Effectiveness and acceptability of the physical exercise and dietary therapy in a healthy life center

Objective: The high burden of eating disorders (EDs) and limited availability of treatment speaks of a need to explore new avenues for treatment delivery. To understand if new treatment avenues are helpful and acceptable to patients, we investigated the effectiveness of Physical Exercise and Dietary Therapy (PED-t) in participants with bulimia nervosa or binge-eating disorder, and acceptability when the PED-t was implemented in a Healthy Life Center in a municipal primary healthcare service. Method: Exercise physiologists and one dietitian were trained in ED literacy and to run PED-t, before screening women for eligibility. Effectiveness (n = 16) of PED-t and participants' experiences (n = 8) were evaluated by a mixed methods study design. Results were analyzed by relevant statistics and reflexive thematic analysis. Results: Of 19 eligible participants, 16 completed treatment. At post-treatment, the Eating Disorder Examination Questionnaire global score, binge-eating frequency, and symptoms of depression were lower, and nine (56% of completers) were in remission. Participants' treatment experiences were classified into two overarching themes: “competence” and “emotional support.” Participants reported high acceptance for PED-t, the local venue and group format, and felt that PED-t provided them with coping tools and increased mental strength. However, many also spoke of an unmet need to address emotional eating. Discussion: Findings point to a potential for making an effective ED therapy more accessible, and that participants find the local low-threshold delivery within a groupformat helpful. With small adjustments, the PED-t could emerge as a promising firstline treatment for bulimic EDs. Public Significance Statement: Limited access to treatment for EDs, patients' high barriers to help-seeking, and the high rates of limited efficacy from psychotherapy speak of a need to explore new therapies and avenues for delivery. In this study, we build on findings from a controlled ED treatment trial and replicate the beneficial effects and find a high patient acceptance of “physical exercise and diet therapy” implemented in a real, non-clinical setting.publishedVersio

Expectations of a new eating disorder treatment and its delivery: Perspectives of patients and new therapists

Background A significant number of people with bulimia nervosa (BN) or binge-eating disorder (BED) do not seek professional help. Important reasons include limited knowledge of eating disorders (EDs), feelings of shame, treatment costs, and restricted access to specialized healthcare. In this study, we explored if a novel therapy delivered in a primary care setting could overcome these barriers. We investigated factors such as motivation and expectations and included the patients' and newly trained therapists' perspectives. Method We interviewed 10 women with BN (n = 2) or BED (n = 8), enrolled in the Physical Exercise and Dietary therapy (PED-t) program, in a Healthy Life Center (HLC) located in a primary healthcare facility. Interview topics discussed were motivations for and expectations of therapy, and the treatment location. In addition, 10 therapists from HLC's were interviewed on their experiences with the PED-t training program and expectations of running PED-t within their service. The semi-structured interviews were analyzed using reflexive thematic analysis. Results Most patients had limited knowledge about EDs and first realized the need for professional help after learning about PED-t. Patients exhibited strong motivations for treatment and a positive perception of both the PED-t, the new treatment setting, and the therapists' competencies. The therapists, following a brief training program, felt confident in their abilities to treat EDs and provide PED-t. With minor operational adjustments, PED-t can seamlessly be integrated into national HLC service locations. Conclusion PED-t is an accessible therapeutic service that can be delivered in a primary care environment in a stepped-care therapy model. Public Significance This study investigates the views and experiences of patients and newly trained therapists of PED-t (Physical Exercise and Dietary therapy), a new program-led primary care therapy for binge-eating spectrum eating disorders. The treatment and the locations for the intervention, that is, local health care centers, were found to be highly acceptable to both patients and therapists, thus PED-t could easily be integrated as a first step into a step-care delivery model.publishedVersio

Probing the Y2 Receptor on Transmembrane, Intra- and Extra-Cellular Sites for EPR Measurements

The function of G protein-coupled receptors is intrinsically linked to their conformational dynamics. In conjugation with site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy provides powerful tools to study the highly dynamic conformational states of these proteins. Here, we explored positions for nitroxide spin labeling coupled to single cysteines, introduced at transmembrane, intra- and extra-cellular sites of the human neuropeptide Y2 receptor. Receptor mutants were functionally analyzed in cell culture system, expressed in Escherichia coli fermentation with yields of up to 10 mg of purified protein per liter expression medium and functionally reconstituted into a lipid bicelle environment. Successful spin labeling was confirmed by a fluorescence assay and continuous wave EPR measurements. EPR spectra revealed mobile and immobile populations, indicating multiple dynamic conformational states of the receptor. We found that the singly mutated positions by MTSL ((1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl) methyl methanesulfonothioate) have a water exposed immobilized conformation as their main conformation, while in case of the IDSL (bis(1-oxyl-2,2,5,5-tetramethyl-3-imidazolin-4-yl) disulfide) labeled positions, the main conformation are mainly of hydrophobic nature. Further, double cysteine mutants were generated and examined for potential applications of distance measurements by double electron–electron resonance (DEER) pulsed EPR technique on the receptor

The Proteasome System in Infection: Impact of β5 and LMP7 on Composition, Maturation and Quantity of Active Proteasome Complexes

Proteasomes are the major enzyme complexes for non-lysosomal protein degradation in eukaryotic cells. Mammals express two sets of catalytic subunits: the constitutive subunits β1, β2 and β5 and the immunosubunits LMP2 (β1i), MECL-1 (β2i) and LMP7 (β5i). The LMP7-propeptide (proLMP7) is required for optimal maturation of LMP2/MECL-1-containing precursors to mature immunoproteasomes, but can also mediate efficient integration into mixed proteasomes containing β1 and β2. In contrast, the β5-propeptide (proβ5) has been suggested to promote preferential integration into β1/β2-containing precursors, consequently favouring the formation of constitutive proteasomes. Here, we show that proβ5 predominantly promotes integration into LMP2/MECL-1-containing precursors in IFNγ-stimulated, LMP7-deficient cells and infected LMP7-deficient mice. This demonstrates that proβ5 does not direct preferential integration into β1/β2-containing precursors, but instead promotes the formation of mixed LMP2/MECL-1/β5 proteasomes under inflammatory conditions. Moreover, the propeptides substantially differ in their capacity to promote proteasome maturation, with proLMP7 showing a significantly higher chaperone activity as compared to proβ5. Increased efficiency of proteasome maturation mediated by proLMP7 is required for optimal MHC class I cell surface expression and is equally important as the catalytic activity of immunoproteasomes. Intriguingly, induction of LMP7 by infection not only results in rapid exchange of constitutive by immunosubunits, as previously suggested, but also increases the total proteasome abundance within the infected tissue. Hence our data identify a novel LMP7-dependend mechanism to enhance the activity of the proteasome system in infection, which is based on the high chaperone activity of proLMP7 and relies on accelerated maturation of active proteasome complexes

EGFL7 loss correlates with increased VEGF-D expression, upregulating hippocampal adult neurogenesis and improving spatial learning and memory

Correction: Volume: 80 Issue: 8 DOI: 10.1007/s00018-023-04835-3 Article Number: 201 Published: AUG 2023Neural stem cells reside in the subgranular zone, a specialized neurogenic niche of the hippocampus. Throughout adulthood, these cells give rise to neurons in the dentate gyrus, playing an important role in learning and memory. Given that these core cognitive processes are disrupted in numerous disease states, understanding the underlying mechanisms of neural stem cell proliferation in the subgranular zone is of direct practical interest. Here, we report that mature neurons, neural stem cells and neural precursor cells each secrete the neurovascular protein epidermal growth factor-like protein 7 (EGFL7) to shape this hippocampal niche. We further demonstrate that EGFL7 knock-out in a Nestin-CreERT2-based mouse model produces a pronounced upregulation of neurogenesis within the subgranular zone. RNA sequencing identified that the increased expression of the cytokine VEGF-D correlates significantly with the ablation of EGFL7. We substantiate this finding with intraventricular infusion of VEGF-D upregulating neurogenesis in vivo and further show that VEGF-D knock-out produces a downregulation of neurogenesis. Finally, behavioral studies in EGFL7 knock-out mice demonstrate greater maintenance of spatial memory and improved memory consolidation in the hippocampus by modulation of pattern separation. Taken together, our findings demonstrate that both EGFL7 and VEGF-D affect neurogenesis in the adult hippocampus, with the ablation of EGFL7 upregulating neurogenesis, increasing spatial learning and memory, and correlating with increased VEGF-D expression.Peer reviewe

Comparative efficacy of pharmacological and non-pharmacological interventions for the acute treatment of adult outpatients with anorexia nervosa: study protocol for the systematic review and network metaanalysis of individual data

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Outpatient treatment studies of anorexia nervosa (AN) are notoriously hard to conduct given the ambivalence of the patient group and high drop-out rates. It is therefore not surprising that previous meta-analyses of pharmacological and psychological treatments for outpatient treatment of adult AN have proved to be inconclusive. Network meta-analysis (NMA) has the potential to overcome the limitations of pairwise meta-analysis, as this approach can compare multiple treatments using both direct comparisons of interventions within randomized controlled trials (RCTs) and indirect comparisons across trials based on a common comparator. To date there is no published example of this approach with eating disorders and the current study provides a protocol which will use NMA to advance knowledge about what outpatient therapy works best for which patients with AN by conducting both direct and indirect comparisons of different treatments and the moderating variables. Methods Searches of electronic data bases will be supplemented with manual searches for published, unpublished and ongoing RCTs in international registries, and clinical trials registries of regulatory agencies and pharmaceutical companies. Two reviewers will independently extract the data and where possible we will access individual data in order to examine moderators of treatment. Two primary outcomes will be selected: changes to body mass index and changes to global eating disorder psychopathology. The secondary outcome is the total number of patients who, at 12-month post-randomization, attained over the previous 28 day period: (i) BMI > 18.5, and (ii) global eating disorder psychopathology to within 1 SD of community norms. We will also provide a statistical evaluation of consistency, the agreement between direct and indirect evidence. Results Descriptive statistics across all eligible trials will be provided along with a network diagram, where the size of the nodes will reflect the amount of evidence accumulated for each treatment. We will use a contribution matrix that describes the percentage contribution of each direct meta-analysis to the entire body of evidence. Discussion Findings will make a major contribution to the literature by summarising individual data across rapidly accumulating outpatient trials of AN using state of the art NMA methodology

Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

Therapist Adherence in the Strong Without Anorexia Nervosa (SWAN) Study: A Randomized Controlled Trial of Three Treatments for Adults with Anorexia Nervosa

The Authors. International Journal of Eating Disorders Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Objective: To develop a psychotherapy rating scale to measure therapist adherence in the Strong Without Anorexia Nervosa (SWAN) study, a multi-center randomized controlled trial comparing three different psychological treatments for adults with anorexia nervosa. The three treatments under investigation were Enhanced Cognitive Behavioural Therapy (CBT-E), the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), and Specialist Supportive Clinical Management (SSCM). Method: The SWAN Psychotherapy Rating Scale (SWAN-PRS) was developed, after consultation with the developers of the treatments, and refined. Using the SWANPRS, two independent raters initially rated 48 audiotapes of treatment sessions to yield inter-rater reliability data. One rater proceeded to rate a total of 98 audiotapes from 64 trial participants. Results: The SWAN-PRS demonstrated sound psychometric properties, and was considered a reliable measure of therapist adherence. The three treatments were highly distinguishable by independent raters, with therapists demonstrating significantly more behaviors consistent with the actual allocated treatment compared to the other two treatment modalities. There were no significant site differences in therapist adherence observed. Discussion: The findings provide support for the internal validity of the SWAN study. The SWAN-PRS was deemed suitable for use in other trials involving CBT-E, MANTRA, or SSCM. VC 2015 The Authors. International Journal of Eating Disorders Published by Wiley Periodicals, Inc