Expression of Zm13, a pollen specific maize protein, in Escherichia coli reveals IgE-binding capacity and allergenic potential

AbstractPlant proteins belong to the most frequent elicitors of type I allergic symptoms in industrialized countries. Several relevant plant allergens have been found to be either specifically expressed or highly upregulated in mature pollen. The cDNA coding for a pollen specific maize protein, Zm13, shows significant sequence homology with a number of pollen or anther specific proteins from monocot and dicot plants as well as with recently described allergens from olive and rye grass. To test whether the Zm13 protein might possess IgE-binding capacity, Zm13 was expressed in E coli. The coding region of Zm13 was PCR amplified from a genomic clone and expressed as as a glutathione-S-transferase fusion protein. The recombinant Zm13 fusion protein bound a Zm13 specific rabbit antiserum and reacted with serum IgE from grass pollen allergic patients indicating that Zm13 and homologous proteins represent a family of conserved plant allergens

Trimesityltriangulene: a persistent derivative of Clar's hydrocarbon

Triangulene, known as Clar’s hydrocarbon, is a prototypical non-Kekule ́ diradical comprised of six benzenoid rings fused in a trian-gular shape. We synthesized and characterized its trimesityl derivative, illustrating that three bulky substituents installed in the centers of the zigzag edges suffice to protect all reactive positions. This work brings prospects to use triangulene and its open-shell analogs in spintronic materials via solution-phase synthesis

Randomized clinical trial to evaluate a cancer pain self-management intervention for outpatients.

Objective Unrelieved pain is common in patients with advanced cancer. Although psychoeducational interventions were found to decrease pain, effects were moderate. The purpose of this study was to evaluate the efficacy of a pain self-management intervention compared with usual care and to explore participants' experiences with pain management and study participation. Methods A multicenter randomized controlled trial design with post-trial interviews was used. Outpatients with cancer pain and their family caregivers were recruited from three Swiss university hospitals. The intervention group (IG) received the six-week intervention consisting of education, skills building, and nurse coaching. The control group (CG) received usual care. Outcome variables were analyzed using multilevel models. Interpretive description guided the qualitative study part. Results Twenty-one patients with advanced cancer and seven family caregivers completed the study. The group x time effect showed a statistically significant decrease in average pain (P ​= ​0.04), but no significant group x time effect for worst pain (P ​= ​0.06). Pain scores, pain-related knowledge, Pain Management Index, self-efficacy, and performance status improved in the IG (P ​< ​0.05). Almost all of the interviewed participants perceived the pain management diary, tailored intervention sessions, and weekly support as useful. None experienced study participation as burdensome. Conclusions This study was the first to test the efficacy of a psychoeducational cancer pain self-management intervention in a German-speaking context, with most patients receiving palliative care. Clinicians can recommend the use of pain management diaries. Tailoring interventions to an individual's situation and dynamic pain trajectory may improve patients' pain self-management. Registration number This study has been registered via ClinicalTrials.gov: NCT02713919.https://clinicaltrials.gov/ct2/show/NCT02713919?term=NCT02713919&amp;draw=2&amp;rank=1

The SMILe integrated care model in allogeneic SteM cell TransplantatIon faciLitated by eHealth: a protocol for a hybrid effectiveness-implementation randomised controlled trial

While effectiveness outcomes of eHealth-facilitated integrated care models (eICMs) in transplant and oncological populations are promising, implementing and sustaining them in real-world settings remain challenging. Allogeneic stem cell transplant (alloSCT) patients could benefit from an eICM to enhance health outcomes. To combat health deterioration, integrating chronic illness management, including continuous symptom and health behaviour monitoring, can shorten reaction times. We will test the 1st-year post-alloSCT effectiveness and evaluate bundled implementation strategies to support the implementation of a newly developed and adapted eICM in allogeneic stem cell transplantation facilitated by eHealth (SMILe-ICM). SMILe-ICM has been designed by combining implementation, behavioural, and computer science methods. Adaptions were guided by FRAME and FRAME-IS. It consists of four modules: 1) monitoring & follow-up; 2) infection prevention; 3) physical activity; and 4) medication adherence, delivered via eHealth and a care coordinator (an Advanced Practice Nurse). The implementation was supported by contextually adapted implementation strategies (e.g., creating new clinical teams, informing local opinion leaders).; Using a hybrid effectiveness-implementation randomised controlled trial, we will include a consecutive sample of 80 adult alloSCT patients who were transplanted and followed by University Hospital Basel (Switzerland). Inclusion criteria are basic German proficiency; elementary computer literacy; internet access; and written informed consent. Patients will be excluded if their condition prevents the use of technology, or if they are followed up only at external centres. Patient-level (1:1) stratified randomisation into a usual care group and a SMILe-ICM group will take place 10 days pre-transplantation. To gauge the SMILe-ICM's effectiveness primary outcome (re-hospitalisation rate), secondary outcomes (healthcare utilization costs; length of inpatient re-hospitalizations, medication adherence; treatment and self-management burden; HRQoL; Graft-versus-Host Disease rate; survival; overall survival rate) and implementation outcomes (acceptability, appropriateness, feasibility, fidelity), we will use multi-method, multi-informant assessment (via questionnaires, interviews, electronic health record data, cost capture methods).; The SMILe-ICM has major innovative potential for reengineering alloSCT follow-up care, particularly regarding short- and medium-term outcomes. Our dual focus on implementation and effectiveness will both inform optimization of the SMILe-ICM and provide insights regarding implementation strategies and pathway, understudied in eHealth-facilitated ICMs in chronically ill populations.; ClinicalTrials.gov. Identifier: NCT04789863 . Registered April 01, 2021

Unraveling implementation context: the Basel Approach for coNtextual ANAlysis (BANANA) in implementation science and its application in the SMILe project

Designing intervention and implementation strategies with careful consideration of context is essential for successful implementation science projects. Although the importance of context has been emphasized and methodology for its analysis is emerging, researchers have little guidance on how to plan, perform, and report contextual analysis. Therefore, our aim was to describe the Basel Approach for coNtextual ANAlysis (BANANA) and to demonstrate its application on an ongoing multi-site, multiphase implementation science project to develop/adapt, implement, and evaluate an integrated care model in allogeneic SteM cell transplantatIon facILitated by eHealth (the SMILe project).; BANANA builds on guidance for assessing context by Stange and Glasgow (Contextual factors: the importance of considering and reporting on context in research on the patient-centered medical home, 2013). Based on a literature review, BANANA was developed in ten discussion sessions with implementation science experts and a medical anthropologist to guide the SMILe project's contextual analysis. BANANA's theoretical basis is the Context and Implementation of Complex Interventions (CICI) framework. Working from an ecological perspective, CICI acknowledges contextual dynamics and distinguishes between context and setting (the implementation's physical location).; BANANA entails six components: (1) choose a theory, model, or framework (TMF) to guide the contextual analysis; (2) use empirical evidence derived from primary and/or secondary data to identify relevant contextual factors; (3) involve stakeholders throughout contextual analysis; (4) choose a study design to assess context; (5) determine contextual factors' relevance to implementation strategies/outcomes and intervention co-design; and (6) report findings of contextual analysis following appropriate reporting guidelines. Partly run simultaneously, the first three components form a basis both for the identification of relevant contextual factors and for the next components of the BANANA approach.; Understanding of context is indispensable for a successful implementation science project. BANANA provides much-needed methodological guidance for contextual analysis. In subsequent phases, it helps researchers apply the results to intervention development/adaption and choices of contextually tailored implementation strategies. For future implementation science projects, BANANA's principles will guide researchers first to gather relevant information on their target context, then to inform all subsequent phases of their implementation science project to strengthen every part of their work and fulfill their implementation goals

Feasibility of electronic patient-reported outcome monitoring and self-management program in aplastic anemia and paroxysmal nocturnal hemoglobinuria-a pilot study (ePRO-AA-PNH).

INTRODUCTION Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). METHODS After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care. RESULTS All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage. CONCLUSION An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use. TRIAL REGISTRATION ClinicalTrials.gov NCT04128943

Theory-driven development of a medication adherence intervention delivered by eHealth and transplant team in allogeneic stem cell transplantation: the SMILe implementation science project

Medication adherence to immunosuppressants in allogeneic stem cell transplantation (alloSCT) is essential to achieve favorable clinical outcomes (e.g. control of Graft-versus-Host Disease). Over 600 apps supporting medication adherence exist, yet they lack successful implementation and sustainable use likely because of lack of end-user involvement and theoretical underpinnings in their development and insufficient attention to implementation methods to support their use in real-life settings. Medication adherence has three phases: initiation, implementation and persistence. We report the theory-driven development of an intervention module to support medication adherence (implementation and persistence phase) in alloSCT outpatients as a first step for future digitization and implementation in clinical setting within the SMILe project (Development, implementation and testing of an integrated care model in allogeneic SteM cell transplantatIon faciLitated by eHealth).; We applied Michie's Behavior Change Wheel (BCW) and the Capability-Opportunity-Motivation and Behavior (COM-B) model using three suggested stages followed by one stage added by our team regarding preparation for digitization of the intervention: (I) Defining the problem in behavioral terms; (II) Identifying intervention options; (III) Identifying content and implementation options; (IV) SMILe Care Model Prototype Development. Scientific evidence, data from a contextual analysis and patients'/caregivers' and clinical experts' inputs were compiled to work through these steps.; (I) Correct immunosuppressant taking and timing were defined as target behaviors. The intervention's focus was determined within the COM-B dimensions Capability (lack of knowledge, lack of routine), Opportunity (lack of cues, interruptions in daily routine) and Motivation (lack of problem solving, trivialization). (II) Five intervention functions were chosen, i.e. education, training, modelling, persuasion and enablement. (III) Twenty-four behavior change techniques were selected, e.g., goal setting, action planning and problem solving. (IV) Finally, seventeen user stories were developed to guide the SMILeApp's software development process.; Our example on the theory-driven development of an intervention module in alloSCT delivered by eHealth and transplant team using a rigorous 3 + 1-stage approach based on BCW, COM-B and agile software development techniques, can be used as methodological guidance for other eHealth intervention developers. Our approach has the potential to enhance successful implementation and sustained use of eHealth solutions in real-life settings

Implementation Science Meets Software Development to Create eHealth Components for an Integrated Care Model for Allogeneic Stem Cell Transplantation Facilitated by eHealth: The SMILe Study as an Example

To describe a process of creating eHealth components for an integrated care model using an agile software development approach, user-centered design and, via the Behavior Change Wheel, behavior theory-guided content development. Following the principles of implementation science and using the SMILe project (integrated care model for allogeneic stem cell transplantation facilitated by eHealth) as an example, this study demonstrates how to narrow the research-to-practice gap often encountered in eHealth projects.; We followed a four-step process: (a) formation of an interdisciplinary team; (b) a contextual analysis to drive the development process via behavioral theory; (c) transfer of content to software following agile software development principles; and (d) frequent stakeholder and end user involvement following user-centered design principles.; Our newly developed comprehensive development approach allowed us to create a running eHealth component and embed it in an integrated care model. An interdisciplinary team's collaboration at specified interaction points supported clear, timely communication and interactions between the specialists. Because behavioral theory drove the content development process, we formulated user stories to define the software features, which were prioritized and iteratively developed using agile software development principles. A prototype intervention module has now been developed and received high ratings on the System Usability Scale after two rounds of usability testing.; Following an agile software development process, structured collaboration between nursing scientists and software specialists allowed our interdisciplinary team to develop meaningful, theory-based eHealth components adapted to context-specific needs.; The creation of high-quality, accurately fitting eHealth components specifically to be embedded in integrated care models should increase the chances of uptake, adoption, and sustainable implementation in clinical practice

IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?

Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.We developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences. ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.Our findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone–brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental–physical co-morbidity trias of alcohol abuse—depression/anxiety—bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental–physical co-morbidity trias