The Utility of Cone Beam Computed Tomography Scans in Diagnosing and Treating Anterior Lesions of the Maxilla and Mandible.

BACKGROUND: The standard screening protocol for radiographic examination in dentistry as per the American Dental Association recommendations is a panoramic radiograph (PAN) and four horizontal bitewings. PAN inherently suffers from several shortcomings like the superimposition of anatomic structures, especially of the cervical spine that obscures a significant portion of the anterior maxilla and mandible. This region has a significant amount of pathology that is not adequately imaged. Three-dimensional (3D) imaging provides circumferential information on the area of interest and adds value to the diagnosis and treatment planning of pathology, especially in the anterior maxilla and mandible. However, there is not an adequate number of well-designed studies that articulate the true value addition of 3D imaging for the evaluation of this region. OBJECTIVES: The objective of this study is to evaluate the value addition of 3D imaging in diagnosing pathologies in the anterior maxilla and mandible when compared to two-dimensional PAN. MATERIALS AND METHODS: A total of 25 cases that had a diagnosis of anterior pathology and had both a PAN and a cone beam computed tomography (CBCT) scan were collected for this study. An institutional review board approval to retrospectively evaluate these data was obtained. The PAN and CBCT scans were randomly evaluated by a second-year dental student, an oral and maxillofacial radiology resident in training, and a board-certified oral radiologist. The scans were evaluated using a three-point modified Likert scale, where 1 represents "not visible or clear," 2 represents "visible but not clear," and 3 represents "visible and clear." The lesions were evaluated for characteristics like lesion location, size & shape, internal contents, borders of the lesion, cortical integrity, locularity, and effect on adjacent structures like root resorption. After the evaluation was completed, a comparison of the lesion diagnosis was done with histopathology to confirm the diagnosis. The evaluators were also asked to comment on the specific feature that 3D imaging provided that added value to the case. Kappa analysis was done to evaluate inter-operator reliability. RESULTS: PAN demonstrated significantly lower efficacy in identifying and diagnosing lesions. Only 56% of cases were analyzed using PAN, with 44% deemed undetectable or poorly visualized. These challenging cases necessitated CBCT scans for accurate diagnosis, which successfully diagnosed all 25 cases. The p-value of 0.0002 for PAN implies a highly significant difference from histopathology, suggesting the distinctions are not due to chance. Conversely, the p-value of 0.3273 for CBCT implies that observed differences may be random, lacking sufficient evidence to reject the null hypothesis. CBCT scans consistently outperformed PAN in visualizing various lesion characteristics, underscoring their superior diagnostic capabilities. CONCLUSIONS: In this study, with a small sample size, 3D imaging provided a significant value addition to the diagnosis and treatment planning by providing additional information regarding the location, extent, internal content, and effect on adjacent structures. The practical implications for clinical settings, along with comparisons to current literature, underscore the study's distinctiveness.

WindCline: Sloping wind tunnel for characterizing flame behavior under variable inclines and wind conditions.

Developing accurate computational models of wildfire dynamics is increasingly important due to the substantial and expanding negative impacts of wildfire events on human health, infrastructure, and the environment. Wildfire spread and emissions depend on a number of factors, including fuel type, environmental conditions (moisture, wind speed, etc.), and terrain/location. However, there currently exist only a few experimental facilities that enable testing of the interplay of these factors at length scales <1 m with carefully controlled and characterized boundary conditions and advanced diagnostics. Experiments performed at such facilities are required for informing and validating computational models. Here, we present the design and characterization of a tilting wind tunnel (the "WindCline") for studying wildfire dynamics. The WindCline is unique in that the entire tunnel platform is constructed to pivot around a central axis, which enables the sloping of the entire system without compromising the quality of the flow properties. In addition, this facility has a configurable design for the test section and diffuser to accommodate a suite of advanced diagnostics to aid in the characterization of (1) the parameters needed to establish boundary conditions and (2) flame properties and dynamics. The WindCline thus allows for the measurement and control of several critical wildfire variables and boundary conditions, especially at the small length scales important to the development of high-fidelity computational simulations (10-100 cm). Computational modeling frameworks developed and validated under these controlled conditions can expand understanding of fundamental combustion processes, promoting greater confidence when leveraging these processes in complex combustion environments.

TRIP6 and LPP, but not Zyxin, are present at a subset of telomeres in human cells.

The protection of chromosome ends requires the inhibition of DNA damage responses at telomeres. This inhibition is exerted in great part by the shelterin complex, known to prevent inappropriate ATM and ATR activation. The molecular mechanisms by which shelterin protects telomeres are incompletely understood. Recently, we have implicated for the first time a class of molecules, LIM domain proteins, in telomere protection. This protection occurred through interaction with shelterin, possibly through POT1, and required the pair of LIM proteins TRIP6 and LPP, themselves part of the Zyxin family. The domain similarity between TRIP6, LPP and Zyxin led us to ask whether the latter also interacted with telomeres. Here, we show that there is specificity in the association of LIM proteins with telomeres: Zyxin, despite a high degree of similarity with TRIP6 and LPP, was not detected at telomeres, nor found in a complex with shelterin. TRIP6 and LPP, however, were detected by immunofluorescence at a small subset of telomeres, perhaps those that are critically short. We speculate that specific LIM proteins are part of complex events occurring in the context of the telomere dysfunction response, and possibly at play during the induction of senescence.

LIM-domain proteins TRIP6 and LPP associate with shelterin to mediate telomere protection.

POT1 is the single stranded telomeric overhang binding protein, and is part of the shelterin complex, a group of six proteins essential for proper telomere function. The reduction or abrogation of POT1 DNA binding activity in mammalian cells results in telomere elongation, or activation of the ATR DNA damage response at telomeres. Therefore, overhang binding represents the functionally relevant activity of POT1. To better understand the roles of POT1, we sought to isolate proteins that interact with the DNA binding domain of the protein. A yeast two-hybrid screen was implemented using a C-terminal truncation termed POT1DeltaC, retaining the DNA binding domain. This screen yielded a partial cDNA corresponding to TRIP6, a member of the LIM domain protein family. TRIP6 could co-immunoprecipitate with POT1, TRF2 and TIN2 in human cells, arguing for association with the whole shelterin complex, and was detected at telomeres by ChIP. TRIP6 depletion by siRNA led to the induction of telomere dysfunction induced foci (TIFs), indicating a role in telomere protection. A closely related LIM domain protein, LPP, was also found at telomeres and was also important for repressing the DNA damage response. We propose that TRIP6 and LPP are both required for telomere protection.