Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

Mott insulators with boundary zeros.

The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green's function zeros defining the "Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of "topological antimatter" annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green's function zeros.

Changes in HIV Prevention and Sexual Experiences During the COVID-19 Pandemic: A Mixed-Methods Study.

BACKGROUND: STI and HIV services and infection rates were affected during the COVID-19 pandemic, because of changes in access to health care and individual behavior. Understanding how individuals made decisions around prevention and sexual activities during different phases of the pandemic is useful to addressing the rising rates of STIs and HIV. SETTING: Federally-qualified health center focused on sexual and gender minority health, Chicago IL, 2021. METHODS: Patients with a history of PrEP use who were contacted by the PrEP retention team as part of standard care were invited to complete an online survey. A subset of survey participants were then contacted to complete one-on-one interviews. Participants were asked about two distinct periods: November 2020 to January 2021 and February to June 2021. RESULTS: From the 356 survey participants (mostly young, insured, and experienced with PrEP), more than half maintained their number of sex partners during the early pandemic and most also maintained PrEP use; during the later pandemic; most reported more or the same number of sex partners and almost all maintained PrEP use. From interviews, we identified diverse and changing experiences regarding sexual practices throughout the pandemic; whereas many participants changed PrEP use in accordance with sexual practices, many others maintained PrEP use as a habit. COVID-19 prevention was also a factor in sexual activities, particularly prevaccination. CONCLUSION: Many PrEP users try to align their HIV prevention with their sexual exposures and establish PrEP as a long-term habit. Removing financial and access barriers is important to improve PrEP use and STI testing.

Characterization data of reference materials used for phase II of the priority program DFG SPP 2005 "Opus Fluidum Futurum - Rheology of reactive, multiscale, multiphase construction materials".

A thorough characterization of base materials is the prerequisite for further research. In this paper, the characterization data of the reference materials (CEM I 42.5 R, limestone powder, calcined clay and a mixture of these three components) used in the second funding phase of the priority program 2005 of the German Research Foundation (DFG SPP 2005) are presented under the aspects of chemical and mineralogical composition as well as physical and chemical properties. The data were collected based on tests performed by up to eleven research groups involved in this cooperative program.

Secondary Dysfunction of the Intestinal Barrier in the Pathogenesis of Complications of Acute Poisoning.

The last decade has been marked by an exponential increase in the number of publications on the physiological role of the normal human gut microbiota. The idea of a symbiotic relationship between the human organism and normal microbiota of its gastrointestinal tract has been firmly established as an integral part of the current biomedical paradigm. However, the type of this symbiosis varies from mutualism to parasitism and depends on the functional state of the host organism. Damage caused to the organism by external agents can lead to the emergence of conditionally pathogenic properties in the normal gut microbiota, mediated by humoral factors and affecting the outcome of exogenous exposure. Among the substances produced by symbiotic microbiota, there are an indefinite number of compounds with systemic toxicity. Some occur in the intestinal chyme in potentially lethal amounts in the case they enter the bloodstream quickly. The quick entry of potential toxicants is prevented by the intestinal barrier (IB), a set of structural elements separating the intestinal chyme from the blood. Hypothetically, severe damage to the IB caused by exogenous toxicants can trigger a leakage and subsequent systemic redistribution of toxic substances of bacterial origin. Until recently, the impact of such a redistribution on the outcome of acute exogenous poisoning remained outside the view of toxicology. The present review addresses causal relationships between the secondary dysfunction of the IB and complications of acute poisoning. We characterize acute systemic toxicity of such waste products of the normal gut microflora as ammonia and endotoxins, and demonstrate their involvement in the formation of such complications of acute poisoning as shock, sepsis, cerebral insufficiency and secondary lung injuries. The principles of assessing the functional state of the IB and the approaches to its protection in acute poisoning are briefly considered.

Red emitting Sm(II) phosphors: thermally switchable luminescence in Sm(AlX4)2 (X = Cl, Br) by 5d-4f and intra-4f transitions.

Divalent samarium compounds of the constitution Sm(AlX4)2, X = Cl, Br, show remarkable luminescence of Sm2+. At room temperature, the luminescence is dominated by parity-allowed broad-band 4f55d1 → 4f6 emission with additional 5D0 → 7FJ narrow-line emission. At 79 K, only the intra-4f-emission is observed, rendering the mechanism thermally switchable. The luminescence processes and their temperature dependence were determined including lifetime investigations for both, room temperature and 79 K, as well as quantum efficiency determinations. In addition, a new pathway for the synthesis of Sm(AlCl4)2 and the previously unknown Sm(AlBr4)2 is reported.

Charge regulated solid-liquid interfaces interacting on the nanoscale: Benchmarking of a generalized speciation code (SINFONIA).

Surface chemistry of mineral phases in aqueous environments generates the electrostatic forces involved in particle-particle interactions. However, few models directly take into account the influence of surface speciation and changes in solution speciation when the diffuse layer potential profiles of approaching particles overlap and affect each other. These electrostatic interactions can be quantified, ideally, through charge regulation, considering solution and surface speciation changes upon particle approach by coupling state-of-the-art surface complexation models for the two particle surfaces with a Poisson-Boltzmann type distribution of electrostatic potential and ions in the inter-particle space. These models greatly improve the accuracy of inter-particle force calculations at small inter-particle separations compared to constant charge and constant potential approaches. This work aims at advancing charge regulation calculations by including full chemical speciation and advanced surface complexation models (Basic Stern-, three-, or four plane models and charge distribution concepts), for cases of similar and dissimilar surfaces involving the numerical solution of the Poisson-Boltzmann equation for arbitrary electrolytes. The concept was implemented as a Python-based code and in COMSOL. The flexibility and precision of both, concept and implementations are demonstrated in several benchmark calculations testing the new codes against published results or simulations using established speciation codes, including aqueous speciation, surface complexation and various interaction force examples. Due to the flexibility in terms of aqueous chemistry and surface complexation models for various geometries, a large variety of potential applications can be tackled with the developed codes including industrial, biological, and environmental systems, from colloidal suspensions to gas bubbles, emulsions, slurries like cement paste, as well as new possibilities to assess the chemistry in nano-confined systems.

Fingerprints of the Local Moment Formation and its Kondo Screening in the Generalized Susceptibilities of Many-Electron Problems.

We identify the precise hallmarks of the local magnetic moment formation and its Kondo screening in the frequency structure of the generalized charge susceptibility. The sharpness of our identification even pinpoints an alternative criterion to determine the Kondo temperature of strongly correlated systems on the two-particle level, which only requires calculations at the lowest Matsubara frequency. We showcase its strength by applying it to the single impurity and the periodic Anderson model as well as to the Hubbard model. Our results represent a significant progress for the general understanding of quantum field theory at the two-particle level and allow for tracing the limits of the physics captured by perturbative approaches for correlated systems.

15 years of the model study course in medicine at the Ruhr University Bochum.

The Faculty of Medicine of the Ruhr University Bochum (RUB) introduced a model study course in medicine (MSM) in the winter semester 2003. For 9 consecutive years, 42 out of 280 first year students at the Ruhr University Bochum had the opportunity to begin their studies in the model study course in medicine. The places were allocated amongst the applicants internally through a raffle. The MSM was consistently problem-, practice- and patient-oriented and largely did away with lectures, broke with the distinction between a pre-clinical and clinical phase and tested basic knowledge in equivalent integrated exams focusing on clinical application. Following a comparative evaluation of the standard degree course (RSM) and the MSM, the faculty merged the two degree courses into the Integrated Reformed Medical Curriculum (IRMC), which has been on offer since 2013 and is characterized by a topic-oriented hybrid curriculum. This article examines experiences relating to the origins, conception and introduction of the MSM.

Permeability of Intestinal and Blood-Tissue Barriers in Rats for Evans Blue Dye under Conditions of Acute Intoxication with Cyclophosphamide.

Myeloablative therapy was modeled by administration of cyclophosphamide to rats in a dose of 2.1 LD50 for 14 days. Under these conditions, increased accumulation of Evans blue dye given by gavage was observed in the blood, brain, lung, liver, kidney, and ileum (by 34, 1.6, 149, 46, 30, and 6.2 times, respectively). After intravenous injection of the dye, its accumulation was increased only in the lung and ileum. Thus, simulation of myeloablation cytostatic therapy by cyclophosphamide injection to rats is associated with impairment of the intestinal and lung-blood barriers. These alterations predispose to penetration of biologically active substances from the small intestine, gastrointestinal chyme, and lungs to the blood, thus contributing to the development of the early toxic effects of cyclophosphamide.

Quantum Criticality in the Two-Dimensional Periodic Anderson Model.

We study the phase diagram and quantum critical region of one of the fundamental models for electronic correlations: the periodic Anderson model. Employing the recently developed dynamical vertex approximation, we find a phase transition between a zero-temperature antiferromagnetic insulator and a Kondo insulator. In the quantum critical region, we determine a critical exponent γ=2 for the antiferromagnetic susceptibility. At higher temperatures, we have free spins with γ=1 instead, whereas at lower temperatures, there is an even stronger increase and suppression of the susceptibility below and above the quantum critical point, respectively.

Experimental and numerical investigations on the effect of fracture geometry and fracture aperture distribution on flow and solute transport in natural fractures.

The impact of fracture geometry and aperture distribution on fluid movement and on non-reactive solute transport was investigated experimentally and numerically in single fractures. For this purpose a hydrothermally altered and an unaltered granite drill core with axial fractures were investigated. Using three injection and three extraction locations at top and bottom of the fractured cores, different dipole flow fields were examined. The conservative tracer (Amino-G) breakthrough curves were measured using fluorescence spectroscopy. Based on 3-D digital data obtained by micro-computed tomography 2.5-D numerical models were generated for both fractures by mapping the measured aperture distributions to the 2-D fracture geometries (x-y plane). Fluid flow and tracer transport were simulated using COMSOL Multiphysics®. By means of numerical simulations and tomographic imaging experimentally observed breakthrough curves can be understood and qualitatively reproduced. The experiments and simulations suggest that fluid flow in the altered fracture is governed by the 2-D fracture geometry in the x-y plane, while fluid flow in the unaltered fracture seems to be controlled by the aperture distribution. Moreover, we demonstrate that in our case simplified parallel-plate models fail to describe the experimental findings and that pronounced tailings can be attributed to complex internal heterogeneities. The results presented, implicate the necessity to incorporate complex domain geometries governing fluid flow and mass transport into transport modeling.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

Stressful life events in childhood and allergic sensitization.

Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children as well as the association between early stressful life events and atopic eczema (AE). Within the LISA plus (Life style - Immune system - Allergy) study, blood samples from children of 6 years of age were analyzed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines IFN-γ and IL-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. Furthermore, lifetime prevalence of AE and incidence after the assessment period of life events were compared. Our data suggest that separation/ divorce of parents increase childrens risk of developing AE later in life. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-γ concentrations in childrens blood but not with neuropeptide levels. Thus, the neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2-shifted immune response in children with separated/divorced parents.

Blocking probe as a potential tool for detection of single nucleotide DNA mutations: design and performance.

Developing strategies to detect single nucleotide DNA mutations associated with treatment decisions in cancer patients from liquid biopsies is a rapidly emerging area of personalized medicine that requires high specificity. Here we report how to design an easy enzyme-free approach that could create a platform for detection of L858R mutation of EGFR that is a predictive biomarker of tyrosine kinase treatment in many cancers. This approach includes the addition of blocking probes with the antisense ssDNA at different blocking positions and different concentrations such as to avoid re-annealing with the respective sense ssDNA. The successful blocking strategy was corroborated by fluorescence spectroscopy in solution using two distinct FRET pairs and quartz crystal microbalance with dissipation (QCM-D) measurements under comparable experimental conditions, as the hybridization rate-limiting step in both methods is the nucleation process. The efficiency of hybridization of each blocking probe was strongly dependent on its position particularly when the analyte possesses a secondary hairpin-structure. We tested the performance of blocking probes in combination with gold nanoparticles; the obtained results were in agreement with those of QCM-D. These findings could facilitate the development of better biosensors, especially those using probes containing secondary structure.

Breakdown of Traditional Many-Body Theories for Correlated Electrons.

Starting from the (Hubbard) model of an atom, we demonstrate that the uniqueness of the mapping from the interacting to the noninteracting Green function, G→G_{0}, is strongly violated, by providing numerous explicit examples of different G_{0} leading to the same physical G. We argue that there are indeed infinitely many such G_{0}, with numerous crossings with the physical solution. We show that this rich functional structure is directly related to the divergence of certain classes of (irreducible vertex) diagrams, with important consequences for traditional many-body physics based on diagrammatic expansions. Physically, we ascribe the onset of these highly nonperturbative manifestations to the progressive suppression of the charge susceptibility induced by the formation of local magnetic moments and/or resonating valence bond (RVB) states in strongly correlated electron systems.

Complementary and alternative medicine (CAM) and atopic eczema.

. There is a substantial and growing interest in complementary and alternative medicine (CAM) in the general population. This paper aims to answer in how far patients with atopic eczema use CAM and which techniques. Furthermore the evidence basis on the efficacy of CAM in the use for atopic eczema should be reviewed. For that purpose randomized controlled trials (RCT) were searched systematically. In Germany about 46% of the general population and up to 51% of inpatients with eczema use CAM. Acupuncture, homeopathy, diets and supplements comprise the most popular techniques. Better educated, middle-aged women use CAM more frequently. In general the evidence basis concerning studies on the efficacy (and safety) of CAM for atopic eczema with appropriate size and quality is limited. Most studies were found on essential fatty acids and Chinese herbs, whereby the results remain conflicting. There was not enough evidence to assess the efficacy of acupuncture, homeopathy and salt baths. A single study on bioresonance did not show superiority compared to a sham procedure. Single studies indicated beneficial effects for topical hypericum, autologous blood injection, massage therapy, Vitamin E and D, and topical Viatmin B12. These results must be confirmed by future studies. CAM are frequently used in atopic eczema, the evidence basis for that, however, is limited.