Overlapping but distinct roles for NOTCH receptors in human cardiovascular disease.

The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome. NOTCH2 mutations lead to the development of Alagille syndrome, while mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. To date, mutations in NOTCH4 have not been associated with cardiovascular disease. This review focuses on the mutations described in NOTCH1, NOTCH2, and NOTCH3 and their associated cardiovascular phenotypes.

A prospective randomized clinical trial of one bis-GMA-based and two ormocer-based composite restorative systems in class II cavities: Five-year results.

OBJECTIVES: Ormocer composites, consisting of a silicon-based polymer, have been developed recently as a tooth-colored restorative material. The purpose of this prospective randomized clinical trial was to evaluate the performance of two small-particle hybrid ormocer-based restorative systems (AD, Admira/Admira Bond, VOCO; DE, Definite/Etch & Prime 3.0, Dentsply) and one small-particle hybrid bis-GMA-based composite restorative system (TC, Tetric-Ceram/Syntac, Ivoclar-Vivadent) in class II cavities. METHODS: From 128 occlusal-proximal restorations (44 AD, 43 DE and 41 TC) placed in 32 adult patients, eventually 77 (22 AD, 29 DE and 26 TC) remained available for evaluation after 5 years. Their clinical performance was scored according to the USPHS criteria and evaluation of bite-wing radiographs. RESULTS: After 5 years, eight AD, six DE and seven TC restorations had failed (p=0.10, log-rank test). The main reason was fracture or marginal gap formation, while secondary caries accounted for four failures. In all restorations the quality of surface, margins and contact point decreased significantly compared to baseline. DE had a significant poorer color match (p<0.01). Statistical evaluation using the KW test showed that failures were concentrated on specific patients. CONCLUSIONS: In a group of class II restorations, there was no significant difference in failures after 5 years between ormocer-based and bis-GMA-based restorative systems.

Chromosome 10q harbors a susceptibility locus for bipolar disorder in Ashkenazi Jewish families.

We report the results of a 10 cM density genome-wide scan and further fine mapping of three chromosomal candidate regions in 10 Belgian multigenerational families with bipolar (BP) disorder. This two-stage approach revealed significant evidence for linkage on chromosome 10q21.3-10q22.3, showing a maximum multipoint parametric heterogeneity logarithm of odds (HLOD) score of 3.28 and a nonparametric linkage (NPL) score of 4.00. Most of the chromosome 10q evidence was derived from a single, large Ashkenazi Jewish pedigree. Haplotype analysis in this pedigree shows that the patients share a 14-marker haplotype, defining a chromosomal candidate region of 19.2 cM. This region was reported previously as a candidate region for BP disorder in several independent linkage analysis studies and in one large meta-analysis. It was also implicated in a linkage study on schizophrenia (SZ) in Ashkenazi Jewish families. Additionally, we found suggestive evidence for linkage on chromosome 19q13.2-13.4 (HLOD 2.01, NPL 1.09) and chromosome 7q21-q22 (HLOD 1.45, NPL 2.28). Together, these observations suggest that a gene located on chromosome 10q21.3-10q22.3 is underlying the susceptibility both for SZ and for BP disorder in at least the Ashkenazi Jewish population.

A prospective randomised clinical trial of one bis-GMA-based and two ormocer-based composite restorative systems in class II cavities: three-year results.

OBJECTIVES: Ormocer composites, consisting of a silicon-based polymer, have been developed recently as a tooth-coloured restorative material. The purpose of this prospective randomised clinical trial was to evaluate the performance of two small-particle hybrid ormocer-based restorative systems (AD, Admira/Admira Bond, VOCO; DE, Definite/Etch & Prime 3.0, Dentsply) and one small-particle hybrid bis-GMA-based composite restorative system (TC, Tetric-Ceram/Syntac, Ivoclar-Vivadent) in occlusal stress-bearing restorations. METHODS: One hundred and twenty-eight occlusal-proximal restorations (44 AD, 43 DE and 41 TC) were placed according to the manufacturer's instructions in thirty-two adult patients. Their clinical performance was scored according to the USPHS criteria and evaluation of bite-wing radiographs. RESULTS: After 3 years, four AD, five DE and four TC restorations had failed due to fracture or marginal gap formation. Surface roughness improved significantly when compared to the baseline in AD and TC (Friedman test, p<0.05) during the first year but returned to baseline values after 3 years. DE had a significant tendency towards discolouration (p<0.05). Bite-wing radiographs showed two AD and one TC restorations with internal porosities. ANOVA showed that larger restorations (> or = 3 surfaces) showed significantly more degradation than smaller ones. CONCLUSIONS: In a group of class II restorations, there was no significant difference in failures after 3 years between ormocer-based and bis-GMA-based restorative systems.