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What differentiates those who are able to adapt well to adverse life events (i.e., persons who are resilient) from those who are not (e.g., persons who develop post-traumatic stress symptoms)? Previous work suggests that enhanced autobiographical integration of trauma memories is associated with more severe post-traumatic stress symptoms. Extending this line of work, the present study looked at whether the integration of trauma memories, repressive coping and cognitive reactivity are related to post-traumatic stress symptomatology following negative life events among otherwise healthy young adults (N = 213). Results show that while enhanced integration of trauma memories and high levels of dissociation are related to elevated levels of post-traumatic stress, people who generally engage in repressive coping report fewer post-traumatic stress symptoms. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message: · Enhanced integration of trauma memories is linked to increased post-traumatic stress. · High levels of trait dissociation are related to elevated levels of post-traumatic stress symptomatology. · A repressive coping style is associated with fewer post-traumatic stress symptoms. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha expression in the synovium before initiation of treatment.Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 > or =1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response.Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNFalpha expression is a significant predictor of response to TNFalpha blocking therapy. TNFalpha expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNFalpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1beta, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNFalpha treatment.Conclusion: The effects of TNFalpha blockade are in part dependent on synovial TNFalpha expression and infiltration by TNFalpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms. [ABSTRACT FROM AUTHOR]

Addressing multiple health behaviours are important in preventing disease and mortality. The present study investigated the clustering of health behaviours, cognitive determinants and stages of change in 2827 adults for the lifestyle factors of physical activity, fruit, vegetable and fat consumption and smoking. The results showed that only 3% of the total population met recommended guidelines for all of the five behaviours. Behaviours were found to be weakly associated. Behaviour-specific cognitions and stages of change for the behaviours clustered more strongly, however. With respect to diet and physical activity, respondents in the preparation stage for one behaviour were likely also to be preparing to change another behaviour. Possible mechanisms for the apparent general willingness to change multiple behaviours are discussed, as well as potential implications for health promotion practice. [ABSTRACT FROM AUTHOR]

This article focuses on the use of brain scans to distinguish between true and false memories in a forensic context. Some authors have argued that these two types of memories have different neural correlates. Because true memories would contain more perceptual details, these memories would lead to more activation in brain areas responsible for perceptual information processing than false memories. We describe techniques designed to elicit false memories and mention two different theoretical accounts explaining why false memories are sometimes created. After briefly introducing different brain imaging techniques, an overview of research on neural correlates distinguishing between true and false memories is given. In some studies, it was found that, compared to false memories, true memories are associated with unique activity in brain areas underlying perceptual processing. However, other studies were unable to find differences in neural correlates between the two types of memories. In addition, research in this area has used false memory paradigms that may tell little about false memories in real life. All together, it seems that brain scans are not yet applicable to assess the veracity of memories in a forensic context. [ABSTRACT FROM AUTHOR]

To explore whether schizotypal traits may undermine source monitoring for actions, 67 undergraduate participants (21 men) completed the Schizotypal Personality Scale and were then given a source-monitoring task in which some specific acts had to be performed, whereas others only had to be imagined. Next, participants had to complete an old-new recognition task and ascribe the source, i.e., whether they had performed or only imagined the items (i.e., source monitoring). Participants also completed a working memory capacity task (i.e., Operation Span task). We found that the higher the Schizotypal Personality Scale scores, the poorer recognition and source attribution scores. Relative to participants with low levels of schizotypal traits (i.e., controls), those with higher levels of schizotypal traits more often falsely claimed to have performed actions when in fact they had only imagined them. Although participants high and low in schizotypical traits did not differ in their working memory capacity, poor working memory capacity was related to source misattribution (i.e., increase false alarms). The present findings indicate that schizotypal traits undermine source monitoring for action in a healthy population. [ABSTRACT FROM AUTHOR]

Obese children are often liable to weight-related teasing, and in earlier studies this childhood teasing has been found to predict body dissatisfaction. Cognitive theory postulates that negative experiences are the source of interpretation biases, implicating that weight-related teasing might make obese children vulnerable to shape- and weight-related interpretation biases. In the present study, it was tested whether young overweight children show interpretation biases related to body weight/shape and self-esteem. A Situation Interpretation Test (SIT) was used to find out whether overweight children (n = 20) interpret neutral and negative ambiguous situations more often in terms of their concerns about body weight/shape and self-esteem than healthy controls (n = 16). The data show that 8- to 12-year-old overweight children indeed show interpretation biases, that is, they were more likely to endorse negative appearance and self-esteem-related interpretations of a neutral or negative event than normal-weight children. Also, the perceived threat value of these events was higher in the overweight group. Interpretation biases like this might increase and maintain body dissatisfaction and psychological distress. It is therefore argued that the vulnerability to the development of an interpretation bias emphasises the need to use cognitive strategies that tackle these biases in the treatment of overweight children. [ABSTRACT FROM AUTHOR]

The relationship between dissociative tendencies, as measured with the Dissociative Experiences Scale and its amnesia, absorption/imaginative involvement, and depersonalization/derealization subscales, and HPA axis functioning was studied in 2 samples of undergraduate students (N = 58 and 67). Acute stress was induced by means of the Trier Social Stress Test. Subjective and physiological stress (i.e., cortisol) responses were measured. Individuals high on the depersonalization/derealization subscale of the Dissociative Experiences Scale exhibited more pronounced cortisol responses, while individuals high on the absorption subscale showed attenuated responses. Interestingly, subjective stress experiences, as indicated by the Tension-Anxiety subscale of the Profile of Mood States, were positively related to trait dissociation. The present findings illustrate how various types of dissociation (i.e., depersonalization/derealization, absorption) are differentially related to cortisol stress responses. [ABSTRACT FROM AUTHOR]

Objectives. Eating-disordered subjects feel unattractive, and the current idea is that this feeling reflects a distorted body image. A distorted body image requires a mismatch between the negative self-judgments and more objective judgments of the body.Design and methods. To examine whether eating-disordered subjects have valid reasons for their feelings of unattractiveness, the body images of eating-symptomatic subjects and control models were compared with inter-subjective evaluations of these bodies given by two community samples (panels; N=72, N=88).Results. Although the objective body sizes of the eating-symptomatic subjects were in the normal range and not different from control bodies, the first panel rated the (headless) bodies of the eating-symptomatic subjects as less attractive. This finding was replicated with the second panel. There was also large agreement between the eating-symptomatic subjects and the second panel on the specific body parts that were indicated as unattractive. Contrary to the eating-symptomatic subjects, the control models showed a strong positively biased perception of their own attractiveness: they rated their own bodies more positively than others rated them.Conclusion. Consensual validation of the harsh body appraisals of eating-symptomatic subjects was found. Interestingly, the normal controls were the ones that showed a biased body image; they rated themselves far more attractive than other people rated them. These data suggest that the real problem in eating disorders is not a distorted body image but a lack of a distorted body image, that is, the lack of a self-serving body-image bias. [ABSTRACT FROM AUTHOR]

It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanis that contribute to the increased susceptiblity of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surfac on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study sugpurified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMB may lead to reduced clearance of bacteria from the joint. [ABSTRACT FROM AUTHOR]

Highlights • 112 healthy participants performed an instrumental learning task. • Individual differences in baseline and stress-induced working memory (WM) were assessed. • Baseline WM capacity modulates effect of stress on instrumental behavior. • Stress induces a shift to less goal-directed behavior at low baseline WM. Abstract Acute stress has been found to impair goal-directed instrumental behaviour, a cognitively flexible behaviour that requires cognitive control. The current study aimed to investigate the role of individual differences in baseline and stress-induced changes in working memory (WM) on the shift to less goal-directed responding under stress. To this end, 112 healthy participants performed an instrumental learning task. In phase 1, participants learned instrumental actions that were associated with two different food rewards. In phase 2, one of these food rewards was devalued by eating until satiety. Before the extinction test in phase 3, participants were subjected to the Maastricht Acute Stress Test or a no-stress control procedure. Results showed that the effect of stress on instrumental behaviour is modulated by baseline, but not stress-induced changes in WM capacity. Specifically, only at low baseline WM capacity did stress induce a shift to less goal-directed behaviour. These findings highlight that our cognitive resources are limited and for those who already have limited resources at baseline taking into account motivational value is impaired under stress. [ABSTRACT FROM AUTHOR]

Reliably eliciting acute stress repeatedly over time is of indispensable value for research into stress vulnerability and for developing interventions aimed at increasing stress resiliency. Here, we evaluated whether the Maastricht Acute Stress Test (MAST), a potent stress protocol that combines physical and psychosocial stress components, can be used to reliably elicit subjective and neuroendocrine stress responses multiple times. Sixty healthy undergraduate participants were exposed to the MAST on three occasions, with intervals of three-weeks and one-month in between sessions. Results showed no significant signs of habituation or sensitization to the MAST in terms of subjective or physiological (salivary alpha-amylase and cortisol) stress reactivity. Fifty-nine percent of the sample displayed a significant physiological stress response (i.e., cortisol) to two MAST exposures and 57% to every MAST exposure. This study demonstrates that the MAST can be used to repeatedly induce significant stress responses. [ABSTRACT FROM AUTHOR]

Asymmetry in frontal electrical activity has been suggested to index tendencies in affective responding and thus may be associated with hormonal stress responses. To assess the functional role of frontal asymmetry (FA) in stress, we measured FA at rest and following exposure to acute stress induced with the Maastricht Acute Stress Task (MAST; N = 70) in the standard 8–13 Hz band as well as based on individual alpha frequency (IAF) band. IAF-based resting FA F4–F3 was associated with the stress-induced neuroendocrine response, such that left individual frontal activity predicted smaller total cortisol increases in response to the MAST. Like previous studies, we found resting left-sided FA F8–F7 to predict trait behavioural activation measured with the BIS/BAS scales. FA remained unaffected by stress-induced cortisol response. These findings suggest that individual FA might reflect a trait-like characteristic that moderates the stress response. Our results underscore the utility of IAF in studying individual differences in stress responding. [ABSTRACT FROM AUTHOR]

Stress initiates a cascade of (neuro)biological, physiological, and behavioral changes, allowing us to respond to a challenging environment. The human response to acute stress can be studied in detail in controlled settings, usually in a laboratory environment. To this end, many studies employ acute stress paradigms to probe stress-related outcomes in healthy and patient populations. Though valuable, these studies in themselves often have relatively limited sample sizes. We established a data-sharing and collaborative interdisciplinary initiative, the STRESS-NL database, which combines (neuro)biological, physiological, and behavioral data across many acute stress studies in order to accelerate our understanding of the human acute stress response in health and disease (www.stressdatabase.eu). Researchers in the stress field from 12 Dutch research groups of 6 Dutch universities created a database to achieve an accurate inventory of (neuro)biological, physiological, and behavioral data from laboratory-based human studies that used acute stress tests. Currently, the STRESS-NL database consists of information on 5529 individual participants (2281 females and 3348 males, age range 6–99 years, mean age 27.7 ± 16 years) stemming from 57 experiments described in 42 independent studies. Studies often did not use the same stress paradigm; outcomes were different and measured at different time points. All studies currently included in the database assessed cortisol levels before, during and after experimental stress, but cortisol measurement will not be a strict requirement for future study inclusion. Here, we report on the creation of the STRESS-NL database and infrastructure to illustrate the potential of accumulating and combining existing data to allow meta-analytical, proof-of-principle analyses. The STRESS-NL database creates a framework that enables human stress research to take new avenues in explorative and hypothesis-driven data analyses with high statistical power. Future steps could be to incorporate new studies beyond the borders of the Netherlands; or build similar databases for experimental stress studies in rodents. In our view, there are major scientific benefits in initiating and maintaining such international efforts. • This article describes a collaborative initiative combining data from human acute stress studies. • There are (neuro)biological, physiological, and behavioral data from 12 Dutch research groups. • The STRESS-NL database has data on 5529 participants stemming from 57 experiments. • The STRESS-NL database illustrates the potential of combining existing stress data. [ABSTRACT FROM AUTHOR]

Acute stress is associated with a shift from goal-directed to habitual behavior. This stress-induced preference for habitual behavior has been suggested as a potential mechanism by which binge eating disorder (BED) patients succumb to eating large amounts of high-caloric foods in an uncontrolled manner (i.e., binge episodes). While in healthy subjects the balance between goal-directed and habitual behavior is subserved by the anterior cingulate cortex (ACC), insular cortex, orbitofrontal cortex (OFC), anterior caudate nucleus, and posterior putamen, the brain mechanism that underlies this (possibly amplified) stress-induced behavioral shift in BED patients is currently unknown. In the current study, 76 participants (38 BED, 38 healthy controls (HCs)) learned six stimulus-response-outcome associations in a well-established instrumental learning task. Subsequently, three outcomes were selectively devalued, after which participants underwent either a stress induction procedure (Maastricht Acute Stress Test; MAST) or a no-stress control procedure. Next, the balance between goal-directed and habitual behavior was assessed during functional magnetic resonance imaging. Findings show that the balance between goal-directed and habitual behavior was associated with activity in the ACC, insula, and OFC in no-stress HCs. Although stress and BED did not modulate the balance between goal-directed and habitual behavior, BED participants displayed a smaller difference in putamen activation between trials probing goal-directed and habitual behavior compared with HCs when using a ROI approach. We conclude that putamen activity differences between BED and HC could reflect changes in monitoring of response accuracy or reward value, albeit perhaps not sufficiently to induce a measurable shift from goal-directed to habitual behavior. Future research could clarify potential boundary conditions of stress-induced shifts in instrumental behavior in BED patients. • Putamen activity differences in goal-directed action and habits was reduced in BED. • BED did not boost the shift in goal-directed to habitual responding. • Acute stress did not impact brain activity or behavior. [ABSTRACT FROM AUTHOR]

Entomopathogenic nematodes (EPNs) have emerged as a promising tool for controlling soil-dwelling crop pests. However, their efficacy varies according to EPN populations and targeted hosts. Wireworms are polyphagous insects causing significant crop losses, especially since the ban on pesticides previously used for their control. They are highly resistant to EPN populations and require high number of infective juveniles (IJs) to achieve optimal mortality rates. In this research, we collected and compared the virulence of 16 EPN populations, of foreign origin, purchased or collected from wireworms infested fields. Then, we have tested two hypotheses: (i) smaller nematodes induce heightened mortality rates against wireworms; (ii) virulence levels can be linked to nematodes-bacteria complex. Mortality rates scaled from three to 43 % after 56 days of continuous exposure across the 16 tested EPN populations (Heterorhabditis spp. and Steinernema spp.). Morphometric analysis of IJs revealed both intra- and interspecific variations in length and diameter among populations. Interestingly, while EPN length influence mortality at three days post-inoculation. We found leaner IJs (< 25 µm) to induce higher mortality rates at 56 days post-inoculation. To better determine the structure and dimensions of the primary entry routes utilized by EPNs, we provide optical microscope micrographs of wireworm Agriotes spp. spiracle, anal sclerotized coating anus and anal muscles. Symbiotic bacteria of each EPN population were identified, and a biochemical characterization was performed using Analytical Profile Index tests. The symbiotic bacteria belong to the species Photorhabdus antumapuensis, P. laumondii subsp. laumondii, P. thracensis, Xenorhabdus bovienii and X. nematophila. Bacteria biochemical profiles did not reflect the differences in virulence of nematodes-bacteria complex against wireworms. These findings highlight the importance of considering EPN morphometry and intraspecific variability in designing applications to control wireworms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: Limited observational evidence suggests that a higher intake of high-fat dairy may be associated with lower prediabetes risk, while opposite associations have been observed for low-fat milk intake. This study aimed to examine associations between baseline and changes in dairy consumption, risk of prediabetes, and glycaemic status., Methods: 7521 participants from the prospective UK Fenland study were included (mean age 48.7 ± 2.0 years, 51.9 % female). Dairy intake was measured using self-reported food frequency questionnaires. Associations with prediabetes risk and glycaemic status were analysed using Poisson regression models adjusted for social demographics, health behaviours, family history of diabetes and food group intake., Results: At a mean follow-up of 6.7 ± 2.0 years, 290 participants developed prediabetes (4.3 %). Most dairy products were not significantly associated with prediabetes risk. A higher baseline intake of high-fat dairy (RR servings/day 1.20, 95%CI 1.03-1.39) and high-fat milk (RR servings/day 1.22, 1.01-1.47) were associated with higher prediabetes risk. Conversely, low-fat milk was associated with lower prediabetes risk (RR servings/day 0.86, 0.75-0.98). In the analyses evaluating dietary changes over time, increases in high-fat milk were inversely associated with risk of progressing from normoglycaemia to prediabetes or type 2 diabetes (RR servings/day 0.86, 95%CI 0.75-0.99)., Conclusions: This population-based study showed that most dairy products are not associated with prediabetes risk or progression in glycaemic status. Positive associations of high-fat dairy, high-fat milk, and the inverse association of low-fat milk with prediabetes risk found were inconsistent with prior literature and suggestive of the need for future research on environmental, behavioural, and biological factors that explain the available evidence., Competing Interests: Conflict of interest SSS-M has received unrestricted grants from the Global Dairy Platform, Dairy Research Institute, and Dairy Australia for a meta-analysis on cheese and blood lipids (2012) and a meta-analysis of dairy and mortality (2015). She received the Wiebe Visser International Dairy Nutrition Prize and has received recent research funding (2023) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association and the Danish Dairy Research Foundation. IS has received recent research funding (2023) for epidemiological studies on dairy products and cardiometabolic diseases from the Dutch Dairy Association. All other authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Acute abdominal pain is a common complaint, caused by a variety of conditions, ranging from acutely life-threatening to benign and self-limiting, with symptom overlap complicating diagnosis. Signs and symptoms may be valuable when assessing a patient to guide clinical work., Aim: Summarising evidence on the accuracy of signs and symptoms for diagnosing serious illness in adults with acute abdominal pain in an ambulatory care setting., Design & Setting: We performed a systematic review, searching for prospective diagnostic accuracy studies that included adults presenting with acute abdominal pain to an ambulatory care setting., Method: Six databases and guideline registers were searched, using a comprehensive search strategy. We assessed the risk of bias, and calculated descriptive statistics and measures of diagnostic accuracy. Results were pooled when at least four studies were available., Results: Out of 18 923 unique studies, 16 studies with moderate to high-risk bias were included. Fourteen clinical features met our criteria, including systolic blood pressure <100 mmHg (positive likelihood ratio [LR+]7.01), shock index >0.85, uterine cervical motion tenderness (LR+5.62 and negative likelihood ratio [LR-]8.60), and a self-assessment questionnaire score >70 (LR+12.20) or <25 (LR-0.19). Clinical diagnosis made by the clinician had the best rule-in ability (LR+24.6)., Conclusions: We identified 14 signs and symptoms that can influence the likelihood of a serious illness, including pain characteristics, systemic signs, gynaecological signs, and clinician's overall assessment. The risk of bias was moderate to high, leading to uncertainty and preventing us from making firm conclusions. This highlights the need for better research in this setting., (Copyright © 2024, The Authors.)

Purpose: A significant proportion of cancer patients suffer from chemotherapy-induced peripheral neuropathy (CIPN). This descriptive study aimed to examine patients' experience of CIPN symptoms, daily limitations, involvement of healthcare professionals, and social support., Methods: Cross-sectional data have been collected in the Netherlands via a national online questionnaire comprising closed items only (February 2021)., Results: Out of 3752 respondents, 1975 received chemotherapy only (i.e., without targeted therapy) and were therefore included. The majority (71.2%) reported symptoms in both hands and feet (e.g., tingling and loss of sensation or diminished sensation). Participants reported most limitations in household chores, social activities, hobbies, sports, walking, and sleeping and least in family/(taking care of) children, cycling, driving, self-care, eating and drinking, and sexuality and intimacy. Many patients indicated that their healthcare professionals informed them about the possibility of CIPN development before treatment (58.4%), and they paid attention to CIPN during and after treatment (53.1%). However, many patients (43%) reported a lack of information on what to do when CIPN develops. Few participants (22%) visited their general practitioner (GP) for CIPN. In general, patients' social environments sometimes to always showed empathy to patients., Conclusions: Symptoms of CIPN are frequently reported and can result in various daily limitations. Support from professionals and peers is crucial in managing CIPN, which is sometimes lacking. Appropriate guidance and support should be provided to patients to decrease the impact of CIPN on daily life. Future research should investigate differences in chemotherapeutic agents and the resulting symptoms and consequences., (© 2023. The Author(s).)

Background: Modest inverse associations have been found between dairy intake, particularly yogurt, and type 2 diabetes risk. Investigating associations of dairy intake with early onset of type 2 diabetes offers opportunities for effective prevention of this condition., Objectives: This study aims to investigate the relationships between the intake of different dairy types, prediabetes risk, and continuous glycemic outcomes., Methods: Systematic literature searches across multiple databases were performed of studies published up to September 2023. Included were prospective cohort studies in healthy adults that examined the association between dairy intake and prediabetes risk according to diagnostic criteria, or continuous glycemic markers. A dose-response random-effects meta-analysis was used to derive incremental relative risks (RRs) for associations of total dairy, fermented dairy, milk, yogurt, cheese (all total, high-fat, and low-fat), cream, and ice cream with prediabetes risk adjusted for sociodemographic, health and cardiometabolic risk factors, and dietary characteristics., Results: The meta-analyses encompassed 6653 prediabetes cases among 95,844 individuals (age range 45.5-65.5 y) including 6 articles describing 9 cohorts. A quadratic inverse association was observed for total dairy intake and prediabetes risk, with the lowest risk at 3.4 servings/d (RR: 0.75; 95% confidence interval: 0.60, 0.93; I 2 = 18%). Similarly, total, and high-fat cheese exhibited nonlinear inverse associations with prediabetes risk, showing the lowest risk at 2.1 servings/d (0.86; 0.78, 0.94; I 2 = 0%, and 0.90; 0.81, 0.99; I 2 = 12%), but a higher risk at intakes exceeding 4 servings/d. Ice cream intake was linearly associated with prediabetes risk (0.85; 0.73, 0.99; I 2 = 0% at the highest median intake of 0.23 servings/d). Other dairy types showed no statistically significant associations. The systematic review on dairy intake and glycemic outcomes showed considerable variabilities in design and results., Conclusions: The findings suggest an inverse association between moderate dairy and cheese intake in preventing prediabetes. The potential for reverse causation and residual confounding highlights the need for studies with comprehensive repeated measurements., Trial Registration Number: PROSPERO 2023 CRD42023431251., (© 2024 The Authors.)

Background and Objectives: Appetitive and aversive conditioning are thought to be involved in the development and maintenance of mental disorders including anxiety, mood, eating, and substance use disorders. However, few studies measure the relative strength of appetitive and aversive associations, and their relevance to the risk of mental disorders. This study aims to address this gap., Methods: We tested how readily healthy volunteers acquire appetitive vs. aversive associations. 150 participants associated complex 3D objects with either gain or loss and made decisions to gain or avoid losing points. We investigated the relationship of a learning asymmetry with neuroticism, impulsivity, and anhedonia, to test the hypothesis that a stronger learning asymmetry corresponds to more extreme scores on these traits., Results: Impulsivity was positively associated with the learning asymmetry (R 2  = .10). This resulted from an inverse relation with the strength of aversive associations, indicating that impulsive individuals are worse at aversive learning. However, appetitive associations did not differ significantly. No correlations with neuroticism or anhedonia were found., Limitations: Conditioning studies typically use primary reinforcers and a CS-. Lacking these may make these results less comparable to other studies., Conclusions: We demonstrate that the learning asymmetry can measure individual differences linked to personality traits, and that impulsivity, normally linked with appetitive learning, also influences aversive learning. These results enable additional studies of learning asymmetry in relation to mental disorders, which could include measurements of mental health symptoms to provide further insight into how appetitive and aversive learning interacts with mental disorders., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and to note the financial contributions to this work. This study is part of the project ‘New Science of Mental Disorders’ (www.nsmd.eu), supported by the Dutch Research Council and the Dutch Ministry of Education, Culture and Science (NWO gravitation grant number 024.004.016). The primary recipient of the grant is Dr. Anita Jansen.We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us.We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved human research participants has been conducted with the ethical approval of the local ethical review committee and that such approvals are acknowledged within the manuscript. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)