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The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis. Expected final online publication date for the Annual Review of Biochemistry, Volume 92 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Emotional bias in explicit memory is theorized to play a prominent role in the etiology, maintenance, and recurrence of depression. Even though this cognitive bias is regarded as one of the most robust phenomena in depression, its magnitude and boundary conditions in depression are currently unknown. This review presents two three-level meta-analyses to estimate the overall effect size and identify moderators of explicit memory bias in depression. Meta-analysis I (153 studies, 686 contrasts) revealed a small overall effect size for naturalistic explicit memory bias in depression (g=0.241, 95% CI [0.179, 0.304]). The magnitude of the overall effect was moderated by emotional valence of stimuli, operational definition of memory bias, depth of processing during encoding, explicit memory task, and the (non-)verbal nature of stimuli. Equivalent effect sizes were found for minors and adults as well as for clinical and subclinical depression. Remarkably, a non-significant effect size emerged for remitted depression. Following up on the latter finding, meta-analysis II (21 studies, 80 contrasts) examined explicit memory bias in remitted depression under naturalistic conditions and under mood/stress induction. Results yielded a nonsignificant overall effect size, g=0.131, 95% CI [-0.045, 0.307], but a significant effect size for study conditions with mood or stress induction, g=0.273, 95% CI [0.004, 0.542]. Both meta-analyses indicated high levels of heterogeneity, even after accounting for variation explained by sample and study characteristics. The findings are consistent with the view that depression is characterized by an explicit memory bias that may persist beyond a depressive episode. These findings have implications for cognitive theories of vulnerability to depression as well as clinical interventions.

Cryogenic environments benefit ion trapping experiments by offering lower motional heating rates, collision energies, and an ultrahigh vacuum (UHV) environment for maintaining long ion chains for extended periods of time. Mechanical vibrations caused by compressors in closed-cycle cryostats can introduce relative motion between the ion and the wavefronts of lasers used to manipulate the ions. Here, we present a novel ion trapping system where a commercial low-vibration closed-cycle cryostat is used in a custom monolithic enclosure. We measure mechanical vibrations of the sample stage using an optical interferometer, and observe a root-mean-square relative displacement of 2.4 nm and a peak-to-peak displacement of 17 nm between free-space beams and the trapping location. We packaged a surface ion trap in a cryopackage assembly that enables easy handling while creating a UHV environment for the ions. The trap cryopackage contains activated carbon getter material for enhanced sorption pumping near the trapping location, and source material for ablation loading. Using $^{171}$Yb$^{+}$ as our ion, we estimate the operating pressure of the trap as a function of package temperature using phase transitions of zig-zag ion chains as a probe. We measured the radial mode heating rate of a single ion to be 13 quanta/s on average. The Ramsey coherence measurements yield 330-ms coherence time for counter-propagating Raman carrier transitions using a 355-nm mode-locked pulse laser, demonstrating the high optical stability.

Objectives: Depression and ADHD often co-occur and are both characterized by altered attentional processing. Differences and overlap in the profile of attention to emotional information may help explain the co-occurence. We examined negative attention bias in ADHD as neurocognitive marker for comorbid depression. Methods: Patients with depression ( n = 63), ADHD ( n = 43), ADHD and depression ( n = 25), and non-psychiatric controls ( n = 68) were compared on attention allocation toward emotional faces. The following eye-tracking indices were used: gaze duration, number of revisits, and location and duration of first fixation. Results: Controls revisited the happy faces more than the other facial expressions. Both the depression and the comorbid group showed significantly less revisits of the happy faces compared to the ADHD and the control group. Interestingly, after controlling for depressive symptoms, the groups no longer differed on the number of revisits. Conclusion: ADHD patients show a relative positive attention bias, while negative attention bias in ADHD likely indicates (sub)clinical comorbid depression.

Enhanced memory for emotional events is a well-known phenomenon and associative networks can be formed to build so-called emotional schemas that will facilitate subsequent processing of information congruent with this schema (van Kesteren et al., 2012; Gilboa & Marlatte, 2017). Emotional memory can be further enhanced by congruency between mood at the time of learning and valence of the emotional information (Faul & LaBar, 2022). A lack of positive emotional memory contributes to depression (Dillon & Pizzagalli, 2019). While this concept has mainly been used to understand the negative processing in affective disorders, activation of positive schemas and subsequent enhancement of learning of positive information can also form an effective mental prevention method. Non-invasive brain stimulation in the form of transcranial direct current stimulation (tDCS) has been shown to alter brain oscillations thereby improving neurocognitive capacity (Ciullo et al., 2020). Combination of tDCS with positive schema activation may further enhance positive emotional memory. We aim to investigate the association of positive schema activation with different operationalizations of emotional schema memory, and whether tDSC during positive schema activation can facilitate retrieval of emotional memory for positive information in dysphoric individuals.

Depression is characterized by a cognitive bias toward negative memory recall (Beck, 1969; Kircanski et al., 2012; LeMoult & Gotlib, 2019). This cognitive bias may last beyond depressive episodes and indicates a risk of relapse in those who are in remission (Everaert et al., 2022; Ingram, 1984; Ronold et al., 2020). While earlier studies have primarily concentrated on negative memory bias (MB) in depression (Beck, 1969; Duyser et al., 2020; Hertel, 2004; Kircanski et al., 2012), less attention has been given to positive MB formation. Recent studies suggest that the absence of positive MB may be a crucial factor distinguishing depressed and never-depressed individuals (Askelund et al., 2019; Everaert et al., 2022; Gaddy & Ingram, 2014), making it a potential target for novel treatment approaches. Worth noting, however, is that research on the prevalence of MB in those remitted from depression has produced inconsistent results (Everaert et al., 2022; Hallford et al., 2022; Romero et al., 2014).This may occur because previous research on MB has primarily been conducted in laboratory settings (Lin et al., 2021; Ridout et al., 2003; Zupan et al., 2017), neglecting the impact of daily-life stressors and context on MB processes. Indeed, contextual factors have been shown to play an important role in this (Vrijsen et al., 2021). Incorporating daily-life context such as stressors in the research design may clarify the presence or absence of MB in this population, as daily-life processes may serve to activate latent depressogenic schemas (Everaert et al., 2022; Fritzsche et al., 2010; Kircanski et al., 2012; Rude et al., 2001; Timbremont & Braet, 2004). Daily life fluctuations in MB under changing contexts can be investigated using ecological momentary assessments (EMA). EMA involves conducting multiple assessments per day during the participant's daily life, providing a more ecologically valid approach to examining MB (Csikszentmihalyi & Larson, 1987). Assessing memory bias and depressotypic negative affect through EMA also allows for the examination of temporaneous and contemporaneous effects, including emotional inertia, which may affect cognitive emotional processing (Brose et al., 2015; Kuppens et al., 2010) . The aim for this pre-registration is to investigate memory bias (MB) in depression in a contextually dependent manner using data from the MEDAL study (Vrijsen et al., 2021). In the MEDAL study, never depressed, depressed, and remitted participants were followed in daily life using EMA questions probing affect, memory bias, and stress. Data will be analyzed to investigate how these dynamics play out in real-life settings.

Contains fulltext : 292768.pdf (Publisher’s version ) (Open Access) Background: Mindfulness-based cognitive therapy (MBCT) is an evidence-based treatment for depression. The current study focused on the long-term effects of MBCT for chronically, treatment-resistant depressed patients during a 6-months follow-up period. Additionally, predictors of treatment outcomes were explored. Method: The outcomes of MBCT on depressive symptoms, remission rates, quality of life, rumination, mindfulness skills and self-compassion were investigated in a cohort of chronically, treatment-resistant depressed outpatients (N = 106), who had taken part in an RCT comparing MBCT with treatment-as-usual (TAU). Measures were assessed pre-MBCT, post-MBCT, at 3-months follow-up, and at 6-months follow-up. Results: Results of linear mixed effect models and Bayesian repeated measures ANOVA's reveal that depressive symptoms, quality of life, rumination, mindfulness skills and self-compassion consolidated during follow-up. Remission rates even further increased over the course of follow-up. When controlling for symptoms at baseline, higher baseline levels of rumination predicted lower depressive symptoms and quality of life at 6-month follow-up. No other predictors (i.e. duration of current depressive episode, level of treatment-resistance, childhood trauma, mindfulness skills, self-compassion) were found. Limitations All participants received MBCT, therefore time or other non-specific effects might have influenced the results and replication in studies including a control condition is needed. Conclusions :Results indicate that the clinical benefits of MBCT for chronically, treatment-resistant depressed patients persist up to 6 months after completing MBCT. Duration of the current episode, level of treatment-resistance, childhood trauma and baseline levels of mindfulness skills and self-compassion did not predict treatment outcome. When controlling for baseline depressive symptoms participants with high levels of rumination seem to benefit more; however more research is needed. Trial Registry: Dutch Trial Registry, number NTR4843. 8 p.

Depression, anxiety, burnout, and other stress-related illnesses are becoming a major cause of disability globally. However, current treatments, including pharmacology and psychotherapy, show high resistance and relapse rates. A transdiagnostic approach that targets underlying mechanisms may provide better results than current treatments. One potential avenue that fits a transdiagnostic approach is exercise as a mood boosting treatment, which can serve as a low-cost and easily accessible tool in treating and preventing mental illness. Exercise has been shown to boost mood, and alleviate symptoms of depression and anxiety, though the mechanisms of how this happens are not well understood. One theory is that exercise acts to modify emotional memory processing, which is often disrupted in psychiatric illness. Laboratory results have shown some support for this argument, yet results from the lab remain mixed, higlhighitng a need to expand research into real-life settings. In addition to understanding the cognitive mechanisms, the neural pathways that are involved in this process are also not well understood. The relationship between exercise and mood and memory may be due to increased neural plasticity, as increased levels of brain-derived neurotrophic factors (BDNF) are often reported following exercise, which are linked to plasticity in the hippocampus. The hippocampus is a central episodic memory hubs, with connections to the default mode network (DMN). The DMN is involved in autobiographical memory and disruptions in this network are reported in a wide range of psychiatric illnesses. By stimulating neural plasticity in the hippocampus through exercise, it may lead to changes in DMN connectivity and alter emotional memory, thereby elevating mood. However, this overarching model encompassing the lab and real-life, as well as examining these processes involved, have yet to be investigated thoroughly.

Contains fulltext : 292378.pdf (Publisher’s version ) (Open Access) BACKGROUND: Heterogeneity and comorbidity in psychiatric disorders are common, however, little is known about the impact on well-being and the role of functional limitations. We aimed to identify transdiagnostic psychiatric symptom profiles and to study their association with well-being and the mediating role of functional limitations in a naturalistic psychiatric patient group. METHODS: We used four disorder-specific questionnaires to assess symptom severity within a sample of 448 psychiatric patients with stress-related and/or neurodevelopmental disorders and 101 healthy controls. Using both exploratory and confirmatory factor analyses we identified transdiagnostic symptom profiles, which we entered into a linear regression analysis to assess their association with well-being and the mediating role of functional limitations in this association. RESULTS: We identified eight transdiagnostic symptom profiles, covering mood, self-image, anxiety, agitation, empathy, non-social interest, hyperactivity and cognitive focus. Mood and self-image showed the strongest association with well-being in both patients and controls, while self-image also showed the highest transdiagnostic value. Functional limitations were significantly associated with well-being and fully mediated the relationship between cognitive focus and well-being. LIMITATIONS: The participant sample consisted of a naturalistic group of out-patients. While this strengthens the ecological validity and transdiagnostic perspective of this study, the patients with a single neurodevelopmental disorder were underrepresented. CONCLUSION: Transdiagnostic symptom profiles are valuable in understanding what reduces well-being in psychiatric populations, thereby opening new avenues for functionally meaningful interventions. 10 p.

Background A longer emergency department length of stay (EDLOS) is associated with poor outcomes. Shortening EDLOS is difficult, due to its multifactorial nature. A potential way to improve EDLOS is through shorter turnaround times for diagnostic testing. This study aimed to investigate whether a shorter laboratory turnaround time (TAT) and time to testing (TTT) were associated with a shorter EDLOS. Methods A retrospective cohort study was performed, including all visits to the emergency department (ED) of an academic teaching hospital from 2017 to 2020 during which a standardized panel of laboratory tests had been ordered. TTT was calculated as the time from arrival in the ED to the ordering of laboratory testing. TAT was calculated as the time from test ordering to the reporting of the results, and was divided into a clinical and a laboratory stage. The outcome was EDLOS in minutes. The effect of TTT and TAT on EDLOS was estimated through a linear regression model. Results In total, 23,718 ED visits were included in the analysis. Median EDLOS was 199.0 minutes (interquartile range [IQR] 146.0–268.0). Median TTT was 7.0 minutes (IQR 2.0–12.0) and median TAT was 51.1 minutes (IQR 41.1–65.0). Both TTT and TAT were positively associated with EDLOS. The laboratory stage comprised a median of 69% (IQR 59–78%) of total TAT. Conclusion Longer TTT and TAT are independently associated with longer EDLOS. As the laboratory stage predominantly determines TAT, it provides a promising target for interventions to reduce EDLOS and ED crowding.

A large research project aiming to assess severeal research questions, regarding the interplay of Covid-19 related stress, anxiety and depressive symptoms.

BackgroundThe benefits of peer support interventions (PSIs) for individuals with mental illness are not well known. The aim of this systematic review and meta-analysis was to assess the effectiveness of PSIs for individuals with mental illness for clinical, personal, and functional recovery outcomes.MethodsSearches were conducted in PubMed, Embase, and PsycINFO (December 18, 2020). Included were randomized controlled trials (RCTs) comparing peer-delivered PSIs to control conditions. The quality of records was assessed using the Cochrane Collaboration Risk of Bias tool. Data were pooled for each outcome, using random-effects models.ResultsAfter screening 3455 records, 30 RCTs were included in the systematic review and 28 were meta-analyzed (4152 individuals). Compared to control conditions, peer support was associated with small but significant post-test effect sizes forclinical recovery,g= 0.19, 95% CI (0.11–0.27),I2= 10%, 95% CI (0–44), andpersonal recovery, g= 0.15, 95% CI (0.04–0.27),I2= 43%, 95% CI (1–67), but not forfunctional recovery,g= 0.08, 95% CI (−0.02 to 0.18),I2= 36%, 95% CI (0–61). Our findings should be considered with caution due to the modest quality of the included studies.ConclusionsPSIs may be effective for the clinical and personal recovery of mental illness. Effects are modest, though consistent, suggesting potential efficacy for PSI across a wide range of mental disorders and intervention types.

A longer emergency department length of stay (EDLOS) is associated with poor outcomes. Shortening EDLOS is difficult, due to its multifactorial nature. A potential way to improve EDLOS is through shorter turnaround times for diagnostic testing. This study aimed to investigate whether a shorter laboratory turnaround time (TAT) and time to testing (TTT) were associated with a shorter EDLOS.A retrospective cohort study was performed, including all visits to the emergency department (ED) of an academic teaching hospital from 2017 to 2020 during which a standardized panel of laboratory tests had been ordered. TTT was calculated as the time from arrival in the ED to the ordering of laboratory testing. TAT was calculated as the time from test ordering to the reporting of the results, and was divided into a clinical and a laboratory stage. The outcome was EDLOS in minutes. The effect of TTT and TAT on EDLOS was estimated through a linear regression model.In total, 23,718 ED visits were included in the analysis. Median EDLOS was 199.0 minutes (interquartile range [IQR] 146.0-268.0). Median TTT was 7.0 minutes (IQR 2.0-12.0) and median TAT was 51.1 minutes (IQR 41.1-65.0). Both TTT and TAT were positively associated with EDLOS. The laboratory stage comprised a median of 69% (IQR 59-78%) of total TAT.Longer TTT and TAT are independently associated with longer EDLOS. As the laboratory stage predominantly determines TAT, it provides a promising target for interventions to reduce EDLOS and ED crowding.

ObjectiveTo uncover transdiagnostic domains of functioning across stress- and neurodevelopmental disorders, and to map these on to the topographic functional organization of cortico-striatal circuitry.MethodsIn a clinical sample (n=186) of subjects with high rates of comorbidity of major depressive disorder, anxiety disorder, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, we use exploratory factor analysis on a wide range of clinical questionnaires to identify consistent functional domains of symptomatology across disorders, then replicate these functional domains in an independent dataset (n=188). Then, we use canonical correlation analysis link these functional domains to the topographic organization of the striatum as represented by connectopic maps.ResultsWe reveal four functional domains that transcend current diagnostic categories relating to negative valence, cognition, social functioning and inhibition/arousal. These functional domains are replicated in an independent sample and are associated with the fine-grained topographical organization of functional connectivity in the striatum (out of sample r=0.20, p=0.026), a central hub in motor, cognitive, affective and reward-related brain circuits.Conclusions and relevanceFunctional domains across stress- and neurodevelopmental disorders are associated with the functional organization of the striatum. We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

Key summary points Aim To retrospectively analyse data obtained from the multi-domain assessment of hospitalized COVID-19 patients, to describe their health status at discharge, and to investigate whether subgroups of patients, more specific ICU patients and older adults (> 70 years), had more (or less) risk to experience specific impairments. Findings The results of the assessment show that physical, functional, cognitive, nutritional, and psychological impairments are highly prevalent in the group of COVID-19 patients, both in ICU and non-ICU patients, adults and older adults. Message The high prevalence of physical, cognitive, psychological, and functional impairments in hospitalized COVID-19 patients, both ICU and non-ICU patients, indicates that assessment of impairments is imperative., Objective To retrospectively analyse data obtained from the multi-domain assessment of hospitalized COVID-19 patients, to describe their health status at discharge, and to investigate whether subgroups of patients, more specific ICU patients and older adults (> 70 years), had more (or less) risk to experience specific impairments. Methods Retrospective case series in the University Hospitals Leuven, Belgium of confirmed COVID-19 patients ‘after surviving an ICU-stay’, ‘aged ≥ 70 years’, or ‘aged 7 days’. Exclusion criteria were ‘unwilling to cooperate’, ‘medically unstable’, or ‘palliative care policy’. Following tests were used: ‘Five Times Sit To Stand Test’, ‘hand grip dynamometry’, ‘Barthel index’, ‘Swallowing screening’, ‘Montreal Cognitive Assessment’, ‘Hospital Anxiety and Depression Scale’, and ‘Nutritional Risk Screening 2002’. Results One or more tests were obtained in 135/163 patients (83.3%). Physical impairments were present in 43.2–82.8% of the patients. Median BI was 10/20 indicating limited self-dependency. Swallow impairments were present in 3/53 (5.7%) and 24/76 (31.6%) had risk of malnutrition. Impaired memory was seen in 26/43 (60.5%) and 22/47 (46.8%) had elevated anxiety/depression scores. Older adults had more physical, functional, and cognitive impairments. ICU patients had a lower hand grip force. Conclusion(s) The high prevalence of physical, cognitive, psychological, and functional impairments in hospitalized COVID-19 patients, both ICU and non-ICU patients, indicates that assessment of impairments is imperative. These results imply that rehabilitation and follow-up is essential for these patients. This paper proposes a short, workable assessment composed with known outcome measures to assess different domains of COVID-19 patients.

The dense co-occurrence of psychiatric disorders questions the categorical classification tradition and motivates efforts to establish dimensional constructs with neurobiological foundations that transcend diagnostic boundaries. In this study, we examined the genetic liability for eight major psychiatric disorder phenotypes under both a disorder-specific and a transdiagnostic framework. In a deeply-phenotyped sample (n=513) consisting of 452 patients from tertiary care with mood disorders, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and/or substance use disorders (SUD) and 61 unaffected comparison individuals, we derived subject-specific multi-base polygenic risk score (PRS) profiles and assessed their associations with psychiatric diagnoses, comorbidity status, as well as cross-disorder behavioral dimensions. High PRS for depression was unselectively associated with the diagnosis of SUD, ADHD, anxiety disorders, mood disorders, and the comorbidities among them. In the dimensional approach, four distinct functional domains were uncovered, namely the negative valence, social, cognitive, and regulatory systems, closely matching the major functional domains proposed by the Research Domain Criteria (RDoC) framework. Critically, the genetic predisposition for depression was selectively reflected in the functional aspect of negative valence systems but not others. This study highlights a misalignment between current psychiatric nosology and the underlying psychiatric genetic etiology, and underscores the effectiveness of the dimensional approach in both the functional characterization of psychiatric patients and the delineation of the genetic liability for psychiatric disorders.

BACKGROUND The chronic nature of depression and limited availability of evidence-based treatments emphasize the need for complementary recovery-oriented services, such as peer support interventions (PSIs). Peer support is associated with positive effects on clinical and personal recovery from mental illness, but little is known about the processes of engagement that foster change. OBJECTIVE This study assesses whether the level of user engagement in an online peer support community for individuals with depression promotes empowerment and the use of self-management strategies, and reduces symptom severity, and disability. METHODS In a longitudinal survey conducted from June 2019 to September 2020 we analyzed the data of users of Depression Connect, an online peer support community hosted by the Dutch Patient Association for Depression and the Pro Persona Mental Health Care institute on measures of empowerment (Netherlands Empowerment List, NEL), self-management (Dutch Assessment of Self-management in Anxiety and Depression questionnaire, ASAD), depression (Beck Depression Inventory-II, BDI-II-NL), and disability (World Health Organization Disability Assessment Schedule, WHODAS 2.0). Of the 301 respondents, 49 completed the survey again after three months and 74 after six months. Analysis of three parameters (ie, total time spend on the platform, number of page views, and number of posts) derived from their data logs yielded four engagement profiles. Linear mixed models were fitted to determine whether outcomes had significantly changed over time and significantly differed for the various profiles. RESULTS Baseline engagement was ‘very low’ (177/301, 59%) or ‘low’ (87/301, 29%) for the majority of the participants, with few showing ‘medium’ (30/301, 10%) or ‘high’ engagement patterns (7/301, 2%), while user profiles did not differ regarding demographic and clinical characteristics. All outcomes improved over time but none were associated with the intensity or nature of user engagement. CONCLUSIONS Improvements in empowerment, self-management, depressive symptoms, and disability were not related to the intensity or nature of user engagement. With the great majority of Depression Connect members showing very-low-to-low engagement and only few being identified as high-frequency, active users, it is likely that this flexibility in use is what provides value to online PSI users, where they can adapt the intensity and nature of their engagement to their current needs on their personal road to recovery. Future studies should explore the content and quality of the interactions in online PSIs to identify optimal user engagement as a function of current, self-reported clinical parameters and reasons to engage in the PSI.

Background The chronic nature of depression and limited availability of evidence-based treatments emphasize the need for complementary recovery-oriented services, such as peer support interventions (PSIs). Peer support is associated with positive effects on clinical and personal recovery from mental illness, but little is known about the processes of engagement that foster change, and studies targeting individuals with depression specifically are limited. Objective This study aimed to evaluate whether the level of user engagement, assessed on several dimensions, in an online peer support community for individuals with depression promotes empowerment and the use of self-management strategies and reduces symptom severity and disability. Methods In a longitudinal survey conducted from June 2019 to September 2020, we analyzed the data of the users of Depression Connect (DC), an online peer support community hosted by the Dutch Patient Association for Depression and the Pro Persona Mental Health Care institute, on measures of empowerment, self-management, depression, and disability. Of the 301 respondents, 49 (16.3%) respondents completed the survey again after 3 months and 74 (24.6%) respondents, after 6 months. Analysis of 3 parameters (ie, total time spent on the platform, number of page views, and number of posts) derived from their data logs yielded 4 engagement profiles. Linear mixed models were fitted to determine whether the outcomes had significantly changed over time and differed for the various profiles. Results Baseline engagement with the online peer support community was “very low” (177/301, 58.8%) or “low” (87/301, 28.9%) for most of the participants, with few showing “medium” (30/301, 9.9%) or “high” engagement patterns (7/301, 2.3%), while user profiles did not differ in demographic and clinical characteristics. Empowerment, self-management, depressive symptoms, and disability improved over time, but none were associated with the intensity or nature of user engagement. Conclusions With most DC members showing very low to low engagement and only a few being identified as high-engaged users, it is likely that this flexibility in use frequency is what provides value to online PSI users. In other more formal supportive environments for depression, a certain level of engagement is predetermined either by their organizational or by their societal context; at DC, users can adapt the intensity and nature of their engagement to their current needs on their personal road to recovery. This study added to the current knowledge base on user engagement for PSIs because previous studies targeting depression with an online format focused on active users, precluding passive and flexible engagement. Future studies should explore the content and quality of the interactions in online PSIs to identify optimal user engagement as a function of current, self-reported clinical parameters and reasons to engage in the PSI.

Significance Mutations in ATP13A2 cause a spectrum of related neurodegenerative disorders. ATP13A2 is a lysosomal exporter of polyamines that contributes to lysosomal health and controls cellular polyamine content. Conversely, loss of ATP13A2 leads to lysosomal dysfunction, a hallmark of neurodegeneration. Here, we show that polyamines transported by ATP13A2 provide cellular protection by lowering reactive oxygen species (ROS), which may relate to the antioxidant properties of polyamines. Consequently, dysfunctional ATP13A2 sensitizes cells to oxidative stress, which impairs mitochondria, and induces toxicity and cell death. ATP13A2-mediated polyamine transport represents a conserved pathway that protects against mitochondrial oxidative stress. The combined protective impact of ATP13A2 on lysosomal health and mitochondrial oxidative stress may explain why ATP13A2 exerts potent neuroprotective effects., Recessive loss-of-function mutations in ATP13A2 (PARK9) are associated with a spectrum of neurodegenerative disorders, including Parkinson’s disease (PD). We recently revealed that the late endo-lysosomal transporter ATP13A2 pumps polyamines like spermine into the cytosol, whereas ATP13A2 dysfunction causes lysosomal polyamine accumulation and rupture. Here, we investigate how ATP13A2 provides protection against mitochondrial toxins such as rotenone, an environmental PD risk factor. Rotenone promoted mitochondrial-generated superoxide (MitoROS), which was exacerbated by ATP13A2 deficiency in SH-SY5Y cells and patient-derived fibroblasts, disturbing mitochondrial functionality and inducing toxicity and cell death. Moreover, ATP13A2 knockdown induced an ATF4-CHOP-dependent stress response following rotenone exposure. MitoROS and ATF4-CHOP were blocked by MitoTEMPO, a mitochondrial antioxidant, suggesting that the impact of ATP13A2 on MitoROS may relate to the antioxidant properties of spermine. Pharmacological inhibition of intracellular polyamine synthesis with α-difluoromethylornithine (DFMO) also increased MitoROS and ATF4 when ATP13A2 was deficient. The polyamine transport activity of ATP13A2 was required for lowering rotenone/DFMO-induced MitoROS, whereas exogenous spermine quenched rotenone-induced MitoROS via ATP13A2. Interestingly, fluorescently labeled spermine uptake in the mitochondria dropped as a consequence of ATP13A2 transport deficiency. Our cellular observations were recapitulated in vivo, in a Caenorhabditis elegans strain deficient in the ATP13A2 ortholog catp-6. These animals exhibited a basal elevated MitoROS level, mitochondrial dysfunction, and enhanced stress response regulated by atfs-1, the C. elegans ortholog of ATF4, causing hypersensitivity to rotenone, which was reversible with MitoTEMPO. Together, our study reveals a conserved cell protective pathway that counters mitochondrial oxidative stress via ATP13A2-mediated lysosomal spermine export.

A method for encryption and safe transmission of data in the shape of molecular weight distributions (MWD) is presented. Relatively simple individual distributions serve as the key to encode information by mixing those in known amounts to an overlapped MWD. Increasing molecular weights are used to denote the position of these individual sub-distributions, and the relative quantity per sub-distribution is used to store data. The concept is demonstrated by a series of messages, whereby two-letter codes can be transmitted per overall MWD. In the final step, the encryption safety is confirmed. Due to the inherent differences in SEC calibrations, samples sent from Australia to Belgium could only be deconvoluted when the recipient of the message owned the physical sub-distributions, which then act as the encryption key.

Contains fulltext : 216652.pdf (Publisher’s version ) (Open Access) Memory bias modification (MBM) is a relatively new approach at targeting biased processing - a central cognitive factor causing and maintaining depression. In this pilot study we aimed to develop a smartphone-based autobiographical memory training, a novel form of MBM. A total of 153 unselected participants were randomly allocated to one of three experimental training conditions (positive, negative or sham memory training) conducted over a period of three days. Autobiographical memory bias and depressive scores were assessed pre- and post-training, whilst recent event recall and explicit self-referent memory bias were assessed post-training. Positive memory bias significantly increased in the positive training condition, however memory bias did not significantly differ post-training between the three conditions. Participants who received positive training recalled a positive autobiographical event more frequently compared to the other conditions. No significant difference between conditions was found in the other outcomes, including symptoms. The novel smartphone-based MBM intervention seems apt to affect autobiographical memory of emotional material. Future research should explore its possible (therapeutic) application. 12 p.

Contains fulltext : 217003.pdf (Publisher’s version ) (Closed access) Achtergrond: De meeste ggz-instellingen in Nederland werken met stoornisspecifieke zorgprogramma’s. Indien er sprake is van comorbiditeit, wat eerder regel is dan uitzondering in de specialistische ggz (sggz), blijkt er onvoldoende evidentie te bestaan als het gaat om het kiezen van de focus van behandeling. Doel: Inzicht krijgen in de prevalentie van comorbiditeit met depressie bij patiënten met angststoornissen volgens de dsm-iv-classificatie (angststoornissen inclusief de dwangstoornissen en de posttraumatische stressstoornis). Tevens nagaan of er een verschil is in behandeleffect bij een protocollaire angstbehandeling tussen patiënten met één (of meerdere) angststoornissen zonder of met een comorbide depressie. Methode: Retrospectieve studie met gegevens uit routine outcome monitoring over de periode 2012-2017. In deze periode identificeerden we 127 patiënten van wie rom-data en diagnostische criteria beschikbaar waren. Diagnostiek en dsm-classificatie vonden plaats met een klinisch interview. De behandeling werd uitgevoerd conform de Multidisciplinaire richtlijn Angststoornissen en elke 12 weken systematisch gemonitord met zelfrapportagelijsten, waaronder de Inventory of Depressive Symptomatology (ids) en de Beck Anxiety Inventory (BAI). Resultaten: Bij 46,5% van de onderzochte patiënten was er een comorbide depressieve stoornis aanwezig. De behandeleffecten bij patiënten met of zonder comorbide depressie verschilden niet van elkaar. Als opvallende bevinding werd gevonden dat de mate van vermindering van de depressieve klachten (gemeten met de ids) voorspellend bleek te zijn voor de mate van vermindering van de angstklachten (gemeten met de BAI): een sterkere vermindering van de stemmingsklachten bleek een gunstiger beloop van het effect van de protocollaire angstbehandeling te voorspellen. Conclusie: Bij iets minder dan de helft van de patiënten in het zorgprogramma angststoornissen was sprake van een comorbide depressieve stoornis. Traag of niet afnemen van de depressieve symptomen lijkt geassocieerd met een slechter behandelresultaat op de angstklachten. 7 p.

UNSTRUCTURED These are author responses to peer review of ms#31269

Contains fulltext : 285334.pdf (Publisher’s version ) (Open Access) Negative memory bias refers to the enhanced recall of negative memories and is a prominent cognitive factor causing and maintaining depression. Surprisingly few studies modify this negative recall. The current study used a smartphone-based autobiographical memory training to increase positive memory recall and thereby alter negative memory bias. A total of 96 dysphoric (>= 13 BDI-II) participants were randomly allocated to a positive, sham or no-training condition, conducted over a period of 6 days. Positive memory bias (i.e., recalled event evaluation) significantly increased from pre- to post-training after positive and sham intervention, suggesting an unspecific training effect. No transfer to memory specificity, implicit memory bias or depressive symptoms was found, nor was the training effect modulated by pre-existing level of positive memory bias. A post-hoc follow-up measurement during the initial COVID-19 crisis revealed that subjects who benefitted most from either of the trainings maintained their stress levels better during a natural stressful period, compared to those who responded least to the training. Future studies should carefully consider the impact of sham training design. Moreover, it is important to examine transfer effects of bias training as practice in daily life. 11 p.

Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum—a central hub in motor, cognitive, affective and reward-related brain circuits—and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

Contains fulltext : 284920.pdf (Publisher’s version ) (Open Access) 5 p.

BackgroundClassic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample.MethodsWe administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling.ResultsIn contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias.ConclusionsThese results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.

Contains fulltext : 252781.pdf (Publisher’s version ) (Open Access) Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders. 16 p.

Background Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders. Methods We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557). Results Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity. Conclusions The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

Background It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). Objective The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. Methods This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged ≥18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. Results We aim to include a total of 650 patients and 150 neurotypical control participants in the time period between 2016 and 2022. In October 2021, we are at 95% of our target. Conclusions The MIND-SET study enables us to investigate the mechanistic underpinnings of nonpsychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

Case summary A 12-year-old neutered female domestic shorthair cat was presented with bilateral progressive forelimb lameness that was unresponsive to anti-inflammatory drugs. Bilateral carpal flexural deformity with hyperflexion of multiple toes of the right forelimb was observed. In the absence of abnormalities detected on radiographs and ultrasound, a bilateral contracture of the carpal and digital flexor muscles was diagnosed. Treatment consisted of single-session bilateral selective tenectomies (5 mm) of the flexor carpi ulnaris, flexor carpi radialis and superficial digital flexor muscle tendons on the left forelimb and tendons of the flexor carpi ulnaris muscle, and branches of the third and fourth digit of the deep digital flexor muscle on the right forelimb. Two months postoperatively, selective tenectomies (10 mm) were performed due to contracture recurrence on the left forelimb. The subjective outcome was rated as good 6 months postoperatively. Relevance and novel information Digital and/or carpal contractures are rarely described in (feline) veterinary medicine and are limited to a few case reports. The exact aetiology remains unknown. A traumatic/iatrogenic origin seems to be the most likely cause. Surgery is indicated, consisting of selective tenectomy and/or tenotomy, and is associated with minor complications and an excellent outcome. This case report describes the presence, treatment and successful outcome of a cat with bilateral carpal and digital flexor muscle contractures resulting in carpal flexural deformity with valgus deviation treated with selective tenectomies.

BACKGROUND It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). OBJECTIVE The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. METHODS This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged ≥18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. RESULTS We aim to include a total of 650 patients and 150 neurotypical control participants in the time period between 2016 and 2022. In October 2021, we are at 95% of our target. CONCLUSIONS The MIND-SET study enables us to investigate the mechanistic underpinnings of nonpsychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

BackgroundIt is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood on the basis of symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the MIND-Set study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). The main objective of the MIND-Set project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels.MethodsThis is an observational, cross-sectional study. Data from different observational levels as defined in the research domain criteria (RDoC; genetics, physiology, neuropsychology, system level neuroimaging, behavior, self-report and experimental neurocognitive paradigms) are collected over four time points. Included are adult (≥ 18 years), non-psychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder and/or addiction disorder) and/or a neurodevelopmental disorder (ASD and/or ADHD). Individuals with no current or past psychiatric diagnosis are included as controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 healthy controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with 1) Standardized clinical examination, physical examination, and blood sampling; 2) Psychological constructs, neuropsychological tests, and biological marker sampling; 3) Neuroimaging measures.DiscussionThe MIND-Set study enables us to investigate the mechanistic underpinnings of non-psychotic psychiatric disorders transdiagnostically. We will identify both shared and disorder-specific markers at different observational levels that can be used as targets for future diagnostic and treatment approaches.

Depression ist eine der haufigsten psychischen Erkrankungen, mit oft chronischem Verlauf und schwierig zu behandeln. Zusatzliche Interventionen, die auf spezielle Risikofaktoren abzielen, konnten neue Behandlungsmoglichkeiten bieten. Vielversprechend sind Trainingsprogramme, die automatische kognitive Prozesse und Verzerrungen beeinflussen. In den letzten Jahren wurden computergestutzte Trainings entwickelt ("Cognitive-bias-modification"[CBM]-Programme), die genau auf diese Prozesse abzielen und zukunftig einfach als "Add-on" in die psychotherapeutische Praxis implementiert werden konnten. Im Folgenden wird der Stand der Forschung dargestellt und anhand eines eigenen klinischen Versuchs der detaillierte Aufbau aktueller Studien verdeutlicht.

A novel continuous flow system for automated high-throughput screening, autonomous optimization, and enhanced process control of polymerizations was developed. The computer-controlled platform comprises a flow reactor coupled to size exclusion chromatography (SEC). Molecular weight distributions are measured online and used by a machine-learning algorithm to self-optimize reactions towards a programmed molecular weight by dynamically varying reaction parameters (i.e. residence time, monomer concentration, and control agent/initiator concentration). The autonomous platform allows targeting of molecular weights in a reproducible manner with unprecedented accuracy (

Over the course of the last century, a large number of synthetic polymers has been developed and introduced. Yet, most polymer materials are based on fossil fuels as raw materials and are associated with a considerable environmental impact. trans,trans-Muconic acid esters are interesting plant-based monomers that have not received much attention yet. The synthesis of a series of dialkyl muconates from muconic acid is described, followed by an optimization of the solution free-radical polymerization of these monomers. Unlike the claim in previous studies, dialkyl muconates can be polymerized efficiently in solution to polymers with significant molecular weights above 105 g mol−1. Polymerizations are, however, relatively slow, as can be expected for diene monomers (48 h at 120 °C). Mark–Houwink coefficients have been determined for diethyl muconate, dibutyl muconate and di(2-ethylhexyl) muconate. Furthermore, glass transition temperatures and thermal stability are assessed for the polymers, showcasing that polymuconates can serve as alternatives to polyacrylate materials. In a last step, also the reversible addition–fragmentation chain transfer (RAFT) polymerization of the muconates is investigated, showing excellent control over the molecular weight when a conventional trithiocarbonate is used to control polymerizations.

Contains fulltext : 234352pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 234352.pdf (Author’s version preprint ) (Open Access) Contains fulltext : 234352appendix.pdf (Author’s version preprint ) (Open Access) Cognitive theories of depression hold that negative contextual triggers (e.g., stressful events) induce more negative and less positive mood, in turn instigating negatively biased memories. However, context-related variability in mood and emotional memory has received insufficient attention, while the dynamic interaction between these factors plays a crucial role in the kindling of new depressive episodes. Experience Sampling Method (ESM) for repeated, daily life measures of context, mood, and autobiographic emotional memory was used in 46 currently depressed, 90 remitted-depressed, and 55 never-depressed individuals. Currently depressed individuals showed strongest negative processing style and never-depressed most positive, with remitted-depressed patients scoring intermediate. The moderated mediation model indicated that context appraisal had a direct effect on the appraisal of the recalled event (i.e., our operationalization of emotional memory), which was mediated by positive (but hardly by negative) mood and was independent of depression status. This mediation strength was relatively similar to the strength of the direct effect of context on memory. Results are in line with cognitive theories of depression. Especially context seems important for emotional memory. The association between context, mood, and memory, however, may be independent of depression status. Yet, the "level" of mood, context, and event appraisal does depend on depression status. 11 p.

Background Individuals with a parental family history of dementia have an increased risk of developing dementia because they share their genes as well as their psychosocial behaviour. Due to this increased risk and their experience with dementia, they may be particularly eager to receive information regarding dementia risk reduction (DRR). This study evaluated the knowledge, beliefs and attitudes towards dementia and DRR among descendants of people with dementia.Method Using a semi-structured topic guide, three focus group discussions were conducted consisting of 12 female (80%) and 3 male (20%) descendants of people with dementia with a mean age of 48.8 ± 12.0 years. Focus group discussions were audio recorded and transcribed. Each transcript was analysed thoroughly, and where appropriate, a code was generated and assigned by two researchers independently. Then, similar codes were grouped together and categorized into themes.Results The items in the topic guide could only be addressed after participants had been given the opportunity to share their experiences of having a parent with dementia. Participants were unaware or uncertain about the possibility of reducing the risk of developing dementia and therefore hesitant to assess their dementia risk without treatment options in sight. Moreover, participants indicated that their general practitioner only gave some information on heritability, not on DRR. Although participants identified a large number of modifiable risk factors as a group during the group discussions, they were eager to receive more information on dementia and DRR. In the end, participants adopted a more positive attitude towards a DRR program and provided suggestions for the development of future DRR programs.Conclusions Although the research aim was to evaluate the knowledge, beliefs and attitudes towards dementia and DRR, sharing experiences of having a parent with dementia seemed a prerequisite for considering participants’ own risk of developing dementia and participating in a DRR program. Knowledge of dementia and DRR was limited. Due to unawareness of the possibility of reducing dementia risk, participants were hesitant about assessing their dementia risk. Group discussions positively changed the perception of dementia risk assessment and participants’ willingness to participate in a DRR program.

Obstructive sleep apnea (OSA) is a prevalent and multifaceted disease. To date, the presence and severity of objectively identified comorbidities and their association with specific OSA phenotypes, CPAP adherence, and survival remain to be elucidated. The aim of this study is to cluster patients with OSA based on 10 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical and polysomnographic characteristics, CPAP adherence, and survival.Seven hundred ten consecutive patients starting CPAP for moderate-to-severe OSA were included. Comorbidities were based on generally accepted cutoffs identified in the peer-reviewed literature. Self-organizing maps were used to order patients based on presence and severity of their comorbidities and to generate clusters.The majority of patients were men (80%). They were generally middle-aged (52 years) and obese (BMI: 31.5 kg/mComorbidity prevalence in patients with OSA is high, and different comorbidity clusters, demonstrating differences in cardiovascular risk, CPAP adherence, and survival, can be identified. These results further substantiate the need for a comprehensive assessment of patients with OSA beyond the AHI.

Cryogenic environments benefit ion trapping experiments by offering lower motional heating rates, collision energies, and an ultra-high vacuum (UHV) environment for maintaining long ion chains for extended periods of time. Mechanical vibrations caused by compressors in closed-cycle cryostats can introduce relative motion between the ion and the wavefronts of lasers used to manipulate the ions. Here, we present a novel ion trapping system where a commercial low-vibration closed-cycle cryostat is used in a custom monolithic enclosure. We measure mechanical vibrations of the sample stage using an optical interferometer, and observe a root-mean-square relative displacement of 2.4 nm and a peak-to-peak displacement of 17 nm between free-space beams and the trapping location. We packaged a surface ion trap in a cryo-package assembly that enables easy handling, while creating a UHV environment for the ions. The trap cryo-package contains activated carbon getter material for enhanced sorption pumping near the trapping location, and source material for ablation loading. Using $^{171}$Yb$^{+}$ as our ion we estimate the operating pressure of the trap as a function of package temperature using phase transitions of zig-zag ion chains as a probe. We measured the radial mode heating rate of a single ion to be 13 quanta/s on average. The Ramsey coherence measurements yield 330 ms coherence time for counter-propagating Raman carrier transitions using a 355 nm mode-locked pulse laser, demonstrating the high optical stability., Comment: 12 pages, 10 figures

Item does not contain fulltext Cognitive behavioral therapy (CBT) is an established first-line intervention for psychological disorders. Numerous randomized controlled trials (RCTs) and meta-analyses indicate that CBT outperforms wait-list and placebo conditions and evidences comparable efficacy to other efficacious interventions such as pharmacotherapies. This chapter provides a narrative review of studies examining putative mechanisms of action of CBT for depression and anxiety disorders, and briefly addresses research in other mental health disorders. It focuses on core behavioral and cognitive mechanisms of action as tested by self-report measures or behavioral measures. Because sustainable treatment effects should be reflected by changes in the brain, specifically in areas related to proposed mechanisms of change, researchers have started relating brain activation in areas related to such processes with CBT outcome. The chapter illustrates how mechanistic research can guide treatment development and finish by offering some directions for research in this important area.

Additional file 1. Definitions of educational levels, criteria to identify erroneous designs, characteristics of the study population that participated in the second visit, characteristics of the responders and non-responders and the list of improvements to provide clearer instructions for the digital RFFT.