Epidermal proteomics demonstrates Elafin as a psoriasis-specific biomarker and highlights increased anti-inflammatory activity around psoriatic plaques.

BACKGROUND: Eczema and psoriasis are common diseases. Despite both showing active epidermal contribution to the inflammatory process, their molecular aetiology and pathological mechanisms are different. OBJECTIVE: Further molecular insight into these differences is therefore needed to enable effective future diagnostic and treatment strategies. The majority of our mechanistic and clinical understanding of psoriasis and eczema is derived from RNA, immunohistology and whole skin biopsy data. METHODS: In this study, non-invasive epidermal sampling of lesional, perilesional and non-lesional skin from diseased and healthy skin was used to perform an in depth proteomic analysis of epidermal proteins. RESULTS: Our findings confirmed the psoriasis-associated cytokine IL-36γ as an excellent protein biomarker for lesional psoriasis. However, ELISA and ROC curve analysis of 53 psoriasis and 42 eczema derived samples showed that the sensitivity and specificity were outperformed by elastase-specific protease inhibitor, elafin. Of note, elafin was also found upregulated in non-lesional psoriatic skin at non-predilection sites demonstrating inherent differences between the non-involved skin of healthy and psoriatic individuals. Mass spectrometry and ELISA analysis also demonstrated the upregulation of the anti-inflammatory molecule IL-37 in psoriatic perilesional but not lesional skin. The high expression of IL-37 surrounding psoriatic plaque may contribute to the sharp demarcation of inflammatory morphology changes observed in psoriasis. This finding was also specific for psoriasis and not seen in atopic dermatitis or autoimmune blistering perilesional skin. Our results confirm IL-36γ and add elafin as robust, hallmark molecules distinguishing psoriasis and eczema-associated inflammation even in patients under systemic treatment. CONCLUSIONS: Overall, these findings highlight the potential of epidermal non-invasive sampling and proteomic analysis to increase our diagnostic and pathophysiologic understanding of skin diseases. Moreover, the identification of molecular differences in healthy-looking skin between patients and healthy controls highlights potential disease susceptibility markers and proteins involved in the initial stages of disease.

Burden of impaired sleep and its improvement through topical treatment in psoriasis and atopic dermatitis.

INTRODUCTION: Patients with chronic inflammatory skin diseases often suffer from sleep disturbances. However, objective data on sleep architecture, especially to evaluate potential overall influences under therapy, are lacking. PATIENTS AND METHODS: Pilot study on sleep quality changes including psoriasis and atopic dermatitis patients before and 2 weeks after intensive topical treatment. In addition to disease activity rating, patient-rated outcomes for itch severity and sleep quality and polygraphy was performed before and after topical therapy. RESULTS: 14 psoriasis, eleven atopic dermatitis patients (10 female, 15 male) with a mean age of 49 years were included. Disease activity scores (EASI and PASI) were significantly reduced with topical therapy after 2 weeks (p < 0.001). Pruritus intensity (NRS) showed a significant influence on deep sleep, which resolved after therapy. Insomnia severity significantly decreased (r > 0.50, p < 0.05) and daytime sleepiness showed a significant reduction in 40% of patients. N3 (deep sleep) and REM sleep significantly improved, showing a strong effect (r > 0.50). The apnea-hypopnea index decreased in one of four patients independent of the individual BMI. CONCLUSIONS: Through polygraphy, we demonstrated impaired sleep patterns in psoriasis and atopic dermatitis patients with itch as a relevant factor and beyond that, rapid sleep improvement under 2 weeks of topical treatment.

Real-world effectiveness and safety of the LAight-therapy in patients with hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Hidradenitis suppurativa (HS)/Acne inversa (Ai) is a chronic debilitating disease with limited therapy options. The device-based LAight therapy was approved in Europe in 2017. The aim of this study was to evaluate the effect of real-world care with at least one treatment with LAight therapy on disease activity and burden in 3,437 patients. PATIENTS AND METHODS: Patients were included in the analysis if they had a diagnosis of HS and received at least one treatment. The endpoints Hidradenitis Suppurativa Severity Score System (IHS4), pain on the numeric rating scale (pain-NRS) and Dermatology Life Quality Index (DLQI) were analyzed using a linear mixed model for repeated measures (MMRM) over 26 weeks of care with LAight therapy. Furthermore, responder rates were calculated for all endpoints, and the therapy's safety profile and patient satisfaction were thoroughly examined. RESULTS: A significant decrease in IHS4, pain-NRS, and DLQI was achieved during 26 weeks of care with LAight. The BMI at baseline had a significant negative effect on therapy response for pain-NRS and DLQI. CONCLUSIONS: This study confirms that LAight therapy leads to satisfactory disease control in all stages of severity and is a valuable addition to the therapeutic repertoire of HS.

Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Bridging the gaps: management of lichen planus subtypes in a joint dermatology-oral surgery clinic.

Lichen planus (LP) presents with a range of clinical subtypes. It can affect the outer skin, involve the nails and present with alopecia and mucosal symptoms to varying degrees. LP of the outer skin mostly shows a self-limiting course; however, this is not the case for lichen planopilaris and the mucosa-affecting subtypes. The pathogenesis of LP is still incompletely understood. As a result, an effective, targeted therapy is currently lacking and different immunomodulatory approaches are being used in clinical practice. The management of patients with severe oral LP mucosae can be particularly challenging. Although the true risk remains controversial, oral LP is considered a risk factor for the development of squamous cell carcinoma and there is a need for regular screening. The quality of life in patients with LP is significantly impaired because of frequent clinical visits, pain, soreness, inability to eat certain foods, side effects to medication, frustrating therapy attempts and worry regarding cancer risk. We highlight here the advantages of an interdisciplinary dermatology and oral surgery clinic, which can address the domains of tooth status, nutrition, pain and malignant transformation and optimized patient management.

Sleep disorders in dermatology - a comprehensive review.

Sleep is a normal physiological process that accounts for approximately one third of a person's life. Disruption of the normal sleep cycle, which maintains physiological homeostasis, can lead to pathology. It is not known whether sleep disturbance causes skin disease or skin disease causes sleep impairment, but a bidirectional influence is suspected. We have compiled the data from published articles on "sleep disorders in dermatology" in PubMed Central from July 2010 to July 2022 (with the option "full text available") and provide an overview of sleep disorders associated with dermatological conditions and certain drugs used in dermatology as well as sleep disturbances for which some drugs used can cause itch or dermatological issues. Atopic dermatitis, eczema and psoriasis have been shown to be exacerbated by sleep problems and vice versa. Sleep deprivation, night-time pruritus and disrupted sleep cycles are often used to assess treatment response and quality of life in these conditions. Some medications used primarily for dermatological conditions have also been associated with alterations in the sleep-wake cycle. Addressing patients sleep disorders should be an integral part of the management of dermatological conditions. More studies are needed to further investigate the influence of sleep and skin disorders.

Examining volumetric gradients based on the frustum surface ratio in the brain in autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is accompanied by neurodevelopmental differences in regional cortical volume (CV), and a potential layer-specific pathology. Conventional measures of CV, however, do not indicate how volume is distributed across cortical layers. In a sample of 92 typically developing (TD) controls and 92 adult individuals with ASD (aged 18-52 years), we examined volumetric gradients by quantifying the degree to which CV is weighted from the pial to the white surface of the brain. Overall, the spatial distribution of Frustum Surface Ratio (FSR) followed the gyral and sulcal pattern of the cortex and approximated a bimodal Gaussian distribution caused by a linear mixture of vertices on gyri and sulci. Measures of FSR were highly correlated with vertex-wise estimates of mean curvature, sulcal depth, and pial surface area, although none of these features explained more than 76% variability in FSR on their own. Moreover, in ASD, we observed a pattern of predominant increases in the degree of FSR relative to TD controls, with an atypical neurodevelopmental trajectory. Our findings suggest a more outward-weighted gradient of CV in ASD, which may indicate a larger contribution of supragranular layers to regional differences in CV.

Atypical measures of diffusion at the gray-white matter boundary in autism spectrum disorder in adulthood.

Autism spectrum disorder (ASD) is a highly complex neurodevelopmental condition that is accompanied by neuroanatomical differences on the macroscopic and microscopic level. Findings from histological, genetic, and more recently in vivo neuroimaging studies converge in suggesting that neuroanatomical abnormalities, specifically around the gray-white matter (GWM) boundary, represent a crucial feature of ASD. However, no research has yet characterized the GWM boundary in ASD based on measures of diffusion. Here, we registered diffusion tensor imaging data to the structural T1-weighted images of 92 adults with ASD and 92 matched neurotypical controls in order to examine between-group differences and group-by-sex interactions in fractional anisotropy and mean diffusivity sampled at the GWM boundary, and at different sampling depths within the superficial white and into the gray matter. As hypothesized, we observed atypical diffusion at and around the GWM boundary in ASD, with between-group differences and group-by-sex interactions depending on tissue class and sampling depth. Furthermore, we identified that altered diffusion at the GWM boundary partially (i.e., ~50%) overlapped with atypical gray-white matter tissue contrast in ASD. Our study thus replicates and extends previous work highlighting the GWM boundary as a crucial target of neuropathology in ASD, and guides future work elucidating etiological mechanisms.

Patterns of Cortical Folding Associated with Autistic Symptoms in Carriers and Noncarriers of the 22q11.2 Microdeletion.

22q11.2 deletion syndrome (22q11.2DS) is a genetic condition accompanied by a range of psychiatric manifestations, including autism spectrum disorder (ASD). It remains unknown, however, whether these symptoms are mediated by the same or distinct neural mechanisms as in idiopathic ASD. Here, we examined differences in lGI associated with ASD in 50 individuals with 22q11.2DS (n = 25 with ASD, n = 25 without ASD) and 81 individuals without 22q11.2DS (n = 40 with ASD, n = 41 typically developing controls). We initially utilized a factorial design to identify the set of brain regions where lGI is associated with the main effect of 22q11.2DS, ASD, and with the 22q11.2DS-by-ASD interaction term. Subsequently, we employed canonical correlation analysis (CCA) to compare the multivariate association between variability in lGI and the complex clinical phenotype of ASD between 22q11.2DS carriers and noncarriers. Across approaches, we established that even though there is a high degree of clinical similarity across groups, the associated patterns of lGI significantly differed between carriers and noncarriers of the 22q11.2 microdeletion. Our results suggest that ASD symptomatology recruits different neuroanatomical underpinnings across disorders and that 22q11.2DS individuals with ASD represent a neuroanatomically distinct subgroup that differs from 22q11.2DS individuals without ASD and from individuals with idiopathic ASD.

A comparison of cannula insufflation device performance for emergency front of neck airway.

BACKGROUND: Pediatric emergency front of neck airway guidelines recommend oxygenation via cannula cricothyroidotomy or tracheotomy. AIM: The primary aim was to measure test lung pressures and volumes generated by cannula insufflation devices recommended for emergency front of neck airway compared with a pressure limit of 50 cm H2 O and volume limit of 20 ml/kg. The secondary aim was to calculate pressure and volume variability. The primary end point was test lung expansion. METHOD: Adult, child, and infant airway models, each with three degrees of upper airway obstruction, were oxygenated using six cannula insufflation devices: 3-way stopcock, Rapid-O2 , Manujet, Enk oxygen flow modulator, Ventrain, and self-inflating bags. Test lung pressures and volumes were recorded. RESULTS: Pressures and volumes from all devices were highly variable, despite oxygen flow calibration and strict adherence to oxygen insufflation protocols. With upper airway occlusion, pressures >50 cm H2 0 were produced by Rapid-O2 and Enk oxygen flow meter in adult and infant lungs, 3-way stopcock in adult and child lungs, and Manujet in all lung sizes. Ventrain produced acceptable pressures <35 cm H2 O in all models. Test lung volumes >20 ml/kg were recorded in airway models with fully obstructed proximal airways using Rapid-O2 and Enk oxygen flow meter in infant lungs, and Manujet in all lung sizes. Rapid-O2 produced lung volumes >20 ml/kg in the infant model with partially obstructed and open upper airways. Test lung volumes >20 ml/kg were produced by the 3-way stopcock in adult, child, and infant models. Insufflation was unsuccessful with the self-inflating bag. Ventrain produced acceptable volumes <7 ml/kg in all airway models. CONCLUSION: Rapid-O2 , Enkoxygen flow meter, Manujet, and 3-way stopcock oxygenation devices produced highly variable and excessive airway pressures and volumes in models with obstructed upper airways. Self-inflating bag insufflation was unsuccessful. Ventrain was the only device that insufflated oxygen with acceptable pressures and volumes in adult, child, and infant airway models with any degree of airway obstruction.

Epidemiology of urticaria in German children.

BACKGROUND: To date, robust epidemiological metrics as well as data on comorbidity in pediatric urticaria are lacking. They form the basis for the design of efficient healthcare. METHODS: Retrospective study to analyze epidemiological data in pediatric urticaria. The analysis is based on routine data of a health insurance company operating throughout Germany (DAK-Gesundheit). Insured people under 18 years of age who received at least one confirmed outpatient or inpatient urticaria diagnosis according to the ICD-10 classification in the years 2010 to 2015 were included in the analysis and compared to children without a corresponding diagnosis. RESULTS: Of 2.3 million insured individuals, 313,581 (13.5 %) were under 18 years of age (153,214 female). Urticaria was diagnosed in 1.7 % of the 313,581 patients. The prevalence of urticaria decreased with age from 3.0 % in the 0-3-year age group to 1.0 % in the 14-18-year age group. Boys and girls were almost equally affected in all age groups. Atopic diseases as comorbidity occurred more frequently in children with urticaria than in the control group (16.0 % vs. 8.0 %). Autoimmune diseases, mental health problems, and obesity also occurred more frequently in children with urticaria than in the control group. CONCLUSIONS: The increased prevalence of specific comorbidities in children with urticaria suggests an increased need for screening. Multimodal treatment strategies need to be developed and interdisciplinary collaboration promoted.

Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and l-DOPA Administration.

Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n = 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (l-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n = 22) and compared the results between both studies. We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS- and l-DOPA-induced activation, and >100 neuronal receptor gene expression maps based on transcriptional data from the Allen Institute for Brain Science. In line with a specific activation of the dopaminergic system, we found that both interventions predominantly activated regions with high expression levels of the dopamine receptors D2 and D3.SIGNIFICANCE STATEMENT Studies in animals and humans provide evidence that transcranial direct current stimulation (tDCS) allows a manipulation of the dopaminergic system. Based on these findings, we used fMRI to assess changes in spontaneous neural activity strength in the human dopaminergic system after prefrontal tDCS compared with the administration of the dopamine precursor and standard anti-Parkinson drug levodopa (l-DOPA). We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. Using whole-brain transcriptional data of >100 neuronal receptor genes, we found that both interventions specifically activated regions with high expression levels of the dopamine receptors D2 and D3.

Sleep Disturbance in Patients with Urticaria and Atopic Dermatitis: An Underestimated Burden.

This study examined the relationship between insomnia and the frequent itching skin diseases, atopic dermatitis and chronic urticaria. Patients with chronic inflammatory dermatological diseases with pruritus were evaluated for insomnia (Insomnia Severity Index; ISI) and impairment in dermatological quality of life (Dermatology Life Quality Index; DLQI). Disease activity was measured using validated scores. A total of 61 patients participated in the study. Patients with atopic dermatitis had a mean ISI score of 8.7 before flares and 16 when a flare occurred. The mean DLQI score in atopic dermatitis was 11.4. The mean ISI score in patients with chronic urticaria was 6.8 before flares and 14.9 when a flare occurred. In patients with chronic urticaria the mean DLQI score was 8.5. An increase in insomnia during a disease flare was demonstrated in both groups. Thus, sleep is a factor to consider during treatment of itching skin diseases. The results of this pilot study indicate that pruritus may not be the only reason for insomnia in patients with atopic dermatitis or chronic urticaria.

Identifying the core attributes of pediatric communication techniques to be taught to anesthetic trainees.

BACKGROUND: Anesthetic induction and other procedures performed by anesthetists are potentially stressful for children. Pediatric anesthetists use communication to rapidly establish rapport and engagement with children and reduce anxiety and discomfort. Communication in pediatric anesthesia is increasingly topical, but there is limited discussion regarding which specific techniques should be taught to trainees. AIMS: The aim of this research was to identify which communication techniques used locally by pediatric anesthetic specialists, trainees, and nurses are viewed as the most effective and valuable to teach trainees. METHODS: Qualitative semi-structured focus groups (7) and in-depth interviews (7) were used to gather data from 30 specialist pediatric anesthetists, trainees, and assistants from a major tertiary pediatric anesthetic department. Inductive and deductive thematic data analysis explored communication techniques used locally. RESULTS: The research identified the range of communication techniques being utilized to establish rapport and engage with children, including methods for distraction and focusing attention such as storytelling, guided imagery, and positive suggestions. Thematic analysis revealed a series of core overarching principles for successful application, using social skills within an adaptable, competent, child-centered approach. Drawing on the experiences of specialist practitioners and trainees, teaching these communication techniques would ideally employ an interactive approach involving both modeling and specific communication education with focus on developing communication skills via experiential learning using self-reflection and feedback. CONCLUSIONS: Within the range of communication techniques being utilized by pediatric anesthetists exist a series of core principles that are essential to engaging and building rapport with children. Focusing on the importance of these common core elements in trainee education, in addition to the range of techniques available, may provide a pragmatic framework for centers providing pediatric anesthesia to consider when designing their trainee curriculum.

Down syndrome is accompanied by significantly reduced cortical grey-white matter tissue contrast.

Increased cortical thickness (CT) has been reported in Down syndrome (DS) during childhood and adolescence, but it remains unclear, which components of the neural architecture underpin these increases and if CT remains altered in adults. Among other factors, differences in CT measures could be driven by reduced tissue contrast between grey and white matter (GWC), which has been reported in neurodegenerative disorders, such as Alzheimer's disease. Using structural magnetic resonance imaging, we therefore examined differences in CT and GWC in 26 adults with DS, and 23 controls, to (1) examine between-group differences in CT in adulthood, (2) establish whether DS is associated with significant reductions in GWC, and (3) determine the influence of GWC variability on between-group differences in CT. As hypothesized, we observed that DS was accompanied by wide-spread increases in CT, and significantly reduced GWC in several large clusters distributed across the cortex. Out of all vertices with a significant between-group difference in CT, 38.50% also displayed a significant reduction in GWC. This percentage of overlap was also statistically significant and extremely unlikely to be obtained by chance (p = .0002). Differences in GWC thus seem to explain some, although not all, of the differences in CT observed in DS. In addition, our study is the first to extend previous in vivo reports of altered CT in DS during childhood and adolescence to older adults, implying that the regional pattern of neuroanatomical differences associated with DS remains stable across the lifespan.