Implementation of a multilevel, multicomponent intervention for obesity control in Native American communities (OPREVENT2): challenges and lessons learned.

OPREVENT2 was a multilevel, multicomponent (MLMC) adult obesity prevention that sought to improve access and demand for healthier food and physical activity opportunities in six Native American communities in the Southwest and Midwest. OPREVENT2 worked with worksites, food stores, schools (grades 2-6), through social media and mailings, and with a local community action committee (CAC), in each of the three intervention communities, and was implemented in six phases. We conducted a process evaluation to assess implementation of each intervention component in terms of reach, dose delivered and fidelity. Implementation of each component was classified as high, medium or low according to set standards, and reported back at the end of each phase, allowing for improvements. The school and worksite components were implemented with high reach, dose delivered and fidelity, with improvement over time. The school program had only moderate reach and dose delivered, as did the social media component. The CAC achieved high reach and dose delivered. Overall, study reach and dose delivered reached a high implementation level, whereas fidelity was medium. Great challenges exist in the consistent implementation of MLMC interventions. The detailed process evaluation of the OPREVENT2 trial allowed us to carefully assess the relative strengths and limitations of each intervention component.

Novel DNMT3A germline mutations are associated with inherited Tatton-Brown-Rahman syndrome.

Tatton-Brown-Rahman syndrome (TBRS) was recently described in 13 isolated cases with de novo mutations in the DNMT3A gene. This autosomal dominant condition is characterized by tall stature, intellectual disability and a distinctive facial appearance. Here, we report six cases of inherited TBRS caused by novel DNMT3A germline mutations. The affected individuals belong to two sib-ships: four from an Old Order Amish family in America and two from a French Canadian family in Canada. All of them presented with characteristic features of TBRS, including dysmorphic facial features, increased height, intellectual disability, and variable additional features. We performed clinical exome sequencing and identified two mutations in the DNMT3A gene, a c.2312G>A (p.Arg771Gln) missense mutation in the Amish family and a c.2296_2297delAA (p.Lys766Glufs*15) small deletion in the French Canadian family. Parental DNA analysis by Sanger sequencing revealed that the Amish mutation was inherited from the healthy mosaic father. This study reflects the first cases with inherited TBRS and expands the phenotypic spectrum of TBRS.

Aortic root dilatation in Ehlers-Danlos syndrome types I, II and III. A report of five cases.

We have identified five families in whom individuals affected with the Ehlers Danlos syndrome (EDS) types I, II or III had aortic root dilatation (ARD). All propositi had a low upper/lower segment ratio but no other diagnostic skeletal or ocular features of Marfan syndrome. Their skin had the soft, velvety texture characteristic of EDS and all had significant joint laxity. Probands included a 4-year-old girl with EDS type I, 4- and 8-year-old girls with EDS type III, a 35-year-old male with EDS type II, and a 51-year-old female with EDS type III. Review of these cases suggests the need for multicenter clinical studies in order to determine the prevalence and the rate of progression of ARD in EDS types I, II, and III. Such studies are necessary to determine whether echocardiograms (including measurement of aortic root diameter) should be considered on initial evaluation of all patients with mild forms of EDS.