The inner ear forms from paired ectodermal primordia that lie to either side of the developing hindbrain. Initially each primordium forms a shallow depression in the ectodermal surface. Invagination to form an otic pit coincides with the formation of several deep folds in the epithelial surface. An initial fold appears parallel to the embryonic axis and at the junction of the rhombencephalon with somitomeric mesoderm. This is followed by formation of cranial and caudal folds perpendicular to the axis and minor folds that are within the pit formed by earlier folding. The central region of the otic primordium remains in close apposition to the lateral surface of the neural tube during the process of fold formation, until the otic pit becomes quite deep. At that time, mesenchymal cells penetrate between the two layers. Experimental analysis of invagination supports the conclusion that otic invagination is controlled differently from that of similar organ primordia, such as the eye and thyroid. Whereas these other primordia can be stimulated to undergo normal morphogenetic shape changes precociously by treatments that presumably activate motile processes in the cytoskeleton, the same conditions have little effect on the otic placode. Similarly, neither inhibitors of calcium transport nor inactivators of calmodulin activity prevent otic pit formation, while these drugs block invagination of other primordia. These results suggest that otic invagination may be caused by changes in the surrounding tissues rather than by an activation of motility within the primordium.

SUMMARY This study aimed to objectively evaluate the radiopacity of different dental composites and their subjective influence on diagnosing secondary caries–like lesions and how these results correlate. For objective analysis, three resin specimens (1 mm thick, with a 4-mm internal diameter) were made with four composites: 1) Charisma; 2) Filtek Z250; 3) Prisma AP.H; and 4) Glacier. Three human teeth were selected and then mesio-distally sectioned (1 mm thick) to make the dental specimens. An aluminum (Al) wedge (12 steps, 1 mm thick, 99.8% purity) was used as an internal standard to calculate the radiopacity. For subjective analysis, 20 human teeth were selected and then prepared with a mesio-occluso-distal (MOD) inlay cavity, with half the teeth receiving a round cavity to simulate the carious lesion. The MOD was restored using the composites at four different times. Standardized radiographs were acquired and then digitized (300 dpi and eight-bit TIFF) for both analyses. A histogram objectively measured the pixel intensity values of the images, which were converted into millimeters of Al using linear regressions. Eight observers subjectively evaluated the images using a five-point rating scale to diagnose the caries. The data were statistically analyzed using the Student t-test, the Kappa test, diagnostic testing, and the Pearson correlation coefficient (α=0.05). All materials showed radiopacity values compatible with dental tissues (p>0.05); Glacier was similar to dentin and Prisma AP.H was similar to enamel, while the remaining materials showed a middle radiopacity. Prisma AP.H and Glacier differed (p<0.05) in relation to their accuracy to caries diagnosis, with Glacier having greater accuracy. There was a correlation between objective and subjective analyses with negative linear dependence. An increase in the material's radiopacity could have a subjectively negative influence on the diagnosis of secondary caries; thus, an ideal radiopacity for a dental composite is closer to the dentin image and produces similar attenuation to X-rays than does dentin.

Myrciaria floribunda (H. West ex Willd.) O. Berg, Myrtaceae, is a native plant species of the Atlantic Rain Forest, from north to south of Brazil. The lyophilized ethyl acetate extract from the leaves of M. floribunda was investigated for its antiproliferative activity in tumor cell lines, antioxidant capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative activity was tested in vitro against seven human cancer cells and against immortalized human skin keratinocytes line (HaCat, no cancer cell). Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbing capacity (ORAC) assays and total phenolic, flavonoid and tannin contents were determined by spectrophotometric techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI) between 69.70 and 172.10 µg/mL. For HaCat cell, TGI value was 213.60 µg/mL. M. floribunda showed a strong antioxidant potential: EC 50 of 45.89±0.42 µg/mL and 0.55±0.05 mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23±0.013g gallic acid equivalents (GAE)/g extract and exhibited 13.10±1.60% of tannins content. The content of flavonoid was 24.08±0.44% expressed as rutin equivalents. These results provide a direction for further researches about the antitumoral potential of M. floribunda.

Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.