A Systematic Review of Thermosensation and Thermoregulation in Anxiety Disorders

Objectives: Sweating, hot flushes, and blushing are symptoms frequently reported by individuals with anxiety disorders. They represent important reinforcers of anxiogenic cognitions and behaviours. One system that may be involved in the manifestation of these symptoms is the thermosensory/thermoregulatory system. The aim of the present study was to investigate to what extent individuals with anxiety disorders are characterised by alterations in this system. Methods: PubMed and PsycINFO were systematically searched. Studies were eligible if they (i) assessed individuals with anxiety disorders, (ii) thermosensation or thermoregulatory effectors/outcomes, and (iii) used a case-control design. Results: N = 86 studies were identified. There was no evidence of altered thermosensation in individuals with anxiety disorders. Regarding thermoregulatory effectors, individuals with social anxiety disorder exhibited altered cutaneous vasodilation upon pharmacological challenge; individuals with specific phobia showed increased sweating upon confrontation with phobic stimuli; individuals with panic disorder showed increased daily sweating as well as increased sweating in response to non-phobic and phobic stimuli. Regarding thermoregulatory outcomes, there was evidence for altered skin temperature in all subtypes of anxiety. Conclusion: Whereas there was no evidence of altered thermoregulation in specific phobia, a subgroup of individuals with social anxiety and panic disorder appears to exhibit altered vasodilation and sweating, respectively. Longitudinal research is warranted to investigate whether this represents a vulnerability to anxiety/panic

Developing Fluent First-Grade Readers Using Repeated Readings

The purpose of this study was to investigate what effects, if any, the implementation of repeated readings, as an intervention, has on first-grade students’ reading fluency. Baseline data was collected, and twelve first-grade students were chosen to participate in the small group repeated reading intervention. Throughout the six-week repeated readings intervention, students practiced short vowel word lists, short leveled passages, and sight word lists until these words became automatic and fluency and accuracy increased. Data collected during this study included benchmark Fountas and Pinnell reading level assessments, benchmark AIMSweb R-CBM assessments, AIMSweb R-CBM progress monitoring, short grade-level passages and sight word lists, weekly student reading surveys, and teacher observation notes. The data showed an overall increase in students’ word recognition, fluency, and accuracy of first-grade text. The results of this study indicate that the repeated readings intervention had a positive effect on students’ reading fluency, and the researchers will continue to implement the intervention with first-grade students

MutationDistiller: user-driven identification of pathogenic DNA variants

MutationDistiller is a freely available online tool for user-driven analyses of Whole Exome Sequencing data. It offers a user-friendly interface aimed at clinicians and researchers, who are not necessarily bioinformaticians. MutationDistiller combines Mutation- Taster’s pathogenicity predictions with a phenotypebased approach. Phenotypic information is not limited to symptoms included in the Human Phenotype Ontology (HPO), but may also comprise clinical diagnoses and the suspected mode of inheritance. The search can be restricted to lists of candidate genes (e.g. virtual gene panels) and by tissue-specific gene expression. The inclusion of GeneOntology (GO) and metabolic pathways facilitates the discovery of hitherto unknown disease genes. In a novel approach, we trained MutationDistiller’s HPO-based prioritization on authentic genotype–phenotype sets obtained from ClinVar and found it to match or outcompete current prioritization tools in terms of accuracy. In the output, the program provides a list of potential disease mutations ordered by the likelihood of the affected genes to cause the phenotype. MutationDistiller provides links to gene-related information from various resources. It has been extensively tested by clinicians and their suggestions have been valued in many iterative cycles of revisions. The tool, a comprehensive documentation and examples are freely available at https://www.mutationdistiller.org

Untersuchung der Nachhaltigkeit eines Programms zur Primärprävention bei Essstörungen an Schulen

Bei der bisherigen Evaluation von Programmen zur Prävention von Essstörungen wurden bisher überwiegend Selbstbeurteilungsbögen eingesetzt. Jedoch bringt diese Methode das Risiko einer leicht manipulierbaren Datenerhebung mit sich. Im Rahmen der vorliegenden Studie soll die Evaluation des primärpräventiven Programms PriMa („Primärprävention Magersucht für Mädchen ab dem 6. Schuljahr“) um ein essstörungsspezifisches Interview (EDE) ergänzt und durch den parallelen Einsatz eines bereits in der PriMa-Evaluation eingesetzten Fragebogens (EAT-26D) die Nachhaltigkeit der Primärprävention des Programms PriMa überprüft werden. Es wurden N = 130 Mädchen im Alter zwischen 12 und 14 Jahren befragt. Für die Anorexie und Bulimie wurden signifikante Zusammenhänge im mittleren Bereich zwischen dem EDE und dem EAT-26D festgestellt. Für die Binge-Eating-Störung waren keine signifikanten Zusammenhänge zwischen den beiden Instrumenten nachweisbar. Bezüglich des Essverhaltens als abhängiger Variable ließ sich über alle vier Messzeitpunkte betrachtet eine signifikante lineare Abnahme des EAT-26D-Summenwerts der Gesamtgruppe nachweisen, jedoch zeigte sich kein signifikanter Unterschied zwischen der Interventions- und Kontrollgruppe. Das Essverhalten der Mädchen der Kontrollgruppe hat sich auch, ohne dass sie an der Intervention teilgenommen haben, vom ersten zum vierten Messzeitpunkt signifikant verbessert. Basierend auf diesen Ergebnissen lässt sich die Annahme formulieren, dass die Durchführung des EDE auf die Mädchen den Effekt einer Intervention hatte. Für ein diagnostisches Interview wurde dieser therapeutische Effekt noch nicht beschrieben und sollte anhand weiterer Studien näher untersucht werden. Der Effekt könnte z.B. im Rahmen von Präventionsprojekten als „Mini-Intervention“ mit gleichzeitiger Datenerhebung genutzt werden

EEG-Ableitung der olfaktorisch evozierten Potenziale bei streng einseitiger Stimulation des Riechepithels mit dem Olfaktometer

Bei der Generierung chemosomatosensorisch (CSSEPs) und olfaktorisch evozierter Potenziale (OEPs) mit einem Flussolfaktometer strömt die duftstoffhaltige Luft auf einer Nasenseite ein, tritt im Nasopharynxbereich auf die kontralaterale Nasenseite über und strömt durch diese wieder aus. Theoretisch können durch die austretende duftstoffhaltige Luft olfaktorische und trigeminale Rezeptorzellen der kontralateralen Seite mit aktiviert und evozierte Potenziale generiert werden. Ein Experiment an 18 gesunden Probanden zwischen 18 und 30 Jahren zeigte, dass eine streng einseitige Generierung olfaktorisch und trigeminal evozierter Potenziale bei verschlossener kontralateraler Nase möglich ist, d.h. dass der Rechteckcharakter der in den Luftstrom eingebetteten kurzen chemosensorischen Reize nicht durch Verwirbelungen durch die auf derselben Nasenseite zurückströmende Olfaktometerluft zerstört wird. Die N1- und P2-Latenzen und N1P2-Amplituden der evozierten Potenziale zeigten bei Reizung mit H2S und CO2 keine signifikanten Unterschiede zwischen offener und geschlossener kontralateraler Nase. Außerdem zeigten die generierten Potenziale keine signifikanten seitenbezogenen Unterschiede. Weiterhin wurden mit geschlossener kontralateraler Nase mehr als 90% der passiven monorhinalen Reize wahrgenommen. Für zukünftige hochauflösende bildgebende Studien (EEG/MEG) zur Untersuchung olfaktorischer und trigeminaler Signalwege sollte die hier vorgestellte streng einseitige Reizmethode verwendet werden, um sicher zu stellen, dass die Ergebnisse nicht Resultat einer Vermischung der ipsilateralen Reizung und kontralateralen Mitreizung sind

5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation

© FASEB. Leukotrienes (LTs) are proinflammatory lipid mediators formed from arachidonic acid in a 2-step reaction catalyzed by 5-lipoxygenase (5-LOX) requiring the formation of 5-HPETE [5(S)-hydroperoxy-6-trans-8,11,14-ciseicosatetraenoic acid] and its subsequent transformation to LTA4 . 5-LOX is thought to receive arachidonic acid from the nuclear membrane-embedded 5-LOX-activating protein (FLAP). The crystal structure of 5-LOX revealed an active site concealed by F177 and Y181 (FY cork). We examined the influence of the FY cork on 5-LOX activity and membrane binding in HEK293 cells in the absence and presence of FLAP. Uncapping the 5-LOX active site by mutation of F177 and/or Y181 to alanine (5-LOX-F177A, 5-LOX-Y181A, 5-LOX-F177/Y181A) resulted in delayed and diminished 5-LOX membrane association in A23187-stimulated cells. For 5-LOX-F177A and 5-LOX-F177/Y181A, formation of 5-LOX products was dramatically reduced relative to 5-LOX-wild type (wt). Strikingly, coexpression of FLAP in A23187-activated HEK293 cells effectively restored formation of 5-H(p)ETE (5-hydroxy- and 5-peroxy-6-trans-8,11,14-cis-eicosatetraenoic acid) by these same 5-LOX mutants (≈60-70% 5-LOX-wt levels) but not of LTA4 hydrolysis products. Yet 5-LOX-Y181A generated 5-H(p)ETE at levels comparable to 5-LOX-wt but reduced LTA4 hydrolysis products. Coexpression of FLAP partially restored LTA4 hydrolysis product formation by 5-LOX-Y181A. Together, the data suggest that the concealed FY cork impacts membrane association and that FLAP may help shield an uncapped active site

A Service-Oriented Operating System and an Application Development Infrastructure for Distributed Embedded Systems

The paradigm of service-orientation promises a significant ease of use in creating and managing distributed software systems. A very important aspect here is that also application domain experts and stakeholders, who are not necessarily skilled in computer programming, get a chance to create, analyze, and adapt distributed applications. However, up to now, service-oriented architectures have been mainly discussed in the context of complex business applications. In this paper we will investigate how to transfer the benefits of a service-oriented architecture into the field of embedded systems, so that this technology gets accessible to a much wider range of users. As an example, we will demonstrate this scheme for sensor network applications. In order to address the problem of limited device resources we will introduce a minimal operating system for such devices. It organizes all pieces of code running on a sensor node in a service-oriented fashion and also features the relocation of code to a different node at runtime. We will demonstrate that it is possible to design a sensor network application from a set of already existing services in a highly modular way by employing already existing technologies and standards

Hydrogenolysis of lignin in ZnCl₂ and KCl as an inorganic molten salt medium

Lignin can be converted into monomeric products with the aid of molten salt media. Molten zinc chloride (ZnCl₂)/potassium chloride (KCl) mixtures are suitable for this purpose. The application of an eutectic mixture with low melting points leads to similar main products as are obtained by pyrolysis. The hydrogenolysis of an organosolv lignin in molten salts of ZnCl₂/KCl was investigated as a function of reaction temperature, residence time, and lignin concentration, and the composition of liquid products and monophenols was analyzed by gas chromatography-mass spectrometry (GC-MS). The yields can be optimized by the proper selection of the reaction temperature. A longer residence time and higher lignin concentrations lead to increased formation of solid residues and gaseous products. The liquid products mainly consist of substituted phenols derived from lignins. Polymeric products are the result of condensation reactions (i.e., the formation of new C-C linkages in the course of secondary reactions)

In situ Formation of Polymer Microparticles in Bacterial Nanocellulose Using Alternative and Sustainable Solvents to Incorporate Lipophilic Drugs

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent N -methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), Cyrene TM and ethyl lactate. Using the best-performing solvents N -methyl-2-pyrrolidone and ethyl lactate, their fast diffusion during phase inversion led to the formation of homogenously distributed polymer microparticles with average diameters between 2.0 and 6.6 µm within the cellulose matrix. Despite polymer inclusion, the water absorption value of the material still remained at ~50% of the original value and the material was able to release 32 g/100 cm 2 of the bound water. Mechanical characteristics were not impaired compared to the native material. The process was suitable for encapsulating the highly lipophilic drugs cannabidiol and 3-O-acetyl-11-keto-β-boswellic acid and enabled their sustained release with zero order kinetics over up to 10 days. Conclusively, controlled drug release for highly lipophilic compounds within bacterial nanocellulose could be achieved using sustainable solvents for preparation