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.

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.

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.

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.

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.

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.

Interplay of Correlations and Kohn Anomalies in Three Dimensions: Quantum Criticality with a Twist.

A general understanding of quantum phase transitions in strongly correlated materials is still lacking. By exploiting a cutting-edge quantum many-body approach, the dynamical vertex approximation, we make important progress, determining the quantum critical properties of the antiferromagnetic transition in the fundamental model for correlated electrons, the Hubbard model in three dimensions. In particular, we demonstrate that-in contradiction to the conventional Hertz-Millis-Moriya theory-its quantum critical behavior is driven by the Kohn anomalies of the Fermi surface, even when electronic correlations become strong.

Model-Independent Determination of the Shear Viscosity of a Trapped Unitary Fermi gas: Application to High-Temperature Data.

Determinations of the shear viscosity of trapped ultracold gases suffer from systematic, uncontrolled uncertainties related to the treatment of the dilute part of the gas cloud. In this work we present an analysis of expansion experiments based on a new method, anisotropic fluid dynamics, that interpolates between Navier-Stokes fluid dynamics at the center of the cloud and ballistic behavior in the dilute corona. We validate the method using a comparison between anisotropic fluid dynamics and numerical solutions of the Boltzmann equation. We then apply anisotropic fluid dynamics to the expansion data reported by Cao et al. In the high-temperature limit we find η=0.282(mT)^{3/2}, which agrees within about 5% with the theoretical prediction η=0.269(mT)^{3/2}.

Label-free versus conventional cellular assays: Functional investigations on the human histamine H1 receptor.

A set of histamine H1 receptor (H1R) agonists and antagonists was characterized in functional assays, using dynamic mass redistribution (DMR), electric cell-substrate impedance sensing (ECIS) and various signaling pathway specific readouts (Fura-2 and aequorin calcium assays, arrestin recruitment (luciferase fragment complementation) assay, luciferase gene reporter assay). Data were gained from genetically engineered HEK293T cells and compared with reference data from GTPase assays and radioligand binding. Histamine and the other H1R agonists gave different assay-related pEC50 values, however, the order of potency was maintained. In the luciferase fragment complementation assay, the H1R preferred ß-arrestin2 over ß-arrestin1. The calcium and the impedimetric assay depended on Gq coupling of the H1R, as demonstrated by complete inhibition of the histamine-induced signals in the presence of the Gq inhibitor FR900359 (UBO-QIC). Whereas partial inhibition by FR900359 was observed in DMR and the gene reporter assay, pertussis toxin substantially decreased the response in DMR, but increased the luciferase signal, reflecting the contribution of both, Gq and Gi, to signaling in these assays. For antagonists, the results from DMR were essentially compatible with those from conventional readouts, whereas the impedance-based data revealed a trend towards higher pKb values. ECIS and calcium assays apparently only reflect Gq signaling, whereas DMR and gene reporter assays appear to integrate both, Gq and Gi mediated signaling. The results confirm the value of the label-free methods, DMR and ECIS, for the characterization of H1R ligands. Both noninvasive techniques are complementary to each other, but cannot fully replace reductionist signaling pathway focused assays.

Fluctuation Diagnostics of the Electron Self-Energy: Origin of the Pseudogap Physics.

We demonstrate how to identify which physical processes dominate the low-energy spectral functions of correlated electron systems. We obtain an unambiguous classification through an analysis of the equation of motion for the electron self-energy in its charge, spin, and particle-particle representations. Our procedure is then employed to clarify the controversial physics responsible for the appearance of the pseudogap in correlated systems. We illustrate our method by examining the attractive and repulsive Hubbard model in two dimensions. In the latter, spin fluctuations are identified as the origin of the pseudogap, and we also explain why d-wave pairing fluctuations play a marginal role in suppressing the low-energy spectral weight, independent of their actual strength.

Liver injury following blunt abdominal trauma: a new mechanism-driven classification.

PURPOSES: The current classifications for blunt liver trauma focus only on the extent of liver injury. However, these scores are independent from the localization of liver injury and mechanism of trauma. METHODS: The type of liver injury after blunt abdominal trauma was newly classified as type A when it was along the falciform ligament with involvement of segments IVa/b, III, or II, and type B when there was involvement of segments V-VIII. With the use of a prospectively established database, the clinical, perioperative, and outcome data were analyzed regarding the trauma mechanism, as well as the radiological and intraoperative findings. RESULTS: In 64 patients, the type of liver injury following blunt abdominal trauma was clearly linked with the mechanism of trauma: type A injuries (n = 28) were associated with a frontal trauma, whereas type B injuries (n = 36) were found after complex trauma mechanisms. The demographic data, mortality, ICU stay, and hospital stay showed no significant differences between the two groups. Interestingly, all patients with type A ruptures required immediate surgical intervention, whereas six patients (16.7 %) with type B ruptures could be managed conservatively. CONCLUSIONS: This new classification for blunt traumatic hepatic injury is based on the localization of parenchymal disruption and correlates with the mechanism of trauma. The type of liver injury correlated with the necessity for surgical therapy.

Trends and geographical variation of primary hip and knee joint replacement in Germany.

OBJECTIVE: Considerable variation in total hip replacement and total knee replacement (THR/TKR) between regions has been described. The aim of this study was to explore geographical variation in THR and TKR in Germany and to analyse potentially explanatory variables. METHOD: We used data of Germany's largest statutory health insurer. Between 2005 and 2009 451,108 THR and 335,022 TKR were performed. Age-standardised joint replacement rates were calculated for 16 federal states and 407 counties. We performed cluster (Moran's I) and spatial error regression analyses including regional deprivation, osteoarthritis rate, urbanity and number of orthopaedic specialists as dependent variables on county level. RESULTS: In 2009 the overall age-standardised and crude rates were 148.9 (95% CI (confidence interval) 147.6-151.1) and 290.2 for THR, and 132.5 (95% CI 131.3-133.6) and 232.7 for TKR. Between counties THR rates differed by factor 2 (106.1-215.8) and showed significant clusters with high utilisation in South and Northwest Germany. TKR rates differed by factor 3.2 (69.1-219.5) and were also high in South Germany whereas almost all areas in East Germany showed low replacement rates. Differences were pronounced when restricting the analysis to cases with an indication of osteoarthritis. All tested predictors could be identified as significant explanatory variables (each P < 0.001). CONCLUSION: This study proofed considerable and consistent geographic variation of THR and TKR in Germany. Thereby relevant explanatory factors were identified. These results may foster the discussion and future research in health services which should include areas of patients' and doctors' expectation, financial aspects and an outcome-based definition of appropriate supply.

Divergent precursors of the Mott-Hubbard transition at the two-particle level.

Identifying the fingerprints of the Mott-Hubbard metal-insulator transition may be quite elusive in correlated metallic systems if the analysis is limited to the single particle level. However, our dynamical mean-field calculations demonstrate that the situation changes completely if the frequency dependence of the two-particle vertex functions is considered: The first nonperturbative precursors of the Mott physics are unambiguously identified well inside the metallic regime by the divergence of the local Bethe-Salpeter equation in the charge channel. In the low-temperature limit this occurs for interaction values where incoherent high-energy features emerge in the spectral function, while at high temperatures it is traceable up to the atomic limit.

German national consensus recommendations on nutrition and lifestyle in pregnancy by the 'Healthy Start - Young Family Network'.

Diet and physical activity before and during pregnancy affect short- and long-term health of mother and child. The energy needs at the end of pregnancy increase only by about 10% compared to nonpregnant women. An excessive energy intake is undesirable since maternal overweight and excessive weight gain can increase the risks for a high birth weight and later child overweight and diabetes. Maternal weight at the beginning of pregnancy is especially important for pregnancy outcome and child health. Women should strive to achieve normal weight already before pregnancy. Regular physical activity can contribute to a healthy weight and to the health of pregnant women. The need for certain nutrients increases more than energy requirements. Before and during pregnancy, foods with a high content of essential nutrients should be preferentially selected. Supplements should include folic acid and iodine, iron (in case of suboptimal iron stores), the ω-3 fatty acid docosahexaenoic acid (in case of infrequent consumption of ocean fish) and vitamin D (in case of decreased sun exposure and decreased endogenous vitamin D synthesis). Pregnant women should not smoke and not stay in rooms where others smoke or have smoked before (passive smoking). Alcohol consumption should be avoided, since alcohol can harm unborn children.

Effects of cyclophosphamide and lactulose on the release of ammonia and medium-molecular-weight substances from the intestine into blood in rats.

The effects of lactulose on the release of ammonia and medium-molecular-weight substances from the intestine into the blood and on the severity of cyclophosphamide intoxication were studied in rats. The pH and urease-dependent component of ammonia-producing activity of the cecal chyme decreased over 6 h after lactulose administration, while ammonia content in the chyme increased. Cyclophosphamide caused an increase in ammonia and, less so, glutamine level in the portal blood and in the blood collected after decapitation; this drug stimulated release of methylene blue and endogenous substances of medium-molecular-weight to the portal blood. Lactulose was virtually inessential for these changes and for the neurological status, mortality, and medium life span of rats. Hence, lactulose did not prevent cyclophosphamide-induced leakage of ammonia and medium-molecular-weight substances from the gastrointestinal tract into blood and did not reduce the severity of intoxication.

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.

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.

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.