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The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer's disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1–42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases. [ABSTRACT FROM AUTHOR]

Yet, it is important to note that the patients' preference on a survival benefit versus a potentially impaired QoL has yet to be studied in MM, e.g. it is unknown whether patients would accept reduced survival for better QoL or vice-versa. Those patients who had received LEN maintenance therapy before the time of the survey and whose LEN therapy had been terminated before the time the survey was undertaken, were significantly more likely to belong to the "in favor QoL"-group. Keywords: Multiple myeloma; Quality of life; Progression-free survival; Endpoint measure; Patient involvement; Lenalidomide maintenance therapy EN Multiple myeloma Quality of life Progression-free survival Endpoint measure Patient involvement Lenalidomide maintenance therapy 12897 12902 6 10/24/23 20231101 NES 231101 This study was previously presented at the 63rd ASH Annual Meeting and Exposition in Atlanta, Georgia, December 11-14, 2021; oral presentation. [Extracted from the article]

To evaluate microstructural cerebral changes in children suffering from typical hemolytic uremic syndrome (HUS) based on apparent diffusion coefficient (ADC) maps. For 12 pediatric HUS patients (0.8 - 14.6 years of age) conventional magnetic resonance imaging (cMRI) at 1.5 T was retrospectively analyzed. ADC values were measured in 35 different brain regions and compared with age-related, previously published ADC reference values from a healthy pediatric control group. The HUS cohort was divided into 2 subgroups depending on clinical outcome. Subgroup A showed poor neurological outcome whereas subgroup B demonstrated improvement without lasting neurological deficits. Qualitative analysis revealed lesions by diffusion-weighted imaging (DWI) with hypointense correlate on the ADC map in basal ganglia and/or thalami and corresponding T2 hyperintensities in the majority of patients in Subgroup A (80%). Those in Subgroup B did not show qualitative DWI alterations with ADC correlate even when T2 hyperintense lesions were detected in basal ganglia and/or thalami. Quantitative analysis demonstrated abnormal ADC values in all HUS patients with a trend to a greater number of affected regions in Subgroup A compared to Subgroup B (16 versus 11 median number of regions respectively, p = 0.56). Conclusion: Using DWI qualitative and quantitative differences were found between HUS patients showing poor neurological outcome and those without neurological deficits at discharge. While ADC values indicated more extensive cerebral changes than conventional qualitative findings, both may provide early prognostic indicators for neurological outcome in pediatric HUS patients. What is Known: • In patients with STEC-HUS and neurological symptoms, MRI may show hyperintense signals on T2 and altered diffusivity mostly affecting basal ganglia, thalami and periventricular white matter. What is New: • In such patients, early MRI including quantitative ADC measurements over different brain regions may allow for detection of signal alterations possibly reflecting microstructural changes in such patients. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between periodontitis and sarcopenia parameters in middle-aged adults is largely unexplored. This study investigated the association between periodontitis and combined handgrip strength and skeletal muscle mass in middle-aged adults. Materials and methods: A sub-cohort of 1912 individuals with complete periodontal and whole-body dual X-ray absorptiometry examinations from the 2013–2014 wave of the National Health and Nutrition Examination Survey (n = 10,175) were analyzed using fully adjusted multiple linear regression models for associations between periodontitis and skeletal muscle mass index (kg/m2) and combined handgrip strength (kg). Results: The mean age of the study cohort was 43 (± 8.4) years and 49.4% of the participants were male. In total, 612 participants (32%) were determined to have periodontitis, of which 513 (26.8%) had non-severe (mild or moderate) periodontitis, and 99 (5.2%) had severe periodontitis. In unadjusted regression models, both non-severe and severe periodontitis were associated with SMMI (βnon-severe = 1.01, 95% CI 0.50; 1.52 and βsevere = 1.42, 95% CI 0.59; 2.25) but not with cHGS. After adjusting for age, sex, education, body mass index, bone mineral density, diabetic status, education, total energy intake, total protein intake, and serum vitamin D2 + D3, periodontitis was associated with cHGS (βnon-severe = -2.81, 95% CI − 4.7; − 1.15 and βsevere = − 2.73, 95% CI − 6.31; 0.83). The association between periodontitis and SMMI remained for non-severe periodontitis (βnon-severe = 0.07, 95% CI − 0.26; 0.40 and βsevere = 0.22, 95% CI − 0.34; 0.78). Conclusion: The present study highlights the need of further prospective research to investigate the nature and direction of the relationship between periodontitis and sarcopenia indicators. Future studies can support the screening, prevention and clinical management of sarcopenia and periodontitis, and emphasize the interdisciplinary and complementary approach between the disciplines of geriatric medicine and periodontology. [ABSTRACT FROM AUTHOR]

Since Purcell's seminal report 75 years ago, electromagnetic resonators have been used to control light-matter interactions to make brighter radiation sources and unleash unprecedented control over quantum states of light and matter. Indeed, optical resonators such as microcavities and plasmonic antennas offer excellent control but only over a limited spectral range. Strategies to mutually tune and match emission and resonator frequency are often required, which is intricate and precludes the possibility of enhancing multiple transitions simultaneously. In this letter, we report a strong radiative emission rate enhancement of Er3+-ions across the telecommunications C-band in a single plasmonic waveguide based on the Purcell effect. Our gap waveguide uses a reverse nanofocusing approach to efficiently enhance, extract and guide emission from the nanoscale to a photonic waveguide while keeping plasmonic losses at a minimum. Remarkably, the large and broadband Purcell enhancement allows us to resolve Stark-split electric dipole transitions, which are typically only observed under cryogenic conditions. Simultaneous radiative emission enhancement of multiple quantum states is of great interest for photonic quantum networks and on-chip data communications. Emission enhancement and extraction from quantum emitters is a major challenge for photon sources in e.g. quantum photonic networks. Here the authors propose a broadband waveguide platform which allows to boost, extract, and guide quantum emission within integrated photonic networks. [ABSTRACT FROM AUTHOR]

Sustainability research has increasingly emphasized the importance of value networks in the design and development of sustainable business models (SBM). This is because SBMs must incorporate economic, environmental and social goals to achieve their desired impacts, hence designing such models requires firms to develop an understanding of value creation from the perspective of all key stakeholders in their networks in order to co-create economic, social and ecological value. To advance our understanding of how value network activities shape SBM development, we conducted a longitudinal case study of RECUP, a born sustainable startup with a circular economy business model that has developed and worked with a broad value network to achieve a major reduction in waste from linear consumption. We identify three sets of value network activities that supported the continuous development of the firm's value proposition and contributed to mutual value creation among stakeholders from business, politics and society: B2B-partnering, political agenda-setting and mobilizing end-consumers. Our contributions to research on SBM innovation and design include demonstrating how value network activities initially emerge through experimentation and consolidate over time through iterative learning processes. Such learning and adaption through dynamic value network activities is especially important, we argue, when value-creating factors are not sufficiently known in advance by startups and/or their stakeholders. [ABSTRACT FROM AUTHOR]

Parent–child communication represents an important variable in clinical child and family psychology due to its association with a variety of psychosocial outcomes. To give an overview of instruments designed to measure the quality of parent–child communication from the child's (8–21 years) perspective and to assess the psychometric quality of these instruments, we performed a systematic literature search in Medline and PsycInfo (last: February 25, 2022). Peer-reviewed journal articles published in English with a child-rated instrument measuring the quality of parent–child communication were included. Initial screening for eligibility and inclusion, subsequent data extraction, and quality assessment were conducted by couples of review team members. Based on the screening of 5115 articles, 106 studies reported in 126 papers were included. We identified 12 parent–child communication instruments across the studies. The Parent-Adolescent Communication Scale (PACS) was used in 75% of the studies. On average, the evidence for psychometric quality of the instruments was low. Few instruments were used in clinical and at-risk samples. Several instruments are available to rate parent–child communication from the child's perspective. However, their psychometric evidence is limited and the theoretical foundation is largely undocumented. This review has limitations with regard to selection criteria and language bias. Registration PROSPERO: CRD42021255264. [ABSTRACT FROM AUTHOR]

We report the direct observation of an electrically-induced magnetic susceptibility in the molecular nano- magnet [Fe3O(O2CPh)6(py)3]ClO4·py, an Fe3 trimer. This magnetoelectric effect results from the breaking of spatial inversion symmetry due to the spin configurations of the antiferromagnetic trimer. Both static and very low frequency electric fields were used. Fractional changes of the magnetic susceptibility of 11 ppb ± 2 per kVm-1 for the temperature range 8.5 < T < 13.5 K were observed for applied electric fields up to 62 kV m−1. The changes in susceptibility were measured using a tunnel diode oscillator operating at liquid helium temperatures while the sample is held at a higher regulated temperature. [ABSTRACT FROM AUTHOR]

The quality of dyadic Parent–Child Communication (PCC) between parents and their adolescent children may be important for the adolescent’s general development and mental health during adolescence. Since German instruments for measuring PCC are still lacking, this study aimed to validate the German translation of the Parent-Adolescent Communication Scale (PACS), an internationally established self-report questionnaire. To examine the theoretical-based two-factor model of the PACS in a German population sample of 1044 parent-adolescent dyads, confirmatory factor analyses were used. Moreover, the cross-group measurement invariance of the instrument was assessed. Two clinical samples were used to assess discriminative validity. Bland–Altman plots were used to asses parent-adolescent agreement. The two-factor structure of the PACS was supported. Scalar measurement invariance was established for parent age groups and adolescent gender but not for adolescent age groups and parent gender. Convergent and divergent validity were established. Discriminative validity was only established for the adolescent version in the adolescent psychiatry sample. Test–retest reliability was satisfactory, and rater agreement was medium. The German translation of the PACS is a reliable and valid measurement to assess parent-adolescent communication quality per self-report. Research directions include the concordance discrepancy in clinical samples and further investigation of changes in parents’ and adolescents’ perspectives on communication problems and open communication. Registration: NCT05332236 (clinicaltrials.gov), first registered 2022-04-11. [ABSTRACT FROM AUTHOR]

Purpose: In infections of the Central Nervous System (iCNS), rapid identification of causing pathogens is crucial for survival and to avoid long-term sequelae. Targeted therapy may reduce side effects and development of antibiotic resistance. New molecular-based syndromic tests such as the "meningitis/encephalitis panel" (MEP) allow accelerated pathogen identification from cerebrospinal fluid. We conducted a clinical study to evaluate the MEP's efficacy in paediatric patients. Methods: Cohort study in a unique clinical setting by comparing the outcome data of two neighbouring Children's Hospitals in Germany which are comparable in size, catchment area and equipment but differ regarding availability of the MEP: study centre 1 (SC1): yes; SC2: no. The study population included 213 paediatric patients with a suspected iCNS (SC1: 106; SC2: 107), with comparable age, CRP at admission and frequency of intensive care. The primary outcome was total use of antibiotics. Results: Total antibiotic use per patient was numerically lower in SC1 than in SC2 (SC1: median 2.83 days; SC2 3.67 days; p = 0.671). Multiple linear regression analysis did not show a relevant association between MEP-availability and total antibiotic use (ß = 0.1, 95% confidence interval [−1.46; +1.67], p = 0.897). In the subcohort with suspected meningoencephalitis (SC1: 18, SC2: 17), duration of acyclovir treatment was shorter in SC1 than in SC2 (median 1.3 days vs. 2.7 days, descriptive p = 0.0397). Conclusions: The add-on use of the MEP in paediatric patients with suspected iCNS was associated with a non-significant reduction in total antibiotic use, and with a reduced exposure to acyclovir in treated patients. [ABSTRACT FROM AUTHOR]

In recent years, a plethora of methods combining neural networks and partial differential equations have been developed. A widely known example are physics-informed neural networks, which solve problems involving partial differential equations by training a neural network. We apply physics-informed neural networks and the finite element method to estimate the diffusion coefficient governing the long term spread of molecules in the human brain from magnetic resonance images. Synthetic testcases are created to demonstrate that the standard formulation of the physics-informed neural network faces challenges with noisy measurements in our application. Our numerical results demonstrate that the residual of the partial differential equation after training needs to be small for accurate parameter recovery. To achieve this, we tune the weights and the norms used in the loss function and use residual based adaptive refinement of training points. We find that the diffusion coefficient estimated from magnetic resonance images with physics-informed neural networks becomes consistent with results from a finite element based approach when the residuum after training becomes small. The observations presented here are an important first step towards solving inverse problems on cohorts of patients in a semi-automated fashion with physics-informed neural networks. [ABSTRACT FROM AUTHOR]

In response to COVID-19, governments worldwide are implementing public health and social measures (PHSM) that substantially impact many areas beyond public health. The new field of PHSM data science collects, structures, and disseminates data on PHSM; here, we report the main achievements, challenges, and focus areas of this novel field of research. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen responsible for significant human morbidity and mortality. Post-transcriptional regulation by small RNAs (sRNAs) has emerged as an important mechanism for controlling virulence. However, the functionality of the majority of sRNAs during infection is unknown. To address this, we performed UV cross-linking, ligation, and sequencing of hybrids (CLASH) in MRSA to identify sRNA-RNA interactions under conditions that mimic the host environment. Using a double-stranded endoribonuclease III as bait, we uncovered hundreds of novel sRNA-RNA pairs. Strikingly, our results suggest that the production of small membrane-permeabilizing toxins is under extensive sRNA-mediated regulation and that their expression is intimately connected to metabolism. Additionally, we also uncover an sRNA sponging interaction between RsaE and RsaI. Taken together, we present a comprehensive analysis of sRNA-target interactions in MRSA and provide details on how these contribute to the control of virulence in response to changes in metabolism. Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, McKellar et al. apply RNase IIICLASH of multi-drug resistant Staphylococcus aureus under different culture conditions to link the network of RNA-RNA interactions to environmental conditions and find that the production of small membrane-permeabilizing toxins is strongly regulated by sRNAs. [ABSTRACT FROM AUTHOR]

Purpose: Major surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured "Enhanced Recovery after Surgery (ERAS)" program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer. Methods: 134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital. Results: Preoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p < 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6–23) vs pre-ERAS: 13 (6–50) days; p < 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group. Conclusion: The implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated. [ABSTRACT FROM AUTHOR]

The reported incidence of incisional hernia following repair of abdominal aortic aneurysm (AAA) via midline laparotomy is up to 69%. This prospective, multicenter, double-blind, randomised controlled trial was conducted at eleven hospitals in Germany. Patients aged 18 years or older undergoing elective AAA-repair via midline incision were randomly assigned using a computer-generated randomisation sequence to one of three groups for fascial closure: with long-term absorbable suture (MonoPlus®, group I), long-term absorbable suture and onlay mesh reinforcement (group II) or extra long-term absorbable suture (MonoMax®, group III). The primary endpoint was the incidence of incisional hernia within 24 months of follow-up, analysed by intention to treat. Physicians conducting the postoperative visits and the patients were blinded. Between February 2011 and July 2013, 104 patients (69.8 ± 7.7 years) were randomised, 99 of them received a study intervention. The rate of incisional hernia within 24 months was not significantly reduced with onlay mesh augmentation compared to primary suture (p = 0.290). Furthermore, the rate of incisional hernia did not differ significantly between fascial closure with slow and extra long-term absorbable suture (p = 0.111). Serious adverse events related to study intervention occurred in five patients (5.1%) from treatment groups II and III. Wound healing disorders were more frequently seen after onlay mesh implantation on the day of discharge (p = 0.010) and three (p = 0.009) and six (p = 0.023) months postoperatively. The existing evidence on prophylactic mesh augmentation in patients undergoing AAA-repair via midline laparotomy probably needs critical review. As the implementation of new RCTs is considered difficult due to the increasing number of endovascular AAA treated, registry studies could help to collect and evaluate data in cases of open AAA-repair. Comparisons between prophylactic mesh implantation and the small bite technique are also required. Trial registration: ClinicalTrials.gov Identifier: NCT01353443. Funding Sources: Aesculap AG, Tuttlingen, Germany. [ABSTRACT FROM AUTHOR]

Emotion work, or the requirement to display certain emotions at the workplace, has been predominantly studied from an individual perspective. However, many services are commonly provided by work-units and teams and, therefore, studying 'unit emotion work' and its effects on customers is of research and practical interest. 'Unit emotion work' refers to shared perceptions developed by unit members regarding their emotional job requirements. In this article, we first empirically test whether emotion work can be considered as a unit shared property in the hospitality industry. Second, we investigate the multilevel effects of 'unit emotion work' on customer satisfaction and loyalty. Survey data were collected from employees of 117 work units and 1069 customers in Spain. We found evidence for shared perceptions of 'unit emotion work' in three dimensions (the requirement to display positive emotions, sensitivity requirements towards customers' emotions, and emotion-rule dissonance). Multilevel analyses showed a significant positive effect of sensitivity requirements on customer loyalty, a significant negative effect of emotion-rule dissonance on customer satisfaction, and a non-significant relationship between requirement of positive emotions and customer outcomes. Our findings provide the first empirical evidence for 'unit emotion work' and its impact on customer outcomes in the hospitality industry. [ABSTRACT FROM AUTHOR]

Interactions with others need social adjustment (i.e., the constant accommodation to changing social situations). Mixed evidence indicates positive as well as negative changes in social adjustment after subthalamic nucleus deep brain stimulation (STN-DBS) in people with Parkinson’s Disease (PwPD). To date, however, no meta-analysis of these changes exists. Thus, the study aim was to review evidence of the effects of STN-DBS on social adjustment in PwPD. For this purpose, a systematic literature search in MEDLINE was conducted. The meta-analysis was performed using a random effects model and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The MINORS tool was used to assess the methodological quality of the studies. The initial literature search identified 13,124 articles, of which 1,550 full texts were assessed for eligibility. Eight studies were finally included; for seven articles sufficient data for a meta-analysis was available. Most studies found mild impairment in social adjustment impairment pre-surgery. The meta-analysis revealed no significant changes but a statistical trend towards improvement in social adjustment up to six months (SMD = 0.25; 95%CI=–0.03,0.53; P = 0.08) and over 12 months (SMD = 0.26; 95%CI=–0.03,0.55; P = 0.07) post-surgery. Methodological quality was moderate in 87.5% of the studies and good in 12.5%. While mild impairment in social adjustment pre-surgery was reported in most studies, the data indicate that STN-DBS might yield beneficial effects toward this outcome. However, not enough data yet exists to draw firm conclusions. As a crucial skill for everyday functioning, social adjustment should be more often defined as an outcome in STN-DBS trials in PwPD and should be considered in clinical routines. [ABSTRACT FROM AUTHOR]

Giant thermal and solutal non-equilibrium fluctuations are observed in shadowgraphy experiments on liquid mixtures subjected to a temperature gradient. For large temperature differences, both the temperature and the composition dependence of the relevant thermophysical parameters and the nonlinear terms in the diffusion equation need to be taken into account, leading to a nonlinear concentration profile. For temperature differences exceeding the inverse of the Soret coefficient, in our example approximately 10 K, the usual data evaluation yields increasingly wrong diffusion and Soret coefficients that are off by almost a factor of two for a temperature difference of 50 K. A local model that treats the measured shadowgraph signal as a superposition of the contributions from every layer of the sample is able to capture the essential trend and yields a good agreement with experimental data. The results are important for the application of shadowgraphy as a tool for the measurement of Soret and diffusion coefficients, where large temperature gradients promise a good signal-to-noise ratio. [ABSTRACT FROM AUTHOR]

Existing social stressor concepts disregard the variety of task-related situations at work that require skillful social behavior to maintain good social relationships while achieving certain task goals. In this article, we challenge the view that social stressors at work are solely dysfunctional aspects evoking employee ill health. Drawing from the challenge-hindrance stressor framework, we introduce the concept of social challenge stressors as a job characteristic and examine their relationships with individual well-and ill-being. In study 1, we developed a new scale for the measurement of social challenge stressors and tested the validity of the scale. Results from two independent samples indicated support for a single-factor structure and showed that social challenge stressors are distinct from related stressor concepts. Using two samples, one of which was already used to test the factor structure, we analyzed the unique contribution of social challenge stressors in predicting employee well- and ill-being. As expected, social challenge stressors were simultaneously related to psychological strain and well-being. Using time-lagged data, study 2 investigated mechanisms that may explain how social challenge stressors are linked to well-being and strain. In line with the stress-as-offense-to-self approach, we expected indirect relationships via self-esteem. Additionally, social support was expected to moderate the relationships between social stressors and self-esteem. Whereas the indirect relationships were mostly confirmed, we found no support for the buffering role of social support in the social hindrance stressors-self-esteem link. Although we found a moderation effect for social challenge stressors, results indicated a compensation model that conflicted with expectations. [ABSTRACT FROM AUTHOR]

Ferrotoroidal order, which represents a spontaneous arrangement of toroidal moments, has recently been found in a few linear magnetoelectric materials. However, tuning toroidal moments in these materials is challenging. Here, we report switching between ferritoroidal and ferrotoroidal phases by a small magnetic field, in a chiral triangular-lattice magnet BaCoSiO4 with tri-spin vortices. Upon applying a magnetic field, we observe multi-stair metamagnetic transitions, characterized by equidistant steps in the net magnetic and toroidal moments. This highly unusual ferri-ferroic order appears to come as a result of an unusual hierarchy of frustrated isotropic exchange couplings revealed by first principle calculations, and the antisymmetric exchange interactions driven by the structural chirality. In contrast to the previously known toroidal materials identified via a linear magnetoelectric effect, BaCoSiO4 is a qualitatively new multiferroic with an unusual coupling between several different orders, and opens up new avenues for realizing easily tunable toroidal orders. Toroidal moments arise from vortex like spin arrangements. These moments can then interact, giving rise to ferri- or ferro-toroidal order, though controlling such order is difficult. Here, the authors demonstrate a ferri-toroidal state in BaCoSiO4, which under an applied magnetic field exhibits multiple toroidal and metamagnetic transitions. [ABSTRACT FROM AUTHOR]

Introduction: Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγT) is a lineage specifying transcription factor for IL-17 expressing cells, which may contribute to the pathogenesis of Inflammatory Bowel Disease (IBD). VPR-254 is a selective in vitro inhibitor of RORγT. Aims: The main goals of our study were twofold: (1) To determine if ex vivo treatment with VPR-254 reduced relevant cytokine (IL-17 and IL-21) secretion from colonic strips of mice with colitis; (2) To determine if treatment of mice with VPR-254 attenuated parameters of colitis, using three murine IBD models. Methods: VPR-254 was evaluated ex vivo in a colonic strip assay, using tissue from mice with Dextran sulfate sodium (DSS)-induced colitis. In vivo, VPR-254 was evaluated for efficacy in DSS, Trintirobenzenesulfonic acid (TNBS) and Anti-CD40 antibody-induced murine models of colitis. Results: VPR-254 reduced the production of key pro-inflammatory cytokines (e.g., IL-17) in ex vivo and in vivo models of colitis. This small molecule inhibitor of RORγT also improved various morphometric and histological parameters associated with three diverse murine models of IBD. Conclusion: Our results support the concept that an inhibitor of ROR-gamma T may have potential utility for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Laser diodes are efficient light sources. However, state-of-the-art laser diode-based lighting systems rely on light-converting inorganic phosphor materials, which strongly limit the efficiency and lifetime, as well as achievable light output due to energy losses, saturation, thermal degradation, and low irradiance levels. Here, we demonstrate a macroscopically expanded, three-dimensional diffuser composed of interconnected hollow hexagonal boron nitride microtubes with nanoscopic wall-thickness, acting as an artificial solid fog, capable of withstanding ~10 times the irradiance level of remote phosphors. In contrast to phosphors, no light conversion is required as the diffuser relies solely on strong broadband (full visible range) lossless multiple light scattering events, enabled by a highly porous (>99.99%) non-absorbing nanoarchitecture, resulting in efficiencies of ~98%. This can unleash the potential of lasers for high-brightness lighting applications, such as automotive headlights, projection technology or lighting for large spaces. Laser-based lighting typically relies on wavelength conversion materials that reduce efficiency. The authors present a 3D boron nitride hollow-tube based foam structure that acts as a broadband diffuser with engineered disorder for conversionless white light generation from laser-diode light sources [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To assess the incidence of acute adverse events (AAEs) in gadolinium-enhanced cardiac magnetic resonance (CMR) imaging.Methods: Gadolinium-based contrast agent (GBCA)-enhanced CMR data from the multinational, multicenter European Society of Cardiovascular Radiology MRCT Registry was included. AAE severity was classified according to the American College of Radiology Manual on Contrast Media (mild, moderate, severe). Multivariable generalized linear mixed effect models were used to assess the likelihood of AAEs in various GBCA, adjusting for pharmacological stressor, main indications (i.e., suspected or known coronary artery disease or myocarditis), age, sex, and submitting center as a random effect.Results: In the study population of 72,839 GBCA-enhanced CMRs, a total of 260 AAEs were reported (0.36%), with a minority of severe AAEs (n = 24, 0.033%). Allergic-like AAEs were less likely than physiologic AAEs (29% versus 71%). Patients without pharmacological stress imaging had a lower AAE rate (0.22%) compared to stress imaging (0.75%), with the highest AAE rates for regadenoson (2.95%). AAE rates also varied by GBCA subtype (overall p < 0.001). There was significant interaction between GBCA and pharmacological stressor (interaction p = 0.025), with AAE rates ranging between 0 and 10% for certain GBCA/stressor combinations. There was further marginal evidence that higher GBCA volume was associated with higher AAE incidence (OR = 1.02, p = 0.05).Conclusion: GBCA-enhanced CMR imaging demonstrates low AAE rates comparable to those of other body regions. AAE likelihood correlates with GBCA subtype, pharmacological stressor, and imaging indication. Intravenous fluid administration in patients with cardiac impairment might contribute to these findings.Key Points: • Acute adverse event rates in cardiac magnetic resonance (CMR) imaging with gadolinium-based contrast agents (GBCAs) are low (0.36%), especially for severe adverse events (0.033%). • Mild and moderate adverse events are more frequent during stress CMR imaging. • Physiologic AAEs are more common than allergic AAEs in CMR imaging. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this study was to map the supervision of European trainees in clinical microbiology and infectious diseases during their training. An international cross-sectional questionnaire survey of 38 questions was distributed among trainees and recently graduated medical specialists from European countries. Descriptive analyses were performed on both the total group of respondents and regionally. In total, 393 respondents from 37 different countries were included. The median of overall satisfaction with the supervisor was 4 (interquartile range 3-4) on a Likert scale (range 1, not satisfied at all-5, completely satisfied). Overall, merely 34% of respondents received constructive feedback from their supervisor on a regularly basis, 36% could evaluate their own supervisor, and just 63% were evaluated on their skills using a written plan. Fifty-two percent did not receive the opportunity to do a part of the specialty training abroad and 63% received support from their supervisors to be involved in research projects or publishing papers. A considerable proportion of trainees, mainly in Southern and Eastern European regions, felt that they did not receive sufficient supervision. This information may be useful in the pursuit of harmonizing the quality of training, achieving a common curriculum, and identifying robust and objective criteria to coach and evaluate trainees in a proper way. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate and classify causes for anterior cruciate ligament (ACL) reconstruction failure. It was hypothesized that specific technical and biological reconstruction aspects would differ when comparing traumatic and non-traumatic ACL reconstruction failures.Materials and Methods: One hundred and forty-seven consecutive patients who experienced ACL reconstruction failure and underwent revision between 2009 and 2014 were analyzed. Based on a systematic failure analysis, including evaluation of technical information on primary ACL reconstruction and radiological assessment of tunnel positions, causes were classified into traumatic and non-traumatic mechanisms of failure; non-traumatic mechanisms were further sub-divided into technical and biologic causes. Spearman's rank correlation coefficient and chi-squared tests were performed to determine differences between groups based on various factors including graft choice, fixation technique, technique of femoral tunnel positioning, tunnel malpositioning, and time to revision.Results: Non-traumatic, i.e., technical, and traumatic mechanisms of ACL reconstruction failure were found in 64.5 and 29.1% of patients, respectively. Biological failure was found only in 6.4% of patients. Non-anatomical femoral tunnel positioning was found the most common cause (83.1%) for technical reconstruction failure followed by non-anatomical tibial tunnel positioning (45.1%). There were strong correlations between non-traumatic technical failure and femoral tunnel malpositioning, transtibial femoral tunnel drilling techniques, femoral transfixation techniques as well as earlier graft failure (p < 0.05).Conclusions: Technical causes, particularly tunnel malpositioning, were significantly correlated with increased incidence of non-traumatic ACL reconstruction failure. Transtibial femoral tunnel positioning techniques and femoral transfixation techniques, showed an increased incidence of non-traumatic, earlier graft failure. [ABSTRACT FROM AUTHOR]

An experimental chamber (CIME2) has been specially designed to simulate wet atmospheric deposition on limestones used in Paris cultural heritage. This instrument is a complementary tool to CIME, a previously developed chamber dedicated to the simulation of dry atmospheric deposition on monuments and artifacts. The aim of this paper is to describe CIME2 and characterize the wet deposits produced inside it. Mist (fog), drizzle, and rainfall are differentiated in order to document their ability to saturate the limestones most currently used in Paris monuments: The Saint-Maximin’s limestone, the Liais of Saint-Maximin, and the Chauvigny’s limestone are tested. The comparison between normalized and environmental petrophysical data shows that in the wet deposition simulations, limestones are not systematically water-saturated. Moreover, the realistic experimental conditions chosen favor a more rapid evaporation of the stone water. The quantification of the non-saturation state is a first step that has to be taken into account to improve the geochemical models used to predict the alteration. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the effect of differential learning of toothbrushing compared to habitual toothbrushing and instruction/demonstration of toothbrushing on plaque reduction and gingival inflammation of primary school children.Methods: Children (6-9 years) were subjected to a toothbrushing training consisting of 15 days (3 × 5 days, interval 2 days, 3 min/day) and randomly assigned to one of three groups (each n = 18): habitual toothbrushing/control, instruction/demonstration of toothbrushing, differential learning of toothbrushing. The differential learning approach comprised 15 different movement exercises (1/day), while instruction/demonstration of toothbrushing was based on repetitive practice of toothbrushing. Plaque (Turesky-modified Quigley-Hein plaque index (T-QHI)) and papilla bleeding (papilla bleeding index (PBI)) scores were assessed prior to the first toothbrushing (t0, baseline) and 21 (t1), 42 (t2) and 63 (t3) days after beginning of the study. Primary statistical analyses were performed with cumulative logit regression models with repeated measures. The global significance level was set to 5% two-sided.Results: At all time points, PBI and T-QHI were significantly reduced by differential learning compared to instruction/demonstration of toothbrushing and habitual toothbrushing. Compared to baseline, differential learning improved PBI and T-QHI significantly at all time points. In the other groups, no significant reduction of PBI compared to baseline was observed. T-QHI was significantly reduced by habitual toothbrushing only at t1 and by instruction/demonstration of toothbrushing at t1 and t2. Differential learning had an improved effect on posterior compared to anterior teeth.Conclusion: Differential learning of toothbrushing improved plaque reduction and reduced gingival inflammation compared to habitual toothbrushing and instruction/demonstration of toothbrushing in 6- to 9-year-old children in mixed dentition.Clinical relevance: Toothbrushing skills of children might be improved by differential learning.Trial registration: ISRCTN14951343, https://www.isrctn.com/ISRCTN14951343? [ABSTRACT FROM AUTHOR]

Objectives: Magnetic resonance imaging (MRI) is regarded as a non-harming and non-invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes.Methods: In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by γH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures.Results: Both cohorts showed a significant increase in the γH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant.Conclusion: Based on our study, γH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells.Key Points: • No evidence for DNA double-strand breaks after cardiac MRI. • Prospective study underlines safe use of MRI with regard to DNA damage. • Controlled trial involving both genders investigating DNA DSBs after 3-T MRI. [ABSTRACT FROM AUTHOR]

Introduction: With the increasing adoption of peroral endoscopic myotomy (POEM) as a first-line therapy for achalasia as well as a growing list of other indications, it is apparent that there is a need for effective training methods for both endoscopists in training and those already in practice. We present a hands-on-focused with pre- and post-testing methodology to teach these skills.Methods: Six POEM courses were taught by 11 experienced POEM endoscopists at two independent simulation laboratories. The training curriculum included a pre-training test, lectures and discussion, mentored hands-on instruction using live porcine and ex-plant models, and a post-training test. The scoring sheet for the pre- and post-tests assessed the POEM performance with a Likert-like scale measuring equipment setup, mucosotomy creation, endoscope navigation, visualization, myotomy, and closure. Participants were stratified by their experience with upper-GI endoscopy (Novices <100 cases vs. Experts ≥100 cases), and their data were analyzed and compared.Results: Sixty-five participants with varying degrees of experience in upper-GI endoscopy and laparoscopic achalasia cases completed the training curriculum. Participants improved knowledge scores from 69.7 ± 17.1 (pre-test) to 87.7 ± 10.8 (post-test) (p < 0.01). POEM performance increased from 15.1 ± 5.1 to 25.0 ± 5.5 (out of 30) (p < 0.01) with the greatest gains in mucosotomy [1.7-4.4 (out of 5), p < 0.01] and equipment (3.4-4.7, p < 0.01). Novices had significantly lower pre-test scores compared with Experts in upper-GI endoscopy (overall pre-score: 11.9 ± 5.6 vs. 16.3 ± 4.6, p < 0.01). Both groups improved significantly after the course, and there were no differences in post-test scores (overall post-score: 23.9 ± 6.6 vs. 25.4 ± 5.1, p = 0.34) between Novices and Experts.Conclusions: A multimodal curriculum with procedural practice was an effective curricular design for teaching POEM to practitioners. The curriculum was specifically helpful for training surgeons with less upper-GI endoscopy experience. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of breast density on the diagnostic accuracy of non-contrast cone-beam breast computed tomography (CBBCT) in comparison to mammography for the detection of breast masses.Methods: A retrospective study was conducted from August 2015 to July 2016. Fifty-nine patients (65 breasts, 112 lesions) with BI-RADS, 5th edition 4 or 5 assessment in mammography and/or ultrasound of the breast received an additional non-contrast CBBCT. Independent double blind reading by two radiologists was performed for mammography and CBBCT imaging. Sensitivity, specificity and AUC were compared between the modalities.Results: Breast lesions were histologically examined in 85 of 112 lesions (76%). The overall sensitivity for CBBCT (reader 1: 91%, reader 2: 88%) was higher than in mammography (both: 68%, p<0.001), and also for the high-density group (p<0.05). The specificity and AUC was higher for mammography in comparison to CBBCT (p<0.05 and p<0.001). The interobserver agreement (ICC) between the readers was 90% (95% CI: 86-93%) for mammography and 87% (95% CI: 82-91%) for CBBCT.Conclusions: Compared with two-view mammography, non-contrast CBBCT has higher sensitivity, lower specificity, and lower AUC for breast mass detection in both high and low density breasts.Key Points: • Overall sensitivity for non-contrast CBBCT ranged between 88%-91%. • Sensitivity was higher for CBBCT than mammography in both density types (p<0.001). • Specificity was higher for mammography than CBBCT in both density types (p<0.05). • AUC was larger for mammography than CBBCT in both density types (p<0.001). [ABSTRACT FROM AUTHOR]