Telemetry discontinuation education for Nurse Practitioners decreases hospital costs-A quality-improvement project.

BACKGROUND: Despite updated American Heart Association guidelines, interventions designed to reduce telemetry misuse are uncommon. LOCAL PROBLEM: There was a systemic failure within the institution to adopt the most recent guidelines, resulting in poor use of resources and downstream costs. METHODS: Case-control. Pre-post educational intervention, quality-improvement (QI) project in an urban academic cancer institution. Baseline telemetry usage was observed in 2,984 nonintensive inpatients in 21 hospital services over 6 months. Outcome measures were weekly telemetry usage in total minutes and cost savings based on a cost-predicted algorithm. Performance was compared between the intervention group and a control group for 3 months. Measures were compared using QI control charts and inferential statistics. INTERVENTION: Three high-using telemetry services primarily staffed by certified nurse practitioners (CNPs) were provided with a telemetry education intervention. The intervention consisted of four ten-minute educational sessions over 2 weeks delivered to the highest three telemetry using services. RESULTS: Forty-five providers received the educational intervention (78% CNPs and physician assistants [PAs] and 22% medical doctors [MDs]) and 272 did not (57% CNPs and PAs and 43% MDs). Only the educational intervention group showed measurable decreases shown by shifts in QI control charts. Decreased usage in the intervention group produced greater cost savings per patient when compared with the control group ($71.98 vs. $60.68), resulting in an estimated total annual cost savings of $94,740. CONCLUSIONS: Educational interventions for inpatient CNPs that reinforce national policies for telemetry discontinuation improve practice efficiency and potentially decrease health care costs.

Oxidative stress-induced YAP1 expression is regulated by NCE102, CDA2, and BCS1.

Maintaining cellular homeostasis in the face of stress conditions is vital for the overall well-being of an organism. Reactive oxygen species (ROS) are among the most potent cellular stressors and can disrupt the internal redox balance, giving rise to oxidative stress. Elevated levels of ROS can severely affect biomolecules and have been associated with a range of pathophysiological conditions. In response to oxidative stress, yeast activator protein-1 (Yap1p) undergoes post-translation modification that results in its nuclear accumulation. YAP1 has a key role in oxidative detoxification by promoting transcription of numerous antioxidant genes. In this study, we identified previously undescribed functions for NCE102, CDA2, and BCS1 in YAP1 expression in response to oxidative stress induced by hydrogen peroxide (H2O2). Deletion mutant strains for these candidates demonstrated increased sensitivity to H2O2. Our follow-up investigation linked the activity of these genes to YAP1 expression at the level of translation. Under oxidative stress, global cap-dependent translation is inhibited, prompting stress-responsive genes like YAP1 to employ alternative modes of translation. We provide evidence that NCE102, CDA2, and BCS1 contribute to cap-independent translation of YAP1 under oxidative stress.

Feasibility of a trauma-focused internet- and mobile-based intervention for youth with posttraumatic stress symptoms.

Background: Many youth with posttraumatic stress symptoms (PTSS) do not receive evidence-based care. Internet- and Mobile-Based Interventions (IMIs) comprising evidence-based trauma-focused components can address this gap, but research is scarce. Thus, we investigated the feasibility of a trauma-focused IMI for youth with PTSS.Methods: In a one-arm non-randomized prospective proof-of-concept study, 32 youths aged 15-21 years with clinically relevant PTSS (CATS ≥ 21) received access to a trauma-focused IMI with therapist guidance, comprising nine sessions on an eHealth platform accessible via web-browser. We used a feasibility framework assessing recruitment capability, sample characteristics, data collection, satisfaction, acceptability, study management abilities, safety aspects, and efficacy of the IMI in PTSS severity and related outcomes. Self-rated assessments took place pre-, mid-, post-intervention and at 3-month follow-up and clinician-rated assessments at baseline and post-intervention.Results: The sample mainly consisted of young adult females with interpersonal trauma and high PTSS levels (CATS, M = 31.63, SD = 7.64). The IMI sessions were found useful and comprehensible, whereas feasibility of trauma processing was perceived as difficult. Around one-third of participants (31%) completed the IMI's eight core sessions. The study completer analysis showed a significant reduction with large effects in self-rated PTSS at post-treatment [t(21) = 4.27; p < .001; d = 0.88] and follow-up [t(18) = 3.83; p = .001; d = 0.84], and clinician-rated PTSD severity at post-treatment [t(21) = 4.52; p < .001; d = 0.93]. The intention-to-treat analysis indicated significant reductions for PTSS at post-treatment and follow-up with large effect sizes (d = -0.97- -1.02). All participants experienced at least one negative effect, with the most common being the resurfacing of unpleasant memories (n = 17/22, 77%).Conclusion: The study reached highly burdened young adults. The IMI was accepted in terms of usefulness and comprehensibility but many youths did not complete all sessions. Exploration of strategies to improve adherence in trauma-focused IMIs for youth is warranted, alongside the evaluation of the IMI's efficacy in a subsequent randomized controlled trial.

Youth often lack access to evidence-based care after trauma. This study assessed the feasibility of a trauma-focused internet- and mobile-based intervention with therapist guidance.The intervention was accepted by youths, and the preliminary evaluation of participant responses suggests its efficacy.Future studies should examine strategies to improve adherence and the IMI's efficacy in a RCT.

BEST FOR CAN - bringing empirically supported treatments to children and adolescents after child abuse and neglect: update to the study protocol.

Background: The implementation trial BESTFORCAN aims to evaluate the dissemination of Trauma-Focused Behavioural Therapy (TF-CBT) for children and adolescents in Germany with posttraumatic stress symptoms (PTSS) after child abuse and neglect (CAN) with a focus on supervision.Objective: This update to the study protocol outlines changes made due to practical reasons in the course of the ongoing trial while maintaining methodological quality.Method: The amendments to the original study protocol comprise (1) a more refined operationalisation of the primary outcome sufficiently adherent TF-CBT therapy (SATT), (2) changes in the study sites and (3) additional inclusion of one post-gradual psychotherapy training institute.Discussion: The adaptions to the original study protocol ensured high methodological quality through the transparent presentation of protocol modification: ensuring the recruitment of participating psychotherapists in training by including a further post-gradual training institute as well as an adaption of the measurement of SATT with high external validity. The objectives, diagnostic set, and secondary outcomes remained unimpaired by the amendment. Therefore, we expect the trial to provide evidence for the effect of model-specific trauma-focused supervision on the implementation outcomes of TF-CBT as compared to supervision as usual.Trial registration: German Clinical Trials Register identifier: DRKS00020516..

Update to the study protocol of the trial BESTFORCAN that investigates the implementation of trauma-focused behavioural therapy for children and adolescents with posttraumatic stress symptoms following abuse with a focus on the role of supervision.Adaptions have been made regarding the specification of the definition of sufficiently adherent intervention, relocation of the data-handling centre and the recruitment of one additional psychotherapy institute.The adaptions have no impact on the objectives, diagnostic set, secondary outcomes, or processes of data handling.

"If we don't speak the language, we aren't offered the same opportunities": Qualitative perspectives of palliative care access for women of color living with advanced breast cancer.

Context: Despite efforts to enhance equity, disparities in early palliative care (PC) access for historically minoritized patients with advanced breast cancer (ABC) persist. Insight into patient and clinician perspectives are needed to inform future models aimed at improving equity in PC access and outcomes. Objectives: To explore qualitative barriers and facilitators to early PC access in an urban setting with Black and Latina women with ABC. Methods: In this qualitative descriptive study, we conducted one-on-one interviews with Black and Latina women with ABC (N = 20) and interdisciplinary clinicians (N = 20) between February 2022 and February 2023. Participants were recruited from urban academic and community cancer clinics. Transcripts were analyzed using an inductive coding and thematic analysis approach. Results: Barriers identified by both patients and clinicians included lack of communication between oncology, PC, and primary care teams, limited understanding of PC among patients and non-PC clinicians, language and health literacy-related communication challenges, and racism and marginalization, including implicit bias and lack of diverse racial/ethnic representation in the supportive care workforce. Facilitators identified by both patients and clinicians included patient-to-patient referrals, support groups breaking cultural stigma on topics including self-advocacy and PC, referrals from trusted providers, and community organizations' abilities to overcome challenges related to social determinants of health, most specifically logistical and financial support. Conclusions: Patients and clinicians reported similar barriers and facilitators to PC access, most commonly through the lens of care coordination and communication. These findings will inform future adaptation of a culturally and linguistically care model to improve access to early PC services for Black and Latina women with ABC.

The perspectives of older adults related to transcatheter aortic valve replacement: An integrative review.

BACKGROUND: Aortic Stenosis (AS) is a common syndrome in older adults wherein the narrowing of the aortic valve impedes blood flow, resulting in advanced heart failure.1 AS is associated with a high mortality rate (50 % at 6 months if left untreated), substantial symptom burden, and reduced quality of life.1-3 Transcatheter aortic valve replacement (TAVR) was approved in 2012 as a less invasive alternative to surgical valve repair, offering a treatment for older frail patients. Although objective outcomes have been widely reported,4 the perspectives of older adults undergoing the TAVR process have never been synthesized. OBJECTIVES: To contextualize the perspectives and experiences of older adults undergoing TAVR. METHODS: An integrative review was conducted using Whittemore and Knafl's five-stage methodology.5 Four electronic databases were searched in April 2023. Articles were included if a qualitative methodology was used to assess the perceptions of older adults (>65 years old) undergoing or recovering from TAVR. RESULTS: Out of 4619 articles screened, 12 articles met the criteria, representing 353 individuals from 10 countries. Relevant themes included the need for an individualized care plan, caregiver and family support, communication and education, persistent psychosocial and physical symptoms, and the unique recovery journey. CONCLUSION: Older adults with AS undergoing TAVR generally perceive their procedure positively. Improved interdisciplinary and holistic management, open communication, symptom assessment, support, and education is needed.

Thermotolerance in S. cerevisiae as a model to study extracellular vesicle biology.

The budding yeast Saccharomyces cerevisiae is a proven model organism for elucidating conserved eukaryotic biology, but to date its extracellular vesicle (EV) biology is understudied. Here, we show yeast transmit information through the extracellular medium that increases survival when confronted with heat stress and demonstrate the EV-enriched samples mediate this thermotolerance transfer. These samples contain vesicle-like particles that are exosome-sized and disrupting exosome biogenesis by targeting endosomal sorting complexes required for transport (ESCRT) machinery inhibits thermotolerance transfer. We find that Bro1, the yeast ortholog of the human exosome biomarker ALIX, is present in EV samples, and use Bro1 tagged with green fluorescent protein (GFP) to track EV release and uptake by endocytosis. Proteomics analysis reveals that heat shock protein 70 (HSP70) family proteins are enriched in EV samples that provide thermotolerance. We confirm the presence of the HSP70 ortholog stress-seventy subunit A2 (Ssa2) in EV samples and find that mutant yeast cells lacking SSA2 produce EVs but they fail to transfer thermotolerance. We conclude that Ssa2 within exosomes shared between yeast cells contributes to thermotolerance. Through this work, we advance Saccharomyces cerevisiae as an emerging model organism for elucidating molecular details of eukaryotic EV biology and establish a role for exosomes in heat stress and proteostasis that seems to be evolutionarily conserved.

Cymoxanil disrupts RNA synthesis through inhibiting the activity of dihydrofolate reductase.

The agricultural fungicide cymoxanil (CMX) is commonly used in the treatment of plant pathogens, such as Phytophthora infestans. Although the use of CMX is widespread throughout the agricultural industry and internationally, the exact mechanism of action behind this fungicide remains unclear. Therefore, we sought to elucidate the biocidal mechanism underlying CMX. This was accomplished by first performing a large-scale chemical-genomic screen comprising the 4000 haploid non-essential gene deletion array of the yeast Saccharomyces cerevisiae. We found that gene families related to de novo purine biosynthesis and ribonucleoside synthesis were enriched in the presence of CMX. These results were confirmed through additional spot-test and colony counting assays. We next examined whether CMX affects RNA biosynthesis. Using qRT-PCR and expression assays, we found that CMX appears to target RNA biosynthesis possibly through the yeast dihydrofolate reductase (DHFR) enzyme Dfr1. To determine whether DHFR is a target of CMX, we performed an in-silico molecular docking assay between CMX and yeast, human, and P. infestans DHFR. The results suggest that CMX directly interacts with the active site of all tested forms of DHFR using conserved residues. Using an in vitro DHFR activity assay we observed that CMX inhibits DHFR activity in a dose-dependent relationship.

Interpersonal factors in internet-based cognitive behavioral therapy for depression: Attachment style and alliance with the program and with the therapist.

Objective This open-trial study examined effects of a culturally-adapted Hebrew version of guided internet-based cognitive behavioural therapy (ICBT) for depression. We examined therapeutic alliance with the therapist and with the programme (content) as potential predictors of outcomes. Furthermore, we examined whether anxious and avoidant attachment styles improved, although relationships were not the focus of treatment. Method: We examined alliance with therapist and alliance with programme and their time-lagged (1 week), longitudinal relationship with depression outcomes, and change in anxious and avoidant attachment during treatment. Results: Depression and insomnia improved significantly (Cohen's d: depression = 1.34, insomnia = 0.86), though dropout was relatively high (49%). Alliance with programme and with the therapist predicted adherence and dropout, whereas only alliance with therapist predicted symptom improvement. Avoidant attachment decreased over treatment whereas anxious attachment did not. Conclusion: A culturally-adapted version of ICBT for depression showed that alliance with therapist and alliance with programme both can play an important role in its effectiveness: alliance with programme and the therapist drive adherence and dropout and alliance with therapist is related to symptom improvement. Although the focus of treatment is not interpersonal, avoidant attachment style can improve following ICBT.

Reciprocal relationships between positive expectancies and positive emotions during the COVID-19 pandemic: a cross-lagged panel study.

INTRODUCTION: Previous research highlighted the importance of investigating distinct protective factors that predict the experience of positive emotions during stressful situations, such as the COVID-19 pandemic. In this longitudinal study, we specifically focused on positive expectancies towards the future (optimism, response expectancy, and response hope) in relation to the experience of positive emotions during the COVID-19 pandemic. Our primary objectives were to identify the best predictors for experiencing short-term and long-term positive emotions and investigate their interrelationships. METHODS: Data from 271 participants (average age = 29.2 years, 84.7% female) were analyzed using four cross-lagged models. RESULTS: Results showed that response expectancy was the best predictor for experiencing positive emotions in the short term, while optimism was the best predictor for experiencing positive emotions in the long term. Additionally, through further exploratory analysis, multiple bidirectional relationships were identified between positive expectancies and positive emotions. DISCUSSION: Our results highlight the significant role played by positive expectancies in predicting the experience of positive emotions. Specifically, dispositional optimism emerged as a stronger predictor of longer-term positive emotions, whereas response expectancy proved to be a better predictor of shorter-term positive emotions. Thus, interventions targeting positive expectancies have the potential to enhance emotional functioning in individuals during challenging situations like the COVID-19 pandemic.

Response expectancy positively predicts positive emotions in the short term.Optimism positively predicts positive emotions in the long term.Response expectancy positively predicts optimism in the short and long term.Response expectancy positively predicts response hope in the short term.Response hope negatively predicts optimism in the short and long term.Positive emotions positively predict positive expectancies (response expectancy, response hope, and optimism) on short term.The discrepancy score negatively predicts positive emotions in the short term.The discrepancy score negatively predicts optimism in the short and long term.

Gene-Environment Interactions in Irrational Beliefs: The Roles of Childhood Adversity and Multiple Candidate Genes.

Cognitive behavioral therapy is based on the view that maladaptive thinking is the causal mechanism of mental disorders. While this view is supported by extensive evidence, very limited work has addressed the factors that contribute to the development of maladaptive thinking. The present study aimed to uncover interactions between childhood maltreatment and multiple genetic differences in irrational beliefs. Childhood maltreatment and irrational beliefs were assessed using multiple self-report instruments in a sample of healthy volunteers (N = 452). Eighteen single-nucleotide polymorphisms were genotyped in six candidate genes related to neurotransmitter function (COMT; SLC6A4; OXTR), neurotrophic factors (BDNF), and the hypothalamic-pituitary-adrenal axis (NR3C1; CRHR1). Gene-environment interactions (G×E) were first explored in models that employed one measure of childhood maltreatment and one measure of irrational beliefs. These effects were then followed up in models in which either the childhood maltreatment measure, the irrational belief measure, or both were substituted by parallel measures. Consistent results across models indicated that childhood maltreatment was positively associated with irrational beliefs, and these relations were significantly influenced by COMT rs165774 and OXTR rs53576. These results remain preliminary until independent replication, but they represent the best available evidence to date on G×E in a fundamental mechanism of psychopathology.

"WOOP is my safe haven": A qualitative feasibility and acceptability study of the Wish Outcome Obstacle Plan (WOOP) intervention for spouses of people living with early-stage dementia.

OBJECTIVES: As symptoms emerge and worsen in people living with dementia, their spouses can benefit from behavioral interventions to support their adjustment as a care partner. The Wish Outcome Obstacle Plan (WOOP) intervention improves the well-being of spouses of people living with dementia early in the disease course, but intervention mechanisms and opportunities for improvement are unclear. The present study gave voice to spouses who participated in a trial of WOOP, describing how WOOP was incorporated into their lives and how it could be improved for future implementation. METHOD: For this qualitative study, we conducted longitudinal semi-structured interviews among 21 spouses of people living with dementia (three interviews over three months; 63 interviews total). Codebook thematic analysis was performed. RESULTS: Three meta-themes were derived: (1) assessing baseline strengths and limitations of WOOP, (2) learning from experience, and (3) fine-tuning and sustaining WOOP. Participants described how WOOP addressed their interpersonal and emotional stressors, their responses to behaviors of the person living with dementia, and their relationship quality. Considerations for future intervention delivery (e.g., solo vs. in group settings) and instructions (e.g., encouraging writing vs. thinking through the four steps of WOOP) were identified as areas of improvement. CONCLUSIONS: WOOP was described as a practical, feasible, and desirable intervention for spouses at the early stages of their partner's dementia. Participants made WOOP easier to incorporate in their everyday lives by adapting the design into a mental exercise that they used as needed. Suggestions from participants specified how to make the everyday use of WOOP more feasible, sustainable, and applicable in a variety of contexts. TRIAL REGISTRATION: ClinicalTrials.gov HIC 2000021852.

Effectiveness of an online recovery training for employees exposed to blurred boundaries between work and non-work: Bayesian analysis of a randomised controlled trial.

BACKGROUND: Blurred work-non-work boundaries can have negative effects on mental health, including sleep. OBJECTIVES: In a randomised control trial, we aimed to assess the effectiveness of an online recovery training programme designed to improve symptoms of insomnia in a working population exposed to blurred boundaries. METHODS: 128 participants with severe insomnia symptoms (Insomnia Severity Index ≥15) and working under blurred work and non-work conditions (segmentation supplies <2.25) were randomly assigned to either the recovery intervention or a waitlist control group (WLC). The primary outcome was insomnia severity, assessed at baseline, after 2 months (T2) and 6 months (T3). FINDINGS: A greater reduction in insomnia was observed in the intervention compared with the WLC group at both T2 (d=1.51; 95% CI=1.12 o 1.91) and T3 (d=1.63; 95% CI=1.23 to 2.03]. This was shown by Bayesian analysis of covariance (ANCOVA), whereby the ANCOVA model yielded the highest Bayes factor (BF 10=3.23×e60] and a 99.99% probability. Likewise, frequentist analysis revealed significantly reduced insomnia at both T2 and T3. Beneficial effects were found for secondary outcomes including depression, work-related rumination, and mental detachment from work. Study attrition was 16% at T2 and 44% at T3. CONCLUSIONS: The recovery training was effective in reducing insomnia symptoms, work related and general indicators of mental health in employees exposed to blurred boundaries, both at T2 and T3. CLINICAL IMPLICATIONS: In addition to demonstrating the intervention's effectiveness, this study exemplifies the utilisation of the Bayesian approach in a clinical context and shows its potential to empower recipients of interventional research by offering insights into result probabilities, enabling them to draw informed conclusions. TRIAL REGISTRATION NUMBER: German Clinical Trial Registration (DRKS): DRKS00006223, https://drks.de/search/de/trial/DRKS00006223.

The Involvement of YNR069C in Protein Synthesis in the Baker's Yeast, Saccharomyces cerevisiae.

Maintaining translation fidelity is a critical step within the process of gene expression. It requires the involvement of numerous regulatory elements to ensure the synthesis of functional proteins. The efficient termination of protein synthesis can play a crucial role in preserving this fidelity. Here, we report on investigating a protein of unknown function, YNR069C (also known as BSC5), for its activity in the process of translation. We observed a significant increase in the bypass of premature stop codons upon the deletion of YNR069C. Interestingly, the genomic arrangement of this ORF suggests a compatible mode of expression reliant on translational readthrough, incorporating the neighboring open reading frame. We also showed that the deletion of YNR069C results in an increase in the rate of translation. Based on our results, we propose that YNR069C may play a role in translation fidelity, impacting the overall quantity and quality of translation. Our genetic interaction analysis supports our hypothesis, associating the role of YNR069C to the regulation of protein synthesis.

Death Anxiety in the COVID-19 Pandemic: Testing REBT Models of Psychopathology and Psychological Health of Death Anxiety.

Objective: This paper aimed to examine the validity of the death anxiety psychopathological and psychological health models of Rational-Emotive Behavior Therapy (REBT). We investigated whether irrational and rational beliefs were associated with death anxiety and if there are possible significant positive correlations between death anxiety and depression, anxiety, and stress. Method: A sample of 200 individuals completed online self-report measures and Structural Equation Modelling (SEM) was chosen to assess the validity of the REBT psychopathological model and the REBT psychological health model. Pearson's correlation analysis was utilized to confirm the relationships between death anxiety and depression, anxiety, and stress. Results: REBT's model of psychopathology provide acceptable fit of the data. Results suggest that LFT beliefs mediate the relationship between DEM and death anxiety, while no mediation effect was found for the psychological health model. Additionally, high correlations were obtained between death anxiety and depression, anxiety, and stress. Conclusions: Results provided empirical support for the REBT models of death anxiety and underline the critical importance of cognitive constructs in the prediction of death anxiety. Results are discussed within the framework of REBT theory, which can serve as a foundation for new research directions regarding death anxiety, both theoretical and clinical.

The Evaluation of the GET.ON Nationwide Web-Only Treatment Service for Depression- and Stress-Related Symptoms: Naturalistic Trial.

BACKGROUND: GET.ON (HelloBetter) treatment interventions have been shown to be efficacious in multiple randomized controlled trials. OBJECTIVE: This study evaluated the effectiveness of 2 GET.ON interventions, GET.ON Mood Enhancer and GET.ON Stress, in a national digital mental health service implemented across Germany. METHODS: Following an initial web-based questionnaire, participants were allocated to either intervention based on their baseline symptom severity and personal choice and received a semistandardized guided, feedback-on-demand guided, or self-guided version of the treatment. Uncontrolled routine care data from 851 participants were analyzed using a pretest-posttest design. Half of the participants (461/851, 54.2%) were allocated to the stress intervention (189/461, 41% semistandardized; 240/461, 52% feedback on demand; and 32/461, 6.9% self-guided), and almost all participants in the mood intervention (349/352, 99.2%) received semistandardized guidance. RESULTS: Results on depression-related symptom severity indicated a reduction in reported symptoms, with a large effect size of d=-0.92 (95% CI -1.21 to -0.63). Results on perceived stress and insomnia indicated a reduction in symptom severity, with large effect sizes of d=1.02 (95% CI -1.46 to -0.58) and d=-0.75 (95% CI -1.10 to -0.40), respectively. A small percentage of participants experienced deterioration in depression-related symptoms (11/289, 3.8%), perceived stress (6/296, 2%), and insomnia (5/252, 2%). After completing treatment, 51.9% (150/289) of participants showed a clinically reliable change in depression-related symptoms, whereas 20.4% (59/289) achieved a close to symptom-free status. Similar improvements were observed in perceived stress and insomnia severity. Guidance moderated the effectiveness of and adherence to the interventions in reducing depressive symptom severity. Effect sizes on depression-related symptom severity were d=-1.20 (95% CI -1.45 to -0.93) for the semistandardized group, d=-0.36 (95% CI -0.68 to -0.04) for the feedback-on-demand group, and d=-0.83 (95% CI -1.03 to -0.63) for the self-guided group. Furthermore, 47.6% (405/851) of the participants completed all modules of the intervention. Participant satisfaction was high across all patient groups and both interventions; 89.3% (242/271) of participants would recommend it to a friend in need of similar help. Limitations include the assignment to treatments and guidance formats based on symptom severity. Furthermore, part of the differences in symptom change between groups must be assumed to be due to this baseline difference in the measures. CONCLUSIONS: Future digital health implementation and routine care research should focus on monitoring symptom deterioration and other negative effects, as well as possible predictors of deterioration and the investigation of individual patient trajectories. In conclusion, this study supports the effectiveness of tailored digital mental health services in routine care for depression- and stress-related symptoms in Germany. The results highlight the importance of guidance in delivering internet-based cognitive behavioral therapy interventions and provide further evidence for its potential delivered as web-only solutions for increasing access to and use of psychological treatments.

Clinical and cognitive insight in panic disorder: phenomenology and treatment effects in internet cognitive behavior therapy.

Clinical observations suggest that individuals with panic disorder (PD) vary in their beliefs about the causes of their panic attacks. Some attribute these attacks to psychological factors, while others to physiological or medical factors. These beliefs also extend to whether individuals perceive panic attacks as dangerous. In other areas of psychiatric nosology, these phenomena are commonly called clinical insight (recognition of disorder and the need for treatment) and cognitive insight (the ability to reflect on one's beliefs). Despite its importance, limited research exists on insight in PD and its relation to symptoms and treatment outcomes. This study examines clinical and cognitive insight in 83 patients with PD who received internet-based cognitive behavioral therapy, investigating their relationship with symptoms, treatment outcomes, and changes in insight. We assessed patients using interview and self-report measures of insight and symptoms. Clinical and cognitive insight were correlated and both constructs improved significantly during treatment. Good clinical insight pretreatment was positively correlated with more severe pretreatment symptoms. Pretreatment clinical and cognitive insight were not correlated with symptom change or attrition. Greater change in clinical and cognitive insight was related to greater change in symptoms. The findings highlight the significance of clinical and cognitive insight in PD, and the importance of distinguishing between them. This suggests the need to develop interventions according to patients' level of insight, particularly focusing on those lacking insight. Further research is essential to advance our understanding of the relationship between insight and the phenomenology and treatment of PD.

Hydrogen peroxide sensitivity connects the activity of COX5A and NPR3 to the regulation of YAP1 expression.

Reactive oxygen species (ROS) are among the most severe types of cellular stressors with the ability to damage essential cellular biomolecules. Excess levels of ROS are correlated with multiple pathophysiological conditions including neurodegeneration, diabetes, atherosclerosis, and cancer. Failure to regulate the severely imbalanced levels of ROS can ultimately lead to cell death, highlighting the importance of investigating the molecular mechanisms involved in the detoxification procedures that counteract the effects of these compounds in living organisms. One of the most abundant forms of ROS is H2 O2 , mainly produced by the electron transport chain in the mitochondria. Numerous genes have been identified as essential to the process of cellular detoxification. Yeast YAP1, which is homologous to mammalian AP-1 type transcriptional factors, has a key role in oxidative detoxification by upregulating the expression of antioxidant genes in yeast. The current study reveals novel functions for COX5A and NPR3 in H2 O2 -induced stress by demonstrating that their deletions result in a sensitive phenotype. Our follow-up investigations indicate that COX5A and NPR3 regulate the expression of YAP1 through an alternative mode of translation initiation. These novel gene functions expand our understanding of the regulation of gene expression and defense mechanism of yeast against oxidative stress.

Are web-based stress management interventions effective as an indirect treatment for depression? An individual participant data meta-analysis of six randomised trials.

QUESTION: Depression is highly prevalent and associated with numerous adverse consequences for both individuals and society. Due to low uptake of direct treatment, interventions that target related, but less stigmatising problems, such as perceived stress, have emerged as a new research paradigm.This individual participant data (IPD) meta-analysis examines if a web-based stress management intervention can be used as an 'indirect' treatment of depression. STUDY SELECTION AND ANALYSIS: Bayesian one-stage models were used to estimate pooled effects on depressive symptom severity, minimally important improvement and reliable deterioration. The dose-response relationship was examined using multilevel additive models, and IPD network meta-analysis was employed to estimate the effect of guidance. FINDINGS: In total, N=1235 patients suffering from clinical-level depression from K=6 randomised trials were included. Moderate-to-large effects were found on depressive symptom severity at 7 weeks post-intervention (d=-0.65; 95% credibility interval (CrI): -0.84 to -0.48) as measured with the Center for Epidemiological Studies' Depression Scale. Effects were sustained at 3-month follow-up (d=-0.74; 95% CrI: -1.01 to -0.48). Post-intervention symptom severity was linearly related to the number of completed sessions. The incremental impact of guidance was estimated at d=-0.25 (95% CrI: -1.30 to 0.82), with a 35% posterior probability that guided and unguided formats produce equivalent effects. CONCLUSIONS: Our results indicate that web-based stress management can serve as an indirect treatment, yielding effects comparable with direct interventions for depression. Further research is needed to determine if such formats can indeed increase the utilisation of evidence-based treatment, and to corroborate the favourable effects for human guidance. STUDY REGISTRATION: Open material repository: osf.io/dbjc8, osf.io/3qtbe. TRIAL REGISTRATION NUMBER: German Clinical Trial Registration (DRKS): DRKS00004749, DRKS00005112, DRKS00005384, DRKS00005687, DRKS00005699, DRKS00005990.