Reflectance confocal microscopy for noninvasive examination of nonmelanocytic tumors and virus‐associated skin lesions in organ transplant recipients

Background: Drug-induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus-associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. Materials and methods: A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. Results: For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I + II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. Conclusion: Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus-associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post-transplantation, larger cohorts of patients are required to confirm and consolidate these findings

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy

Background: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. Methods: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase) and immediately after intravenous application of the chemotherapy (T1). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength-tunable diode laser-based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. Results: Healthy subjects showed significantly (P <.001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase. An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. Conclusion: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co-medication. © 2020 The Authors. Skin Research and Technology Published by John Wiley & Sons Ltd

Recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB for localized bone regeneration. Histologic and radiographic outcomes of a rabbit study

OBJECTIVES: Improvement in localized bone regeneration is needed to avoid the use of autogenous tissue. For that purpose, the use biologic mediators was proposed. The aim was to test whether or not one of two biologic mediators, recombinant human bone morphogenetic protein-2 (rhBMP-2) or recombinant platelet-derived growth factor (rhPDGF-BB), is superior to the other and to control groups for localized bone regeneration. MATERIALS AND METHODS: Four cylinders (height: 5 mm; diameter: 7 mm) were screwed on the parietal and frontal bones at the cranium in 12 rabbits. The cylinders either received (i) deproteinized bovine bone mineral (DBBM) mixed rhBMP-2 (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB (DBBM/PDGF), (iii) DBBM (DBBM), and (iv) empty control (control). Rabbits were euthanized at 2 and 8 weeks (n = 6, respectively). Conventional histomorphometric and micro-CT analyses were performed. Parametric linear mixed models were applied for the analyses with Bonferroni correction for the multiple group comparisons. RESULTS: The area of bone regeneration (histology; AAHisto ) at 2 weeks peaked for DBBM (41.91%) with statistically significantly greater values compared to DBBM/PDGF and the control group (P < 0.05). At 8 weeks, mean AAHisto values were 96.29% (DBBM/BMP-2), 46.37% (DBBM/PDFG), 39.66% (DBBM), and 35.98% (control) (DBBM/BMP-2 vs. all groups (P < 0.05)). At 8 weeks, bone regeneration was greatest for DBBM/BMP-2 (35.62%) with statistically significant differences compared to all other groups (P < 0.05). The area of bone regeneration (micro-CT; AAm-CT ) at 2 weeks amounted to 43.87% (DBBM/BMP-2), 42.81% (DBBM/PDFG), 48.71% (DBBM), and 0.96% (control). The control group demonstrated statistically significantly less AAm-CT compared to all groups (P < 0.05). At 8 weeks, mean AAm-CT values were 63.65% (DBBM/BMP-2), 50.21% (DBBM/PDFG), 44.81% (DBBM), and 4.57% (control) (P > 0.05). CONCLUSIONS: The use of rhBMP-2 significantly enhanced bone regeneration compared to all other groups including the group with rhPDGF-BB

Barriers to Outpatient Hospital-Based Cardiac Rehabilitation in Korean Patients With Acute Coronary Syndrome

ObjectiveTo investigate factors associated with enrollment and participation in cardiac rehabilitation (CR) in Korea.MethodsPatients admitted to four university hospitals with acute coronary syndrome between June 2014 and May 2016 were enrolled. The Cardiac Rehabilitation Barriers Scale (CRBS) made of 21-item questionnaire and divided in four subdomains was administered during admission. CRBS items used a 5-point Likert scale and ≥2.5 was considered as a barrier. Differences between CR non-attender and CR attender, or CR non-enroller and CR enroller in subscale and each items of CRBS were examined using the chi-square test.ResultsThe CR participation rate in four hospitals was 31% (170 of the 552). Logistical factors (odds ratio [OR]=7.61; 95% confidence interval [CI], 4.62–12.55) and comorbidities/functional status (OR=6.60; 95% CI, 3.95–11.01) were identified as a barrier to CR enrollment in the subdomain analysis. Among patients who were enrolled (agreed to participate in CR during admission), only work/time conflict was a significant barrier to CR participation (OR=2.17; 95% CI, 1.29–3.66).ConclusionDiverse barriers to CR participation were identified in patients with acute coronary syndrome. Providing the tailored model for CR according to the individual patient's barrier could improve the CR utilization. Further multicenter study with large sample size including other CR indication is required

Air-stable van der Waals PtTe2 conductors with high current-carrying capacity and strong spin- orbit interaction

High-performance van der Waals (vdW) integrated electronics and spintronics require reliable current-carrying capacity. However, it is challenging to achieve high current density and air-stable performance using vdW metals owing to the fast electrical breakdown triggered by defects or oxidation. Here, we report that spin-orbit interacted synthetic PtTe2 layers exhibit significant electrical reliability and robustness in ambient air. The 4-nm-thick PtTe2 synthesized at a low temperature (similar to 400 degrees C) shows intrinsic metallic transport behavior and a weak antilocalization effect attributed to the strong spin-orbit scattering. Remarkably, PtTe2 sustains a high current density approaching approximate to 31.5 MA cm(-2), which is the highest value among electrical interconnect candidates under oxygen exposure. Electrical failure is caused by the Joule heating of PtTe2 rather than defect-induced electromigration, which was achievable by the native TeOx passivation. The high-quality growth of PtTe2 and the investigation of its transport behaviors lay out essential foundations for the development of emerging vdW spin-orbitronics

Korean Version of the Longer-Term Unmet Needs After Stroke Questionnaire

Objective To translate the 22-item Longer-term Unmet Needs after Stroke (LUNS) questionnaire, validate it in the Korean stroke population, and assess the reliability of face-to-face and telephone surveys. Methods Sixty-six adult patients with stroke from Seoul National University Bundang Hospital and Kangwon National University Hospital were involved in the validation. Participants were interviewed twice using the LUNS Korean version: first, a face-to-face survey for validation, and second, a telephone survey for test-retest reliability. Participants completed the Frenchay Activities Index (FAI) and Short Form 12 (SF-12) Mental and Physical Component Summary (MCS and PCS) scores at the first interview. For concurrent validity, the differences in health status (FAI, SF-12 MCS and PCS) between the groups that reported unmet needs and those that did not were analyzed for each item. Cohen’s kappa and percentage of agreement between the first and second administrations were calculated for each item to determine the test-retest reliability. Results The average age of the participants was 61.2±12.8 years and 74.2% were male. Fifty-seven patients were involved in the second interview. Depending on the unmet needs, SF-12 MCS, PCS, and FAI were significantly different in 12 of 22 items. In the test-retest reliability test, 12 items had a kappa of 0.6 or higher, and two had a kappa of <0.4. Conclusion The LUNS instrument into Korean (LUNS-K) is a reliable and valid instrument for assessing unmet health needs in patients with stroke. In addition, telephone surveys can be considered reliable

In vivo Skin Penetration, Radical Protection, and Structural Changes after Topical Application of a Herbal Oil Cream Compared to Topical Calcipotriol in Mild to Moderate Psoriasis

Background: The chronicity of psoriasis often requires continuous topical treatment. Materials and Methods: Here, the radical protection of a cream containing various herbal oils was evaluated in vivo by electron paramagnetic resonance (EPR) spectroscopy and its skin penetration by Raman microscopy in intact and barrier-disturbed skin. Changes in skin barrier properties were evaluated after 4 weeks of daily topical application using in vivo laser scanning microscopy (LSM) and transepidermal water loss in 26 healthy volunteers. A randomized, controlled, double-blind, three-arm parallel clinical study evaluated the efficacy of the herbal oil cream compared to a 0.05% calcipotriol-containing cream and to a vehicle cream, in 135 patients with mild to moderate plaque psoriasis with the change in Psoriasis Area and Severity Index (PASI) from baseline to week 12 as the primary endpoint. Results: EPR spectroscopy disclosed a significantly higher radical formation in untreated than skin treated with the herbal oil cream (p ≤ 0.05). LSM measurements indicated a protective skin barrier effect in treated compared to untreated skin. In the clinical trial, the topical application of herbal oils showed a significant reduction of the PASI score compared to topical calcipotriol at week 12 (p = 0.016). The mean reduction in PASI was 49% for the herbal oil cream, 38% for calcipotriol, and 55% for the vehicle cream. The percentage of patients, who reached PASI 50 and 75 at any time point, was 55.9% and 29.4% for the herbal oil cream, 47.4% and 15.8% for calcipotriol, and 23 (60.5%) and 13 (34.2%) for the vehicle, respectively (p > 0.05). The vehicle, originally designed as a placebo, contained a main ingredient of the herbal oil cream and therefore showed corresponding results. Conclusion: The herbal oil cream demonstrated effectiveness in the treatment of mild to moderate plaque psoriasis

In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy

Background: Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. Methods: Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase) and immediately after intravenous application of the chemotherapy (T1). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength‐tunable diode laser‐based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. Results: Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase. An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. Conclusion: The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co‐medication

The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasomemediated degradation of PPAR gamma

Peroxisome proliferator-activated receptor gamma (PPAR??) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPAR?? is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPAR??, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPAR??, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPAR??. The stable expression of TRIM25 reduced PPAR?? protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPAR?? protein levels and stimulated adipocyte differentiation. Furthermore, TRIM25-knockout mouse embryonic fibroblasts (MEFs) exhibited an increased adipocyte differentiation capability compared with wild-type MEFs. Taken together, these data indicate that TRIM25 is a novel E3 ubiquitin ligase of PPAR?? and that TRIM25 is a novel target for PPAR??-associated metabolic diseases