Study protocol to investigate the efficacy of confocal laser endomicroscopy-based selective single-elimination diet over standard fivefold elimination diet in patients with endomicroscopically proven food intolerance: app-assisted, monocentric, double-blind, randomised and controlled trial in Germany.

INTRODUCTION: Imprecise nutritional recommendations due to a lack of diagnostic test accuracy are a frequent problem for individuals with adverse reactions to foods but no precise diagnosis. Consequently, patients follow very broad and strict elimination diets to avoid uncontrolled symptoms such as diarrhoea and abdominal pain. Dietary limitations and the uncertainty of developing gastrointestinal symptoms after the inadvertent ingestion of food have been demonstrated to reduce the quality of life (QoL) of affected individuals and subsequently might increase the risk of malnutrition and intestinal dysbiosis. This trial aims to investigate the effects of a tailored diet based on the confocal laser endoscopy (CLE) examination result to limit the side effects of unspecific and broad elimination diets and to increase the patient's QoL. METHODS AND ANALYSIS: The study is designed as a prospective, double-blind, monocentric, randomised and controlled trial conducted at the University Hospital of Schleswig-Holstein, Campus Lübeck, Germany. One hundred seventy-two patients with non-IgE-related food allergies and positive CLE results will be randomised to either a tailored diet or a standard fivefold elimination diet. The primary endpoints are the difference between the end and the start of the intervention in health-related QoL and the sum score of the severity of symptoms after 12 weeks. Key secondary endpoints are changes in the severity of symptoms, further QoL measurements, self-assessed state of health and number of days with a pathologically altered stool. Microbiome diversity and metabolome of stool, urine and blood will also be investigated. Safety endpoints are body composition, body mass index and adverse events. ETHICS AND DISSEMINATION: The study protocol was accepted by the ethical committee of the University of Lübeck (AZ: 22-111) on 4 May2022. Results of the study will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00029323).

Repressive and vigilant coping styles in stress and relaxation: evidence for physiological and subjective differences at baseline, but not for differential stress or relaxation responses.

Introduction: Previous research suggested differential stress reactivity depending on individuals' coping style, e.g., as classified by the model of coping modes. Specifically, stronger physiological reactivity and weaker subjective stress ratings were found for repressors than for sensitizers. However, it remains to be investigated (i) whether these findings, which are largely based on social stress induction protocols, also generalize to other stressors, (ii) whether repressors vs. sensitizers also exhibit differential stress recovery following the application of a relaxation method, and (iii) which stress reactivity and recovery patterns are seen for the two remaining coping styles, i.e., fluctuating, and non-defensive copers. The current study thus examines stress reactivity in physiology and subjective ratings to a non-social stressor and the subsequent ability to relax for the four coping groups of repressors, sensitizers, fluctuating, and non-defensive copers. Methods: A total of 96 healthy participants took part in a stress induction (Mannheim Multicomponent Stress Test) and a subsequent relaxation intervention. Subjective ratings of stress and relaxation, heart rate (HR), heart rate variability (HRV), and blood pressure were assessed during the experiment. HR and blood pressure are markers of the sympathetic stress response that can be regulated by relaxation, while HRV should increase with relaxation. To investigate long-term relaxation effects, subjective ratings were also assessed on the evening of testing. Results: Despite successful stress induction, no differential responses (baseline to stress, stress to relaxation) were observed between the different coping groups on any of the measures. In contrast, a strong baseline effect was observed that persisted throughout the experiment: In general, fluctuating copers showed lower HR and higher HRV than non-defensive copers, whereas repressors reported lower subjective stress levels and higher levels of relaxation during all study phases. No differences in subjective ratings were observed in the evening of testing. Conclusion: Contrary to previous research, no differential stress reactivity pattern was observed between coping groups, which could be due to the non-social type of stressor employed in this study. The novel finding of physiological baseline differences between fluctuating and non-defensive individuals is of interest and should be further investigated in other stressor types in future research.

Cardiac response in aversive and appetitive olfactory conditioning: Evidence for a valence-independent CS-elicited bradycardia.

While the examination of conditioned cardiac responses is well established in human fear conditioning research, comparable studies using less-aversive or rather appetitive unconditioned stimuli (UCS) are sparse and results are mixed. Therefore, the aim of this study was a systematic analysis of cardiac reactions in aversive and appetitive conditioning. Olfactory stimuli were used as unconditioned stimuli as they are suitable reinforcers in both an aversive and an appetitive conditioning offering the opportunity for a comparison between conditioned responses. In total, n = 86 participants took part in both an aversive and an appetitive differential conditioning task with a counterbalanced order across participants. Aversive or appetitive odors, respectively, served as UCS and neutral geometrical figures as CS. Subjective ratings, skin conductance response (SCRs), and evoked cardiac reactions were analyzed and compared between tasks. Conditioned responses in subjective ratings could be observed in both aversive conditioning and appetitive conditioning, while SCRs discriminated between CS+ and CS- in aversive conditioning only. Regarding conditioned cardiac responses, the deceleration for the CS+ was longer than for the CS- in both tasks. In addition, a higher deceleration magnitude and a shorter acceleration for the CS+ as compared to the CS- were found in aversive but not in appetitive conditioning. There were medium-size correlations between aversive and appetitive CRs for subjective ratings and none for physiological responses. The results suggest similarities between cardiac response patterns in aversive and appetitive conditioning, which implies that bradycardia in conditioning might not be fear-specific but presents a valence-independent CS-elicited bradycardia.

Validation of the Four-Dimensional Symptom Questionnaire (4DSQ) in a mental health setting.

Mental health problems are highly prevalent in primary care. Validated tools to detect mental disorders in general practice are needed. The Four-Dimensional Symptom Questionnaire (4DSQ) was designed to help GPs differentiating between psychological distress and psychopathological conditions (depression, anxiety, somatization). The aim of the current study was to examine psychometric properties of the 4DSQ in a mental health setting. Reliability, factorial, construct, and criterion validity of the English translation of the 4DSQ were analyzed in an American sample of 159 patients attending a psychotherapy outpatient clinic. Measurement equivalence across languages was determined by analyzing differential item functioning (DIF) and differential test functioning (DTF) in the American sample and a Dutch mental health sample, matched by age and sex. A confirmatory factor analysis confirmed all 4DSQ subscales to be unidimensional. All 4DSQ subscales revealed excellent reliability (Cronbach's alpha and McDonald omega ≥.90) and high correlations with a symptom distress subscale of an instrument that is commonly used to monitor psychotherapy progress, the Outcome Questionnaire-45. Eight items were flagged with DIF. The Depression subscale was free of DIF. DTF analyses showed an impact of DIF on scale level for the lower cutoff score of the Distress scale. The 4DSQ Distress score was the best predictor of a mood disorder diagnosis and the Anxiety score outperformed other 4DSQ scales to predict an anxiety disorder. In conclusion, the 4DSQ demonstrates excellent reliability and validity in a mental health setting. Further research is needed to determine reliable cutoff values on 4DSQ subscales to predict psychiatric diagnoses.

Cross-cultural validation of the German version of the Four-Dimensional Symptom Questionnaire (4DSQ) in multimorbid elderly people.

PURPOSE: Psychosomatic symptoms and mental health problems are highly prevalent in multimorbid elderly people challenging general practitioners to differentiate between normal stress and psychopathological conditions. The 4DSQ is a Dutch questionnaire developed to detect anxiety, depression, somatization, and distress in primary care. This study aims to analyze measurement equivalence between a German version and the original Dutch instrument. METHODS: A Dutch and a German sample of multimorbid elderly people, matched by gender and age, were analyzed. Equivalence of scale structures was assessed by confirmatory factor analysis (CFA). To evaluate measurement equivalence across languages, differential item functioning (DIF) was analyzed using Mantel-Haenszel method and hybrid ordinal logistic regression analysis. Differential test functioning (DTF) was assessed using Rasch analysis. RESULTS: A total of 185 German and 185 Dutch participants completed the questionnaire. The CFA confirmed one-factor models for all scales of both 4DSQ versions. Nine items in three scales were flagged with DIF. The anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale impact of DIF. CONCLUSIONS: The German 4DSQ demonstrated measurement equivalence to the original Dutch instrument. Hence, it can be considered a valid questionnaire for the screening for mental health problems in primary care.