Critical review of polymer and hydrogel deposition methods for optical and electrochemical bioanalytical sensors correlated to the sensor’s applicability in real samples

Sensors, ranging from in vivo through to single-use systems, employ protective membranes or hydrogels to enhance sample collection or serve as filters, to immobilize or entrap probes or receptors, or to stabilize and enhance a sensor’s lifetime. Furthermore, many applications demand specific requirements such as biocompatibility and non-fouling properties for in vivo applications, or fast and inexpensive mass production capabilities for single-use sensors. We critically evaluated how membrane materials and their deposition methods impact optical and electrochemical systems with special focus on analytical figures of merit and potential toward large-scale production. With some chosen examples, we highlight the fact that often a sensor’s performance relies heavily on the deposition method, even though other methods or materials could in fact improve the sensor. Over the course of the last 5 years, most sensing applications within healthcare diagnostics included glucose, lactate, uric acid, O2, H+ ions, and many specific metabolites and markers. In the case of food safety and environmental monitoring, the choice of analytes was much more comprehensive regarding a variety of natural and synthetic toxicants like bacteria, pesticides, or pollutants and other relevant substances. We conclude that more attention must be paid toward deposition techniques as these may in the end become a major hurdle in a sensor’s likelihood of moving from an academic lab into a real-world product

Weiterbildungsbedarfsanalysen: Ergebnisse aus dem Projekt "Weiterbildung im Prozess der Arbeit" (WAP)

"Das Thema Lernen in der Arbeit ist ein bedeutendes Forschungsund Handlungsfeld in der beruflichen Bildung. Auch im Bereich der beruflichen Weiterbildung werden zunehmend Konzepte des arbeitsorientierten Lernens entwickelt und erprobt (z.B. APO-IT). In der Weiterbildungsdiskussion ist dabei auffällig, dass nicht alle Beschäftigungsbereiche gleichermaßen thematisiert werden. So mangelt es sowohl an Untersuchungen zu den Weiterbildungsbedarfen und -möglichkeiten im Bereich der 'einfachen' Arbeit als auch an konkreten Weiterbildungskonzepten für Beschäftigte unterhalb des Facharbeiterniveaus. Vor dem Hintergrund der gestiegenen Anforderungen im Bereich der 'einfachen Arbeit' sowie der geringen Weiterbildungschancen von an- und ungelernten Arbeitern ist dies nahezu unverantwortlich. Des Weiteren erfordert das primär informelle Lernen am Arbeitsplatz, welches oft beiläufig und manchmal sogar unbewusst geschieht, Instrumente zur Planung, Organisation und Reflexion von Lernen und Erfahrungserwerb. Hier besteht ebenfalls ein Forschungs- und Entwicklungsbedarf. Das Projekt 'Weiterbildung im Prozess der Arbeit für Fachkräfte in der Metall- und Elektroindustrie in Baden- Württemberg' (WAP) widmet sich diesem Themenfeld. Ziel des Projektes ist es, ein arbeitsorientiertes Lernkonzept für an- und ungelernte Beschäftigte zu erproben und gleichzeitig praktikable Instrumente in den Unternehmen einzuführen, die diese Lernform dauerhaft in die Personal- und Organisationsentwicklung integrierten. Eines der Instrumente ist die Analyse von Weiterbildungsbedarfen, deren Ergebnisse in diesem Forschungsbericht vorgestellt werden." (Autorenreferat)"Work process knowledge and workplace learning have become crucial issues of VET research and practice in recent years. In the field of continuing vocational training (CVT) there have been developed new learning strategies at the workplace (e.g. APO-IT). Regarding these activities it has to be noted that it is still a research task to investigate the change of work of unskilled or semi-skilled workers in German industry. These workers also have a low participation in continuing vocational training. Behind the background of the increasing requirements of so called 'simple' work it is almost irresponsible not to offer more learning possibilities for low qualified workers. Learning at the workplace is rather informal learning which often occurs casually without a proper learning intention. The goal to embed learning in the workplace needs didactical instruments for the planning, organisation and evaluation of learning arrangements. The three-year project 'learning in the work process for employees in the metal and electrical industry in Baden-Wurttemberg' (WAP) is working on this topic. The overall goal of the project is to improve CVT for those employees who are usually underrepresented in CVT or HRD. Therefore we develop several instruments for enterprises to integrate a culture of learning at the workplace into the organisation and personal development. One of those instruments is the training need analysis. The concept and the results of the need analysis in the project WAP is described in this paper." (author's abstract

Weiterbildungsprofile und Arbeits- und Lernprojekte: Ergebnisse aus dem Projekt "Weiterbildung im Prozess der Arbeit" (WAP)

"Der vorliegende Forschungsbericht ist die Fortführung des Forschungsberichtes Nr. 27, in dem das Konzept und die Ergebnisse der Weiterbildungsbedarfsanalyse vorgestellt wurden. In diesem Bericht werden das arbeitsorientierte Weiterbildungskonzept und die eingesetzten Instrumente im Projekt 'Weiterbildung im Prozess der Arbeit für an- und ungelernte Fachkräfte in der Metall- und Elektroindustrie in Baden-Württemberg' (WAP) beschrieben. Hierzu werden zunächst betriebliche Handlungsfelder mittels der partizipativen Methodik der Experten-Workshops analysiert und in Form von Arbeitsaufgaben beschrieben und geordnet. Diese Arbeitsaufgaben bilden den Ausgangspunkt für die Entwicklung von betrieblichen Weiterbildungsprofilen. Die Umsetzung des Lernkonzeptes erfolgt in Arbeitsprozessen durch das didaktische Instrument der 'Arbeits- und Lernprojekte' (ALP), die aus authentischen betrieblichen Aufgabenstellungen oder Aufträgen abgeleitet werden und sich immer auf eine Arbeitsaufgabe im Profil beziehen. Im Bericht werden die im Projekt entwickelten Weiterbildungsprofile und die Arbeits- und Lernprojekte vorgestellt." (Autorenreferat)"This report is the second part of the ITB report no.27. In the first report the concept and results of the further need analysis was presented. The second report deals with the WAP learning mode and its didactical instruments which were developed and tested in the project 'continuing vocational training in work process for unskilled and semi-skilled employees in the metal and electrical industry in Baden-Wurttemberg'. In a first step we analysed occupational fields with the participatory methodology of expert workers' work-shops. In the workshops we identified and described the work tasks of expert workers in a work area, and ordered the tasks using a competence model. These work tasks form the starting point for the development of the CVT programmes. To each work task in the profile we developed a set of work-based learning projects (WBLP) which is the didactical instrument to design learning at the workplace. In this report the principles of the tasks analysis, the development of CVT curricula and the design of work-based learning projects are described." (author's abstract

Hypothermia Improves Oral and Gastric Mucosal Microvascular Oxygenation during Hemorrhagic Shock in Dogs

Hypothermia is known to improve tissue function in different organs during physiological and pathological conditions. The aim of this study was to evaluate the effects of hypothermia on oral and gastric mucosal microvascular oxygenation (μHbO2) and perfusion (μflow) under physiological and hemorrhagic conditions. Five dogs were repeatedly anesthetized. All animals underwent each experimental protocol (randomized cross-over design): hypothermia (34°C), hypothermia during hemorrhage, normothermia, and normothermia during hemorrhage. Microcirculatory and hemodynamic variables were recorded. Systemic (DO2) and oral mucosal (μDO2) oxygen delivery were calculated. Hypothermia increased oral μHbO2 with no effect on gastric μHbO2. Hemorrhage reduced oral and gastric μHbO2 during normothermia (−36 ± 4% and −27 ± 7%); however, this effect was attenuated during additional hypothermia (−15 ± 5% and −11 ± 5%). The improved μHbO2 might be based on an attenuated reduction in μflow during hemorrhage and additional hypothermia (−51 ± 21 aU) compared to hemorrhage and normothermia (−106 ± 19 aU). μDO2 was accordingly attenuated under hypothermia during hemorrhage whereas DO2 did not change. Thus, in this study hypothermia alone improves oral μHbO2 and attenuates the effects of hemorrhage on oral and gastric μHbO2. This effect seems to be mediated by an increased μDO2 on the basis of increased μflow

An overview of the higher level classification of Pucciniomycotina based on combined analyses of nuclear large and small subunit rDNA sequences

Mycologia, Vol. 98, nº6In this study we provide a phylogenetically based introduction to the classes and orders of Pucciniomycotina (5Urediniomycetes), one of three subphyla of Basidiomycota. More than 8000 species of Pucciniomycotina have been described including putative saprotrophs and parasites of plants, animals and fungi. The overwhelming majority of these(,90%) belong to a single order of obligate plant pathogens, the Pucciniales (5Uredinales), or rust fungi. We have assembled a dataset of previously published and newly generated sequence data from two nuclear rDNA genes (large subunit and small subunit) including exemplars from all known major groups in order to test hypotheses about evolutionary relationships among the Pucciniomycotina. The utility of combining nuc-lsu sequences spanning the entire D1-D3 region with complete nuc-ssu sequences for resolution and support of nodes is discussed. Our study confirms Pucciniomycotina as a monophyletic group of Basidiomycota. In total our results support eight major clades ranked as classes (Agaricostilbomycetes, Atractiellomycetes, Classiculomycetes,Cryptomycocolacomycetes,Cystobasidiomycetes, Microbotryomycetes,Mixiomycetes and Pucciniomycetes) and 18 orders

Functional Characterization of Rare RAB12 Variants and Their Role in Musician's and Other Dystonias

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician's dystonia (MD) and writer's dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A> G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson's disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val (n = 6); p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias

LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol:Deep Phenotyping of an International Genetic Cohort

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions.Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants.Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021).Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivityClinical Trial Registration:ClinicalTrials.gov, NCT04214509

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects

Large-Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes

© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.[Background] Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD).[Objectives] To screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes.[Methods] We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next-generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature.[Results] We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with GCH1 variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic.[Conclusion] This study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT-KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants.This work was supported by the German Ministry of Education and Research (BMBF, DYSTRACT consortium, 01GM1514B, to A.A.K., T.B., C.Klein and K.L.) and the German Research Foundation (DFG, LO1555/10-1 to H.B., C.Klein, and K.L. and Project-ID 424778381-TRR 295 to A.A.K). The DysTract registry was further supported by the Arbeitskreis Botulinumtoxin der DGN e.V., Merz Therapeutics, AbbVie/Allergan, and Ipsen Pharma. The Korean DNA samples for this study were provided by the Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols. Several authors are members of the European Reference Network for Rare Neurological Diseases (Project ID No. 739510). Open Access funding enabled and organized by Projekt DEAL.Peer reviewe