7-9 years. We studied the associations among demographic data, home environment, and new onset and remission of food allergy, atopic dermatitis, and asthma and allergic rhinitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Results: Data from 211 participants were included in the analysis. During the first year of life, food allergy was the most common symptom (39%), followed by atopic dermatitis (35%) and asthma (12%). When comparing diagnoses at ages 7-9 years with the first year of life, food allergy had decreased by as much as 18.6%, atopic dermatitis decreased by as much as 23.8%, and asthma decreased by as much as 8%, whereas asthma and allergic rhinitis had increased from 6% to 14.8%. More frequent house cleaning negatively correlated with the new onset of atopic dermatitis and of asthma and allergic rhinitis. Hypersensitivity to seasonal allergens and mites and to any other allergen positively correlated with new onset of food allergy, atopic dermatitis, and asthma and allergic rhinitis. Parental atopy positively correlated with the new onset of asthma and negatively correlated with asthma remission. Conclusion: Analysis of our findings indicated that new onset and/or remission of allergic diseases was linked with hypersensitivity to house-dust mites in children who were polysensitized and with parental atopy. In addition, children who had food allergy, allergic rhinitis, or atopic dermatitis at the age of 1 year had more of a chance developing other atopic disease (except asthma) at ages 7-9 years and less of a chance of having a remission of the disease.

Prenatal and postnatal exposure to polycyclic aromatic hydrocarbons and allergy symptoms in city children.

BACKGROUND: Studies indicate that exposure to polycyclic aromatic hydrocarbons (PAH) is associated with adverse respiratory and allergy outcomes. Exposure to PAH may impair the immune function of the foetus and, subsequently, be responsible for an increased susceptibility of children to allergic diseases. OBJECTIVES: The aim of the present study was to assess the association between mother's exposure to PAH during pregnancy and allergy diseases in their infants. We also assessed the above associations using measured PAH exposure in children's urine during the first two years of life. METHODS: The current analysis was restricted to 455 mothers and their children from Lodz district. The women were interviewed three times during the pregnancy in order to collect demographic, socio-economic and medical history data. Children's health status was assessed at the age of 10-18 months and repeated at two years of age. The associations between dependent dichotomous variables and urine concentrations of 1-hydroxypyrene (1-HP) were analysed using logistic regression. RESULTS: We showed that higher urine concentrations of 1-HP in mothers at 20-24 weeks of pregnancy increased the risk of more frequent respiratory infections (p=0.02) in children during their first year of life. Higher 1-HP concentrations in children's urine increased the risk of food allergy (p=0.002) in children during their first two years of life. CONCLUSIONS: This study suggests awareness of environmental factors, which may affect children's health since PAH showed to be a risk factor for airway infections and food allergy in children after adjustment for other risk factors.

Triangular Spin-Orbit-Coupled Lattice with Strong Coulomb Correlations: Sn Atoms on a SiC(0001) Substrate.

Two-dimensional (2D) atom lattices provide model setups with Coulomb correlations that induce competing ground states. Here, SiC emerges as a wide-gap substrate with reduced screening. We report the first artificial high-Z atom lattice on SiC(0001) by Sn adatoms, based on experimental realization and theoretical modeling. Density-functional theory of our triangular structure model closely reproduces the scanning tunneling microscopy. Photoemission data show a deeply gapped state (∼2 eV gap), and, based on our calculations including dynamic mean-field theory, we argue that this reflects a pronounced Mott-insulating scenario. We also find indications that the system is susceptible to antiferromagnetic superstructures. Such artificial lattices on SiC(0001) thus offer a novel platform for coexisting Coulomb correlations and spin-orbit coupling, with bearing for unusual magnetic phases and proposed topological quantum states of matter.

Occupational, life stress and family functioning: does it affect semen quality?

BACKGROUND AND AIMS: Although psychological stress has been implicated as a cause of idiopathic infertility in both men and women, it has received little scientific attention among males as compared to females. The aim of the study was to examine the association between occupational, life stress, family functioning and semen quality. METHODS AND RESULTS: The study population consisted of 327 men who were attending an infertility clinic for diagnostic purposes. Psychological stress was assessed based on two questionnaires: The Subjective Work Characteristics Questionnaire and the Perceived Stress Scale. The level of satisfaction with family functioning and support was evaluated by means of the APGAR Family Scale. The findings suggest that, on the one hand, exposure to occupational stressors can be negatively associated with semen quality (there was a positive association between stress and the percentage of sperm with DNA damage (p = 0.03) and atypical sperm (p = 0.05)); on the other hand, there was no correlation between the level of life stress and semen quality indicators. Negative associations were found between satisfaction with family functioning and the percentage of motile sperm cells (p = 0.02), VAP (p = 0.05), VSL (p = 0.05) and VCL (p = 0.04). CONCLUSION: The study indicates that occupational stress can affect male semen quality; however, due to limited data on this issue, the obtained results should be confirmed in longitudinal studies.

Elemental topological insulator with tunable Fermi level: strained α-Sn on InSb(001).

We report on the epitaxial fabrication and electronic properties of a topological phase in strained α-Sn on InSb. The topological surface state forms in the presence of an unusual band order not based on direct spin-orbit coupling, as shown in density functional and GW slab-layer calculations. Angle-resolved photoemission including spin detection probes experimentally how the topological spin-polarized state emerges from the second bulk valence band. Moreover, we demonstrate the precise control of the Fermi level by dopants.

Three-dimensional spin rotations at the Fermi surface of a strongly spin-orbit coupled surface system.

The spin texture of the metallic two-dimensional electron system (sqrt[3]×sqrt[3])-Au/Ge(111) is revealed by fully three-dimensional spin-resolved photoemission, as well as by density functional calculations. The large hexagonal Fermi surface, generated by the Au atoms, shows a significant splitting due to spin-orbit interactions. The planar components of the spin exhibit a helical character, accompanied by a strong out-of-plane spin component with alternating signs along the six Fermi surface sections. Moreover, in-plane spin rotations toward a radial direction are observed close to the hexagon corners. Such a threefold-symmetric spin pattern is not described by the conventional Rashba model. Instead, it reveals an interplay with Dresselhaus-like spin-orbit effects as a result of the crystalline anisotropies.

Glycated and carbamylated albumin are more "nephrotoxic" than unmodified albumin in the amphibian kidney.

There is increasing evidence that proteins in tubular fluid are "nephrotoxic." In vivo it is difficult to study protein loading of tubular epithelial cells in isolation, i.e., without concomitant glomerular damage or changes of renal hemodynamics, etc. Recently, a unique amphibian model has been described which takes advantage of the special anatomy of the amphibian kidney in which a subset of nephrons drains the peritoneal cavity (open nephrons) so that intraperitoneal injection of protein selectively causes protein storage in and peritubular fibrosis around open but not around closed tubules. There is an ongoing debate as to what degree albumin per se is nephrotoxic and whether modification of albumin alters its nephrotoxicity. We tested the hypothesis that carbamylation and glycation render albumin more nephrotoxic compared with native albumin and alternative albumin modifications, e.g., lipid oxidation and lipid depletion. Preparations of native and modified albumin were injected into the axolotl peritoneum. The kidneys were retrieved after 10 days and studied by light microscopy as well as by immunohistochemistry [transforming growth factor (TGF)-ß, PDGF, NF-κB, collagen I and IV, RAGE], nonradioactive in situ hybridization, and Western blotting. Two investigators unaware of the animal groups evaluated and scored renal histology. Compared with unmodified albumin, glycated and carbamylated albumin caused more pronounced protein storage. After no more than 10 days, selective peritubular fibrosis was seen around nephrons draining the peritoneal cavity (open nephrons), but not around closed nephrons. Additionally, more intense expression of RAGE, NF-κB, as well as PDGF, TGF-ß, EGF, ET-1, and others was noted by histochemistry and confirmed by RT-PCR for fibronectin and TGF-ß as well as nonradioactive in situ hybridization for TGF-ß and fibronectin. The data indicate that carbamylation and glycation increase the capacity of albumin to cause tubular cell damage and peritubular fibrosis.

Hydrodynamic determination of the moving direction of an artificial fin by a harbour seal (Phoca vitulina).

Harbour seals can use their vibrissal system to detect and follow hydrodynamic trails left by moving objects. In this study we determined the maximum time after which a harbour seal could indicate the moving direction of an artificial fish tail and analysed the hydrodynamic parameters allowing the discrimination. Hydrodynamic trails were generated using a fin-like paddle moving from left to right or from right to left in the calm water of an experimental box. The blindfolded seal was able to recognise the direction of the paddle movement when the hydrodynamic trail was up to 35 s old. Particle Image Velocimetry (PIV) revealed that the seal might have perceived and used two different hydrodynamic parameters to determine the moving direction of the fin-like paddle. The structure and spatial arrangement of the vortices in the hydrodynamic trail and high water velocities between two counter-rotating vortices are characteristic of the movement direction and are within the sensory range of the seal.

The impact of glide phases on the trackability of hydrodynamic trails in harbour seals (Phoca vitulina).

The mystacial vibrissae of harbour seals (Phoca vitulina) constitute a highly sensitive hydrodynamic receptor system enabling the seals to detect and follow hydrodynamic trails. In the wild, hydrodynamic trails, as generated by swimming fish, consist of cyclic burst-and-glide phases, associated with various differences in the physical parameters of the trail. Here, we investigated the impact of glide phases on the trackability of differently aged hydrodynamic trails in a harbour seal. As fish are not easily trained to swim certain paths with predetermined burst-and-glide phases, the respective hydrodynamic trails were generated using a remote-controlled miniature submarine. Gliding phases in hydrodynamic trails had a negative impact on the trackability when trails were 15 s old. The seal lost the generated trails more often within the transition zones, when the submarine switched from a burst to a glide moving pattern. Hydrodynamic parameter analysis (particle image velocimetry) revealed that the smaller dimensions and faster decay of hydrodynamic trails generated by the gliding submarine are responsible for the impaired success of the seal tracking the gliding phase. Furthermore, the change of gross water flow generated by the submarine from a rearwards-directed stream in the burst phase to a water flow passively dragged behind the submarine during gliding might influence the ability of the seal to follow the trail as this might cause a weaker deflection of the vibrissae. The possible ecological implications of intermittent swimming behaviour in fish for piscivorous predators are discussed.

Hydrodynamic trail-following in harbor seals (Phoca vitulina).

Marine mammals often forage in dark or turbid waters. Whereas dolphins use echolocation under such conditions, pinnipeds apparently lack this sensory ability. For seals hunting in the dark, one source of sensory information may consist of fish-generated water movements, which seals can detect with their highly sensitive whiskers. Water movements in the wake of fishes persist for several minutes. Here we show that blindfolded seals can use their whiskers to detect and accurately follow hydrodynamic trails generated by a miniature submarine. This shows that hydrodynamic information can be used for long-distance prey location.

Bismuthene on a SiC substrate: A candidate for a high-temperature quantum spin Hall material.

Quantum spin Hall materials hold the promise of revolutionary devices with dissipationless spin currents but have required cryogenic temperatures owing to small energy gaps. Here we show theoretically that a room-temperature regime with a large energy gap may be achievable within a paradigm that exploits the atomic spin-orbit coupling. The concept is based on a substrate-supported monolayer of a high-atomic number element and is experimentally realized as a bismuth honeycomb lattice on top of the insulating silicon carbide substrate SiC(0001). Using scanning tunneling spectroscopy, we detect a gap of ~0.8 electron volt and conductive edge states consistent with theory. Our combined theoretical and experimental results demonstrate a concept for a quantum spin Hall wide-gap scenario, where the chemical potential resides in the global system gap, ensuring robust edge conductance.

Sperm DNA damage-the effect of stress and everyday life factors.

The clinical significance of sperm DNA damage lies in its association with natural conception rates and also might have a serious consequence on developmental outcome of the newborn. The aim of the present study is to determine whether stress and everyday life factors are associated with sperm DNA damage in adult men. The study population consisted of 286 men who attended the infertility clinic for diagnostic purposes and who had normal semen concentration of 20-300 m ml(-1) or with slight oligozoospermia (semen concentration of 15-20 m ml(-1)) (WHO, 1999). Participants were interviewed and provided a semen sample. The sperm chromatin structure assay was assessed using flow cytometry. In the present study, we found evidence for a relationship between sperm DNA damage parameters and everyday life factors. High and medium level of occupational stress and age increase DNA fragmentation index (P=0.03, P=0.004 and P=0.03, respectively). Other lifestyle factors that were positively associated with percentage of immature sperms (high DNA stainability index) included: obesity and cell phone use for more than 10 years (P=0.02 and P=0.04, respectively). Our findings indicate that stress and lifestyle factor may affect sperm DNA damage. Data from the present study showed a significant effect of age, obesity, mobile phone radiation and occupational stress on sperm DNA damage. As DNA fragmentation represents an extremely important parameter indicative of infertility and potential outcome of assisted reproduction treatment, and most of the lifestyle factors are easily modifiable, the information about factors that may affect DNA damage are important.

The lowest conductance state of the alamethicin pore.

High resolution experiments of the alamethicin pore demonstrate the existence of a further pore state at low conductance values. This lowest resolved conductance state is found at 19 pS in 1 M KCl at room temperature. The value differs from that of the next higher conductance state by a factor of 14--15 and is approx. 20% lower than the gramicidin A pore conductance. The lowest conductance state seems to be impermeable to Ca2+, Cl-, Tris-H+ and Hepes-, whereas the higher conductance states are not.

Pore-forming protein from Entamoeba histolytica forms voltage- and pH-controlled multi-state channels with properties similar to those of the barrel-stave aggregates.

Pore-forming protein from Entamoeba histolytica forms cation-selective channels in planar bilayers. With increasing potentials, the open-state probability of these channels decreases, and channel aggregates collapse (Young, J.D.-E. and Cohn, Z.A. (1985) J. Cell. Biochem. 29, 299-308). In this communication we report the following observations: (i) incorporation of the pore in black-lipid membranes was stimulated by membrane potential, (ii) pores were rectifying, (iii) breakdown of pores resulted in a continuous spectrum of subconductance states, (iv) the open-state probability increased strongly with pH. This pattern of behaviour is similar to that of the barrel-stave aggregates (alamethicin and related toxins). We therefore conclude that the amebal pores, like those of the barrel-stave class, may consist of complexes involving variable numbers of membrane-spanning subunits.

Melittin and a chemically modified trichotoxin form alamethicin-type multi-state pores.

The bee venom constituent, melittin, is structurally and functionally related to alamethicin. By forming solvent-free planar bilayers of small area (approx. 100 microns 2) on the tip of fire-polished glass pipettes we could observe single melittin pores in these membranes. An increase in the applied voltage induced further non-integral conductance levels. This indicates that melittin forms multi-level pores similar to those formed by alamethicin. Trichotoxin A40, an antibiotic analogue of alamethicin, also induces a voltage-dependent bilayer conductivity, but no stable pore states are resolved. However, chemical modification of the C-terminal molecule part by introduction of a dansyl group leads to a steeper voltage-dependence and pore state stabilization. Comparing structure and activity of several natural and synthetic amphiphilic polypeptides, we conclude that a lipophilic, N-terminal alpha-helical part of adequate length (dipole moment) and a large enough hydrophilic, C-terminal region are sufficient prerequisites for voltage-dependent formation of multi-state pores.

Characterization of the channel properties of a neuronal acetylcholine receptor reconstituted into planar lipid bilayers.

An alpha-toxin-binding membrane protein, isolated from the head and thoracic ganglia of the locus (Locusta migratoria), was reconstituted into planar lipid bilayers. Cholinergic agonists such as acetylcholine, carbamylcholine, and suberyldicholine induced fluctuations of single channels, which suggests that the protein represents a functional cholinergic receptor channel. The antagonist d-tubocurarine blocked the activation of the channels, whereas hexamethonium had only a weak effect; similar properties have been described for nicotinic insect receptors in situ. The channel was selectively permeable to monovalent cations but was impermeable to anions. The conductance of the channel (75 pS in 100 mM NaCl) was independent of the type of agonist used to activate the receptor. Kinetic analysis of the channel gating revealed that, at high agonist concentrations (50 microM carbamylcholine), more than one closed state exists and that multiple gating events, bursting as well as fast flickering, appeared. At very high agonist concentrations (500 microM carbamylcholine), desensitization was observed. Channel kinetics were dependent on the transmembrane potential. Comparing the conductance, the kinetics, and the pharmacology of nicotinic acetylcholine receptor from insect ganglia and fish electroplax reconstituted into bilayers revealed obvious similarities but also significant differences.

Single chloride channels from Torpedo electroplax. Activation by protons.

Single-channel fluctuations of a chloride-specific channel from Torpedo californica electroplax were studied with high current and time resolution. Channels were incorporated into virtually solvent-free planar bilayer membranes formed from phospholipid monolayers, and the substructure of the open channel was analyzed. The single channel displays three well-defined substates of conductances 0, 10, and 20 pS in 200 mM Cl-. These three substates are interpreted in terms of a dimeric channel complex composed of two identical "protochannels" gating independently in parallel on a time scale of milliseconds, but coupled together by a bursting process on a time scale of seconds. The probability of forming an open protochannel is voltage dependent and is increased strongly as aqueous pH is lowered. Variations of pH are effective only on the same side of the bilayer as the addition of electroplax vesicles. The dependence of single-channel kinetics on pH and voltage lead to a minimal four-state model in which both open and closed states can be protonated on a residue that changes its pK from 6 to 9 upon opening of the protochannel.

Reconstitution of acetylcholine receptors into planar lipid bilayers.

Obviously, bilayer reconstitution experiments have largely contributed to the understanding of the AChR-channel function. Nevertheless, at present there are many unanswered questions concerning the minimum structural requirements for AChR-channel function, agonist cooperativity, and different types of AChR. Another complex of parameters important for receptor function which must be explored in much more detail, is the dependence of AChR-channel function on membrane composition and its physical state. This important but rather neglected field is predestined to be explored by reconstitution techniques. All the results on AChRs reconstituted in planar lipid bilayers cannot adequately be discussed without the data obtained by other techniques, thus coming back to the statements already mentioned in the introductory section about strategies for investigating ion channels in general. Only such a strategy can lead to a molecular understanding of channel function.