The alarms detected in the CUSUM analysis followed the same pattern. This significant increase in the frequency of LRD could have been biased by the improvement in prenatal diagnosis and derivation of those cases with fetal anomalies to referral hospitals participants of ECLAMC. Our proactive surveillance led to the identification of two cases compatible with TE, although maternal use of thalidomide could not be proven. However, the availability of this information often depends on individual conditions, such as maternal memory and fear of social prejudice due to of the use of a medication that is contraindicated during pregnancy. Moreover, there is the possibility of self-medication, which is a habitual behavior among the Brazilian population and lies behind the unadvised use of several drugs during pregnancy. This is a problem observed not only with thalidomide but also with other drugs with teratogenic potential. In three recent clinically characteristic cases of embryopathy recorded in Brazil, maternal interview was negative for the use of thalidomide. It is important to point out that thalidomide is not the only etiological factor for the phenotypes that we included as suggestive of TE. Syndromes whose characteristics are similar to those of TE include: Roberts syndrome, Holt-Oram syndrome, Fanconis pancytopenia, radial aplasia-thrombocytopenia, among others syndromes, as well and Femur-Fibula-Ulna complex, besides unspecified developmental conditions. One limitation of the present surveillance is that the main endemic areas of leprosy in Brazil are located in rural regions, especially in the north and center-west regions, where many births take place outside hospital settings and where coverage and monitoring by ECLAMC is not present. In any case, the percentage of coverage of births is also a limiting factor in surveillance systems. Yang et al. evaluated the ability of monitoring systems to detect TE alarms and suggested that the surveillance of all LRD is insufficient for the detection of this type of embryopathy. The TE surveillance system presented herein is highly sensitive because all the LRD described in the syndrome are included, but the system has low specificity because it groups different types of LRD not related to TE. One mechanism by which Rac activation is localized to generate spines. These filopodia-like spines are highly dynamic and protrude and retract frequently; since MIIB is not required for this activity, it is likely that this arises AbMole Oleandrin largely from actin polymerization and depolymerization. In contrast, the maturation into a compact, mushroom-shaped structure requires MIIB contractile activity; however, Arp2/3-driven actin polymerization may contribute as well to drive spine head expansion, in analogy with the broad protrusions it mediates in migrating fibroblasts. Finally, MIIB may also serve to localize signals that affect spine morphology and function.