Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis.

RATIONALE: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia and primary immunodeficiency disorders), but most cases remain idiopathic. OBJECTIVES: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. METHODS: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived, cells, cell cultures and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. MEASUREMENTS AND MAIN RESULTS: We identified bi-allelic pathogenic variants in WFDC2 in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and thus secretion of mature WFDC2. CONCLUSIONS: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Climate change-related concerns in psychotherapy: therapists' experiences and views on addressing this topic in therapy.

BACKGROUND: While adverse impacts of climate change on physical health are well-known, research on its effects on mental health is still scarce. Thus, it is unclear whether potential impacts have already reached treatment practice. Our study aimed to quantify psychotherapists' experiences with patients reporting climate change-related concerns and their views on dealing with this topic in psychotherapy. METHODS: In a nationwide online survey, responses were collected from 573 psychotherapists from Germany. Therapists reported on the presence of such patients, their socio-demographic characteristics, and climate change-related reactions. Psychotherapists' views on dealing with this topic in psychotherapy were also assessed. Descriptive statistics were used to analyse the responses. RESULTS: About 72% (410/573) of psychotherapists indicated having had patients expressing concerns about climate change during treatment. Out of these therapists, 41% (166/410) stated that at least one patient sought treatment deliberately because of such concerns. Patients were mainly young adults with higher education. Most frequent primary diagnoses were depression, adjustment disorder, and generalized anxiety disorder. Psychotherapists having encountered such patients differed from those without such encounters in their views on potential functional impairment and the necessity to target the concerns in treatment. Although 79% (326/415) of all respondents felt adequately prepared by their current therapeutic skills, 50% (209/414) reported a lack of information on how to deal with such concerns in therapy. CONCLUSIONS: Results indicate that psychotherapists are frequently confronted with climate change-related concerns and regard the mental health impact of climate change on their patients as meaningful to psychotherapeutic care. Regular care could be improved by a continuous refinement of the conceptualization and knowledge of the mental health influences of climate change. This would allow providing tailored methods of assessing and addressing climate change-related concerns in practice.

Stability of Treatment Effects and Caregiver-Reported Outcomes: A Meta-Analysis of Trauma-Focused Cognitive Behavioral Therapy for Children and Adolescents.

The efficacy of trauma-focused treatments for children and adolescents is well researched. However, less is known about the long-term and caregiver-reported effects. Searched databases were PsychInfo, MEDLINE, Cochrane Library, PTSDPubs, PubMed, Web of Science, and OpenGrey. Treatment effects of trauma-focused cognitive behavioral therapy (TF-CBT) were computed at 12-month follow-up with posttraumatic stress symptoms (PTSS) as primary outcome and symptoms of depression, anxiety, and grief as secondary outcomes. Concordance between participant and caregiver ratings were investigated. TF-CBT showed large improvements across all outcomes from pre-treatment to 12-month follow-up (PTSS: g = 1.71, CI 1.27-2.15) and favorable results compared to active treatments and treatment as usual at 12-month follow-up (PTSS: g = .35, CI .13-.56). More pronounced effects were found in group settings. No significant differences were detected between participant and caregiver ratings with high reliability across almost all outcomes and assessment points. TF-CBT is a reliable treatment for pediatric PTSS and secondary symptoms with stable results at 12-month follow-up.

Effects of prenatal Doppler ultrasound on the retina of the chick embryo in ovo.

Currently, the effect of prenatal ultrasound on foetal development is intensively discussed and the guidelines for prenatal diagnostics have been changed. However, data supporting these concerns are scarce. Therefore, we used an established in ovo model of the chicken embryo to investigate cell proliferation and apoptosis within the retina. A total of 21 chicken eggs were fenestrated on Day 5 and allocated to either the control (n = 8) or exposition group (n = 13). The exposition group was treated with pulsed-wave Doppler ultrasound (PWD) for 10 min while controls remained without treatment. After subsequent incubation (6-48 h), the eggs were sacrificed, and chicken embryos were examined morphologically (HE-staining) and immunohistochemically. Counting of apoptotic and proliferating cells per retina was performed using antibodies specific for phospho-histone-H3 and active caspase-3 in combination with a biotin-labelled secondary antibody and peroxidase conjugated avidin-biotin complex for chromogenic detection. Due to a rather low number of specimens at each time point after ultrasound exposition, we neglected the effects of incubation time and focused on treatment effects. This approach revealed that the median number of proliferating cells is reduced after 10 min of exposure to PWD (569 vs. 766), while the number of apoptotic cells is fairly comparable between groups (5 vs. 6). Our data contribute to a better understanding of prenatal US on foetal development by suggesting that PWD could have an impact on the number of proliferating cells in the developing chicken retina and therefore justify further investigations.

Fecal microbiota transplantation for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS. AIM: To assess the efficacy and safety of FMT for the treatment of IBS. METHODS: We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence. RESULTS: Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision. CONCLUSION: We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.

The influence of reward in the Simon task: Differences and similarities to the Stroop and Eriksen flanker tasks.

Previous studies have suggested that performance-contingent reward can modulate cognitive control by biasing irrelevant location-response associations in the Simon task. However, the influence of reward in the case of irrelevant words (Stroop task) or irrelevant flankers (Eriksen Flanker task) remains unclear. Across two preregistered experiments, the present study investigated the influence of reward on conflict processing with different types of distractors. Conflict effects on mean reaction time (RT) were reduced in the Simon task (Experiments 1 and 2) when incongruent versus congruent trials were rewarded, and this modulating effect of reward on conflict processing was also observed in the Eriksen flanker task (Experiment 2), but not in the Stroop task (Experiment 1). We propose that cognitive control adjustments to distractor-specific reward contingencies can be generalized across distractor types producing both perceptual-related (Flanker task) and motor-related (Simon task) conflict, but, if any, to a limited degree when distractors produce additional higher-level task conflict (Stroop task). In addition, distributional RT analyses (delta plots) revealed that rewarded distractor-response associations modulate cognitive control not only via biasing the strength (Simon and Eriksen tasks) but also the time-course of suppressing distractor processing (Eriksen task). Overall, the present study dissociated distractor-general and distractor-specific effects of reward on cognitive control.

MR microscopy of the developing upper extremity of the chicken in ovo using 7 Tesla MRI.

MR microscopy (MRM) is known as ultra-high-field (UHF) magnetic resonance imaging with an in-plane spatial resolution of <100 µm, yields highly resolved non-invasive anatomical imaging and allows longitudinal assessment of embryonic avian development. The aim of the present study was to evaluate the feasibility of in vivo anatomical MRI assessment of the developing upper extremity of the chicken. Thirty-eight fertilized chicken eggs were examined at 7 Tesla acquiring high-resolution T2-weighted images with an in-plane resolution of 74 × 74 µm. To reduce motion artefacts, the eggs were moderately cooled before and during MRI. Development of the upper extremity was anatomically and quantitatively assessed. Chondrification and ossification on MRI were correlated with histological examination. MRM allowed the identification of the embryo from stage D5 onwards. First chondrification of the upper extremity was visible at stage D7, and the differentiation of the forearm was possible from stage D9 throughout the developmental period with excellent correlation to histology. MRM also allowed the differentiation between cortical and medullary bone as well as the detection of chondrified areas. UHF MRM allows the in vivo and in ovo evaluation of the upper limb during embryonic development and provides non-invasive longitudinal anatomical information. This technique allows longitudinal studies of the same embryo during the developmental period and may therefore provide further insights into the development of the upper extremity. With improved coil technique and increasing availability of UHF MR systems, there is great potential regarding several research topics in experimental musculoskeletal radiology.

Multi-Strain Probiotic Mixture Affects Brain Morphology and Resting State Brain Function in Healthy Subjects: An RCT.

Probiotics can alter brain function via the gut-brain axis. We investigated the effect of a probiotic mixture containing Bifidobacterium longum, Lactobacillus helveticus and Lactiplantibacillus plantarum. In a randomized, placebo-controlled, double-blinded crossover design, 22 healthy subjects (6 m/16 f; 24.2 ± 3.4 years) underwent four-week intervention periods with probiotics and placebo, separated by a four-week washout period. Voxel-based morphometry indicated that the probiotic intervention affected the gray matter volume of a cluster covering the left supramarginal gyrus and superior parietal lobule (p < 0.0001), two regions that were also among those with an altered resting state functional connectivity. Probiotic intervention resulted in significant (FDR < 0.05) functional connectivity changes between regions within the default mode, salience, frontoparietal as well as the language network and several regions located outside these networks. Psychological symptoms trended towards improvement after probiotic intervention, i.e., the total score of the Hospital Anxiety and Depression Scale (p = 0.056) and its depression sub-score (p = 0.093), as well as sleep patterns (p = 0.058). The probiotic intervention evoked distinct changes in brain morphology and resting state brain function alongside slight improvements of psycho(bio)logical markers of the gut-brain axis. The combination of those parameters may provide new insights into the modes of action by which gut microbiota can affect gut-brain communication and hence brain function.

Persistent Maintenance of Intermediate Memory B Cells Following SARS-CoV-2 Infection and Vaccination Recall Response.

Robust population-wide immunity will help to curb the SARS-CoV-2 pandemics. To maintain the immunity at protective levels, the quality and persistence of the immune response elicited by infection or vaccination must be determined. We analyzed the dynamics of B cell response during 12 months following SARS-CoV-2 infection on an individual level. In contrast to antibodies, memory B cells specific for the spike (S) protein persisted at high levels throughout the period. These cells efficiently secreted neutralizing antibodies and correlated with IFN-γ-secreting CD4+ T cells. Interestingly, the CD27-CD21+ intermediate memory B cell phenotype was associated with high B cell receptor avidity and the production of neutralizing antibodies. Vaccination of previously infected individuals triggered a recall response enhancing neutralizing antibody and memory B cell levels. Collectively, our findings provide a detailed insight into the longevity of SARS-CoV-2-infection-induced B cell immunity and highlight the importance of vaccination among previously infected. IMPORTANCE To efficiently maintain immunity against SARS-CoV-2 infection, we must first determine the durability of the immune response following infection or vaccination. Here, we demonstrated that, unlike antibodies, virus-specific memory B cells persist at high levels for at least 12 months postinfection and successfully respond to a secondary antigen challenge. Furthermore, we demonstrated that vaccination of previously infected individuals significantly boosters B cell immunity.

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial.

Background: Evidence from preclinical studies suggests that probiotics affect brain function via the microbiome-gut-brain axis, but evidence in humans remains limited. Objective: The present proof-of-concept study investigated if a probiotic product containing a mixture of Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 (in total 3 × 109 CFU/day) affected functional brain responses in healthy subjects during an emotional attention task. Design: In this double-blinded, randomized, placebo-controlled crossover study (Clinicaltrials.gov, NCT03615651), 22 healthy subjects (24.2 ± 3.4 years, 6 males/16 females) were exposed to a probiotic intervention and a placebo for 4 weeks each, separated by a 4-week washout period. Subjects underwent functional magnetic resonance imaging while performing an emotional attention task after each intervention period. Differential brain activity and functional connectivity were assessed. Results: Altered brain responses were observed in brain regions implicated in emotional, cognitive and face processing. Increased activation in the orbitofrontal cortex, a region that receives extensive sensory input and in turn projects to regions implicated in emotional processing, was found after probiotic intervention compared to placebo using a cluster-based analysis of functionally defined areas. Significantly reduced task-related functional connectivity was observed after the probiotic intervention compared to placebo. Fecal microbiota composition was not majorly affected by probiotic intervention. Conclusion: The probiotic intervention resulted in subtly altered brain activity and functional connectivity in healthy subjects performing an emotional task without major effects on the fecal microbiota composition. This indicates that the probiotic effects occurred via microbe-host interactions on other levels. Further analysis of signaling molecules could give possible insights into the modes of action of the probiotic intervention on the gut-brain axis in general and brain function specifically. The presented findings further support the growing consensus that probiotic supplementation influences brain function and emotional regulation, even in healthy subjects. Future studies including patients with altered emotional processing, such as anxiety or depression symptoms are of great interest. Clinical Trial Registration: [http://clinicaltrials.gov/], identifier [NCT03615651].

Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization?

BACKGROUND: In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS: We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS: Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS: Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.

Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study.

Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.

Fear of childbirth measurement: appraisal of the content overlap of four instruments.

OBJECTIVE: To evaluate empirically the degree of content overlap between four self-report measures of fear of childbirth (FoC) identified as 'best in class' by a recent review. BACKGROUND: FoC and tokophobia is an area of increasing clinical concern and has been linked to poor maternal and neonatal outcomes. Clinical pathways have been established to improve care and interventions for FoC however, ambiguity and inconsistency remain regarding the most appropriate assessment measures. METHOD: A multi-rater and consensus content analysis was undertaken to determine the degree of overlap between four 'best in class' measures of FoC/tokophobia. RESULTS: The Slade-Pais expectations of childbirth scale (SPECS) was found to be the preferred measure in terms of symptom overlap of the tools evaluated, however, the overall level of overlap among these measures was weak. CONCLUSION: Limitations inherent to the current battery of preferred measures of FoC suggests both the desirability and urgency to develop a theoretically-grounded, psychometrically robust and accurate FoC assessment measure. Current measures of FoC are not interchangeable.

The German Translation of the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) Scale: Results from Healthcare Workers during the Second Wave of COVID-19.

Healthcare workers (HCW) are among those most directly affected by the COVID-19 pandemic. Most research with this group has used ad hoc measures, which limits comparability across samples. The Stress and Anxiety to Viral Epidemics-9 scale (SAVE-9) is a nine-item scale first developed in Korea, and has since been translated into several languages. We report on data collected from 484 German HCW between November 2020 and March 2021, during the "second wave" of coronavirus infections. We conducted item analysis, confirmatory factor analysis on the previously found factor solutions of the SAVE-9, examined correlations with established measures of depression, generalized anxiety, and insomnia, and compared scores between different groups of HCW. The psychometric properties of the German SAVE-9 were satisfactory and comparable to previous findings from Korea and Russia. Correlations with mental health measures were positive, as expected. We found some significant differences between groups of HCW on the SAVE-9 which were consistent with the literature but did not appear on the other mental health measures. This suggests that the SAVE-9 taps into specifically work-related stress, which may make it a helpful instrument in this research area.

Screening for Posttraumatic Stress Symptoms in Young Refugees: Comparison of Questionnaire Data with and without Involvement of an Interpreter.

Background: The substantial number of young refugees who have arrived in Europe since 2015 requires rapid screening to identify those in need of treatment. However, translated versions of screening measures are not always available, necessitating the support of interpreters. The Child and Adolescent Trauma Screen (CATS) is a validated questionnaire for posttraumatic stress symptoms. Here, we report on the psychometric properties of the CATS in a sample of young refugees as a function of interpreter involvement. Methods: A total of N = 145 (Mage = 16.8, SD = 1.54; 93% male) were assessed with the CATS, with half of the screenings conducted with and half without interpreters. Post hoc analyses included calculating internal consistency using Cronbach's α. We used confirmative factor analysis to investigate the factor structure. Results: The CATS total scale showed good reliability (α = 0.84). Differences in psychometric properties between the interpreter vs. the no interpreter group were minor and tended to be in favor of the interpreter group. Results of a confirmatory factor analysis were acceptable after the exclusion of items with low item-scale correlations. Conclusions: The sample and the administration of the assessment represent the situation of young refugees in Germany, where resources are low and translated versions not always available. The CATS may be a helpful screening tool for clinicians working with young refugees, even when administered with an interpreter. Limitations include the post hoc design of the analysis without randomization of participants and the lack of a third comparison group using translated questionnaire versions.

Short intense psychological stress induced by skydiving does not impair intestinal barrier function.

BACKGROUND AND AIM: Psychological stress has been shown to increase intestinal permeability and is associated with the development of gastrointestinal disorders. This study aimed to investigate skydiving as an alternative model to analyse the effect of acute psychological stress on intestinal barrier function. MATERIALS AND METHODS: Twenty healthy subjects participated in a tandem skydive followed by a negative control visit, of which 19 (9 females and 10 males, 25.9 ± 3.7 years) were included in the study. Intestinal permeability was assessed by a multi-sugar urinary recovery test. Sucrose recovery and lactulose/rhamnose ratio in 0-5h urine indicated gastroduodenal and small intestinal permeability, respectively, and sucralose/erythritol ratio in 5-24h urine indicated colonic permeability. Blood samples were taken to assess markers associated with barrier function. This study has been registered at ClinicalTrials.gov (NCT03644979) on August 23, 2018. RESULTS: Skydiving resulted in a significant increase in salivary cortisol levels directly after skydiving compared to the control visit. Cortisol levels were still increased two hours after landing, while cortisol levels before skydiving were not significantly different from the baseline at the control visit. Skydiving did not induce a significant increase in gastroduodenal, small intestinal or colonic permeability. There was also no significant increase in plasma intestinal and liver fatty acid-binding proteins, suggesting no damage to the enterocytes. DISCUSSION: These results show that the acute intense psychological stress induced by skydiving does not affect intestinal permeability in healthy subjects. Future models aiming to investigate the effect of stress on human intestinal barrier function should consider a more sustained exposure to the psychological stressor.

Sauna dehydration as a new physiological challenge model for intestinal barrier function.

The intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-É£ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

Young people's trauma-related cognitions before and after cognitive processing therapy for post-traumatic stress disorder.

OBJECTIVES: Cognitive processing therapy (CPT) is a psychotherapy for post-traumatic stress disorder (PTSD) with a broad evidence base. Change in trauma-related cognitions is considered its primary working mechanism. When trying to integrate a traumatic event into existing cognitive schemas, the adaptive mechanism is changing the schema (accommodation). However, PTSD patients frequently either change their schemas too much (over-accommodation), or cognitively distort the event (assimilation). We aimed to test the hypothesized connections between the three types of cognition and symptom load. DESIGN: This study adds to the literature using 'impact statements', essays on their trauma-related thoughts written by patients at the beginning and end of CPT, to investigate cognitive change and its relationship to symptomatic outcome. METHODS: We analysed statements written by 31 adolescents and young adults who received developmentally adapted CPT (a longer treatment where CPT is the core component) in a randomized controlled trial. RESULTS: As expected, post-CPT statements contained more accommodated and fewer over-accommodated and assimilated clauses than pre-CPT statements. Correlations between cognition frequencies and concurrent symptom load were as expected for assimilation, and, in part, over-accommodation and accommodation. Decreased PTSD and depressive symptoms were correlated with increased accommodated thoughts. For over-accommodation and assimilation, however, expected correlations could not be shown. CONCLUSIONS: Our results support the notion that cognitive change is an important mechanism of change in CPT in a sample of younger, non-English-speaking clients.

Butyrate Rescues Oxidative Stress-Induced Transport Deficits of Tryptophan: Potential Implication in Affective or Gut-Brain Axis Disorders.

INTRODUCTION: Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions. OBJECTIVE: Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives. METHODS: Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (3H) was used as a tracer to measure the transport of tryptophan across the cell membranes (n = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (n = 2). RESULTS: As hypothesized,oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan. CONCLUSIONS: Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.