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Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET–fMRI study ( n = 17), we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying. MOR availability was measured with positron emission tomography (PET) using the high-affinity agonist radioligand [ 11 C]carfentanil. Haemodynamic responses to social laughter and crying vocalizations were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, and primary and secondary motor cortex; crying sounds led to more restricted activation in the auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in the primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of the MOR system in modulating acute brain responses to both positive and negative social signals. This article is part of the theme issue ‘Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience’.

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

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Patients with atopic dermatitis have an increased risk of herpes simplex virus (HSV) infections.We carried out a retrospective, cross-sectional study to investigate the association of disease severity, concomitant atopic diseases and filaggrin mutations with the risk of cutaneous HSV infections in 463 patients with atopic dermatitis.The correlation between predisposing factors and HSV infections was analysed using chi-square and Mann Whitney U-tests, and the relationship was further studied with binomial logistic regression to ascertain odds ratios.Allergic conjunctivitis (aOR: 1.770; CI: 1.008-3.109; p = 0.047) and patient age (aOR: 1.022; CI: 1.007-1.036; p = 0.004) showed statistically significant associations with recurrent HSV infections and eczema herpeticum. HSV infections were not linked to severity of atopic dermatitis (p = 0.435) or filaggrin mutation status (p = 0.886).The results highlight the importance for attentiveness of HSV infections in atopic dermatitis patients with concomitant allergic conjunctivitis.

BACKGROUND Atopic dermatitis (AD) is a frequent and heterogeneous inflammatory skin disease, for which personalized medicine remains a challenge. High-throughput approaches have improved understanding of the complex pathophysiology of AD. However, a purely data-driven AD classification is still lacking. METHODS To address this question, we applied an original unsupervised approach on the largest available transcriptome dataset of AD lesional (n = 82) and healthy (n = 213) skin biopsies. RESULTS Taking into account pathological and physiological state, a variance-based filtering revealed 222 AD-specific hyper-variable genes that efficiently classified the AD samples into 4 clusters that turned out to be clinically and biologically distinct. Comparison of gene expressions between clusters identified 3 sets of upregulated genes used to derive metagenes (MGs): MG-I (19 genes) was associated with IL-1 family signaling (including IL-36A and 36G) and skin remodeling, MG-II (23 genes) with negative immune regulation (including IL-34 and 37) and skin architecture, and MG-III (17 genes) with B lymphocyte immunity. Sample clusters differed in terms of disease severity (p = .02) and S. aureus (SA) colonization (p = .02). Cluster 1 contained the most severe AD, highest SA colonization, and overexpressed MG-I. Cluster 2 was characterized by less severe AD, low SA colonization, and high MG-II expression. Cluster 3 included mild AD, mild SA colonization, and mild expression of all MGs. Cluster 4 had the same clinical features as cluster 3 but had hyper-expression of MG-III. Last, we successfully validated our method and results in an independent cohort. CONCLUSION Our study revealed unrecognized AD endotypes with specific underlying biological pathways, highlighting novel pathophysiological mechanisms. These data could provide new insights into personalized treatment strategies.

Publisher Copyright: © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. Background: Severity-associated factors in atopic dermatitis (AD) have focussed on early onset, concomitant atopic diseases, markers of Th2-shifted inflammation and filaggrin mutations. Objectives: To investigate factors associated with severe AD in Finnish patients. Methods: We conducted a single-centre, cross-sectional observational study with 502 AD patients aged 4.79 to 79.90 years (mean 32.08 years). Disease severity was assessed with the Rajka–Langeland severity score and EASI and associated clinical signs were evaluated. Data regarding onset, relatives, atopic and other comorbidities was gathered retrospectively. We investigated total serum IgE-levels, a panel of filaggrin null mutations and functional variants of genes associated with skin barrier defects. Results: Factors more frequent in severe AD included early onset (P = 0.004, 95%CI 0.000–0.024), male sex (P = 0.002, 95%CI 0.000–0.11), history of smoking (P = 0.012, 95%CI 0.000–0.024), concomitant asthma (P = 0.001, 95%CI 0.000–0.011), palmar hyperlinearity (P = 0.013, 95%CI 0.014–0.059), hand dermatitis (P = 0.020, 95%CI 0.000–0.029) and history of contact allergy (P = 0.042, 95%CI 0.037–0.096). Body mass indices (P < 0.000, 95%CI 0.000–0.011) and total serum IgE-levels (P < 0.000, 95%CI 0.000–0.011) were higher in severe AD. No differences were observed for allergic rhinitis, allergic conjunctivitis, food allergy, peanut allergy, prick positivity, keratosis pilaris, history of herpes simplex infections, filaggrin null mutations and other gene variants. Conclusions: Severity determinants in Finnish patients seem to be early-onset, male sex, smoking, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis and high IgE-levels. A sub-typing of patients in relation to confirmed severity determinants may be useful for course prediction, prognosis and targeted AD management.

The burden of atopic dermatitis (AD) appears to be increasing in adult and elderly patients. The aim of this study was to analyse the nationwide database of the Finnish Institute for Health and Welfare regarding the number of patients with AD and of general practitioner consultations in Finland during 2018. The database comprised the main diagnoses of all visits to public primary healthcare. There were 2,094,673 primary care patients (males/females 43.19/56.81%) and 20,905 patients with AD (1.00%) and 24,180 consultations due to AD (0.45%). The highest numbers of patients with AD were in the age groups 0–14 years (9,922 patients, 47.46%) and 15–65 years (9,144 patients, 43.74%). A substantial proportion of patients with AD were aged > 50 years (3,515 patients, 16.81%) or >65 years (1,947 patients, 9.31%). Regression analysis indicated a statistically significant association of age group with patient numbers (p = 0.032) and number of consultations (p = 0.030). There were no differences between direct age group comparisons (p = 0.303), sex (p = 0.389), or number of consultations/patient (p = 0.235). Patients with AD are prevalent in all age groups in Finnish primary care. Patient numbers were also relatively high in groups other than childhood, indicating that age-related distribution in primary care may be shifting to older ages.

BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

Funding Information: Jari Tiihonen has participated in research projects funded by grants from Janssen-Cilag and Eli Lilly to his employing institution, and has been a consultant and/or advisor to and/or has received honoraria from: Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Orion, Otsuka, Mediuutiset, Sidera, and Sunovion. Funding Information: The study was supported by the Academy of Finland (grants numbers 294897 and 332225, to L.N.), Valon Vuoksi Foundation (grants to L.S. and L.L.) and Turku Collegium for Science and Medicine, University of Turku (to L.S.). Publisher Copyright: © 2022 The Authors The goal of this study was to elucidate the anatomical brain basis of social cognition through two disorders with distinctively different phenotypes of social interaction. We compared structural MR images of 20 individuals with autism spectrum disorder (ASD), 19 violent offenders with high psychopathic traits, and 19 control participants using voxel-based morphometry (VBM). Our earlier study showed lower grey matter volume (GMV) values in the insula, frontal cortex, and sensorimotor cortex of the offender group compared to controls. In the present study, the images of the ASD group revealed lower GMV in the left precuneus, right cerebellum, and right precentral gyrus in comparison with controls. The comparison between the offender and ASD groups showed lower GMV values for the right temporal pole and left inferior frontal gyrus in the offender group. There was also an overlap of both disorders in the right pre-central cortex, showing lower GMV compared to controls. Our findings suggest structural differences between violent offenders with high psychopathy traits and ASD individuals in the frontotemporal social brain network areas, previously associated with empathy. We also provide evidence of similar abnormal structures in the motor cortex for both of these disorders, possibly related to uniting issues of social cognition.

Contains fulltext : 251811.pdf (Publisher’s version ) (Closed access) BACKGROUND: Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive. OBJECTIVE: In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD. METHODS: Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (AD(Mut)) (n = 15), along with matched wild-type (AD(Wt)) patients and healthy controls. Detailed clinical characterization, microarray gene expression and 16 S rRNA-based microbial marker gene data were generated and analyzed. RESULTS: In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of AD(Wt) demonstrated the specific upregulation of pro-inflammatory cytokines and T-cell proliferation. S. aureus dominated the microbiome in both patient groups, however, shifting microbial communities could be observed when comparing healthy with non-lesional AD(Wt) or AD(Mut) skin, offering the opportunity to identify microbe-associated transcriptomic signatures. Moreover, an AD core signature with 28 genes, including CCL13, CCL18, BTC, SCIN, RAB31 and PCLO was identified. CONCLUSIONS: Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.

Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.

Background Nickel‐induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated. Methods To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96 hours after nickel patch test in six nickel‐allergic patients. Gene expression profiles were analyzed via microarray. Results Leukocyte deconvolution of nACD‐affected skin identified major leukocyte compositional changes at 48 and 96 hours, including natural killer (NK) cells, macrophage polarization, and T‐cell immunity. Gene set enrichment analysis mirrored cellular‐linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD‐affected skin compared to sodium lauryl sulfate–induced irritant skin reactions. Conclusion These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets., Late‐phase nickel challenge induces major changes in leukocyte composition including influx and activation of NK cells, macrophage polarization, and T‐cell immunity. MMP12 and SOCS3 are highly upregulated, linking our human findings to previous findings in mice. NK cell infiltration and cytotoxic pathways were found to be uniquely upregulated in nickel‐induced allergic skin responses compared to SLS‐induced irritant skin responses. Abbreviations: MMP12, matrix metallopeptidase 12; NiSO4, nickel sulfate; SLS, sodium lauryl sulfate; SOCS3, suppressor of cytokine signaling 3.

It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease‐related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations—an "AD‐like microbiome," but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation., Distinct disease‐related gene expression profiles depend on anatomical location—keratinization is dominating in the posterior thigh and lipid metabolism in the upper back. Relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. The abundance of S aureus in posterior thigh is associated with keratinization and circadian rhythm regulating genes

Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.Method: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set-up a web-based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. Results: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusions: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients. Keywords: COVID-19, allergen immunotherapy (AIT), SARS-CoV-2, practicability, survey, safety, pandemic

Background Left ventricle rotation and torsion are fundamental components of myocardial function, and several software packages have been developed for analysis of these components. The purpose of this study was to compare the suitability of two software packages with different technical principles for analysis of rotation and torsion of the left ventricle during systole. Methods A group of hypertrophic cardiomyopathy (HCM) patients (N = 14, age 43 ± 11 years), mutation carriers without hypertrophy (N = 10, age 34 ± 13 years), and healthy relatives (N = 12, age 43 ± 17 years) underwent a cardiovascular magnetic resonance examination, including spatial modulation of magnetization tagging sequences in basal and apical planes of the left ventricle. The tagging images were analyzed offline using a harmonic phase image analysis method with Gabor filtering and a non-rigid registration-based free-form deformation technique. Left-ventricle rotation and torsion scores were obtained from end-diastole to end-systole with both software. Results Analysis was successful in all cases with both software applications. End-systolic torsion values between the study groups were not statistically different with either software. End-systolic apical rotation, end-systolic basal rotation, and end-systolic torsion were consistently higher when analyzed with non-rigid registration than with harmonic phase-based analysis (p p Conclusions When comparing absolute values of rotation and torsion between different individuals, software-specific reference values are required. Harmonic phase flow with Gabor filtering and non-rigid registration-based methods can both be used reliably in the analysis of systolic rotation and torsion patterns of the left ventricle.

Significance Contact dermatitis is an inflammatory skin disorder that arises from direct skin contact with irritants or allergens. Representing over 90% of occupational skin disorders, it has a considerable socioeconomic impact, and patients suffering from contact dermatitis can develop a notable physical handicap. Current diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits. However, distinguishing the clinical phenotype of irritant and allergic contact dermatitis, which is important for appropriate therapeutic strategies, remains challenging. This study identifies and validates biomarkers to distinguish allergic and irritant contact dermatitis in human skin, to be used for the development of novel diagnostic methods and to guide clinical diagnosis., Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.

Objectives: The sensitivity and specificity of the conventional 12-lead ECG to identify carriers of hypertrophic cardiomyopathy (HCM) - causing mutations without left ventricular hypertrophy (LVH) has been limited. We assessed the ability of novel electrocardiographic parameters to improve the detection of HCM mutation carriers. Methods: We studied 140 carriers (G+) of the TPM7-Asp175Asn or MYBPC3-Glnl 061X pathogenic variants for HCM: The G+/LVH+ group (n = 98) consisted of mutation carriers with LVH and the G+/LVH- group (n = 42) without LVH. The control group consisted of 30 subjects. The standard 12-lead ECG was comprehensively analyzed and two novel ECG variables were introduced: RVlRV3 and septal remodeling. A subset of 65 individuals underwent cardiac magnetic resonance imaging and 2D strain echocardiography. Results: Conventional major ECG criteria were sensitive (90%) and specific (97%) in identifying G+/LVH+ subjects. RV1RV3 and septal remodeling were more prevalent in the G+/LVH- subjects compared to the control group (33% vs 3%, p = 0.005 and 45% vs 3%, p

Background and aims: Obesity and metabolic syndrome (MetS) are risk factors of atrial fibrillation (AF), but limited data exist on their effect on left atrial (LA) function. The aim of the study was to evaluate the effects of cardiac, hepatic and intra-abdominal ectopic fat depots and cardiometabolic risk factors on LA function in non-diabetic male subjects. Methods and results: Myocardial and hepatic triglyceride contents were measured with 1.5T H-1-magnetic resonance spectroscopy and LA and left ventricular function, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial and pericardial fat by magnetic resonance imaging (MRI) in 33 men with MetS and 40 men without MetS. LA volumes were assessed using a novel three-chamber orientation based MRI approach. LA ejection fraction (EF) was lower in MetS patients than in the control group (44 +/- 7.7% in MetS vs. 49 +/- 8.6% in controls, p = 0.013) without LA enlargement, indicating LA dysfunction. LA EF correlated negatively with waist circumference, body mass index, SAT, VAT, fasting serum insulin, and homeostasis model assessment of insulin resistance index, and positively with fasting serum high-density lipoprotein cholesterol. VAT was the best predictor of reduced LA EF. Conclusions: MetS associates with subclinical LA dysfunction. Multiple components of MetS are related to LA dysfunction, notably visceral obesity and insulin resistance. Further studies are needed to elucidate the role of mechanical atrial remodeling in the development of AF. (C) 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

BackgroundRight ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus.MethodsThe study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function.ResultsSevere pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p2or in controls.ConclusionsIn patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.

Oral retinoids and tetracyclines have a major role in acne treatment. Here, we report for the first time the effect of isotretinoin and lymecycline therapy on the skin microbiota in cheek, back and armpit swab samples of acne vulgaris patients using 16S ribosomal RNA (16S rRNA) gene amplicon sequencing. Propionibacterium acnes was the most common in sebaceous areas of healthy and untreated acne skin and more abundant in back than cheek samples. Five taxa, including a Streptococcus taxon, differed significantly between the cheek samples of healthy controls and acne patients, and acne severity was positively correlated with the abundance of Propionibacterium. Both treatments reduced clinical acne grades and the abundance of Propionibacterium, while the abundance of several other taxa was significantly higher in treated cheek samples compared with untreated ones. Less variation was observed in back samples and none in armpit samples. There were no differences in alpha diversity between control and acne patients in any of the sampled skin areas, but the diversity of the microbiota on the cheek and the back was significantly increased after acne treatments. This study provides insight into the skin microbiota in acne and how it is modulated by systemic acne treatment.

Neonatal sepsis (NS) is a frequent problem in neonatal intensive care, especially in preterm and very low birthweight (VLBW) infants. The objective of the study was to characterize the cutaneous bacterial microbiome in VLBW infants treated in the neonatal intensive care unit (NICU). Non-invasive skin microbiome specimens were taken repeatedly from 12 VLBW infants during treatment in NICU starting on the first day of life. All infants received benzylpenicillin and netilmicin during the first 1-5 postnatal days. Samples were also collected from incubators. High cutaneous microbial diversity was present at birth in 11 of 12 of the infants, but the diversity decreased substantially after the first weeks of life in all infants regardless of their infection status. After the loss of diversity, one Staphylococcus operational taxonomic unit dominated the skin microbiome. Recovery of microbial diversity was seen in six of 12 neonates. The microbiome of incubators showed typical environmental bacterial genera. Maternal antibiotic treatment, the aetiology of the preterm birth or being born by C-section did not appear to affect the diversity of skin microbiota at birth, and no correlation was found between cutaneous microbiome and NS.

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis., Atopic dermatitis (AD) and psoriasis (PSO) are associated with dysbiosis. Here, by analyses of skin microbiome and host transcriptome of AD and PSO patients, the authors find distinct microbial and disease-related gene transcriptomic signatures that differentiate both diseases.

This manuscript has not been published before and is not currently being considered for publication elsewhere. Increased septal convexity of left ventricle has been described in subjects with hypertrophic cardiomyopathy (HCM)-causing mutations without left ventricular hypertrophy (LVH). Our objective was to study septal convexity by cardiac magnetic resonance (CMR) in subjects with the Finnish founder mutation Q1016X in the myosin-binding protein C gene (MYBPC3). Septal convexity was measured in end-diastolic 4-chamber CMR image in 67 study subjects (47 subjects with the MYBPC3-Q1061X mutation and 20 healthy relatives without the mutation). Septal convexity was significantly increased in subjects with the MYBPC3-Q1061X mutation and LVH (n = 32) compared to controls (11.4 +/- 4.3 vs 2.7 +/- 3.2 mm, P

Objectives Postoperative patients with tetralogy of Fallot (TOF) are often compromised by chronic pulmonary regurgitation and chronic right ventricular volume load. We sought to determine whether pulmonary regurgitation (PR) would affect right and left ventricle (RV and LV) strain. Materials and methods This cross-sectional analysis included 40 patients who had TOF with surgical repair, with an average follow-up period of 11.8 ± 3.0 years. Altogether, 44 healthy volunteers with similar age and gender distribution were recruited. A cardiovascular magnetic resonance imaging study with feature tracking analysis was performed on all patients and controls. Results RV peak longitudinal strain was increased in TOF patients with PR > 30 ml/m2 when compared to those with PR 2 (− 22.5% ± 2.7% vs − 19.7% ± 3.5%, p = 0.018) and controls (p = 0.007). PR volume correlated with peak RV longitudinal strain (R = − 0.37, p = 0.030) and peak RV longitudinal strain rate (systolic: R = 0.37, p = 0.03; diastolic: R = 0.39, p = 0.021). The peak RV circumferential strain, from base to apex, increased more than in healthy controls (apex-base difference 7.6% ± 4.2% vs 3.3% ± 2.4%, p Conclusions Pediatric patients with TOF and a severe pulmonary regurgitation show an enhanced longitudinal strain when compared to patients with milder regurgitation or to control subjects. In addition, mean RV circumferential strain of the patients is significantly enhanced compared to healthy individuals.

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients’ organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

OBJECTIVES Sonographic artifacts known as B-lines can been used to estimate alterations of lung parenchyma. Multiple B-lines on sonography are seen in congestive heart disease, interstitial lung disease, respiratory infections, and neonates. The aim of this study was to compare the amount of B-lines on sonography to the extent of parenchymal changes on computed tomography (CT) in children. METHODS Lung sonography was performed on 60 patients aged 18 years and younger referred for chest CT at our institution. B-lines were counted from 5 anterolateral intercostal spaces bilaterally. The CT findings were documented and graded as absent, minimal, partial, or complete. RESULTS The number of B-lines on sonography increased consistently with the growing extent of parenchymal changes on CT. The differences in the B-line counts between the patients grouped according to the extent of parenchymal changes on CT were statistically significant except between patients with minimal and no changes (P < .01 Kruskal-Wallis and Tukey tests). CONCLUSIONS The number of B-lines on sonography correlates with the extent of parenchymal changes on CT. Various parenchymal changes were seen in patients with B-lines on sonography. B-lines were more frequently seen in patients with no changes on CT when imaged during general anesthesia.

Background: Large myocardial infarction (MI) is associated with adverse left ventricular (LV) remodeling (LVR). We studied the nature of LVR, with specific attention to non-transmural MIs, and the association of peak CK-MB with recovery and chronic phase scar size and LVR. Methods: Altogether 41 patients underwent prospectively repeated cardiovascular magnetic resonance at a median of 22 (interquartile range 9-29) days and 10 (8-16) months after the first revascularized MI. Transmural MI was defined as >= 75% enhancement in at least one myocardial segment. Results: Peak CK-MB was 86 (40-216) mu g/L in median, while recovery and chronic phase scar size were 13 (3-23) % and 8 (2-19) %. Altogether 33 patients (81%) had a non-transmural MI. Peak CK-MB had a strong correlation with recovery and chronic scar size (r >= 0.80 for all, r >= 0.74 for non-transmural MIs; p = 0.75 for all, r >= 0.73 for non-transmural MIs; p

Gaining vascular access in a neonate during cardiopulmonary resuscitation is crucial and challenging. Intraosseous (IO) access can offer a fast and reliable method for achieving emergency access for fluids and drugs when venous access fails in a critically ill child. IO access can however result in rare, but serious adverse events including compartment syndrome and amputation. We describe a case resulting in leg amputation due to IO infusion in a neonate after resuscitation and therapeutic hypothermia. We compared 10 tibia X-rays in three age groups. The mean medullary diameter of the proximal tibia at the recommended site for IO access was 7 mm in neonate, 10 mm in 1- to 12-month-old infants, and 12 mm in 3- to 4-year-old children. This provides a narrow margin of safety for the correct positioning and the avoidance of dislodgement of the IO needle. The correct position of the IO needle should be confirmed by bone marrow aspiration and fluid bolus. Unnecessary touching of the IO needle after fixing it in place should be avoided by inserting a luer-lock catheter with a three-way stop-cock for IO drug and fluid administration. Regular observation of the circulation and possible swelling of the leg should be performed. The IO administration of inotropic infusions should also be avoided after the initial resuscitation phase. When treating with therapeutic hypothermia, it may be wise to remove the IO needle much earlier than the currently recommended 24 h because of the problems in peripheral circulation and its monitoring.

As in many European countries, Finnish psychiatric services experienced a rapid process of deinstitutionalization in the 1990s. In recent decades, the decrease in numbers of psychiatric hospital beds has in several countries been found to be linked with increasing criminality among severely mentally ill individuals. It has been concluded that deinstitutionalization could be the main reason for this development.To investigate whether the prevalence of severely mentally ill persons to prison is a growing trend also in Finland.We searched for the annual data in electronic case files of all prisoners about the ICD-10 diagnostic group of the most severe psychotic disorders. We also searched for the comorbid substance use disorders. Psychotic disorders due to substance abuse only were excluded from this study.During the years 2005-2016, a rapid 10-fold increase in psychotic disorders has occurred in Finnish prisons. In 2016, 185 prisoners (5.9% of all Finnish prisoners) were diagnosed as having a psychotic disorder that was not induced by substance abuse. The causes of this dramatic change are unclear. Comorbid substance abuse disorders were detected in only 39.5% of these prisoners and therefore substance abuse can only partly explain the increasing criminality of the severely mentally ill persons. 80.5% of psychotic disorders were diagnosed in Psychiatric Hospital for prisoners and 19.5% in prison policlinic services.Trans-institutionalization has become a serious challenge for the Finnish criminal justice and mental health systems. Further studies are needed to detect the causes of this change. More specialized services for severely mentally ill persons are needed both in the community psychiatry and also inside the prison services.

Staphylococcal enterotoxins have been shown to promote lymphoma-associated immune dysregulation. This study examined changes in the skin microbiome of parapsoriasis compared with intact skin. Swab microbiome specimens were taken of the parapsoriasis lesions of 13 patients. Control samples were taken from contralateral healthy sides of the body. Microbiotas were characterized by sequencing the V1–V3 region of the 16S ribosomal RNA bacterial genes on the Illumina MiSeq platform. The most common genera in the microbiome data were Propionibacterium (27.13%), Corynebacterium (21.20%) and Staphylococcus (4.63%). Out of the Staphylococcus sequences, 39.6% represented S. epidermidis, with the rest including S. hominis, S. capitis and unidentified species. No significant differences were observed between the patients’ parapsoriasis and contralateral healthy skin or between large- and small-plaque parapsoriasis. Notable interpersonal variation was demonstrated. These results suggest that parapsoriasis is not associated with significant alterations in the cutaneous bacterial microbiome.

In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

Background Assessment of myocardial infarct (MI) size is important for therapeutic and prognostic reasons. We used body surface potential mapping (BSPM) to evaluate whether single-lead electrocardiographic variables can assess MI size. Methods We performed BSPM with 120 leads covering the front and back chest (plus limb leads) on 57 patients at different phases of MI: acutely, during healing, and in the chronic phase. Final MI size was determined by contrast-enhanced cardiac magnetic resonance imaging (DE-CMR) and correlated with various computed depolarization- and repolarization-phase BSPM variables. We also calculated correlations between BSPM variables and enzymatic MI size (peak CK-MBm). Results BSPM variables reflecting the Q- and R wave showed strong correlations with MI size at all stages of MI. R width performed the best, showing its strongest correlation with MI size on the upper right back, there representing the width of the “reciprocal Q wave” (r = 0.64–0.71 for DE-CMR, r = 0.57–0.64 for CK-MBm, P < 0.0001). Repolarization-phase variables showed only weak correlations with MI size in the acute phase, but these correlations improved during MI healing. T-wave variables and the QRSSTT integral showed their best correlations with DE-CMR defined MI size on the precordial area, at best r = −0.57, P < 0.0001 in the chronic phase. The best performing BSPM variables could differentiate between large and small infarcts at all stages of MI. Conclusions Computed, single-lead electrocardiographic variables can estimate the final infarct size at all stages of MI, and differentiate large infarcts from small.

2,4-Dinitrochlorobenzene (DNCB) is widely used in human clinical studies and in experimental animal studies to evoke allergic contact dermatitis. 2,4-Dinitrochlorobenzene is a potent immunogen capable of inducing contact sensitization in all humans exposed. However, the mechanism by which DNCB evokes such symptoms is presently unknown. TRPA1 is a nonselective cation channel that is expressed in peptidergic sensory neurons and fibroblasts. TRPA1 activation was recently implicated in the pathophysiology of atopic dermatitis especially in transducing cutaneous itch signals. Here, we test the hypothesis that DNCB acts as a TRPA1 agonist and thereby evokes allergic symptoms. We found that DNCB activates human TRPA1 dose dependently in FLIPR experiments with an EC50 of 167 nM, an effect that was fully blocked by selective TRPA1 antagonists Chembridge-5861528 and A-967079. Similarly, DNCB activated nonselective TRPA1 current in patch clamp studies. Neutralization of 3 critical cysteines in TRPA1 resulted in a loss of DNCB agonism.

Objectives The aim of this study was to introduce a single centre “real life” experience of performing MRI examinations in clinical practice on patients with cardiac pacemaker systems. Additionally, we aimed to evaluate the safety of using a dedicated safety protocol for these patients. Materials and methods We used a 1.5 T MRI scanner to conduct 68 MRI scans of different body regions in patients with pacing systems. Of the cardiac devices, 32% were MR-conditional, whereas the remaining 68% were MR-unsafe. We recorded the functional parameters of the devices prior, immediately after, and approximately one month after the MRI scanning, and compared the device parameters to the baseline values. Results All MRI examinations were completed safely, and each device could be interrogated normally following the MRI. We observed no changes in the programmed parameters of the devices. For most of the participants, the distributions of the immediate and one-month changes in the device parameters were within 20% of the baseline values, although some changes approached clinically important thresholds. Furthermore, we observed no differences in the variable changes between MR-conditional and MR-unsafe pacing systems, or between scans of the thorax area and other scanned areas. Conclusion MRI in patients with MR-conditional pacing systems and selected MR-unsafe systems could be performed safely under strict conditions in this study.

Objective Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. Limited data exist on cardiac adiposity in subjects with dilated cardiomyopathy (DCM). The aim of the study was to examine the components of cardiac steatosis and their relationship to LV structure and function in non-diabetic DCM patients. Methods Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy (MRS), and LV function, visceral adipose (VAT) and abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MRI in 10 non-diabetic men with DCM and in 20 controls. Results In face of comparable intra-abdominal fat depots, myocardial TG [0.41% (0.21–2.19) vs 0.86% (0.31–2.24), p=0.038] was markedly lower and epicardial (895 mm 2 ±110 vs 664 mm 2 ±180, p=0.002) and pericardial fat [2173 mm 2 (616–3673) vs 1168 mm 2 (266–2319), p=0.039] depots were larger in patients with DCM compared with controls. In subjects with DCM, the LV global function index was decreased to a greater extent than the LV EF [21%±6 vs 34% (16–40)]. Conclusions Myocardial TG content decreased and epicardial and pericardial fat depots increased in non-diabetic subjects with DCM. Although recognised as a site of ectopic fat accumulation, the derangement of myocardial TG seems to play a specific role in the myocardial energy metabolism in congestive heart failure.

Cardiac steatosis has been related to increased risk of heart disease. We investigated the association between cardiac steatosis, electrocardiographic (ECG) abnormalities, and individual components of the metabolic syndrome (MetS).A 12-lead ECG and laboratory data were examined in 31 men with the MetS and in 38 men without the MetS. Myocardial triglyceride (MTG) content was measured with 1.5 T magnetic resonance (MR) spectroscopy and epicardial and pericardial fat by MR imaging. MTG content, epicardial and pericardial fat depots were higher in men with the MetS compared with subjects without the MetS (p0.001). The heart rate was increased (p0.001), the PR interval was longer (p0.044), the frontal plane QRS axis shifted to the left (p0.001), and the QRS voltage (p0.001) was lower in subjects with the MetS. The frontal plane QRS axis and the QRS voltage were inversely correlated with MTG content, waist circumference (WC), body mass index (BMI), TGs, and fasting blood glucose. High-density lipoprotein cholesterol correlated positively and measures of insulin resistance negatively with the QRS voltage. MTG content and hypertriglyceridemia were determinants of the frontal plane QRS and WC and hyperglycemia were predictors of the QRS voltage.The MetS and cardiac steatosis appear to associate with multiple changes on 12-lead ECG. The frontal plane QRS axis is shifted to the left and the QRS voltage is lower in subjects with the MetS. Standard ECG criteria may underestimate the presence of left ventricular hypertrophy in obese subjects with cardiometabolic risk factors.

Background Recent studies provided insights into the recruitment and activation pathways of leukocytes in atopic dermatitis, however, the underlying mechanisms of tissue remodeling in atopic skin inflammation remain elusive. Objective To identify chemokine-mediated communication pathways regulating tissue remodeling during atopic skin inflammation. Methods Analysis of the chemokine receptor repertoire of human dermal fibroblasts using flow cytometry and immunofluorescence. Quantitative real-time polymerase chain reaction and immunohistochemical analyses of chemokine expression in atopic vs. non-atopic skin inflammation. Investigation of the function of chemokine receptor CCR3 on human dermal fibroblasts through determining intracellular Ca 2+ mobilization, cell proliferation, migration, and repair capacity. Results Analyses on human dermal fibroblasts showed abundant expression of the chemokine receptor CCR3 in vitro and in vivo . Among its corresponding ligands (CCL5, CCL8, CCL11, CCL24 and CCL26) CCL26 demonstrated a significant and specific up-regulation in atopic when compared to psoriatic skin inflammation. In vivo , epidermal keratinocytes showed most abundant CCL26 protein expression in lesional atopic skin. In structural cells of the skin, T H 2-cytokines such as IL-4 and IL-13 were dominant inducers of CCL26 expression. In dermal fibroblasts, CCL26 induced CCR3 signaling resulting in intracellular Ca 2+ mobilization, as well as enhanced fibroblast migration and repair capacity, but no proliferation. Conclusion Taken together, findings of the present study suggest that chemokine-driven communication pathways from the epidermis to the dermis may modulate tissue remodeling in atopic skin inflammation.

Central dopamine regulation is involved in postural control and in the pathophysiology of restless legs syndrome (RLS) and Parkinson’s disease (PD). Postural control abnormalities have been detected in PD, but there are no earlier studies with regard to RLS and postural control. Computerized force platform posturography was applied to measure the shift and the velocity (CPFV) of center point of forces (CPF) with eyes open (EO) and eyes closed (EC) in controls (n = 12) and prior and after a single day intervention with pramipexole in RLS subjects (n = 12). CPFV (EO) was significantly lower in the RLS group (p < 0.05) than in controls. After pramipexole intake, the difference disappeared and the subjective symptom severity diminished. Pramipexole did not significantly influence CPFV (EC) or CPF shift direction. Subjects with RLS used extensively visual mechanisms to control vestibule-spinal reflexes to improve or compensate the postural stability. Further research is needed to clarify altered feedback in the central nervous system and involvement of dopamine and vision in the postural control in RLS.

Background: Delayed postnatal removal of lung liquid may result in respiratory distress, which is more common in infants born by cesarean section. Vertical artefacts (B-lines) arising from the lung surface in lung ultrasound have been shown to correlate with the liquid content of the lungs. Objectives: We studied whether lung ultrasound could be used for the assessment of postnatal lung liquid in healthy term infants born vaginally and by cesarean section. Methods: Lung ultrasound was performed 1, 3 and 24 h after birth to 22 vaginally born infants and 20 infants born by elective cesarean section. The abundance of B-lines was scored for each infant and time point by two independent observers blinded to the mode of delivery and time point on the examination on a five-step scale. Results: In both groups, a significant decrease in abundance of B-lines, indicative of lung liquid absorption, was observed during the first 24 h. 3 h after birth cesarean section was associated with significantly higher lung liquid content than vaginal delivery. Conclusion: The noninvasive bedside ultrasound method for estimation of lung liquid is a promising tool for the early identification of infants at risk for pulmonary maladaptation.

We assessed the value of speckle tracking two-dimensional (2D) strain echocardiography (2DSE) measured mechanical dispersion (MD) with other imaging and electrocardiographic parameters in differentiating hypertrophic cardiomyopathy (HCM) patients with and without nonsustained ventricular tachycardia (NSVT) on 24-h ambulatory ECG monitoring.We studied 31 patients with HCM caused by the Finnish founder mutation MYBPC3-Q1061X and 20 control subjects with comprehensive 2DSE echocardiography and cardiac magnetic resonance imaging (CMRI). The presence of NSVT was assessed from ambulatory 24-h ECG monitoring. NSVT episodes were recorded in 11 (35%) patients with HCM. MD was significantly higher in HCM patients with NSVT (93 ± 41 ms) compared to HCM patients without NSVT (50 ± 18 ms, p = 0.012) and control subjects (41 ± 16 ms, p 0.001). MD was the only variable independently associated with the presence of NSVT (OR: 1.60, 95% CI: 1.05-2.45, p = 0.030). Assessed by ROC curves, MD performed best in differentiating between HCM patients with and without NSVT (AUC = 0.81).Increased mechanical dispersion was associated with NSVT in HCM patients on 24-h ambulatory ECG monitoring. Key messages The prediction of sudden cardiac death in hypertrophic cardiomyopathy remains a challenge and novel imaging methods are required to identify individuals at risk of malignant ventricular arrhythmias. Mechanical dispersion by speckle tracking echocardiography is associated with NSVT on 24-h ambulatory ECG monitoring in patients with hypertrophic cardiomyopathy.

The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

During the early 20th century, psychopathy referred to "borderland states" between normality and mental illness, corresponding to the current personality disorders. In psychiatric assessment, a significant proportion of psychopaths were considered to be not of sound mind, i.e. of diminished responsibility in contemporary language, which in most cases also led to shorter punishments. Psychopathy as diagnosis was abandoned in 1969, after which use has been made of the terms disorders of character and, later on, personality disorders. Nowadays, personality disorders can have a punishment-shortening effect only if they come close to a psychotic disorder. A psychopathy assessed by using current methods may even result in a longer verdict.

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.

High-throughput DNA sequencing has shown that the cutaneous microbiome varies due to different exogenous and endogenous factors.To characterize the microbiome of cutaneous melanomas and melanocytic nevi.Non-invasive swab specimens were taken from 15 cutaneous melanomas and 17 benign melanocytic nevi. Partial sequencing of the 16S ribosomal RNA gene was carried out on the 454 GS-FLX Titanium platform and the resulting sequence data was analysed by bioinformatics and statistical methods. 95% of the OTUs (Operational Taxonomic Units) belonged to four phyla: Firmicutes, Actinobacteria, Proteobacteria and Bacteroidetes. The genus Propionibacterium was overall the most common genus, followed by Staphylococcus and Corynebacterium. Statistical analysis showed no significant differences in the relative abundances of bacterial genera or bacterial diversity between the patient groups. Melanoma samples showed a marginally decreased cutaneous microbial diversity.Our data suggests that the skin microbiome may not be a useful diagnostic tool for melanoma and melanocytic nevi.