Increasing Role of Targeted Immunotherapies in the Treatment of AML

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.     

Image quality and the aesthetic judgment of photographs: Contrast, sharpness, and grain teased apart and put together.

We examined the individual and combined effects of contrast, sharpness, and grain degradations on the aesthetic judgments of photographs depicting natural and human-made scenes. Our systematic approach demonstrated that certain degradations, and their combinations, had more impact on aesthetic judgments than others, and that the effects varied depending on the type of scene. We also showed that the degradations were additive in that the more degradations to which an image was subjected, the less it was liked. Finally, we found evidence for a contrast effect in which the aesthetic judgments of high-quality images were more positive as the images they were presented with were more degraded. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation

Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The “red complex” and “cluster B” abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.     

Selective improvement of porcine fat firmness by a diet enriched in medium-chain fatty acids

The effects of 4% fat either rich in medium-chain fatty acids (MCFA; saturated fat) or in polyenoic fatty acids (PUFA; unsaturated fat) isoenergetically exchanging carbohydrates of a low-fat diet (control) on performance and product quality were evaluated with 180 growing pigs. Growth, carcass and meat quality were not affected by the fat treatments. Although elevated in blood serum, cholesterol was not increased in belly meat when the MCFA-rich diet was fed. Fatty acid composition of backfat reflected dietary fat composition. The significantly lowest shelf life and melting temperatures were found with the unsaturated-fat diet. When compared with control, fat tissue PUFA contents were slightly higher in the saturated-fat diet, and fat melting temperatures were somewhat lower. In contrast, the use of this MCFA-enriched diet increased penetrometer firmness in pure 4°C temperated backfat by more than 50% as compared with control and to about the tenfold level of the firmness obtained in the unsaturated-fat diet. Impression of flavour and odor in lean and fatty meat were not systematically affected by the diets. The present results show a high potential of MCFA-enriched diets to selectively increase fat firmness in pigs without greater undesired side effects on other traits of product quality.     

Comparison of two quantitative proton density mapping methods in multiple sclerosis

Objective

Proton density (PD) mapping requires correction for the receive profile (RP), which is frequently performed via bias-field correction. An alternative RP-mapping method utilizes a comparison of uncorrected PD-maps and a value ρ(T1) directly derived from T1-maps via the Fatouros equation. This may be problematic in multiple sclerosis (MS), if respective parameters are only valid for healthy brain tissue. We aimed to investigate whether the alternative method yields correct PD values in MS patients.

Materials/methods

PD mapping was performed on 27 patients with relapsing-remitting MS and 27 healthy controls, utilizing both methods, yielding reference PD values (PD_ref, bias-field method) and PD_alt (alternative method).

Results

PD_alt-values closely matched PD_ref, both for patients and controls. In contrast, ρ(T1) differed by up to 3 % from PD_ref, and the voxel-wise correlation between PD_ref and ρ(T1) was reduced in a patient subgroup with a higher degree of disability. Still, discrepancies between ρ(T1) and PD_ref were almost identical across different tissue types, thus translating into a scaling factor, which cancelled out during normalization to 100 % in CSF, yielding a good agreement between PD_alt and PD_ref.

Conclusion

RP correction utilizing the auxiliary parameter ρ(T1) derived via the Fatouros equation provides accurate PD results in MS patients, in spite of discrepancies between ρ(T1) and actual PD values.

     

Microscopic investigation of the formation of a thermoset wheat gluten network in a model system relevant for bread making

Although the impact of heat on molecular properties of wheat gluten is well understood, changes in its microstructure have rarely been studied. Here, formation of the thermoset gluten network in a model system relevant for bread baking was studied with confocal laser scanning microscopy and protein network analysis. From 65 °C onwards, gluten converts from thick aligned protein strands in a highly branched and homogeneous network of small thin protein threads. Neither gliadin incorporation in the network nor application of aqualysin 1, the thermo-active serine peptidase from Thermus aquaticus which recently has been reported to hydrolyse gluten proteins in dough only at temperatures exceeding 80 °C, impacts on the gluten microstructure. As starch causes structure setting itself and thereby decreases protein mobility, molecular scale changes in the gluten network at temperatures exceeding 80 °C brought about by aqualysin 1 do not impact its microstructure.     

Increasing body satisfaction of body concerned women through evaluative conditioning using social stimuli.

Objective: Many women show weight and body concerns that leave them vulnerable to body dissatisfaction, lowered self-esteem, psychological distress, and eating disorders. This study tested whether body satisfaction could be increased by means of evaluative conditioning. Design: In the experimental condition (n = 26), women with low and high body concern completed a conditioning procedure in which pictures of their bodies were selectively linked to positive social stimuli (pictures of smiling faces). Pictures of control bodies were linked to neutral or negative social stimuli (neutral and frowning faces). In a control condition (n = 28), low and high body concerned women underwent a procedure in which pictures of their own body and of control bodies were randomly followed by positive, neutral, and negative social stimuli. Main Outcome Measures: Changes in body satisfaction and self-esteem before and after the conditioning task. Results: Women with high body concern demonstrated an increase in body satisfaction and global self-esteem when pictorial representations of their own bodies were associated with positive stimuli that signaled social acceptance. Conclusion: A simple conditioning procedure increased body satisfaction in healthy, normal weight women who were concerned about their shape and weight. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A theory building study of enterprise architecture practices and benefits

Academics and practitioners have made various claims regarding the benefits that Enterprise Architecture (EA) delivers for both individual projects and the organization as a whole. At the same time, there is a lack of explanatory theory regarding how EA delivers these benefits. Moreover, EA practices and benefits have not been extensively investigated by empirical research, with especially quantitative studies on the topic being few and far between. This paper therefore presents the statistical findings of a theory-building survey study (n?=?293). The resulting PLS model is a synthesis of current implicit and fragmented theory, and shows how EA practices and intermediate benefits jointly work to help the organization reap benefits for both the organization and its projects. The model shows that EA and EA practices do not deliver benefits directly, but operate through intermediate results, most notably compliance with EA and architectural insight. Furthermore, the research identifies the EA practices that have a major impact on these results, the most important being compliance assessments, management propagation of EA, and different types of knowledge exchange. The results also demonstrate that projects play an important role in obtaining benefits from EA, but that they generally benefit less than the organization as a whole.