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The determination of molar masses and their distributions is crucial in polymer synthesis and design. This work presents the current performance and limitations of diffusion-ordered spectroscopy (DOSY) on a low-field (benchtop) NMR spectrometer (at 90 MHz) as an alternative to size exclusion chromatography (SEC) for determining diffusion coefficient distributions (DCDs) and molar mass distributions (MMDs). After optimization for narrowly distributed homopolymers, MMDs obtained with inverse Laplace transformation (ILT) and log-normal distribution are compared with average molar masses obtained with mono- and bi-exponential fits, as well as MMDs obtained from SEC. This approach enables ILT to determine DCDs and MMDs even for bimodal homopolymers with fully spectrally overlapping signals and block copolymers with various chemical compositions, for which chemical composition profiles are determined. The feasibility of low-field diffusion NMR with samples dissolved in non-deuterated solvents is further demonstrated and methods for solvent suppression are discussed., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

In response to nutrients, intestinal L- and K-cells naturally secrete glucagon-like peptide 1 (GLP-1). GLP-1 regulates postprandial blood glucose by increasing insulin secretion, slowing down gastric emptying and inducing satiety. A selection of specifically developed collagen hydrolysates was screened for their ability to enhance natural GLP-1 production in vitro. The best performing hydrolysate, H80 (Nextida GC), was orally administered at different doses to lean, normoglycemic mice and overweight, prediabetic mice. Lean mice were acutely challenged 45 min before an oral glucose load. While daily supplemented for 6 weeks, prediabetic mice were acutely challenged at day 21 and 34. Oral glucose tolerance, plasma insulin and GLP-1 levels were assessed, and a gastric emptying assay performed in prediabetic mice. H80 significantly lowered the blood glucose response in lean and prediabetic mice, at a 4 g/kg dose (-25% and -36%, respectively), compared to vehicle. In chronically supplemented, prediabetic mice, acute H80 administration slowed down gastric emptying (-60%) after 21 days and increased plasma insulin (+166%) after 35 days of supplementation. H80 increased plasma active GLP-1 in lean (+217%) and prediabetic (+860%) mice. Overall, the data indicate that the specific collagen hydrolysate, H80, has significant GLP-1-mediated effects on oral glucose tolerance in lean and prediabetic mice. Furthermore, effects on postprandial glucose tolerance were evaluated in a small, human, proof of concept study. H80 reduced the postprandial glucose response at a 5 g dose in healthy, normoglycemic and prediabetic participants. Oral supplementation with H80 might thus be a promising strategy to maintain normal glucose tolerance., Competing Interests: Elien Gevaert, Sara Vleminckx, Janne Prawitt and Nicolina Virgilio are employees of Rousselot BV. Estelle Grasset, François Briand, Thierry Sulpice are employees of Physiogenex SAS, Christiane Schön is an employee of BioTeSys GmbH., (© 2024 Rousselot BV. Food Science & Nutrition published by Wiley Periodicals LLC.)

The onflow hyphenation of high-performance liquid chromatography (HPLC) in adsorption mode with a benchtop 1 H nuclear magnetic resonance (NMR) spectrometer is described for the first time. Protonated solvents and isocratic conditions are used. The sensitivity was increased by choosing suitable NMR acquisition parameter as well as optimizing injection parameters and postacquisition data processing methods. With optimized conditions, the limit of detection (LOD) and the limit of quantification (LOQ) were LOD = 0.010 g L -1 and LOQ = 0.031 g L -1 for the methoxy 1 H of methyl paraben at 4.07 ppm, LOD = 0.038 g L -1 and LOQ = 0.134 g L -1 for the aromatic 1 H of pentyl paraben between 7.00 and 8.50 ppm. These are expressed in injection concentration and are comparable to existing HPLC hyphenation with high-field NMR spectrometers. The analysis of a 2 g L -1 paraben mixture, far below the legal limits for usage in cosmetics, illustrates the applicability of the method. Taking advantage of the spectral resolution, chromatographically overlapping peaks are resolved using analyte-specific NMR elution traces. A methodology is detailed to facilitate the transfer of the optimized method to other (analyte) systems.

Previous studies have shown that the nonlinear rheological behavior of 3-arm star polymer melts in fast extensional flow is identical to that of linear polymers with the same span molecular weight, because the star polymers are highly aligned and have a similar conformation as the corresponding linear polymers. However, with more arms, it would be more difficult for the stars to be aligned like linear chains, and the nonlinear extensional rheology of star polymers with more arms under large deformations has not been investigated yet. Here we show that the star polystyrene (8-10 arms) melts behave differently from the linear polystyrenes. A transient stress overshoot is observed in the fast extensional flow, probably due to the difference in entanglement density near and far away from the branch point.

Beneficial health effects of omega-3 polyunsaturated fatty acids ( n -3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n -3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n -3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n -3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n -3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation.

We present a model-driven predictive scheme for the uniaxial extensional viscosity and strain hardening of branched polymer melts, specifically for the pom-pom architecture, using the small amplitude oscillatory shear mastercurve and the polymer architecture. A pom-pom shaped polymer is the simplest architecture with at least two branching points, needed to induce strain hardening. It consists of two stars, each with q arms of the molecular weight M w , a , connected by a backbone of M w , b . Despite the pom-pom constitutive model, experimental data of systematic investigations lack due to synthetic complexity. With an optimized approach, we synthesized polystyrene pom-pom model systems with systematically varied M w , a and M w , b . Experimentally, we identify four characteristic strain rate dependent regimes of the extensional viscosity, which can be predicted from the rheological mastercurve. Furthermore, we find that the industrially important maximum strain hardening factor depends only on the arm number by [ q 2 / ln ( 3 q ) ] . This framework offers a model-based design of branched polymers with predictable melt flow behavior., (© 2024. The Author(s).)

Pluronic (Plu) hydrogels mixed with variable fractions of Pluronic diacrylate (PluDA) have become popular matrices to encapsulate bacteria and control their growth in engineered living materials. Here we study the rheological response of 30 wt% Plu/PluDA hydrogels with PluDA fraction between 0 and 1. We quantify the range of viscoelastic properties that can be covered in this system by varying in the PluDA fraction. We present stress relaxation and creep-recovery experiments and describe the variation of the critical yield strain/stress, relaxation and recovery parameters of Plu/PluDA hydrogels as function of the covalent crosslinking degree using the Burgers and Weilbull models. The analyzed hydrogels present two stress relaxations with different timescales which can be tuned with the covalent crosslinking degree. We expect this study to help users of Plu/PluDA hydrogels to estimate the mechanical properties of their systems, and to correlate them with the behaviour of bacteria in future Plu/PluDA devices of similar composition.

Superabsorbers based on crosslinked sodium polyacrylate polymers cannot be easily recycled, resulting in 2 million tons of superabsorbers being landfilled or burned every year. A fast and efficient strategy to recycle superabsorbers would significantly alleviate environmental pollution and promote a sustainable use of these polymers. Herein, the rapid recycling of crosslinked sodium polyacrylate hydrogels based on their inherent UV degradation is demonstrated without the need for chemicals besides water. A quantitative conversion of crosslinked sodium polyacrylate into soluble sodium polyacrylate is achieved in minutes, almost 200 times faster than a previous approach based on de-esterification. The obtained soluble sodium polyacrylate can be used, for example, as a thickener for aqueous dyes or can be esterified with n -butanol or 2-ethylhexanol to serve as a pressure-sensitive adhesive. The UV photodegradation and esterification of superabsorbers is fast, scalable, safe, and economical and yields polymers with controllable molecular weight in the range of 100-400 kg/mol. It thus offers distinct advantages over the chemical de-crosslinking strategies presented previously.

Background: Digital cytology (DC) with artificial intelligence (AI) is a new approach. The authors compared DC with liquid-based cytology (LBC) using computer assistance (CAS) in a retrospective, noninterventional study., Methods: In total, 1994 ThinPrep LBC slides (Hologic), which were previously analyzed in 2020 using an imaging system with CAS in routine cotesting for cytology/human papillomavirus, were reviewed in a blinded mode using the Genius Digital Diagnostics System (Hologic). In 555 cases, a histology result was available. The slides were digitally scanned (volumetric scan) at 14 levels integrated into one. AI algorithms were used to present a gallery of six tiles each (containing objects of interest) in five categories. Six additional tile rows were available, from which the diagnoses were made. All cases with a mismatch between DC and imaging system results were reviewed by an additional cytopathologist., Results: In 86.56% of cases, a complete match between both systems was observed using the same cytology categories. When also considering the histology results, the match was 90.37%. In addition, when a cytology follow-up and/or a retrospective review was applied, the match reached 97.34%. In only 0.65% of cases was a major discrepancy observed (two grades of cytology or a low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion [LSIL/HSIL] shift), and none were identified by DC. Significantly more cases of higher severity (atypical squamous cells cannot exclude high grade [ASC-H], high-grade squamous intraepithelial lesion [HSIL]) were identified with DC, and its negative predictive value was higher. The screening time was significantly shorter with DC., Conclusions: With the Genius system for DC, the sensitivity for HSIL+/ASC-H and the specificity for LSIL and HSIL were superior to LBC and CAS. Screening time was significantly lower., (© 2023 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Teaching medicine is a complex task because medical teachers are also involved in clinical practice and research and the availability of cases with rare diseases is very restricted. Automatic creation of virtual patient cases would be a great benefit, saving time and providing a wider choice of virtual patient cases for student training., Objective: This study explored whether the medical literature provides usable quantifiable information on rare diseases. The study implemented a computerized method that simulates basic clinical patient cases utilizing probabilities of symptom occurrence for a disease., Methods: Medical literature was searched for suitable rare diseases and the required information on the respective probabilities of specific symptoms. We developed a statistical script that delivers basic virtual patient cases with random symptom complexes generated by Bernoulli experiments, according to probabilities reported in the literature. The number of runs and thus the number of patient cases generated are arbitrary., Results: We illustrated the function of our generator with the exemplary diagnosis "brain abscess" with the related symptoms "headache, mental status change, focal neurologic deficit, fever, seizure, nausea and vomiting, nuchal rigidity, and papilledema" and the respective probabilities from the literature. With a growing number of repetitions of the Bernoulli experiment, the relative frequencies of occurrence increasingly converged with the probabilities from the literature. For example, the relative frequency for headache after 10.000 repetitions was 0.7267 and, after rounding, equaled the mean value of the probability range of 0.73 reported in the literature. The same applied to the other symptoms., Conclusions: The medical literature provides specific information on characteristics of rare diseases that can be transferred to probabilities. The results of our computerized method suggest that automated creation of virtual patient cases based on these probabilities is possible. With additional information provided in the literature, an extension of the generator can be implemented in further research., (©Christian Schmidt, Dorothea Kesztyüs, Martin Haag, Manfred Wilhelm, Tibor Kesztyüs. Originally published in JMIR Medical Education (https://mededu.jmir.org), 09.03.2023.)

Vitrimers can combine the advantageous properties of cross-linked materials with thermoplastic processability. For the prominent case of polyethylene, established post-polymerization introduction of cross-linkable moieties results in extremely heterogeneous compositions of the chains. Here, we report the generation of functionalized polyethylenes directly by catalytic insertion polymerization, with incorporated cross-linkable aryl boronic esters or alternatively acetal-protected groups suited for cross-linking with difunctional boronic esters. In addition to the desired homogeneous in-chain distribution, the reactive cross-linkable groups are enriched at the chain ends. This enables the incorporation of all chains in the network, as also supported by simulations of all chains' compositions. The uniform molecular composition of the chains reflects in resulting vitrimers' material properties, particularly lack of leaching with solvents. At the same time, cross-linking is indeed fully reversible and the vitrimers can be recycled.

Charge transport, diffusion properties, and glassy dynamics of blends of imidazolium-based ionic liquid (IL) and the corresponding polymer (polyIL) were examined by Pulsed-Field-Gradient Nuclear Magnetic Resonance (PFG-NMR) and rheology coupled with broadband dielectric spectroscopy (rheo-BDS). We found that the mechanical storage modulus (G') increases with an increasing amount of polyIL and G' is a factor of 10,000 higher for the polyIL compared to the monomer (GIL'= 7.5 Pa at 100 rad s -1 and 298 K). Furthermore, the ionic conductivity (σ0) of the IL is a factor 1000 higher than its value for the polymerized monomer with 3.4×10-4 S cm -1 at 298 K. Additionally, we found the Haven Ratio (HR) obtained through PFG-NMR and BDS measurements to be constant around a value of 1.4 for the IL and blends with 30 wt% and 70 wt% polyIL. These results show that blending of the components does not have a strong impact on the charge transport compared to the charge transport in the pure IL at room temperature, but blending results in substantial modifications of the mechanical properties. Furthermore, it is highlighted that the increase in σ0 might be attributed to the addition of a more mobile phase, which also possibly reduces ion-ion correlations in the polyIL.

The inverse vulcanization produces high sulfur content polymers from alkenes and elemental sulfur. Control over properties such as the molar mass or the solubility of polymers is not well established, and existing strategies lack predictability or require large variations of the composition. Systematic design principles are sought to allow for a targeted design of materials. Herein, we report on the inverse vulcanization of norbornenylsilanes (NBS), with a different number of hydrolysable groups at the silicon atom. Inverse vulcanization of mixtures of NBS followed by polycondensation yielded soluble high sulfur content copolymers (50 wt % S) with controllable weight average molar mass (M W ), polydispersity (Đ), glass transition temperature (T G ), or zero-shear viscosity (η 0 ). Polycondensation was conducted in the melt with HCl as a catalyst, abolishing the need for a solvent. Purification by precipitation afforded polymers with a greatly reduced amount of low molar mass species., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Methods that increase sensitivity are a constant topic in research. To increase the sensitivity for high-performance liquid chromatography (HPLC) a continuous injection method with a sinusoidal analyte concentration profile was developed. The sinusoidal analyte concentration profile is obtained by a sinusoidal variation of the relative volume contents between two solvent reservoirs, one containing a pure solvent and the other an analyte stock solution prepared with the same solvent. Discrete Fourier transformation enables the analyte-specific phase angle shift to be calculated from the chromatograms. The proposed method is established and evaluated for size exclusion chromatography (SEC). Accordingly, the phase angle shift is used for molecular weight determination by establishing a molecular weight calibration using different narrowly distributed polystyrene (PS) calibration standards. In a comparison with conventional SEC, the Signal-to-Noise ratio (S/N), normalized to the square root of the time of the evaluated data set, increases by a factor of approximately 50.

Understanding polymer gelation over multiple length-scales is crucial to develop advanced materials. An experimental setup is developed that combines rheological measurements with simultaneous time-domain 1 H NMR relaxometry (TD-NMR) techniques, which are used to study molecular motion (<10 nm) in soft matter. This so-called low-field RheoNMR setup is used to study the impact of varying degrees of crosslinking (DC) on the gelation kinetics of acrylic acid (AAc) and N,N'-methylene bisacrylamide (MBA) free radical crosslinking copolymerization. A stretched exponential function describes the T 2 relaxation curves throughout the gelation process. The stretching exponent β decreases from 0.90 to 0.67 as a function of increasing DC, suggesting an increase in network heterogeneity with a broad T 2 distribution at higher DC. The inverse correlation of the elastic modulus G' with T 2 relaxation times reveals a pronounced molecular rigidity for higher DC at early gelation times, indicating the formation of inelastic, rigid domains such as crosslinking clusters. The authors further correlate G' with the polymer concentration during gelation using a T 1 filter for solvent suppression. A characteristic scaling exponent of 2.3 is found, which is in agreement with theoretical predictions of G' based on the confining tube model in semi-dilute entangled polymer solutions., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The plant Santa herba ( Eriodictyon californicum ) contains high flavonoids, thus potentially exerting beneficial effects in context of obesity, often accompanied by inflammation and metabolic imbalance. The study assessed the impact of Santa herba on oxidative stress, energy metabolism, weight reduction, and eating behavior, combining in vitro models with clinical data. Santa herba binding of the adenosine receptor A2A (ADORA2A) was assessed using a radioligand binding assay. A Caenorhabditis elegans model was used to determine mobility boosting effects, and Santa herba oxygen radical absorbance capacity (ORAC) values were determined in comparison to antioxidative plants. Clinical data, that is, body weight and appetite-related parameters, were obtained from overweight and obese women receiving either Santa herba or placebo for 12 weeks. Results showed that Santa herba extract binds to ADORA2A, stimulates C. elegans motility (+7.5%) and locomotion, and yields high antioxidative capacities (ORAC: 819 trolox equivalent). Clinical data, obtained from 24 overweight and 25 obese women (mean: 47.5 years), demonstrated a reduced body weight ( P  = .042) and body fat ( P  = .044), and by trend reduced leptin levels ( P  = .065) in women with obesity after Santa herba consumption compared to placebo. In conclusion, Santa herba extract has energizing and antioxidative properties and may aid in weight management of people with obesity. ClinicalTrials.gov Identifier: NCT03853603.

This article presents a fast, straightforward synthesis approach to polymerize alternating multiblock copolymers, ultra-high molecular weight (UHMW) (homo)polymers as well as precursors for complex macromolecular topologies such as comb or barbwire architectures. The one-pot synthesis strategy proposed in this work is based on anionic polymerization via a bifunctional initiator and the subsequent linking of macro dianions with a bifunctional linker, additionally overcoming the limitations associated with the monomer reactivity. Thus, the synthetic route guarantees the repeating size of polymer blocks and an equal distribution of functional groups in precursors for complex topologies. Dianions of polystyrene (PS), polyisoprene-b-polystyrene-b-polyisoprene, and poly-2-vinylpyridine-b-polystyrene-b-poly-2-vinylpyridine are linked with α , α ' -dibromo-para-xylene to UHMW and multiblock copolymers. Multiblock copolymers with on average up to 50 well-defined alternating A and B blocks are accessible within 15 min., (© 2021 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Herein, we report the design of styrene-based poly(ethylene oxide) (PEO) side-chain block copolymers featuring a microphase separation and their application as solid polymer electrolytes in high-voltage lithium-metal batteries. A straightforward synthesis was established, overcoming typical drawbacks of PEO block copolymers prepared by anionic polymerization or ester-based PEO side-chain copolymers. Both the PEO side-chain length and the LiTFSI content were varied, and the underlying relationships were elucidated in view of polymer compositions with high ionic conductivity. Subsequently, a selected composition was subjected to further analyses, including phase-separated morphology, providing not only excellent self-standing films with intrinsic mechanical stability but also the ability to suppress lithium dendrite growth as well as good flexibility, wettability, and good contacts with the electrodes. Furthermore, good thermal and electrochemical stability was demonstrated. To do so, linear sweep and cyclic voltammetry, lithium plating/stripping tests, and galvanostatic overcharging using high-voltage cathodes were conducted, demonstrating stable lithium-metal interfaces and a high oxidative stability of around 4.75 V. Consequently, cycling of Li||NMC622 cells did not exhibit commonly observed rapid cell failure or voltage noise associated with PEO-based electrolytes in Li||NMC622 cells, attributed to the high mechanical stability. A comprehensive view is provided, highlighting that the combination of PEO and high-voltage cathodes is not impossible per se .

It is well known that shear has an effect on fat crystallization. Whereas rheo-NMR has been used to study the impact of shear on the crystallization kinetics in the past, these methods mostly used a simple Teflon mixing shaft inside a sophisticated NMR instrument to apply shear to the sample. However, this method did not enable the determination of rheological parameters. In this work, a custom made low-field rheo-NMR device was evaluated, consisting of a commercial rheometer combined with a low-field permanent magnet to enable simultaneous rheological and NMR measurements. Two fats, i.e. partially hardened sunflower oil (PHSO) and soft palm mid fraction (sPMF), were submitted to several rheo-NMR experiments. The results of these experiments clearly indicated that these fats crystallized differently. First, PHSO crystallized faster than sPMF. Moreover, the latter seemed to crystallize in two steps. Initially a weak structure was formed when a low amount of solids was present, but this structure was replaced by a stronger network once more crystals were present. Both fats were studied under stagnant conditions, but also when submitted to low shear rates (1 s -1 and 5 s -1 ). It was shown that the amount of solids necessary to obtain a viscosity of 10 ​Pa ​s was higher when the shear rate was higher. The strength of the formed crystal network at a given percentage of solids was also weaker as the shear rate during crystallization increased. Whereas these experiments were done non-isothermally, it was shown that rheo-NMR can also perfectly be used for isothermal measurements., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Rheo-NMR setup is now being further developed at Bruker BioSpin GmbH, current employer of co-author Karl-Friedrich Ratzsch., (© 2021 The Authors.)

Background: The assessment of improvement or maintenance of joint health in healthy subjects is a great challenge. The aim of the study was the evaluation of a joint stress test to assess joint discomfort in subjects with activity-related knee joint discomfort (ArJD)., Results: Forty-five subjects were recruited to perform the single-leg-step-down (SLSD) test (15 subjects per group). Subjects with ArJD of the knee (age 22-62 years) were compared to healthy subjects (age 24-59 years) with no knee joint discomfort during daily life sporting activity and to subjects with mild-to-moderate osteoarthritis of the knee joint (OA, Kellgren score 2-3, age 42-64 years). The subjects performed the SLSD test with two different protocols: (I) standardization for knee joint discomfort; (II) standardization for load on the knee joint. In addition, range of motion (ROM), reach test, acute pain at rest and after a single-leg squat and knee injury, and osteoarthritis outcome score (KOOS) were assessed. In OA and ArJD subjects, knee joint discomfort could be reproducibly induced in a short time interval of less than 10 min (200 steps). In healthy subjects, no pain was recorded. A clear differentiation between study groups was observed with the SLSD test (maximal step number) as well as KOOS questionnaire, ROM, and reach test. In addition, a moderate to good intra-class correlation was shown for the investigated outcomes., Conclusions: These results suggest the SLSD test is a reliable tool for the assessment of knee joint health function in ArJD and OA subjects to study the improvements in their activities. Further, this model can be used as a stress model in intervention studies to study the impact of stress on knee joint health function.

Water-soluble bis( N -acylpiperidone)s with aldehyde-like reactivity are reported to react rapidly with polyvinylamine at room temperature, providing unprecedented clean reaction products. Unlike most amine/ketone reactions that result in arbitrary mixtures of imines, aminals, hemiaminals, or hydrates, in the present study hemiaminals, aminals, or hemiaminal/aminal mixtures are exclusively found. Detailed NMR spectroscopy of solutions, gels, and solids, aided by model reactions, reveals that the hemiaminal/aminal ratio depends on pH, water content, and cross-linking density. Network formation is fully reversible upon changes in pH, with the resulting moduli from rheology spanning almost 3 orders of magnitude. The self-healing ability of the system is probed by rheology as well, demonstrating maintained material properties of fractured and healed samples. The unusually clean, fast, and reversible chemistry highlights bispiperidones as a class of efficient building blocks with unprecedented possibilities in dynamic covalent chemistry.

(6S)-5-Methyltetrahydrofolic acid ((6S)-5-Methyl-THF) salts and folic acid may differ in their abilities to raise plasma (6S)-5-Methyl-THF levels. We compared the area under the curve (AUC), C max , and T max of plasma (6S)-5-Methyl-THF after intakes of (6S)-5-Methyl-THF-Na salt (Arcofolin ® ) and folic acid. Moreover, we compared the AUCs after intakes of (6S)-5-Methyl-THF-Na and the calcium salt, (6S)-5-Methyl-THF-Ca, that were tested against folic acid in two independent studies. The study was randomized, double blind, and cross over. Twenty-four adults (12 men and 12 women) received a single oral dose of 436 µg (6S)-5-Methyl-THF-Na and an equimolar dose of folic acid (400 µg) on two kinetic days with two weeks washout period in between. The plasma concentrations of (6S)-5-Methyl-THF were measured at 9 time points between 0 and 8 h. We found that the AUC 0-8 h of plasma (6S)-5-Methyl-THF (mean (SD) = 126.0 (33.6) vs. 56.0 (25.3) nmol/L*h) and C max (36.8 (10.8) vs. 11.1 (4.1) nmol/L) were higher after administration of (6S)-5-Methyl-THF-Na than after the administration of folic acid ( p < 0.001 for both). These differences were present in men and women. Only administration of folic acid resulted in a transient increase in plasma unmetabolized folic acid (2.5 (2.0) nmol/L after 0.5 h and 4.7 (2.9) nmol/L after 1 h). Intake of (6S)-5-Methyl-THF-Na was safe. The ratios of the AUC 0-8 h for (6S)-5-Methyl-THF-Na and (6S)-5-Methyl-THF-Ca to the corresponding folic acid reference group and the delta of these AUC 0-8 h did not differ between the studies. In conclusion, a single oral dose of (6S)-5-Methyl-THF-Na caused higher AUC 0-8 h and C max of plasma (6S)-5-Methyl-THF compared to folic acid. The Na- and Ca- salts of (6S)-5-Methyl-THF are not likely to differ in their pharmacokinetics. Further studies may investigate whether supplementation of the compounds for a longer time will lead to differences in circulating or intracellular/tissue folate concentrations.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM., Competing Interests: C.S., A.W., T.D., T.S.: employees of contracted research organization. M.W. is an independent statistician supporting with data analysis. The study was financially supported by Ingredia S.A., France. The sponsors contributed to the discussion about the study design and selection of outcome measures prior to the study start. Planning and organization of the study and its realization, data analysis and report generating were independently undertaken solely by BioTeSys GmbH and M.W. The authors from BioTeSys GmbH and M.W. declare no conflict of interest regarding the publication of this paper.

Objective: Resonant vibrations of implanted structures during a magnetic resonance imaging (MRI) procedure pose a risk to the patient in the form of soft tissue irritation and degradation of the implant. In this paper, the mechanical behavior of implant structures in air, water, and viscoelastic materials was explored., Methods: The static and dynamic transfer functions of various test samples in air and immersed in both water and hydrogels were analyzed. The laser-based acquisition method allowed for high-angular-resolution (10  μDeg) and high-dynamic-range (0-6 kHz) measurements. Additional MRI experiments were conducted to investigate the dependence of vibration strength on magnetic resonance (MR) sequence parameters in combination with the obtained transfer functions., Results: The largest forces were found to be in the micronewton to millinewton range, which is comparable to forces applied during implantation. Of additional concern was the damping introduced by viscoelastic tissue, which was less than expected, leading to an underdamped system. In contrast to current wisdom, the imaging experiments demonstrated drastically different vibration amplitudes for identical gradient slew rates, but different timing parameters TR, mainly due to resonant amplification., Conclusion: The results showed that a safe force-free MR procedure depends not only on the gradient slew rate, but also and more drastically on the choice of secure timing parameters., Significance: These findings delineate design improvements to achieve longevity of implants and will lead to increased patient safety during MRI. A prudent choice of mechanical characteristics of implanted structures is sufficient to avoid resonant excitation due to mismatched MR sequence parameters.

：Linear and nonlinear rheological properties of model comb polystyrenes (PS) with loosely to densely grafted architectures were measured under small and medium amplitude oscillatory shear (SAOS and MAOS) flow. This comb PS set had the same length of backbone and branches but varied in the number of branches from 3 to 120 branches. Linear viscoelastic properties of the comb PS were compared with the hierarchical model predictions. The model underpredicted zero-shear viscosity and backbone plateau modulus of densely branched comb with 60 or 120 branches because the model does not include the effect of side chain crowding. First- and third-harmonic nonlinearities reflected the hierarchy in the relaxation motion of comb structures. Notably, the low-frequency plateau values of first-harmonic MAOS moduli scaled with Mw-2 (total molecular weight), reflecting dynamic tube dilution (DTD) by relaxed branches. Relative intrinsic nonlinearity Q 0 exhibited the difference between comb and bottlebrush via no low-frequency Q 0 peak of bottlebrush corresponding to backbone relaxation, which is probably related to the stretched backbone conformation in bottlebrush., Competing Interests: The authors declare no conflict of interest.

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix, while the nanofiller is based on graphene oxide to enhance the printability and cell proliferation. Our results show that the incorporation of graphene oxide into the hydrogel inks considerably improved the shape fidelity and resolution of 3D printed scaffolds because of a faster viscosity recovery post extrusion of the ink. Moreover, the nanocomposite inks produce anisotropic threads after the 3D printing process because of the templating of the graphene oxide liquid crystal. The in vitro proliferation assay of human adipose tissue-derived mesenchymal stem cells (hADMSCs) shows that bioconjugated scaffolds present higher cell proliferation than pure alginate, with the nanocomposites presenting the highest values at long times. Live/Dead assay otherwise displays full viability of hADMSCs adhered on the different scaffolds at day 7. Notably, the scaffolds produced with nanocomposite hydrogel inks were able to guide the cell proliferation following the direction of the 3D printed threads. In addition, the bioconjugated alginate hydrogel matrix induced chondrogenic differentiation without exogenous pro-chondrogenesis factors as concluded from immunostaining after 28 days of culture. This high cytocompatibility and chondroinductive effect toward hADMSCs, together with the improved printability and anisotropic structures, makes these nanocomposite hydrogel inks a promising candidate for cartilage tissue engineering based on 3D printing.

Various poly(sodium acrylate) hydrogels with different architectures, such as single networks, interpenetrating double networks and surface crosslinked hydrogels, are synthesized with a systematic change in their degree of crosslinking. The influence of these 3D structures on the absorbency of aqueous NaCl solutions is investigated. The local polymer mobility in water is probed in the form of transverse (T2) 1H-relaxation at a low field, which allowed confirming the structural aspects of the studied network topologies. Salt partitioning between the gel and the surrounding solution phase in NaCl solutions with an initial salt concentration of c0 = 0.017-0.60 mol L-1 (≙1-35 g L-1) is investigated. The data are compared with an idealized mean-field Donnan model, which fit the experimental findings only under the assumption of a drastically reduced effective charge density of feff ≈ 25 mol% independent of the hydrogel used. The unequal salt distribution allows desalination of salt water by applying an external pressure to a swollen hydrogel to recover its water which has a lower salinity. The specific energy needed to desalinate 1 m3 was estimated to be 6-18 kW h m-3. This value decreases with a lower degree of swelling independent of the network topology. Besides the experiments, simulations based on a Poisson-Boltzmann mean-field model and MD simulations are performed to determine the degree of swelling and salt partitioning as a function of c0 for different hydrogels. Both simulations describe qualitatively the experimental data, where deviations can be ascribed to model simplifications and the imperfect structure of the hydrogels synthesized via free radical polymerization.

As an essential nutrient, the organic water-soluble compound choline is important for human health. Choline is required for numerous biological processes, including the synthesis of neurotransmitters, and it is an important prerequisite for structural integrity and the functioning of cells. A choline-rich diet provides crucial choline sources, yet additional choline dietary supplements might be needed to fully meet the body's requirements. Dependent on the structure of choline in different sources, absorption and metabolism may differ and strongly impact the bioavailability of circulating choline. This study in healthy volunteers aimed to compare the pharmacokinetics of free choline and of selected choline metabolites between the single dose intake of phosphatidylcholine, present in Superba Boost TM krill oil, and choline bitartrate salt. Results demonstrate that albeit free choline levels in plasma were comparable between both choline sources, peak choline concentration was reached significantly later upon intake of Superba Boost TM . Moreover, the occurrence of choline metabolites differed between the study products. Levels of the biologically important metabolites betaine and dimethylglycine (DMG) were higher, while levels of trimethylamine N-oxide (TMAO) were substantially lower upon intake of Superba Boost TM compared to choline bitartrate.

Online chemically sensitive detectors for size exclusion chromatography (SEC) through coupled setups based on infrared (IR) (or NMR) spectrometers present new possibilities through unprecedented levels of polymer detail with respect to molecular weight and chemical composition. Herein, a new external cavity quantum cascade laser (EC-QCL) mid-IR spectrometer as a chemically sensitive online detector for SEC is custom-designed, built, and tested. This unique spectrometer features multiple broadly tunable EC-QCL sources, which can be operated in continuous wave and pulsed mode, accompanied with balanced liquid nitrogen cooled mercury cadmium telluride (MCT) detectors and a new custom-built transmission flow cell. Automated data analysis is done with a self-written MATLAB code. The limit of detection (LOD) is measured online, coupled with SEC chromatography, where on average, one carbonyl functionality in 530 000 g mol -1 at chromatographic conditions for SEC could be detected. It is possible to detect 0.46 µg (LOD) PMMA, which is approximately a factor of 30 lower than that reported for SEC-Fourier transform infrared., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cannabidiol (CBD), a phytocannabinoid compound of Cannabis sativa , shows limited oral bioavailability due to its lipophilicity and extensive first-pass metabolism. CBD is also known for its high intra- and inter-subject absorption variability in humans. To overcome these limitations a novel self-emulsifying drug delivery system (SEDDS) based on VESIsorb ® formulation technology incorporating CBD, as Hemp-Extract, was developed (SEDDS-CBD). The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions. As reference formulation, the same Hemp-Extract diluted with medium-chain triglycerides (MCT-CBD) was used. CBD dose was standardized to 25 mg. Pharmacokinetic parameters were analyzed from individual concentration-time curves. Single oral administration of SEDDS-CBD led to a 4.4-fold higher C max and a 2.85-/1.70-fold higher AUC 0-8h /AUC 0-24h compared to the reference formulation. T max was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h). Subgroup analysis demonstrated a higher bioavailability in women compared to men. This difference was seen for MCT-CBD while SEDDS-CBD mitigated this gender effect. Overall, SEDDS-CBD showed a significant improvement for all determined pharmacokinetic parameters: increased CBD plasma values (C max ), favorably enhanced bioavailability (AUC) and fast absorption (T max ). No safety concerns were noted following either administration.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo ( p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA 1c values ( p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM., Competing Interests: C.S., A.W., T.D., T.S.: employees of contracted research organization. M.W. is an independent statistician supporting with data analysis. The study was financially supported by Ingredia S.A., France. The sponsors contributed to the discussion about the study design and selection of outcome measures prior to the study start. Planning and organization of the study and its realization, data analysis and report generating were independently undertaken solely by BioTeSys GmbH and M.W. The authors from BioTeSys GmbH and M.W. declare no conflict of interest regarding the publication of this paper.

Comb and bottlebrush polymers present a wide range of rheological and mechanical properties that can be controlled through their molecular characteristics, such as the backbone and side chain lengths as well as the number of branches per molecule or the grafting density. This review investigates the impact of these characteristics specifically on the zero shear viscosity, strain hardening behavior, and plateau shear modulus. It is shown that for a comb polymer with an entangled backbone and entangled side chains, a maximum in the strain hardening factor and minimum in the zero shear viscosity η 0 can be achieved through selection of an optimum number of branches q. Bottlebrush polymers with flexible filaments and extremely low plateau shear moduli relative to linear polymers open the door for a new class of solvent-free supersoft elastomers, where their network modulus can be controlled through both the degree of polymerization between crosslinks, n x , and the length of the side chains, n sc , with G B B 0 ≈ ρ k T n x - 1 ( n s c + 1 ) - 1 ., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Low folate status is a risk factor for birth defects. We studied concentrations of red blood cell (RBC)- and serum folate in 198 German women in relation to information on dietary folate intake, demographic and lifestyle factors. Median serum- and RBC-folate levels were; (14.7 and 589 nmol/L, respectively. Serum < 7.0 nmol/L or RBC-folate < 405 nmol/L were observed in 3.5% and 18.7% of the women, respectively. Three per cent of the women had both lowered serum and RBC-folate. Whereas RBC-folate > 952 nmol/L (optimal levels around conception) were observed in 9.6%. Serum- and RBC-folate were positively associated; they showed the expected correlations with homocysteine, but only weak correlations with folate intake. Younger age, lower fibre and higher carbohydrate intakes were associated with lower blood folate. Thus, folate intake of approximately 278 µg/d was not sufficient to achieve optimal folate status in young women. In conclusion, in the absence of fortification with folic acid, the majority of the women did not achieve folate status that is optimal for prevention of birth defects.

Objectives: Each year, adults suffer about two to four upper respiratory tract infections (URTIs), mostly in winter. The aim of the study was to evaluate the effects of brewers' yeast (1,3)-(1,6)-beta-glucan on incidence and severity of upper respiratory tract infections (URTIs)., Methods: Generally healthy men and women (n = 299) reporting at least three URTIs during the previous year were randomized to receive either a placebo or 900 mg of yeast beta-glucan daily for 16 weeks during winter. In cases of acute URTI, the severity of URTI symptoms was assessed via the WURSS-21 questionnaire and the Jackson scale, and a clinical confirmation was implemented by the investigator., Results: Overall, 70 subjects under placebo and 71 subjects under yeast beta-glucan experienced at least one clinically confirmed URTI episode. The global severity using WURSS-21 had been quite similar between the study groups (p = 0.5267), whereas during the first days of URTIs the severity was less pronounced in the yeast beta-glucan group. On the episode level, the severity of physical symptoms was significantly lower for all investigated time intervals up to 7 days under yeast beta-glucan (WURSS (Q2-11) (days 1-2: p = 0.0465, days 1-3: p = 0.0323, days 1-4: p = 0.0248, days 1-7: p = 0.0278), also confirmed for the Jackson scale). The reduction of severity was accompanied by a significant increase in the joy subscore of the Perceived Stress Questionnaire (PSQ20) (p = 0.0148). In addition, there was a reduction of systolic (p = 0.0458) and diastolic (p = 0.1439) blood pressure., Conclusion: Subjects supplementing with yeast beta-glucan benefit by a reduced severity of physical URTI symptoms during the first week of an episode, even though the incidence and global severity of common colds could not be altered in comparison to placebo. Furthermore, accompanying benefits in terms of blood pressure and mood were identified. Altogether, yeast beta-glucan supports the immune function.

This work demonstrates a new method for the generation of mechanical shear wave during magnetic resonance elastography (MRE) that creates greater forces at higher vibrational frequencies as opposed to conventionally used pneumatic transducers. We developed an MR-compatible pneumatic turbine with an eccentric mass that creates a sinusoidal centrifugal force. The turbine was assessed with respect to its technical parameters and evaluated for MRE on a custom-made anthropomorphic prostate phantom. The silicone-based tissue-mimicking materials of the phantom were selected with regard to their complex shear moduli examined by rheometric testing. The tissue-mimicking materials closely matched human soft tissue elasticity values with a complex shear modulus ranging from 3.21 kPa to 7.29 kPa. We acquired MRE images on this phantom at 3 T with actuation frequencies of 50, 60 Hz, 70 Hz, and 80 Hz. The turbine generated vibrational wave amplitudes sufficiently large to entirely penetrate the phantoms during the feasibility study. Increased wave length in the stiffer inclusions compared to softer background material were detected. Our initial results suggest that silicone-based phantoms are useful for the evaluation of elasticities during MRE. Furthermore, our turbine seems suitable for the mechanical assessment of soft tissue during MRE., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Folate required to achieve desirable red blood cell (RBC) folate concentrations within 4-8 weeks pre-pregnancy is not known. We studied the effect of supplementation with 400 or 800 µg/day folate in achieving RBC-folate ≥906 nmol/L., Methods: Non-pregnant women were randomized to receive multinutrient supplements containing 400 µg/day (n = 100) or 800 µg/day (n = 101) folate [folic acid and (6S)-5-CH 3 -H 4 folate-Ca (1:1)]. The changes of folate biomarkers were studied after 4 and 8 weeks in the 198 women who returned at least for visit 2., Results: At baseline, 12 of the 198 participants (6.1%) had RBC-folate <340 nmol/L, but 88% had levels <906 nmol/L. The RBC-folate concentrations increased significantly in the 800 µg/day (mean ± SD = 652 ± 295 at baseline; 928 ± 330 at 4 weeks; and 1218 ± 435 nmol/L at 8 weeks) compared with the 400 µg/day [632 ± 285 at baseline (p = 0.578); 805 ± 363 at 4 weeks (p < 0.001); 1021 ± 414 nmol/L at 8 weeks (p < 0.001)]. The changes of RBC-folate were greater in the 800 µg/day than in the 400 µg/day at any time (changes after 8 weeks: 566 ± 260 vs. 389 ± 229 nmol/L; p < 0.001). Significantly more women in the 800 µg group achieved desirable RBC-folate concentrations at 4 weeks (45.5 vs. 31.3%; p = 0.041) or 8 weeks (83.8 vs. 54.5%; p < 0.001) compared with the 400 µg group. RBC-folate levels below the population median (590 nmol/L) were associated with a reduced response to supplements., Conclusions: 88% of the women had insufficient RBC-folate to prevent birth defects, while 6.1% had deficiency. Women with low RBC-folate were unlikely to achieve desirable levels within 4-8 weeks, unless they receive 800 µg/day. The current supplementation recommendations are not sufficient in countries not applying fortification., Trials Register: The trial was registered at The German Clinical Trials Register: DRKS-ID: DRKS00009770.

Context: Intake of hormonal contraceptives (HC) is associated with higher total 25-hydroxyvitamin D [25(OH)D] concentrations, but the effect of HC on free 25(OH)D is unclear., Objective: We investigated whether free 25(OH)D concentrations differ according to use of HC., Design: This is a post hoc analysis of a randomized open trial., Setting: This study was conducted from 13 January to 9 May, 2016, at a clinical research organization in Esslingen, Germany., Participants: We included 201 apparently healthy women of childbearing age., Intervention: Participants were randomly assigned to receive a daily multimicronutrient supplement for 8 weeks; the supplement contained 200 IU (n =100) or 800 IU (n = 101) of vitamin D3., Main Outcome Measures: Primary outcome was the difference in free 25(OH)D between users and nonusers of HC., Results: Overall, 176 participants [median (25th to 75th percentiles) age: 25 (22 to 29) years] with available free 25(OH)D were included in the present analysis. At baseline, total 25(OH)D was significantly higher in users (n = 110) than in nonusers (n = 66) of HC [49.2 (33.4 to 63.4) vs 39.1 (23.8 to 52.5) nmol/L; P < 0.001], whereas there was no difference in free 25(OH)D [7.87 (6.50 to 10.11) vs 7.88 (6.35 to 10.12) pmol/L; P = 0.923]. These results were confirmed after multimicronutrient supplementation and in subgroups according to treatment allocation., Conclusions: Use of HC was associated with, on average, 26% higher total 25(OH)D, whereas free 25(OH)D values did not differ according to use of HC. These findings are relevant for epidemiological studies, but the physiological implications remain to be clarified.

A state-of-the-art, medium-resolution 1 H-NMR spectrometer (62 MHz) is used as a chemically sensitive online detector for size-exclusion chromatography of polymers such as polymethylmethacrylate (PMMA) and polystyrene (PS). The method uses protonated eluents and works at typical chromatographic conditions with trace amounts of analytes (<0.5 g L -1 after separation). Strong solvent suppression, e.g., by a factor of 500, is achieved by means of T 1 -filtering and mathematical subtraction methods. Substantial improvements are made with respect to previous work in terms of the sensitivity (signal-to-noise ratio up to 130:1, PMMA OCH 3 ) and selectivity (peak width, full width half maximum (FWHM) 4 Hz on-flow). Typical homopolymers and a blend are investigated to deformulate their composition along the dimensions of molecular weight and NMR chemical shift. These results validate this new hyphenated chromatography method, which can greatly facilitate analysis and is much more effective than previously published results., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: The aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of L-arginine with the vitamins B 6 , folic acid and B 12 (Telcor ® Arginin plus) on endothelial dysfunction., Methods: Subjects aged 40-65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post-pre, visit 3-visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration., Results: The primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators., Conclusions: This trial confirmed the effective and safe use of dietary management with L-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of L-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation.

Scope: We modeled red blood cell (RBC)-folate response to supplementation and developed personalized folate supplementation concepts., Methods and Results: The changes of RBC-folate were modeled in a time- (4 or 8 weeks) and dose- (400 or 800 μg d -1 folate) dependent manner. Post-supplementation RBC-folate levels were predicted from folate-loading capacities (= measured RBC-folate - [baseline RBC-folate × RBC-survival]). The prediction equations were validated in 119 participants. The median increase of RBC-folate was higher in the 800 μg d -1 than in the 400 μg d -1 group (275 vs 169 nmol L -1 after 4 weeks, and 551 vs 346 nmol L -1 after 8 weeks). Medians (interquartile range) of RBC-folate loading were (4 weeks: 299 (160) vs 409 (237) nmol L -1 ) and (8 weeks: 630 (134) versus 795 (187) nmol L -1 ) in the 400 and 800 μg d -1 group, respectively. The individual measured and predicted RBC-folate values (after 4 weeks/400 μg d -1 = 25 + 1.27 × baseline RBC-folate) and (after 4 weeks/800 μg d -1 = 65 + 1.41 × baseline RBC-folate) did not differ significantly. The measured and predicted concentrations showed high agreement in the validation cohort., Conclusions: The models can guide nutritional recommendations in women when baseline RBC-folate concentrations are measured and the time to pregnancy between 4 and 8 weeks., (© 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product., Methods: The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22-50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise., Results: Participants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength ( p  = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend ( p  = 0.0681) and less movement induced pain ( p  = 0.0788) by trend. Creatine kinase and IL-6 didn't show significant discrimmination between groups., Conclusion: Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise., Trial Registration: The trial was registered in the clinical trials registry (clinical trial.gov NCT02923102). Registered 28 September 2016., Competing Interests: SBW, Pharmacist, PhD in Pharmaceutical Chemistry, over 20 years experience in the natural product industry for health and nutrition. Managing Director and head of R&D at Vital Solutions GmbH, Hausingerstrasse 6, Langenfeld, 40,764, Germany. IN, Dipl. Chemical engineer, Master in Natural product chemistry, Scientific Manager at Vital Solutions GmbH, Hausingerstrasse 6, Langenfeld, 40,764, Germany. CS (Dipl. Nutrition science) and CAR (PhD Sports science and examin. Biol.), both clinical research scientists at BioTeSys GmbH, a company with over 15 years experience in the field of nutrition research and clinical nutrition studies. ES, student of molecular nutritional science at University of Hohenheim and trainee at BioTeSys GmbH, Schelztorstrasse 54–56, Esslingen, D-73728, Germany. MW, professor for mathematics and statistics at the. Ulm University of Applied Sciences, Albert-Einstein-Allee 55, 89,081 Ulm, Germany.Ethical approval was obtained from the ethical committee of the “Landesärztekammer Baden-Württemberg” without concerns (F-2016-080 September 13th, 2016) prior to study start and all subjects signed the IRB-approved informed consent prior to any procedures.Not applicable.The study was sponsored by Vital Solutions GmbH. The sponsors contributed to discussion about study design and selection of outcome measures prior to study start. During study realization and data analysis all data were completely blinded and study realization, data analysis and report generating were undertaken independently by BioTeSys GmbH and Ulm University of Applied Sciences. Vital Solutions own the proprietary ingredient used in the study. The authors from BioTeSys GmbH and Ulm University of Applied Sciences declare that there is no conflict or interest regarding the publication of this paper.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The development of coupled techniques based on chemically sensitive detectors, such as FTIR or NMR spectrometers, for size exclusion chromatography (SEC) provides sophisticated methods for determining the molecular-weight-dependent chemical composition in polymers. However, the detection of rare functionalities such as end groups or branching points presents a challenge, especially for online coupled SEC detection, which is based on low-concentration chromatography. To address this issue, for the first time, an external cavity quantum cascade laser (EC-QCL) infrared spectrometer is coupled to an SEC. The system is evaluated using polystyrene/poly(methyl methacrylate) (PS/PMMA) blends. The current limit of detection for the carbonyl (PMMA) stretch vibration at 1730 cm -1 with this technique is 3.5 µg PMMA on a semipreparative column (typical load of 2.5 mg polymer in total). That equals 0.15 mol% of PMMA in the PS/PMMA blend and corresponds to one carbonyl group per 70 kg mol -1 polymer., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Poly(acrylic acid)-based hydrogels can swell up to 100-1000 times their own weight in desalinated water due to osmotic forces. As the swelling is about a factor of 2-12 lower in seawater-like saline solutions (4.3 wt% NaCl) than in deionized water, cyclic swelling, and shrinking can potentially be used to move a piston in an osmotic motor. Consequently, chemical energy is translated into mechanical energy. This conversion is driven by differences in chemical potential and by changes in entropy. This is special, as most thermodynamic engines rely instead on the conversion of heat into mechanical energy. To optimize the efficiency of this process, the degree of neutralization, the degree of crosslinking, and the particle size of the hydrogels are varied. Additionally, different osmotic engine prototypes are constructed. The maximum mean power of 0.23 W kg -1 dry hydrogel is found by using an external load of 6 kPa, a polymer with 1.7 mol% crosslinking, a degree of neutralization of 10 mol%, and a particle size of 370-670 µm. As this is achieved only in the first round of optimization, higher values of the maximum power average over one cycle seem realistic.

The linear and nonlinear oscillatory shear, extensional and combined rheology-dielectric spectroscopy of hybrid polymer nanocomposites for semiconductive applications were investigated in this study. The main focus was the influence of processing conditions on percolated poly(ethylene-butyl acrylate) (EBA) nanocomposite hybrids containing graphite nanoplatelets (GnP) and carbon black (CB). The rheological response of the samples was interpreted in terms of dispersion properties, filler distortion from processing, filler percolation, as well as the filler orientation and distribution dynamics inside the matrix. Evidence of the influence of dispersion properties was found in linear viscoelastic dynamic frequency sweeps, while the percolation of the nanocomposites was detected in nonlinearities developed in dynamic strain sweeps. Using extensional rheology, hybrid samples with better dispersion properties lead to a more pronounced strain hardening behavior, while samples with a higher volume percentage of fillers caused a drastic reduction in strain hardening. The rheo-dielectric time-dependent response showed that in the case of nanocomposites containing only GnP, the orientation dynamics leads to non-conductive samples. However, in the case of hybrids, the orientation of the GnP could be offset by the dispersing of the CB to bridge the nanoplatelets. The results were interpreted in the framework of a dual PE-BA model, where the fillers would be concentrated mainly in the BA regions. Furthermore, better dispersed hybrids obtained using mixing screws at the expense of filler distortion via extrusion processing history were emphasized through the rheo-dielectric tests.

The German Nutrition Society raised in 2012 the recommended daily vitamin D intake from 200 to 800 international units (IU) to achieve 25-hydroxyvitamin D (25(OH)D) levels of at least 50 nmol/L, even when endogenous vitamin D synthesis is minimal such as in winter. We aimed to evaluate this recommendation in women of childbearing age. This is a single-center, randomized, open trial conducted from 8 January to 9 May 2016 in Esslingen, Germany. We randomized 201 apparently healthy women to receive for 8 weeks a daily multimicronutrient supplement containing either 200 IU ( n = 100) or 800 IU vitamin D3 ( n = 101). Primary outcome measure was serum 25(OH)D. 196 participants completed the trial. Increases in 25(OH)D (median with interquartile range) from baseline to study end were 13.2 (5.9 to 20.7) nmol/L in the 200 IU group, and 35.8 (18.2 to 52.8) nmol/L in the 800 IU group ( p < 0.001 for the between group difference). At study end, levels of ≥50 nmol/L were present in 70.4% of the 200 IU group and in 99% of the 800 IU group. Participants on hormonal contraceptives had higher baseline levels and a stronger increase in 25(OH)D. In conclusion, daily supplementation of 800 IU vitamin D3 during wintertime in Germany is sufficient to achieve a 25(OH)D level of at least 50 nmol/L in almost all women of childbearing age, whereas 200 IU are insufficient., Competing Interests: This study was sponsored by Merck Selbstmedikation GmbH. The sponsor contributed to discussions about study design and selection of outcome measures prior to the start of the study. Study realization, data analysis, and reporting were undertaken independently from the sponsor. S.P. and A.H. received consultant and speakers honoraria from Merck Selbstmedikation GmbH. The other authors declare no potential conflict of interest.

The leading nonlinear stress response in a periodically strained concentrated colloidal dispersion is studied experimentally and by theory. A thermosensitive microgel dispersion serves as well-characterized glass-forming model, where the stress response at the first higher harmonic frequency (3ω for strain at frequency ω) is investigated in the limit of small amplitude. The intrinsic nonlinearity at the third harmonic exhibits a scaling behavior which has a maximum in an intermediate frequency window and diverges when approaching the glass transition. It captures the (in-) stability of the transient elastic structure. Elastic stresses in-phase with the third power of the strain dominate the scaling. Our results qualitatively differ from previously derived scaling behavior in dielectric spectroscopy of supercooled molecular liquids. This might indicate a dependence of the nonlinear response on the symmetry of the external driving under time reversal.

Hyphenated low-field NMR techniques are promising characterization methods for online process analytics and comprehensive offline studies of soft materials. By combining different analytical methods with low-field NMR, information on chemical and physical properties can be correlated with molecular dynamics and complementary chemical information. In this review, we present three hyphenated low-field NMR techniques: a combination of near-infrared spectroscopy and time-domain NMR (TD-NMR) relaxometry, online (1) H-NMR spectroscopy measured directly after size exclusion chromatographic (SEC, also known as GPC) separation and a combination of rheometry and TD-NMR relaxometry for highly viscous materials. Case studies are reviewed that underline the possibilities and challenges of the different hyphenated low-field NMR methods. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size., Methods: A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire., Results: The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence., Conclusions: Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span., (© 2014 Wiley Periodicals, Inc.)

A novel adaptable network based on the reversible hetero Diels-Alder reaction of a cyanodithioester and cyclopentadiene is presented. Reversible between 50-120 °C, the adjustable and self-healing features of the network are evidenced via temperature dependent rheology experiments and repetitive tensile tests whereas the network's chemical structure is explored by temperature dependent (1) H MAS-NMR spectroscopy., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work introduces a tunable mid-infrared (mid-IR) external cavity quantum cascade laser (EC-QCL) as a new molecular specific detector in liquid chromatography. An EC-QCL with a maximum tunability of 200 cm(-1) (1030-1230 cm(-1)) was coupled to isocratic high performance liquid chromatography (HPLC) for the separation of sugars with a cation exchange column (counter ion: Ca(2+)) and distilled water as the mobile phase. Transmission measurements in a 165 μm thick flow cell allowed for on-line coupling and independent quantification of glucose, fructose and sucrose in the concentration range from 5 mg mL(-1) to 100 mg mL(-1) in several beverages. The results obtained with the EC-QCL detector were found to be in good agreement with those obtained using a differential refractive index detector as a reference. The standard deviation of the method for the linear calibration was better than 5 mg mL(-1) for all sugars and reached a minimum of 1.9 mg mL(-1), while the DRI detector reached a minimum of 1 mg mL(-1). Besides the quantification of sugars for which a calibration was performed, also chromatographic peaks of other components could be identified on the basis of their IR absorption spectra. This includes taurine, ethanol, and sorbitol.