Ultra-low-dose CBCT scan: rational map for ear surgery.

PURPOSE: This study will evaluate the clinical quality and usability of peripheral image data from the temporal bone area obtained using a sinonasal ultra-low-dose (ULD) cone-beam computed tomography (CBCT) scan and compare them to those obtained using a high-resolution (HR) CBCT. METHODS: The population consisted of 66 anatomical sites (ears of 33 subjects) imaged using two modalities: an HR CBCT (Scanora 3Dx scanner; Soredex, Tuusula, Finland) and a ULD CBCT (Promax 3D Mid scanner; Plandent, Helsinki, Finland). The image quality (IQ) for every anatomical site in each image was rated using a Likert scale from 0 to 5. RESULTS: The quality of ULD CBCT scans was clinically sufficient in over 95% of the assessed images of the sigmoid sinus, jugular bulb, epitympanum and mastoid antrum as well as external acoustic meatus (all p > 0.05 compared to HR CBCT). The IQ was clinically sufficient in 75-94% of the assessed images of the scutum, mastoid segment of the facial nerve, cochlea and semicircular canals (all p < 0.05 compared to HR CBCT). The overall IQ of the HR CBCT scans was good or excellent. CONCLUSION: CBCT imaging and the data at image margins are underutilized. CBCT can produce excellent structural resolution with conventional imaging parameters, even with off-focus images. Using ultra-low doses of radiation, the produced IQ is clinically sufficient. We encourage ear surgeons to check the patients' imaging history and to consider the use of imaging modalities that involve lower radiation doses especially when conducting repetitive investigations and with children.

Exploring hydrophilic 2,2-di(indol-3-yl)ethanamine derivatives against Leishmania infantum.

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 µM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 µM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 µM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells.

Deep learning for 3D cephalometric landmarking with heterogeneous multi-center CBCT dataset.

Cephalometric analysis is critically important and common procedure prior to orthodontic treatment and orthognathic surgery. Recently, deep learning approaches have been proposed for automatic 3D cephalometric analysis based on landmarking from CBCT scans. However, these approaches have relied on uniform datasets from a single center or imaging device but without considering patient ethnicity. In addition, previous works have considered a limited number of clinically relevant cephalometric landmarks and the approaches were computationally infeasible, both impairing integration into clinical workflow. Here our aim is to analyze the clinical applicability of a light-weight deep learning neural network for fast localization of 46 clinically significant cephalometric landmarks with multi-center, multi-ethnic, and multi-device data consisting of 309 CBCT scans from Finnish and Thai patients. The localization performance of our approach resulted in the mean distance of 1.99 ± 1.55 mm for the Finnish cohort and 1.96 ± 1.25 mm for the Thai cohort. This performance turned out to be clinically significant i.e., ≤ 2 mm with 61.7% and 64.3% of the landmarks with Finnish and Thai cohorts, respectively. Furthermore, the estimated landmarks were used to measure cephalometric characteristics successfully i.e., with ≤ 2 mm or ≤ 2° error, on 85.9% of the Finnish and 74.4% of the Thai cases. Between the two patient cohorts, 33 of the landmarks and all cephalometric characteristics had no statistically significant difference (p < 0.05) measured by the Mann-Whitney U test with Benjamini-Hochberg correction. Moreover, our method is found to be computationally light, i.e., providing the predictions with the mean duration of 0.77 s and 2.27 s with single machine GPU and CPU computing, respectively. Our findings advocate for the inclusion of this method into clinical settings based on its technical feasibility and robustness across varied clinical datasets.

Comparison of subjective image analysis and effective dose between low-dose cone-beam computed tomography machines.

OBJECTIVES: To compare the cone-beam computed tomography (CBCT) image quality and effective dose between low-dose scanning and standard manufacturer-recommended protocols among different CBCT units. METHODS: Three human-equivalent phantoms were scanned using the ultra-low-dose (ULD), low dose (LD), and standard dose (STD) modes of ProMax 3D Mid (Planmeca Oy, Helsinki, Finland) and Orthophos SL (Sirona, Bensheim, German) for the CBCT images. The quality of the dental anatomical images was assessed by four experienced oral and maxillofacial radiologists using a 5-point Likert scale. OnDemand3D (Cybermed Co., Seoul, Korea) was used as the third-party software for viewing. The percentage of absolute agreement was calculated to determine intra- and interrater agreements among the observers. The effective doses for all CBCT scanning protocols were also calculated. RESULTS: The STD protocol yielded a higher image quality than did the ULD and LD protocols in both ProMax 3D Mid and Orthophos SL. The ULD and LD protocols demonstrated an "acceptable-to-good" sense of visual perception of the CBCT images. The visibility scores significantly differed between the ULD and LD and the STD protocols in ProMax 3D Mid and Orthophos SL, except for the 120-kVp setting in ProMax 3D Mid. The average intra- and interrater agreement scores ranged from 0.63 to 0.89 and from 0.44 to 0.76, respectively. The ULD and LD protocols reduced the radiation dose sixfold compared with the STD protocol. CONCLUSIONS: High-tube-voltage protocols could remarkably reduce the imaging dose without degrading the image quality. Specifically, ULD and LD CBCT protocols may be adopted as routine practice for diagnosis and treatment planning.

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists.

Protein kinase C (PKC) modulators hold therapeutic potential for various diseases, including cancer, heart failure, and Alzheimer's disease. Targeting the C1 domain of PKC represents a promising strategy; the available protein structures warrant the design of PKC-targeted ligands via a structure-based approach. However, the PKC C1 domain penetrates the lipid membrane during binding, complicating the design of drug candidates. The standard docking-scoring approach for PKC lacks information regarding the dynamics and the membrane environment. Molecular dynamics (MD) simulations with PKC, ligands, and membranes have been used to address these shortcomings. Previously, we observed that less computationally intensive simulations of just ligand-membrane interactions may help elucidate C1 domain-binding prospects. Here, we present the design, synthesis, and biological evaluation of new pyridine-based PKC agonists implementing an enhanced workflow with ligand-membrane MD simulations. This workflow holds promise to expand the approach in drug design for ligands targeted to weakly membrane-associated proteins.

Geographic Information System and tools of spatial analysis in a pneumococcal vaccine trial.

BACKGROUND: The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns. METHOD: A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area. RESULTS: We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way. CONCLUSIONS: The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN62323832.