Obesity is a major reason for the recent increase in incidence of reflux disease and cancers at the distal esophagus and gastroesophageal junction (GOJ) and is mediated through a rise in the intra-abdominal pressure (IAP) but the exact mechanisms are unclear. Raised IAP from obesity and with application of waist belt produces mechanical distortion of the GOJ through formation of partial hiatus hernia. Even though there is no trans-sphincteric acid reflux, there is increased ingress of acid into the lower sphincter (intra-sphincteric reflux) as a consequence of raised IAP. In addition, short segment acid reflux is more evident in obese subjects with a belt on. Acid pocket is also enlarged in hiatus hernia, and acts as a reservoir of acid available to reflux whenever the sphincter fails. Above mechanisms may explain the common occurrence of cardiac lengthening and inflammation found in asymptomatic obese subjects. The inflamed cardia is also immunohistochemically similar to non-intestinal Barrett's mucosa, which is of etiological importance for cancers at the GOJ. Interventions that can reduce the mechanical distortion and acid exposure at the GOJ, including diet, exercise, drugs, sphincter augmentation therapy, and surgery, are clinically relevant in the treatment of gastroesophageal reflux disease but more data are needed whether if these strategies are also effective in preventing cancer. As a conclusion, raised IAP produces silent mechanical disruption of the GOJ, which may explain the high occurrence of cancers in this region and it is potentially reversible with early interventions.
Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.