Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Trans-Pacific tele-ultrasound image transmission of fetal central nervous system structures

Objective: To assess the quality of images and video clips of fetal central nervous (CNS) structures obtained by ultrasound and transmitted via tele-ultrasound from Brazil to Australia.

Methods: In this cross-sectional study, 15 normal singleton pregnant women between 20 and 26 weeks were selected. Fetal CNS structures were obtained by images and video clips. The exams were transmitted in real-time using a broadband internet and an inexpensive video streaming device. Four blinded examiners evaluated the quality of the exams using the Likert scale. We calculated the mean, standard deviation, mean difference, and p values were obtained from paired t tests.

Results: The quality of the original video clips was slightly better than that observed by the transmitted video clips; mean difference considering all observers = 0.23 points. In 47/60 comparisons (78.3%; 95% CI?=?66.4–86.9%) the quality of the video clips were judged to be the same. In 182/240 still images (75.8%; 95% CI?=?70.0–80.8%) the scores of transmitted image were considered the same as the original.

Conclusion: We demonstrated that long distance tele-ultrasound transmission of fetal CNS structures using an inexpensive video streaming device provided images of subjective good quality.     

Continuing education in the child health handbook: an educational software for primary care1

ObjectiveTo present, the process of development and evaluation of an educational software on the Child Health Handbook proposed for the continuing education of primary care nurses and physicians.MethodsQuantitative study of methodological development. For software development, the following steps were followed: definition of objectives; determination of the target audience; choice of pedagogical and theoretical reference for content; content selection and structuring; software development and evaluation by experts (five nurses and four physicians). All responded to an instrument that included four domains: pedagogical; content; functionality; system presentation and usability. The evaluation criteria were arranged on a Likert-type scale. The percentage of agreement and Content Validity Index were used for the quantitative analysis of the degree of agreement, considering a Content Validity Index cutoff point equal to 0.80.ResultsThe overall agreement index, calculated by the arithmetic mean of the Contents Validity Index of the evaluated domains, was 0.96, with scores ranging from 0.90 to 1.00. The average percentage of agreement of the experts per domain was 92.86%, with lower agreement in the content (80.95%), presentation, and usability (90.48%) domains. 100% of percentage of agreement was observed in the pedagogical and functionality domains among the evaluated specialists.ConclusionThe percentage of agreement, Content Validity Index and overall agreement index of the Child Health Handbook educational software in the context of primary care disclosed the software adequacy as an educational resource for continuing education of primary care nurses and physicians. Considering the assessed dimensions, it can also be used by other health professionals and undergraduate students.