Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges

Colorectal cancer (CRC) is a leading cause of death among cancer patients. This heterogeneous disease is characterized by alterations in multiple molecular pathways throughout its development. Mutations in RAS, along with the mismatch repair gene deficiency, are currently routinely tested in clinics. Such biomarkers provide information for patient risk stratification and for the choice of the best treatment options. Nevertheless, reliable and powerful prognostic markers that can identify “high-risk” CRC patients, who might benefit from adjuvant chemotherapy, in early stages, are currently missing. To bridge this gap, genomic information has increasingly gained interest as a potential method for determining the risk of recurrence. However, due to several limitations of gene-based signatures, these have not yet been clinically implemented. In this review, we describe the different molecular markers in clinical use for CRC, highlight new markers that might become indispensable over the next years, discuss recently developed gene expression-based tests and highlight the challenges in biomarker research

Individualisierte Therapieplanung mithilfe des Gewichtsmappings bei Anorexia nervosa

Die Anorexia nervosa ist eine seltene, schwerwiegende Erkrankung, deren Therapie bislang oft nur mäßig wirksam ist. Stagnierende Verläufe oder ein erhebliches Auf und Ab in der Gewichtsentwicklung zwischen stationären Behandlungen und dem häuslichen Transfer sind verbreitet und können stationäre Aufnahmen bzw. Wiederaufnahmen notwendig machen. Im Folgenden werden daher Techniken des Gewichtsmappings vorgestellt, die eine individualisierte Therapieplanung ermöglichen. Hierzu zählt zum einen die retrospektive Analyse des Lifecharts, in der die Gewichtsentwicklung über die Lebenspanne aufgezeigt wird und die damit Schweregrad der Essstörung, Krankheitsdauer und -verlauf sowie transdiagnostisch relevante Prozesse veranschaulichen kann. Zum anderen gehört dazu die prospektive Technik des Gewichtsmappings, die in einem standardisierten Vorgehen die individuell relevanten Gewichtsmarker erfasst und visualisiert. Diese diagnostischen Informationen können eine personalisierte Therapieplanung unterstützen, die sowohl den Zeitverlauf als auch den Schwierigkeitsgrad des Bewältigungsprozesses antizipiert. Mithilfe der Techniken des Gewichtsmanagements kann die Expositionsbehandlung zielgerichtet therapeutisch angeleitet und begleitet werden. Dabei werden die Arbeit mit Intervallmodulen und ihre Rolle für eine bewältigungsorientierte Expositionsbehandlung diskutiert.Anorexia nervosa is a rare and severe disease with often only moderate treatment effects. Stagnating courses of disease or considerable fluctuations of weight between inpatient treatment and transfer to home are common and can often necessitate hospitalization or rehospitalization. This article presents weight mapping techniques that enable an individualized treatment planning. These include the retrospective analysis of the life chart, in which weight development over the life span is shown and which can thus illustrate the severity of the eating disorder, the duration and course of the disease as well as transdiagnostically relevant processes. Also presented is the prospective technique of weight mapping, which applies a standardized procedure to record and visualize the individually relevant weight markers. This diagnostic information can support personalized therapy planning that anticipates both the course over time and the degree of difficulty of the coping process. With the help of weight management techniques, exposure treatment can be therapeutically guided and accompanied. Furthermore, working with intermittent treatment modules and the role of interval therapy in coping-oriented exposure treatment are discussed

Total Pelvic Exenteration for Gynecologic Malignancies

Total pelvic exenteration (PE) is a radical operation, involving en bloc resection of pelvic organs, including reproductive structures, bladder, and rectosigmoid. In gynecologic oncology, it is most commonly indicated for the treatment of advanced primary or locally recurrent cancer. Careful patient selection and counseling are of paramount importance when considering someone for PE. Part of the evaluation process includes comprehensive assessment to exclude unresectable or metastatic disease. PE can be curative for carefully selected patients with gynecologic cancers. Major complications can be seen in as many as 50% of patients undergoing PE, underscoring the need to carefully discuss risks and benefits of this procedure with patients considering exenterative surgery

Implicit approach-avoidance tendencies toward food and body stimuli absent in individuals with anorexia nervosa, bulimia nervosa, and healthy controls

Objective Body and food-related information are thought to activate cognitive biases and contribute to the maintenance of eating disorders (ED). Approach-avoidance biases may play an important role in the maintenance of dietary restriction and excessive food intake. Therefore, the present study aimed to examine approach-avoidance biases toward food and body stimuli in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and healthy controls (HC). Methods The study included 42 individuals with AN, 24 individuals with BN, and 38 HCs. We used two implicit Approach-Avoidance Tasks (AAT) to assess approach-avoidance biases: participants completed a Food-AAT (high-calorie vs. low-calorie food) and a Body-AAT (thin vs. normal weight bodies). Additionally, explicit ratings of food and body stimuli were assessed. Results There were no significant Group × Stimulus × Direction interactions in the implicit Food-AAT or implicit Body-AAT. In explicit ratings, individuals with AN and BN reported less urge to eat and more regret if they ate high-calorie and low-calorie food; individuals with AN and BN rated normal weight bodies as less normal weight, less attractive and less desirable than HCs. There were no group differences in explicit ratings of the thin body. Discussion We did not find evidence for biased approach-avoidance tendencies toward food or body stimuli in individuals with AN or BN. Future studies are necessary to understand conflicting findings regarding approach-avoidance biases toward food and body stimuli in individuals with ED

Safety and efficacy of a lifestyle intervention for pregnant women to prevent excessive maternal weight gain: a cluster-randomized controlled trial

Background: Excessive gestational weight gain (GWG) is associated with short- and long-term health problems among mothers and their offspring. There is a strong need for effective intervention strategies targeting excessive GWG to prevent adverse outcomes. Methods: We performed a cluster-randomized controlled intervention trial in eight gynecological practices evaluating the feasibility and effectiveness of a lifestyle intervention presented to all pregnant women; 250 healthy, pregnant women were recruited for the study. The intervention program consisted of two individually delivered counseling sessions focusing on diet, physical activity, and weight monitoring. The primary outcome was the proportion of pregnant women exceeding weight gain recommendations of the Institute of Medicine (IOM). Secondary outcome variables were maternal weight retention and short-term obstetric and neonatal outcomes. Results: The intervention resulted in a lower proportion of women exceeding IOM guidelines among women in the intervention group (38\%) compared with the control group (60\%) (odds ratio (OR): 0.5; 95\% confidence interval (CI): 0.3 to 0.9) without prompting an increase in the proportion of pregnancies with suboptimal weight gain (19\% vs. 21\%). Participants in the intervention group gained significantly less weight than those in the control group. Only 17\% of the women in the intervention group showed substantial weight retention of more than 5 kg compared with 31\% of those in the control group at month four postpartum (pp) (OR: 0.5; 95\% CI: 0.2 to 0.9). There were no significant differences in obstetric and neonatal outcomes. Conclusions: Lifestyle counseling given to pregnant women reduced the proportion of pregnancies with excessive GWG without increasing suboptimal weight gain, and may exert favorable effects on pp weight retention

Stationäre Behandlung depressiver Erkrankungen wohnortnah oder wohnortfern: Gibt es Unterschiede im Therapieergebnis?

Background: Advantages and disadvantages of inpatient treatment for mental disorders in facilities located either close to or distant from the patients' homes have been controversially discussed since the Psychiatry Enquiry. However, the question whether the distance between residence and clinic influences the treatment outcome has so far only been examined in substance-dependent patients in residential medical rehabilitation. Therefore, in the present study, we aimed to investigate potential effects of the distance between residence and clinic on the treatment outcome in depressive patients. Patients and Methods: For this purpose, routine data of 1,959 clinically depressed inpatients were analyzed. Using the Patient Health Questionnaire, depression, anxiety, and somatization were assessed at admission, discharge, and the 6-month follow-up to analyze the treatment outcome. Results: The findings demonstrate that the distance between the residence and the treatment facility does not moderate depressive, anxious, and somatoform symptom changes during and after treatment. Moreover, the distance between clinic and residence and the symptom improvement from admission until follow-up do not correlate significantly. Conclusions: Hence, there is no empirical evidence showing that the distance between the residence and the treatment facility influences the treatment outcome. Therefore, future research should focus on the impact of specific treatment qualities close to or far away from home, like the facility's degree of specialization and the implementation of individualized aftercare

Soluble CD83 Triggers Resolution of Arthritis and Sustained Inflammation Control in IDO Dependent Manner

Interference with autoimmune-mediated cytokine production is a key yet poorly developed approach to treat autoimmune and inflammatory diseases such as rheumatoid arthritis. Herein, we show that soluble CD83 (sCD83) enhances the resolution of autoimmune antigen-induced arthritis (AIA) by strongly reducing the expression levels of cytokines such as IL-17A, IFNγ, IL-6, and TNFα within the joints. Noteworthy, also the expression of RANKL, osteoclast differentiation, and joint destruction was significantly inhibited by sCD83. In addition, osteoclasts which were cultured in the presence of synovial T cells, derived from sCD83 treated AIA mice, showed a strongly reduced number of multinuclear large osteoclasts compared to mock controls. Enhanced resolution of arthritis by sCD83 was mechanistically based on IDO, since inhibition of IDO by 1-methyltryptophan completely abrogated sCD83 effects on AIA. Blocking experiments, using anti-TGF-β antibodies further revealed that also TGF-β is mechanistically involved in the sCD83 induced reduction of bone destruction and cartilage damage as well as enhanced resolution of inflammation. Resolution of arthritis was associated with increased numbers of regulatory T cells, which are induced in a sCD83-IDO-TGF-β dependent manner. Taken together, sCD83 represents an interesting approach for downregulating cytokine production, inducing regulatory T cells and inducing resolution of autoimmune arthritis

Negation and the functional sequence

There exists a general restriction on admissible functional sequences which prevents adjacent identical heads. We investigate a particular instantiation of this restriction in the domain of negation. Empirically, it manifests itself as a restriction the stacking of multiple negative morphemes. We propose a principled account of this restriction in terms of the general ban on immediately consecutive identical heads in the functional sequence on the one hand, and the presence of a Neg feature inside negative morphemes on the other hand. The account predicts that the stacking of multiple negative morphemes should be possible provided they are separated by intervening levels of structure. We show that this prediction is borne out

Towards a Better Understanding of Texturization during High-Moisture Extrusion (HME)—Part II: Characterization of Thermophysical Properties of High-Moisture Meat Analogues

It is crucial to determine the thermophysical properties of high-moisture extruded samples (HMESs) to properly understand the texturization process of high-moisture extrusion (HME), especially when the primary objective is the production of high-moisture meat analogues (HMMAs). Therefore, the study’s aim was to determine thermophysical properties of high-moisture extruded samples made from soy protein concentrate (SPC ALPHA® 8 IP). Thermophysical properties such as the specific heat capacity and the apparent density were experimentally determined and further investigated to obtain simple prediction models. These models were compared to non-HME-based literature models, which were derived from high-moisture foods, such as soy-based and meat products (including fish). Furthermore, thermal conductivity and thermal diffusivity were calculated based on generic equations and literature models and showed a significant mutual influence. The combination of the experimental data and the applied simple prediction models resulted in a satisfying mathematical description of the thermophysical properties of the HME samples. The application of data-driven thermophysical property models could contribute to understanding the texturization effect during HME. Further, the gained knowledge could be applied for further understanding in related research, e.g., with numerical simulation studies of the HME process

Body image disturbance in body dysmorphic disorder and eating disorders : similarities and differences

Hintergrund: Sowohl die körperdysmorphe Störung (KDS) als auch Essstörungen (ESS) sind durch eine Störung des Körperbildes gekennzeichnet, jedoch ist wenig über Gemeinsamkeiten und Unterschiede hinsichtlich spezifischer Körperbildmerkmale bekannt. Fragestellung: Nach der vergleichenden Befunddarstellung zu perzeptiven, kognitiv-affektiven und behavioralen Körperbildmerkmalen hat die Arbeit das Ziel, kognitiv-affektive Körperbildcharakteristika im direkten Vergleich von KDS mit ESS zu untersuchen. Methode: Personen mit einer KDS (n = 31), Anorexia nervosa (n = 32), Bulimia nervosa (n = 34) und eine gesunde (n = 33) Kontrollgruppe wurden untersucht (Fragebögen, Interviews). Ergebnisse: KDS und ESS zeigten starke Körperunzufriedenheit und körper- und gewichtsbezogene Schamgefühle. Nicht nur bei der KDS, sondern auch bei den ESS zeigte sich eine Vielzahl subjektiver Makel im äußeren Erscheinungsbild. Die KDS-Gruppe sorgte sich jedoch seltener als ESS um Körpergewicht, Brust und Gesäß. Die ESS-Gruppen berichteten erwartungsgemäß stärkere Figur-/Gewichtssorgen und körper-/gewichtsbezogene Schuldgefühle. Diskussion: Körperunzufriedenheit charakterisiert sowohl KDS als auch ESS. Von den kognitiv-affektiven Körperbildmerkmalen differenzieren nur die Ausprägung von Figur-/Gewichtssorgen und körper-/gewichtsbezogene Schuldgefühle die beiden Gruppen. Vergleichsstudien zu perzeptiven und behavioralen Körperbildaspekten stehen aus.Background: Body dysmorphic disorder (BDD) and eating disorders (ED) are considered to be body image disorders; however, little is known about similarities and differences concerning specific body image characteristics. Objective: The aim of this study is to integrate findings on similarities and differences concerning body image characteristics in people with BDD and ED and to examine cognitive and affective features of disturbed body image in BDD and ED. Methods: Individuals with BDD (n = 31), anorexia nervosa (n = 32), bulimia nervosa (n = 34), and healthy controls (n = 33) were examined (questionnaire and interview measures). Results: There were high levels of body dissatisfaction and weight- and body-related shame in BDD and EDs. BDD and EDs worried about a considerable number of body parts. The BDD group worried less about weight, buttocks and breasts than the ED groups. The ED groups reported higher levels of shape and weight concerns and of weight- and body-related guilt. Discussion: BDD and EDs are characterized by high levels of body dissatisfaction. Disorder-specific cognitive-affective measures of body image, such as weight and shape concerns as well as weight- and body-related guilt, differ between the groups. Comparative studies are warranted that examine perceptional and behavioural features of body image