ABSTRACT
The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.
Subject(s)
Epstein-Barr Virus Infections , Heart Failure , Herpesvirus 4, Human , Myocarditis , Humans , Herpesvirus 4, Human/genetics , Heart Failure/virology , Heart Failure/genetics , Heart Failure/pathology , Male , Female , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/pathology , Middle Aged , Myocarditis/virology , Myocarditis/pathology , Aged , High-Throughput Nucleotide Sequencing , Myocardium/pathology , Myocardium/metabolism , DNA, Viral/genetics , Adult , BiopsyABSTRACT
Stepped, evidence-based and integrated care service models have the potential to be used as a reference for mental health services. RECOVER aimed to evaluate cost savings, effectiveness, and cost-effectiveness of such a model within a two arm, assessor- and data analysist-blinded RCT in Hamburg, Germany. Participants aged 16-79 years with mental disorders were randomly assigned either to RECOVER or treatment as usual (TAU). Primary outcomes comprised costs, effectiveness (combined symptoms, functioning, quality of life), and cost-effectiveness, hierarchically ordered. Outcomes were evaluated according to the ITT principle, group differences regarding costs with adjusted generalized linear models, effectiveness with ANCOVA models, and cost-effectiveness with the incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curves (CEACs). Between 1/1/2018 and 12/31/2020, n = 891 were finally included (n = 477 in RECOVER, n = 444 in TAU). RECOVER was associated with significantly lower annual total costs (-22 %), health and social care costs (-25 %) and hospital costs (-50 %). Effectiveness analyses showed a significantly better outcome for RECOVER with the fully imputed data . The CEACs descriptively demonstrated that RECOVER was cost-effective with a probability of >95 %. Treatment in RECOVER resulted in substantial cost reductions with better cost-effectiveness. RECOVER can be recommended as a reference model for comprehensive and integrated mental health services.
Subject(s)
Cost-Benefit Analysis , Delivery of Health Care, Integrated , Mental Disorders , Humans , Middle Aged , Adult , Female , Male , Aged , Adolescent , Mental Disorders/therapy , Mental Disorders/economics , Young Adult , Germany , Delivery of Health Care, Integrated/economics , Mental Health Services/economics , Quality of Life , Health Care Costs/statistics & numerical data , Outcome Assessment, Health CareABSTRACT
The AAA-type ATPase VPS4 is recruited by proteins of the endosomal sorting complex required for transport III (ESCRT-III) to catalyse membrane constriction and membrane fission. VPS4A accumulates at the cytoplasmic viral assembly complex (cVAC) of cells infected with human cytomegalovirus (HCMV), the site where nascent virus particles obtain their membrane envelope. Here we show that VPS4A is recruited to the cVAC via interaction with pUL71. Sequence analysis, deep-learning structure prediction, molecular dynamics and mutagenic analysis identify a short peptide motif in the C-terminal region of pUL71 that is necessary and sufficient for the interaction with VPS4A. This motif is predicted to bind the same groove of the N-terminal VPS4A Microtubule-Interacting and Trafficking (MIT) domain as the Type 2 MIT-Interacting Motif (MIM2) of cellular ESCRT-III components, and this viral MIM2-like motif (vMIM2) is conserved across ß-herpesvirus pUL71 homologues. However, recruitment of VPS4A by pUL71 is dispensable for HCMV morphogenesis or replication and the function of the conserved vMIM2 during infection remains enigmatic. VPS4-recruitment via a vMIM2 represents a previously unknown mechanism of molecular mimicry in viruses, extending previous observations that herpesviruses encode proteins with structural and functional homology to cellular ESCRT-III components.
Subject(s)
Cytomegalovirus , Endosomal Sorting Complexes Required for Transport , Molecular Mimicry , Vacuolar Proton-Translocating ATPases , Virus Assembly , Humans , Endosomal Sorting Complexes Required for Transport/metabolism , Vacuolar Proton-Translocating ATPases/metabolism , Vacuolar Proton-Translocating ATPases/genetics , Cytomegalovirus/metabolism , Cytomegalovirus/genetics , Cytomegalovirus/physiology , Virus Assembly/physiology , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/metabolism , ATPases Associated with Diverse Cellular Activities/metabolism , ATPases Associated with Diverse Cellular Activities/genetics , Viral Proteins/metabolism , Viral Proteins/geneticsABSTRACT
Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here, we addressed how murine adult hippocampal NSC fate is regulated and described how scaffold attachment factor B (SAFB) blocks oligodendrocyte production to enable neuron generation. We found that SAFB prevents NSC expression of the transcription factor nuclear factor I/B (NFIB) by binding to sequences in the Nfib mRNA and enhancing Drosha-dependent cleavage of the transcripts. We show that increasing SAFB expression prevents oligodendrocyte production by multipotent adult NSCs, and conditional deletion of Safb increases NFIB expression and oligodendrocyte formation in the adult hippocampus. Our results provide novel insights into a mechanism that controls Drosha functions for selective regulation of NSC fate by modulating the post-transcriptional destabilization of Nfib mRNA in a lineage-specific manner.
Subject(s)
Hippocampus , NFI Transcription Factors , Neural Stem Cells , Nuclear Matrix-Associated Proteins , RNA, Messenger , Animals , Mice , Cell Differentiation , Hippocampus/metabolism , Hippocampus/cytology , Neural Stem Cells/metabolism , NFI Transcription Factors/metabolism , NFI Transcription Factors/genetics , Nuclear Matrix-Associated Proteins/metabolism , Oligodendroglia/metabolism , Ribonuclease III/metabolism , Ribonuclease III/genetics , RNA Stability , RNA, Messenger/metabolism , RNA, Messenger/geneticsABSTRACT
The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening. To exemplify the utility of the model, we exposed the engineered OA cartilage organoids to factors known to attenuate pathological features, including IL-1Ra, and carried out mass spectrometry-based proteomics. We identified that IL-1Ra strongly reduced production of the transcription factor CCAAT/enhancer-binding protein beta [2] and demonstrated that inhibition of the C/EBPß-activating kinases could revert the degradative processes. Human OA cartilage organoids thus represent a relevant tool towards the discovery of new molecular drivers of cartilage degeneration and the assessment of therapeutics targeting associated pathways.
Subject(s)
Organoids , Osteoarthritis , Tissue Engineering , Humans , Organoids/metabolism , Organoids/pathology , Osteoarthritis/pathology , Osteoarthritis/metabolism , Tissue Engineering/methods , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Chondrogenesis , Chondrocytes/metabolism , Chondrocytes/pathology , Cartilage, Articular/pathology , Cartilage, Articular/metabolism , Cartilage/pathology , Cartilage/metabolism , CCAAT-Enhancer-Binding Protein-beta/metabolism , ProteomicsABSTRACT
Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates ("hibernation"). However, a newly isolated Pseudomonas aeruginosa phage, named Paride, can directly replicate and induce the lysis of deep-dormant hosts. While non-growing bacteria are notoriously tolerant to antibiotic drugs, the combination with Paride enables the carbapenem meropenem to eradicate deep-dormant cultures in vitro and to reduce a resilient bacterial infection of a tissue cage implant in mice. Our work might inspire new treatments for persistent bacterial infections and, more broadly, highlights two viral strategies to infect dormant bacteria (hibernation and direct replication) that will guide future studies on phage-host interactions.
Subject(s)
Bacteriophages , Pseudomonas Infections , Animals , Mice , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Pseudomonas Infections/microbiologyABSTRACT
The current society consists of an increasing number of people vulnerable to infections. For certain people with severe immunodeficiency, a neutropenic or low-microbial diet is being prescribed, which substitutes high-risk foods that are more likely to contain human (opportunistic) pathogens with lower-risk alternatives. These neutropenic dietary guidelines are typically set up from a clinical and nutritional perspective, rather than from a food processing and food preservation perspective. In this study, the current guidelines in use by the Ghent University Hospital were evaluated based on the current knowledge of food processing and preservation technologies and the scientific evidence on microbiological quality, safety, and hygiene of processed foods. Three criteria are identified to be important: (1) the microbial contamination level and composition; (2) the potential presence of established foodborne pathogens such as Salmonella spp. (to which a zero-tolerance policy is recommended); and (3) an increased vigilance for L. monocytogenes as an opportunistic foodborne pathogen with a high mortality rate in immunocompromised individuals (to which a zero-tolerance policy should apply). A combination of these three criteria was used as a framework for the evaluation of the suitability of foodstuffs to be included in a low-microbial diet. Differences in processing technologies, initial contamination of products, etc., however, lead to a high degree of variability in microbial contamination and make it difficult to unambiguously accept or reject a certain type of foodstuff without prior knowledge of the ingredients and the processing and preservation technologies applied during manufacturing and subsequent storage conditions. A restricted screening on a selection of (minimally processed) plant-based foodstuffs on the retail market in Flanders, Belgium supported decision-making on the inclusion of these food types in a low-microbial diet. Still, when determining the suitability of a foodstuff to be included in a low-microbial diet, not only the microbiological status but also nutritional and sensorial properties should be assessed, which requires multidisciplinary communication and collaboration.
ABSTRACT
Low-threshold e-health approaches in prevention to reduce suicide stigma are scarce. We developed an online program containing video reports on lived experience of suicide and evidence-based information on suicidality. We evaluated the program by a mixed methods design. We examined pre-post-changes of program completers (n = 268) in suicide literacy, suicide stigma (self and perceived), and self-efficacy expectation of being able to seek support in psychologically difficult situations using linear mixed models. To examine reported changes and helpful program elements 12-26 weeks after program completion, we content analyzed transcripts of telephone interviews (n = 16). Program completers showed more suicide literacy (Cohen's d = .74; p < .001), higher self-efficacy expectations to seek support (d = .09; p < .01), lower self-stigma (subscales glorification/normalization: d = -.13, p = .04; isolation/depression: d = -.14; p = .04; stigma: d = -.10; p = .07; n = 168) compared to baseline. We found no significant differences in perceived suicide stigma. We identified lived experience reports, the possibility of sharing own narrative on stigma and suicidality, and information on support as helpful elements. The current online program can increase suicide literacy and self-efficacy expectations to seek support and reduce self-stigma. We recommend a larger randomized controlled trial with longer follow-up to confirm these findings.
Subject(s)
Health Literacy , Suicide , Humans , Suicide Prevention , Social Stigma , Suicidal IdeationABSTRACT
OBJECTIVE: Development and psychometric evaluation of a German 6-item instrument to assess self-efficacy expectations to seek support in psychologically difficult situations (SWEP). METHODS: Development of items, determination of distribution characteristics, factor structure, and internal consistency of the scale based on a paper-pencil survey (N=269) and a survey of an online intervention on suicide prevention (N=802). RESULTS: Principal component analysis revealed the SWEP scale to be a one-dimensional construct with high internal consistency (Cronbach's α=.83 and α=.89). We found content-plausible correlations to other constructs and initial evidence of a high retest reliability. CONCLUSION: The SWEP provides a reliable, valid, brief instrument for assessing self-efficacy expectations of being able to seek support.
Subject(s)
Motivation , Self Efficacy , Humans , Psychometrics , Reproducibility of Results , Germany , Surveys and QuestionnairesABSTRACT
Fabry-Pérot-based refractometry has demonstrated the ability to assess gas pressure with high accuracy and has been prophesized to be able to realize the SI unit for pressure, the pascal, based on quantum calculations of the molar polarizabilities of gases. So far, the technology has mostly been limited to well-controlled laboratories. However, recently, an easy-to-use transportable refractometer has been constructed. Although its performance has previously been assessed under well-controlled laboratory conditions, to assess its ability to serve as an actually transportable system, a ring-type comparison addressing various well-characterized pressure balances in the 10-90 kPa range at several European national metrology institutes is presented in this work. It was found that the transportable refractometer is capable of being transported and swiftly set up to be operational with retained performance in a variety of environments. The system could also verify that the pressure balances used within the ring-type comparison agree with each other. These results constitute an important step toward broadening the application areas of FP-based refractometry technology and bringing it within reach of various types of stakeholders, not least within industry.
ABSTRACT
BACKGROUND: Sport-for-All emphasizes that every individual has the right to participate in sport. Despite all efforts to deliver Sport-for-All during the past decades, studies indicate that sport participation rates have been stagnating, whereas social inequalities in sport continue to exist. By applying an institutional theory lens, this study sheds light on how the dual mission of sport federations, i.e., providing Sport-for-All and high performance sport, affects the Sport-for-All projects of Flemish sport federations (e.g., amount of projects and target groups). In particular, Sport-for-All projects have to reduce barriers to engage in the sport system and be supported by a sport federation. Furthermore, this study seeks to better understand the impact of the underlying institutional logic on the institutional pressure and legitimacy of the sport federations. METHOD: This study implemented a cross-sectional field study in sport federations. In particular, the sport federations selected for our study are the 47 Flemish sport federations. Both qualitative (i.e., document analysis) and quantitative research methods (i.e., a new questionnaire was developed based on institutional theory) were applied in the study. RESULTS: Results indicated that sport federations are important partners in support of Sport-for-All projects, but also suggested that there is a discrepancy between the projects of the high performance-oriented and the Sport-for-All-oriented federations. Specifically, the high performance-oriented federations were targeting youth participants, whereas Sport-for-all-oriented federations aimed to reach disadvantaged groups. Furthermore, the results indicated that high performance-oriented federations endured more institutional pressure than Sport-for-All-oriented federations. CONCLUSION: The results of our study indicated that the Sport-for-All projects of performance-oriented federations are often more superficial compared to Sport-for-All oriented federations, and that the latter federations play an important role in attaining public health targets. Moreover, policymakers should consider how they can optimize the role of the performance-oriented federations in the Sport-for-All delivery (e.g., they could function as a bridge to guide participants who prefer a less competitive setting towards Sport-for-All oriented federations).
Subject(s)
Awards and Prizes , Sports , Adolescent , Cross-Sectional Studies , Goals , Humans , Vulnerable PopulationsABSTRACT
BACKGROUND: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both - HT and PS - to provide further evidence for a recovery-oriented treatment of psychiatric patients. METHODS: In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. DISCUSSION: This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients' recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.
Subject(s)
Mental Disorders , Mental Health , Counseling/methods , Humans , Mental Disorders/psychology , Mental Disorders/therapy , Personal Satisfaction , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated HCCs. Here we present an integrated proteogenomic analysis of HCCs across clinical stages and etiologies. Pathways related to cell cycle, transcriptional and translational control, signaling transduction, and metabolism are dysregulated and differentially regulated on the genomic, transcriptomic, proteomic and phosphoproteomic levels. We describe candidate copy number-driven driver genes involved in epithelial-to-mesenchymal transition, the Wnt-ß-catenin, AKT/mTOR and Notch pathways, cell cycle and DNA damage regulation. The targetable aurora kinase A and CDKs are upregulated. CTNNB1 and TP53 mutations are associated with altered protein phosphorylation related to actin filament organization and lipid metabolism, respectively. Integrative proteogenomic clusters show that HCC constitutes heterogeneous subgroups with distinct regulation of biological processes, metabolic reprogramming and kinase activation. Our study provides a comprehensive overview of the proteomic and phophoproteomic landscapes of HCCs, revealing the major pathways altered in the (phospho)proteome.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Proteogenomics , Carcinoma, Hepatocellular/metabolism , Humans , Liver Neoplasms/metabolism , Mutation , Proteomics , beta Catenin/metabolismABSTRACT
Fear of being stigmatized by others, self-stigmatization, and inadequate information can limit those affected by suicidality from seeking help. Emental-health interventions provide a low-threshold way to reach many individuals with information about the topic. This enables those affected to prepare themselves for personal offers of help. As part of the funding priority "Suicide Prevention (A: Destigmatization)" of the German Federal Ministry of Health, a complex intervention was developed at the University Medical Center Hamburg-Eppendorf. The development and content of this online intervention are described in this article.Following a representative telephone survey of the German general population, which investigated gaps in knowledge and stigmatization tendencies on the subject of suicide, the online intervention "8 lives - lived experience reports and facts on suicide" was developed on the basis of an Australian suicide prevention project and involved persons with a lived experience of suicide. The intervention highlighted both scientific and clinical facts about suicidality as well as a socio-cultural perspective and offered self-help options and professional support services. Video reports of persons with a lived experience of suicide were shown within the intervention. The project is currently being evaluated. A continuation is planned.The intervention is a multi-layered offer in which different perspectives on the topic of suicidality are presented. Participants are addressed on a cognitive and emotional level. Given the prevalence of suicidality and the fact that the subject is still taboo, serious, evidence-based, and low-threshold prevention and information offers seem particularly relevant.
Subject(s)
Internet-Based Intervention , Suicide Prevention , Australia , Germany , Humans , Suicidal IdeationABSTRACT
This paper addresses issues currently present in the aircraft cabin design process. It focuses on making the design process more time and cost efficient, while altogether involving the end-users (passengers and cabin crew) in the development process in its earliest stages. By understanding the underlying issues and reasons the cabin is developed according to the current approach, new methods are established and adapted to suit the needs of such a complex process. In this paper, the preposition is made that Virtual Reality is the key technology for achieving the following goals: shortening the initial cabin design process (from sketch to concept design) and including the end-users and their wishes and ideas into the ideation phase. Through cooperation with an external design agency, a Virtual Reality tool is implemented and tested to ensure the theory behind the established design methodology can also be put into practice.
ABSTRACT
Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.
Subject(s)
Hydrogels , Sulfhydryl Compounds , Animals , Cattle , Ether , Gastric Mucins , Hydrogels/chemistry , Polymers , Sulfhydryl Compounds/chemistry , SwineABSTRACT
The German concept of a trialogue in medicine is at its best a cooperation between patients, relatives, and professionals as partners on equal footing. Prerequisites, and also the aim of the trialogue, are mutual respect, an open attitude from professionals, and self-confidence from patients and relatives. The expertise of each of these groups is to be strengthened through the trialogue and should benefit all. Trialogue cooperation brings about a change of perspective and promotes mutual understanding. By establishing a therapeutic relationship on equal footing with the patient with involvement of their relatives, individual and family resources can be better utilized, professional assistance can be designed to better meet the patient's needs, and acceptance of and commitment to treatment can be increased. In addition, early symptoms and new phases of the disease can be recognized earlier and adequate treatment can be initiated more quickly. A favorable course of the disease is thus more likely, and relapses are less likely to present. The use of peers has proven to be quite helpful. The consistently trialogue structure within the German Society for Bipolar Disorder (Deutsche Gesellschaft für Bipolare Störungen e.V./DGBS: Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main) as a medical society enables further development of the trialogue on many levels, for example, the drafting and updating of the German guidelines for bipolar disorder with the trialogue in mind.
Subject(s)
Bipolar Disorder , Bipolar Disorder/drug therapy , Germany , Humans , Societies, MedicalABSTRACT
Hyaluronic acid (HA)-based hydrogels are very commonly applied as cell carriers for different approaches in regenerative medicine. HA itself is a well-studied biomolecule that originates from the physiological extracellular matrix (ECM) of mammalians and, due to its acidic polysaccharide structure, offers many different possibilities for suitable chemical modifications which are necessary to control, for example, network formation. Most of these chemical modifications are performed using the free acid function of the polymer and, additionally, lead to an undesirable breakdown of the biopolymer's backbone. An alternative modification of the vicinal diol of the glucuronic acid is oxidation with sodium periodate to generate dialdehydes via a ring opening mechanism that can subsequently be further modified or crosslinked via Schiff base chemistry. Since this oxidation causes a structural destruction of the polysaccharide backbone, it was our intention to study a novel synthesis protocol frequently applied to selectively oxidize the C6 hydroxyl group of saccharides. On the basis of this TEMPO/TCC oxidation, we studied an alternative hydrogel platform based on oxidized HA crosslinked using adipic acid dihydrazide as the crosslinker.
Subject(s)
Cyclic N-Oxides/chemistry , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Mesenchymal Stem Cells/cytology , Adipates/chemistry , Cell Differentiation , Cell Survival , Chondrogenesis , Cross-Linking Reagents/chemistry , Elastic Modulus , Humans , Hyaluronan Receptors/metabolism , Hyaluronic Acid/metabolism , Oxidation-Reduction , Schiff Bases/chemistry , Surface Plasmon ResonanceABSTRACT
BACKGROUND: Fear of stigmatization, self-stigmatization, and insufficient information can lead to secrecy, reduced help-seeking, lower self-esteem, and lower self-efficacy among people affected by suicidality or suicide. Therefore, we developed an online suicide prevention program aiming to improve knowledge about suicidality and suicide stigma. METHODS: Inspired by the Australian program The Ripple Effect, a German team comprising people with lived experience of suicide, researchers, and clinicians was established for developing an online suicide prevention program. Therefore, we oriented on guidelines for evidence-based health information, for reporting on suicide, and on dealing with suicidality. The lived experience team discussed and developed concept, structure, and content of the program. This manuscript presents summaries of protocols from 16 team meetings and 3 written text reviews to outline the program development process. A summative evaluation 3 years after program development began was qualitatively analyzed based on thematic analysis. RESULTS: Between 2018 und 2021, the lived experience team (n = 10) discussed possibilities of support in suicidal crises, attitudes towards suicide, content, and design of the online program. In a structured process, six members of the lived experience team reviewed the content. Eight persons shared their lived experience of suicide in video reports by focusing on constructive ways of dealing with suicidality or a loss by suicide, conveying hope and encouraging people to continue living. Team members recommended greater public and patient involvement from the application stage, as well as more financial and personnel resources. CONCLUSIONS: Through contributions to discussions and text reviews, the lived experience team shaped decisions in the program development process. While involving persons with lived experiences of suicide, it is important to consider that suicidality is 1. emotionally challenging, 2. a stigmatized issue, and 3. that the aspect of safety must be a priority. A distinction must be made between the duty of care based on actual risk and inappropriate overprotection. Hereby, transparency, autonomy, and a clear structure appeared to be helpful. For further research, we recommend a structured formative review process of the development of the program. Additionally, we recommend discussing the purpose and the specific design of the evaluation with a lived experience team in advance. Trial registration German Clinical Trial RegisterDRKS00015071 on August 6, 2018.
A team of persons with a lived experience of suicide and researchers jointly developed an online suicide prevention program. This online program addresses the taboo and stigmatized topic of suicidality from the perspective of people with lived experience. In our team are people who tried to take their own lives, thought about suicide, and people who lost a close person by suicide. For the program we wrote texts on suicidality and suicide on a scientific basis. In videos the team shared their experiences with suicide. The team told what helped them to continue living and gave them hope. Online program participants can read these texts and watch these videos. Participants can learn about suicidality and are encouraged to seek help if needed.During the development of the program, the researchers created a working atmosphere characterized by respect, empathy, transparency, and openness. Dealing with suicidality can be emotionally stressful. The team felt comfortable and safe. The team was proud of the developed online program.We describe strengths and weaknesses of the program development. We did not evaluate the involvement during the program development. If one wants to do this, the purpose should be explained to the team. The team should have a say in the design, such as what questions are asked.Our program gained enormously from involvement of people with a lived experience of suicide. Involvement is possible and necessary even with complex and sensitive topics such as suicidality. Antistigma work should involve those affected. Involvement is important to create a credible program.