Asymmetric lipid membranes: Towards more realistic model systems

Despite the ubiquity of transbilayer asymmetry in natural cell membranes, the vast majority of existing research has utilized chemically well-defined symmetric liposomes, where the inner and outer bilayer leaflets have the same composition. Here, we review various aspects of asymmetry in nature and in model systems in anticipation for the next phase of model membrane studies

Contact sensitization to essential oils: IVDK data of the years 2010–2019

Background: Essential oils (EOs) are widely used in cosmetics, perfumes, massage fluids, aroma therapy and natural medicine. Some EOs contain contact sensitizers. Objectives: To describe the frequency of sensitization to EOs in dermatitis patients presenting in skin clinics including concomitant reactions, to evaluate the EO patch test preparations and to identify patient groups with an increased risk of EO sensitization. Patients and methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010-2019. Results: Twelve EOs were patch tested in an aimed manner in 10 930 patients, of whom 908 (8.3%) reacted to at least 1 EO. Only 6 EOs elicited more than 1% positive patch test reactions: ylang ylang (I + II) oil (3.9%), lemongrass oil (2.6%), jasmine absolute (1.8%), sandalwood oil (1.8%), clove oil (1.6%) and neroli oil (1.1%). Concomitant reactions among EOs or to EOs and fragrances were frequent. Among EO-positive patients, women, leg dermatitis patients, patients aged 40 years or more, masseurs and cosmeticians were over-represented. Conclusions: Sensitization to EOs occurs, albeit infrequently in most cases. Masseurs and cosmeticians have an increased risk of sensitization to EOs. Keywords: clinical epidemiology; contact allergy; essential oils; fragrances; patch testin

A springtime source of toxic Pseudo-nitzschia cells on razor clam beaches in the Pacific Northwest

Concentrations of domoic acid (DA) above the regulatory limit in Washington coast razor clams are usually higher on northern beaches from summer to fall. Recent field studies have confirmed that the primary source of toxic Pseudo-nitzschia (PN) cells in those seasons is a semi-retentive topographically trapped seasonal eddy located offshore and north of the clamming beaches. Another semi-retentive coastal feature, Heceta Bank, that has been shown to support toxic PN cells in summer, is located south of Washington's clamming beaches. In this paper we present evidence to demonstrate that Heceta Bank, although not a likely source of toxic cells to Washington in summer due to the prevailing southward seasonal currents, may be a source of cells in springtime before the southward currents develop. In contrast to summer and fall seasons, concentrations of DA in razor clams are typically higher at southern beaches in spring. The likelihood of a southern source is explored using biological and transport data surrounding a period of toxic razor clams in April 2005. In particular, satellite-derived chlorophyll data confirm that a bloom occurred over Heceta Bank in March of that year, just prior to a period of strong storm-driven northward transport. PN cells of the same species observed in the April bloom on Washington beaches and in offshore waters were documented in Oregon offshore waters on the northern edge of Heceta Bank. That species, P. australis, has been shown to be highly toxic in this region; shore-based data show that razor clams on Oregon beaches were also toxic at the time when P. australis was observed offshore. Both measured and modeled currents show that transport was more than sufficient to move cells from the vicinity of Heceta Bank, Oregon to southern Washington beaches by the time the toxic cells were observed on those beaches. The rapid transport was due in part to the presence of the buoyant plume from the Columbia River, a common feature in winter and spring in nearshore waters of the U.S. Pacific Northwest. (c) 2013 Elsevier B.V. All rights reserved.Keywords: Coastal currents, Heceta Bank, Domoic acid, HAB, Pseudo-nitzschia, Juan de Fuca edd

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of theESSCAnetwork, 2015-2018

BACKGROUND Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen

Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers

Homozygosity for the Pi∗Z variant of the gene that encodes the alpha-1 antitrypsin peptide (AAT), called the Pi∗ZZ genotype, causes a liver and lung disease called alpha-1 antitrypsin deficiency. Heterozygosity (the Pi∗MZ genotype) is a risk factor for cirrhosis in individuals with liver disease. Up to 4% of Europeans have the Pi∗MZ genotype; we compared features of adults with and without Pi∗MZ genotype among persons without preexisting liver disease.info:eu-repo/semantics/publishedVersio

Colour as a cue to eat : effects of plate colour on snack intake in pre-school children

Environmental cues, such as the colour of food and dishware, have been shown to influence food and drink consumption in adult populations. This proof of concept study investigated whether plate colour could be utilised as a strategy to reduce intake of high energy density (HED) snacks and increase intake of low energy density (LED) snacks in pre-school children. In a between and within-subjects design, children were randomly assigned to either a control group (no colour message) or intervention group (received a colour message: red = stop, green = go) and were provided a snack at nursery on three occasions on differently coloured plates (red, green and white), for each snack type (HED, LED). Snack intake, colour preference, colour association, and anthropometrics were recorded for each child. The results showed that there was no effect of group (control vs intervention) on HED (p=0.540) and LED intake (p=0.575). No effect of plate colour on HED (p=0.147) or LED snack intake (p=0.505) was evident. Combining red and green plates for a chromatic versus achromatic comparison showed that there was no significant effect of chromatic plate on HED (p=0.0503) and LED (p=0.347) intakes. Despite receiving a brief learning intervention, the use of plate colour was found in the present study to be an ineffective strategy to control snack food intake in pre-school aged children. Rather, we suggest that food intake in young children may best be predicted by portion size, energy density and eating behaviour traits

Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA\xe2\x80\x99s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Segmental synchronity and change of left ventricular volume during ventricular pacemaker stimulation - ultrasound based analysis by Real Time 3D echocardiography

1.1.1 Hintergrund Es ist bekannt, dass eine ventrikuläre Schrittmacherstimulation zu einer Abnahme der Ejektionsfraktion und auch zu einer Verschlechterung der linksventrikulären Synchronität führt. Eine genaue 3D Evaluierung und segmentale Analyse des linken Ventrikels wurde bisher nicht durchgeführt, da die dazu geeignete MRT-Diagnostik bei Schrittmacherträgern kontraindiziert ist. In der vorliegenden Studie untersuchten wir die Veränderung von globalen und segmentalen linksventrikulären Parametern unter Schrittmacherstimulation im Vergleich zum Eigenrhythmus durch real time 3D Echokardiographie. 1.1.2 Methoden Wir untersuchten 27 Patienten (71 ± 13 Jahre), die unter Eigenrhythmus eine normale oder nur geringgradig eingeschränkte linksventrikuläre Pumpfunktion aufwiesen und zum Untersuchungszeitpunkt eine ausreichend hohe Eigenfrequenz (>40/min) hatten. Zunächst erfolgte eine Ultraschalluntersuchung im Eigenrhythmus und danach unter rechtsventrikulärer Stimulation (VVI-Modus), welche 15 Herzschläge über der Grundfrequenz programmiert wurde. Zur Echokardiographie benutzen wir ein 4D fähiges Ultraschallgerät (Philips Sonos 7500 mit x4 Schallkopf), das nativ oder – bei schlechter Schallqualität -auch Kontrastmittel-gestützt (mechanical index 0,5; repetitive Bolusgabe von 0,5ml SonoVue®) eingesetzt werden konnte, und zeichneten einen kompletten Datensatz zur off-line Analyse auf (Q-Lab®, Philips). Durch eine manuell korrigierte, halbautomatische Endokarderkennung wurden die enddiastolischen und endsystolischen linksventrikulären Volumina berechnet und durch eine Bild-für-Bild-Korrektur die Endokardbewegung im Herzzyklus analysiert. Das Maß der Synchronität wurde durch den Zeitversatz der segmentalen Volumenverkürzung in einem 16-Segment-Model bestimmt (time-to-minimalsegmental-volume - Tmsv 16). 1.1.3 Ergebnisse Die Herzfrequenz lag in Ruhe bei 67 ± 11/min und unter VVI-Stimulation bei 77 ± 11/min. Während sich sowohl in den enddiastolischen (Ruhe 133 ± 40ml vs. Stimulation 124 ± 38ml, n.s.) als auch in den endsystolischen linksventrikulären Volumina (Ruhe 60 ± 28ml vs. Stimulation 65 ± 28ml, n.s.) keine signifikante Änderung ergab, zeigte sich in der Ejektionsfraktion eine signifikante Abnahme während ventrikulärer Stimulation (Ruhe 56 ± 11% vs. Stimulation 49 ± 10%, p<0,01). Die Analyse der Synchronität (Tmsv 16) erbrachte eine hoch signifikante linksventrikuläre Deformation mit Anstieg des segmentalen Zeitversatzes (Ruhe 35% ± 11% vs. Stimulation 56% ± 17%, p<0,0005). Den größten Zeitversatz konnten wir vor allem in den apikoseptalen Abschnitten beobachten. 1.1.4 Zusammenfassung Die rechtsventrikuläre Herzschrittmacherstimulation führt im Vergleich zum Eigenrhythmus zu einer deutlichen Abnahme der Ejektionsfraktion und Verschlechterung der linksventrikulären Synchronität. Dabei erlaubt die real time 3D Echokardiographie eine genaue Analyse der linksventrikulären Deformierung und kann somit eine suffiziente Methode beim Management der Resynchronisationstherapie sein.1.2.1 Background It is already known that ventricular pacing decreases ejection fraction and may worsen left ventricular synchrony. However, accurate 3D quantification and segmental assessment has not been possible to be done so far, because MRI as a 3D-method is contraindicated in patients with pacemakers. In this study we tried to assess these global and segmental left ventricular parameters by real time 3D echocardiography at rest and during ventricular pacing. 1.2.2 Methods We examined 27 patients (age 71 ± 13) with normal to minimally limited left ventricular function whose own heart rhythm was higher than 40/min during examination. After baseline examination, pacing with a heart rate 15 bpm above baseline was performed (VVI). For echocardiography we used a 4D modus (Philips Sonos 7500 with x4 transducer) in conventional as well as in contrast enhanced mode (mechanical index 0.5; repetitive boli of 0.5ml SonoVue® followed by saline) and recorded a complete cardiac volume set for off-line analysis (Q-Lab®, Philips). By semiautomatic and hand-corrected border detection we calculated end-diastolic and endsystolic volumes and analysed endocardial motion frame by frame. For assessment of synchrony we assigned the time offset of peak segmental volumetric shortening in a 16 segment model (time-to-minimal-segmentalvolume - Tmsv 16). 1.2.3 Results Heart rate at rest was 67 ± 11bpm and 77 ± 11bpm during VVI-stimulation. While left ventricular volumes showed no significant differences in enddiastolic (rest 133 ± 40ml vs. stimulation 124 ± 38ml, n.s.) and end-systolic volumes (rest 60 ± 28ml vs. stimulation 65 ± 28ml, n.s.), ejection fraction decreased significantly during ventricular pacing (rest 56 ± 11% vs. stimulation 49 ± 10%, p<0,01). Analysis of synchrony (Tmsv 16) provided a high significant deformation of the left ventricle with increased segmental time offset (rest 35% ± 11% vs. stimulation 56% ± 17%, p<0,0005). This was particularly pronounced in the apical septal segments. 1.2.4 Conclusion Right ventricular pacing decreased ejection fraction and worsened left ventricular synchrony. Real time 3D echocardiography allows an accurate assessment of segmental synchrony and volumetric changes during ventricular pacing and may be a helpful method in management of resynchronisation therapy