Public Continuum Beliefs for Different Levels of Depression Severity

Introduction: The notion that depression is a disorder that moves along a continuum is well-established. Similarly, the belief in the continuity of mental illness is considered an important element in the stigma process. Against this background, it is the aim of this study to examine whether public continuum beliefs vary with the severity of depressive symptoms. Methods: Analyses were based on computer-assisted telephone interviews (CATIs) conducted in winter 2019/2020 in Germany (N = 1,009, response rate 46.8%). Using three vignettes representing mild, moderate, and severe depressive symptoms, beliefs regarding the continuity of symptoms, specifically a fundamental difference, were assessed with seven items. Sociodemographic characteristics and own experiences with depression (affliction and contact) were introduced as covariates. Results: Significant differences between the three groups of severity were found for the majority of the items measuring continuum beliefs or perceived fundamental difference. However, only few items showed a linear trend indicating a parallel between symptom severity and beliefs. Multivariate regression models showed that a moderate degree of depression was positively associated with stronger continuum beliefs but also with greater perceived difference compared to the mild degree, while no significant associations emerged for the severe vignette. Limitations: Although a comparison of our sample with official statistics supports the external validity, we cannot rule out a selection bias. It is arguable in how far short case vignettes convey a holistic picture of a person affected by depressive symptoms. Conclusion: Our results do not indicate a parallel between symptom severity and public continuum beliefs

Public Continuum Beliefs for Different Levels of Depression Severity

Introduction: The notion that depression is a disorder that moves along a continuum is well-established. Similarly, the belief in the continuity of mental illness is considered an important element in the stigma process. Against this background, it is the aim of this study to examine whether public continuum beliefs vary with the severity of depressive symptoms.Methods: Analyses were based on computer-assisted telephone interviews (CATIs) conducted in winter 2019/2020 in Germany (N = 1,009, response rate 46.8%). Using three vignettes representing mild, moderate, and severe depressive symptoms, beliefs regarding the continuity of symptoms, specifically a fundamental difference, were assessed with seven items. Sociodemographic characteristics and own experiences with depression (affliction and contact) were introduced as covariates.Results: Significant differences between the three groups of severity were found for the majority of the items measuring continuum beliefs or perceived fundamental difference. However, only few items showed a linear trend indicating a parallel between symptom severity and beliefs. Multivariate regression models showed that a moderate degree of depression was positively associated with stronger continuum beliefs but also with greater perceived difference compared to the mild degree, while no significant associations emerged for the severe vignette.Limitations: Although a comparison of our sample with official statistics supports the external validity, we cannot rule out a selection bias. It is arguable in how far short case vignettes convey a holistic picture of a person affected by depressive symptoms.Conclusion: Our results do not indicate a parallel between symptom severity and public continuum beliefs

Public Beliefs About Somatic Symptom Disorders

Objectives: Despite satisfactory effectiveness of treatment for somatic symptom disorders (SSD), treatment rates are low and treatment is usually initiated many years after first symptoms. In order to understand whether a lack of public mental health literacy might contribute to these poor treatment rates, we aimed to focus on two research questions: (1) What does the German public know and think about SSD? (2) Are knowledge and beliefs associated with socio-demographic factors and experiences with the disorder?Methods: Two vignettes with symptoms of a SSD were used in a national telephone survey in Germany (N = 1,004). Vignettes differed regarding main type of symptom (pain vs. fatigue) and existence of an earlier somatic disease (yes vs. no). Respondents were asked concerning knowledge and beliefs about causes, symptoms, and treatment using a standardized questionnaire.Results: 66% of the respondents agreed that a possible cause of the symptoms is a misinterpretation of body signals. About 1/3 recognized a mental health problem when confronted with the vignettes of cases with SSD. This rate was lower in case of a SSD with pain as the main symptom without a comorbid somatic disease (24.8%, 95%-CI: 21.1–28.6) compared to a case with fatigue as the main symptom and an earlier severe somatic disease (44.0%, 95%-CI: 39.6–48.3). Female respondents tended to have a more positive view on treatability and effectiveness of psychotherapy, while associations of knowledge and beliefs with education and age were inconsistent. Respondents who had contact with a person with SSD were more likely to think that psychotherapy is effective and that they know a lot about SSD compared to those who never had contact.Conclusions: While most of the German public seems to be well informed about causes of SSD as well as treatability and the effectiveness of psychotherapy, the majority has problems with interpreting symptoms and does not think they know a lot about symptoms like that. Increasing knowledge about SSD by education interventions may help to promote adequate help seeking

Comparison of diagnostic value of 68 Ga-DOTATOC PET/MRI and standalone MRI for the detection of intracranial meningiomas

To evaluate the diagnostic performance of magnetic resonance imaging (MRI) alone in comparison to positron emission tomography/ magnetic resonance imaging (PET/MRI) in patients with meningiomas. 57 patients with a total of 112 meningiomas of the brain were included. PET/MRI, including a fully diagnostic contrast enhanced MRI and PET, were acquired. PET/MRI was used as reference standard. The size and location of meningiomas was recorded. Likelihood-ratio chi-square tests were used to calculate p-values within logistic regression in order to compare different models. A multi-level logistic regression was applied to comply the hierarchical data structure. Multi-level regression adjusts for clustering in data was performed. The majority (n=103) of meningiomas could be identified based on standard MRI sequences compared to PET/MRI. MRI alone achieved a sensitivity of 95% (95% CI 0.78, 0.99) and specificity of 88% (95% CI 0.58, 0.98). Based on intensity of contrast medium uptake, 97 meningiomas could be diagnosed with intense uptake (93.75%). Sensitivity was lowest with 74% for meningiomas2cm(3) and highest with 100% for meningiomas 0.5-1.0 cm(3). Petroclival meningiomas showed lowest sensitivity with 88% compared to sphenoidal meningiomas with 94% and orbital meningiomas with 100%. Specificity of meningioma diagnostic with MRI was high with 100% for sphenoidal and hemispherical-dural meningiomas and meningiomas with 0.5-1.0 and 1.0-2.0 cm(3). Overall MRI enables reliable detection of meningiomas compared to PET/MRI. PET/MRI imaging offers highest sensitivity and specificity for small or difficult located meningiomas

The Expression of a Xylanase Targeted to ER-Protein Bodies Provides a Simple Strategy to Produce Active Insoluble Enzyme Polymers in Tobacco Plants

Background Xylanases deserve particular attention due to their potential application in the feed, pulp bleaching and paper industries. We have developed here an efficient system for the production of an active xylanase in tobacco plants fused to a proline-rich domain (Zera) of the maize storage protein γ-zein. Zera is a self-assembling domain able to form protein aggregates in vivo packed in newly formed endoplasmic reticulum-derived organelles known as protein bodies (PBs). Methodology/Principal Findings Tobacco leaves were transiently transformed with a binary vector containing the Zera-xylanase coding region, which was optimized for plant expression, under the control of the 35S CaMV promoter. The fusion protein was efficiently expressed and stored in dense PBs, resulting in yields of up to 9% of total protein. Zera-xylanase was post-translationally modified with high-mannose-type glycans. Xylanase fused to Zera was biologically active not only when solubilized from PBs but also in its insoluble form. The resistance of insoluble Zera-xylanase to trypsin digestion demonstrated that the correct folding of xylanase in PBs was not impaired by Zera oligomerization. The activity of insoluble Zera-xylanase was enhanced when substrate accessibility was facilitated by physical treatments such as ultrasound. Moreover, we found that the thermostability of the enzyme was improved when Zera was fused to the C-terminus of xylanase. Conclusion/Significance In the present work we have successfully produced an active insoluble aggregate of xylanase fused to Zera in plants. Zera-xylanase chimeric protein accumulates within ER-derived protein bodies as active aggregates that can easily be recovered by a simple density-based downstream process. The production of insoluble active Zera-xylanase protein in tobacco outlines the potential of Zera as a fusion partner for producing enzymes of biotechnological relevance. Zera-PBs could thus become efficient and low-cost bioreactors for industrial purposes.This work was mainly supported by ERA Biotech (www.erabiotech.com). Additional support was supplied by grant SGR 2009/703 funded by the Generalitat de Catalunya (www10.gencat.net) and grants CDS2007/00036 of Consolider Ingenio program and TRA 2009/0124 of TRACE program funded by Ministerio de Ciencia e Inovación (MICINN, www.micinn.es). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Depression stigma and migration – results of a survey from Germany

Abstract Background There are barely any studies focusing on migration in relation to mental illness stigma. We explore present attitudes regarding depression among migrants (either born in Germany or born abroad) and non-migrants in Germany, drawing upon three components of public stigma: stereotypes, emotional reactions and desire for social distance. Furthermore, differences in self-stigma of depression between the two groups are analyzed. Methods Analyses are based on a representative telephone survey (N = 2013) in Germany. Respondents were presented with a vignette depicting either someone from Turkey or from Germany affected by depression, followed by questions on stereotypes, emotional reactions and desire for social distance. The (anticipated) self-stigma of depression was also assessed. Analyses of variance tested for differences between migrant and non-migrant respondents, stratified by migrant status in the vignette. Results Regarding the depression vignette depicting a non-migrant, there were only few differences between subgroups. However, when presented with a vignette describing someone from Turkey, respondents with migrant background who were foreign-born expressed greater stigmatizing attitudes, e.g. when it comes to stereotypes or desire for social distance. Furthermore, this subsample displayed higher levels of self-stigma of depression, especially regarding the ascription of own responsibility. Conclusions The results underline the need to incorporate migration status/ethnicity in stigma research. Differences in attitudes as well as in (anticipated) self-stigma of depression identify foreign-born migrants in Germany as important target groups for tailored anti-stigma interventions, which need to consider diverse cultural backgrounds