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.

The feasibility and effectiveness of a novel online mental health literacy course in supporting university student mental health: a pilot study.

BACKGROUND: There is a need for effective universal approaches to promote and support university student mental health that are scalable and sustainable. In this pilot study we assess the feasibility and acceptability of a fully-digitalized, comprehensive mental health literacy course co-created with and tailored to the needs of undergraduate students. We also explore preliminary associations with mental health and positive behaviour change. METHODS: An accredited online mental health literacy course was developed using state-of-the-art pedagogical principles and a reverse mentorship approach. The course was offered as an interdisciplinary undergraduate elective. Students completed an online survey before and after the 12-week course that collected demographic information and assessed mental health knowledge, emotional self-awareness, mental health, stigma, and health-related behaviors using validated measures. Dependent group t-tests were used to compare pre- and post-course levels of knowledge, mental health, sleep quality and substance use. Mental health outcomes of students who completed the course were compared to an age and sex-matched sample of students not enrolled in the course and who completed the same survey measures over the same academic year. Multivariable linear regression was used to examine the effect of course participation on outcomes at follow-up. RESULTS: The course had good uptake and was positively reviewed by participants. Specifically, students found the course engaging, relevant, and applicable, and agreed they would recommend it to their peers. Among course participants there was improvement in mental health knowledge (p < 0.001) and emotional self-awareness (p = 0.02) at course completion. Compared to the matched comparison group, taking the course was associated with reduced alcohol (ß = - 0.41, p = 0.01) and cannabis use (ß = - 0.35, p = 0.03), and improved sleep quality (ß = 1.56, p = 0.09) at the end of the term. CONCLUSIONS: Findings suggest that delivering mental health literacy as an online accredited course may be an acceptable and effective way of promoting university student mental health through improved knowledge, emotional self-awareness, and healthy lifestyle choices. As the course is expanded to larger and more diverse student cohorts we will be able to further examine the short and long-term effectiveness of the course in supporting student mental health and the underlying mechanisms.

Improved electrochemical performance and solid electrolyte interphase properties of electrolytes based on lithium bis(fluorosulfonyl)imide for high content silicon anodes.

Electrodes containing 60 wt% micron-sized silicon were investigated with electrolytes containing carbonate solvents and either LiPF6 or lithium bis(fluorosulfonyl)imide (LiFSI) salt. The electrodes showed improved performance, with respect to capacity, cycling stability, rate performance, electrode resistance and cycle life with the LiFSI salt, attributed to differences in the solid electrolyte interphase (SEI). Through impedance spectroscopy, cross sectional analysis using transmission electron microscopy (TEM) and focused ion beam (FIB) in combination with scanning electron microscopy (SEM), and electrode surface characterization by X-ray photoelectron spectroscopy (XPS), differences in electrode morphological changes, SEI composition and local distribution of SEI components were investigated. The SEI formed with LiFSI has a thin, inner, primarily inorganic layer, and an outer layer dominated by organic components. This SEI appeared more homogeneous and stable, more flexible and with a lower resistivity than the SEI formed in LiPF6 electrolyte. The SEI formed in the LiPF6 electrolyte appears to be less passivating and less flexible, with a higher resistance, and with higher capacitance values, indicative of a higher interfacial surface area. Cycling in LiPF6 electrolyte also resulted in incomplete lithiation of silicon particles, attributed to the inhomogeneous SEI formed. In contrast to LiFSI, where LiF was present in small grains in-between the silicon particles, clusters of LiF were observed around the carbon black for the LiPF6 electrolyte.

The effect of gender dyads on the quality of narrative assessments of general surgery trainees.

BACKGROUND: Prior studies have shown that gender can influence how learners are assessed and the feedback they receive. We investigated the quality of faculty narrative comments in general surgery trainee evaluation using trainee-assessor gender dyads. METHODS: Narrative assessments of surgical trainees at the University of British Columbia were collected and rated using the McMaster Narrative Comment Rating Scale (MNCRS). Variables from the MNCRS were inputted into a generalized linear mixed model to explore the impact of gender dyads on the quality of narrative feedback. RESULTS: 2,469 assessments were collected. Women assessors tended to give higher-quality comments (p's < 0.05) than men assessors. Comments from men assessors to women trainees were significantly more positive than comments from men assessors to men trainees (p = 0.02). Men assessors also tended to give women trainees more reinforcing than corrective comments than to men trainees (p < 0.01). CONCLUSIONS: There are significant differences in the quality of faculty feedback to trainees by gender dyads. A range of solutions to improve and reduce differences in feedback quality are discussed.

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany.

BACKGROUND: Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. OBJECTIVES: To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. METHODS: Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015-30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD-10-GM codes). Twelve-month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. RESULTS: Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second-generation H1 -antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). CONCLUSIONS: In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes.

Using localized Twitter activity to assess harmful algal bloom impacts of Karenia brevis in Florida, USA.

Red tide blooms of the dinoflagellate Karenia brevis (K. brevis) produce toxic coastal conditions that can impact marine organisms and human health, while also affecting local economies. During the extreme Florida red tide event of 2017-2019, residents and visitors turned to social media platforms to both receive disaster-related information and communicate their own sentiments and experiences. This was the first major red tide event since the ubiquitous use of social media, thus providing unique crowd-sourced reporting of red tide impacts. We evaluated the spatial and temporal accuracy of red tide topic activity on Twitter, taking tweet sentiments and user types (e.g. media, citizens) into consideration, and compared tweet activity with reported red tide conditions, such as K. brevis cell counts, levels of dead fish and respiratory irritation on local beaches. The analysis was done on multiple levels with respect to both locality (e.g., entire Gulf coast, county-level, city-level, zip code tabulation areas) and temporal frequencies (e.g. daily, every three days, weekly), resulting in strong correlations between local per-capita Twitter activity and the actual red tide conditions observed in the area. Moreover, an association was observed between proximity to the affected coastal areas and per-capita counts for relevant tweets. Results show that Twitter presents a trustworthy reflection of the red tide's local impacts and development over time, and can potentially augment the already existing tools for efficient assessment and a more coordinated response to the disaster.

Patch test informed consent form: position statement by European Academy of Dermatology and Venereology Task Force on Contact Dermatitis.

BACKGROUND: To our knowledge, an international consensus is lacking regarding the development of an adequate informed consent form for a patch test (PT) and the information that should be included in such document. OBJECTIVES: The aim of the study was to reach a consensus on the specific points that need to be addressed in a PT consent form. METHODS: A Delphi survey, comprising 2 rounds and 1 final discussion, was used to gather and analyse data, which was conducted over the Internet. Each statement that reached a consensus with the respondents (9 expert dermatologists from Europe) was defined as a median consensus score (MED) of ≥7 and agreement among panelists as an interquartile range (IQR) of ≤3. All study participants were members of the EADV task force on contact dermatitis. RESULTS: The expert panel addressed several topics that should be included in an informed consent form for a PT: introduction, preparation for PT, testing procedure, allowed activities, adverse events and additional authorizations. CONCLUSIONS: Our results assess recommendations regarding points to be contained in an informed consent form for a PR. Future actions towards standardization and harmonization of this specific consent form are needed.

Quantification of U, Th and specific radionuclides in coal from selected coal fired power plants in South Africa.

Most of South Africa's energy is derived from the combustion of coal in pulverized coal-fired power plants (CFPP). However, when compared with the rest of the world, limited information regarding the main radioactive elements (U and Th) and specific radionuclides of interest (K40, Ra226 and Th232) from South African CFPP is available in the public domain. This paper aims to quantify the U, Th and specific radionuclides found in the coal used in selected South African CFPP in comparison to world averages found in literature. The U and Th concentrations were obtained by ICP-MS. The main radionuclides, K40, Ra226 and Th238, were quantified using gamma spectrometry. The U concentration and Th concentrations for the coal used in all the power plants was above the world average of 1.9 mg/kg and 3.2 mg/kg respectively. The coals with the highest Th content originated from the Mpumalanga power plant, while the U content in the Freestate power plant samples was the highest of the three. The concentrations of the K40 were between 88.43±10.75-110.76±8.92 Bq/kg, which are in-line with world averages of 4-785 Bq/kg. Similarly, the Ra226 and Th232 values were between 21.69±2.83-52.63±4.04 Bq/kg and 19.91±1.24-22.97±1.75 Bq/kg respectively, which are also in line with the world averages of 1-206 Bq/kg and 1-170 Bq/kg respectively. Radiological hazard indices such as radium equivalent (Raeq); external hazard index (Hex) and internal hazard index (Hin), that were estimated from these average radionuclide concentrations were less than the prescribed values found in literature. This indicated that no significant health risk was posed by the coal being used from these coal fields.

Data on statistical experimental design to formulate amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis.

Data described in this article are related to the research article entitled "Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) for the treatment of vulvovaginal candidiasis" [1]. In this work, we report original data on the statistical experimental design to formulate uncoated AMP EUD nanoparticles, data on the validation of spectrophotometric method to quantify the AMP released from uncoated EUD nanoparticles and coated with HA to obtain the in vitro drug release profiles as well as the drug encapsulation efficiency. In addition, we describe original data on characterization, including diameter size, polydispersity index, zeta potential, FTIR, DSC/TG, and XRD; data on diameter of in vitro inhibition halos of Candida albicans; and on the vaginal burden of infected animals treated with uncoated AMP EUD nanoparticles and AMP EUD nanoparticles/HA. Finally, different histological sections of endocervix collected from treated and untreated animals were inserted into this manuscript.

[Contact allergy due to insulin pumps and glucose sensor systems]. / Kontaktallergie auf Glukosemesssysteme und Insulinpumpen.

The design and development of insulin pumps and various glucose sensor systems has an enormous impact on life quality of diabetic patients. Surveillance and therapy of diabetes has improved due to the new diabetic devices, which are affixed to the patients' skin for several days. Since their introduction, irritant and allergic contact dermatitis have been frequently reported. Patients often acquire contact sensitization to isobornyl acrylate, N,N-dimethylacrylamide or formerly to 2­ethyl-cyanoacrylate. These contact allergens were found in the patch, in the glue to affix the box on the patch or in the casing of the system itself. Development of contact allergy to substances of these systems may result in the need to abandon modern diabetic devices.

Toll-like receptor 2-deficiency on bone marrow-derived cells augments vascular healing of murine arterial lesions.

AIMS: Neointimal hyperplasia contributes to arterial restenosis after percutaneous transluminal coronary angioplasty or vascular surgery. Neointimal thickening after arterial injury is determined by inflammatory processes. We investigated the role of the innate immune receptor toll-like receptor 2 (TLR2) in neointima formation after arterial injury in mice. MATERIALS AND METHODS: Carotid artery injury was induced by 10% ferric chloride in C57Bl/6J wild type (WT), TLR2 deficient (B6.129-Tlr2tm1Kir/J, TLR2-/-) and WT mice treated with a TLR2 blocking antibody. 21 days after injury, carotid arteries were assessed histomorphometrically and for smooth muscle cell (SMC) content. To identify the contribution of circulating cells in mediating the effects of TLR2-deficiency, arterial injury was induced in WT/TLR2-/--chimeric mice and the paracrine modulation of bone marrow-derived cells from WT and TLR2-/- on SMC migration compared in vitro. KEY FINDINGS: TLR2-/- mice and WT mice treated with TLR2 blocking antibodies exhibited reduced neointimal thickening (23.7 ± 4.2 and 6.5 ± 3.0 vs. 43.1 ± 5.9 µm, P < 0.05 and P < 0.01), neointimal area (5491 ± 1152 and 315 ± 76.7 vs. 13,756 ± 2627 µm2, P < 0.05 and P < 0.01) and less luminal stenosis compared to WT mice (8.5 ± 1.6 and 5.0 ± 1.3 vs. 22.4 ± 2.2%, both P < 0.001n = 4-8 mice/group). The phenotypes of TLR2-/- vs. WT mice were completely reverted in WT/TLR2-/- bone marrow chimeric mice (5.9 ± 1.5 µm neointimal thickness, 874.2 ± 290.2 µm2 neointima area and 2.7 ± 0.6% luminal stenoses in WT mice transplanted with TLR2-/- bone marrow vs. 23.6 ± 5.1 µm, 3555 ± 511 µm2 and 12.0 ± 1.3% in WT mice receiving WT bone marrow, all P < 0.05, n = 6/group). Neointimal lesions of WT and WT mice transplanted with TLR2-/- bone marrow chimeric mice showed increased numbers of SMC (10.8 ± 1.4 and 12.6 ± 1.4 vs. 3.8 ± 0.9 in TLR2-/- and 3.5 ± 1.1 cells in WT mice transplanted with TLR2-/- bone marrow, all P < 0.05, n = 6). WT bone marrow cells stimulated SMC migration more than TLR2-deficient bone marrow cells (1.7 ± 0.05 vs. 1.3 ± 0.06-fold, P < 0.05, n = 7) and this effect was aggravated by TLR2 stimulation and diminished by TLR2 blockade (1.1 ± 0.03-fold after stimulation with TLR2 agonists and 0.8 ± 0.02-fold after TLR2 blockade vs. control treated cells defined as 1.0, P < 0.05, n = 7). SIGNIFICANCE: TLR2-deficiency on hematopoietic but not vessel wall resident cells augments vascular healing after arterial injury. Pharmacological blockade of TLR2 may thus be a promising therapeutic option to improve vessel patency after iatrogenic arterial injury.

Digital Communication Technology: Does Offering a Choice of Modality Improve Medication Adherence and Outcomes in a Persistent Asthma Population?

BACKGROUND: Use of digital communication technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at patient preference around mode of medication reminders used to improve and maintain asthma medication adherence. OBJECTIVE: To determine if, in a population already receiving automated medication reminders, offering a choice for preferred mode of reminder (text, email, phone) would improve their adherence and asthma outcomes over a 1-year period. METHODS: This was a pragmatic, randomized controlled trial conducted at Kaiser Permanente Colorado involving 7522 adult patients with persistent asthma. Study patients were randomized to receive usual care or their choice of medication reminder. Differences between the 2 groups in both medication adherence and asthma outcomes were then assessed over the following year. RESULTS: Only 30% of those offered a choice of medication reminder modality responded by making a choice, with 52% preferring text messaging. There was less of a decrease in adherence rate over the 1-year period in those who made a choice regarding the mode of medication refill reminder. There was no difference in asthma outcomes between those who did make a choice compared with those who did not make a choice regarding the mode of medication refill reminder. CONCLUSION: In a patient population already receiving medication reminders, offering a choice about what type of technology-enabled asthma medication reminder patients wanted did not improve outcomes but did enable a subgroup to better maintain their medication adherence.

[Increasing overhead ressources of the trauma room]. / Steigender Vorhalteaufwand für den Schockraum.

BACKGROUND: Every year up to 35,000 people in Germany are severely injured in accidents in traffic, during work or leisure activities. The 24-h availability of the trauma room as well as surgical and intensive care unit capacities are essential to provide optimal acute care. This study analyzed the frequency of utilization of the resource trauma room in a level I trauma center in the past. METHODS: Data of a level I trauma center from 2005 to 2016 including trauma room alerts deployed by the rescue coordination center and the number of patients found to be severely injured (ISS ≥ 16) during trauma room diagnostics were analyzed retrospectively. Additionally, alerts due to trauma mechanism, accompanying by the emergency physician, ventilation and resuscitation were evaluated via a web-based interdisciplinary care capacity system (IVENA) from 2012 to 2016. Therefore, a comparison between the number of trauma room alerts and the number of severely injured patients was performed for the time after 2012. RESULTS: For the time from 2012 to 2016, data obtained by IVENA showed a continuous increase in the number of trauma room alerts (n = 367 to n = 623). At the same time, the number of patients admitted under resuscitation (n = 15 to n = 45) as well as ventilated patients (n = 78 to n = 139) increased significantly; however, there was also an increase in the number of trauma alerts due to trauma mechanisms (n = 84 to n = 194) as well as the number of patients admitted to the trauma room not accompanied by an emergency physician (n = 38 to n = 132). The ratio between the number of trauma room alerts and severely injured patients (ISS ≥ 16) increased from 3.1 in 2012 to 5.4 in 2015 and 4.6 in 2016. CONCLUSION: The data at hand showed a constant number of severely injured trauma patients admitted to a level I trauma center over the past few years. At the same time, there was a significant increase in utilization of the trauma room; however, in a considerable number of patients admitted to the trauma room the diagnostic process resulted in non-traumatic diagnostic findings. In the analyzed cohort, especially patients admitted to the trauma room due to trauma mechanism or without an accompanying emergency physician contributed to this development, necessitating an increased operational readiness of the trauma room team.

Dynamic properties of different liquid states in systems with competing interactions studied with lysozyme solutions.

Recent studies of colloidal systems with a short-range attraction and long-range repulsion (SALR) have been demonstrated to have a generalized phase diagram with multiple liquid states defined by their structures. In this paper, we identify the different liquid states of previous experimentally studied lysozyme samples within this proposed generalized state diagram and explore the dynamic properties of each liquid state. We show that most lysozyme samples studied here and previously at low and intermediate concentrations are dispersed fluids while a few high concentration samples are randomly percolated liquids. In the dispersed fluid region, the short-time diffusion coefficient measured by neutron spin echo agrees well with the long time diffusion coefficient estimated with the solution viscosity. This dynamic feature is maintained even for some samples in the random percolated region. However, the short-time and long-time diffusion coefficients of random percolated fluids deviate at larger concentration and attraction strength. At high enough concentrations, the mean square displacement can be as slow as those of many glassy colloidal systems at time scales near the characteristic diffusion time even though these lysozyme samples remain in liquid states at the long-time limit. We thus identify the region in the generalized phase diagram where these equilibrium states with extremely slow local dynamics exist relative to bulk percolation and kinetic arrest (gel and glassy) transitions.

The differential impact of adverse childhood experiences in the development of pre-diabetes in a longitudinal cohort of US adults.

BACKGROUND: ACEs have a dose-response relationship with diabetes. The relationship between ACEs and pre-diabetes is not well known and may represent an effective area for prevention efforts. METHODS: Data from 1054 participants from two waves of the longitudinal MIDUS study were used. Multivariate general linear regression models assessed the relationship between ACEs and biomarker outcomes. Correlation tests and mediation models investigated the relationship between ACE and pre-diabetes. RESULTS: Individuals reporting ACEs were statistically significantly more likely to have higher BMI (1.13 (0.34-1.92)), higher waist circumference (2.74 (0.72-4.76)), elevated blood fasting insulin levels (2.36 (0.71-4.02)) and higher insulin resistance (HOMA-IR (0.57 (0.08-1.06)). BMI/waist circumference and insulin resistance did not maintain independent relationships with ACEs once HOMA-IR was included in the dichotomized ACE model (p = 0.05 and p = 0.06, respectively), suggesting the relationship between BMI and ACEs may be mediated by insulin resistance. CONCLUSIONS: These results represent one of the first studies to examine the differential impact of ACEs on a diverse set of clinical pre-diabetes measures. Findings suggest sexual and physical abuse, and financial strain during childhood are important factors associated with higher risk for pre-diabetes, and should be considered during intervention development.

Physics, chemistry, and Hirshfeld surface analyses of gamma-irradiated thalidomide to evaluate behavior under sterilization doses.

Thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy (fourfold the usual sterilizing dose for pharmaceutics). The ß polymorph of thalidomide was obtained in an isothermal experiment at 270 °C. All samples underwent gamma irradiation for specific times. At different doses, decomposition of the pharmaceutical was not observed up to 100 kGy. The observed effect was angle turning between the phthalimide and glutarimide rings modulated by repulsion towards the carbonyl group, leading to a stable energetic configuration, as measured by the equilibrium in the torsion angle after irradiation. The thalidomide molecule has a center of symmetry, so a full turn starting from 57.3° will lead to an identical molecule. Further irradiation will start the process again. Samples irradiated at 30 and 100 kGy have more compact unit cells and a lower volume, which leads to an increase in the intermolecular hydrogen interaction within the unit cell, resulting in higher thermal stability for polymorph α.

Physicochemical characterization, the Hirshfeld surface, and biological evaluation of two meloxicam compounding pharmacy samples.

Meloxicam (MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently between samples. The FTIR and 1H NMR spectra showed characteristic assignments. 13C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph III in an experimental model of acute inflammation in mice. Our results highlighted the need for complete crystallographic characterization and the separation of freely used raw materials in compounding pharmacies, as a routine procedure, to ensure the desired dose/effect.

Notch inhibition counteracts Paneth cell death in absence of caspase-8.

Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8∆int mice. The secretory cell metaplasia in DBZ-treated casp8∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8∆int background. Our data suggest that casp8 acts in the intestinal Notch network.

High volume of polysorbate-containing (Tween® 80) solutions induces false-positive results in intradermal test.

BACKGROUND: Intradermal test is used to detect causative allergens in IgE-mediated hypersensitivity. The surfactant polysorbate 80 can be added to intradermal test solutions to more reliably dissolve the allergen and ensure a constant bioavailability of the injected allergen. Polysorbate 80 has, however, some histamine-releasing properties which could blur the difference to the histamine-induced wheal. Routinely serving as a control. OBJECTIVE: Allergen-free polysorbate 80 containing (0.005%) test solutions were therefore systematically tested at different injection volumes to see whether polysorbate can falsify skin reactions and if yes whether conditions can be identified to avoid this. METHODS: In a partly blinded study, 30 patients were tested intracutaneously at the back: each received at three separate sites 0.05 mL of polysorbate-containing solvent, 0.02 mL polysorbate-containing solvent as well as 0.02 mL polysorbate-free solvent. After 15 min, wheal and erythema were documented and planimetrically quantified. RESULTS: Unexpectedly 23 of 30 (77%) patients showed false-positive test reactions to the volume of 0.05 mL of the polysorbate-containing solvent whereas the polysorbate-containing solvent with 0.02 mL and the polysorbate-free solvent with 0.02 mL injection volume had no reinforcing effect on skin test reaction. CONCLUSIONS: Different volumes of polysorbate-containing solutions, all recommended by manufacturers for intradermal tests, may significantly influence test results. The study shows that a polysorbate 80 used at 0.005% in solvents for intradermal test to provide a better bioavailability of allergens produces false-positive reactivity in a surprising and a hitherto unknown 77% if the 0.05 mL volume is injected. It is, therefore, mandatory to strictly adhere to an intradermal test volume of 0.02 mL as only then falsifying effects of the polysorbate additive are avoided, and comparable test results are ensured.