Effectiveness of a Web-Based Cognitive Behavioral Self-Help Intervention for Binge Eating Disorder: A Randomized Clinical Trial.

Importance: Binge eating disorder (BED) is one of the most frequent eating pathologies and imposes substantial emotional and physical distress, yet insufficient health care resources limit access to specialized treatment. Web-based self-help interventions emerge as a promising solution, offering more accessible care. Objective: To examine the effectiveness of a web-based cognitive behavioral self-help intervention for individuals with BED. Design, Setting, and Participants: This 2-arm, parallel-group randomized clinical trial conducted from January 15, 2021, to August 3, 2022, in Germany and other German-speaking countries enrolled patients aged 18 to 65 years who met the diagnostic criteria for BED (according to the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]). Data analysis occurred between January 27 and September 4, 2023, following our statistical analysis plan. Interventions: Participants were randomized to a web-based self-help intervention or a waiting-list control condition. Main Outcomes and Measures: The primary outcome was a change in objective binge eating episodes from baseline to after treatment. Secondary outcomes included global eating pathology, clinical impairment, work capacity, well-being, comorbid psychopathology, self-esteem, and emotion regulation. Results: A total of 1602 patients were screened, of whom 154 (mean [SD] age, 35.93 [10.59] years; 148 female [96.10%]) fulfilled the criteria for BED and were randomized (77 each to the intervention and control groups). The web-based intervention led to significant improvements in binge eating episodes (Cohen d, -0.79 [95% CI, -1.17 to -0.42]; P < .001), global eating psychopathology (Cohen d, -0.71 [95% CI, -1.07 to -0.35]; P < .001), weekly binge eating (Cohen d, -0.49 [95% CI, -0.74 to -0.24]; P < .001), clinical impairment (Cohen d, -0.75 [95% CI, -1.13 to -0.37]; P < .001), well-being (Cohen d, 0.38 [95% CI, 0.01 to 0.75]; P = .047), depression (Cohen d, -0.49 [95% CI, -0.86 to -0.12]; P = .01), anxiety (Cohen d, -0.37 [95% CI, -0.67 to -0.07]; P = .02), self-esteem (Cohen d, 0.36 [95% CI, 0.13 to 0.59]; P = .003), and emotion regulation (difficulties: Cohen d, -0.36 [95% CI, -0.65 to -0.07]; P = .01 and repertoire: Cohen d, 0.52 [95% CI, 0.19 to 0.84]; P = .003). Conclusion and Relevance: In this randomized clinical trial of a web-based self-help intervention for patients with BED, the findings confirmed its effectiveness in reducing binge eating episodes and improving various mental health outcomes, highlighting a scalable solution to bridge the treatment gap for this condition. Trial Registration: ClinicalTrials.gov Identifier: NCT04876183.

Contextual variations in emotion polyregulation: How do regulatory goals shape the use and success of emotion regulation strategies in everyday life?

Emotion regulation strategies are frequently combined within one emotional episode, a phenomenon labeled emotion polyregulation. Nevertheless, there is a scarcity of studies examining which regulatory strategies are commonly combined across different contexts and how effective these combinations are in everyday life. Targeting this research gap, the present ecological momentary assessment study modeled emotion polyregulation and its success for contexts of (a) downregulation, (b) upregulation, and (c) maintenance goals in N = 321 adults. The endorsement and success of 15 different emotion regulation strategies derived from the process model of emotion regulation were measured 5 times a day for 7 days. Multilevel factor analyses revealed that individuals tend to combine different regulatory strategies depending on the activated regulatory goal: When examining downregulation, four factors best described the combined use of regulatory strategies: Situation Modification, Repetitive Processing, Emotional Avoidance, and Interpersonal Regulation. In contrast, three-factor models characterized emotion polyregulation for upregulation (Emotional Acceptance, Repetitive Processing, and Interpersonal Regulation) and maintenance goals (Unspecific Regulation, Emotional Acceptance, and Interpersonal Regulation). Moreover, multilevel structural equation modeling revealed that the success of emotion polyregulation is goal-dependent. While combining interpersonal and situation modification strategies was related to beneficial outcomes for downregulation goals, acceptance-based strategies were most strongly associated with emotion regulation success in situations of upregulation and maintenance. These results add to a more complex understanding of emotion regulation in daily life and highlight the necessity of broadening the focus of emotion regulation research to examine emotion polyregulation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluation of a Web-Based Self-Help Intervention for Patients With Generalized Anxiety Disorder: Protocol for a Randomized Controlled Trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a highly prevalent and severely distressing condition that can lead to functional impairments and is considered one of the most difficult anxiety disorders to treat. Following new technological developments, a highly structured cognitive behavioral therapy (CBT) approach that has already shown success in face-to-face psychotherapy can be implemented: internet-delivered CBT (iCBT). There is now evidence for the efficacy of both guided and unguided iCBT interventions for GAD regarding symptom reduction. OBJECTIVE: To establish the usefulness of such interventions, we plan to evaluate the efficacy of a web-based self-help program (Selfapy) for GAD in a relatively large sample. We aim to assess effects beyond symptom reduction, including effects on well-being, functioning, and mental health literacy, as well as the effect on health care burden, while testing the intervention in conditions comparable to routine care. METHODS: Patients (n=156) who have been diagnosed with GAD, are aged between 18 and 65 years, have internet access, and have sufficient German language skills will be recruited for this study. The intervention group (n=78) will receive access to the 12-week self-help web-based program Selfapy. The waitlist control group (n=78) will receive no intervention in the context of the study. However, both groups will be allowed to access further health care services (eg, psychotherapy, medication), reflecting current routine care in Germany. Outcome measures will be assessed at baseline (T1) and 6 weeks (T2) and 12 weeks (T3) after the start of the intervention. The primary outcome will be generalized anxiety symptoms and quality of life at T3. Additional outcomes include depression, work capacity, therapy-related expenses and burdens, health literacy, and negative effects. RESULTS: By May 2023, all participants had finished the trial and the report was being prepared for publication. CONCLUSIONS: Web-based interventions may be an important addition to the German health care system to reduce barriers to treatment access. Further, they may prove cost-effective for the treatment of GAD. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00023799; https://tinyurl.com/22bds38x. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41440.

Multiple Functions of the Type II Thioesterase Associated with the Phoslactomycin Polyketide Synthase.

Polyketide synthases (PKSs) are molecular assembly lines that condense basic chemical building blocks for the production of structurally diverse polyketides. Many PKS biosynthetic gene clusters contain a gene encoding for a type II thioesterase (TEII). It is believed that TEIIs exert a proofreading function and restore or increase the productivity of PKSs by removing aberrant modifications on the acyl-carrier proteins (ACPs) of the PKS assembly line. Yet biochemical evidence is still sparse. Here, we investigated the function of PnG, the TEII of the phoslactomycin PKS (Pn PKS), in the context of its cognate assembly line in vitro. Biochemical analysis revealed that PnG preferentially hydrolyzes alkyl-ACPs over (alkyl)malonyl-ACPs by up to three orders of magnitude, supporting a proofreading role of the enzyme. We further demonstrate that PnG increases the in vitro production of different native and non-native tetra-, penta-, and hexaketide derivatives of phoslactomycin by more than one order of magnitude and show that these effects are caused by the initial clearing of the Pn PKS, as well as proofreading of the active assembly line. Finally, we demonstrate that PnG is able to release intermediate but notably also terminal polyketides from the Pn PKS. This allows PnG to functionally replace and overcome the terminal TEI activity of chimeric in vitro Pn PKS systems, as showcased with a phoslactomycin hexaketide system. Altogether, our experiments provide detailed insights into the molecular mechanisms and the multiple functions of PnG in its native context, as well as their potential use in future applications.

Applying a web-based self-help intervention for bulimia nervosa in routine care: Study protocol for a randomized controlled trial.

BACKGROUND: Individuals with bulimia nervosa (BN) experience persistent episodes of binge eating and inappropriate compensatory behavior associated with impaired physical and mental health. Despite the existence of effective treatments, many individuals with BN remain untreated, leading to a high burden and an increased risk of chronicity. Web-based interventions may help facilitate access to evidence-based treatments for BN by reducing barriers to the health care system. METHODS: The present study will investigate the effectiveness of a web-based self-help intervention for BN in a two-armed randomized controlled trial. Individuals diagnosed with BN (N = 152) will be randomly assigned to either (1) an intervention group receiving a 12-week web-based intervention or (2) a waitlist control group with delayed access to the intervention. Further assessments will be scheduled 6 (mid-treatment) and 12 (post-treatment) weeks after baseline. Changes in the number of binge eating episodes and compensatory behaviors will be examined as primary outcomes. Secondary outcomes include global eating pathology, functional impairments, well-being, comorbid psychopathology, self-esteem, and emotion regulation abilities. DISCUSSION: Adding web-based interventions into routine care is a promising approach to overcome the existing treatment gap for patients with BN. Therefore, the current study will test the effectiveness of a web-based intervention for BN under standard clinical care settings. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04876196 (registered on May 6th, 2021).

Integrating a web-based intervention into routine care of binge-eating disorder: Study protocol for a randomized controlled trial.

Background: Although binge eating disorder (BED) is the most common eating pathology and carries a high mental and physical burden, access to specialized treatment is limited due to patient-related barriers and insufficient healthcare resources. Integrating web-based self-help programs into clinical care for BED may address this treatment gap by making evidence-based eating disorder interventions more accessible. Methods: A two-armed randomized controlled trial will be conducted to evaluate the effectiveness of a web-based self-help intervention for BED in routine care settings. Patients aged 18-65 years fulfilling the diagnostic criteria for BED (N = 152) will be randomly allocated to (1) an intervention group receiving a 12-week web-based self-help program or (2) a waitlist control group with delayed access to the intervention. The primary outcome will be the number of binge eating episodes. Secondary outcomes include global eating pathology, functional impairments, work capacity, well-being, comorbid psychopathology, self-esteem, and emotion regulation abilities. Measurements will be conducted at baseline (study entrance), 6 weeks after baseline (mid-treatment), and 12 weeks after baseline (post-treatment). To capture outcomes and treatment mechanisms in real-time, traditional self-reports will be combined with weekly symptom monitoring and ecological momentary assessment. Discussion: Evaluating the effectiveness of web-based interventions is essential to overcome the treatment gap for patients with BED. When adequately integrated into standard care, these programs have the potential to alleviate the high burden of BED for individuals, their families, and society. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04876183, Identifier: NCT04876183 (registered on May 6th, 2021).

Stability liabilities of biotherapeutic proteins: Early assessment as mitigation strategy.

Identification of molecular liabilities and implementation of mitigation strategies are key aspects that need to be considered by pharmaceutical companies developing therapeutic proteins. In the field of monoclonal antibodies, an efficient and streamlined process known as developability assessment is used for the selection of the "fittest" candidate. Other protein modalities, have in most cases only a limited number of possible candidates, requiring a paradigm change to a concept of candidate enabling. The assessment of liabilities at early project phases with the possibility to re-engineer candidates becomes essential for the success of these projects. Each protein possesses a unique stability profile resulting from the interplay of conformational, colloidal, chemical and physical stability attributes. All of these attributes strongly depend on external factors. Conformational and colloidal stability profiles of three non-immunoglobulin domain based proteins, namely Carbonic anhydrase, Ovalbumin and Thyroglobulin, and of two monoclonal antibodies were assessed in dependence of solution pH, ionic strength and varying buffering agents. The impact of screened external factors on proteins' stability attributes varied significantly, indicating presence of molecule specific liabilities. Screening of such a broad space of conditions at early project phases is only feasible using low-material consuming, high-throughput analytical methods as exemplified in this study.

Resuspendable Powders of Lyophilized Chalcogen Particles with Activity against Microorganisms.

Many organic sulfur, selenium and tellurium compounds show considerable activity against microorganisms, including bacteria and fungi. This pronounced activity is often due to the specific, oxidizing redox behavior of the chalcogen-chalcogen bond present in such molecules. Interestingly, similar chalcogen-chalcogen motifs are also found in the elemental forms of these elements, and while those materials are insoluble in aqueous media, it has recently been possible to unlock their biological activities using naturally produced or homogenized suspensions of respective chalcogen nanoparticles. Those suspensions can be employed readily and often effectively against common pathogenic microorganisms, still their practical uses are limited as such suspensions are difficult to transport, store and apply. Using mannitol as stabilizer, it is now possible to lyophilize such suspensions to produce solid forms of the nanoparticles, which upon resuspension in water essentially retain their initial size and exhibit considerable biological activity. The sequence of Nanosizing, Lyophilization and Resuspension (NaLyRe) eventually provides access to a range of lyophilized materials which may be considered as easy-to-handle, ready-to-use and at the same time as bioavailable, active forms of otherwise insoluble or sparingly substances. In the case of elemental sulfur, selenium and tellurium, this approach promises wider practical applications, for instance in the medical or agricultural arena.

An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy.

The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.

Rapid protein expression analysis with an interferometric biosensor for monitoring protein production.

The concentration of a recombinantly expressed protein has to be monitored to select optimal expression conditions throughout the protein production process. Today this is usually achieved semiquantitatively with sodium dodecyl sulfate polyacrylamide gel electrophoresis/western blotting or with ELISAs, which are time- and labor-intensive methods. In this paper the applicability of a label-free sensor system based on a Young interferometer is presented as an alternative for the monitoring of recombinant protein production. Once a protein is successfully produced, the interferometric biosensor allows any protein-protein interaction to be characterized in a label-free manner. This is demonstrated with an antibody/antigen pair, where the antibody is directed against a four-amino-acid tag used for protein expression analysis as well as purification during recombinant protein production. Label-free detection of the tagged protein is shown both in buffer and in bacterial cell lysate as a sample matrix. The system exhibiting a low limit of detection, low drift and reliable operation is compared with a commercial surface plasmon resonance sensor and a competitive ELISA.

A semi-automated large-scale process for the production of recombinant tagged proteins in the Baculovirus expression system.

The efficient preparation of recombinant proteins at the lab-scale level is essential for drug discovery, in particular for structural biology, protein interaction studies and drug screening. The Baculovirus insect-cell expression system is one of the most widely applied and highly successful systems for production of recombinant functional proteins. However, the use of eukaryotic cells as host organisms and the multi-step protocol required for the generation of sufficient virus and protein has limited its adaptation to industrialized high-throughput operation. We have developed an integrated large-scale process for continuous and partially automated protein production in the Baculovirus system. The instrumental platform includes parallel insect-cell fermentation in 10L BioWave reactors, cell harvesting and lysis by tangential flow filtration (TFF) using two custom-made filtration units and automated purification by multi-dimensional chromatography. The use of disposable materials (bags, filters and tubing), automated cleaning cycles and column regeneration, prevent any cross-contamination between runs. The preparation of the clear cell lysate by sequential TFF takes less than 2 h and represents considerable time saving compared to standard cell harvesting and lysis by sonication and ultra-centrifugation. The process has been validated with 41 His-tagged proteins with molecular weights ranging from 20 to 160 kDa. These proteins represented several families, and included 23 members of the deubiquitinating enzyme (DUB) family. Each down-stream unit can process four proteins in less than 24 h with final yields between 1 and 100 mg, and purities between 50 and 95%.