Multiphoton tissue imaging by using moxifloxacin

Multiphoton microscopy has been widely used for in-vivo tissue imaging of various biological studies. However, its application to clinical studies has been limited due to either lack of clinically compatible exogenous contrast agents or weak autofluorescence of tissues. We investigated moxifloxacin as a contrast agent of cells for multiphoton tissue imaging. Moxifloxacin is an FDA approved antibiotic with relatively good pharmacokinetic properties for tissue penetration and intrinsic fluorescence. Two-photon microscopy (TPM) of moxifloxacin treated mouse corneas showed good tissue penetration and high concentration inside the corneal cells [1]. Cell labeling of moxifloxacin was tested in both cultured cells and isolated immune cells. Moxifloxacin tissue applications were tested in various mouse organs such as the skin, small intestine, and brain. Most of tissues were labeled well via topical administration, and only the skin required additional gentle removal of the outermost stratum corneum by tape stripping. TPM of these tissues showed non-specific cell labeling of moxifloxacin and fluorescence enhancement [2]. Although most of experimental results were from mouse tissues, its clinical application would be possible. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence. Moxifloxacin labeling of cultured cells was demonstrated by comparing TPM images with and without moxifloxacin treatment. Bright fluorescence inside cells were observed only with moxifloxacin at the same imaging condition. TPM of the skin dermis visualized many dermal cells with increased fluorescence, and TPM of the villus in the small intestine showed the covering epithelial cells and cells inside the villus clearly. Please click Additional Files below to see the full abstract

The expertise of internal accounting control personnel and financial statement conservatism: Korean evidence

The purpose of this study is to analyze how the expertise of internal accounting control personnel impacts financial statement conservatism. This study analyzed companies listed on the Korean stock market. Listed companies in Korea have been disclosing information on internal accounting personnel since 2012. Using a fixed-effect regression model, an analysis of 3,276 firm-years from 2012 to 2018 shows a positive correlation between the expertise of internal accounting control personnel and financial statement conservatism. The results from Ball and Shivakumar’s (2006) CF, DD, and Jones models are all significant at the 1% level, enhancing the robustness of the study’s findings. The coefficients were 0.872, 0.869, and 0.846, and the t-values were 3.93, 3.95, and 3.83 in each model. This indicates that firms with CPAs (Certified Public Accountant) among their internal accounting control personnel show stronger tendencies toward conservatism compared to those without CPAs. Furthermore, an analysis based on the firm ownership structure reveals a positive correlation between internal accounting control personnel expertise and financial statement conservatism in a non-Chaebol subsample (coefficient = 1.043, t-value = 3.58 in CF model); however, the results in the Chaebol subsample were not significant. This suggests that while having CPAs involved in non-Chaebol firms’ internal control is effective, it is not effective in Chaebol companies that are highly influenced by their owners

Hearing Abilities at Ultra-High Frequency in Patients with Tinnitus

ObjectivesTo compare tinnitus patients who have normal hearing between 250 Hz and 8 kHz with normal controls with regard to the ability of each group to hear extended high-frequency pure tone thresholds.MethodsWe enrolled 18 tinnitus patients, each of whom had a threshold of HL <25 dB and threshold differences of <10 dB between ears at frequencies of 250 and 500 Hz and 1, 2, 4, and 8 kHz. We also enrolled age- and gender-matched normal volunteers (10 ears), for each patient. Extended high frequency pure tone audiometry was performed, and the mean hearing thresholds at 10, 12, 14, and 16 kHz of each tinnitus ear were compared with those of the 10 age- and sex-matched normal ears.ResultsOf the 18 patients with tinnitus, 12 had significantly increased hearing thresholds at more than one of the four high frequencies, compared with the normal group. When we assessed results according to frequency, we found that 8 patients had decreased hearing ability at 10 kHz, 10 at 12 kHz, 8 at 14 kHz, and 4 at 16 kHz.ConclusionSome patients with tinnitus who have normal hearing below 8 kHz have decreased hearing ability at extended high-frequencies. Thus, the proportion of patients with tinnitus who have normal hearing over the entire audible range is smaller than in previous reports

Persistent Pemphigus Vulgaris Showing Features of Tufted Hair Folliculitis

Pemphigus vulgaris is an autoimmune blistering disease that commonly involves the scalp. Lesions of pemphigus vulgaris that persist on the scalp for a long period may be accompanied by tufted hair folliculitis. Only two previous accounts of tufted hair folliculitis developing in a lesion of pemphigus vulgaris have been reported. We report a 51-year-old-man with erosions and clusters of hair on the scalp. The scalp lesion had persisted for about 20 years. A histopathological examination of the skin lesion on the scalp revealed separation of the epidermis and clusters of several adjacent hair follicles. The patient was diagnosed with persistent pemphigus vulgaris of the scalp showing features of tufted hair folliculitis

Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin

AbstractMurine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2Å and 2.5Å resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase

The Clinical Usefulness of 18F-FDG PET/CT for the Evaluation of Lymph Node Metastasis in Periorbital Malignancies

PURPOSE: Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an oral condition unfavorable for prosthodontic rehabilitation. This study assessed the quality of life related to oral function in edentulous head and neck cancer patients following oncology treatment of malignancies in the lower region of the oral cavity. MATERIALS AND METHODS: Patients treated between 1990 and 2000 with surgery and radiotherapy for a squamous cell carcinoma in the oral cavity who were edentulous in the mandible and had been treated with a conventional, non-implant-retained denture received an invitation for a clinical check-up (clinical assessment, questionnaires regarding oral function and quality of life). RESULTS: Sixty-seven of the 84 patients who fulfilled the inclusion criteria were willing to participate in the study. The mean irradiation dosage that these patients had received in the oral region was 61.8 +/- 5.4 Gy. Half of the patients (n=33) were not very satisfied with their prostheses; they wore their mandibular prostheses at most a few hours per day. It was concluded from the clinical assessment that two thirds of the patients (n 4) could benefit from an implant-retained mandibular denture. Analyses of the questionnaires revealed no significant associations between functional assessments, quality of life, and parameters such as size of the primary tumor, location of the primary tumor, and different treatment regimes. Despite cancer treatment, the patients reported a rather good general quality of life. CONCLUSIONS: Sequelae resulting from radiotherapy probably dominate oral function and quality of life after oncology treatment. In two thirds of the patients, improvement of oral function and related quality of life would be expected with the use of an implant-retained mandibular denture

Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study

To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypocalcemic symptoms after total thyroidectomy on the basis of serum calcium and intact parathyroid hormone (PTH) levels measured 1 hour after surgery, a prospective study was performed on 817 patients who underwent a total thyroidectomy with central compartment node dissection (CCND) due to well-differentiated thyroid cancer. We evaluated the correlations between hypocalcemic symptom development and clinicopathological factors. And the predictability for hypocalcemic symptom development of intact PTH cut-offs (<10 pg/mL and <20 pg/mL, resp.) according to serum calcium level subgroup was analyzed. Female gender (P<0.001) was the only independent risk factor for hypocalcemic symptom development in multivariate regression analysis. The negative predictive value (NPV) of intact PTH, signifying nondevelopment of hypocalcemic symptoms, was higher than the positive predictive value (PPV) which signified development of hypocalcemic symptoms. In addition, when we applied the different adoption of the intact PTH cut-off according to serum calcium level, we could obtain more increased NPVs. A female gender and the application of more specific cut-offs for intact PTH according to the serum calcium levels measured 1 hour after surgery may help the patients to be more safely discharged

In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. Intrinsic multiphoton fluorescence properties of moxifloxacin and gatifloxacin were characterized, and their distributions in mouse cornea in vivo were measured by 3D MPM imaging. Both moxifloxacin and gatifloxacin had similar multiphoton spectra, while moxifloxacin had stronger fluorescence than gatifloxacin. MPM imaging of mouse cornea in vivo showed (1) moxifloxacin had good penetration through the superficial corneal epithelium, while gatifloxacin had relatively poor penetration, (2) both ophthalmic solutions had high intracellular distribution. In vivo MPM results were consistent with previous studies. This study demonstrates the feasibility of MPM as a method for in vivo direct measurement of moxifloxacin and gatifloxacin in the cornea.1175Ysciescopu