Since their introduction to the toad-free Australian continent cane toads (Bufo marinus) have caused a dramatic increase in naïve varanid mortality when these large lizards attempt to feed on this toxic amphibian. In contrast Asian–African varanids, which have coevolved with toads, are resistant to toad toxin. Toad toxins, such as Bufalin target the H1-H2 domain of the α₁ subunit of the sodium-potassium-ATPase enzyme. Sequencing of this domain revealed identical nucleotide sequences in four Asian as well as in three African varanids, and identical sequences in all 11 Australian varanids. However, compared to the Asian–African varanids, the Australian varanids showed four-base-pair substitutions, resulting in the alteration in three of the 12 amino acids representing the H1-H2 domain. The phenotypic effect of the substitutions was investigated in human embryonic kidney (HEK) 293 cells stably transfected with the Australian and the Asian–African H1-H2 domains. The transfections resulted in an approximate 3000-fold reduction in resistance to Bufalin in the Australian HEK293 cells compared to the Asian–African HEK293 cells, demonstrating the critical role of this minor mutation in providing Bufalin resistance. Our study hence presents a clear link between genotype and phenotype, a critical step in understanding the evolution of phenotypic diversity.

Purpose: Incorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a possible solution. However, only through quantification of the fluorescence signal can an objective and reproducible evaluation of tissue perfusion be obtained. This narrative review aims to provide an overview of the available quantification methods for perfusion assessment using ICG NIR fluorescence imaging and to present an overview of current clinically utilized software implementations. Methods: PubMed was searched for clinical studies on the quantification of ICG NIR fluorescence imaging to assess tissue perfusion. Data on the utilized camera systems and performed methods of quantification were collected. Results: Eleven software programs for quantifying tissue perfusion using ICG NIR fluorescence imaging were identified. Five of the 11 programs have been described in three or more clinical studies, including Flow® 800, ROIs Software, IC Calc, SPY-Q™, and the Quest Research Framework®. In addition, applying normalization to fluorescence intensity analysis was described for two software programs. Conclusion: Several systems or software solutions provide a quantification of ICG fluorescence; however, intraoperative applications are scarce and quantification methods vary abundantly. In the widespread search for reliable quantification of perfusion with ICG NIR fluorescence imaging, standardization of quantification methods and data acquisition is essential.

Context Colorectal cancer patients have increased risk of metabolic diseases including diabetes. Exercise training may counteract metabolic dysregulation, but the impact of exercise training on glycaemic control including post-prandial glycemia has never been explored in colorectal cancer patients Objective to examine the effects of home-based interval walking on aerobic and metabolic fitness, and quality of life in colorectal cancer patients. Design Randomized Controlled Trial Setting Clinical research centre Participants Thirty-nine sedentary (less than 150 min moderate intensity exercise per week), stage I-III colorectal cancer patients, who had completed primary treatment. Intervention Home-based interval-walking 150 min per week or usual care for 12 weeks Main Outcome Measures changes from baseline to week 12 in VO_2peak by cardiopulmonary exercise test; glycemic control by oral glucose tolerance test (OGTT); body composition by DXA-scan; blood biochemistry, and quality of life. Results Compared to control, interval-walking had no effect on VO_2peak (mean between-group difference: -0.32ml O₂*kg^-1*min^-1 [-2.09; 1.45], p = 0.721) but significantly improved post-prandial glycaemic control with lower glucose OGTT-area under the curve (-126 mM*min [-219; -33], p=0.009), 2-hour glucose concentration (-1.1 mM [-2.2;0.0], p=0.056), and improved Matsuda index +1.94 [0.34; 3.54], p=0.019. Also, interval walking counteracted an increase in fat mass in the control-group (-1.47 kg [-2.74; -0.19], p=0.025). Conclusion A home-based interval walking program led to significant improvements in post-prandial glycaemic control and counteracted fat gain in post-treatment colorectal cancer patients possibly providing a novel and effective strategy for prevention of secondary metabolic diseases.

Although there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation. The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option ‘tolerance’ to cancer. Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer. Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival.