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 biallelic pathogenic variants in WAP four-disulfide core domain 2 (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.

A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.

BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.

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.

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.

Advanced cryo-tomography workflow developments - correlative microscopy, milling automation and cryo-lift-out.

Cryo-electron tomography (cryo-ET) is a groundbreaking technology for 3D visualisation and analysis of biomolecules in the context of cellular structures. It allows structural investigations of single proteins as well as their spatial arrangements within the cell. Cryo-tomograms provide a snapshot of the complex, heterogeneous and transient subcellular environment. Due to the excellent structure preservation in amorphous ice, it is possible to study interactions and spatial relationships of proteins in their native state without interference caused by chemical fixatives or contrasting agents. With the introduction of focused ion beam (FIB) technology, the preparation of cellular samples for electron tomography has become much easier and faster. The latest generation of integrated FIB and scanning electron microscopy (SEM) instruments (dual beam microscopes), specifically designed for cryo-applications, provides advances in automation, imaging and the preparation of high-pressure frozen bulk samples using cryo-lift-out technology. In addition, correlative cryo-fluorescence microscopy provides cellular targeting information through integrated software and hardware interfaces. The rapid advances, based on the combination of correlative cryo-microscopy, cryo-FIB and cryo-ET, have already led to a wealth of new insights into cellular processes and provided new 3D image data of the cell. Here we introduce our recent developments within the cryo-tomography workflow, and we discuss the challenges that lie ahead. LAY DESCRIPTION: This article describes our recent developments for the cryo-electron tomography (cryo-ET) workflow. Cryo-ET offers superior structural preservation and provides 3D snapshots of the interior of vitrified cells at molecular resolution. Before a cellular sample can be imaged by cryo-ET, it must be made accessible for transmission electron microscopy. This is achieved by preparing a 200-300 nm thin cryo-lamella from the cellular sample using a cryo-focused ion beam (cryo-FIB) microscope. Cryo-correlative light and electron microscopy (cryo-CLEM) is used within the workflow to guide the cryo-lamella preparation to the cellular areas of interest. We cover a basic introduction of the cryo-ET workflow and show new developments for cryo-CLEM, which facilitate the connection between the cryo-light microscope and the cryo-FIB. Next, we present our progress in cryo-FIB software automation to streamline cryo-lamella preparation. In the final section we demonstrate how the cryo-FIB can be used for 3D imaging and how bulk-frozen cellular samples (obtained by high-pressure freezing) can be processed using the newly developed cryo-lift-out technology.

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.

Faecal microbiota transfer in patients with microscopic colitis - a pilot study in collagenous colitis.

OBJECTIVES: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota. METHODS: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors. RESULTS: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed. CONCLUSIONS: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.

The German W-DEQ version B-Factor structure and prediction of posttraumatic stress symptoms six weeks and one year after childbirth.

The Wijma Delivery Expectancy/Experience Questionnaire is a frequently used measure in the context of childbirth. There are two versions with identical items for use during pregnancy (version A, fear of childbirth) and postpartum (version B, subjective experience) respectively. The original authors report that the measure is unidimensional, but since, very different factor structures have been found with different language versions. In this study, I tested the previously found factor structures in a sample of 338 German new mothers with confirmatory factor analysis. As none showed an adequate fit, I conducted an exploratory factor analysis, which yielded six factors with satisfactory internal consistencies.

Difficulties in Conducting Long Term Follow Ups in Psychotherapy Research-Issues in the Literature and Data From a Randomized Therapy Comparison Study for Posttraumatic Stress Disorder.

Studies of psychotherapy for posttraumatic stress disorder (PTSD) typically encompass short follow-up periods, leading to a dearth of information on the long-term course of symptoms after treatment. We summarize existing long-term follow-up studies and highlight the issues making such research difficult. In this context, we report on a 2-year follow-up on a randomized treatment study comparing dialogical exposure therapy and cognitive processing therapy for adults with PTSD after type I trauma. Many of the problems connected to long-term follow-up also pertained to this study. Attrition was high, and the recruited sample was not representative of the study completers. Gains made during therapy were mostly stable, with no significant differences between interventions. At least for an originally successful subset of patients, the gains made during both treatments in our study tended to stay stable 2 years after the end of treatment.

A Randomized Controlled Clinical Trial of Dialogical Exposure Therapy versus Cognitive Processing Therapy for Adult Outpatients Suffering from PTSD after Type I Trauma in Adulthood.

BACKGROUND: Although there are effective treatments for posttraumatic stress disorder (PTSD), there is little research on treatments with non-cognitive-behavioural backgrounds, such as gestalt therapy. We tested an integrative gestalt-derived intervention, dialogical exposure therapy (DET), against an established cognitive-behavioural treatment (cognitive processing therapy, CPT) for possible differential effects in terms of symptomatic outcome and drop-out rates. METHODS: We randomized 141 treatment-seeking individuals with a diagnosis of PTSD to receive either DET or CPT. Therapy length in both treatments was flexible with a maximum duration of 24 sessions. RESULTS: Dropout rates were 12.2% in DET and 14.9% in CPT. Patients in both conditions achieved significant and large reductions in PTSD symptoms (Impact of Event Scale - Revised; Hedges' g = 1.14 for DET and d = 1.57 for CPT) which were largely stable at the 6-month follow-up. At the posttreatment assessment, CPT performed statistically better than DET on symptom and cognition measures. For several outcome measures, younger patients profited better from CPT than older ones, while there was no age effect for DET. CONCLUSIONS: Our results indicate that DET merits further research and may be an alternative to established treatments for PTSD. It remains to be seen whether DET confers advantages in areas of functioning beyond PTSD symptoms.

Interpersonal Subtypes and Therapy Response in Patients Treated for Posttraumatic Stress Disorder.

UNLABELLED: Interpersonal traits may influence psychotherapy success. One way of conceptualizing such traits is the interpersonal circumplex model. In this study, we analyse interpersonal circumplex data, assessed with the Inventory of Interpersonal Problems (Horowitz, Strauß, & Kordy, 1994) from a randomized study with 138 patients suffering from posttraumatic stress disorder after trauma in adulthood. The study compared cognitive processing therapy and dialogical exposure therapy, a Gestalt-based intervention. We divided the interpersonally heterogeneous sample according to the quadrants of the interpersonal circumplex. The division into quadrants yielded subgroups that did not differ in their general psychological distress, but the cold-submissive quadrant tended to exhibit higher posttraumatic stress disorder symptom severity and interpersonal distress than the other three. There was also a trend for patients in different quadrants to be affected differently by the treatments. Correlation analyses supported these results: in cognitive processing therapy, more dominant patients had more successful therapies, while in dialogical exposure therapy, success was not correlated with interpersonal style. Results indicate that especially patients with cold interpersonal styles profited differentially from the two treatments offered. Dividing samples according to the interpersonal circumplex quadrants seems promising. KEY PRACTITIONER MESSAGE: Interpersonal traits may contribute to psychotherapy outcome. Dividing the sample according to the quadrants of the interpersonal circumplex, as opposed to cluster analysis, yielded promising results. Patients higher in dominance fared better with cognitive processing therapy, while interpersonal style had no correlations with therapy success in dialogical exposure therapy.

Amnion-derived mesenchymal stromal cells show a mesenchymal-epithelial phenotype in culture.

The amnionic membrane is a rich source of multipotent mesenchymal stromal cells (hAMSC), which are readily available and show a potential use in regenerative medicine and tissue engineering. Before these cells can be applied clinically, careful characterization is necessary, especially as primary cells are known to change their phenotype in culture. We analyzed the mesenchymal phenotype of hAMSC at different stages after isolation using immunohistochemistry. Shortly after isolation (1 day), 92 % (± 7 %) of the hAMSC expressed the mesenchymal marker vimentin, 2 % (± 1 %) stained for the epithelial marker cytokeratin-7 and 5 % (± 4 %) co-expressed these markers. After 5 days, the double positive cells slightly increased to 7 % (± 3 %), while exclusive expression of cytokeratin-7 or vimentin remained unchanged (1 % ± 2 % and 92 % ± 1 %, respectively). After the first passage, all attached cells were vimentin-positive, while 54 % (± 9 %) co-expressed cytokeratin-7 and vimentin. Thus, we conclude that under culture, hAMSC adopt a hybrid mesenchymal-epithelial phenotype. It is also essential to perform microscopical examination during the first days after isolation to detect contaminations with human amnion-derived epithelial cells in cultures of hAMSC.

Feasibility and outcome of dialogical exposure therapy for posttraumatic stress disorder: a pilot study with 25 outpatients.

OBJECTIVE: The research on psychotherapy for posttraumatic stress disorder (PTSD) stems predominantly from a cognitive-behavioral orientation while other approaches are underrepresented. We evaluated dialogical exposure in trauma therapy (DET), a treatment for PTSD combining cognitive-behavioral elements with an interpersonal, gestalt-based framework. METHODS: In this uncontrolled pilot trial, 25 PTSD patients were treated with DET in an outpatient setting and 21 completed therapy. RESULTS: There was a significant reduction in self-rated PTSD symptoms from pre- to posttreatment. Effect sizes were large in the completer sample and moderate to large in the intent-to-treat sample. General psychopathology also decreased significantly. The dropout rate was rather low at 16%. CONCLUSION: These results show that further research on DET as a treatment for PTSD is warranted.

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.

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.

Associations between various markers of intestinal barrier and immune function after a high-intensity exercise challenge.

Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.

Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia.

Pregestational diabetes retards early embryonic growth. Placental and fetal growth are closely associated, suggesting that placental growth is also impaired. During the first trimester of gestation, oxygen tension rises steeply, leading to excessive production of reactive oxygen species (ROS), which is exacerbated in diabetes and may affect placental development. We hypothesized that oxygen modifies hyperglycemic effects on ROS formation, resulting in decreased first-trimester trophoblast growth. This was tested using a first trimester trophoblast-derived cell line (ACH-3P). Normoglycemia did not alter ACH-3P proliferation at 2.5%, 8%, and 21% oxygen. Hyperglycemic conditions for up to 3 days reduced cell number by 65% and resulted in cell cycle (G(1)- and S-phase) changes but only at 21% oxygen. Proliferation reduction could be partially restored by an inhibitor of mitogen-activated protein kinase (MAPK) ERK1/2 but not of Akt/PkB. Intracellular ROS elevation under hyperglycemia was oxygen independent, whereas mitochondrial superoxide levels were enhanced under hyperglycemia only at 21% oxygen. Intervention to modulate cytosolic and mitochondrial ROS, using ROS formation inducers and inhibitors, did not alter cell growth under hyperglycemia at 21% oxygen. The combination of hyperglycemia and high oxygen levels (21%) reduces proliferation of human first-trimester trophoblasts in a ROS-independent manner involving MAPK. This may account for reduced placental growth and, therefore, also for embryonic growth during the first-trimester pregestational diabetic pregnancies when the oxygen tension increases.

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.

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.