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20 maart 2023, Item does not contain fulltext, Background: Despite considerable research efforts, consistent predictors of cognitive behavioral therapy (CBT) outcome for social anxiety disorder (SAD) are scarce. A dynamic focus on individual symptom reactivity and resilience patterns may show promise in predicting treatment response. This pilot study is the first to investigate whether rate of return to baseline after a one-session positive interpretation training indicates resilience and predicts CBT-response among individuals with SAD. Method: Participants (N = 39) completed an interpretation bias assessment before and after training, and once a day for three days after the training, followed by a six-week CBT-program. Participants completed SAD-assessments pre-treatment, during treatment, and post-treatment. Return to baseline was operationalized as the individualized slope of negative and positive interpretations across interpretation bias assessments. Results: Intention-to-treat analyses showed no significant relation between both negative and positive interpretation bias and CBT-response. Similarly, for completers-only, most analyses also showed no such relationship. Conclusion: These findings suggest that slower return to baseline as a resilience index does not have predictive value for CBT-outcome in individuals with SAD. Future studies should incorporate experience-sampling to capture subtle changes in interpretation bias.

Over the past decade, theranostic imaging has emerged as a powerful clinical tool in oncology for identifying patients likely to respond to targeted therapies and for monitoring the response of patients to treatment. Herein, we report a theranostic approach to pretargeted radioimmunotherapy (PRIT) based on a pair of radioisotopes of copper: positron-emitting copper-64 (64Cu, t1/2 = 12.7 h) and beta particle-emitting copper-67 (67Cu, t1/2 = 61.8 h). This strategy is predicated on the in vivo ligation between a trans-cyclooctene (TCO)-bearing antibody and a tetrazine (Tz)-based radioligand via the rapid and bioorthogonal inverse electron-demand Diels–Alder reaction. Longitudinal therapy studies were conducted in a murine model of human colorectal carcinoma using an immunoconjugate of the huA33 antibody modified with TCO (huA33-TCO) and a 67Cu-labeled Tz radioligand ([67Cu]Cu-MeCOSar-Tz). The injection of huA33-TCO followed 72 h later by the administration of 18.5, 37.0, or 55.5 MBq of [67Cu]Cu-MeCOSar-Tz produced a dose-dependent therapeutic response, with the median survival time increasing from 68 d for the lowest dose to >200 d for the highest. Furthermore, we observed that mice that received the highest dose of [67Cu]Cu-MeCOSar-Tz in a fractionated manner exhibited improved hematological values without sacrificing therapeutic efficacy. Dual radionuclide experiments in which a single administration of huA33-TCO was followed by separate injections of [64Cu]Cu-MeCOSar-Tz and [67Cu]Cu-MeCOSar-Tz revealed that the positron emission tomography images produced by the former accurately predicted the efficacy of the latter. In these experiments, a correlation was observed between the tumoral uptake of [64Cu]Cu-MeCOSar-Tz and the subsequent therapeutic response to [67Cu]Cu-MeCOSar-Tz.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throu

Item does not contain fulltext, Objective: Children of parents with an anxiety disorder have a higher risk of developing an anxiety disorder than children of parents without an anxiety disorder. Parental anxiety is not regarded as a causal risk factor itself, but is likely to be mediated via other mechanisms, for example via cognitive factors. We investigated whether children of parents with an anxiety disorder would show an interpretation bias corresponding to the diagnosis of their parent. We also explored whether children's interpretation biases were explained by parental anxiety and/or children’s levels of anxiety. Method: In total, 44 children of parents with a panic disorder (PD), 27 children of parents with a social anxiety disorder (SAD), 7 children of parents with SAD/PD, and 84 children of parents without an anxiety disorder (controls) participated in this study. Parents and children filled out the Screen for Child Anxiety Related Disorders (SCARED) questionnaire, and children performed two ambiguous scenario tasks: one with and one without video priming. Results: Children of parents with PD displayed significantly more negative interpretations of panic scenarios and social scenarios than controls. Negative interpretations of panic scenarios were explained by parental PD diagnosis and children’s anxiety levels. These effects were not found for children of parents with SAD. Priming did not affect interpretation. Conclusion: Our results showed that children of parents with PD have a higher chance of interpreting ambiguous situations more negatively than children of parents without anxiety disorders. More research is needed to study whether this negative bias predicts later development of anxiety disorders in children.

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Contains fulltext : 169545.pdf (publisher's version ) (Open Access), Models of cognitive processing in anxiety disorders state that socially anxious children display several distorted cognitive processes that maintain their anxiety. The present study investigated the role of social threat thoughts and social skills perception in relation to childhood trait and state social anxiety. In total, 141 children varying in their levels of social anxiety performed a short speech task in front of a camera and filled out self-reports about their trait social anxiety, state anxiety, social skills perception and social threat thoughts. Results showed that social threat thoughts mediated the relationship between trait social anxiety and state anxiety after the speech task, even when controlling for baseline state anxiety. Furthermore, we found that children with higher trait anxiety and more social threat thoughts had a lower perception of their social skills, but did not display a social skills deficit. These results provide evidence for the applicability of the cognitive social anxiety model to children.

BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited. METHODS: We deployed an integrated approach combining genomics, metabolomics, and phenotypic analysis on a unique cohort of patient-derived pancreatic cancer cell lines (PDCLs). Genome analysis was performed via targeted sequencing of the mitochondrial genome (mtDNA) and nuclear genes encoding mitochondrial components and metabolic genes. Phenotypic characterization of PDCLs included measurement of cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a Seahorse XF extracellular flux analyser, targeted metabolomics and pathway profiling, and radiolabelled glutamine tracing. RESULTS: We identified 24 somatic mutations in the mtDNA of 12 patient-derived pancreatic cancer cell lines (PDCLs). A further 18 mutations were identified in a targeted study of ~1000 nuclear genes important for mitochondrial function and metabolism. Comparison with reference datasets indicated a strong selection bias for non-synonymous mutants with predicted functional effects. Phenotypic analysis showed metabolic changes consistent with mitochondrial dysfunction, including reduced oxygen consumption and increased glycolysis. Metabolomics and radiolabeled substrate tracing indicated the initiation of reductive glutamine metabolism and lipid synthesis in tumours. CONCLUSIONS: The heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different ge

Item does not contain fulltext, Background and objectives: Research shows that people tend to consider believable conclusions as valid and unbelievable conclusions as invalid (belief bias). When applied to anxiogenic beliefs, this belief bias could well hinder the correction of dysfunctional convictions. Previous work has shown that high socially anxious students indeed display such fear-confirming, belief biased, reasoning. A critical next question is whether these findings translate to a clinical population of people with social anxiety disorder (SAD). We test whether (i) patients with SAD show belief bias with regard to SAD-relevant themes, (ii) this belief bias is specific for SAD patients or can also be found in panic disorder (PD) patients, (iii) differential belief bias effects in SAD are restricted to social anxiety concerns or are also evident in the context of reasoning with neutral themes. Method: 45 SAD patients, 24 PD patients, and 45 non-symptomatic controls (NSCs) completed a syllogistic belief bias task with SAD-relevant and neutral content. Results: SAD patients displayed belief bias for social anxiety related materials, while the PD group and the NSC group did not. Yet, the difference between SAD and PD was not significant. All groups showed similar belief bias effects for neutral content. Limitations: Content of the belief bias task was not tailored to idiosyncratic beliefs. The study lacked power to detect medium or small differences. Conclusions: SAD patients showed concern-congruent belief biased interference effects when judging the logical validity of social anxiety relevant syllogisms. Such concern-relevant belief bias may contribute to the persistence of anxiogenic beliefs.