Developing diagnostic criteria for tooth wear, a preliminary beta version based on expert opinion, and a narrative literature review

Background: Tooth wear is a multifactorial condition, leading to the irreversible loss of dental hard tissues. The availability of an unambiguous, universally applicable assessment protocol remains lacking. Objectives: The goal of the authors is to develop a set of diagnostic criteria for the assessment of tooth wear (DC-TW). A two-step approach will be used to achieve this objective: (1) to develop a preliminary beta version of the DC-TW, based on the authors' clinical experience and their shared expertise and supported by a narrative review of the existing literature, and (2) to develop the final DC-TW, with input from a larger group of experts using an international Delphi process. This paper relates to the first step. Methods: The authors outlined the components that should be incorporated into the DC-TW. The literature search was performed to investigate if their concept was in line with the available literature. The search was conducted to identify eligible publications from inception to July 11, 2022. Two authors independently screened all publications, and differences in judgements were resolved through a consensus procedure. Results: The search yielded 5362 publications, resulting in the final inclusion of 383. These publications were divided into four main topics: (1) nomenclature/taxonomies; (2) self-report tools; (3) clinical assessment tools; and (4) clinical decision-making. Conclusions: The information from the publications was used and fused with the clinical experience and shared expertise of the authors to contribute to the development of a preliminary beta version of the DC-TW.</p

Alternative Splicing of the Human Rab6A Gene Generates Two Close but Functionally Different Isoforms

Analysis of the human Rab6A gene structure reveals the presence of a duplicated exon, and incorporation of either of the two exons by alternative splicing is shown to generate two Rab6 isoforms named Rab6A and Rab6A′, which differ in only three amino acid residues located in regions flanking the PM3 GTP-binding domain of the proteins. These isoforms are ubiquitously expressed at similar levels, exhibit the same GTP-binding properties, and are localized to the Golgi apparatus. Overexpression of the GTP-bound mutants of Rab6A (Rab6A Q72L) or Rab6A′ (Rab6A′ Q72L) inhibits secretion in HeLa cells, but overexpression of Rab6A′ Q72L does not induce the redistribution of Golgi proteins into the endoplasmic reticulum. This suggests that Rab6A′ is not able to stimulate Golgi-to-endoplasmic reticulum retrograde transport, as described previously for Rab6A. In addition, Rab6A′ interacts with two Rab6A partners, GAPCenA and “clone 1,” but not with the kinesin-like protein Rabkinesin-6, a Golgi-associated Rab6A effector. Interestingly, we found that the functional differences between Rab6A and Rab6A′ are contingent on one amino acid (T or A at position 87). Therefore, limited amino acid substitutions within a Rab protein introduced by alternative splicing could represent a mechanism to generate functionally different isoforms that interact with distinct sets of effectors

Do Pre-Analytical Parameters Explain KRAS Test Sensitivity Disparities?

Contains fulltext : 110952.pdf (publisher's version ) (Closed access

Implementation of formalin-fixed, paraffin-embedded cell line pellets as high-quality process controls in quality assessment programs for KRAS mutation analysis.

Contains fulltext : 108255.pdf (publisher's version ) (Closed access)In recent years, the mutational status of the KRAS oncogene has become incorporated into standard medical care as a predictive marker for therapeutic decisions related to patients with metastasized colorectal cancer. This is necessary, because these patients benefit from epidermal growth factor receptor (EGFR)-targeted therapy with increased progression-free survival only if the tumor does not carry a mutation in KRAS. Many different analytical platforms, both those commercially available and those developed in house, have been used within pathology laboratories to assess KRAS mutational status. For a testing laboratory to become accredited to perform such tests, it is essential that they perform reliability testing, but it has not previously been possible to perform this kind of testing on the complete workflow on a large scale without compromising reproducibility or the mimicry of the control sample. We assessed a novel synthetic control for formalin-fixed, paraffin-embedded (FFPE) tumor samples in a blind study conducted within nine laboratories across Europe. We show that FFPE material can, at least in part, mimic clinical samples and we demonstrate this control to be a valuable tool in the assessment of platforms used in testing for KRAS mutational status