Percutaneous gastrostomy tubes in children with Pierre Robin sequence: efficacy, maintenance and complications.

BACKGROUND: Children with Pierre Robin sequence (PRS) have significant oropharyngeal abnormalities, with respiratory and feeding difficulties. Gastrostomy tubes (G-tube) provide a means for nutrition. OBJECTIVE: To evaluate the safety and efficacy of percutaneous G-tube insertion in children with PRS. MATERIALS AND METHODS: Of 120 children with PRS (1996-2009), 40 were referred for G-tube insertion; clinical details were reviewed in 37/40 children (18M, 19F) at three time periods: (1) pre-G-tube insertion, (2) at G-tube insertion, (3) at G-tube removal. RESULTS: Pre-G-tube: 32/37 were term infants; 5 were preterm; 16/37 children were ≤ 10th weight percentile. At G-tube insertion, mean age was 66 days, mean weight 4.4 kg (1.1-7.0 kg); 19 dropped ≥10 weight percentiles; 12 tolerated nil by mouth; 2/37 were intubated for the procedure. All G-tubes were successfully placed, with five minor technical issues. Early postprocedure, there were eight minor complications and two dislodgements (classified as major). At G-tube removal mean G-tube dwell time was 2 years, with an average of 3.6 maintenance procedures per child, approximately 3 tube changes/1,000 tube days. At G-tube removal, 76% had maintained or increased weight centiles. CONCLUSION: G-tubes in PRS provide a safe method for nutrition until children feed adequately by mouth.

MRI surveillance for women with dense breasts and a previous breast cancer and/or high risk lesion.

BACKGROUND: The role of surveillance breast MRI for women with mammographically dense breasts, a personal history of breast cancer (BC), atypical hyperplasia (AH), or lobular carcinoma in situ (LCIS) is unclear. We estimated the performance of annual surveillance MRI in women with a combination of these risk factors. METHODS: We performed a retrospective review of the clinical, radiological, and pathological parameters of women who received annual concurrent surveillance breast MRI and mammography between 04/2013 and 12/2015 and fulfilled all of the following criteria: 1) age <70; 2) prior diagnosis of AH, LCIS or BC; 3) heterogeneously or extremely dense breast(s); and 4) did not qualify for our provincial breast MRI high risk screening program. RESULTS: This study included 198 patients (266 MRI exams). MRI detected 15 cancers: 11 invasive stage I and 4 in-situ. All but 1 were mammographically occult and there were no interval cancers. The cancer detection rate (CDR) and false positive (FP) rate were 6.1% and 21% for round one and 4.7% and 12.5% for round two, respectively. Not being on anti-estrogen therapy and having a 1st degree relative with BC significantly increased the likelihood of tumor detection. CONCLUSIONS: The CDR and FP rate of surveillance MRI in this study were comparable to those reported for women with BRCA mutations. The addition of annual MRI to mammography should be considered for surveillance of women with a combination of these risk factors, particularly if they have a family history of BC and are not on anti-estrogen therapy.

Integrin alpha5beta1 function is regulated by XGIPC/kermit2 mediated endocytosis during Xenopus laevis gastrulation.

During Xenopus gastrulation alpha5beta1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the alpha5 subunit and regulates the activity of alpha5beta1 integrin. The interaction of kermit2 with alpha5beta1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates alpha5beta1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the alpha5beta1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the alpha5beta1 integrin through receptor endocytosis.

An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes.

The heterohexameric origin recognition complex (ORC) acts as a scaffold for the G(1) phase assembly of pre-replicative complexes (pre-RC). Only the Orc1-5 subunits appear to be required for origin binding in budding yeast, yet Orc6 is an essential protein for cell proliferation. Imaging of Orc6-YFP in live cells revealed a punctate pattern consistent with the organization of replication origins into subnuclear foci. Orc6 was not detected at the site of division between mother and daughter cells, in contrast to observations for metazoans, and is not required for mitosis or cytokinesis. An essential role for Orc6 in DNA replication was identified by depleting it at specific cell cycle stages. Interestingly, Orc6 was required for entry into S phase after pre-RC formation, in contrast to previous models suggesting ORC is dispensable at this point in the cell cycle. When Orc6 was depleted in late G(1), Mcm2 and Mcm10 were displaced from chromatin, cells failed to progress through S phase, and DNA combing analysis following bromodeoxyuridine incorporation revealed that the efficiency of replication origin firing was severely compromised.