Endocannabinoid-related molecules predict the metabolic efficacy of GLP-1 receptor agonism in humans with obesity.

OBJECTIVE: N-acylethanolamines (NAEs) include endocannabinoid (EC) and EC-related molecules that impact the anti-obesity and anti-diabetic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RA) in animal studies. However, the clinical relevance of these findings remains to be determined. Here, we tested whether GLP-1RA treatment affects circulating NAE levels and whether NAEs may predict the efficacy of GLP-1RA treatment in humans with obesity undergoing weight loss maintenance. MATERIALS AND METHODS: We profiled plasma levels of NAEs in participants with obesity undergoing weight loss maintenance with (n = 23)/or without (n = 20) treatment with the GLP-1RA liraglutide. NAE levels were measured at three different time points: before the start of the study, at the end of the diet-induced weight loss, and after 52-weeks treatment. Linear regression analyses were used to investigate whether pharmacological responses could be predicted by NAEs levels. RESULTS: Liraglutide treatment reduced plasma concentrations of the NAE and oleoyl-ethanolamide (OEA), without altering arachidonoyl-ethanolamide (AEA) levels and palmitoyl-ethanolamide (PEA) levels. High pre-treatment levels of OEA were predictive of superior compound-mediated effects on fasting insulin and triglyceride levels. High pre-treatment PEA and AEA levels were also predictive of superior Liraglutide-mediated effects on triglyceride levels. CONCLUSIONS: Our data suggests that specific NAEs such as OEA and AEA are promising biomarkers of GLP-1RA metabolic efficacy in humans with obesity during weight loss maintenance. Plasma profiling of EC-related molecules may be a promising strategy to tailor GLP-1R-based therapies to individual needs in obesity and diabetes management.

National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

From laboratory to the field: biological control of Fusarium graminearum on infected maize crop residues.

AIM: To evaluate biological control agents (BCAs) against Fusarium graminearum on infected maize stalks as a means to reduce Fusarium head blight (FHB) in subsequently grown wheat. METHODS AND RESULTS: In the laboratory, BCAs were applied against F. graminearum on maize stalk pieces. Clonostachys rosea inhibited the perithecia development and ascospore discharge when applied before, simultaneously with and after the pathogen. In the field, we simulated a system with high disease pressure, that is, a maize-wheat rotation under no-tillage, by preparing maize stalks inoculated with F. graminearum. The infected stalks were treated with formulations of C. rosea selected in vitro or the commercial BCA strain Trichoderma atrobrunneum ITEM908 and exposed to field conditions over winter and spring between winter wheat rows. Monitoring with spore traps and of FHB symptoms, as well as quantification of F. graminearum incidence and DNA in harvested grain revealed significant reductions by C. rosea by up to 85, 91, 69 and 95% compared with an inoculated but untreated positive control, respectively. Deoxynivalenol (DON) and zearalenone (ZEN) contents were reduced by up to 93 and 98%, respectively. Treatments with T. atrobrunneum were inconsistent, with significant reductions of DON and ZEN under warm and wet climatic conditions only. CONCLUSIONS: The findings support the application of C. rosea against F. graminearum on residues of maize to suppress the primary inoculum of FHB. SIGNIFICANCE AND IMPACT OF THE STUDY: As sustainable agriculture requires solutions to control FHB, hence, the application of C. rosea during the mulching of maize crop residues should be evaluated in on-farm experiments.

[Auditory group therapy in adult cochlear implant rehabilitation]. / Hörtherapeutische Gruppenkonzepte in der Cochleaimplantat-Rehabilitation bei Erwachsenen.

BACKGROUND: Auditory training is an established intervention in adult cochlear implant (CI) aural rehabilitation. In most cases, training is implemented in an individual therapy setting. Increasing patient numbers and the associated time-economic and cost-related demands as well as psychosocial and communicative aspects support the use of aural group interventions. OBJECTIVES: This study aimed 1) to describe concepts and contents of group interventions for adult CI users and 2) to present results of a questionnaire-based evaluation. METHODS: Group interventions have been offered at the CI Centre Erlangen CICERO for several years. In Auditory Training Groups, exercises have priority, while Thematic Group Workshops focus on psychosocial aspects and provide information for the participants. The Auditory Training Groups were evaluated based on a patient questionnaire. Additionally, the reliability of the questionnaire was analyzed. RESULTS: The median overall satisfaction of CI users participating in Auditory Training Groups was rated as good. Training of speech perception in noise as well as communicative exchange are of great importance for CI users. They rated the therapeutic design as very good to good. Reliability analysis showed significant positive intercorrelations of the questionnaire items. CONCLUSION: Group interventions are well accepted by CI users and represent a useful complement to individual therapy during the rehabilitation process. As group interventions place special demands on patients and therapists, structured and well-proven concepts should be used in practice.

Stress Management Training (SMT) Improves Coping of Tremor-Boosting Psychosocial Stressors and Depression in Patients with Parkinson's Disease: A Controlled Prospective Study.

BACKGROUND: Stress reduction and relaxation exercises are therapeutically suggested to patients with Parkinson's disease (PD) and tremor, but data regarding efficacy or preferential methods are missing. OBJECTIVE: To investigate the effect of a standardized stress management training (SMT) according to Kaluza on coping with tremor-boosting psychosocial stress factors. METHODS: 8-week SMT was applied to 82 PD patients with tremor and 30 controls. Changes in stress-associated factors were measured applying four scales: Kaluza's "warning signs for stress" and "stress-amplifying thoughts" and Beck Depression Inventory (BDI) and quality of life (PDQ-8). Short-term outcome (8 weeks) was evaluated in both groups, and long-term outcome (3-6 months) was evaluated only in PD patients. RESULTS: At baseline, PDQ-8 was worse in PD patients compared to controls. PD patients improved significantly regarding short- and long-term outcome scores of "warning signs for stress," "stress-amplifying thoughts," and BDI scores, independently of disease severity or duration. Younger and male PD patients showed the best benefit. Controls improved comparably to PD patients but significantly only with respect to "stress-amplifying thoughts." Retrospectively, 88% (29/33) of PD patients were rated SMT as helpful 12-18 months later. Self-practicing SMT exercises correlated significantly with subjectively better coping with tremor-related daily impairment and subjective short-term and long-term tremor reduction. CONCLUSION: SMT should be a part of therapy of PD patients with tremor.

Chasing quantitative biases in neutron imaging with scintillator-camera detectors: a practical method with black body grids.

We propose a method for improving the quantification of neutron imaging measurements with scintillator-camera based detectors by correcting for systematic biases introduced by scattered neutrons and other sources such as light reflections in the detector system. This method is fully experimental, using reference measurements with a grid of small black bodies (BB) to measure the bias contributions directly. Using two test samples, one made of lead alloy and having a moderate (20%) neutron transmission and one made of stainless-steel and having a very low (1%) transmission, we evaluated the improvement brought by this method in reducing both the average quantification bias and the uncertainty around this average bias after tomographic reconstruction. The results show that a reduction of the quantification bias of up to one order of magnitude can be obtained. For moderately transparent samples, little sensitivity is observed to the parameters used for the correction. For the more challenging sample with very low transmission, a correct placement of the BB grid is of utmost importance for a successful correction.

[Subjective improvement of hearing through cochlear implantation]. / Subjektive Hörverbesserung durch Cochleaimplantatversorgung.

BACKGROUND: During the past few decades various questionnaires have been developed to evaluate quality of life using audiological measures. The Hearing Implant Sound Quality Index (HISQUI) was developed especially for patients with a cochlear implant (CI). The aim of this study was to evaluate subjective hearing improvement after CI surgery and to correlate the results with objective measuring methods such as pure-tone and speech audiometry. MATERIALS AND METHODS: Pre- and postoperative data of 57 patients who received a cochlear implant (CIs) were retrospectively analyzed. For evaluation of subjective hearing ability the HISQUI questionnaire consisting of 19 questions was used as reference. Pure-tone audiometry and Freiburger monosyllable word tests were used as objective measurements for hearing. RESULTS: The mean HISQUI score increased on average from 53.0 prior to surgery to 69.0 after surgery. In addition, there were significant improvements in all seven subgroups of the questionnaire divisions. A correlation of rSp = 0.53 before surgery and rSp = 0.36 after surgery between the HISQUI scores and Freiburg monosyllable word test was recorded. In addition the 4FPTA (four frequency pure tone average) value correlated negatively with rSp = -0.48 with the HISQUI total score before surgery. CONCLUSION: The moderate correlation of both subjective and objective measurement methods underlines the importance of enquiring the patients' subjective perception and satisfaction. Through the combination of subjective statements and measurements of speech comprehension it is possible to obtain a comprehensive picture of the hearing performance of CI recipients.

A Monte Carlo approach for scattering correction towards quantitative neutron imaging of polycrystals.

The development of neutron imaging from a qualitative inspection tool towards a quantitative technique in materials science has increased the requirements for accuracy significantly. Quantifying the thickness or the density of polycrystalline samples with high accuracy using neutron imaging has two main problems: (i) the scattering from the sample creates artefacts on the image and (ii) there is a lack of specific reference attenuation coefficients. This work presents experimental and simulation results to explain and approach these problems. Firstly, a series of neutron radiography and tomography experiments of iron, copper and vanadium are performed and serve as a reference. These materials were selected because they attenuate neutrons mainly through coherent (Fe and Cu) and incoherent (V) scattering. Secondly, an ad hoc Monte Carlo model was developed, based on beamline, sample and detector parameters, in order to simulate experiments, understand the physics involved and interpret the experimental data. The model, developed in the McStas framework, uses a priori information about the sample geometry and crystalline structure, as well as beamline settings, such as spectrum, geometry and detector type. The validity of the simulations is then verified with experimental results for the two problems that motivated this work: (i) the scattering distribution in transmission imaging and (ii) the calculated attenuation coefficients.

Unlocking high spatial resolution in neutron imaging through an add-on fibre optics taper.

The demand for high resolution neutron imaging has been steadily increasing over the past years. The number of facilities offering cutting edge resolution is however limited, due to (i) the design complexity of an optimized device able to reach a resolution in the order of ≈ 10 µm and (ii) limitations in available neutron flux. Here we propose a simple addition, based on a Fibre Optics Taper (FOT), that can be easily attached to an already existing scintillator-camera imaging detector in order to efficiently increase its spatial resolution and hence boost the capability of an instrument into high resolution applications.

Factors associated with fractures in HIV-infected persons: which factors matter?

This study aims to determine what factors are associated with increased risk of fracture among patients with HIV, in particular whether an important medication used to treat HIV, tenofovir, is associated with fracture. Our study found that while co-infection with hepatitis C and markers of HIV severity were associated with fracture, tenofovir was not. INTRODUCTION: Growing evidence suggests that tenofovir disoproxil fumarate decreases bone density among patients with HIV, but there are conflicting reports as to whether this decrease in bone density translates to higher fracture risk. We aimed to determine what factors were associated with an increased risk of fracture for patients with HIV, in particular whether tenofovir is associated with elevated fracture risk. METHODS: We conducted a retrospective cohort study at two tertiary care hospitals in Boston, MA, between 2001 and 2012 to determine whether tenofovir use is associated with elevated all-site fracture risk, as compared to other antiretroviral medications. We also examined other potential factors associated with fracture among patients with HIV. RESULTS: We identified 1981 HIV-infected patients who had at some point used tenofovir and 682 patients who had not. The mean age was 43 years, and 72 % were male. The hepatitis C co-infection rate was 28 %, about 40 % had nadir CD4 count <200, and about 40 % had a history of an AIDS-defining illness. We did not find an association between risk of fracture and tenofovir disoproxil fumarate (TDF) (adjusted RR (aRR) 0.8, 95 % CI 0.6-1.1). However, co-infection with hepatitis C did increase risk of fracture (aRR 1.6, 95 % CI 1.1-2.3), as did nadir CD4 count <200 (aRR 3.1, 95 % CI 1.9-5.0) and history of AIDS-defining illness (aRR 1.6, 95 % CI 1.1-2.2). CONCLUSION: There was no association found between fracture and tenofovir use, but there were associations between co-infection with hepatitis C and markers of advanced HIV disease and fracture.

Solvent and solute ingress into hydrogels resolved by a combination of imaging techniques.

Using simultaneous neutron, fluorescence, and optical brightfield transmission imaging, the diffusion of solvent, fluorescent dyes, and macromolecules into a crosslinked polyacrylamide hydrogel was investigated. This novel combination of different imaging techniques enables us to distinguish the movements of the solvent and fluorescent molecules. Additionally, the swelling or deswelling of the hydrogels can be monitored. From the sequence of images, dye and solvent concentrations were extracted spatially and temporally resolved. Diffusion equations and different boundary conditions, represented by different models, were used to quantitatively analyze the temporal evolution of these concentration profiles and to determine the diffusion coefficients of solvent and solutes. Solute size and network properties were varied and their effect was investigated. Increasing the crosslinking ratio or partially drying the hydrogel was found to hinder solute diffusion due to the reduced pore size. By contrast, solvent diffusion seemed to be slightly faster if the hydrogel was only partially swollen and hence solvent uptake enhanced.

Water distribution in a sorption enhanced methanation reactor by time resolved neutron imaging.

Water adsorption enhanced catalysis has been recently shown to greatly increase the conversion yield of CO2 methanation. However, the joint catalysis and adsorption process requires new reactor concepts. We measured the spatial water distribution in a model fixed bed reactor using time resolved neutron imaging. Due to the high neutron attenuation coefficient of hydrogen, the absorbed water in the sorption catalyst gives a high contrast allowing us to follow its formation and map its distribution. At the same time, the product gas was analysed by FTIR-gas analysis. The measurements provided crucial insights into the future design of sorption reactors: during the sorption enhanced reaction, a reaction front runs through the reactor. Once the extension of the reaction front reaches the exhaust, the conversion rate of sorption enhanced methanation decreases. The existence of a reaction front running through the reactor is prerequisite for a high conversion rate. We give a simple model of the experimental results, in particular the conditions, under which a reaction front is established. In particular the latter effect must be taken into account for the dimensions of a large scale reactor.

[Improved IgG Antibody Diagnostics of Feather Duvet Lung by an Antibody Screening Test]. / Optimierte IgG-Antikörperdiagnostik der Bettfedern-Alveolitis mittels EAA-Suchtest.

The underdiagnosed feather duvet lung, an extrinsic allergic alveolitis (hypersensitivity pneumonitis) caused by duck and goose feathers, can be more frequently diagnosed, if duck and goose feather antibodies are included in the panel of the routinely applied IgG antibody screening test. This does not necessarily require extending the screening test to include duck and goose feather antigens. By analysing 100 sera with duck and goose antibodies we found that the commonly used pigeon and budgerigar antibodies can also screen for feather duvet antibodies. All examined sera lacking pigeon and budgerigar antibodies also lacked clear-cut duck and goose feather antibodies. The examined sera with strong pigeon or budgerigar antibodies always also contained feather duvet antibodies. However, sera with medium or low concentrated pigeon or budgerigar antibodies are not always associated with feather duvet antibodies. In the light of these observations, we find that 71% of the duck and goose antibody analyses would be dispensable without essential loss of quality, if the results of screening for pigeon and budgerigar antibodies were incorporated into the procedure of a step-by- step diagnostics.

Neutron, fluorescence, and optical imaging: An in situ combination of complementary techniques.

An apparatus which enables the simultaneous combination of three complementary imaging techniques, optical imaging, fluorescence imaging, and neutron radiography, is presented. While each individual technique can provide information on certain aspects of the sample and their time evolution, a combination of the three techniques in one setup provides a more complete and consistent data set. The setup can be used in transmission and reflection modes and thus with optically transparent as well as opaque samples. Its capabilities are illustrated with two examples. A polymer hydrogel represents a transparent sample and the diffusion of fluorescent particles into and through this polymer matrix is followed. In reflection mode, the absorption of solvent by a nile red-functionalized mesoporous silica powder and the corresponding change in fluorescent signal are studied.

Quantification of the sensitivity range in neutron dark-field imaging.

In neutron grating interferometry, the dark-field image visualizes the scattering properties of samples in the small-angle and ultra-small-angle scattering range. These angles correspond to correlation lengths from several hundred nanometers up to several tens of micrometers. In this article, we present an experimental study that demonstrates the potential of quantitative neutron dark-field imaging. The dark-field signal for scattering from different particle sizes and concentrations of mono-dispersive polystyrene particles in aqueous solution is compared to theoretical predictions and the good agreement between measurements and calculations underlines the quantitative nature of the measured values and reliability of the technique with neutrons.

Cold neutron diffraction contrast tomography of polycrystalline material.

Traditional neutron imaging is based on the attenuation of a neutron beam through scattering and absorption upon traversing a sample of interest. It offers insight into the sample's material distribution at high spatial resolution in a non-destructive way. In this work, it is expanded to include the diffracted neutrons that were ignored so far and obtain a crystallographic distribution (grain mapping). Samples are rotated in a cold neutron beam of limited wavelength band. Projections of the crystallites formed by the neutrons they diffract are captured on a two dimensional imaging detector. Their positions on the detector reveal their orientation whereas the projections themselves are used to reconstruct the shape of the grains. Indebted to established synchrotron diffraction contrast tomography, this 'cold neutron diffraction contrast tomography' is performed on recrystallized aluminium for experimental comparison between both. Differences between set-up and method are discussed, followed by the application range in terms of sample properties (crystallite size and number, mosaicity and typical materials). Neutron diffraction contrast tomography allows to study large grains in bulky metallic structures.

Dual spectrum neutron radiography: identification of phase transitions between frozen and liquid water.

In this Letter, a new approach to distinguish liquid water and ice based on dual spectrum neutron radiography is presented. The distinction is based on arising differences between the cross section of water and ice in the cold energy range. As a significant portion of the energy spectrum of the ICON beam line at Paul Scherrer Institut is in the thermal energy range, no differences can be observed with the entire beam. Introducing a polycrystalline neutron filter (beryllium) inside the beam, neutrons above its cutoff energy are filtered out and the cold energy region is emphasized. Finally, a contrast of about 1.6% is obtained with our imaging setup between liquid water and ice. Based on this measurement concept, the temporal evolution of the aggregate state of water can be investigated without any prior knowledge of its thickness. Using this technique, we could unambiguously prove the production of supercooled water inside fuel cells with a direct measurement method.

Energy-selective neutron imaging for morphological and phase analysis of iron-nickel meteorites.

We propose energy-selective neutron imaging as a new and non-destructive method to investigate rare metallic meteorites. It is based on attenuation of a neutron beam of limited spectral distribution in a sample depending on the elemental composition and crystalline structure. Radiography and tomography allow obtaining the presence, morphology and orientation information in the bulk of mineral inclusions, oxide crust and crystalline structure. Its usage in classification and meteor formation studies would be of great value.

Hydride generation using a metallic atomizer after microwave-assisted extraction for inorganic arsenic speciation in biological samples.

The present speciation method reports the determination of inorganic arsenic forms, using metallic furnace hydride generation atomic absorption spectrometry. The inorganic As speciation is carried out using mild conditions for hydride formation, such as slightly acid pH media (4.50) and low tetrahydridoborate(1-) concentration (0.1% (w/v)). Limits of detection and quantification of 2.0 and 6.6 µg L(-1) of iAs(III) are obtained using optimized conditions. Additionally, microwave-assisted extraction using water as solvent is carried out to provide the appropriate environment for As species extraction as well as impeding inter-conversion between species. With these analytical strategies, As was accurately determined (at 99.9% confidence level) in water and plankton samples.