Mechanism of dentin hardness measurements using a dentin hardness measuring device with a light-emitting diode.

Significance: Managing caries is imperative in a rapidly aging society. Current diagnoses use qualitative indices. However, a quantitative evaluation of hardness in a clinical setting may lead to more accurate diagnoses. Previously, hardness meter using indenter with light for tooth monitoring (HAMILTOM) was developed to quantitatively measure tooth hardness. Herein, the physical interpretation of dentin hardness measured using HAMILTOM and the dentin hardness measurement mechanism are discussed. Aim: This study evaluates the mechanism of dentin hardness measurements using HAMILTOM physically and compare the invasiveness to dentin by HAMILTOM with those using a dental probe for palpation. Approach: Eleven bovine dentin samples were used to create caries models. HAMILTOM measured the dark areas, and its indentations were observed using scanning electron microscopy. Also, its invasiveness was evaluated by comparing the results with those from dental probe palpation. Results: The indentation areas were smaller than the dark areas in HAMILTOM, which may be due to exuded water from the dentin sample and the elastic recovery of dentin sample. Additionally, the dental probe indentation was deeper than the HAMILTOM indentations. Conclusions: The results demonstrate that the indentation areas were smaller than the dark areas measured by HAMILTOM, which might contain the influence of exuded water and the deformation of dentin sample. Also, HAMILTOM is less invasive than dental probe palpation. In the future, HAMILTOM may become a standard hardness measuring method to diagnose root caries.

Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations.

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.

Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. Methods: This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. Discussion: The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. Clinical trial registration: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

Development of a New Two-Arm Transurethral Surgical System for En Bloc Resection of Bladder Tumor: A Preclinical Study.

Backgrounds and Objectives: To overcome the piecemeal nature of bladder tumor resection, en bloc resection of bladder tumor (ERBT) has been introduced. ERBT is difficult for surgeons to perform using the currently available system because it has only one arm. Herein, we aimed to develop a new transurethral surgical system to facilitate two-arm ERBT and to report the results of preclinical experiments using tumor phantoms. Methods: Initially, we aimed to develop a brand-new surgical system for ERBT but, after trial and error, we redirected our development to the creation of three elements: the left arm to grasp the tumor; the right arm to cut the tumor; and the system to operate the arms that can be attached to the existing surgical system (UES-40 SurgMaster® [Olympus Co. Ltd., Tokyo, Japan]). The current system was evaluated by performing simulated ERBTs using tumor phantoms made from konjac jelly. Results: Following the assembly of developed arms into the UES-40 SurgMaster, we conducted preliminary ERBTs. After performing several resections, we adopted a basket-shaped forceps as the left arm instead of grasping forceps and an arched electrode as the right arm. The two arms and single endoscope were placed in an equilateral triangle. We performed ERBT for the tumor phantoms that ranged from 0.5 to 2.0 cm without major redo. Conclusion: Herein, we introduced our development for two-arm ERBT. The current concept of "two-hand transurethral surgery" has the potential to be developed in future in vivo and clinical trials.

Demonstration of an optical dentin hardness measuring device using bovine dentin with different demineralization times.

Significance: The increase in root caries is a serious problem as society ages. Root caries is diagnosed by inspection and palpation, which are qualitative. A method to objectively and quantitatively evaluate the progress of root caries in a clinical setting is strongly desired. The root caries could be diagnosed by measuring hardness because dentin becomes softer as the caries progresses. Vickers hardness has been customarily used as an indicator of tooth hardness. However, this method cannot be used to in vivo teeth because the teeth must be dried prior to measurement to make the indentation. A hardness meter using an indenter with light for tooth monitoring (HAMILTOM) is proposed as an optical device. HAMILTOM could measure hardness of teeth in wet condition as a dark area while applying a load to dentins without drying. Therefore, HAMILTOM may realize hardness measurements of in vivo teeth in a clinical setting quantitatively. Aim: The aim of our study is to demonstrate the optical dentin hardness measuring device HAMILTOM using bovine dentin with different demineralization times and to evaluate the correlation between the dark areas measured by HAMILTOM and the Vickers hardness measured by the Vickers hardness tester. Approach: The samples were 20 bovine dentins. They were demineralized by a lactic acid solution with different times and divided into groups 1 and 2 of 10 samples each. In both groups, the dark areas and Vickers hardness were measured for each sample. Group 1 was used to obtain a calibration curve to calculate Vickers hardness from the dark area. Group 2 was used to validate the calibration curve obtained from the dentin samples of group 1. Results: The areas appearing black without a total internal reflection of the indenter measured by HAMILTOM increased as the demineralization time increased. Additionally, the Vickers hardness of group 2 calculated by the dark areas of group 2 and the calibration curve obtained in group 1 and the Vickers hardness of group 2 measured by the Vickers hardness tester were strongly correlated with a determination coefficient of 0.99. Conclusions: The results demonstrate that HAMILTOM may be a suitable alternative to the conventional method. Unlike the conventional method, which cannot be used for in vivo teeth, HAMILTOM holds potential to quantitatively evaluate the progress of caries in in vivo teeth.

Photodynamic therapy induces interleukin secretion from dendritic cells.

Dendritic cells (DC) pulsed with tumor-derived peptides, proteins, genes, or lysates have been studied as therapeutic cancer vaccines. However, the overall therapeutic efficacy of this approach has been limited, indicating a need to either enhance its potency or combine it with other treatment modalities. Photodynamic therapy (PDT) process consists of injecting a photosensitizer, which selectively accumulates at the lesion site, followed by local illumination of the tumor with a laser of the appropriate wavelength to activate the specific drug. PDT has the potential to create an environment at the tumor site that favors both tumor antigen loading and activation of DCs, key requirements for induction of antitumor immunity. Here, we report that PDT can induce IL-1 and IL-6 and reduce TNF-alpha expression from DCs. This finding has potentially broad clinical implications since these changes are mechanistically involved in the observed effects of PDT on host immune responses. Not all tumors are amenable to PDT, either because of size or location, and one could conceive of an adjuvant use for PDT vaccines in conjunction with other cancer modalities that do not enhance the host antitumor immune response.

Evaluation of oxygen consumption of culture medium and in vitro photodynamic effect of talaporfin sodium in lung tumor cells.

OBJECTIVE: Successful photodynamic therapy (PDT) requires high production of radical ions and singlet oxygen to kill target cells. However, PDT also induces angiogenesis through production of vascular endothelial growth factor (VEGF), which promotes cell regrowth and vascularization. In this study, we evaluated the importance of oxygen in PDT by measuring oxygen consumption, photosensitizer bleaching, and reactive oxygen species (ROS) production in the culture medium, and VEGF secretion either during or after PDT treatment using mouse Lewis lung carcinoma (LLC) cells. BACKGROUND DATA: Local hypoxia is induced under a low oxygen environment. Oxygen is consumed when ROS and singlet oxygen are produced during PDT. The effect of oxygen consumption on cytotoxicity and VEGF secretion has not been clarified. MATERIALS AND METHODS: Mouse Lewis lung carcinoma (LLC) cells treated with the photosensitizer talaporfin sodium were irradiated by a continuous wave semiconductor laser (wavelength, 664 +/- 1 nm). We used oxygen microelectrode for oxygen measurement, a fluorescent probe to detect ROS, MTT assay to evaluate the PDT efficacy, and enzyme-linked immunosorbent assay to measure VEGF concentration. RESULTS: During PDT, oxygen consumption was higher with high doses of talaporfin sodium solution compared with low doses. In addition, the fluorescence of 2-[6-(4'-amino)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, a probe for highly reactive oxygen species such as hydroxyl radicals (*OH), dramatically increased when the dose of talaporfin sodium solution was high. Moreover, VEGF concentration increased after PDT due to hypoxia in a manner dependent on photosensitizer concentration. CONCLUSION: These results indicate that the efficiency of PDT might be improved by sustaining a replete oxygen environment during PDT, not only for ROS and singlet oxygen production, but also for inhibiting neoangiogenesis.