Journal of internal medicine
-
The relationship of evolution with diet and environment can provide insights into modern disease. Fossil evidence shows apes, and early human ancestors were fruit eaters living in environments with strongly seasonal climates. Rapid cooling at the end of the Middle Miocene (15-12 Ma: millions of years ago) increased seasonality in Africa and Europe, and ape survival may be linked with a mutation in uric acid metabolism. ⋯ The earliest fossils of Homo sapiens appeared about 300 kyr, but they had separated from Neanderthals by 480 kyr or earlier. Their diet shifted towards grain-based foods about 100 kyr ago, and settled agriculture developed about 10 kyr ago. This pattern remains for many populations to this day and provides important insights into current burden of lifestyle diseases.
-
Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. ⋯ The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.
-
Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. ⋯ Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.
-
Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early-stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low-density lipoprotein (LDL)-cholesterol. ⋯ FH children display higher PBMC expression of immune-related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL-C plays an important role in modulating expression of different immune-related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression.