Skin and systemic inflammation in adults with atopic dermatitis before and after whole-body topical betamethasone 17-valerate 0.1% or tacrolimus 0.1% treatment:A randomized controlled study

BackgroundAtopic dermatitis (AD) is mainly driven by type 2 inflammation and often treated with topical agents. Studies comparing differences in biomarkers between these treatments are lacking.ObjectivesThe aim of this study was to evaluate the effects of topical betamethasone 17-valerate 0.1% and tacrolimus 0.1% ointment on skin barrier function and inflammatory biomarkers in skin and blood in adults with AD.MethodsIn this randomized parallel-group double-blind double-dummy active-comparator study design, 36 adults with AD were treated with either whole-body topical corticosteroid (betamethasone ointment 0.1% plus placebo once daily, n = 18) or calcineurin inhibitor (tacrolimus ointment 0.1% twice daily, n = 18). At baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment, we evaluated AD severity, levels of natural moisturizing factor (NMF) and cytokines in the skin and blood and characterized circulating T cells.ResultsMean AD severity at baseline corresponded to moderate disease and decreased significantly in both groups. Levels of NMF increased significantly in the tacrolimus group after 2 weeks of treatment (p = 0.002) and tended to increase more than betamethasone at week 6 (p = 0.06). Most skin cytokines decreased with both treatments. However, IL-8, IL-18, IL-22, IP-10, MDC, MMP-9 and TARC were significantly more decreased with betamethasone than tacrolimus after 2 weeks, while after 6 weeks this was only the case for IL-8 and MMP-9. Approximate half of the systemic cytokines decreased significantly with both treatments, but betamethasone decreased MDC significantly more after 2 weeks of treatment. T-cell characterization analyses indicated slight differences in the expression and activation of T cells between groups.ConclusionTopical treatment of AD with betamethasone and tacrolimus ointment effectively reduced disease severity, cutaneous and systemic inflammatory markers. Betamethasone was more effective in decreasing inflammation, but tacrolimus improved skin hydration (NMF levels) more than betamethasone.Background: Atopic dermatitis (AD) is mainly driven by type 2 inflammation and often treated with topical agents. Studies comparing differences in biomarkers between these treatments are lacking. Objectives: The aim of this study was to evaluate the effects of topical betamethasone 17-valerate 0.1% and tacrolimus 0.1% ointment on skin barrier function and inflammatory biomarkers in skin and blood in adults with AD. Methods: In this randomized parallel-group double-blind double-dummy active-comparator study design, 36 adults with AD were treated with either whole-body topical corticosteroid (betamethasone ointment 0.1% plus placebo once daily, n = 18) or calcineurin inhibitor (tacrolimus ointment 0.1% twice daily, n = 18). At baseline, after 2 weeks of daily treatment and after further 4 weeks of twice-weekly maintenance treatment, we evaluated AD severity, levels of natural moisturizing factor (NMF) and cytokines in the skin and blood and characterized circulating T cells. Results: Mean AD severity at baseline corresponded to moderate disease and decreased significantly in both groups. Levels of NMF increased significantly in the tacrolimus group after 2 weeks of treatment (p = 0.002) and tended to increase more than betamethasone at week 6 (p = 0.06). Most skin cytokines decreased with both treatments. However, IL-8, IL-18, IL-22, IP-10, MDC, MMP-9 and TARC were significantly more decreased with betamethasone than tacrolimus after 2 weeks, while after 6 weeks this was only the case for IL-8 and MMP-9. Approximate half of the systemic cytokines decreased significantly with both treatments, but betamethasone decreased MDC significantly more after 2 weeks of treatment. T-cell characterization analyses indicated slight differences in the expression and activation of T cells between groups. Conclusion: Topical treatment of AD with betamethasone and tacrolimus ointment effectively reduced disease severity, cutaneous and systemic inflammatory markers. Betamethasone was more effective in decreasing inflammation, but tacrolimus improved skin hydration (NMF levels) more than betamethasone.</p

Comprehensive two-dimensional gas chromatography as a tool for targeted and non-targeted analysis of contaminants of emerging concern in wastewater

Wastewater is a major reservoir for chemical contaminants, both anthropogenic and biogenic. Recent chemical and toxicological analysis reveals the abundance and impact of these compounds, often termed contaminants of emerging concern (CECs). Concurrently, incomplete removal of these compounds in wastewater treatment plants sets a precedent for detailed characterisation and monitoring of such substances. Although liquid chromatography (LC) is frequently used for analysis of CECs in wastewater, gas chromatography (GC) maintains its significance for non-polar to mid-polar analytes. GC offers advantages such as increased separation efficiency, fewer matrix effects, and greater availability and reliability of reference mass spectra compared to LC. Comprehensive two-dimensional gas chromatography (GC × GC) delivers unmatched peak capacity and separational capabilities, critical in the resolution of diverse compound groups present within wastewater. When coupled with high resolution mass spectrometry, it provides a powerful identification tool with spectral databases and both 1st and 2nd dimensional retention indices, and has allowed for the separation, reliable annotation and characterisation of diverse CECs within wastewater in recent years. Herein, on the basis of recent studies from the last fifteen years, we outline cutting-edge methodologies and strategies for wastewater analysis using GC × GC. This includes sample preparation, derivatization of polar analytes, instrumental setup, and data analysis, ultimately providing the reader a framework for future non-targeted analysis of wastewater and other complex environmental matrices

Forskningsbaseret undervisning og tvivlens goder

De senere årtiers debatter om forholdet mellem forskning og undervisning på universitetet har peget på, at forskningsbaseret undervisning må gentænkes i masseuniversitetet. Det er imidlertid ikke entydigt, hvad en sådan gentænkning involverer i praksis. Med afsæt i et etnografisk studie af en række kurser, der har eksperimenteret med at integrere forskning i undervisningen, argumenterer denne artikel for, at en gentænkning af forskningsbaseret undervisning fordrer en opmærksomhed på tvivlens goder. Artiklen peger på, at et væsentligt aspekt, når studerende arbejder i forsknings- eller forskningslignende processer er, at de kommer i tvivl. På denne baggrund indkredser artiklen, hvordan vi kan forstå tvivlens rolle i forskningsbaseret undervisning på baggrund af den amerikanske pragmatismes idéer om tvivl som forudsætning for videnskabelig tænkning, samt den nyere franske pragmatismes idéer om tvivl som grundlag for kritik. Artiklen udpeger opmærksomhedspunkter omkring organiseringen af undervisningen, så studerende kan spejle sig i hinandens og forskerens produktive tvivl

Predictors of subacute postoperative pain after total knee arthroplasty:A secondary analysis of two randomized trials

BackgroundMethods for identifying high-pain responders undergoing total knee arthroplasty remain important to improve individualized pain management. This study aimed at evaluating pre- and perioperative predictors of pain on Days 2–7 after total knee arthroplasty.MethodsThis is a secondary analysis of data from 227 patients participating in two randomized trials. Pain outcomes were mean pain during walking on Days 2–7 and on Days 2, 4 and 7. Multivariable linear and logistic regressions were carried out in two steps. First, only preoperative available variables including demographics, comorbidities, pain catastrophizing scale and preoperative pain were evaluated while controlling for trial intervention and recruitment site. In the second step, perioperative variables and pain during walking 24 h postoperatively were added.ResultsThe model with only preoperative predictors for mean pain Days 2–7 showed preoperative pain (R-squared 0.097) as the only predictor. In the second model, adding postoperative available variables, only pain 24 h postoperatively (R-squared 0.248) was significant, with a significant main effect of recruitment site. Results for the separate day analysis similarly showed preoperative pain and pain during walking 24 h postoperatively as predictors. The overall best sensitivity (60%) and specificity (74%) for predicting a high-subacute postoperative pain response on Days 2–7 was with cut-off values of VAS 45.5 (out of 100) for pain during walking 24 h postoperatively.ConclusionsPostoperative pain during walking at 24 h is predictive of subacute postoperative pain on Days 2–7 after total knee arthroplasty, while preoperative pain was only a weak predictor.Background: Methods for identifying high-pain responders undergoing total knee arthroplasty remain important to improve individualized pain management. This study aimed at evaluating pre- and perioperative predictors of pain on Days 2–7 after total knee arthroplasty. Methods: This is a secondary analysis of data from 227 patients participating in two randomized trials. Pain outcomes were mean pain during walking on Days 2–7 and on Days 2, 4 and 7. Multivariable linear and logistic regressions were carried out in two steps. First, only preoperative available variables including demographics, comorbidities, pain catastrophizing scale and preoperative pain were evaluated while controlling for trial intervention and recruitment site. In the second step, perioperative variables and pain during walking 24 h postoperatively were added. Results: The model with only preoperative predictors for mean pain Days 2–7 showed preoperative pain (R-squared 0.097) as the only predictor. In the second model, adding postoperative available variables, only pain 24 h postoperatively (R-squared 0.248) was significant, with a significant main effect of recruitment site. Results for the separate day analysis similarly showed preoperative pain and pain during walking 24 h postoperatively as predictors. The overall best sensitivity (60%) and specificity (74%) for predicting a high-subacute postoperative pain response on Days 2–7 was with cut-off values of VAS 45.5 (out of 100) for pain during walking 24 h postoperatively. Conclusions: Postoperative pain during walking at 24 h is predictive of subacute postoperative pain on Days 2–7 after total knee arthroplasty, while preoperative pain was only a weak predictor. Significance Statement: This study investigated factors associated with pain after total knee arthroplasty beyond the immediate postoperative period. The analysis revealed significant associations between preoperative pain levels and, particularly, pain 24 h postoperatively, with subsequent subacute pain the following week. These findings can assist in identifying patients who would benefit from enhanced, individualized analgesic interventions to facilitate postoperative recovery.</p

Liberalism

Liberalism covers a long and broad intellectual tradition that has fed into contemporary theorizing about the political and ethical implications of human communication. This chapter revisits the ambiguity of liberalism, charts the influence of the tradition on the formation of modern national media systems, and takes stock of its place in the process currently unfolding to regulate global digital communication systems. The first section briefly retraces the trajectory of the idea of freedom, highlighting the shift that registered in the 1776 American and 1789 French Revolutions and which gave rise to a concerted conservative backlash, in theory as well as in practice. The middle section of the chapter characterizes the national media systems that emerged from the eighteenth century onward and which were systematized by the interdisciplinary field of media and communication research that was consolidated from the mid-twentieth century. The final section considers what may come after media systems. A new category of communication systems is taking shape, in which media constitute one type of front offices sharing back offices and infrastructures with other private companies and public services

TimelyMon:A Streaming Parallel First-Order Monitor

First-order monitors analyze data-carrying event streams. When event streams are generated by distributed systems, it may be difficult to ensure that events arrive at the monitor in the right order. We develop a new monitoring tool for metric first-order temporal logic, called TimelyMon, that can process out-of-order events. Using the stream processing framework Timely Dataflow, TimelyMon also supports parallelized monitoring. We demonstrate TimelyMon’s good performance and scalability on synthetic and real-world benchmarks.</p

Cross-reactivity between thiuram disulfides and dithiocarbamates. A study of TETD and ZDEC using mouse models

Background: Rubber accelerators are used in the vulcanization of rubber. However, rubber accelerators for example tetraethylthiuram disulfide (TETD) and zinc diethyldithiocarbamate (ZDEC) may cause contact allergy. Concomitant reactions between ZDEC and TETD have been observed in patients which could be explained by co- or cross-reactivity. Objectives: To investigate cross-reactivity between TETD and ZDEC and vice versa. Methods: Groups of mice were sensitized with TETD or ZDEC based on reported EC3-values. Proliferation of lymphocytes were measured on day 5. To test cross-reactivity, mice were sensitized and challenged 3 weeks later with TETD or ZDEC. The inflammatory response was measured by changes in ear thickness and the proliferative response in CD4+ and CD8+ T cells in the submandibular and cervical draining lymph nodes. Results: Sensitization of mice with doses of ZDEC 3%, TETD 5.6% or TETD 16.2% induced significant increased ear thickness and proliferation of CD4+ and CD8+ T cells. Challenge with ZDEC or TETD in these groups induced significant increased ear thickness. Challenge with ZDEC in mice sensitized to TETD 5.6% or TETD 16.2% induced significant increased proliferation of CD4+ and CD8+ T cells. Conclusions: We show cross-reactivity between TETD and ZDEC. Patients sensitized to TETD or ZDEC should avoid exposure to both ZDEC and TETD.</p

Is lifestyle different in male partners experiencing recurrent pregnancy loss compared to men fathering a live birth?

Background: Recurrent pregnancy loss is characterized by three or more consecutive pregnancy losses. Although the causes of recurrent pregnancy loss are often unknown, chromosomal defects and fetal anomalies account for a significant proportion of cases. Previous research has primarily focused on maternal factors, but recent attention has shifted to the role of male lifestyle factors. Objectives: This study examined how male lifestyle factors and chronic illnesses affect recurrent pregnancy loss in a Danish cohort. Objectives included analyzing demographic and clinical features, as well as assessing lifestyle factors and pregnancy outcomes. Materials and methods: We included 741 males referred to the Danish recurrent pregnancy loss unit between 2009 and 2021, alongside a control group of 1173 males from the PREGCO study. Data on demography, clinical features, lifestyle factors, and pregnancy outcomes were collected and analyzed. Results: The recurrent pregnancy loss group had a higher mean age compared to the controls. Although there was a trend suggesting a higher prevalence of obesity in the recurrent pregnancy loss group, statistical significance was not reached. The prevalence of chronic illnesses was similar in both groups. In the recurrent pregnancy loss group, a higher body mass index and history of previous or current smoking were associated with a lower pregnancy rate, and men who never smoked had an increased likelihood of achieving pregnancy. However, these associations lost significance after adjusting for potential confounders. Discussion: The study suggests an association between male obesity and smoking, and decreased pregnancy rates after referral for recurrent pregnancy loss. However, further research is needed to understand the underlying mechanisms and establish causality in this association. Conclusion: The study reveals potential associations between male smoking, male obesity, and reduced pregnancy rates in individuals referred for recurrent pregnancy loss. These findings emphasize the importance of considering male lifestyle factors in the evaluation and management of recurrent pregnancy loss.</p

Strain Patterns With Ultrasound for Assessment of Abdominal Aortic Aneurysm Vessel Wall Biomechanics

Background: Abdominal aortic aneurysms (AAAs) are an important cause of death. Small AAAs are surveyed with ultrasound (US) until a defined diameter threshold, often triggering a computer tomography scan and surgical repair. Nevertheless, 5%–10% of AAA ruptures are below threshold, and some large AAAs never rupture. AAA wall biomechanics may reveal vessel wall degradation with potential for patient-centred risk assessment. This clinical study investigated AAA vessel wall biomechanics and deformation patterns, including reproducibility. Methods: In 50 patients with AAA, 183 video clips were recorded by two sonographers. Prototype software extracted AAA vessel wall principal strain characteristics and patterns. Functional principal component analysis (FPCA) derived strain pattern statistics. Results: Strain patterns demonstrated reduced AAA wall strains close to the spine. The strain pattern “topography” (i.e., curve phases or “peaks” and “valleys”) had a 3.9 times lower variance than simple numeric assessment of strain amplitudes, which allowed for clustering in two groups with FPCA. A high mean reproducibility of these clusters of 87.6% was found. Median pulse pressure-normalised mean principal strain (PPPS) was 0.038%/mm Hg (interquartile range: 0.029–0.051%/mm Hg) with no correlation to AAA size (Spearman's ρ = 0.02, false discovery rate-p = 0.15). Inter-operator reproducibility of PPPS was poor (limits of agreement: ±0.031%/mm Hg). Discussion: Strain patterns challenge previous numeric stiffness measures based on anterior-posterior-diameter and are reproducible for clustering. This study's PPPS aligned with prior findings, although clinical reproducibility was poor. In contrast, US-based strain patterns hold promising potential to enhance AAA risk assessment beyond traditional diameter-based metrics.</p