Positive psychotherapy and cognitive behavioral therapy in anxiety patients - A study protocol for a randomized control trial in an online group setting.

BACKGROUND: Anxiety disorders are common and debilitating which is why treatment is so important. According to the guidelines, Cognitive Behavioral Therapy (CBT) has the highest level of effectiveness among psychotherapeutic treatments and is the recommended procedure. However, not everyone responds well or at all to CBT which makes a wider range of therapy options valuable. Positive Psychotherapy (PPT) comes to mind as an alternative with its strength-based approach focusing on enhancing well-being and life satisfaction. Additionally, it has not yet been extensively studied how the processes that occur during treatment sessions and between treatment sessions effect treatment outcome. Thus, to lessen the lack of evidence regarding the efficacy of PPT as an anxiety treatment the planned study examines and compares the effectiveness of CBT and PPT as well as the effect of intrasession and intersession processes of the two therapy approaches. METHOD: The study is in the planning stage and consists of an efficacy and a process study. The efficacy study is a randomized controlled comparative study of patients with anxiety disorders (generalized anxiety disorder and/or panic disorder with or without agoraphobia) with two active treatment conditions (PPT and CBT) and a control group (CG; positive psychotherapy with minimal therapeutic supervision) in an online group setting. There are three measurement time points: before treatment begins (T0), at the end of the ten-week treatment (T1), and a follow-up after three months (T2). The aim of the study is to evaluate the efficacy of PPT and CBT in the treatment of anxiety disorders, and to compare the efficacy of online-based PPT with minimal therapeutic supervision and online-based PPT with intensive therapeutic supervision in the treatment of anxiety disorders. The process study will be used to evaluate both the intrasession processes and the intersession processes of the therapy in the two intervention groups. In addition, the process variables that predict the success of the therapy and the extent to which PPT and CBT differ in the therapy processes will be tested. The study is registered at the German Clinical Trial Register (№ DRKS00027521). DISCUSSION: To our knowledge, this is the first randomized controlled comparative study to examine the effectiveness of CBT and PPT for anxiety disorders in an online group setting.

[General practice care for patients with chronic non-cancer pain: A rapid review as part of the RELIEF project]. / Hausärztliche Versorgung von Patient:innen mit chronischen nicht-tumorbedingten Schmerzen: ein Rapid Review im Rahmen des RELIEF-Projekts.

INTRODUCTION: Approximately one fifth of the German population suffers from chronic pain, which is often associated with limitations in coping with everyday life, social isolation and psychological comorbidities such as anxiety and depression. The importance of a treatment approach that considers biological, psychological, and social factors (bio-psycho-social model) as well as non-drug interventions is emphasized in current guidelines, but presents challenges for primary care practices. To support the implementation of evidence-based best practice recommendations, the RELIEF project (Resource-oriented case management to implement recommendations for patients with chronic pain and frequent use of analgesics in general practices) aims to develop a case management program for the primary care of patients with chronic non-tumor pain. METHODS: Prior to intervention development, a rapid review was conducted to identify best practice recommendations for the care of patients with chronic non-tumor pain, barriers and strategies to their implementation, and gaps in care in current guidelines and literature. Selective searches of guidelines, PubMed, the Cochrane Library, bibliographies of relevant publications, and the gray literature focused on assessment and monitoring, education, promotion of self-care, and rational pharmacotherapy. RESULTS: Numerous recommendations on assessment and monitoring were identified, but only a few studies examined their feasibility in primary care practices. Guidelines contained few specific recommendations on content and format of patient education on chronic pain. Recommendations for non-drug self-care measures were mainly related to physical activity, relaxation techniques, behavioral therapy techniques and external applications. Especially for the area of physical activity, numerous barriers but also strategies for a successful implementation could be identified. DISCUSSION: In a potential primary care model for patients with chronic non-tumor pain, pain assessment should aim to identify patients who need support in implementing medication and non-medication interventions in the primary care setting and/or could benefit from specialized care. To implement recommendations for pain education, primary care physicians need educational materials in a variety of formats and levels of detail that ideally could be processed by patients at home and then get addressed in practices using simple key questions. Non-drug measures should be an explicit part of the treatment plan. CONCLUSION: Many of the identified recommendations for the treatment of patients with chronic non-tumor pain can also be considered relevant for the primary care setting. Specific guidelines and concepts for primary care physicians that include setting-specific characteristics at the physician, patient, and system levels would be desirable for a successful implementation of these recommendations.

[Interprofessional weaning boards and weaning consults for long-term ventilated patients: A qualitative study of perceived potential for patient care]. / Interprofessionelle Weaning-Boards und Weaning-Konsile für Langzeitbeatmungspatient*innen: Eine qualitative Studie zum wahrgenommenen Potenzial für die Patientenversorgung.

BACKGROUND: The PRiVENT project aims to improve the care of invasively ventilated patients and to reduce the number of out-of-hospital long-term ventilated patients. PRiVENT offers intensive care units the opportunity to exchange information with experts from specialized weaning centers in interprofessional weaning boards and weaning consults and to exploit the full weaning potential of the patients. In the context of the accompanying process evaluation, the PRiVENT intervention components will be examined for sustainability, scalability and effectiveness, and the interprofessional collaboration between intensive care units and the responsible weaning centers will be investigated in order to identify potentials for the care of invasively managed patients. METHODS: In a qualitative cross-sectional study, semistructured, problem-oriented interviews were conducted with care providers of participating ICUs. The data were digitally recorded, pseudonymized and verbatim transcribed. Data analysis was based on Brown and Clarke's Thematic Analysis and the Consolidated Framework for Implementation Research. MAXQDA 2020 software was used to organize the data. RESULTS: Fourteen interviews were conducted with ICU care providers. The early transfer of patients to a weaning center and the integration of pulmonary expertise into routine care were identified as positively perceived potentials of the weaning boards and weaning consults. Especially in critically ill, multimorbid patients suffering from COVID-19, the expertise of the weaning centers was considered helpful. Due to heavy workloads, nurses were unable to participate in weaning boards and weaning consults. CONCLUSION: Interprofessional collaboration between weaning centers and ICUs in weaning boards and weaning consults can improve the care of invasively ventilated patients. Strategies to promote the involvement of nurses should be discussed and developed.

HLA antibody affinity determination: From HLA-specific monoclonal antibodies to donor HLA specific antibodies (DSA) in patient serum.

Organs transplanted across donor-specific HLA antibodies (DSA) are associated with a variety of clinical outcomes, including a high risk of acute kidney graft rejection. Unfortunately, the currently available assays to determine DSA characteristics are insufficient to clearly discriminate between potentially harmless and harmful DSA. To further explore the hazard potential of DSA, their concentration and binding strength to their natural target, using soluble HLA, may be informative. There are currently a number of biophysical technologies available that allow the assessment of antibody binding strength. However, these methods require prior knowledge of antibody concentrations. Our objective within this study was to develop a novel approach that combines the determination of DSA-affinity as well as DSA-concentration for patient sample evaluation within one assay. We initially tested the reproducibility of previously reported affinities of human HLA-specific monoclonal antibodies and assessed the technology-specific precision of the obtained results on multiple platforms, including surface plasmon resonance (SPR), bio-layer interferometry (BLI), Luminex (single antigen beads; SAB), and flow-induced dispersion analysis (FIDA). While the first three (solid-phase) technologies revealed comparable high binding-strengths, suggesting measurement of avidity, the latter (in-solution) approach revealed slightly lower binding-strengths, presumably indicating measurement of affinity. We believe that our newly developed in-solution FIDA-assay is particularly suitable to provide useful clinical information by not just measuring DSA-affinities in patient serum samples but simultaneously delivering a particular DSA-concentration. Here, we investigated DSA from 20 pre-transplant patients, all of whom showed negative CDC-crossmatch results with donor cells and SAB signals ranging between 571 and 14899 mean fluorescence intensity (MFI). DSA-concentrations were found in the range between 11.2 and 1223 nM (median 81.1 nM), and their measured affinities fall between 0.055 and 24.7 nM (median 5.34 nM; 449-fold difference). In 13 of 20 sera (65%), DSA accounted for more than 0.1% of total serum antibodies, and 4/20 sera (20%) revealed a proportion of DSA even higher than 1%. To conclude, this study strengthens the presumption that pre-transplant patient DSA consists of various concentrations and different net affinities. Validation of these results in a larger patient cohort with clinical outcomes will be essential in a further step to assess the clinical relevance of DSA-concentration and DSA-affinity.

Phosphorylation-linked complex profiling identifies assemblies required for Hippo signal integration.

While several computational methods have been developed to predict the functional relevance of phosphorylation sites, experimental analysis of the interdependency between protein phosphorylation and Protein-Protein Interactions (PPIs) remains challenging. Here, we describe an experimental strategy to establish interdependencies between protein phosphorylation and complex formation. This strategy is based on three main steps: (i) systematically charting the phosphorylation landscape of a target protein; (ii) assigning distinct proteoforms of the target protein to different protein complexes by native complex separation (AP-BNPAGE) and protein correlation profiling; and (iii) analyzing proteoforms and complexes in cells lacking regulators of the target protein. We applied this strategy to YAP1, a transcriptional co-activator for the control of organ size and tissue homeostasis that is highly phosphorylated and among the most connected proteins in human cells. We identified multiple YAP1 phosphosites associated with distinct complexes and inferred how both are controlled by Hippo pathway members. We detected a PTPN14/LATS1/YAP1 complex and suggest a model how PTPN14 inhibits YAP1 via augmenting WW domain-dependent complex formation and phosphorylation by LATS1/2.

Characterisation of the first enzymes committed to lysine biosynthesis in Arabidopsis thaliana.

In plants, the lysine biosynthetic pathway is an attractive target for both the development of herbicides and increasing the nutritional value of crops given that lysine is a limiting amino acid in cereals. Dihydrodipicolinate synthase (DHDPS) and dihydrodipicolinate reductase (DHDPR) catalyse the first two committed steps of lysine biosynthesis. Here, we carry out for the first time a comprehensive characterisation of the structure and activity of both DHDPS and DHDPR from Arabidopsis thaliana. The A. thaliana DHDPS enzyme (At-DHDPS2) has similar activity to the bacterial form of the enzyme, but is more strongly allosterically inhibited by (S)-lysine. Structural studies of At-DHDPS2 show (S)-lysine bound at a cleft between two monomers, highlighting the allosteric site; however, unlike previous studies, binding is not accompanied by conformational changes, suggesting that binding may cause changes in protein dynamics rather than large conformation changes. DHDPR from A. thaliana (At-DHDPR2) has similar specificity for both NADH and NADPH during catalysis, and has tighter binding of substrate than has previously been reported. While all known bacterial DHDPR enzymes have a tetrameric structure, analytical ultracentrifugation, and scattering data unequivocally show that At-DHDPR2 exists as a dimer in solution. The exact arrangement of the dimeric protein is as yet unknown, but ab initio modelling of x-ray scattering data is consistent with an elongated structure in solution, which does not correspond to any of the possible dimeric pairings observed in the X-ray crystal structure of DHDPR from other organisms. This increased knowledge of the structure and function of plant lysine biosynthetic enzymes will aid future work aimed at improving primary production.

Recombinant functional multidomain hemoglobin from the gastropod Biomphalaria glabrata.

The extracellular hemoglobin multimer of the planorbid snail Biomphalaria glabrata, intermediate host of the human parasite Schistosoma mansoni, is presumed to be a 1.44 MDa complex of six 240 kDa polypeptide subunits, arranged as three disulfide-bridged dimers. The complete amino acid sequence of two subunit types (BgHb1 and BgHb2), and the partial sequence of a third type (BgHb3) are known. Each subunit encompasses 13 paralogus heme domains, and N-terminally a smaller plug domain responsible for subunit dimerization. We report here the recombinant expression of different functional fragments of BgHb2 in Escherichia coli, and of the complete functional subunits BgHb1 and BgHb2 in insect cells; BgHb1 was also expressed as disulfide-bridged dimer (480 kDa). Oxygen-binding measurements of the recombinant products show a P(50) of about 7 mmHg and the absence of a significant cooperativity or Bohr effect. The covalently linked dimer of BgHb1, but not the monomer, is capable to form aggregates closely resembling native BgHb molecules in the electron microscope.

Arabidopsis stromal-derived Factor2 (SDF2) is a crucial target of the unfolded protein response in the endoplasmic reticulum.

Stresses increasing the load of unfolded proteins that enter the endoplasmic reticulum (ER) trigger a protective response termed the unfolded protein response (UPR). Stromal cell-derived factor2 (SDF2)-type proteins are highly conserved throughout the plant and animal kingdoms. In this study we have characterized AtSDF2 as crucial component of the UPR in Arabidopsis thaliana. Using a combination of biochemical and cell biological methods, we demonstrate that SDF2 is induced in response to ER stress conditions causing the accumulation of unfolded proteins. Transgenic reporter plants confirmed induction of SDF2 during ER stress. Under normal growth conditions SDF2 is highly expressed in fast growing, differentiating cells and meristematic tissues. The increased production of SDF2 due to ER stress and in tissues that require enhanced protein biosynthesis and secretion, and its association with the ER membrane qualifies SDF2 as a downstream target of the UPR. Determination of the SDF2 three-dimensional crystal structure at 1.95 A resolution revealed the typical beta-trefoil fold with potential carbohydrate binding sites. Hence, SDF2 might be involved in the quality control of glycoproteins. Arabidopsis sdf2 mutants display strong defects and morphological phenotypes during seedling development specifically under ER stress conditions, thus establishing that SDF2-type proteins play a key role in the UPR.