26 results on '"Stark R."'
Search Results
2. Transgenerational transmission of psychopathology: when are adaptive emotion regulation strategies protective in children?
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Luczejko, Arleta A., Werkmann, Naomi Leona, Hagelweide, K., Stark, R., Weigelt, S., Christiansen, H., Kieser, M., Otto, K., Reck, C., Steinmayr, R., Wirthwein, L., Zietlow, A.-L., and Schwenck, C.
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MENTAL illness genetics ,EMOTION regulation ,CHILDREN of people with mental illness ,SCALE analysis (Psychology) ,ACADEMIC medical centers ,CRONBACH'S alpha ,DATA analysis ,PARENT-child relationships ,QUESTIONNAIRES ,BRIEF Symptom Inventory ,INTERVIEWING ,PARENTING ,PSYCHOLOGICAL adaptation ,DESCRIPTIVE statistics ,MULTIVARIATE analysis ,ANALYSIS of covariance ,CHI-squared test ,CHILD Behavior Checklist ,RESEARCH ,STATISTICS ,COMPARATIVE studies ,DATA analysis software ,FACTOR analysis ,CONFIDENCE intervals ,PATHOLOGICAL psychology ,INTERGENERATIONAL relations ,DISCRIMINANT analysis ,REGRESSION analysis ,CHILDREN - Abstract
Background: Children of parents with a mental illness (COPMI) have multiple psychological and developmental risks, including an increased lifetime risk of developing a mental illness themselves. Emotion regulation (ER) has been identified as a potential underlying mechanism of the transgenerational transmission of mental disorders. This study compares ER strategies in parents with and without a mental illness and their children. Further, it aims to examine the relationship between parents and children's psychopathology with a focus on the role of parental and child ER. Methods: Participants were 96 COPMI (77% female) and 99 children of parents without mental illness (COPWMI, 83% female) aged 4–16 years and their parents. Psychopathology and ER strategies of parents and children were assessed with a series of questionnaires. Results: Both COPMI and their parents showed significantly more psychopathology and more maladaptive and adaptive ER strategies in comparison with COPWMI and their parents. Parent and child adaptive ER strategies mediated the relationship between the psychopathology of parents and children only when child maladaptive ER strategies were low. Conclusions : The findings further our understanding of the processes by which parental psychopathology affects child outcomes. Our findings highlight the importance of implementing preventive programs that specifically target the reduction of maladaptive ER in children to interrupt the transgenerational transmission of psychopathological symptoms. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Objective functional biomarkers to find druggable targets for tinnitus and hyperacusis.
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Knipper, M., Wertz, J., Dapper, K., Dalhoff, E., Stark, R., Wolpert, S., Klose, U., Munk, M. H. J., and Ruttiger, L.
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TINNITUS treatment ,HYPERACUSIS ,TREATMENT effectiveness ,CONFERENCES & conventions ,TINNITUS ,COGNITIVE therapy ,BIOMARKERS ,COMORBIDITY - Abstract
Currently, conflicting views on the neural correlate of tinnitus hinder the development of effective diagnosis and therapy for tinnitus (Knipper et al., Ruttiger, 2020). Although hyperacusis often co-occurs with tinnitus, it is until now considered neither in clinical diagnosis nor for targeted, individualized therapies. On the basis of findings with objective functional biomarkers (PTT, ABR, fMRI, EEG) used in patients, we challenge the hypothesis that co-occurance of hyperacusis worsens tinnitus percept towards a disease that most requires treatment and therapy. In this context, the hypothesis of the successful use of cognitive therapies for hyperacusis and tinnitus is particularly interesting for future therapy development. [ABSTRACT FROM AUTHOR]
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- 2024
4. The PornLoS Treatment Program: Study protocol of a new psychotherapeutic approach for treating pornography use disorder.
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Stark R, Markert C, Golder S, Psarros R, Discher JP, Khatib S, Metzger J, Palmer S, Rechmann J, Storz F, Walter B, Allard S, Antons S, Bledzka M, Brand M, Dörrenbächer S, Englisch J, Friehs T, Da Cunha Gonçalves K, Haberkamp A, Hall M, Kananian S, Kemmerer P, Klingelhöfer D, Lutz W, Melzig CA, Michael T, Neumann A, Neusser S, Niemann A, Odenthal M, Rubel J, Schlierenkamp S, Speckemeier C, Ünlü L, Vogt R, Wölfling K, Zachariassen W, Zur Hausen G, and Heinz C
- Abstract
Background: The introduction of Compulsive Sexual Behavior Disorder (CSBD) into the 11th International Classification of Diseases has raised expectations for better treatment options for CSBD. Furthermore, the treatment demand has increased, particularly for pornography use disorder (PUD), a subtype of CSBD. Presumably due to the easy access to Internet pornography an increasing prevalence of PUD is observed. Consequently, providing tailored and effective treatment is essential., Methods: This article provides an overview of the manualized short-term PornLoS Treatment Program (Pornografienutzungsstörung effektiv behandeln- Leben ohne Suchtdruck; translation: Treating pornography use disorder effectively - life without craving). The program combines 24 individual and 6 group psychotherapy sessions with an interdisciplinary approach by offering a novel treatment framework. This includes, e.g., a mobile app, establishment of self-help groups, and access to other social services such as couple counseling. The cognitive-behavioral treatment program contains interventions addressing psychoeducation, cue exposure, impulse control, cognitive restructuring, emotional regulation, and relapse management.We here also describe the study protocol of an ongoing four-arm randomized controlled trial. The aim is to test two variants of the PornLoS Treatment Program differing with respect to their treatment goal (abstinence or reduced pornography use) against cognitive-behavioral treatment as usual and against a waitlist control group. The primary outcome is the absence of a PUD diagnosis at the end of therapy. The total target sample size will comprise n = 316 patients with PUD across eight study sites., Results: The results will be presented at international conferences and published in a scientific peer-reviewed journal.
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- 2024
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5. Hunger signalling in the olfactory bulb primes exploration, food-seeking and peripheral metabolism.
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Stark R, Dempsey H, Kleeman E, Sassi M, Osborne-Lawrence S, Sheybani-Deloui S, Austin-Muttitt K, Mullins J, Zigman JM, Davies JS, and Andrews ZB
- Abstract
Objective: Although the metabolic state of an organism affects olfactory function, the precise mechanisms and their impact on behavior and metabolism remain unknown. Here, we assess whether ghrelin receptors (GHSRs) in the olfactory bulb (OB) increase olfactory function and influence foraging behaviors and metabolism., Methods: We performed a detailed behavioural and metabolic analysis in mice lacking GHSRs in the OB (OB
GHSR deletion). We also analsyed OB scRNA-seq and spatial transcriptomic datasets to assess GHSR+ cells in the main and accessory olfactory bulbs, as well as the anterior olfactory nucleus., Results: OBGHSR deletion affected olfactory discrimination and habituation to both food and non-food odors. Anxiety-like and depression-like behaviors were significantly greater after OBGHSR deletion, whereas exploratory behavior was reduced, with the greatest effect under fasted conditions. OBGHSR deletion impacted feeding behavior as evidenced by altered bout number and duration, as well as buried food-seeking. OBGHSR deletion increased body weight and fat mass, spared fat utilisation on a chow diet and impaired glucose metabolism indicating metabolic dysfunction. Cross referenced analysis of OB scRNA-seq and spatial transcriptomic datasets revealed GHSR+ glutamate neurons in the main and accessory olfactory bulbs, as well as the anterior olfactory nucleus. Ablation of glutamate neurons in the OB reduced ghrelin-induced food finding and phenocopied results seen after OBGHSR deletion., Conclusions: OBGHSRs help to maintain olfactory function, particularly during hunger, and facilitate behavioral adaptations that optimise food-seeking in anxiogenic environments, priming metabolic pathways in preparation for food consumption., Competing Interests: Declaration of competing interest J.M.Z. receives research funding from Novo Nordisk for another project and consulted for Helsinn Healthcare S.A. and Dexcel Pharma Technologies Ltd. during the time these studies were performed. The other authors have nothing to disclose. All other authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)- Published
- 2024
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6. The promise and pitfalls of care standardization in congenital diaphragmatic hernia.
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Dimmer A, Stark R, Skarsgard ED, and Puligandla PS
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- Humans, Standard of Care standards, Hernias, Diaphragmatic, Congenital therapy
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The aim of standardizing care is to enhance patient outcomes and optimize healthcare delivery by minimizing variations in care and ensuring the efficient allocation of healthcare resources. Despite these potential benefits to patients, healthcare providers and the healthcare system, standardization may also disadvantage these groups. With a specific focus on congenital diaphragmatic hernia, this article will review the promise and pitfalls of standardization, as well as a potential path forward that uses standardization to improve outcomes in this rare and complex disease process., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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7. Long-term in vitro maintenance of plasma cells in a hydrogel-enclosed human bone marrow microphysiological 3D model system.
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Martini S, Drzeniek NM, Stark R, Kollert MR, Du W, Reinke S, Ort M, Hardt S, Kotko I, Kath J, Schlickeiser S, Geißler S, Wagner DL, Krebs AC, and Volk HD
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- Humans, Cell Survival drug effects, Hyaluronic Acid chemistry, Hyaluronic Acid pharmacology, Bone Marrow Cells cytology, Collagen chemistry, Bone Marrow metabolism, Cells, Cultured, Cell Culture Techniques, Three Dimensional, Models, Biological, Tissue Scaffolds chemistry, Sepharose chemistry, Plasma Cells cytology, Plasma Cells metabolism, Hydrogels chemistry
- Abstract
Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g. in various malignant and non-malignant diseases such as multiple myeloma, primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived from in vivo studies in mice, as in vitro studies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survival in vitro for up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCs in vitro . Our innovative model system is suitable for in-depth in vitro studies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics., (Creative Commons Attribution license.)
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- 2024
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8. Facial emotion recognition in children of parents with a mental illness.
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Werkmann NL, Luczejko AA, Hagelweide K, Stark R, Weigelt S, Christiansen H, Kieser M, Otto K, Reck C, Steinmayr R, Wirthwein L, Zietlow AL, and Schwenck C
- Abstract
Objective: Facial emotion recognition (FER) is a fundamental social skill essential for adaptive social behaviors, emotional development, and overall well-being. FER impairments have been linked to various mental disorders, making it a critical transdiagnostic mechanism influencing the development and trajectory of mental disorders. FER has also been found to play a role in the transgenerational transmission of mental disorders, with the majority of research suggesting FER impairments in children of parents with a mental illness (COPMI). Previous research primarily concentrated on COPMI of parents with internalizing disorders, which does not cover the full spectrum of outpatient mental health service populations. Furthermore, research focuses on varying components of FER by using different assessment paradigms, making it challenging to compare study results. To address these gaps, we comprehensively investigated FER abilities in COPMI using multiple tasks varying in task characteristics., Methods: We included 189 children, 77 COPMI and 112 children of parents without a diagnosed mental illness (COPWMI), aged 6 to 16 years. We assessed FER using three tasks with varying task demands: an emotional Go/NoGo task, a morphing task, and a task presenting short video sequences depicting different emotions. We fitted separate two-level hierarchical Bayesian models (to account for sibling pairs in our sample) for reaction times and accuracy rates for each task. Good model fit was assured by comparing models using varying priors., Results: Contrary to our expectations, our results revealed no general FER deficit in COPMI compared to COPWMI. The Bayesian models fitted for accuracy in the morphing task and Go/NoGo task yielded small yet significant effects. However, Bayes factors fitted for the models suggested that these effects could be due to random variations or noise in the data., Conclusions: Our study does not support FER impairments as a general feature of COPMI. Instead, individual factors, such as the type of parental disorder and the timing of its onset, may play a crucial role in influencing FER development. Future research should consider these factors, taking into account the diverse landscape of parental mental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Werkmann, Luczejko, Hagelweide, Stark, Weigelt, Christiansen, Kieser, Otto, Reck, Steinmayr, Wirthwein, Zietlow, Schwenck and the COMPARE-family research group.)
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- 2024
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9. Love yourself as a therapist, doubt yourself as an institution? Therapist and institution effects on outcome, treatment length, and dropout.
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Deisenhofer AK, Hehlmann MI, Rubel JA, Lutz W, Schwartz B, Bräscher AK, Christiansen H, Fehm L, Glombiewski JA, Heider J, Helbig-Lang S, Hermann A, Hoyer J, In-Albon T, Lincoln T, Margraf J, Risch AK, Schöttke H, Schulze L, Stark R, Teismann T, Velten J, Willutzki U, Wilz G, Witthöft M, and Odyniec P
- Abstract
Objective: Research suggests that some therapists achieve better outcomes than others. However, an overlooked area of study is how institution differences impact patient outcomes independent of therapist variance. This study aimed to examine the role of institution and therapist differences in adult outpatient psychotherapy., Method: The study included 1428 patients who were treated by 196 therapists at 10 clinics. Two- and three-level hierarchical linear regression models were employed to investigate the effects of therapists and institutions on three dependent patient variables: (1) symptom change, (2) treatment duration, and (3) dropout. Level three explanatory variables were tested., Results: The results showed that therapist effects (TE) were significant for all three types of treatment outcome (7.8%-18.2%). When a third level (institution) was added to the model, the differences between therapists decreased, and significant institution effects (IE) were found: 6.3% for symptom change, 10.6% for treatment duration, and 6.5% for dropout. The exploratory analyses found no predictors able to explain the systematic variation at the institution level., Discussion: TE on psychotherapy outcomes remain a relevant factor but may have been overestimated in previous studies due to not properly distinguishing them from differences at the institution level.
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- 2024
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10. Appetitive conditioning with pornographic stimuli elicits stronger activation in reward regions than monetary and gaming-related stimuli.
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Krikova K, Klein S, Kampa M, Walter B, Stark R, and Klucken T
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- Humans, Male, Young Adult, Adult, Female, Video Games, Brain physiology, Brain diagnostic imaging, Conditioning, Classical physiology, Arousal physiology, Reward, Magnetic Resonance Imaging, Erotica, Galvanic Skin Response physiology, Brain Mapping
- Abstract
Appetitive conditioning plays an important role in the development and maintenance of pornography-use and gaming disorders. It is assumed that primary and secondary reinforcers are involved in these processes. Despite the common use of pornography and gaming in the general population appetitive conditioning processes in this context are still not well studied. This study aims to compare appetitive conditioning processes using primary (pornographic) and secondary (monetary and gaming-related) rewards as unconditioned stimuli (UCS) in the general population. Additionally, it investigates the conditioning processes with gaming-related stimuli as this type of UCS was not used in previous studies. Thirty-one subjects participated in a differential conditioning procedure in which four geometric symbols were paired with either pornographic, monetary, or gaming-related rewards or with nothing to become conditioned stimuli (CS +
porn , CS +game , CS +money , and CS-) in an functional magnetic resonance imaging study. We observed elevated arousal and valence ratings as well as skin conductance responses for each CS+ condition compared to the CS-. On the neural level, we found activations during the presentation of the CS +porn in the bilateral nucleus accumbens, right medial orbitofrontal cortex, and the right ventral anterior cingulate cortex compared to the CS-, but no significant activations during CS +money and CS +game compared to the CS-. These results indicate that different processes emerge depending on whether primary and secondary rewards are presented separately or together in the same experimental paradigm. Additionally, monetary and gaming-related stimuli seem to have a lower appetitive value than pornographic rewards., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)- Published
- 2024
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11. The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism.
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Stark R
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- Animals, Humans, Smell physiology, Energy Metabolism physiology, Olfactory Bulb physiology, Olfactory Bulb metabolism, Neurosecretory Systems physiology, Neurosecretory Systems metabolism, Feeding Behavior physiology
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Olfaction is the most ancient sense and is needed for food-seeking, danger protection, mating and survival. It is often the first sensory modality to perceive changes in the external environment, before sight, taste or sound. Odour molecules activate olfactory sensory neurons that reside on the olfactory epithelium in the nasal cavity, which transmits this odour-specific information to the olfactory bulb (OB), where it is relayed to higher brain regions involved in olfactory perception and behaviour. Besides odour processing, recent studies suggest that the OB extends its function into the regulation of food intake and energy balance. Furthermore, numerous hormone receptors associated with appetite and metabolism are expressed within the OB, suggesting a neuroendocrine role outside the hypothalamus. Olfactory cues are important to promote food preparatory behaviours and consumption, such as enhancing appetite and salivation. In addition, altered metabolism or energy state (fasting, satiety and overnutrition) can change olfactory processing and perception. Similarly, various animal models and human pathologies indicate a strong link between olfactory impairment and metabolic dysfunction. Therefore, understanding the nature of this reciprocal relationship is critical to understand how olfactory or metabolic disorders arise. This present review elaborates on the connection between olfaction, feeding behaviour and metabolism and will shed light on the neuroendocrine role of the OB as an interface between the external and internal environments. Elucidating the specific mechanisms by which olfactory signals are integrated and translated into metabolic responses holds promise for the development of targeted therapeutic strategies and interventions aimed at modulating appetite and promoting metabolic health., (© 2024 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)
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- 2024
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12. Establishment of the deuterium oxide dilution method as a new possibility for determining the transendothelial water permeability.
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Müller H, Hahn J, Gierke A, Stark R, Brunner C, Hoffmann TK, Greve J, Wittekindt O, and Lochbaum R
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- Humans, Electric Impedance, Water metabolism, Endothelial Cells metabolism, Endothelial Cells drug effects, Permeability, Animals, Endothelium, Vascular metabolism, Endothelium, Vascular drug effects, Capillary Permeability drug effects, Human Umbilical Vein Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells drug effects, Deuterium Oxide metabolism
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Increase in transendothelial water permeability is an essential etiological factor in a variety of diseases like edema and shock. Despite the high clinical relevance, there has been no precise method to detect transendothelial water flow until now. The deuterium oxide (D
2 O) dilution method, already established for measuring transepithelial water transport, was used to precisely determine the transendothelial water permeability. It detected appropriate transendothelial water flow induced by different hydrostatic forces. This was shown in four different endothelial cell types. The general experimental setup was verified by gravimetry and absorbance spectroscopy. Determination of transendothelial electrical resistance (TEER) and immunocytochemical staining for proteins of the cell-cell contacts were performed to ensure that no damage to the endothelium occurred because of the measurements. Furthermore, endothelial barrier function was modulated. Measurement of transendothelial water flux was verified by measuring the TEER, the apparent permeability coefficient and the electrical capacity. The barrier-promoting substances cyclic adenosine monophosphate and iloprost reduced TEER and electrical capacity and increased permeability. This was accompanied by a reduced transendothelial water flux. In contrast, the barrier-damaging substances thrombin, histamine and bradykinin reduced TEER and electrical capacity, but increased permeability. Here, an increased water flow was shown. This newly established in vitro method for direct measurement of transendothelial water permeability was verified as a highly precise technique in various assays. The use of patient-specific endothelial cells enables individualized precision medicine in the context of basic edema research, for example regarding the development of barrier-protective pharmaceuticals., (© 2024. The Author(s).)- Published
- 2024
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13. A distinct, high-affinity, alkaline phosphatase facilitates occupation of P-depleted environments by marine picocyanobacteria.
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Torcello-Requena A, Murphy ARJ, Lidbury IDEA, Pitt FD, Stark R, Millard AD, Puxty RJ, Chen Y, and Scanlan DJ
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- Phosphorus metabolism, Bacterial Proteins metabolism, Bacterial Proteins genetics, Synechococcus genetics, Synechococcus metabolism, Phylogeny, Seawater microbiology, Alkaline Phosphatase metabolism, Alkaline Phosphatase genetics, Prochlorococcus genetics, Prochlorococcus metabolism
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Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus , the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity. We demonstrate that Psip1 has undergone convergent evolution with PhoX, requiring both iron and calcium for activity and likely possessing identical key residues around the active site, despite generally very low sequence homology. Interrogation of metagenomes and transcriptomes from TARA oceans and an Atlantic Meridional transect shows that psip1 is abundant and highly expressed in picocyanobacterial populations from the Mediterranean Sea and north Atlantic gyre, regions well recognized to be phosphorus (P)-deplete. Together, this identifies psip1 as an important oligotrophy-specific gene for P recycling in these organisms. Furthermore, psip1 is not restricted to picocyanobacteria and is abundant and highly transcribed in some α-proteobacteria and eukaryotic algae, suggesting that such a high-affinity phosphatase is important across the microbial taxonomic world to occupy low-P environments., Competing Interests: Competing interests statement:The authors declare no competing interest.
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- 2024
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14. The impact of extinction timing on pre-extinction arousal and subsequent return of fear.
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Kampa M, Stark R, and Klucken T
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- Animals, Humans, Extinction, Psychological physiology, Pituitary-Adrenal System, Fear physiology, Arousal physiology, Hypothalamo-Hypophyseal System, Galvanic Skin Response
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Exposure-based therapy is effective in treating anxiety, but a return of fear in the form of relapse is common. Exposure is based on the extinction of Pavlovian fear conditioning. Both animal and human studies point to increased arousal during immediate compared to delayed extinction (>+24 h), which presumably impairs extinction learning and increases the subsequent return of fear. Impaired extinction learning under arousal might interfere with psychotherapeutic interventions. The aim of the present study was to investigate whether arousal before extinction differs between extinction groups and whether arousal before extinction predicts the return of fear in a later (retention) test. As a highlight, both the time between fear acquisition and extinction (immediate vs. delayed) and the time between extinction and test (early vs. late test) were systematically varied. We performed follow-up analyses on data from 103 young, healthy participants to test the above hypotheses. Subjective arousal ratings and physiological arousal measures of sympathetic and hypothalamic pituitary adrenal axis activation (tonic skin conductance and salivary cortisol) were collected. Increased pre-extinction arousal in the immediate extinction group was only confirmed for subjective arousal. In linear regression analyses, none of the arousal measures predicted a significant return of fear in the different experimental groups. Only when we aggregated across the two test groups, tonic skin conductance at the onset of extinction predicted the return of fear in skin conductance responses. The overall results provide little evidence that pre-extinction arousal affects subsequent extinction learning and memory. In terms of clinical relevance, there is no clear evidence that exposure could be improved by reducing subjective or physiological arousal., (© 2024 Kampa et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2024
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15. Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk.
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de Biase MS, Massip F, Wei TT, Giorgi FM, Stark R, Stone A, Gladwell A, O'Reilly M, Schütte D, de Santiago I, Meyer KB, Markowetz F, Ponder BAJ, Rintoul RC, and Schwarz RF
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- Humans, Smoking adverse effects, Smoking genetics, Lung metabolism, Nicotiana, Nasal Mucosa metabolism, Transcriptome, Lung Neoplasms genetics, Lung Neoplasms metabolism
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Background: Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers., Methods: We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer., Results: We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier., Conclusions: Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality., (© 2024. The Author(s).)
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- 2024
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16. Empathy and psychopathology in children and adolescents: the role of parental mental illness and emotion regulation.
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Luczejko AA, Hagelweide K, Stark R, Weigelt S, Christiansen H, Kieser M, Otto K, Reck C, Steinmayr R, Wirthwein L, Zietlow AL, and Schwenck C
- Abstract
Objective: Although empathy is known to be a strength, recent studies suggest that empathy can be a risk factor for psychopathology under certain conditions in children. This study examines parental mental illness as such a condition. Further, it aims to investigate whether maladaptive emotion regulation (ER) mediates the relationship between empathy and psychopathological symptoms of children., Methods: Participants were 100 children of parents with a mental illness (55% female) and 87 children of parents without a mental illness (50% female) aged 6 - 16 years and their parents., Results: Greater cognitive empathy was related to more psychopathological symptoms in COPMI, but not in COPWMI. In addition, in COPMI maladaptive ER mediated this relationship. In contrast, greater affective empathy was associated with more psychopathological symptoms regardless of whether parents had a mental illness., Conclusion: Our findings highlight the importance of implementing preventive programs for COPMI that specifically target the reduction of maladaptive ER., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luczejko, Hagelweide, Stark, Weigelt, Christiansen, Kieser, Otto, Reck, Steinmayr, Wirthwein, Zietlow, Schwenck and the COMPARE-family research group.)
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- 2024
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17. A non-inferiority clinical trial comparing probiotics and oral corticosteroids for the management of acute exacerbation of atopic dermatitis patients.
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Gamal NA, Shoaib MA, Farag AG, Stark R, and Tso S
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A prospective controlled pilot study on the feasibility of utilization of a probiotic mixture for management of acute exacerbation of atopic dermatitis (AD). Patients were allocated to either standard of care (SOC) therapy with tapering dose of steroids or a probiotic mixture over 3 weeks. After the 3-week intervention, patients on steroids achieved significantly higher clinical response rates and significantly deeper response as measured by the change in SCORAD score. No gut microbiome changes could be appreciated in either group after the treatment period. We could conclude that probiotics cannot replace SOC therapy for the management of acute exacerbation of AD., Competing Interests: All authors have no conflicts to declare., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)
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- 2024
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18. Compulsive sexual behavior disorder in an inpatient sample with substance use disorder.
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Golder S, Walter B, Bengesser I, Kramer D, Muhl C, Tahmassebi N, Storz F, Markert C, and Stark R
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Background: Several studies indicate that compulsive sexual behavior disorder (CSBD) shares core elements with substance use disorder (SUD). These findings support the assumption of common mechanisms in addiction, which may lead to a higher tendency in patients with SUD to have comorbid CSBD. Nevertheless, this relationship between CSBD and SUD is poorly understood to date., Aim: This study aimed to compare the prevalence of CSBD and its subtype pornography use disorder (PUD) between a SUD group and a matched control group. Herein, we aimed to test whether patients with SUD are more likely to have a comorbid CSBD/PUD. We further hypothesized that a higher CSBD/PUD prevalence in patients with SUD is accompanied by more pronounced CSBD- and PUD-related personal characteristics., Methods: We assessed CSBD, PUD, and related personal characteristics in an inpatient SUD sample ( N = 92) and a healthy control sample matched by age, gender, and educational level., Outcomes: Primary outcomes were the diagnoses of CSBD/PUD as assessed by questionnaires. CSBD/PUD-related personal characteristics were the early onset of problematic pornography consumption, relationship status as a single person, a high sexual motivation, a high level of time spent watching pornography, and a high degree of problematic pornography consumption (Problematic Pornography Consumption Scale, short version)., Results: There was no significant difference between groups regarding CSBD prevalence (SUD sample, 3.3%; control sample, 7.6%) and PUD prevalence (SUD sample, 2.2%; control sample, 6.5%). We found relationship status as a single person and the sexual motivation dimension of importance of sex to be the only CSBD-related personal characteristics that were more pronounced in the SUD sample than the matched control group., Clinical Implications: Results indicate no higher tendency for patients with SUD to develop comorbid CSBD/PUD, yet important vulnerabilities (eg, emotional dysregulation) should be considered when treating addictive disorder to prevent possible symptom displacement., Strengths and Limitations: A strength of the study is that we compared a sample of patients with SUD with a matched control sample and used an instrument based on ICD-11 criteria for CSBD. Possible limitations are significant differences between the groups because of the restrictions in an inpatient clinic that may have influenced responses (eg, roommates) and that the control group was not screened for SUD. Therefore, the results should be interpreted with some caution., Conclusion: We found no evidence of an overcomorbidity of SUD and CSBD/PUD. However, a higher rate of vulnerability factors for CSBD/PUD in the SUD sample might suggest some similarities between SUD and CSBD/PUD., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)
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- 2024
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19. Reply on "Why compulsive sexual behavior is not a form of addiction like drug addiction".
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Stark R, Walter B, Bengesser I, Kramer D, Muhl C, Tahmassebi N, Khatib S, Storz F, Markert C, and Golder S
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Competing Interests: The authors report no conflicts of interest.
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- 2024
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20. The impact of past childhood adversity and recent life events on neural responses during fear conditioning.
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Kampa M, Stark R, and Klucken T
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- Child, Humans, Fear physiology, Fear psychology, Brain pathology, Conditioning, Classical physiology, Brain Mapping, Magnetic Resonance Imaging, Adverse Childhood Experiences, Psychological Tests, Self Report
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Background and Purpose: Many studies have shown that exposure to life events can have a negative impact on mental health. Life events like the death of a spouse or the birth of a child pose a challenge and require temporal or permanent adjustments. Meta-analyses on brain stress responses found bilateral anterior insula activation in response to acute stress. Fear conditioning is assumed a crucial mechanism for the development of anxiety disorders associated with increased activation in the bilateral amygdala. Empirical evidence is lacking regarding the relationship of exposure to recent life events and past childhood adversity with neural processing during fear conditioning., Methods: In the present study, we analyzed data from 103 young, healthy participants. Multiple linear regressions were performed on functional magnetic resonance imaging activation during fear conditioning with the Life Events Scale for Students and the Childhood Trauma questionnaire included as covariates in two separate models., Results: We found a positive relationship between the number of life events in the last year and left amygdala activation to the conditioned stimulus. A second finding was a positive relationship between childhood adversity and right anterior insula response to the unconditioned stimulus., Conclusions: Many studies have shown increased amygdala activity after stressful life events. In addition, the anterior insula is activated during acute stress. The present study points to stressor-induced increased salience processing during fear conditioning. We suggest that this could be a potential mechanism for resilience versus mental illness., (© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)
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- 2024
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21. Parenting stress in parents with and without a mental illness and its relationship to psychopathology in children: a multimodal examination.
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Seipp V, Hagelweide K, Stark R, Weigelt S, Christiansen H, Kieser M, Otto K, Reck C, Steinmayr R, Wirthwein L, Zietlow AL, and Schwenck C
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Objective: Children of parents with a mental illness are at heightened risk to develop a mental illness themselves due to genetics and environmental factors. Although parenting stress (PS) is known to be associated with increased psychopathology in parents and children, there is no study investigating PS multimodally in a sample of parents with a mental illness. This study aims to compare PS of parents with and without a mental illness and further to examine the relationship between PS and psychopathology of children., Methods: Participants were parents with a mental illness and parents without a mental illness and their children aged four to sixteen years. We assessed PS multimodally using a questionnaire, parents' evaluation of children's behavior (relational schemas) and psychophysiological arousal of parents during free speech task., Results: Self-reported PS was increased, and evaluation of children's behavior was more negative and less positive in parents with a mental illness compared to parents without a mental illness. Children's psychopathology was associated with self-reported PS and relational schemas of parents. Regarding psychophysiological arousal, parents with a mental illness showed reduced reactivity in heart rate from baseline to free speech task in comparison to parents without a mental illness., Conclusions: Our findings highlight the importance of implementing intervention programs to reduce PS for parents and children. In particular, parents with a mental illness might benefit from specific intervention programs in order to interrupt the transgenerational transmission of mental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Seipp, Hagelweide, Stark, Weigelt, Christiansen, Kieser, Otto, Reck, Steinmayr, Wirthwein, Zietlow, Schwenck and the COMPARE-Family Research Group.)
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- 2024
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22. Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.
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Fricke S, Seinsche RJ, Neudert MK, Schäfer A, Zehtner RI, Stark R, and Hermann A
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- Humans, Conditioning, Classical physiology, Extinction, Psychological physiology, Galvanic Skin Response, Mental Recall physiology, Magnetic Resonance Imaging methods, Phobia, Social diagnostic imaging
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Background: There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event., Methods: During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses., Results: Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions., Conclusions: Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.
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- 2024
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23. Adipositas Care and Health Therapy (ACHT) after Bariatric-Metabolic Surgery: A Prospective, Non-Randomized Intervention Study.
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Stark R, Renz A, Hanselmann M, Haas C, Neumann A, Martini O, Seyfried F, Laxy M, Stier C, Zippel-Schultz B, Fassnacht M, and Koschker AC
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- Humans, Prospective Studies, Germany, Adult, Treatment Outcome, Female, Male, Obesity, Morbid surgery, Obesity surgery, Postoperative Care methods, Middle Aged, Bariatric Surgery, Quality of Life
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Introduction: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term postoperative care. Since no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers., Methods: ACHT is a multicenter, prospective, non-randomized control group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric bypass or sleeve gastrectomy (months 1-18 postoperatively), intervention group 2 begins the program 18 months after surgery (months 19-36 postoperatively). Intervention groups are compared to respective control groups that had surgery 18 and 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care., Results: The primary endpoint to compare intervention and control groups is the adapted King's score, a composite tool evaluating physical, psychological, socioeconomic, and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the 3 years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period., Conclusions: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life, and the feasibility of such a program outside of specialized obesity centers., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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24. Carotid Artery Patency and Neurodevelopmental Outcomes After Decannulation in Pediatric Extracorporeal Life Support.
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Kwon EG, Anderson JE, DiGeronimo R, Kirk CCJ, Billimoria ZC, Rothstein DH, Stark R, McMullan DM, Brogan TV, Riehle KJ, and Rice-Townsend SE
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- Female, Humans, Child, Infant, Newborn, Carotid Arteries, Catheterization methods, Retrospective Studies, Extracorporeal Membrane Oxygenation adverse effects, Extracorporeal Membrane Oxygenation methods, Meconium Aspiration Syndrome, Hernias, Diaphragmatic, Congenital
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Introduction: Decannulation from veno-arterial extracorporeal life support may involve ligation or repair of the carotid artery; however, differences in outcomes are not clear. This study aimed to describe short- and long-term artery patency and neurodevelopmental outcomes in neonatal and pediatric patients who underwent carotid artery repair (CAR) versus ligation at decannulation., Methods: Patients supported on veno-arterial extracorporeal life support during the first 15 mo of life from 2010 to 2020 at a large, tertiary care children's hospital were included. Decannulation strategy, postdecannulation imaging, and follow-up visits were reviewed., Results: 74 patients were identified with median age at cannulation 2 d (interquartile range [IQR] = 1-21 d) and median weight 3.7 kg (interquartile range= 3.2-4.4 kg). Indications included congenital cardiac conditions (27%), congenital diaphragmatic hernia (19%), pulmonary hypertension (19%), meconium aspiration (16%), and pneumonia/sepsis (14%). Forty-two patients (57%) underwent CAR. Patients on extracorporeal life support >5 d were 95% less likely to undergo CAR (P < 0.001). Of CAR patients, 18 (43%) had doppler ultrasound performed within the 2-y follow-up period. Ten of 18 patients (55.6%) had >50% stenosis (3) or complete occlusion (7). Only 36% (27/74) had formal neurodevelopmental follow-up within 6 mo and 41% (30/74) within 2 y; however, no significant differences in function were seen between groups., Conclusions: Neonates and young toddler patients undergoing CAR following extracorporeal life support decannulation are at risk for partial or complete artery occlusion. In our study population, repair and ligation at decannulation appear to have similar neurodevelopmental outcomes; however, follow-up to assess function is not standardized. Longer term follow-up and risk stratification are needed to guide decannulation strategy., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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25. Emotional Changes during Imagery Rescripting of Aversive Social Memories in Social Anxiety Disorder: A Randomized Controlled Trial.
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Seinsche RJ, Fricke S, Neudert MK, Zimmer RI, Stark R, and Hermann A
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- Humans, Female, Male, Adult, Middle Aged, Mental Recall physiology, Memory, Phobia, Social therapy, Phobia, Social psychology, Heart Rate physiology, Imagery, Psychotherapy methods, Emotions physiology
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Introduction: Imagery rescripting (ImRs) is a psychotherapeutic intervention targeting aversive memories. During the three-phase intervention, patients reexperience their aversive memory (phase 1), observe the scene from their adult perspective, and intervene to help their former selves (phase 2), and reexperience it again with the positive changes (phase 3). Previous studies have rarely investigated emotional and regulatory processes taking place during the intervention., Objective: This randomized controlled trial investigated self-reported affective and physiological responses during ImRs., Methods: Seventy-seven patients with social anxiety disorder (SAD) were randomly assigned to a single session of ImRs or a control intervention (recall and discussion of the memory) targeting an aversive social memory. Heart rate (HR) and heart rate variability (HRV) were assessed during and post hoc ratings of positive and negative feelings after baseline and the intervention phases., Results: Relative to the control intervention, ImRs resulted in an initial increase in negative feelings from baseline to phase 1 and a following larger (phase 1 to phase 2) and more stable (phase 2 to phase 3) decrease in negative feelings/increase in positive feelings. On the physiological level, during ImRs compared to the control intervention, mean HR was significantly higher during phase 1 and HRV during phase 3, each compared to baseline., Conclusions: These results provide further information about the specific sequence of emotional responses on different response levels during ImRs, being consistent with known theories of emotional processing and supposed mechanisms of ImRs., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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26. Decontextualized fear memories? Stronger conditioned fear responses during extinction learning and extinction recall in a safe context predict the development of long-term analog intrusions.
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Neudert MK, Schäfer A, Zehtner RI, Fricke S, Seinsche RJ, Stark R, and Hermann A
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- Humans, Female, Fear physiology, Conditioning, Classical physiology, Mental Recall physiology, Magnetic Resonance Imaging, Extinction, Psychological physiology, Galvanic Skin Response
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Background: Difficulties in the context-dependent modulation of conditioned fear are known for posttraumatic stress disorder and may explain the occurrence of intrusive memories in safe contexts. The current study therefore investigated if reduced context-dependent modulation of conditioned fear and its underlying neural circuitry constitute risk factors for the development of analog intrusions in response to an experimental trauma., Methods: Eighty-five healthy women participated in the trauma film paradigm to investigate the development of analog intrusions as well as explicit memory for an experimental trauma after one week and three months, respectively. Before, participants underwent a context-dependent fear conditioning paradigm during functional magnetic resonance imaging with fear acquisition in context A and extinction training in context B on a first day, as well as extinction recall in context B and fear renewal in a novel context C one day later. Skin conductance responses (SCRs) and blood oxygen level dependent responses were main outcome measures., Results: In addition to stronger fear acquisition in context A, stronger conditioned fear responses in the safe context B, as indicated by stronger conditioned SCRs or stronger activation of fear expressing regions during extinction learning and recall, predicted the development of long-term analog intrusions., Conclusions: Stronger fear responses in safe and danger contexts were risk factors for the development of long-term analog intrusions and point to decontextualized fear memories and difficulties in the context-dependent modulation of conditioned fear. Altered fear conditioning processes and reduced storage of contextual information may cause the occurrence of fear independent of context.
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- 2024
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