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Background & Aims: A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined., Methods: We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance., Results: Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche., Conclusions: ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

Background: Reports of long-term incidence trends of endemic diarrhea-associated hemolytic uremic syndrome (D+HUS) are few and inconclusive., Objective: To define and analyze the incidence and outcomes of D+HUS over a period of approximately 25 years in a highly endemic region of southern Alberta., Methods: Annual incidence rates of confirmed cases of D+HUS were compared between two 12-year periods (1980 to 1992 and 1994 to 2006). Differences in therapies used, and some short- and long-term complications observed were also compared between the two periods., Results: The absolute yearly number of D+HUS cases was highly variable. The comparison between the 1980 to 1992, and 1994 to 2006 periods demonstrated a modest 8.8% decrease in the total number of cases. The population-based average annual incidence rates were not significantly different between the two time periods (3.33 cases versus 2.58 cases per 100,000 population per year, respectively; P=0.30). Only supportive care measures were used in the latter period. A mortality rate of lower than 1% in the latter period was one of the lowest ever reported for a large cohort of D+HUS patients., Conclusion: The present long-term retrospective study of D+HUS in a highly endemic area documented a modest decrease in the absolute number of cases but no difference in the average annual incidence over an extended period of time.

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 10(3)/mm(3) and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.

Objective: To test the null hypothesis that no difference in bracket failure characteristics is noted when use of a new ceramic bracket debonding instrument is compared with the use of conventional pliers., Materials and Methods: Thirty maxillary premolars were randomly assigned to one of two groups. In group 1, Clarity collapsible ceramic brackets (3M Unitek, Monrovia, Calif) were debonded with the use of conventional Utility/Weingart (3M Unitek, Monrovia, Calif) pliers. In group 2, Clarity brackets were debonded with a new Debonding Instrument (3M Unitek). For all teeth, the same bracket bonding system was used. Following debonding, teeth and brackets were examined under 10x magnification for assessment of bracket failure (fracture) and of residual adhesive on the enamel surface. Enamel surfaces were visualized with transillumination prior to bonding and after removal of the residual adhesive, so the effect of the debonding forces could be determined., Results: The results of Adhesive Remnant Index comparisons indicated that a statistically significant difference (chi2 = 8.73; P = .013) in bond failure patterns was apparent when the two groups were compared. Brackets debonded with the new instrument showed a greater tendency for the adhesive to be removed from the tooth during debonding., Conclusions: The hypothesis is rejected. Although the incidence of enamel damage following debonding was similar in the two groups, the use of the new Debonding Instrument decreased the incidence of bracket fracture.

Objective: To determine the influence of self-etching primer (SEP) application time on the shear bond strength of orthodontic brackets., Materials and Methods: Forty human molars were cleaned, mounted, and randomly divided into two groups. The same SEP, adhesive, and brackets were used in both groups. Twenty teeth were conditioned following the manufacturers' recommendations by rubbing the SEP on the enamel surface for 3 to 5 seconds. The remaining 20 teeth were conditioned using the same SEP, but the application time was increased to 15 seconds. The teeth were debonded within half an hour following initial bonding using a universal testing machine. After debonding, the amount of residual adhesive remaining on the tooth was determined. Student's t-test was used to compare the shear bond strength (SBS) of the two groups, and the chi2 test was used to compare the Adhesive Remnant Index (ARI) scores for the two adhesive systems., Results: The mean SBS of the brackets bonded to the teeth subjected to the SEP for 3 to 5 seconds was 8.0+/-4.6 MPa and was not significantly different (t=-0.69, P=.494) from the SBS of the brackets bonded using a 15-second SEP application time (x=8.9+/-3.4 MPa). The comparisons of the ARI scores between the two groups (chi2=2.16) indicated that bracket failure mode was not significantly different (P=.340) for both groups, and most failures were at the bracket-adhesive interface., Conclusion: The present findings indicate that increasing the SEP application from 3 to 5 seconds to 15 seconds does not result in a significant increase in SBS.

This study examined Ogbu's widely accepted thesis that African American students reject high academic achievement because they perceive its limited utility in a world where their upward mobility is constrained by racial discrimination. Boykin's psychosocial integrity model contends that Black students value high achievement but that discrepancies between their formative cultural experiences and those imposed in school lead them to reject the modes of achievement available in classrooms. Ninety Black children completed a measure of attitudes toward students who achieve via mainstream or African American cultural values. Participants rejected the mainstream achievers and embraced the African American cultural achievers. Moreover, they expected their teachers to embrace the mainstream achievers and reject those who achieved through high-verve behavior. Results suggest that Boykin's thesis is a needed refinement to Ogbu's ideas. They indicate that Black children may reject not high achievement but some of the mainstream cultural values and behaviors on which success in mainstream classrooms is made contingent.

Background: Graft survival in children who undergo kidney transplantation is lower than that in adults. The objective of the study was to review the experience of the first 22 years of operation of the regional pediatric kidney transplantation unit for Atlantic Canada, based at the IWK-Grace Health Centre, Halifax, and to use the results to improve graft survival., Methods: All cases of kidney transplantation performed at the centre from 1971 to 1992 were reviewed and the data compiled with the use of a predetermined database outline. Data for first transplants were analysed and compared with those in North American databases. Of the 40 graft failures, 19 (48%) occurred within the first 3 months after transplantation, a rate similar to that at other centres. The overall survival rates tended to be slightly lower than those of international databases. The introduction of cyclosporine A as an immunosuppressant, in 1985, did not provide the expected marked improvement in survival. Infection frequently accompanied acute rejection, and there was a delay in treatment of infections and rejection after discharge home. On the basis of these preliminary findings, several program changes were made: 1) a sequential immunosuppression protocol was implemented, 2) the intensity of the medical surveillance was increased for the first 3 months after transplantation, with aggressive treatment of infections and rejections, 3) a dedicated pediatric transplantation team was established as a subset of the adult team and 4) pediatric-specific selection criteria for cadaver donors were formulated. After these changes were implemented, data were collected and analysed up to June 30, 1997., Results: Graft survival rates at 1, 2 and 5 years improved dramatically. After the beginning of 1993, there were only 2 graft losses among 22 transplants. Only one of these occurred in the first 3 months, and it was due to recurrent disease. Twenty-four rejection episodes occurred (10 in the first 3 months after transplantation), but all were reversed easily with high-dose steroid therapy., Interpretation: Sequential immunosuppression with close medical surveillance and early aggressive treatment of infection and rejection contribute to a marked improvement in kidney graft survival in children.