Behandlung psychotischer Störungen - Aspekte der Therapiebeziehung und Untersuchung unmedizierter Menschen mit psychotischen Störungen

Die vorliegende kumulative Dissertation befasst sich mit der Behandlung psychotischer Störungen und setzt sich aus drei Studien zusammen. Dabei werden mit dem Fokus auf Therapieprozesse im Rahmen der Kognitiven Verhaltenstherapie für Psychosen (Studien 1 und 2) sowie auf die spezifische Gruppe der unmedizierten Personen mit psychotischen Störungen (Studie 3) zwei inhaltliche Schwerpunkte gesetzt. Die therapeutische Beziehung in der kognitiven Verhaltenstherapie für Psychosen (KVT-P) stellt den ersten Schwerpunkt dieser Arbeit dar. Die Wirksamkeit der KVT-P wurde in zahlreichen Studien belegt. Erste Studien deuten darauf hin, dass KVT-P auch für unmedizierte Betroffene eine wirksame Behandlung darstellt. Weniger bekannt ist, welche Mechanismen und Wirkfaktoren für den Therapieerfolg relevant sind. Im Rahmen des ersten Teils der Dissertation wurde mit dem Fokus auf die Therapiebeziehung ein allgemeiner Wirkfaktor untersucht. Die therapeutische Beziehung zeigt konsistente Zusammenhänge zum Therapieerfolg, unabhängig von der therapeutischen Schule oder der zugrunde liegenden Störung, und stellt somit einen wichtigen Wirkfaktor in der Psychotherapie dar. Daher scheint die Kenntnis von Prädiktoren der Therapiebeziehung wichtig zu sein, um Hindernisse des Beziehungsaufbaus zu reduzieren und mit der Verbesserung der Beziehungsqualität auch den Erfolg der Therapie zu fördern. In der KVT-P wurden bisher vorwiegend Patientenmerkmale als mögliche Prädiktoren der Therapiebeziehung untersucht, mit teilweise uneinheitlichen Ergebnissen. Vor diesem Hintergrund wurden in der ersten Studie dieser Dissertation Patientenmerkmale als Prädiktoren der frühen Therapiebeziehung untersucht. Dabei zeigte sich die Negativsymptomatik als negativer Prädiktor der von Patienten und Therapeuten eingeschätzten Qualität der Therapiebeziehung. Zahlreiche Studien deuten darauf hin, dass auch Unterschiede zwischen Therapeuten einen Einfluss auf den Zusammenhang zwischen Beziehungsqualität und Therapieergebnis haben und somit auch Therapeutenmerkmale zur Erklärung der Therapiebeziehung relevant sind. Im Rahmen der zweiten Studie wurden daher Therapeutenmerkmale als Prädiktoren der therapeutischen Beziehung untersucht. Dabei zeigten sich die wahrgenommene Echtheit der Therapeuten sowie die durch Patienten eingeschätzte Kompetenz als positive Prädiktoren der Therapiebeziehung. Ein besseres Verständnis von Therapieprozessen eröffnet die Möglichkeit, Behandlungsverläufe zu verbessern. Die Ergebnisse dieser Studien sind relevant für die klinische Praxis. Therapeuten, die mit Patienten mit deutlicher Negativsymptomatik arbeiten, sollten dies als mögliches Hindernis der Beziehung antizipieren und sich besonders um den Aufbau einer positiven Therapiebeziehung bemühen. Therapeutische Basisfertigkeiten, insbesondere Echtheit oder Authentizität, sollten im Rahmen der Ausbildung neben spezifischen Techniken stärker gefördert werden. Der zweite thematische Fokus liegt auf der Untersuchung von Menschen mit psychotischen Störungen, die keine antipsychotische Medikation einnehmen. Medikamentöse Behandlungsansätze mit Antipsychotika gelten als Therapie „erster Wahl“ und stellen die Standardbehandlung für psychotische Störungen dar. Unregelmäßige Einnahme oder eigenständiges Absetzen sind jedoch weit verbreitete Phänomene. Zahlreiche Studien deuten darauf hin, dass eine Vielzahl von Betroffenen keine antipsychotische Medikation einnimmt. Dabei gibt es Hinweise darauf, dass unmedizierte Patienten weniger starke Symptomatik und ein besseres Funktionsniveau aufzeigen als Patienten, die Antipsychotika einnehmen. Über alternative Bewältigungsstrategien dieser Personen ist bisher jedoch wenig bekannt. Im Rahmen einer quantitativ-qualitativen Interviewstudie (dritte Studie) wurden soziodemographische und klinische Variablen sowie soziale Unterstützung und Krankheitsbewältigungsstrategien in einer Gruppe von unmedizierten Personen mit Psychosen erhoben und mit einer medizierten Gruppe verglichen. In Übereinstimmung mit früheren Befunden zeigte die Gruppe der Unmedizierten ein höheres allgemeines Funktionsniveau. Dies deutet darauf hin, dass es für einen Teil der Betroffenen möglich ist, auch ohne Antipsychotika im Alltag gut zu funktionieren. Keine Unterscheide zeigten sich jedoch in der Symptomatik, der sozialen Unterstützung oder in der Anzahl und subjektiv bewerteten Wirkung der Bewältigungsstrategien. Vor dem Hintergrund der möglichen schweren Nebenwirkungen und Risiken der Langzeiteinnahme von Antipsychotika sind insbesondere prospektive Langzeitstudien nötig, um Prädiktoren für positive Störungsverläufe ohne Einnahme von Antipsychotika zu identifizieren und damit die individuelle Behandlungsplanung zu verbessern. Die Förderung des Zugangs zu alternativen oder ergänzenden Behandlungsmethoden, etwa zur KVT-P, stellt darüber hinaus ein wichtiges gesundheitspolitisches Ziel dar und könnte ebenfalls zur Verbesserung der Behandlung psychotischer Störungen beitragen

Development of microsatellite markers for the wetland grasshopper Stethophyma grossum

Stethophyma grossum is a threatened Eurosiberian grasshopper species. Since it is bound to wetlands, S. grossum is often used as indicator for extensive wet meadows. To study its movement capability and dispersal habitat in landscape genetic analyses, we developed ten polymorphic microsatellite markers, making use of next generation sequencing. Markers were tested on 75 individuals collected in five populations from Switzerland. We found four to 18 alleles per locus. Observed and expected heterozygosities varied between 0.215-0.893 and 0.397-0.831, respectively. One marker seems to be sex-chromosome X-linked and one showed high null allele frequencies, a phenomenon generally detected in microsatellite studies on grasshopper

Eight microsatellite markers for Armillaria cepistipes and their transferability to other Armillaria species

We isolated eight polymorphic microsatellite markers for the basidiomycete Armillaria cepistipes and characterised them by analysing 50 isolates representing two geographically distinct populations from Switzerland and the Ukraine. The number of alleles per locus and population varied from one to eight, resulting in 43 alleles over the eight loci and two populations. In both populations, no significant linkage disequilibrium was observed between pairs of loci. Significant (P < 0.05) deviations from Hardy-Weinberg equilibrium were observed at one locus in the Swiss population and at three loci in the Ukrainian population. Of the eight loci developed for A. cepistipes, six were also polymorphic in A. gallica, four in A. ostoyae, two in A. mellea, and one in A. borealis. Beside the potential to be used for population genetic studies on A. cepistipes, these microsatellites thus represent additional molecular markers for three of the four annulated Armillaria species occurring in Europ

Does training matter? : construction quality for a new start transit system : the case of Tren Urbano

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 2002.Includes bibliographical references (p. 99-104).As with many other large-scale infrastructure projects, the construction of a transit project is potentially vulnerable to quality failures, which can lead to completion delays and cost overruns. Especially with technologically advanced, new-start transit projects, a limitation or lack of skilled labor can exacerbate those risks. This thesis examines the case of Tren Urbano in San Juan, Puerto Rico, a rapid rail project currently being constructed in an area with limited on-island experience in the design, construction, operation or maintenance of such a technologically sophisticated transit system. The motivating question for this thesis is, does training matter for construction quality? The research findings of this thesis show that the multiple prime contractors operating under similar contractual arrangements and resource conditions in San Juan exhibit variations in the quality of construction. Research findings also reveal variations in the type of training programs established by the contractors. A limited conclusion is drawn that although training of inexperienced labor does not single-handedly insure high quality of construction, it nevertheless is important to the successful implementation of project design. Thus, this thesis argues that in order to maximize the quality of construction in a new transit system, the client-owners should create an appropriate strategy which carefully assesses and matches three factors: 1) procurement strategy, whether the conventional design-bid-build or innovative design-build arrangement, 2) contractor competence and experience, and 3) the existent local labor skill level or training capacity. A successful procurement strategy for the construction of future extensions to Tren Urbano should therefore consider: 1) choosing best-value bids over low bids, where the contractor has exhibited expertise and 2) training a broad range of skill sets, that includes explicit attention paid to the construction laborers and monitoring inspectors crucial for the quality of construction. Successful training should be tailored to pre-empt potential breakdowns of a particular procurement strategy. Furthermore, the training should also be an intentional, collaborative effort between the public education sector, the private construction sector, and an expanded labor union presence, and should fit within an overall industrial development policy of the government. An important theoretical contribution of this thesis is the expansion of the technology transfer discourse from a focus on an educated managerial class to include the ramping-up of skills for low-skilled, often uneducated, labor in order to expand the labor market for economic development while improving the profitability of the private sector ventures utilizing local labor.by Esther J. Lee.M.C.P

Investigating Neural Plasticity and Cortical Reorganization via fMRI Following Tumor Resection

The brain is known to dynamically repair and reorganize itself after sustaining damage. Patients undergoing tumor resection display cortical reorganization, but the specific processes remain relatively unknown. Our longitudinal study investigates the effectiveness of task-based functional magnetic resonance imaging (fMRI) in detecting recovery of eloquent function in brain tumor patients. We assessed the changes in brain activity as the brain recovers from tumor growth and surgery through the correlations between neuropsychological analysis and changes in fMRI activation.https://digitalcommons.unmc.edu/surp2021/1026/thumbnail.jp

Urinary Phthalate Metabolites and Slow Walking Speed in the Korean Elderly Environmental Panel II Study

Background: Previous epidemiological studies have suggested that phthalate exposure may contribute to neurocognitive and neurobehavioral disorders and decreased muscle strength and bone mass, all of which may be associated with reduced physical performance. Walking speed is a reliable assessment tool for measuring physical performance in adults age 60 y and older. Objective: We investigated associations between urinary phthalate metabolites and slowness of walking speed in community-dwelling adults ages 60-98 y. Methods: We analyzed 1,190 older adults [range, 60-98 y of age; mean ± standard deviation (SD), 74.81 ± 5.99] from the Korean Elderly Environmental Panel II study and measured repeatedly up to three times between 2012 and 2014. Phthalate exposure was estimated using the following phthalate metabolites in urine samples: mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP). Slowness was defined as a walking speed of < 1.0 meter/second. We used logistic and linear regression models to evaluate the association between each urinary phthalate metabolite and slowness or walking-speed change. We also used Bayesian kernel machine regression (BKMR) to examine overall mixture effects on walking speed. Results: At enrollment, MBzP levels were associated with an increased odds of slowness [odds ratio (OR) per doubling increase: 1.15, 95% confidence interval (CI): 1.02, 1.30; OR for the highest vs. lowest quartile: 2.20 (95% CI: 1.12, 4.35) with p-trend across quartiles = 0.031]. In longitudinal analyses, MEHHP levels showed an increased risk of slowness [OR per doubling increase: 1.15 (95% CI: 1.02, 1.29), OR for the highest vs. lowest quartile: 1.47 (95% CI: 1.04, 2.06), p−trend=0.035]; whereas those with higher MnBP showed a reduced risk of slowness [OR per doubling increase: 0.84 (95% CI: 0.74, 0.96), OR in the highest (vs. lowest) quartile: 0.64 (95% CI: 0.47, 0.87), p−trend=0.006]. For linear regression models, MBzP quartiles were associated with slower walking speed (p−trend=0.048) at enrollment, whereas MEHHP quartiles were associated with slower walking speed, and MnBP quartiles were associated with faster walking speed in longitudinal analysis (p−trend=0.026 and <0.001, respectively). Further, the BKMR analysis revealed negative overall trends between the phthalate metabolite mixtures and walking speed and DEHP group (MEHHP, MEOHP, and MECPP) had the main effect of the overall mixture. Discussion: Urinary concentrations of prevalent phthalates exhibited significant associations with slow walking speed in adults ages 60-98 y. https://doi.org/10.1289/EHP10549.This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korea Ministry of Education and the Korea Ministry of Science and Information and Communication Technology (grant numbers 2013R1A6A3A04059556; 2020R1A2C110170311). Also, this study was supported by the Susceptible Population Research Program (2008–2010) from the Korea Ministry of Environment (grant numbers 0411-20080013, 0411-20090007, 0411-20100016). E.G.-E. was supported by the Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) (ESP21PI04/2021). The funders had no role in this study design, data collection, and analysis and prepared all results. All authors participated in literature search and data interpretation. Y.C. supervised the study; Y.C. and Y.H. participated in designing the study; H.K., S.K., and K.K. acquired the data; J.Y., J. Kim, and J. Kwak analyzed data; J.Y. wrote the manuscript; E.G.-E., J. Kim, J. Kwak, H.K., Y.H., and Y.C. critically revised the manuscript. Patient consent was obtained. This study was approved by the institutional review board (IRB) of Seoul National University Hospital/College of Medicine (IRB No. H-1209-004-424).S

Development of a practical dietitian road map for the nutritional management of phenylketonuria (PKU) patients on pegvaliase

Funding Information: Outside the submitted work, the authors disclose the following. Bausell H received personal fees from BioMarin, Ultragenyx, Horizon and Vitaflo. Bélanger-Quintana A reports personal fees from BioMarin, Nutricia, Vitaflo, Orphan Europe, Takeda and Genzyme. Rocha JC received research grants from BioMarin, Glutamine and Cambrooke, as well as personal fees from BioMarin, Applied Pharma Research, Nutricia, Merck Serono, Vitaflo, Cambrooke, PIAM and Lifediet. MacDonald A reports research funding from BioMarin, Nutricia, Applied Pharma Research, Vitaflo, Galen, Metax, Mevalia and Arla, as well as lecture fees from BioMarin, Applied Pharma Research, Nutricia and Vitaflo, and consultancy fees from BioMarin, Applied Pharma Research, Arla, Nutricia and Vitaflo. Met Ed reports grant funding from BioMarin, Nutricia, Vitaflo and Horizon Pharmaceuticals. Bernstein L and Rohr F report lecture fees from Vitaflo. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Background: The metabolic dietitian/nutritionist (hereafter ‘dietitian’) plays an essential role in the nutritional management of patients with phenylketonuria (PKU), including those on pegvaliase. Currently, more educational support and clinical experience is needed to ensure that dietitians are prepared to provide optimal nutritional management and counselling of pegvaliase-treated patients. Methods: Via a face-to-face data-review meeting, followed by a virtual consolidation meeting, a group of expert dietitians and one paediatrician discussed and developed a series of recommendations on the nutritional evaluation and management of patients receiving pegvaliase. The consensus group consisted of 10 PKU experts: six dietitians and one paediatrician from Europe and three dietitians from the US. One European and three US dietitians had experience with pegvaliase-treated patients. Results: The consensus group recommended that a physician, dietitian and nurse are part of the pegvaliase treatment team. Additionally, a psychologist/counsellor should be included if available. Practical proposals for the nutritional evaluation of pegvaliase-treated patients at baseline, during the induction and titration phases and for long-term maintenance were developed. The consensus group suggested assessment of blood Phe at least monthly or every 2 weeks in the event of low blood Phe (i.e., blood Phe <30 μmol/L). It may be appropriate to increase blood Phe monitoring when adjusting protein intake and/or pegvaliase dose. It was recommended that natural protein intake is increased by 10–20 g increments if blood Phe concentrations decrease to <240 μmol/L in patients who are not meeting the dietary reference intake for natural protein of 0.8 g/kg. It was proposed that with pegvaliase treatment blood Phe levels could be maintained <240 μmol/L but more evidence on the safety of achieving physiological blood Phe levels is necessary before any recommendation on the lower blood Phe target can be given. Finally, both patients and dietitians should have access to educational resources to optimally support patients receiving pegvaliase. Conclusion: This practical road map aims to provide initial recommendations for dietitians monitoring patients with PKU prescribed pegvaliase. Given that practical experience with pegvaliase is still limited, nutritional recommendations will require regular updating once more evidence is available and clinical experience evolves.publishersversionpublishe

Cross-Kingdom RNAi of Pathogen Effectors Leads to Quantitative Adult Plant Resistance in Wheat

Cross-kingdom RNA interference (RNAi) is a biological process allowing plants to transfer small regulatory RNAs to invading pathogens to trigger the silencing of target virulence genes. Transient assays in cereal powdery mildews suggest that silencing of one or two effectors could lead to near loss of virulence, but evidence from stable RNAi lines is lacking. We established transient host-induced gene silencing (HIGS) in wheat, and demonstrate that targeting an essential housekeeping gene in the wheat powdery mildew pathogen (Blumeria graminis f. sp. tritici) results in significant reduction of virulence at an early stage of infection. We generated stable transgenic RNAi wheat lines encoding a HIGS construct simultaneously silencing three B.g. tritici effectors including SvrPm3(a1/f1), a virulence factor involved in the suppression of the Pm3 powdery mildew resistance gene. We show that all targeted effectors are effectively downregulated by HIGS, resulting in reduced fungal virulence on adult wheat plants. Our findings demonstrate that stable HIGS of effector genes can lead to quantitative gain of resistance without major pleiotropic effects in wheat

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population