Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

Lung parenchyma and structure visualisation in paediatric chest MRI: a comparison of different short and ultra-short echo time protocols.

AIM: To evaluate image quality acquired at lung imaging using magnetic resonance imaging (MRI) sequences using short and ultra-short (UTE) echo times (TEs) with different acquisition strategies (breath-hold, prospective, and retrospective gating) in paediatric patients and in healthy volunteers. MATERIALS AND METHODS: End-inspiratory and end-expiratory three-dimensional (3D) spoiled gradient (SPGR3D) and 3D zero echo-time (ZTE3D), and 3D UTE free-breathing (UTE3D), prospective projection navigated radial ZTE3D (ZTE3D vnav), and four-dimensional ZTE (ZTE4D) were performed using a 1.5 T MRI system. For quantitative assessment, the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) values were calculated. To evaluate image quality, qualitative scoring was undertaken on all sequences to evaluate depiction of intrapulmonary vessels, fissures, bronchi, imaging noise, artefacts, and overall acceptability. RESULTS: Eight cystic fibrosis (CF) patients (median age 14 years, range 13-17 years), seven children with history of prematurity with or without bronchopulmonary dysplasia (BPD; median 10 years, range 10-11 years), and 10 healthy volunteers (median 32 years, range 20-52 years) were included in the study. ZTE3D vnav provided the most reliable output in terms of image quality, although scan time was highly dependent on navigator triggering efficiency and respiratory pattern. CONCLUSIONS: Best image quality was achieved with prospective ZTE3D and UTE3D readouts both in children and volunteers. The current implementation of retrospective ZTE3D readout (ZTE4D) did not provide diagnostic image quality but rather introduced artefacts over the entire imaging volume mimicking lung pathology.

Local and diffusive dynamics of LiCl aqueous solutions in pristine and modified silica nanopores.

We use 1H, 2H, and 7Li nuclear magnetic resonance to investigate local and diffusive dynamics of LiCl-7H2O and LiCl-7D2O solutions in pristine and functionalized silica nanopores in a component-selective manner. Recently, we showed that the solution dynamics become slower when the diameter of the pristine pores is reduced. Here, we determine the effects of (aminopropyl)triethoxysilane and dye surface functionalizations on the motions of the water molecules and lithium ions from ambient temperatures down to the glass transition. The local and diffusive solution dynamics are similar in both functionalized pores but, on average, slower than in pristine pores with comparable diameters. When the exchange between different confinement regions is sufficiently slow at reduced temperatures, bimodal water and lithium dynamics may be observed. We attribute this bimodality to bulk-like motion in the pore centers and slowed-down motion at the pore walls. For the lithium ions, a bimodality observed in the pristine pores is absent in the functionalized ones. We conjecture that the steric hindrance and electrostatic interactions associated with the grafted functional groups interfere with the formation of a defined electric double layer, while the enhanced surface roughness and unequal charge distribution result in overall slower dynamics. Thus, the nature of the walls is an important parameter for the solution dynamics. Thereby, in situ measurements of the pH value inside the silica pores using the grafted dye molecules reveal that observed changes in the pH value in response to the surface functionalization are of limited relevance for the water reorientation.

The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing.

BACKGROUND: To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework. METHODS: A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS. RESULTS: Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. EVALUATION: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. IMPLEMENTATION: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to. CONCLUSIONS: This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.

Relations between thermodynamics, structures, and dynamics for modified water models in their supercooled regimes.

We use molecular dynamics simulations to study relations between thermodymamic, structural, and dynamical properties of TIP4P/2005 water models with systematically reduced partial charges and, thus, weaker hydrogen bonds. Observing a crossing of isochores in the P-T diagram, we show that these water-like models have a readily accessible liquid-liquid critical point (LLCP) associated with a transition between high-density liquid (HDL) and low-density liquid (LDL) forms and determine the dependence of the critical temperature Tc, pressure Pc, and density ρc on the charge-scaling factor from fits to a two-structure equation of states. The results indicate that the water-like models exhibit liquid polyamorphism in a wide range of interaction parameters. Considering elongated systems, we observe a decomposition into extended and stable HDL-like and LDL-like regions at appropriate pressures and low temperatures and analyze the respective structural and dynamical properties. We show that the diverse local order results in very different correlation times of local dynamics, while the fragility is hardly changed. The results yield insights into the origin of a dynamical crossover, which is observed when lowering the temperature along isobars and was previously interpreted in terms of a fragile-to-strong transition. Our findings imply that the effect does not involve two liquid phases with an exceptionally large difference of the fragility but rather a high temperature dependence near the LLCP results from a rapid conversion from HDL-like environments with faster dynamics to LDL-like ones with slower dynamics.

MD simulations of charged binary mixtures reveal a generic relation between high- and low-temperature behavior.

Experimental studies of the glassy slowdown in molecular liquids indicate that the high-temperature activation energy E∞ of glass-forming liquids is directly related to their glass transition temperature Tg. To further investigate such a possible relation between high- and low-temperature dynamics in glass-forming liquids, we analyze the glassy dynamics of binary mixtures using molecular dynamics simulations. We consider a binary mixture of charged Lennard-Jones particles and vary the partial charges of the particles and, thus, the high-temperature activation energy and the glass transition temperature of the system. Based on previous results, we introduce a phenomenological model describing relaxation times over the whole temperature regime from high temperatures to temperatures well inside the supercooled regime. By investigating the dynamics of both particle species on molecular and diffusive length scales along isochoric and isobaric pathways, we find a quadratic charge dependence of both E∞ and Tg, resulting in an approximately constant ratio of both quantities independent of the underlying observable, the thermodynamic ensemble, and the particle species, and this result is robust against the actual definition of Tg. This generic relation between the activation energy and the glass transition temperature indicates that high-temperature dynamics and the glassy slowdown are related phenomena, and the knowledge of E∞ may allow us to approximately predict Tg.

Molecular dynamics simulations vs field-cycling NMR relaxometry: Structural relaxation mechanisms in the glass-former glycerol revisited.

We combine field-cycling (FC) relaxometry and molecular dynamics (MD) simulations to study the rotational and translational dynamics associated with the glassy slowdown of glycerol. The 1H NMR spin-lattice relaxation rates R1(ω) probed in the FC measurements for different isotope-labelled compounds are computed from the MD trajectories for broad frequency and temperature ranges. We find high correspondence between experiment and simulation. Concerning the rotational motion, we observe that the aliphatic and hydroxyl groups show similar correlation times but different stretching parameters, while the overall reorientation associated with the structural relaxation remains largely isotropic. Additional analysis of the simulation results reveals that transitions between different molecular configurations are slow on the time scale of the structural relaxation at least at sufficiently high temperatures, indicating that glycerol rotates at a rigid entity, but the reorientation is slower for elongated than for compact conformers. The translational contribution to R1(ω) is well described by the force-free hard sphere model. At sufficiently low frequencies, universal square-root laws provide access to the molecular diffusion coefficients. In both experiment and simulation, the time scales of the rotational and translational motions show an unusually large separation, which is at variance with the Stokes-Einstein-Debye relation. To further explore this effect, we investigate the structure and dynamics on various length scales in the simulations. We observe that a prepeak in the static structure factor S(q), which is related to a local segregation of aliphatic and hydroxyl groups, is accompanied by a peak in the correlation times τ(q) from coherent scattering functions.

Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study.

PURPOSE: Approximately 40-70% of biochemically persistent or recurrent prostate cancer (PCa) patients after radical prostatectomy (RPE) are oligo-metastatic in 68gallium-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET). Those lesions are frequently located outside the prostate bed, and therefore not cured by the current standards of care like external-beam radiotherapy (EBRT) of the prostatic fossa. This retrospective study analyzes the influence of oligo-metastases' site on outcome after metastasis-directed radiotherapy (MDR). METHODS: Retrospectively, 359 patients with PET-positive PCa recurrences after RPE were analyzed. Biochemical recurrence-free survival (BRFS) (prostate-specific antigen (PSA) < post-radiotherapy nadir + 0.2 ng/mL) was assessed using Kaplan-Meier survival and Cox regression analysis. RESULTS: All patients were initially clinically without distant metastases (cM0). Seventy-five patients had local recurrence within the prostatic fossa, 32 patients had pelvic nodal plus local recurrence, 117 patients had pelvic nodal recurrence, 51 patients had paraaortic lymph node metastases with/without locoregional recurrence, and 84 patients had bone or visceral metastases with/without locoregional recurrence. Median PSA before MDR was 1.2 ng/mL (range, 0.04-47.5). Additive androgen deprivation therapy (ADT) was given in 35% (125/359) of patients. Median PSA nadir after MDR was 0.23 ng/mL (range, < 0.03-18.30). After a median follow-up of 16 months (1-57), 239/351 (68%) patients had no biochemical recurrence. Patients with distant lymph node and/or distant metastases, the so-called oligo-body cohort, had an overall in-field control of 90/98 (91%) but at the same time, an ex-field progress of 44/96 (46%). In comparison, an ex-field progress was detected in 28/154 (18%) patients with local and/or pelvic nodal recurrence (oligo-pelvis group). Compared with the oligo-pelvis group, there was a significantly lower BRFS in oligo-body patients at the last follow-up. CONCLUSION: Overall, BRFS was dependent on patterns of metastatic disease. Thus, MDR of PSMA PET-positive oligo-metastases can be offered considering that about one-third of the patients progressed within a median follow-up of 16 months.

NMR studies on the influence of silica confinements on local and diffusive dynamics in LiCl aqueous solutions approaching their glass transitions.

We use 1H, 2H, and 7Li NMR to investigate the molecular dynamics of glass-forming LiCl-7H2O and LiCl-7D2O solutions confined to MCM-41 or SBA-15 silica pores with diameters in the range of d = 2.8 nm-5.4 nm. Specifically, it is exploited that NMR experiments in homogeneous and gradient magnetic fields provide access to local and diffusive motions, respectively, and that the isotope selectivity of the method allows us to characterize the dynamics of the water molecules and the lithium ions separately. We find that the silica confinements cause a slowdown of the dynamics on all length scales, which is stronger at lower temperatures and in narrower pores and is more prominent for the lithium ions than the water molecules. However, we do not observe a temperature-dependent decoupling of short-range and long-range dynamics inside the pores. 7Li NMR correlation functions show bimodal decays when the pores are sufficiently wide (d > 3 nm) so that bulk-like ion dynamics in the pore centers can be distinguished from significantly retarded ion dynamics at the pore walls, possibly in a Stern layer. However, we do not find evidence for truly immobile fractions of water molecules or lithium ions and, hence, for the existence of a static Stern layer in any of the studied silica pores.

On the microscopic origins of relaxation processes in aqueous peptide solutions undergoing a glass transition.

We combine broadband dielectric spectroscopy (BDS) with 1H and 2H nuclear magnetic resonance (NMR) to study molecular dynamics in mixtures of ε-polylysine with H2O or D2O. In BDS, four relaxation processes can be attributed to molecular dynamics. While the fastest process P1 obeys the Arrhenius law, the slowest process P4 shows prominent non-Arrhenius behavior typical of structural α relaxation. For the intermediate processes P2 and P3, the temperature dependence changes at the glass transition temperature Tg. The 1H and 2H NMR results yield insights into the molecular origins of these relaxation phenomena. In these NMR analyses, we exploit, in addition to the isotope selectivity of the method, the possibility to distinguish between various types of motion based on their respective line-shape effects and the capability to single out specific molecular moieties based on different spin-lattice relaxation behaviors. In this way, we reveal that process P1 results from the rotation of side and end groups of the peptide, while process P2 is caused by a reorientation of essentially all water molecules, which are quasi-isotropic and survive well below Tg. As for the peptide backbone dynamics, we find evidence that rotational motion of polar groups is involved in process P3 and that nonpolar regions show a dynamical process, which is located between P3 and P4. Thus, the NMR analyses do not yield evidence for coexisting fast peptide-decoupled and slow peptide-coupled water species, which contribute to BDS processes P2 and P3, respectively, but minor bimodality of water motion may remain undetected. Finally, it is demonstrated that the proton/deuteron exchange needs to be considered when interpreting experimental results for molecular dynamics in aqueous peptide solutions.

Compressed Sensing 3D-GRASE for faster High-Resolution MRI.

PURPOSE: High-resolution three-dimensional (3D) structural MRI is useful for delineating complex or small structures of the body. However, it requires long acquisition times and high SAR, limiting its clinical use. The purpose of this work is to accelerate the acquisition of high-resolution images by combining compressed sensing and parallel imaging (CSPI) on a 3D-GRASE sequence and to compare it with a (CS)PI 3D-FSE sequence. Several sampling patterns were investigated to assess their influence on image quality. METHODS: The proposed k-space sampling patterns are based on two undersampled k-space grids, variable density (VD) Poisson-disc, and VD pseudo-random Gaussian, and five different trajectories described in the literature. Bloch simulations are performed to obtain the transform point spread function and evaluate the coherence of each sampling pattern. Image resolution was assessed by the full-width at half-maximum (FWHM). Prospective CSPI 3D-GRASE phantom and in vivo experiments in knee and brain are carried out to assess image quality, SNR, SAR, and acquisition time compared to PI 3D-GRASE, PI 3D-FSE, and CSPI 3D-FSE acquisitions. RESULTS: Sampling patterns with VD Poisson-disc obtain the lowest coherence for both PD-weighted and T2 -weighted acquisitions. VD pseudo-random Gaussian obtains lower FWHM, but higher sidelobes than VD Poisson-disc. CSPI 3D-GRASE reduces acquisition time (43% for PD-weighted and 40% for T2 -weighted) and SAR (∼45% for PD-weighted and T2 -weighted) compared to CSPI 3D-FSE. CONCLUSIONS: CSPI 3D-GRASE reduces acquisition time compared to a CSPI 3DFSE acquisition, preserving image quality. The design of the sampling pattern is crucial for image quality in CSPI 3D-GRASE image acquisitions.

Effects of confinement on supercooled tetrahedral liquids.

We use molecular dynamics simulations to ascertain the effects of geometrical restriction on glass-forming tetrahedral liquids. Striving for a broad approach, we study families of waterlike and silicalike liquids, for which we systematically scale the partial charges and, hence, the relevance of the tetrahedral networks. The confined liquids and the confining matrices consist of the same type of particles to avoid disruptive interactions and distorted structures at the interfaces. Spatially resolved analyses show that these neutral confinements still impose static mobility gradients and density correlations on the liquids. We quantify the increasing degree and range of the altered properties upon cooling. For both families of models, common relations describe the confinement effects of all systems with tetrahedral order, while deviations occur for systems with lower polarities and different structures. The observations are rationalized by considering the fact that a pinned wall imprints a static energy landscape to a neighboring liquid. We explore the properties of this landscape based on changes in vibrational motion and structural relaxation and find that typical barrier heights amount to two to three times the activation energy of bulk dynamics. Combining the present and previous results, we predict the evolution of confinement effects down to the glass transition temperature for liquids without fragile-to-strong crossover. In addition, it is found for silicalike liquids that the temperature dependence of dynamic and static correlation lengths from confinement studies is not affected when cooling through fragile-to-strong transitions of the bulk materials, casting doubt on the relevance of these length scales for the glassy slowdown.

[Analysis of a first responder system for emergency medical care in rural areas: first results and experiences]. / Analyse eines First-responder-Systems zur notfallmedizinischen Versorgung im ländlichen Raum: erste Ergebnisse und Erfahrungen.

BACKGROUND: In emergency situations it is essential to get access to medical treatment as early as possible. In Germany, the time interval from alarm to arrival should be less than 10-15 min. The emergency medical service (EMS) cannot comply with this recommendation in approximately 10% of the emergencies in Baden-Württemberg. In addition to the traditional EMS system, a voluntary system of first responders has been developed over the last years to reduce this interval. They are incorporated into the alarm system of the traditional EMS and are alarmed as soon as an emergency call arrives. Data on process times (from alarm to begin of treatment or duration of treatment until arrival of EMS) and quality are rare. In Baden-Württemberg, the emergency aid "Deutsche Lebens-Rettungs-Gesellschaft e.V. (DLRG)" Nordhardt can only estimate times and quality of primary care. The objective of this analysis was to describe and evaluate such a first responder system. METHODS: The presented study investigated the emergency responses of a first responder system in Nordhardt, close to Karlsruhe, Germany. A total of 367 emergency data sets from 2017 containing information on operating time, medical history, suspected diagnosis and medical treatment, were evaluated. Of these, 363 anonymized emergency records including the complete information (concerning process time and medical treatment) were analyzed. The focus was on different time intervals from alarm to treatment and until arrival of the EMS. Additionally, the quality of medical treatment and the measured vital data were examined. RESULTS: The median response time and time to access to the patient was 2 min in both. The patient was reached within approximately 4 min and treated for another 5 min until the EMS arrived. In two thirds of the patients, the vital parameters were measured, 5 patients were resuscitated, 23 received supplementary oxygen, 4 patients were ventilated and 11 patients suffering from hypoglycemia showed a clinical benefit from the early treatment. A total of 50 trauma patients were treated, 5 with cervical spine stabilization and 38 received a body check. CONCLUSION: The first responders from Nordhardt received an emergency call nearly every day. In two thirds of the calls they were faster than the EMS as they usually have local sites with a shorter distance to the emergency scene where they are able to deal with critical medical cases until the EMS arrives. Despite the small case numbers, it could be concluded that the early medical treatment with respect to resuscitation based on earlier arrival on site may help to increase the survival rate of patients. The first responders were also able to manage airway problems with additional oxygen or other airway devices. Other medical treatment performed by the first responders, such as administration of glucose in hypoglycemic patients positively affected the patient's condition. There is a tactical advantage to include first responders in traditional EMS services. Further studies are needed to examine these questions in larger samples also over a longer time period. Standardization and digitalization of the records could help to gain more data in this field.

Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.

BACKGROUND: The goal of allergen-specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus-like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. METHODS: We differentiated human mast cells in vitro from blood-derived stem cell progenitors and sensitized the cells with a monoclonal Fel d 1-specific IgE. We compared the capability of Fel d 1 to induce mast cell activation in its free form versus displayed on VLPs and we performed allergen binding studies by surface plasmon resonance as well as flow cytometry. RESULTS: We show that free Fel d 1 induces degranulation of IgE-sensitized mast cells whereas Fel d 1 displayed on VLPs fails to induce mast cell activation. We demonstrate that this inability to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface-bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation. CONCLUSION: These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.

Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid-treated eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy. METHODS: Medical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components. RESULTS: Patients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, that is, the kallikreins (KLK)-5 and KLK-7, were observed as compared with controls, while reduced expression of lympho-epithelial Kazal-type-related inhibitor (LEKTI), filaggrin, E-cadherin, claudin, occludin, desmoglein-1 was found, independent of CS therapy. In CS-treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS-naive EoE. CONCLUSION: This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.

NMR studies on the coupling of ion and water dynamics on various time and length scales in glass-forming LiCl aqueous solutions.

We combine 1H, 2H, and 7Li NMR methods to investigate the dynamics of water molecules and lithium ions in LiCl aqueous solutions over wide ranges of time and length scales down to their glass transitions. Structural relaxation times τ and self-diffusion coefficients D reveal that water and lithium dynamics are faster for lower salt content at ambient temperatures, while the differences vanish upon cooling when fractional freezing leads to similar salt concentrations in the remaining liquid phases. Relaxation times and diffusion coefficients of water molecules agree with those of lithium ions in the weakly supercooled regime, indicating that the dynamics are strongly coupled. Furthermore, non-Arrhenius temperature dependence is found and the Stokes-Einstein relation is obeyed in this temperature range. However, we observe various decoupling phenomena for the motion of the constituents and for dynamics on different length scales in the deeply supercooled regime. Most notably, the rotational motion of the water molecules does not follow the glassy slowdown of the studied salt solutions below ∼145 K, but it rather resembles that in nanoscopic confinement, molecular solutions, and high-density amorphous ice at low temperatures. This common low-temperature water dynamics is characterized by large-angle reorientation and Arrhenius temperature dependence.

Effects of the bond polarity on the structural and dynamical properties of silica-like liquids.

Silica is a network-forming liquid that shares many properties with water due to its tetrahedral structure. It undergoes a transition from a fragile to a strong liquid as the temperature is decreased, which is accompanied by a structural change to lower density and higher tetrahedral order. In order to disentangle the effects of Coulomb and van der Waals interactions on the structure and dynamics of liquid silica, we modify the bond polarity by changing the partial charges assigned to each atom. Using molecular dynamics simulations, we show that density, tetrahedral order, and structural relaxation times decrease when reducing bond polarity. Moreover, we find that the density maximum and the fragile-to-strong transition move to lower temperatures until they eventually vanish when the partial charges are decreased below approximately 75% of their regular value. Irrespective of whether strong or fragile behavior exists, structural relaxation is governed by hopping motion at sufficiently low temperatures. As long as there is a strong regime, the energy barrier associated with strong dynamics decreases with decreasing partial charges, but the dependence on the bond polarity differs from that of the activation energy in the Arrhenius regime at high temperatures. We show that the fragile-to-strong transition is associated with structural changes occurring between the first and second coordination shells that lead to a decrease in density and an increase in tetrahedral order. In particular, independent of the value of the partial charges, the distribution of the local structures is the same at this dynamic crossover, but we find no evidence that the effect occurs upon crossing the Widom line. In the fragile regime at intermediate temperatures, the relaxation times are well described by a previously proposed model which decomposes the apparent activation energy into a constant single-particle contribution and a temperature-dependent collective contribution. However, our results for silica-like melts do not obey several common relations of the model parameters reported for molecular glass formers.

Factors associated with the emotional health of children: high family income as a protective factor.

Anxiety and depressive symptoms have adverse effects on children's development. The present study investigates the associations of socioeconomic factors as well as maternal emotional health with children's emotional health status. The data were collected between 2011 and 2015 in the LIFE Child study, a population-based cohort study in Leipzig, Germany. The emotional health status of 1093 children (2.5-11.9 years old) was investigated using the subscale 'emotional problems' of the Strengths and Difficulties Questionnaire. Associations of maternal emotional health, family status, and socioeconomic status (SES) with the emotional health status of children were estimated via regression analyses. 21.13% of the participating children were assigned to the 'risk' group for emotional problems. The results furthermore revealed that children of mothers reporting more depressive symptoms, children living in single-parent families, and children of families with lower SES scored higher in the emotional problems scale. When considering the different indicators of SES (parental education, occupational status, and monthly net income) separately, only income showed significant associations with children's emotional health status. The prevalence of emotional problems in children in Leipzig, a city in East Germany, appears to be higher than the previously reported German average. Maternal depressive symptoms, single-parent families, lower SES, and especially lower income can be seen as risk factors for children's emotional health.

[Prevalence of Gastroschisis, Omphalocele, Spina Bifida and Orofacial Clefts of Neonates from January 2000 to December 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany]. / Prävalenz von Gastroschisis, Omphalozele, Spina bifida und orofazialen Spaltbildungen bei Neugeborenen im Zeitraum Januar 2000­Dezember 2010 in Leipzig, Sachsen, Sachsen-Anhalt und Deutschland.

BACKGROUND: Malformations are the most common cause of death in infancy. Numerous studies indicate an increased prevalence of malformations in neonates in recent years in some countries around the world. This study analyzed local and national trends of the prevalences of gastroschisis, omphalocele, spina bifida and orofacial clefts during 2000 till 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany. METHODS: The prevalence of neonatal malformations was studied retrospectively from January 2000 till December 2010 using 4 sources from Leipzig, Saxony, Saxony-Anhalt and Germany. RESULTS: Between 2000 and 2010, the prevalence in Germany and in Saxony, respectively was 1.97/2.12 (gastroschisis), 1.63/1.48 (omphalocele), 5.80/8.11 (orofacial clefts) and 2.92/2.50 (spina bifida) of 10 000 live births. In Saxony, a small increase in prevalence was detected (OR/year: 1.01-1.09). In Germany, the prevalence of malformations also increased significantly (OR/year: 1.01-1.04) with the exception of the prevalence of spina bifida which seemed to decline (OR/year 0.986 (0.97-1.0), p-adjust=0.04). CONCLUSION: Whether or not there has been an actual increase in the prevalence of neonatal malformations in Germany over the years or the apparent increase is just due to bias, coding errors, multiple reporting and/or false registration and codification remains unclear. Importantly, in Germany, since prevalence of malformations is monitored prospectively only in Saxony-Anhalt and Rhineland-Palatinate, only in these states is it possible to recognize recent changes. For early identification of changes in prevalence and timely implementation of preventive measures, a nationwide register or additional regional registers are deemed necessary.

Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans.

BACKGROUND/OBJECTIVES: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO2), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers and insulin sensitivity in humans. SUBJECTS/METHODS: Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week very-low-calorie diet (VLCD, 500 kcal day-1; WL), and a subsequent 4-week weight stable diet (WS). Body composition, AT pO2 (optochemical monitoring), ATBF (133Xe washout), and whole-body insulin sensitivity were determined, and AT biopsies were collected at baseline, end of WL (week 5) and end of WS (week 9). RESULTS: Body weight, body fat percentage and adipocyte size decreased significantly during the DI period. The DI markedly decreased AT pO2 and improved insulin sensitivity, but did not alter ATBF. Finally, the DI increased AT gene expression of pathways related to mitochondrial biogenesis and non-mitochondrial oxygen consumption. CONCLUSIONS: VLCD-induced WL markedly decreases abdominal subcutaneous AT pO2, which is paralleled by a reduction in adipocyte size, increased AT gene expression of mitochondrial biogenesis markers and non-mitochondrial oxygen consumption pathways, and improved whole-body insulin sensitivity in humans.