Der dicke Körper und sein Konsum im Visier von Wissenschaft und Politik in der DDR und der BRD

The Fat Body and his Consumption in the Focus of Science and Politics in GDR and FRG In modern society, speaking about the body includes speaking about virtues like responsibility, discipline, efficiency and rationality as foundations of western societies. Insofar, the fat body is a political problem. The paper reconstructs the history of overweight in the GDR and FRG, which both had to face the problem. It analyses the discourse in regard to its function as an indicator of political communication. Doing so, it works out, how overweight was rated on both sides of the wall and which alternative models of consumption were developed and realized

Hunger – ein Bedürfnis zwischen Politik, Physiologie und persönlicher Erfahrung (Deutschland, 19. und 20. Jahrhundert)

Hunger has never been a stable term. How people have understood and defined it, changed over time, along with a changing understanding of the body, its functions, physiological mechanisms and its needs. The paper follows these changes in a long-term multiperspective approach for the last two centuries. It argues, that hunger first was understood as a dangerous feeling, that eventually developed political power. To define hunger by physiology can thus be meant and understood as a means to articulate bodily needs and to point to the necessity of their satisfaction. Nonetheless, these definitions of hunger are not neutral or objective, moreover they may not be used for certain groups of people or under certain economic or social conditions, they may even be counterproductive, as they reduce empathy with the hungry

Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1–23.8) versus 9.4 months (cohort B, 95% CI: 6.1–14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities

Optimizing immune checkpoint blockade in metastatic uveal melanoma: exploring the association of overall survival and the occurrence of adverse events

IntroductionDespite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable.MethodsIn this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57).ResultsIn the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively).ConclusionsThis data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens

Real‐world outcomes using PD‐1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

Abstract Background Programmed death‐1 (PD‐1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high‐risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real‐world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. Methods Multicenter, retrospective study investigating stage III–IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12‐month recurrence‐free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear‐regression machine learning model to assess the risk of early melanoma recurrence. Results In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD‐1 therapies (n = 1003). Twelve‐month RFS for anti PD‐1 and BRAF + MEK inhibitor‐treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335–2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD‐1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow‐up of 17 months. Data indicates that anti PD‐1 treated patients who develop immune‐related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443–0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD‐1 treatment (p > 0.05). In both, anti PD‐1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12‐month RFS and 12‐month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. Conclusions Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk

Des perceptions de la minceur et de l’obésité de 1850 à nos jours

It is commonplace that body image and beauty ideals have changed over time and that today beauty is identified with lean bodies. Food and eating have always played, and still play, a prominent role in the discussion of the ideal of obesity, since eating too much was clearly identified as its evil cause, from which illness or premature death would result. Numerous inquiries have tried to prove this relationship and great effort has been made to make the obese eat less, and so to turn them into leaner individuals. But a closer look, and a look at the work body history has done in recent years, shows that this explanation is a construct itself and leanness has been disassociated from the concrete, bodily sphere. In fact, being lean has turned into a central virtue of modern societies, as for example the use of the term “lean management” shows.Analysing different semantic fields, the papers focuses on the meaning read into lean and fat bodies respectively, following the hypothesis that the medical discourse on fatness/leanness had succeeded in dominating all other discourses on health and disease in modern societies. This may be one of the most important results of the successful medicalization of society, in which “health” became not only a cultural value, but a virtue, defined in “objective” measures, of which leanness has become the most important

Modeling silicate–nitrate–ammonium co-limitation of algal growth and the importance of bacterial remineralization based on an experimental Arctic coastal spring bloom culture study

Arctic coastal ecosystems are rapidly changing due to climate warming. This makes modeling their produc- tivity crucially important to better understand future changes. System primary production in these systems is highest dur- ing the pronounced spring bloom, typically dominated by di- atoms. Eventually the spring blooms terminate due to sili- con or nitrogen limitation. Bacteria can play an important role for extending bloom duration and total CO2 fixation through ammonium regeneration. Current ecosystem mod- els often simplify the effects of nutrient co-limitations on al- gal physiology and cellular ratios and simplify nutrient re- generation. These simplifications may lead to underestimations of primary production. Detailed biochemistry- and cell- based models can represent these dynamics but are difficult to tune in the environment. We performed a cultivation experiment that showed typical spring bloom dynamics, such as extended algal growth via bacterial ammonium remineralization, reduced algal growth and inhibited chlorophyll synthesis under silicate limitation, and gradually reduced nitrogen assimilation and chlorophyll synthesis under nitrogen limitation. We developed a simplified dynamic model to represent these processes. Overall, model complexity in terms of the number of parameters is comparable to the phytoplankton growth and nutrient biogeochemistry formulations in common ecosystem models used in the Arctic while improv- ing the representation of nutrient-co-limitation-related processes. Such model enhancements that now incorporate in- creased nutrient inputs and higher mineralization rates in a warmer climate will improve future predictions in this vulnerable system

Structural basis for the final steps of human 40S ribosome maturation

Eukaryotic ribosomes consist of a small 40S and a large 60S subunit that are assembled in a highly coordinated manner. More than 200 factors ensure correct modification, processing and folding of ribosomal RNA and the timely incorporation of ribosomal proteins1,2. Small subunit maturation ends in the cytosol, when the final rRNA precursor, 18S-E, is cleaved at site 3 by the endonuclease NOB13. Previous structures of human 40S precursors have shown that NOB1 is kept in an inactive state by its partner PNO14. The final maturation events, including the activation of NOB1 for the decisive rRNA-cleavage step and the mechanisms driving the dissociation of the last biogenesis factors have, however, remained unresolved. Here we report five cryo-electron microscopy structures of human 40S subunit precursors, which describe the compositional and conformational progression during the final steps of 40S assembly. Our structures explain the central role of RIOK1 in the displacement and dissociation of PNO1, which in turn allows conformational changes and activation of the endonuclease NOB1. In addition, we observe two factors, eukaryotic translation initiation factor 1A domain-containing protein (EIF1AD) and leucine-rich repeat-containing protein 47 (LRRC47), which bind to late pre-40S particles near RIOK1 and the central rRNA helix 44. Finally, functional data shows that EIF1AD is required for efficient assembly factor recycling and 18S-E processing. Our results thus enable a detailed understanding of the last steps in 40S formation in human cells and, in addition, provide evidence for principal differences in small ribosomal subunit formation between humans and the model organism Saccharomyces cerevisiae.ISSN:0028-0836ISSN:1476-468