The effect of ultrasonic access cavity preparation on dentinal inner walls: a micro-CT study on cadaveric samples

ObjectiveThe objective of this study is to evaluate the occurrence of coronal dentinal micro-cracks after access cavity refinement using high-speed burs and ultrasonic tips by means of micro-computed tomography (micro-CT) analysis.MethodsIn this study, 18 mandibular cadaveric incisors were divided into two groups according to the protocol of the preparation of the conventional access cavity. The diamond bur 802 # 12 was used until the perforation of the pulp roof. Then, the Endo-Z bur was used for the group #1 and the ultrasonic tip Start-X # 1 for the group #2 to finish and refine the access cavity. The preparation time of each access cavity has been recorded. The teeth underwent a micro-CT scan before and after the preparation of the access cavity. Fisher's exact test, the Chi-square test, the Kolmogorov-Smirnov test, the Mann-Whitney test, and the Student's test were used for statistical evaluation.ResultsThe percentage of teeth with new micro-cracks is not significantly different between the two groups (-p-value < 0.5). The number of newly formed micro-cracks and extension size were not significantly different between the two groups. The direction of extension of the micro- cracks was occluso-apical. The average duration of the access cavity is significantly smaller with the Endo-Z system (-p- value < 0.001). The roughness of walls surfaces has no statistically difference between the two groups.ConclusionThe use of ultrasound, although slower, is considered safe in the creation of dentinal micro-cracks, in the preparation of the access cavity

Performance of the LHCb muon system with cosmic rays

The LHCb Muon system performance is presented using cosmic ray events collected in 2009. These events allowed to test and optimize the detector configuration before the LHC start. The space and time alignment and the measurement of chamber efficiency, time resolution and cluster size are described in detail. The results are in agreement with the expected detector performance.Comment: Submitted to JINST and accepte

Performance of the LHCb muon system

The performance of the LHCb Muon system and its stability across the full 2010 data taking with LHC running at ps = 7 TeV energy is studied. The optimization of the detector setting and the time calibration performed with the first collisions delivered by LHC is described. Particle rates, measured for the wide range of luminosities and beam operation conditions experienced during the run, are compared with the values expected from simulation. The space and time alignment of the detectors, chamber efficiency, time resolution and cluster size are evaluated. The detector performance is found to be as expected from specifications or better. Notably the overall efficiency is well above the design requirementsComment: JINST_015P_1112 201

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction

Background: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. Objective: We sought to characterize the role of EIF4A2 variants in dystonic conditions. Methods: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. Results: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. Conclusions: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Loss-of-Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities.

OBJECTIVES: The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. METHODS: We undertook weighted burden analysis of whole-exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case-finding from international databases, first for the gene implicated by the burden analysis (VPS16), and then for other functionally related genes. Electron microscopy was performed on patient-derived cells. RESULTS: Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 109 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome-lysosome fusion. A total of 18 individuals harboring heterozygous loss-of-function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss-of-function variants in VPS41, another HOPS-complex encoding gene, in an individual with infantile-onset generalized dystonia. Electron microscopy of patient-derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. INTERPRETATION: Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867-877