Changing attitudes towards psychotherapy via social observations: are similarities more important than discrepancies?

OBJECTIVES: Therapy expectations and attitudes towards psychotherapy contribute substantially to the outcome, process and duration of psychotherapy. The a priori use of role model videos seems to be promising for changing expectations and attitudes towards psychotherapy. In contrast, underlying mechanisms, like identifying with the role model, have been sparsely investigated in studies so far. For instance, the effects of similarities and differences between the role model and the observer are not clear yet. METHODS: A total of 158 persons were recruited and randomly assigned to four groups. In one of three experimental groups, participants watched an expectation-optimised video with patients giving information about their mostly positive therapy outcomes (positive model). Two further experimental groups saw the same video, but either received instructions to focus on similarities (similarity group) or on differences (discrepancy group) between the patients and themselves. A further control group watched a video with patients who gave information about their symptoms. As the primary outcome variable, we assessed attitudes towards psychotherapy using the Questionnaire on Attitudes towards Psychotherapy (QAPT). It was filled in before and after watching the video and after a two-week follow-up period. RESULTS: Contrary to the hypotheses, the discrepancy group and the experimental group without further intervention (positive model) showed significant improvements in their attitudes towards psychotherapy after watching the video, while such an effect was not found in the similarity group or control group. CONCLUSION: Focusing on similarities between patient examples and the observer does not support a change in therapy expectations or attitudes through observation, while a positive video model without instructions, or with the instruction to focus on differences does. Attentional interference and depth of cognitive evaluation are discussed as possible reasons. TRIAL REGISTRATION: Ethical approval (2018-19k) was obtained from the ethics committee of the Psychological Department, University of Marburg, and the trial was registered at Aspredicted.org (#22,205; 16.04.2019).

Using expectation violation models to improve the outcome of psychological treatments.

Expectations are a central maintaining mechanism in mental disorders and most psychological treatments aim to directly or indirectly modify clinically relevant expectations. Therefore, it is crucial to examine why patients with mental disorders maintain dysfunctional expectations, even in light of disconfirming evidence, and how expectation-violating situations should be created in treatment settings to optimize treatment outcome and reduce the risk of treatment failures. The different psychological subdisciplines offer various approaches for understanding the underlying mechanisms of expectation development, persistence, and change. Here, we convey recommendations on how to improve psychological treatments by considering these different perspectives. Based on our expectation violation model, we argue that the outcome of expectation violation depends on several characteristics: features of the expectation-violating situation; the dynamics between the magnitude of expectation violation and cognitive immunization processes; dealing with uncertainties during and after expectation change; controlled and automatic attention processes; and the costs of expectation changes. Personality factors further add to predict outcomes and may offer a basis for personalized treatment planning. We conclude with a list of recommendations derived from basic psychology that could contribute to improved treatment outcome and to reduced risks of treatment failures.

Maintenance vs. Change of Negative Therapy Expectation: An Experimental Investigation Using Video Samples.

Introduction: Therapy expectations contribute substantially to the outcome of psychotherapy. In contrast, psychotherapy expectations are rarely addressed and systematically optimised in studies on psychotherapy. Materials and Methods: A total of 142 mostly healthy participants with critical attitudes towards psychotherapy were randomised into two groups: (1) a control group that watched a video with patients who gave information about their symptoms or (2) an experimental group that watched an expectation-optimised video with the same patients giving additional information about their mostly positive therapy outcomes. The primary outcome was the Milwaukee Psychotherapy Expectation Questionnaire (MPEQ), which was filled in before and after watching the video. Results: Both groups showed a significant improvement of their process expectations and attitudes towards psychotherapy after watching the video. Participants in the experimental group changed their therapy outcome expectation while there was no change in the control group [F(1,140) = 9.72, p = 0.002, η2 = 0.065]. Conclusion: A video intervention with patients presenting their positive therapy experiences improves therapy expectations in persons with critical attitudes. Expectation-optimised videos could be used for prevention programmes and when starting therapy. Trial Registration: Trial was registered at clinicaltrials.gov (NCT03594903) on November 2018.

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up.

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, p = 0.012; W% at baseline vs. follow-up, p = 0.025; DP-factor at baseline vs. follow-up, p = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, p = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression.

Body impedance analysis to estimate malnutrition in inflammatory bowel disease patients - A cross-sectional study.

OBJECTIVE: Malnutrition is a common clinical problem in patients with inflammatory bowel diseases (IBD). However, a gold standard for the detection of malnutrition in IBD patients is lacking. METHODS: A cross-sectional study to assess malnutrition in patients with IBD and healthy controls (HCs). Clinical characteristics (Montreal classification, disease activity, previous surgery) and mutations in the NOD2 gene in patients with Crohn's disease (CD) were obtained. We performed a nutritional assessment with screening for nutritional risk and diagnosis for malnutrition (Malnutrition Universal Screening Tool [MUST]) score, NRS-2002, European Society for Clinical Nutrition and Metabolism (ESPEN), and Global Leadership Initiative on Malnutrition (GLIM) criteria and performed body impedance analysis (BIA). RESULTS: 101 IBD patients (57 CD and 44 ulcerative colitis (UC) and 50 HC were included in a single northern German tertiary center. GLIM criteria detected malnutrition significantly more often compared to the ESPEN criteria. Active disease, a long-standing disease course, and previous surgery were associated with reduced muscle mass. IBD patients had a higher fat mass index compared to HC. Mutations in the NOD2 gene had no effect on nutritional status. CONCLUSIONS: The GLIM criteria detect malnutrition at a higher rate compared to ESPEN. Specific disease factors might put IBD patients at a higher risk for the development of malnutrition, so these patients might benefit from a frequently performed screening, which might result in a favorable disease course.

The Role of the Nuclear Factor κB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation.

Astronauts are exposed to considerable doses of space radiation during long-term space missions. As complete shielding of the highly energetic particles is impracticable, the cellular response to space-relevant radiation qualities has to be understood in order to develop countermeasures and to reduce radiation risk uncertainties. The transcription factor Nuclear Factor κB (NF-κB) plays a fundamental role in the immune response and in the pathogenesis of many diseases. We have previously shown that heavy ions with a linear energy transfer (LET) of 100⁻300 keV/µm have a nine times higher potential to activate NF-κB compared to low-LET X-rays. Here, chemical inhibitor studies using human embryonic kidney cells (HEK) showed that the DNA damage sensor Ataxia telangiectasia mutated (ATM) and the proteasome were essential for NF-κB activation in response to X-rays and heavy ions. NF-κB's role in cellular radiation response was determined by stable knock-down of the NF-κB subunit RelA. Transfection of a RelA short-hairpin RNA plasmid resulted in higher sensitivity towards X-rays, but not towards heavy ions. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) showed that after exposure to X-rays and heavy ions, NF-κB predominantly upregulates genes involved in intercellular communication processes. This process is strictly NF-κB dependent as the response is completely absent in RelA knock-down cells. NF-κB's role in the cellular radiation response depends on the radiation quality.

Linear Energy Transfer Modulates Radiation-Induced NF-kappa B Activation and Expression of its Downstream Target Genes.

Nuclear factor kappaB (NF-κB) is a central transcription factor in the immune system and modulates cell survival in response to radiotherapy. Activation of NF-κB was shown to be an early step in the cellular response to ultraviolet A (UVA) and ionizing radiation exposure in human cells. NF-κB activation by the genotoxic stress-dependent sub-pathway after exposure to different radiation qualities had been evaluated to a very limited extent. In addition, the resulting gene expression profile, which shapes the cellular and tissue response, is unknown. Therefore, in this study the activation of NF-κB after exposure to low- and high-linear energy transfer (LET) radiation and the expression of its target genes were analyzed in human embryonic kidney (HEK) cells. The activation of NF-κB via canonical and genotoxic stress-induced pathways was visualized by the cell line HEK-pNF-κB-d2EGFP/Neo L2 carrying the destabilized enhanced green fluorescent protein (d2EGFP) as reporter. The NF-κB-dependent d2EGFP expression after irradiation with X rays and heavy ions was evaluated by flow cytometry. Because of differences in the extent of NF-κB activation after irradiation with X rays (significant NF-κB activation for doses >4 Gy) and heavy ions (significant NF-κB activation at doses as low as 1 Gy), it was expected that radiation quality (LET) played an important role in the cellular radiation response. In addition, the relative biological effectiveness (RBE) of NF-κB activation and reduction of cellular survival were compared for heavy ions having a broad LET range (∼0.3-9,674 keV/µm). Furthermore, the effect of LET on NF-κB target gene expression was analyzed by real-time reverse transcriptase quantitative PCR (RT-qPCR). The maximal RBE for NF-κB activation and cell killing occurred at an LET value of 80 and 175 keV/µm, respectively. There was a dose-dependent increase in expression of NF-κB target genes NF-κB1A and CXCL8. A qPCR array of 84 NF-κB target genes revealed that TNF and a set of CXCL genes (CXCL1, CXCL2, CXCL8, CXCL10), CCL2, VCAM1, CD83, NF-κB1, NF-κB2 and NF-κBIA were strongly upregulated after exposure to X rays and neon ions (LET 92 keV/µm). After heavy-ion irradiations, it was noted that the expression of NF-κB target genes such as chemokines and CD83 was highest at an LET value that coincided with the LET resulting in maximal NF-κB activation, whereas expression of the NF-κB inhibitory gene NFKBIA was induced transiently by all radiation qualities investigated. Taken together, these findings clearly demonstrate that NF-κB activation and NF-κB-dependent gene expression by heavy ions are highest in the LET range of ∼50-200 keV/µm. The upregulated chemokines and cytokines (CXCL1, CXCL2, CXCL10, CXCL8/IL-8 and TNF) could be important for cell-cell communication among hit as well as nonhit cells (bystander effect).

Development and Clinical Utility of a Blood-Based Test Service for the Rapid Identification of Actionable Mutations in Non-Small Cell Lung Carcinoma.

Nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours. We focused on targetable variants in advanced non-small cell lung carcinoma-epidermal growth factor receptor gene (EGFR) variant L858R, exon 19 deletion (ΔE746-A750), and T790M; GTPase Kirsten ras gene (KRAS) variants G12C/D/V; and echinoderm microtubule associated protein like and 4 anaplastic lymphoma receptor tyrosine kinase fusion (EML4-ALK) transcripts 1/2/3. Test development included method and clinical validation using samples from donors with (n = 219) or without (n = 30) cancer. Clinical sensitivity and specificity for each variant ranged from 78.6% to 100% and 94.2% to 100%, respectively. We also report on 1643 non-small cell lung carcinoma samples processed in our CLIA-certified laboratory. Mutation results were available within 72 hours for 94% of the tests evaluated. We detected 10.5% mutations for EGFR sensitizing (n = 2801 samples tested), 13.8% mutations for EGFR resistance (n = 1055), 13.2% mutations in KRAS (n = 3477), and 2% mutations for EML4-ALK fusion (n = 304). This rapid, highly sensitive, and actionable blood-based assay service expands testing options and supports faster treatment decisions.

Increased pCO2 and temperature reveal ecotypic differences in growth and photosynthetic performance of temperate and Arctic populations of Saccharina latissima.

MAIN CONCLUSION: The Arctic population of the kelp Saccharina latissima differs from the Helgoland population in its sensitivity to changing temperature and CO 2 levels. The Arctic population does more likely benefit from the upcoming environmental scenario than its Atlantic counterpart. The previous research demonstrated that warming and ocean acidification (OA) affect the biochemical composition of Arctic (Spitsbergen; SP) and cold-temperate (Helgoland; HL) Saccharina latissima differently, suggesting ecotypic differentiation. This study analyses the responses to different partial pressures of CO2 (380, 800, and 1500 µatm pCO2) and temperature levels (SP population: 4, 10 °C; HL population: 10, 17 °C) on the photophysiology (O2 production, pigment composition, D1-protein content) and carbon assimilation [Rubisco content, carbon concentrating mechanisms (CCMs), growth rate] of both ecotypes. Elevated temperatures stimulated O2 production in both populations, and also led to an increase in pigment content and a deactivation of CCMs, as indicated by 13C isotopic discrimination of algal biomass (ε p) in the HL population, which was not observed in SP thalli. In general, pCO2 effects were less pronounced than temperature effects. High pCO2 deactivated CCMs in both populations and produced a decrease in the Rubisco content of HL thalli, while it was unaltered in SP population. As a result, the growth rate of the Arctic ecotype increased at elevated pCO2 and higher temperatures and it remained unchanged in the HL population. Ecotypic differentiation was revealed by a significantly higher O2 production rate and an increase in Chl a, Rubisco, and D1 protein content in SP thalli, but a lower growth rate, in comparison to the HL population. We conclude that both populations differ in their sensitivity to changing temperatures and OA and that the Arctic population is more likely to benefit from the upcoming environmental scenario than its Atlantic counterpart.

Short- and long-term acclimation patterns of the giant kelp Macrocystis pyrifera (Laminariales, Phaeophyceae) along a depth gradient.

The giant kelp, Macrocystis pyrifera, is exposed to highly variable irradiance and temperature regimes across its geographic and vertical depth gradients. The objective of this study was to extend our understanding of algal acclimation strategies on different temporal scales to those varying abiotic conditions at various water depths. Different acclimation strategies to various water depths (0.2 and 4 m) between different sampling times (Jan/Feb and Aug/Sept 2012; long-term acclimation) and more rapid adjustments to different depths (0.2, 2 and 4 m; short-term acclimation) during 14 d of transplantation were found. Adjustments of variable Chl a fluorescence, pigment composition (Chl c, fucoxanthin), and the de-epoxidation state of the xanthophyll cycle pigments were responsible for the development of different physiological states with respect to various solar radiation and temperature climates. Interestingly, the results indicated that phlorotannins are important during long-term acclimation while antioxidants have a crucial role during short-term acclimation. Furthermore, the results suggested that modifications in total lipids and fatty acid compositions apparently also might play a role in depth acclimation. In Aug/Sept (austral winter), M. pyrifera responded to the transplantation from 4 m to 0.2 m depth with a rise in the degree of saturation and a switch from shorter- to longer-chain fatty acids. These changes seem to be essential for the readjustment of thylakoid membranes and might, thus, facilitate efficient photosynthesis under changing irradiances and temperatures. Further experiments are needed to disentangle the relative contribution of solar radiation, temperature and also other abiotic parameters in the observed physiological changes.

Increased Frequency of CD49b/LAG-3(+) Type 1 Regulatory T Cells in HIV-Infected Individuals.

In HIV-1 infection elevated serum levels of interferon-α (IFN-α) and interleukin-10 (IL-10) are associated with immune hyperactivation and disease progression. Recently, coexpression of CD49b and LAG-3 was shown to identify Type 1 regulatory T (Tr1) cells, which secrete large amounts of the immunosuppressive cytokine IL-10. We analyzed the frequency of CD49b/LAG-3(+) Tr1 cells in the peripheral blood of HIV-infected individuals at different stages of the disease. We found increased levels of CD49b/LAG-3(+) Tr1 cells as well as IL-10 in HIV patients. With disease progression, Tr1 cells negatively correlate with frequency of plasmacytoid dendritic cells (pDCs), the main producers of IFN-α. However, elevated IL-10 levels could not be ascribed to the CD49b/LAG-3(+)Tr1 cell population. Moreover, we showed in vitro that IFN-α leads to an upregulation of IL-10 as well as CD49b/LAG-3(+) Tr1 cell counts in healthy controls, recapitulating effects observed in vivo during HIV infection. Our results suggest that overexpression of IFN-α during HIV infection drives the generation of CD49b/LAG-3(+) Tr1 cells and the immunosuppressive cytokine IL-10. Furthermore, it remains unclear whether elevated IL-10 levels are beneficial or detrimental in regard to disease progression.