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The persistence of leukemic stem cells (LSCs) represents a problem in the therapy of chronic myeloid leukemia (CML). Hence, it is of utmost importance to explore the underlying mechanisms to develop new therapeutic approaches to cure CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1 mouse model for chronic phase CML, we previously demonstrated that the loss of the docking protein GAB2 counteracts the infiltration of mast cells (MCs) in the bone marrow (BM) of BCR::ABL1 positive mice. Here, we show for the first time that BCR::ABL1 drives the cytokine independent expansion of BM derived MCs and sensitizes them for FcεRI triggered degranulation. Importantly, we demonstrate that genetic mast cell deficiency conferred by the Cpa3Cre allele prevents BCR::ABL1 induced splenomegaly and impairs the production of pro-inflammatory cytokines. Furthermore, we show in CML patients that splenomegaly is associated with high BM MC counts and that upregulation of pro-inflammatory cytokines in patient serum samples correlates with tryptase levels. Finally, MC-associated transcripts were elevated in human CML BM samples. Thus, our study identifies MCs as essential contributors to disease progression and suggests considering them as an additional target in CML therapy.

Cells pre-treated for 3h with 10 µM brefeldin A

Supplementary Methods, figures and tables

The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)–refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting. The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology. We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9–based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity. Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum. Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response. Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids. Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation. Conversely, depletion of fatty acids/cholesterol pools by the FDA-approved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro. These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI–refractory multiple myeloma.Significance:Nelfinavir induces lipid bilayer stress in cellular organelles that disrupts mitochondrial respiration and transmembrane protein transport, resulting in broad anticancer activity via metabolic rewiring and activation of the unfolded protein response.

Antiapoptotic Bcl-2 family members have recently (re)emerged as key drug targets in cancer, with a tissue- and tumor-specific activity profile of available BH3 mimetics. In multiple myeloma, MCL-1 has been described as a major gatekeeper of apoptosis. This discovery has led to the rapid establishment of clinical trials evaluating the impact of various MCL-1 inhibitors. However, our understanding about the clinical impact and optimal use of MCL-1 inhibitors is still limited. We therefore explored mechanisms of acquired MCL-1 inhibitor resistance and optimization strategies in myeloma. Our findings indicated heterogeneous paths to resistance involving baseline Bcl-2 family alterations of proapoptotic (BAK, BAX, and BIM) and antiapoptotic (Bcl-2 and MCL-1) proteins. These manifestations depend on the BH3 profile of parental cells that guide the enhanced formation of Bcl-2:BIM and/or the dynamic (ie, treatment-induced) formation of Bcl-xL:BIM and Bcl-xL:BAK complexes. Accordingly, an unbiased high-throughput drug-screening approach (n = 528) indicated alternative BH3 mimetics as top combination partners for MCL-1 inhibitors in sensitive and resistant cells (Bcl-xL>Bcl-2 inhibition), whereas established drug classes were mainly antagonistic (eg, antimitotic agents). We also revealed reduced activity of MCL-1 inhibitors in the presence of stromal support as a drug-class effect that was overcome by concurrent Bcl-xL or Bcl-2 inhibition. Finally, we demonstrated heterogeneous Bcl-2 family deregulation and MCL-1 inhibitor cross-resistance in carfilzomib-resistant cells, a phenomenon linked to the MDR1-driven drug efflux of MCL-1 inhibitors. The implications of our findings for clinical practice emphasize the need for patient-adapted treatment protocols, with the tracking of tumor- and/or clone-specific adaptations in response to MCL-1 inhibition.

Patients with Anorexia Nervosa (AN) show a moderate deficit in overall neuropsychological functioning. Since previous studies on memory performance mainly employed cross-sectional designs, the present study aims to investigate changes in verbal memory following weight-gain.Verbal memory was assessed with the Wechsler Memory Scale-Revised (WMS-R; 'logical memory'-story-recall-subtest) and the California Verbal Learning Test-II (CVLT-II; 'verbal learning'). Included were 31 female patients with AN (18 restricting-, 13 purging-subtype; average disease duration: 5.1 years; average baseline BMI: 14.4 kg/mAt baseline, patients with AN as compared to healthy women displayed deficits in logical memory. In the follow-up assessment, patients with AN improved their logical memory significantly compared to healthy controls (p 0.006). Furthermore, groups did not differ in verbal learning neither before nor after inpatient treatment.Enhanced logical memory in patients with AN following weight-gain is probably due to the impaired memory as compared to healthy controls at T0. A survivorship bias could explain the improved memory performance in longitudinal data in contrast to cross-sectional studies. Patients with AN with poorer memory performance before inpatient treatment are at higher risk to drop out and need support.

COVID-19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) betacoronavirus, affects children in a different way than it does in adults, with milder symptoms. However, several cases of neurological symptoms with neuroinflammatory syndromes, such as the multisystem inflammatory syndrome (MIS-C), following mild cases, have been reported. As with other viral infections, such as rubella, influenza, and cytomegalovirus, SARS-CoV-2 induces a surge of proinflammatory cytokines that affect microglial function, which can be harmful to brain development. Along with the viral induction of neuroinflammation, other noninfectious conditions may interact to produce additional inflammation, such as the nutritional imbalance of fatty acids and polyunsaturated fatty acids and alcohol consumption during pregnancy. Additionally, transient thyrotoxicosis induced by SARS-CoV-2 with secondary autoimmune hypothyroidism has been reported, which could go undetected during pregnancy. Together, those factors may pose additional risk factors for SARS-CoV-2 infection impacting mechanisms of neural development such as synaptic pruning and neural circuitry formation. The present review discusses those conditions in the perspective of the understanding of risk factors that should be considered and the possible emergence of neurodevelopmental disorders in COVID-19-infected children.

In everyday life, adults need to manipulate numbers in several ways. A large range of measures evaluating arithmetic fluency is currently used, differing in definitions and operationalizations of the underlying construct. The basic arithmetic operations include addition, subtraction, multiplication, and division. Here, we introduce an instrument for assessing arithmetic skills (Math4Speed) and evaluate the relation between the basic arithmetic operations in adults. This speeded paper-and-pencil test measures arithmetic performance in the four basic operations graded by difficulty. It was administered to a sample of young neurotypical adults (n = 131 English, n = 134 German, n = 102 Polish, and n = 61 Belgian).Regarding the construct of arithmetic, associations of addition with subtraction and multiplication with division were the highest. We provide norms and criterion validity measures for subscales (4 operations x 2 difficulties) and an overall score. Concerning convergent validity: correlations of Math4Speed and basic number processing were higher for processing two-digit than single-digit numbers. Descriptively, magnitude comparison was stronger related to Math4Speed than different types of parity judgments. Self-reported math grade, math anxiety, and non-verbal intelligence were stronger related to complex arithmetic performance – indicating the necessity to cover a range of item difficulties. None or very weak correlations of Math4Speed to self-reported language grades provided evidence for discriminant validity. Cultural and gender differences in overall performance for subtraction and division were adapted in our norms.Math4Speed is openly available and thus a speeded arithmetic fluency test, which can quickly be employed by researchers to control for math performance in adult samples from different cultural backgrounds.

Die Partizipation von Kindern und Jugendlichen ist sowohl fachlich als auch rechtlich seit vielen Jahren fest verankert und gilt als ein zentrales gesellschaftspolitisches Anliegen. Langst fand eine Abwendung von einem bevormundenden, autoritaren Erziehungsstil hin zu einer demokratischen und selbstbestimmten Bildung und Erziehung der jungen Menschen statt. Dieser Anspruch richtet sich auch an die Leistungserbringer der Hilfen zur Erziehung und erfahrt in diesem Handlungsfeld einen immer hoheren Stellenwert (vgl. Rauschenbach 2012; BMFSFJ 2013). Im Rahmen der wissenschaftlichen Begleitung zum Dialogprozess der SGB-VIII-Reform „Mitreden – Mitgestalten: Die Zukunft der Kinder- und Jugendhilfe“ wurden die Erfahrungen der Beteiligten und Betroffenen mit der Kinder- und Jugendhilfe gesammelt und systematisch ausgewertet, um strukturelle Veranderungsbedarfe aus ihrer Perspektive aufzunehmen.

Level of personality functioning and attachment style as predictors of the successful referral to outpatient psychotherapyObjectives: Outpatient psychotherapy is a key element in the effective treatment of mental health problems. First results suggest that interpersonal problems lead to difficulties in receiving outpatient psychotherapeutic treatment. The relationship between these difficulties, attachment style, and the level of personality functioning is still unclear. Methods: We invited 1011 patients of a psychosomatic-psychotherapeutic university outpatient clinic to participate in the study. The clinical diagnoses according to ICD-10, as well as symptoms of depression (PHQ-D), and quality of life (SF-36) were recorded. Hypothesized predictors for the successful referral to outpatient therapy were patient age, availability of local outpatient treatment, number of ICD-10 diagnoses, the motivation for psychotherapy (FPTM), fear of stigmatization (Stig-9), level of personality functioning (OPD-SQ), and attachment style (ECR-RD). Results: We were able to catamnestically reassess n = 300 patients (67.3 % of patients initially referred to outpatient therapy). A smaller number of clinical diagnoses, greater availability of psychotherapeutic care and higher therapy motivation, as well as a lower level of personality functioning predicted the successful referral to outpatient psychotherapy, while the combination of impaired personality functioning and avoidant attachment style was a negative predictor. Conclusions: Contrary to expectations, patients with a lower level of personality functioning are more successful in receiving outpatient psychotherapy. However, patients with a combination of impaired personality functioning and a high degree of attachment avoidance run the risk of not asserting their need for treatment.

Hintergrund: Psychodynamische Psychotherapien spielen eine wichtige Rolle im deutschen Gesundheitssystem. Der Nachweis ihrer Lehrbarkeit bekommt vor dem Hintergrund des neuen Psychotherapiestudiums eine neue Bedeutung. Dies bezieht sich insbesondere auf erfahrungsbasierte di­daktische Modelle und auf das spezifische Üben von Interventionen. Hier ist bisher unklar, welche Aspekte kompetenz­orientierter psychodynamischer Lehre mit dem subjektiven Lernerfolg zusammenhängen. Methode: In einer Stichprobe mit 47 Kandidatinnen und Kandidaten eines Ausbildungsinstitutes wurden psychodynamische Interventionen mit ­Videofeedback, Peer-Rollenspielen und Simulationspatientinnen und -patienten unterrichtet. Der subjektive Kompetenzgewinn von Prä zu Post wurde in Bezug auf die Interventionen Klarifizieren, Konfrontieren und Deuten mithilfe von t-Tests abgebildet. Zudem wurden in einer multiplen linearen Regression verschiedene Prädiktoren für den subjektiven Lernerfolg getestet. Ergebnisse: Die subjektive Kompetenz nahm für die Interventionen Klarifizieren und Konfrontieren mit großen Effekten, für Deuten mit einem kleinen bis ­mittleren Effekt zu. Der Lernerfolg war korreliert mit einem antizipierten Transfer in den therapeutischen Alltag, einem positiven Erleben der Arbeit mit den Simulationspatientinnen und -patienten sowie mit hilfreich erlebtem Feedback durch die Dozentinnen und Dozenten. Schlussfolgerungen: Psychodynamische Interventionen sind mit erfahrungsbasierten und kompetenzorientierten Unterrichtsformaten lehrbar. Dabei ist wichtig, dass praxisorientierte Formate eine Lernumgebung schaffen, in der die Arbeit mit Simulationspatientinnen und -patienten und das Feedback als konstruktiv und hilfreich erlebt werden. Zukünftige Untersu­chungen sollten den Transfer in den Alltag sowie longitudinale Curricula in den Fokus nehmen.

This study investigated the interplay between agency and therapeutic bond in predicting patient symptoms in outpatient psychotherapy. A total of

We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections.

Objective: This study aimed to develop an observer-rated measure of Insight into Conflictual Relationship Patterns (ICR) applicable to audio- or videotapes of psychotherapy sessions and conduct a f...

BackgroundAnorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN.MethodsTwenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task.ResultsIn comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN.ConclusionsThese results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.

OBJECTIVE This study examined the reciprocal effects between therapeutic agency, working alliance, and symptoms during psychotherapy. We aimed to predict symptom improvement by previous changes in either agency or alliance. In addition, we examined whether alliance development was predicted by previous changes in agency. METHOD A sample of 386 patients in psychodynamic outpatient psychotherapy answered the Therapeutic Agency Inventory (TAI), the Working Alliance Inventory-SR (WAI-SR), and the Symptom Checklist-K11 (SCL-K11) after Sessions 1, 5, 10, 15, and 20. Dynamic panel models were estimated using structural equation modeling. Associations were tested while controlling for autoregressive effects and differentiating within-person changes over time from between-person differences. RESULTS Increases in agency predicted subsequent symptom improvement. Similarly, increases in alliance predicted subsequent symptom improvement. For agency and alliance, we found a more complex pattern with varying reciprocal effects over time. CONCLUSIONS Findings show evidence for agency and alliance as curative change factors in psychodynamic psychotherapy. The study supports the importance of both agency and alliance and further suggests that both mechanisms may need to be balanced in successful psychotherapies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Zusammenfassung

Die Veranderungen in der psychotherapeutischen Landschaft stellen auch an psychodynamische Ausbildungsinstitute neue Anforderungen. Hierzu zahlen die Etablierung moderner Lehr- und Supervisionsformen ebenso wie die Beteiligung an Forschungsaktivitaten, sei es zur Entwicklung psychotherapeutischer Kompetenzen, sei es im Rahmen von Prozess- und Wirksamkeitsforschung. Beschrieben werden die historische und die institutionelle Entwicklung des Heidelberger Instituts fur Psychotherapie (HIP, gegrundet 2010), das als universitatsnahes psychodynamisches Ausbildungsinstitut versucht, den genannten Aufgaben gerecht zu werden. Dargestellt werden Aufbau, curriculare Struktur und Finanzierungsmodell und die Entwicklung von Forschungsstrukturen. Die Tatigkeit des HIP verlauft in jeder Hinsicht erfolgreich und zeigt damit, dass Vielfalt im Bereich der Psychotherapie(ausbildung) realisierbar und nachgefragt ist.

Der Person des Therapeuten kommt eine entscheidende Bedeutung innerhalb des psychotherapeutischen Behandlungsprozesses zu. Somit ruckt auch die Psychotherapieausbildung, als wichtiger Teil der Entwicklung einer therapeutischen Personlichkeit und Kompetenz, zunehmend in den Fokus der Psychotherapieforschung. Bisher ist jedoch wenig bekannt, welche personlichen und inhaltlichen Erwartungen und Wunsche Psychologen zu Beginn ihrer Therapieausbildung an dieselbe haben. Bisherige Untersuchungen beschrankten sich masgeblich auf quantitative Fragebogenerhebungen, was der Vielschichtigkeit der personlichen Erwartungen haufig nicht gerecht werden kann. Es wurden 24 Psychologen zu Beginn ihrer Ausbildung an einem Institut fur tiefenpsychologisch fundierte Psychotherapie (TfP, n = 12) und an einem Institut fur Verhaltenstherapie (VT, n = 12) in einem halbstandardisierten Einzelinterview zu ihren Erwartungen an die gerade begonnene Ausbildung befragt. Die wortlich transkribierten Interviews wurden uber eine qualitative Inhaltsanalyse nach Mayring als deduktive Erhebung mithilfe der Software MaxQDA ausgewertet. Eine zentrale Erwartung an die Ausbildung war die Durchfuhrung praktischer therapeutischer Ubungen in einem geschutzten Rahmen mit Fokus auf die Behandlungstechnik bei VT-Kandidaten und auf die Patient-Therapeut-Beziehung bei TfP-Kandidaten. Bezuglich der Vermittlung theoretischer Inhalte strebten TfP-Kandidaten Theoriearbeit an, berichteten aber Sorgen vor der Umsetzung in die Praxis, wohingegen VT-Kandidaten eine direkte Vermittlung storungs- und behandlungsrelevanten Wissens erwarteten. Die Kandidaten schatzten die Zugehorigkeit zu einem Ausbildungsjahrgang, wobei in der VT-Gruppe Befurchtungen von Erwartungsdruck und Konkurrenz ausgepragter erschienen. Gemeinsam waren beiden Gruppen die Betonung der zeitlichen und der finanziellen Belastungen, insbesondere in der Praktikumszeit, sowie die Bedeutung von Supervision, Selbsterfahrung und personlicher Weiterentwicklung im Rahmen der Ausbildung. Die Erwartungen und Wunsche bezuglich der Ausbildung werden vor dem Hintergrund einer curricularen Bestandsaufnahme beleuchtet und mogliche Konsequenzen fur die bedarfsgerechte Weiterentwicklung der Psychotherapieausbildung abgeleitet.

Objectives: Therapeutic agency is defined as a patient’s intentional influence over the process of psychotherapeutic change. However, there is a lack of conceptually sound self-report measures with...

As a result of the implementation of the CE-marking in the European Union, the testing method as defined in prEN 16516 is about to become the new volatile organic compounds (VOC) testing standard and replace a multitude of testing methods and regulative systems in Europe that assess the existence of VOC in building materials, including wood-based materials. The aim of this study is, first, to compile expert positions regarding testing methods and regulative systems for VOC in wood-based materials, and second, to examine the suitability of using an Argument-Delphi approach to point out consent or dissent regarding testing methods for VOC. A systematic content analysis of initial interviews with 13 experts produced 130 arguments which were subscribed to 13 categories, resulting in 6 potential positions of which 5 were actively taken by experts. While the second step was undertaken as a cross verification of the analysis, the experts were asked to choose a final position as a last step. It was observed that several experts changed their initial position to testing methods and regulative systems for VOC, but still without a consensus arising within the expert panel. Hence, the results of the study reveal that no verifiable consent exists within the group of experts—neither concerning testing methods, nor regulative systems. The Argument-Delphi approach applied constitutes a useful method in pointing out dissent between the experts towards a legal requirement like a European standard.

Forestry operations in urban forests are often perceived negatively by forest visitors seeking recreation. This study investigates the range of attitudes present among such forest visitors and how their perceptions towards forestry operations can be influenced by targeted information measures. First, in order to identify the specific attributes and values associated with forestry operations, a hierarchical value map (HVM) was derived from a pre-study with 12 participants. Second, 51 forest visitors were surveyed in the Vienna Woods, Austria. For the latter, the laddering method was used to identify the focal points and shifts in HVM attributes and values. The results show that the public information boards used in the experiments reduce the visual impact of the harvesting as well as ecology-related factors and redirect attention towards timber-related or commercial items. We conclude that information provided at a site of emotional concern is easily picked up and leads to attitude changes. These attitude changes are directly linked to the information provided (e.g. concerning the environment, the eco-social market economy, or support of the regional economy).

Fossil energy input, energy output, and energy use- efficiency (EUE) are important indicators of the environmental effects, resource consumption and economic performance of farming systems. In this study, the energy balance (process analysis) and EUE of different organic and conventional farming systems – mixed farming, arable farming, and agroforestry (AGFS) systems – were analyzed due to their importance in Germany. The analysis was based on long-term experiments at the Scheyern Research Farm in southern Germany. The results showed that the conversion from multi-structured organic mixed farming to a specialized organic arable farming system reduced the fossil energy input in crop production only marginally (from 5.9 to 5.5 GJ ha −1 yr −1 ), but considerably decreased dry matter yield (from 5.4 to 2.5 Mg ha −1 yr −1 ), energy output (from 99 to 46 GJ ha −1 yr −1 ) and EUE (from 16.8 to 8.3). Improved management in the conventional arable farming system (with high-yielding varieties and better N management) reduced the energy input from 14.0 to 12.2 GJ ha −1 yr −1 , increased the energy output from 155 to 179 GJ ha −1 yr −1 , and elevated the EUE from 11.1 to 14.6. The establishment of AGFS with short rotation trees (without fertilization and pesticide use) led to the reduction of energy input. Based on the results, we concluded that mixed farming is one of the best ways of producing food with high EUE under the conditions of organic farming. Therefore the conversion from organic mixed farming to an organic arable farming system is not recommended. Our AGFS results were from the first stage of a long-term experiment; it showed no negative effects on DM yield and energy output and positive effects on energy-use efficiency at this stage. However, further research is needed to know the long-term influence of AGFS.

Biomass equations for tree species and the early stages of growth used in short-rotation coppices and agroforestry systems are still lacking. Further, discussion about the structure and parameters of biomass equations are still ongoing. Yield estimations should be precise, while keeping efforts low. To determine the influence of tree species, farming system, and tree position (inner and outer row) on allometric relationships, we derived biomass equations for various tree species from organic and conventional silvoarable agroforestry systems with an alley-cropping configuration. The allometric equations were based on the power relationship between aboveground dry biomass and stem base diameter (SBD) as a single variable or in combination with tree height (H) and were calculated by log-linear mixed-effect regression. Equations span the third and fourth growth year of the first rotation and were validated on the fourth year. Neither farming system nor row position influenced allometric relationship, although biometric variables varied between trees from inner and outer rows. A general model across species explained 95% ( $$R_{\text{cond}}^{2}$$ ) of the variation for tree dry weight or 97% ( $$R_{\text{cond}}^{2}$$ ) with H as covariate. Yet, for the sake of precision, species-specific equations were necessary. The best fitting equation with only SBD as predictor had species-specific allometric factors and a general exponent across species. However, predicted yields were biased by 8–31%. Thus, functions incorporating H are recommended, as compensation for variances in height-diameter relationships due to the ontogenetic stage, site differences, or social status of the tree reduced the bias of biomass estimation (

Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow-up data, was analyzed by immunohistochemistry using an antibody directed against the membrane-bound full-length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both P

The increasing demand for bioenergy and the combination of agricultural production with conservation has made short-rotation agroforestry systems (SRAFS) a sustainable land-management option. Aboveground woody biomass is a decisive factor in economic and ecological assessment of those systems. To study the yields of organic and conventional SRAFS, the tree species black alder, black locust, poplar clone Max 3, poplar clone Androscoggin, willow clone Inger, and a mixture of different native species were established in an alley-cropping configuration in 2009 and coppiced in 2012. Biomass was determined by harvesting the inner rows of the tree strips and, to investigate row differences within a strip, by an allometric model which estimates tree biomass from stem diameter. Significant variation was observed between species. For inner rows and at the conventional system, highest harvested average annual yield was observed for poplar Androscoggin (10.5 todt ha−1 year−1), followed by black locust (9.7 todt ha−1 year−1), poplar Max 3 (8.6 todt ha−1 year−1), black alder (7.6 todt ha−1 year−1), the native mix (4.9 todt ha−1 year−1), and willow (3.9 todt ha−1 year−1). At the organic system, highest yields were observed for poplar Max 3 (Androscoggin not planted) (10.9 todt ha−1 year−1), followed by black locust (8.1 todt ha−1 year−1), black alder (7.4 todt ha−1 year−1), willow (6.4 todt ha−1 year−1), and the native mix (4.7 todt ha−1 year−1). Farming system differences were only significant for willow and poplar Max 3; however, the higher yields of the organic system seemed to be a result of varying small-scale site properties rather than a management effect. Border rows showed 18–111 % more yield than inner rows because of greater tree diameters or heights and higher number of stems. This edge effect was emphasized in the conventional systems, possibly indicating that trees benefit from fertilizers applied at adjacent crop fields.

Heart failure (HF) is a prevalent disease that remains costly and associated with a high mortality rate. HF is also associated with poor neurocognitive functioning. For the treatment for HF patients with severe mitral regurgitation, the MitraClip device has emerged as a promising interventional tool that reduces the mitral valve leakage and thus increases cardiac output. Currently, there is only limited knowledge on changes in cognitive and psychosocial functioning before and after the MitraClip intervention.Cognitive function (memory and executive function) and psychosocial measures (depression, anxiety, and quality of life) were assessed before and after the MitraClip intervention in 24 HF patients and 23 healthy participants (comparison group).MitraClip intervention in HF patients was followed by improvements in figural long-term memory (p = .003) and executive function (planning ability, p < .001) relative to the comparison group. In addition, the intervention resulted in a significant improvement in depression (p = .002), anxiety (p = .003) and quality of life scores (physical p = .017, mental p = .013) as well as improved 6-minute walk test results over time (p = .002).The presented data provide evidence of a significant improvement in memory and executive function as well as in depression, anxiety, and quality of life scores in patients with chronic HF after MitraClip intervention. Further research is needed to shed light on the long-term development of cognitive function, psychosocial well-being, and clinical parameters after MitraClip intervention and how these factors depend on one another.

Gab2 is essential for Bcr-Abl-mediated leukemic transformation and hydronephrosis in a chronic myeloid leukemia mouse model

Nitrogen (N) is the most important yield-limiting factor in agricultural systems, however, N application can lead to emissions and environmental problems such as global warming (N2O) and groundwater contamination (NO3 −). This study analyses the N balance, nitrogen-use efficiency, and N loss potential of conventional farming systems (arable farming, improved arable farming, and agroforestry) and organic farming systems (mixed farming, arable farming, and agroforestry) based on long-term field experiments in southern Germany. The effects of the conversion of farm structure and N management are identified. The conventional farming systems in this study were high N-input and high N-output systems. The conventional arable farming system had the lowest nitrogen-use efficiency and the highest N surplus. An optimised N management and the use of high-yielding crop varieties improved its nitrogen-use efficiency. The establishment of conventional agroforestry resulted in the reduction of N input, N output and N surplus, while maintaining high yields. The organic mixed farming system is characterised by a relatively high N input and N output, the accumulation of soil organic nitrogen, the highest nitrogen-use efficiency, and the lowest N surplus of all analysed systems. These good results can be attributed to the intensive farm N cycle between soil–plant–animal. The shift from organic mixed farming to organic arable farming system extensified the N cycle, reduced N input, crop yield and N output. The change from organic arable farming to organic agroforestry reduced the N input, increased the biomass yield, and remained the N surplus within an optimal range.

Einleitung: Ab dem ersten Studienjahr kommt es im Medizinstudium zu einer Zunahme von psychischen Belastungen. Unklar bleibt, wie das Auftreten dieser Belastungen mit dem Bindungsmuster oder mit strukturellen Funktionen der Personlichkeit in Verbindung steht. Ziel dieser Studie war es, zu eruieren, ob ein Zusammenhang zwischen den uberdauernden Personlichkeitsvariablen Bindungsstil und Strukturniveau mit dem akuten Stresserleben zu Studienbeginn besteht. Material & Methoden: Im Rahmen dieser Studie wurden im WS 2013/2014 alle Studierenden des ersten Semesters Humanmedizin eingeladen, an einer Fragebogenuntersuchung zur Identifizierung von Belastungsfaktoren teilzunehmen (MBI-SS, PSQ, PHQ-9, GAD-7). Gleichzeitig wurde der vorherrschende Bindungsstil ermittelt (RQ-2) und eine Beurteilung der strukturellen Kompetenzen vorgenommen (OPD-SFK). Ergebnisse: Es nahmen 293 Studierende teil (Rucklauf: 91,3%). Sicher gebundene Studierende erlebten signifikant weniger Stress als unsicher gebundene Studierende (p=0,019). Studierende mit hohem Strukturniveau zeigten sich signifikant weniger stressbelastet (p Diskussion: Es bestehen signifikante Korrelationen zwischen Bindungsstil und Strukturniveau mit dem Burnoutrisiko sowie der Stressbelastung. Das Strukturniveau der Personlichkeit mediiert den Zusammenhang zwischen dem bindungsbezogenen „Modell des Selbst“ und Stresserleben, d. h. ein positives „Modell des Selbst“ kann eine stressprotektive Wirkung haben, wenn gute strukturelle Fahigkeiten vorhanden sind. Fazit fur die Praxis: Ein unsicherer Bindungsstil und ein niedrigeres Strukturniveau konnten mit einem hoheren Stresserleben im Rahmen der Schwellensituation des Studienbeginns einhergehen. Die Ergebnisse legen nahe, dass die uberdauernde Personlichkeitsvariable Bindungsstil, vermittelt uber die Personlichkeitsstruktur, zu einem hoheren Stresserleben fuhrt. Betroffene konnten fruhzeitig Praventionsmasnahmen wahrnehmen, um eine nachhaltige Vorbereitung auf diese Schwellensituation zu ermoglichen. Longitudinal-prospektive Studien sind notwendig, um zu erforschen, ob die Vermutung, dass eine in der Schulzeit vorbestehende Vulnerabilitat erst in der Schwellensituation zur Exazerbation der psychischen Belastungen fuhrt, zutreffend ist.

OBJECTIVE The aim of this study was to investigate associations between patients' subjective agency, their observable in-session behavior, and the patient-therapist interaction during the early phase of psychotherapy. METHODS The sample included 52 depressed patients in psychodynamic psychotherapy. After Session 5, the patients' agency and the quality of the therapeutic alliance were assessed. Based on session recordings, two independent observers rated the patients' involvement, their interpersonal behavior, and the therapists' directiveness. RESULTS Higher agency was associated with stronger therapeutic alliances. Patients who indicated higher agency in their therapy participated more actively in the session and showed less hostile impact messages. Patients' agency was not related to therapists' directiveness. CONCLUSIONS Patients' sense of agency in psychotherapy was associated with more active involvement and affiliative interaction. The findings support the idea that patients need to feel capable of acting within and having an influence on their therapy to benefit from it.

An increased understanding of repetitive dysfunctional patterns and their relationship to an individual's life history is regarded as a key mechanism of change in insight-oriented therapies. At the same time, empirical research on the insight-outcome relationship is rare, and its generalizability is restricted by the use of a wide range of definitions and methods among studies. The authors conducted a meta-analysis to systematically examine the association between patient insight and psychotherapy outcome across a range of treatment modalities.Insight was defined as patients' understanding of associations between past and present experiences, typical relationship patterns, and the relation between interpersonal challenges, emotional experience, and psychological symptoms. From 13,849 initially identified abstracts, the authors extracted 23 independent effect sizes. A random-effects meta-analysis was performed to assess the magnitude of the insight-outcome relationship. Risk of publication bias was assessed with funnel plot inspections, Egger's regression test, and Duval and Tweedie's trim-and-fill procedure as sensitivity analyses.A significant, moderate correlation (r=0.31) was observed between insight and treatment outcome. Sensitivity analyses demonstrated the robustness of the results.The findings support the importance of insight for psychotherapy outcome. Insight may be a relevant mechanism of change across different treatment modalities.