Brown fat does not cause cachexia in cancer patients: A large retrospective longitudinal FDG-PET/CT cohort study

BACKGROUND Brown adipose tissue (BAT) is a specialized form of adipose tissue, able to increase energy expenditure by heat generation in response to various stimuli. Recently, its pathological activation has been implicated in the pathogenesis of cancer cachexia. To establish a causal relationship, we retrospectively investigated the longitudinal changes in BAT and cancer in a large FDG-PET/CT cohort. METHODS We retrospectively analyzed 13 461 FDG-PET/CT examinations of n = 8 409 patients at our institution from the winter months of 2007-2015. We graded the activation strength of BAT based on the anatomical location of the most caudally activated BAT depot into three tiers, and the stage of the cancer into five general grades. We validated the cancer grading by an interreader analysis and correlation with histopathological stage. Ambient temperature data (seven-day average before the examination) was obtained from a meteorological station close to the hospital. Changes of BAT, cancer, body mass index (BMI) and temperature between the different examinations were examined with Spearman's test and a mixed linear model for correlation, and with a causal inference algorithm for causality. RESULTS We found n = 283 patients with at least two examinations and active BAT in at least one of them. There was no significant interaction between the changes in BAT activation, cancer burden or BMI. Temperature changes exhibited a strong negative correlation with BAT activity (ϱ = -0.57, p<0.00001). These results were confirmed with the mixed linear model. Causal inference revealed a link of Temperature ➜ BAT in all subjects and also of BMI ➜ BAT in subjects who had lost weight and increased cancer burden, but no role of cancer and no causal links of BAT ➜ BMI. CONCLUSIONS Our data did not confirm the hypothesis that BAT plays a major role in cancer-mediated weight loss. Temperature changes are the main driver of incidental BAT activity on FDG-PET scans

Three cases of humeral shaft fracture during police arrest - Biomechanical aspects and reconstruction of events

Objectives: First, to evaluate humeral fracture patterns created by torque and transverse force, to test the breaking force required and evaluate maximum force applied by volunteers; second, to apply the results of these experiments and review relevant literature to three clinical cases of spiral humeral shaft fracture during police arrest with contradicting statements of the involved persons. Material and Methods: The study consisted of a review of the literature as well as an experimental model study. Controlled torque force and direct force was applied to a set of artificial and human humerus bones. In addition, maximum force was measured in 33 healthy volunteers. Fracture thresholds were compared using t-test. Results: Torque forces result in spiral fractures, direct force results in transverse fractures of both artificial and human bones. The threshold level for fractures was significantly lower in human bones than in artificial bones. Maximum force was higher in male than in female volunteers. Nevertheless, all volunteers achieved sufficient force to fracture both artificial and human bones. Conclusion: The findings of this study indicate that the humerus fracture in all three clinical cases occurred as a result of torque forces to the arm. Since there were no lesions to the adjacent joints (shoulder, elbow), the injury mechanism concurs with the situation of a resisted arrest. © 2013 Elsevier Ltd

Promiscuous behaviour of archaeal ribosomal proteins: Implications for eukaryotic ribosome evolution

In all living cells, protein synthesis occurs on ribonucleoprotein particles called ribosomes. Molecular models have been reported for complete bacterial 70S and eukaryotic 80S ribosomes; however, only molecular models of large 50S subunits have been reported for archaea. Here, we present a complete molecular model for the Pyrococcus furiosus 70S ribosome based on a 6.6 A cryo-electron microscopy map. Moreover, we have determined cryo-electron microscopy reconstructions of the Euryarchaeota Methanococcus igneus and Thermococcus kodakaraensis 70S ribosomes and Crenarchaeota Staphylothermus marinus 50S subunit. Examination of these structures reveals a surprising promiscuous behavior of archaeal ribosomal proteins: We observe intersubunit promiscuity of S24e and L8e (L7ae), the latter binding to the head of the small subunit, analogous to S12e in eukaryotes. Moreover, L8e and L14e exhibit intrasubunit promiscuity, being present in two copies per archaeal 50S subunit, with the additional binding site of L14e analogous to the related eukaryotic r-protein L27e. Collectively, these findings suggest insights into the evolution of eukaryotic ribosomal proteins through increased copy number and binding site promiscuity

Detection of GABA, Aspartate and Glutathione in the Human Spinal Cord

The aim of this investigation was to expand the number of predictive markers of in vivo MR spectroscopy measurements of the human spinal cord. Therefore, data was acquired in healthy volunteers with sophisticated motion and instability correction methods as well as advanced hardware enabling the acquisition with excellent spectral quality. Aspartate, Glutathione, and GABA could be additionally identified. In addition, for the first time, the findings were cross-validated with those retrieved from a cadaveric spinal cord sample using high resolution, magic angle spinning NMR measurements enabling a qualitative indication of the presence of the additional metabolite markers found in vivo

The ABCs of the ribosome

An ABC protein that binds the ribosomal exit site suggests a new mechanism for direct regulation of translation in response to changing ATP levels in the cell

Brown fat does not cause cachexia in cancer patients: A large retrospective longitudinal FDG-PET/CT cohort study

Background Brown adipose tissue (BAT) is a specialized form of adipose tissue, able to increase energy expenditure by heat generation in response to various stimuli. Recently, its pathological activation has been implicated in the pathogenesis of cancer cachexia. To establish a causal relationship, we retrospectively investigated the longitudinal changes in BAT and cancer in a large FDG-PET/CT cohort. Methods We retrospectively analyzed 13 461 FDG-PET/CT examinations of n = 8 409 patients at our institution from the winter months of 2007–2015. We graded the activation strength of BAT based on the anatomical location of the most caudally activated BAT depot into three tiers, and the stage of the cancer into five general grades. We validated the cancer grading by an interreader analysis and correlation with histopathological stage. Ambient temperature data (seven-day average before the examination) was obtained from a meteorological station close to the hospital. Changes of BAT, cancer, body mass index (BMI) and temperature between the different examinations were examined with Spearman’s test and a mixed linear model for correlation, and with a causal inference algorithm for causality. Results We found n = 283 patients with at least two examinations and active BAT in at least one of them. There was no significant interaction between the changes in BAT activation, cancer burden or BMI. Temperature changes exhibited a strong negative correlation with BAT activity (ϱ = -0.57, p<0.00001). These results were confirmed with the mixed linear model. Causal inference revealed a link of Temperature ➜ BAT in all subjects and also of BMI ➜ BAT in subjects who had lost weight and increased cancer burden, but no role of cancer and no causal links of BAT ➜ BMI. Conclusions Our data did not confirm the hypothesis that BAT plays a major role in cancer-mediated weight loss. Temperature changes are the main driver of incidental BAT activity on FDG-PET scans. © 2020 Public Library of ScienceISSN:1932-620