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Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the ¾-power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.

Syntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S. aciditrophicus However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S. aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that S. aciditrophicus uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA. acs1 mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of S. aciditrophicus grown in pure culture and coculture. Cell extracts of S. aciditrophicus had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from S. aciditrophicus and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in S. aciditrophicus cells support the operation of Acs1 in the acetate-forming direction. Thus, S. aciditrophicus has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase. Bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA. Syntrophus aciditrophicus apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that S. aciditrophicus uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA.

Neoplastic diseases are currently one of the most common causes of mortality in both animals and humans. Therefore, much of the recent research focuses on the search for biomarkers to enable qualitative and temporal improvement in the detectability as well as prognostic and predictive assessments in patients suffering from neoplastic diseases. One such biomarker seems to be cyclooxygenase-2 (COX-2), also known as prostaglandin G/H synthase (PTGS). The wide dissemination of COX isoforms and prostanoids synthesized with their involvement in the tissues indicates the significant role they serve in the regulation of the functioning of several organs and systems, particularly the gastrointestinal, nervous, circulatory, reproductive, urinary and respiratory systems. Until recently, COX-2 has only been associated with the response to stress and inflammation initiators. It is currently known that its expression increases significantly in the course of numerous pathological processes that involve inflammation, pain or fever. Results obtained during previous studies demonstrated a significant increase in COX-2 expression in several types and subtypes of neoplasms in humans and animals, particularly in dogs and cats, the two animal species that have been studied the most frequently. COX-2 has not been adopted yet as one of the biomarkers for routine oncological diagnostics, which indicates the possibility for wider use of the assessment of its expression in the diagnostics and therapy of neoplasms in humans and animals. It may therefore be possible to use an assessment of COX-2 overexpression to improve cancer diagnostics and therapy and for prognostic and/or predictive purposes. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to discuss whether 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) study protocol should include brain imaging. Materials and methods: Analysis of international societies recommendations compared with the original data obtained in over 1000 consecutive torso and brain 18F-FDG PET/CT studies collected in 2010. Results: According to the international societies recommendations, the 18F-FDG should not be the radiotracer of choice considering the brain region PET/CT study. However, it can be performed as an additional brain imaging tool. Based on at least a 3-year follow-up, we detected 8 cases of suspicious brain findings and no primary lesion among over 1000 consecutive torso and brain 18F-FDG PET/CT scans performed in 2010. However, in 5 out of 8 patients, the brain lesion was the only metastasis detected, affecting further therapy. Conclusions: The 18F-FDG PET/CT study may help detect malignant brain lesions and, therefore, including brain region imaging into the study protocol should be considered. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of selectivity of ionizing radiation between normal and cancer cells, it is important to improve the existing radiation patterns. Lowering the risk of cancer recurrence and comfort during treatment are priorities in radiotherapy. Materials and methods: In the experiment we used dose verification to determine the irradiation time calculated by a treatment planning system for 6XFFF and 10XFFF beams. Cells cultured under standard conditions were irradiated with a dose of 2 Gy at different beam rates 400 MU/min, 600 MU/min, 800 MU/min, 1000 MU/min, 1400 MU/min, 1600 MU/min and 2400 MU/min using 6XFFF, 10XFFF and 6XFF beams. Results: The experiment was aimed at comparing the biological response of normal prostate cells after clinically applied radiation patterns. No statistically significant differences in the cellular response were observed. The wide range of beam rates as well as the beam profiles did not significantly affect cell proliferation. Conclusions: High beam rates, without significantly affecting the clonogenic capacity of cells, have an impact on the quality of patient's treatment. With the increasing beam rate the irradiation time is shortened, which has an important impact on patients' health. This experiment can have a practical significance. [ABSTRACT FROM AUTHOR]

• An overall improvement in image quality was obtained for the 70 keV PMR. • iMAR method provided best reduction of metal artefacts observed on CT. • Combining the 70 keV PMR with the iMAR bring benefits for CT use in RT. To evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method. Pseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70–130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers. AD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034). The use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning. [ABSTRACT FROM AUTHOR]

One of the most important test in every quality assurances process of medical linear accelerators is the Winston-Lutz test, allowing an evaluation of the treatment isocentre in the light of uncertainty of the position of the collimator, the gantry and the couch. The purpose of this work was analysis of the results of the Winston-Lutz test performed with three different phantoms for two different accelerators. Measurements were performed on two Varian machines: TrueBeam equipped with aS1200 EPID and TrueBeam equipped with aS1000 EPID. During the study three different phantoms dedicated for verification of the radiation isocentre were used: PTW Isoball, AQUILAB Isocentre Phantom and Varian Isocentre Cube. Analysis of the DICOM images was performed in Artiscan software. For TrueBeam with as1200 EPID, gantry MV isocentre was about 0.18 mm larger for Varian Isocentre Cube than for two other phantoms used in this study. The largest variability of this parameter was observed for the couch. The results differed to 1.16 mm. For TrueBeam with as1000 EPID, results for collimator isocentre with PTW Isoball phantom were about 0.10 mm larger than for two other phantoms. For the gantry, results obtained with Varian Isocentre Cube were 0.21 mm larger. The obtained results for all three phantoms are within the accepted tolerance range. The largest differences were observed for treatment couch, which may be related to the phantom mobility during couch movement. [ABSTRACT FROM AUTHOR]

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• Quality of monoenergetic images was evaluated for the application for RT. • Monoenergetic images need individual calibration curves. • High contrast resolution is comparable for each evaluated energy. • Low contrast resolution, noise and uniformity were the best for 60 and 70 keV. • The best value of SNR was detected for energy of 60 keV. Quantification analysis for monoenergetic computed tomography (CT) images obtained from dual-energy CT scanning was performed in the light of their potential use for structures delineation during radiotherapy. Parameters that describe the quality of the images are: linearity, low and high contrast resolution, uniformity, noise and signal to noise ratio (SNR). To evaluate these parameters, a Catphan phantom was scanned using a dual-energy mode at Somatom Definition AS. Based on the polyenergetic CT images, sixteen monoenergetic series (ranged from 40 keV to 190 keV) were created by CT scanner software and automatically analyzed using Artiscan software. Analysis of linearity shows that a potential use of any monoenergetic images in radiotherapy planning requires that individual calibration curves are implemented for each of them. While the results of the high contrast resolution analysis were comparable for each energy (5 lp/cm), the results of the analyses for uniformity, low contrast resolution, noise and SNR allowed us to select the best imaging energies. The highest relative uniformity was detected for images reconstructed for energies of 60 keV and 70 keV (98.54% and 98.61%). Similar results were observed for low contrast resolution, where the largest number of disks was detected for these energies, and the noise values (0.42% for 60 keV, 0.44% for 70 keV). The best SNR was observed for images reconstructed for energy of 60 keV. Taking into account these results, the energy of 70 keV was selected as potentially the best for reconstruction of monoenergetic images used for structures delineation during radiotherapy. [ABSTRACT FROM AUTHOR]