A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19.

In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

Tuberculous Lymphadenitis in a Patient Treated with Dupilumab: A Case Report.

Tuberculous lymphadenitis is among the most frequent presentations of extrapulmonary tuberculosis; the most common presentation is isolated chronic non-tender lymphadenopathy in young adults without systemic symptoms. Dupilumab is a fully human monoclonal antibody directed against interleukin-4 receptor-α that blocks the synergistic effects of interleukin-4 and interleukin-13 on allergic inflammation. Its well-known adverse events are allergic conjunctivitis, injection site reaction, and dupilumab facial redness. A 32-year-old female with severe atopic dermatitis was treated with dupilumab for 2 months at our clinic. She complained of multiple enlarged palpable lymph nodes on the right side of the neck and inguinal area for 2 months. Laboratory tests showed an increased total eosinophil count and immunoglobulin E level, as well as positive interferon-γ release assays. Radiological examination showed multiple low echoic and heterogeneous well-enhancing lymph nodes in level II, III, IV, and V of the neck. Histological examination revealed caseous necrosis and tuberculoid granuloma. The lymph node enlargements were completely relieved after antituberculosis treatment. The mechanism for the development of tuberculous lymphadenitis in a patient receiving dupilumab is not fully understood yet. In some previous studies, treatment with dupilumab suppressed the expression of genes related not only to T helper 2 and eosinophil response but also to proinflammatory responses. It could not inhibit the intracellular growth of Mycobacterium tuberculosis in macrophages, predisposing them to the development of tuberculous infection. To the best of our knowledge, this is the first report on the development of tuberculosis lymphadenitis in a patient treated with dupilumab.

Focal nodular enhancement on DCE MRI of the prostatectomy bed: radiologic-pathologic correlations and prognostic value.

OBJECTIVES: To determine the concordance of dynamic contrast-enhanced (DCE) imaging findings with clinico-pathologic characteristics and their prognostic impact for predicting biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP) for prostate cancer. METHODS: This retrospective study included patients who underwent MRI within 1 year after RP between November 2019 and October 2020. DCE findings and their concordance with the presence and location of positive surgical margin (PSM) were assessed using RP specimens. Kaplan-Meier and logistic regression analyses were used to evaluate the prognostic impact of DCE findings for BCR. RESULTS: Among the 272 men (mean age ± standard deviation, 66.6 ± 7.4 years), focal nodular enhancement was more frequently observed in those with PSM compared to those with negative margin (85.4% versus 14.6%; p < 0.001). The sites of focal nodular enhancement were 72.9% (35/48) concordant with the PSM locations. Focal nodular enhancement was associated with a higher Gleason score, higher preoperative PSA (≥ 10 ng/mL), higher Gleason grade at the surgical margin, and non-limited margin involvement (p = 0.002, 0.006, 0.032, and 0.001, respectively). In patients without BCR at the time of MRI, focal nodular enhancement was associated with a shorter time to BCR (p < 0.001) and a significant factor predicting 1-year BCR in both univariate (odds ratio = 8.4 [95% CI: 2.5-28.3]; p = 0.001) and multivariate (odds ratio = 5.49 [1.56-19.3]; p = 0.008) analyses. CONCLUSIONS: Focal nodular enhancement on post-prostatectomy MRI was associated with adverse clinico-pathologic characteristics of high risk for recurrence and can be a predictor for 1-year BCR in patients undergoing RP. KEY POINTS: • Focal nodular enhancement (PI-RR DCE score ≥ 4) was 72.9% (35/48) concordant with the site of positive resection margin by radiologic-histologic correlation. • Focal nodular enhancement (PI-RR DCE score ≥ 4) was associated with higher Gleason score ( ≥ 8), preoperative PSA ( > 10 ng/mL), and Gleason grade 4 or 5 at the surgical margin and non-limited margin involvement (p ≤ 0.032). • In patients without BCR at the time of MRI, focal nodular enhancement was a significant factor predicting 1-year BCR (odds ratio = 5.49; 95% CI: 1.56-19.3; p = 0.008).

Proportion of malignancy in Bosniak classification of cystic renal masses version 2019 (v2019) classes: systematic review and meta-analysis.

OBJECTIVES: Determine the proportion of malignancy within Bosniak v2019 classes. METHODS: MEDLINE and EMBASE were searched. Eligible studies contained patients with cystic renal masses undergoing CT or MRI renal protocol examinations with pathology confirmation, applying Bosniak v2019. Proportion of malignancy was estimated within Bosniak v2019 class. Risk of bias was assessed using QUADAS-2. RESULTS: We included 471 patients with 480 cystic renal masses. No class I malignant masses were observed. Pooled proportion of malignancy were class II, 12% (6/51, 95% CI 5-24%); class IIF, 46% (37/85, 95% CI 28-66%); class III, 79% (138/173, 95% CI 68-88%); and class IV, 84% (114/135, 95% CI 77-90%). Proportion of malignancy differed between Bosniak v2019 II-IV classes (p = 0.004). Four studies reported the proportion of malignancy by wall/septa feature. The pooled proportion of malignancy with 95% CI were class III thick smooth wall/septa, 77% (41/56, 95% CI 53-91%); class III obtuse protrusion ≤ 3 mm (irregularity), 83% (97/117, 95% CI 75-89%); and class IV nodule with acute angulation, 86% (50/58, 95% CI 75-93%) or obtuse angulation ≥ 4 mm, 83%, (64/77, 95% CI 73-90%). Subgroup analysis by wall/septa feature was limited by sample size; however, no differences were found comparing class III masses with irregularity to class IV masses (p = 0.74) or between class IV masses by acute versus obtuse angles (p = 0.62). CONCLUSION: Preliminary data suggest Bosniak v2019 class IIF masses have higher proportion of malignancy compared to the original classification, controlling for pathologic reference standard. There are no differences in proportion of malignancy comparing class III masses with irregularities to class IV masses with acute or obtuse nodules. KEY POINTS: • The proportion of malignancy in Bosniak v2019 class IIF cystic masses is 46% (37 malignant/85 total IIF masses, 95% confidence intervals (CI) 28-66%). • The proportion of malignancy in Bosniak v2019 class III cystic masses is 79% (138/173, 95% CI 68-88%) and in Bosniak v2019 class IV cystic masses is 84% (114/135, 95% CI 77-90%). • Class III cystic masses with irregularities had similar proportion of malignancy (83%, 97/117, 95% CI 75-89%) compared to Bosniak class IV masses (84%, 114/135, 95% CI 77-90%) overall (p = 0.74) with no difference within class IV masses by acute versus obtuse angulation (p = 0.62).

Fast T2-Weighted Imaging With Deep Learning-Based Reconstruction: Evaluation of Image Quality and Diagnostic Performance in Patients Undergoing Radical Prostatectomy.

BACKGROUND: Deep learning-based reconstruction (DLR) can potentially improve image quality by reduction of noise, thereby enabling fast acquisition of magnetic resonance imaging (MRI). However, a systematic evaluation of image quality and diagnostic performance of MRI using short acquisition time with DLR has rarely been investigated in men with prostate cancer. PURPOSE: To assess the image quality and diagnostic performance of MRI using short acquisition time with DLR for the evaluation of extraprostatic extension (EPE). STUDY TYPE: Retrospective. POPULATION: One hundred and nine men. FIELD STRENGTH/SEQUENCE: 3 T; turbo spin echo T2-weighted images (T2WI), echo-planar diffusion-weighted, and spoiled gradient echo dynamic contrast-enhanced images. ASSESSMENT: To compare image quality, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) and subjective analysis using Likert scales on three T2WIs (MRI using conventional acquisition time, MRI using short acquisition time [fast MRI], and fast MRI with DLR) were performed. The diagnostic performance for EPE was evaluated by three independent readers. STATISTICAL TESTS: SNR, CNR, and image quality scores across the three imaging protocols were compared using Friedman tests. The diagnostic performance for EPE was assessed using the area under receiver operating characteristic curves (AUCs). P < 0.05 was considered statistically significant. RESULTS: Fast MRI with DLR demonstrated significantly higher SNR (mean ± SD, 14.7 ± 6.8 vs. 8.8 ± 4.9) and CNR (mean ± SD, 6.5 ± 6.3 vs. 3.4 ± 3.6) values and higher image quality scores (median, 4.0 vs. 3.0 for three readers) than fast MRI. The AUCs for EPE were significantly higher with the use of DLR (0.86 vs. 0.75 for reader 2 and 0.82 vs. 0.73 for reader 3) compared with fast MRI, whereas differences were not significant for reader 1 (0.81 vs. 0.74; P = 0.09). DATA CONCLUSION: DLR may be useful in reducing the acquisition time of prostate MRI without compromising image quality or diagnostic performance. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world.

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety.

Bosniak Classification of Cystic Renal Masses Version 2019: Comparison With Version 2005 for Class Distribution, Diagnostic Performance, and Interreader Agreement Using CT and MRI.

BACKGROUND. The Bosniak classification system for cystic renal masses (CRMs) was updated in 2019, requiring further investigation. OBJECTIVE. The purpose of this study was to compare versions 2005 and 2019 of the Bosniak classification system in terms of class distribution, diagnostic performance, interreader agreement, and intermodality agreement between CT and MRI. METHODS. This retrospective study included 100 patients (mean age, 52.4 ± 11.6 years; 68 men, 32 women) with 104 CRMs (74 malignant) who underwent CT, MRI, and resection between 2010 and 2019. Two radiologists independently evaluated CRMs in separate sessions for each combination of version and modality and assigned a Bosniak class. Diagnostic performance was compared using McNemar tests. Interreader and intermodality agreement were analyzed using weighted kappa coefficients. RESULTS. Across readers and modalities, the proportion of class IIF CRMs was higher for version 2019 than version 2005 (reader 1: 28.8-30.8% vs 6.7-12.5%; reader 2: 26.0-28.8% vs 8.7-19.2%), although 95% CIs overlapped for reader 2 on CT. The proportion of class III CRMs was lower for version 2019 than version 2005 (reader 1: 33.7-35.6% vs 49.0-51.9%; reader 2: 31.7-40.4% vs 37.5-52.9%), although 95% CIs overlapped for all comparisons. Version 2019 showed lower sensitivity for malignancy than version 2005 across readers and modalities (all p < .05); for example, using CT, sensitivity was 75.7% for both readers with version 2019 versus 85.1-87.8% with version 2005. However, version 2019 showed higher specificity than version 2005, which was significant (all p < .05) for reader 1. For example, using CT, specificity was 73.3% (reader 1) and 70.0% (reader 2) with version 2019 versus 50.0% (reader 1) and 56.7% (reader 2) with version 2005. Diagnostic accuracy was not different between versions (version 2005: 76.9-85.6%; version 2019: 74.0-78.8%). Interreader and intermodality agreement were substantial for version 2005 (κ = 0.676-0.782 and 0.711-0.723, respectively) and version 2019 (κ = 0.756-0.804 and 0.704-0.781, respectively). CONCLUSION. Use of version 2019 versus version 2005 of the Bosniak classification system results in a shift in CRM assignment from class III to class IIF. Version 2019 results in lower sensitivity, higher specificity, and similar accuracy versus version 2005. Interreader and intermodality agreement are similar between versions. CLINICAL IMPACT. Version 2019 facilitates recommending imaging surveillance for more CRMs.

Preoperative MRI-based estimation of risk for positive resection margin after radical prostatectomy in patients with prostate cancer: development and validation of a simple scoring system.

OBJECTIVES: To develop a simplified MRI-based model to predict the risk for positive surgical margins (PSMs) after radical prostatectomy (RP) in patients with prostate cancer (PCa). METHODS: Consecutive patients who underwent RP for PCa were retrospectively identified from a tertiary referral hospital. Patients who underwent RP between January 2014 and June 2014 were assigned as derivation cohort (n = 330) and those between January 2018 and February 2018 were assigned as validation cohort (n = 100). MRI-based predictors associated with PSM were assessed: tumor size, tumor-capsule contact length, the Prostate Imaging Reporting and Data System (PI-RADS) category, tumor location (tumor contact to the apex or posterolateral side near the neurovascular bundle), apical depth, and prostate volume. A prediction model was developed by using multivariable logistic regression, and then it was transformed into a scoring system. The prediction and calibration performance of this scoring system was evaluated using the C statistics and Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 121 (36.7%) and 32 (32.0%) of patients in the derivation and validation cohorts had PSMs after RP. The scoring system consisted of the following variables: tumor-capsule contact length, PI-RADS category, tumor located at the apex and/or posterolateral side. This scoring system provided good prediction performance for PSM in the derivation (C statistics, 0.80 [95% CI: 0.76, 0.85]) and validation (C statistics, 0.77 [95% CI: 0.68, 0.87]) cohorts, and also showed good calibration in both cohorts (p = 0.83 and 0.86, respectively). CONCLUSIONS: An MRI-based scoring system can help estimate the risk of PSM after RP. KEY POINTS: • An MRI-based scoring system served as a tool to estimate the risk of positive surgical margin (C statistics, 0.80 and 0.77 in the derivation and validation cohorts, respectively) after radical prostatectomy. • Tumor with contact to the apex or posterolateral aspect, the tumor contact length to capsule, and higher PI-RADS category were independent predictors for the presence of positive resection margins after radical prostatectomy in men with prostate cancer. • High-risk patients as determined by the scoring system demonstrated adverse post-surgical outcomes compared with low- or intermediate-risk patients, in regard to longer length (mean length, 13.0 mm versus 3.9 mm in low risk or 6.2 mm in intermediate risk; p ≤ 0.001) and higher Gleason grade at the margin (grades 4 and 5 in 69.4% and 20.4% versus 16.7% and 16.7% in low risk or 46.7% and 5.4% in intermediate risk; p < 0.001).

Facial erythema after the treatment of dupilumab in SLE patient.

BACKGROUND: Dupilumab is a receptor antagonist binding to the alpha subunit of the interleukin-4 receptor. Through binding to it, dupilumab inhibits signaling of both IL-4 and IL-13, the representative Th2 biomarkers. Recently, in addition to the treatment effects for atopic dermatitis (AD), there is an emerging adverse event as facial erythema. CASE PRESENTATION: A twenty-seven-year-old female patient developed erythema and desquamation on the face and neck after dupilumab administration. She had AD on her arms, legs, and trunk before the treatment but there was no atopic clinical feature in her face and neck. With the treatment of dupilumab, her skin lesions of the body have improved from the beginning of the treatment. In the patch test, including dupilumab, there was no specific finding other than the 1+ response to neomycin on day 2. In the intradermal test to dupilumab, a positive result was observed 15 min later, but negative both days 1 and 2. The blood examination showed an elevation of both ANA as 1:80 and anti-phospholipid antibodies (Anti-cardiolipin IgM, IgG, and Anti- beta 2 GPI IgG). She was diagnosed with Systemic lupus erythematosus (SLE) based on diagnostic criteria by a rheumatologist. CONCLUSION: Dupilumab is an emerging therapeutic agent for AD, and treatment cases are increasing in Korea. However, there are several adverse events during the treatment of dupilumab. Herein, we report the unexpected adverse event during the treatment of dupilumab in SLE patients.

Comparison of biopsy strategies for prostate biopsy according to lesion size and PSA density in MRI-directed biopsy pathway.

PURPOSE: To investigate whether the detection of clinically significant prostate cancer (csPCa) and the added value of focal saturation biopsy and systematic biopsy (SBx) differ according to index lesion size, and to compare the current guidelines for csPCa detection. METHODS: This retrospective study included consecutive men who underwent MRI and subsequent SBx and MRI-targeted biopsy (TBx) for a suspicious lesion between April 2019 and February 2020. Lesion visibility on transrectal ultrasound (US) and added value of focal saturation biopsy and SBx were compared according to index lesion size using chi-square and McNemar tests. csPCa detection rates and the proportion of biopsy-indicated men were compared among four biopsy strategies based on current guidelines. RESULTS: Of 313 men evaluated (median age, 65; interquartile range 60‒71), csPCa was detected in 110 (35%). In lesions < 10 mm, greater US invisibility (42.7% of lesions < 10 mm versus 20.0% of lesions ≥ 10 mm; p < 0.001) and higher added value of focal saturation biopsy and SBx (11.1% and 17.1% in lesions < 10 mm versus 4.2% and 6.3% in lesions ≥ 10 mm) were observed, compared with lesions ≥ 10 mm. Consideration of prostate-specific antigen (PSA) density > 0.15 ng/mL/mL as a cutoff in unsuspicious MRI led to a 14% reduction (44/313) in men who needed biopsy. CONCLUSION: Determination of the biopsy strategy in terms of the need for focal saturation biopsy or SBx should be made considering lesion size. The use of PSA density in non-suspicious MRI can lead to a reduction in biopsy-indicated men.

Retrospective Study of Dupilumab Treatment for Moderate to Severe Atopic Dermatitis in Korea: Efficacy and Safety of Dupilumab in Real-World Practice.

Among biological agents for the treatment of atopic dermatitis (AD), dupilumab is a front-runner. Although many studies have been conducted on the real-world use of dupilumab, the sample size is often small and data is primarily on Western people. Therefore, we investigated the efficacy and safety of dupilumab in patients with moderate-to-severe AD in Korea. All patients with moderate-to-severe AD treated with dupilumab from September 2018 to June 2019 in this institution were included and analyzed by medical records. They were evaluated using the Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI), respectively on admission, after two weeks (only EASI and NRS) and after 16 weeks. Laboratory tests were measured before and 16 weeks after treatment. A total of 101 patients were included. All efficacy tools showed a significant decrease after 16 weeks; EASI 77.4%, NRS 70.0%, POEM 60.7%, and DLQI 65.0%. EASI was characterized by a marked improvement of 51.5% in just two weeks. The treatment response was not significantly different according to the interval of treatment. Elevated Lactate Dehydrogenase (LDH) at 16 weeks was associated with poor treatment response. Moreover, a high eosinophil count was related to a lower change in EASI and POEM. In the correlation analysis, EASI was not correlated to DLQI before treatment. For changes after 16 weeks, POEM showed the highest correlation with DLQI. (R = 0.66, p < 0.001) In the additional analysis for factors affecting treatment response, the female gender was associated with good treatment response. (odds ratio = 5.4, p = 0.04) Adverse events from treatment included facial erythema (9.9%) and conjunctivitis (5.0%). Overall, it was confirmed that the efficacy of dupilumab in the real-world is similar to that of the existing clinical trials. We suggest that POEM is a useful tool for identifying the quality of life. The female gender was associated with a good treatment response. Both an elevated LDH and a high eosinophil count could be a therapeutic biomarker. Further research will be needed for a long-term period.

Occupational Lead Exposure and Brain Tumors: Systematic Review and Meta-Analysis.

(1) Background: Due to inconsistencies in epidemiological findings, there has been uncertainty regarding the association of lead compounds with brain tumors. We performed a meta-analysis of published case-control and cohort studies exploring lead compound exposure and brain tumor risk. (2) Methods: We searched PubMed, Embase®, and Cochrane to find eligible studies. Eighteen studies were selected for assessment of occupational exposure to lead compound and brain tumor. Pooled estimates of odds ratios (ORs) were obtained using random effects models. We assessed the differences through subgroup analysis according to tumor type, study design, measurements of exposure, and tumor outcome. Statistical tests for publication bias, heterogeneity, and sensitivity analysis were applied. (3) Results: Our systematic review and meta-analysis showed a not significant association with lead exposure and risk of benign and malignant brain tumors (pooled OR = 1.11, 95% Confidence Interval (CI): 0.95-1.29). Including only malignant brain tumors, the risk of brain tumor was significantly increased (pooled OR = 1.13, 95% CI: 1.04-1.24). (4) Conclusions: This meta-analysis provides suggestive evidence for an association between lead compound exposure and brain tumor. In future studies, it will be necessary to identify the effect of lead compounds according to the types of brain tumor.

Extent of Subprosthetic Pannus after Aortic Valve Replacement: Changes Over Time and Relationship with Echocardiographic Findings.

Purpose: This study aimed to evaluate changes of subprosthetic pannus on cardiac CT and determine its relationship to echocardiographic findings in patients with mechanical aortic valve replacement (AVR). Materials and Methods: Between April 2011 and November 2017, 17 AVR patients (56.8 ± 8.9 years, 12% male) who showed pannus formation on CT and had undergone both follow-up CT and echocardiography were included. The mean interval from AVR to the date of pannus detection was 10.5 ± 7.1 years. In the initial and follow-up CT and echocardiography, the pannus extent and echocardiographic parameters were compared using paired t-tests. The relationship between the opening angle of the prosthetic valve and the pannus extent was evaluated using Pearson correlation analysis. Results: The pannus extent was significantly increased on CT (p < 0.05). The peak velocity (3.9 ± 0.8 m/s vs. 4.2 ± 0.8 m/s, p = 0.03) and mean pressure gradient (36.4 ± 15.5 mm Hg vs. 42.1 ± 15.8 mm Hg, p = 0.03) were significantly increased. The mean opening angles of the mechanical aortic leaflets were slightly decreased, but there was no statistical significance (73.1 ± 8.3° vs. 69.4 ± 12.1°, p = 0.12). The opening angle of the prosthetic leaflets was inversely correlated with the pannus extent (r = -0.57, p < 0.001). Conclusion: The pannus extent increases over time, increasing transvalvular peak velocity and the pressure gradient. CT can be used to evaluate the pannus extent associated with hemodynamic changes that need to be managed by surgical intervention.

New Pyrene Derivatives Having Rigid Imidazole Moiety for Blue Emitters.

Pyrene, imidazole and dibenzofuran were used to synthesize new blue emitters of 1-(4-(dibenzo[b,d]furan-4-yl)phenyl)-2-(pyren-1-yl)-1H-phenanthro[9,10-d]imidazole (BFP-PI) and 1-(4-(dibenzo[b,d]furan-4-yl)phenyl)-4,5-diphenyl-2-(pyren-1-yl)-1H-imidazole (BFP-DPI). In the film state, BFP-PI and BFP-DPI show photoluminescence (PL) maximum values of 462 nm and 459 nm. The relative PL quantum efficiency (PLQY) of BFP-PI and BFP-DPI is 89.16% and 79.2% by using reference compound of 9,10-diphenylanthracene. The device using BFP-PI in the non-doped state as emitting material showed current efficiency (C.E.) of 3 cd/A and external quantum efficiency (E.Q.E.) of 2.15%, and the device using BFP-DPI as emitting material exhibited C.E. of 2.64 cd/A and E.Q.E. of 1.6%.

A Two-Photon Ratiometric Fluorescent Probe for Imaging of Hydrogen Peroxide Levels in Rat Organ Tissues.

Hydrogen peroxide (H2O2) is important in the regulation of a variety of biological processes and is involved in various diseases. Quantitative measurement of H2O2 levels at the subcellular level is important for understanding its positive and negative effects on biological processes. Herein, a two-photon ratiometric fluorescent probe (SHP-Cyto) with a boronate-based carbamate leaving group as the H2O2 reactive trigger and 6-(benzo[d]thiazol-2'-yl)-2-(N,N-dimethylamino) naphthalene (BTDAN) as the fluorophore was synthesized and examined for its ability to detect cytosolic H2O2 in situ. This probe, based on the specific reaction between boronate and H2O2, displayed a fluorescent color change (455 to 528 nm) in response to H2O2 in the presence of diverse reactive oxygen species in a physiological medium. In addition, ratiometric two-photon microscopy (TPM) images with SHP-Cyto revealed that H2O2 levels gradually increased from brain to kidney, skin, heart, lung, and then liver tissues. SHP-Cyto was successfully applied to the imaging of endogenously produced cytosolic H2O2 levels in live cells and various rat organs by using TPM.

[A Structural Equation Model of Pressure Ulcer Prevention Action in Clinical Nurses].

PURPOSE: The purpose of this study was to construct and test a structural equation model for pressure ulcer prevention action by clinical nurses. The Health Belief Model and the Theory of Planned Behavior were used as the basis for the study. METHODS: A structured questionnaire was completed by 251 clinical nurses to analyze the relationships between concepts of perceived benefits, perceived barriers, attitude, subjective norm, perceived control, intention to perform action and behavior. SPSS 22.0 and AMOS 22.0 programs were used to analyze the efficiency of the hypothesized model and calculate the direct and indirect effects of factors affecting pressure ulcer prevention action among clinical nurses. RESULTS: The model fitness statistics of the hypothetical model fitted to the recommended levels. Attitude, subjective norm and perceived control on pressure ulcer prevention action explained 64.2% for intention to perform prevention action. CONCLUSION: The major findings of this study indicate that it is essential to recognize improvement in positive attitude for pressure ulcer prevention action and a need for systematic education programs to increase perceived control for prevention action.

A small molecule two-photon fluorescent probe for intracellular sodium ions.

We report a small-molecule two-photon fluorescent probe (ANa2) for Na(+) that shows a strong TPEF enhancement in response to Na(+) and can be easily loaded into live cells and can real time monitor the fluctuation of [Na]i in live cells and living tissue at more than 100 µm depth.

Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious.

Effects of Ecklonia cava polyphenol in individuals with hypercholesterolemia: a pilot study.

We evaluated the efficacy and safety of Ecklonia cava polyphenol (Seapolynol™, a polyphenol antioxidant and anti-inflammatory agent purified from E. cava) during a 12-week treatment period (400 mg orally once daily) in individuals with hypercholesterolemia and performed subgroup analysis for metabolic syndrome (MetS). As a noncomparative study, forty-six individuals (M:F=22:24, mean age=54±11 years) with fasting total cholesterol concentration >240 mg/dL or low-density lipoprotein cholesterol (LDL-C) concentration >130 mg/dL were enrolled. Hip circumference (100±7 cm vs. 98±7 cm, P<.01), total cholesterol (244±25 mg/dL vs. 225±37 mg/dL, P<.01), LDL-C (161±24 mg/dL vs. 146±34 mg/dL, P<.01), and C-reactive protein (2.51±3.55 mg/L vs. 1.37±1.32 mg/L, P<.05) were significantly decreased without significant adverse effect. A differential assessment according to the presence [MetS(+) group, n=18] and absence [MetS(-) group, n=28] of MetS showed that Hb(A1c) decreased significantly following 12-week Seapolynol treatment in the MetS(+) compared with the MetS(-) group (-0.3%±0.5% vs. 0.1%±0.3%, P<.01). In conclusion, although our results showed that Seapolynol treatment is effective and safe without significant adverse events or abnormal laboratory findings during a 12-week period in individuals with hypercholesterolemia, more research in a larger population with a longer-term follow-up period in a randomized placebo-controlled study is needed to confirm the results.

Melanogenesis effect of Cordyceps militaris culture broth on the melanin formation of B16F0 melanoma cells.

The effect of Cordyceps militaris culture broth (CMB) on melanogenesis in B16F0 melanoma cells was evaluated by measurement of the melanin concentration after 3 days of incubation. The B16F0 melanoma cells were treated with various concentrations of CMB 10-100 µg/mL and arbutin of 200 µM. Phenolic content and antioxidant activity of CMB were also measured. Phenolic content of CMB was 3.28 mg/g. The DPPH radical scavenging and ferric ion donating activities were 79.64% and 0.16, respectively. The melanin concentration and cell viability of melanoma cells by arbutin treatment decreased to 43% and 91% of the control, respectively. The CMB treatment showed a significant inhibitory effect of melanin production by 29%, 50%, and 56% at 50, 80, and 100 µg/mL concentration treatment, respectively, while over 90% of cells were viable. The CMB treatment at 50, 80, and 100 µg/mL concentrations in cultivation decreased extracellular melanin release induced by 3-isobutyl-1-methylxanthine (IBMX) treatment by 19%, 38%, and 48%, respectively. The CMB showed inhibitory activity against intracellular tyrosinase extracted from melanoma cells, while it had no inhibition on the activity of mushroom tyrosinase. The cellular glutathione contents were enhanced by CMB treatment in a concentration-dependent manner. These results suggested that CMB suppressed cellular tyrosinase activity and total melanin content in cultured B16F0 melanoma cells without any significant effects on cell proliferation and it might be candidate anti-melanogenic agent.