Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations

Context: Biallelic mutations in the PTF1A enhancer are the commonest cause of isolated pancreatic agenesis. These patients do not have severe neurological features associated with loss-of-function PTF1A mutations. Their clinical phenotype and disease progression have not been well characterized. Objective: To evaluate phenotype and genotype characteristics and long-term follow-up of patients with PTF1A enhancer mutations. Setting: Twelve tertiary pediatric endocrine referral centers. Patients: Thirty patients with diabetes caused by PTF1A enhancer mutations. Median follow-up duration was 4 years. Main outcome measures: Presenting and follow-up clinical (birthweight, gestational age, symptoms, auxology) and biochemical (pancreatic endocrine and exocrine functions, liver function, glycated hemoglobin) characteristics, pancreas imaging, and genetic analysis. Results: Five different homozygous mutations affecting conserved nucleotides in the PTF1A distal enhancer were identified. The commonest was the Chr10:g.23508437A>G mutation (n = 18). Two patients were homozygous for the novel Chr10:g.23508336A>G mutation. Birthweight was often low (median SDS = -3.4). The majority of patients presented with diabetes soon after birth (median age of diagnosis: 5 days). Only 2/30 presented after 6 months of age. All patients had exocrine pancreatic insufficiency. Five had developmental delay (4 mild) on long-term follow-up. Previously undescribed common features in our cohort were transiently elevated ferritin level (n = 12/12 tested), anemia (19/25), and cholestasis (14/24). Postnatal growth was impaired (median height SDS: -2.35, median BMI SDS: -0.52 SDS) with 20/29 (69%) cases having growth retardation. Conclusion: We report the largest series of patients with diabetes caused by PTF1A enhancer mutations. Our results expand the disease phenotype, identifying recurrent extrapancreatic features which likely reflect long-term intestinal malabsorption.This article is available to RD&E staff via NHS OpenAthens (subject to any publisher embargo). Click on the Publisher URL, and log in with NHS OpenAthens if prompted.Genetic testing for neonatal diabetes was funded through a Wellcome Trust Senior Investigator award (grant number: 098395/Z/12/Z). EDF is a Diabetes UK RD Law rence Fellow (19/005971), and SEF has a Sir Henry Dale Fellow ship jointly funded by the Wellcome Trust and the Royal Society (105636/Z/14/Z).published version, accepted version (12 month embargo), submitted versio

Resistência ao cisalhamento da colagem com compósitos utilizando potencializador de adesão Shear bond strength of composites using an adhesion booster

OBJETIVO: avaliar a resistência ao cisalhamento dos compósitos Transbond XT e Concise Ortodôntico utilizando o potencializador de adesão Ortho Primer. MÉTODOS: a amostra consistiu de 90 incisivos bovinos divididos em seis grupos (n=15). Todos os dentes receberam profilaxia com pedra-pomes e condicionamento do esmalte com ácido fosfórico. No Grupo I, utilizou-se Transbond XT de maneira convencional. O Grupo II foi semelhante ao I, porém, aplicou-se o Ortho Primer ao invés do XT Primer. No Grupo III, após condicionamento, o esmalte foi contaminado com saliva, aplicou-se o Ortho Primer e colagem com Transbond XT. No Grupo IV, utilizou-se o Concise Ortodôntico de maneira convencional. O Grupo V foi semelhante ao IV, porém, utilizou-se o Ortho Primer ao invés da resina fluida. No Grupo VI, após condicionamento, o esmalte foi contaminado com saliva, aplicou-se o Ortho Primer e colagem com Concise. Os corpos de prova foram armazenados em água destilada em estufa a 37ºC por 24h e submetidos ao ensaio de resistência ao cisalhamento. Os dados foram submetidos à ANOVA e ao teste de Tukey (5%). RESULTADOS: a resistência da colagem no Grupo IV foi estatisticamente superior à dos Grupos II, III e VI (p<0,05). Entre os Grupos I, IV e V; e entre os Grupos I, II, III e VI não foram encontradas diferenças estatísticas significativas (p>0,05). O Transbond XT e o Concise utilizados convencionalmente obtiveram os maiores valores adesivos. O Ortho Primer em esmalte seco atuou efetivamente como agente de união dos compósitos avaliados. Em esmalte contaminado, a colagem com Concise obteve baixa resistência adesiva.<br>OBJECTIVE: The aim of this study was to evaluate the shear bond strength of the Transbond XT and Concise Orthodontics composites using the Ortho Primer adhesion booster. METHODS: The sample consisted of 90 bovine incisors divided in 6 groups (n=15). All teeth were submitted to prophylaxes with pumice stone and etching with phosphoric acid. In Group I the Transbond XT was used conventionally. Group II was similar to Group I, however, Ortho Primer was used instead of XT Primer. In Group III, after the acid etching, the enamel was contaminated with human saliva, the Ortho Primer was applied and bonding was done with Transbond XT. In Group IV Concise Orthodontics was used conventionally. Group V was similar to Group IV, but Ortho Primer was applied instead of fluid resin. In Group VI after acid etching, enamel was contaminated with human saliva, Ortho Primer was applied and bonding was done with Concise. The samples were stored in distilled water in incubator at 37ºC for 24h and submitted to the shear strength test. The data were submitted to the ANOVA and the Tukey´s test (5%). RESULTS: Group IV shear bond strength was statistically superior to the Groups II, III and VI (p<0.05). Among the Groups I, IV and V, and among I, II, III and VI there were no significant statistical differences (p>0.05). The Concise and Transbond XT used conventionally presented the most high bonding values. The Ortho Primer in dry enamel acted indeed as bonding agent of evaluated composites. The bonding with Concise in contaminated enamel had obtained low adhesive resistance