SummaryAdult stem cells may acquire mutations that modify cellular behavior, leading to functional declines in homeostasis or providing a competitive advantage resulting in premalignancy. However, the frequency, phenotypic impact, and mechanisms underlying spontaneous mutagenesis during aging are unclear. Here, we report two mechanisms of genome instability in adult Drosophila intestinal stem cells (ISCs) that cause phenotypic alterations in the aging intestine. First, we found frequent loss of heterozygosity arising from mitotic homologous recombination in ISCs that results in genetic mosaicism. Second, somatic deletion of DNA sequences and large structural rearrangements, resembling those described in cancers and congenital diseases, frequently result in gene inactivation. Such modifications induced somatic inactivation of the X-linked tumor suppressor Notch in ISCs, leading to spontaneous neoplasias in wild-type males. Together, our findings reveal frequent genomic modification in adult stem cells and show that somatic genetic mosaicism has important functional consequences on aging tissues.

The effects of a custom moulded insole and a rockerbar on peak pressure and force impulse as well as on pain scores in subjects with a history of metatarsalgia were studied. In addition the subjects' preference for the type of intervention was determined. Forty-two subjects with a history of primary metatarsalgia were selected. They were all provided with the same brand of extra depth shoes with a ready made insole. The effect of custom moulded insoles, a rockerbar and the interaction between the two interventions were studied by testing the four possible combinations: ready made insole without a rockerbar, ready made insole with a rockerbar, custom moulded insole without a rockerbar and custom moulded insole with rockerbar. At the most important region, the central distal forefoot, a rockerbar caused a decrease in force impulse of 15.1% and a decrease in peak pressure of 15.7%. The custom moulded insole produced a decrease of 10.1% in force impulse and of 18.2% in peak pressure. Pain scores were significantly lower for interventions with a custom moulded insole, while the rockerbar showed no influence on pain scores. Subjects with pain preferred a custom moulded insole more often than subjects without pain. Decrease of peak pressure or force impulse was not correlated to pain scores. The use of either a custom moulded insole or a rockerbar proudced an important decrease of peak pressure and force impulse at the central distal forefoot and, therefore, either is suitable in any situation which a decrease of pressure is vital.

FLG and POSTN expression may be downregulated and upregulated, respectively, in the esophageal mucosa of patients with active EoE, and these changes may be restored with treatment in a significant percentage of cases.