Effect of the glyceryl monooleate-based lyotropic phases on skin permeation using in vitro diffusion and skin imaging

AbstractGlyceryl monooleate (GMO) is a polar lipid that can exist in various liquid crystalline phases in the presence of different amounts of water. It is regarded as a permeation enhancer due to its amphiphilic property. Various phases of GMO/solvent system containing sodium fluorescein were prepared to compare permeability using confocal laser scanning microscopy (CLSM). GMO was melted in a vial in a water bath heated to 45 °C. Propylene glycol and hexanediol were homogeneously dissolved in the melted GMO. Sodium fluorescein in aqueous solution was diluted to various ratios and thoroughly mixed by an ultrasonic homogenizer. Each GMO/Solvent system with fluorescein was applied onto the epidermal side of excised pig skin and incubated overnight. CLSM was performed to observe how the GMO/solvent system in its different phases affect skin permeability. Cubic and lamellar phase formulations enhanced the fluorescein permeation through the stratum corneum. A solution system had the weakest permeability compared to the other two phases. Due to the amphiphilic nature of GMO, cubic and lamellar phases might reduce the barrier function of stratum corneum which was observed by CLSM as fluorescein accumulated in the dermis. Based on the results, the glyceryl monooleate lyotropic mixtures could be applied to enhance skin permeation in various topical and transdermal formulations

A differential risk assessment and decision model for Transarterial chemoembolization in hepatocellular carcinoma based on hepatic function

Background The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. Methods A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). Results Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system (ASAR). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570–0.871) in the derivation, 0.700 (95% CI = 0.445–0.905) in the internal validation, and 0.680 (95% CI = 0.652–0.707) in the external validation, respectively. Patients with ASAR< 4 showed significantly longer OS than patients with ASAR≥4 in all three datasets (all P < 0.001). Among Child-Pugh class B patients, a modified model without TACE response, i.e., ASA(R), discriminated OS with a c-index of 0.788 (95% CI, 0.703–0.876) in the derivation, and 0.745 (95% CI, 0.646–0.862) in the internal validation, and 0.670 (95% CI, 0.605–0.725) in the external validation, respectively. Child-Pugh B patients with ASA(R) < 4 showed significantly longer OS than patients with ASA(R) ≥ 4 in all three datasets (all P < 0.001). Conclusions ASAR provides refined prognostication for repetition of TACE in patients with unresectable HCC. For Child-Pugh class B patients, a modified model with baseline factors might guide TACE initiation

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Diagnostic Accuracy of Magnetic Resonance Imaging for Sagittal Cervical Spine Alignment: A Retrospective Cohort Study

(1) Background: Although radiography performed on the subject in an upright position is considered the standard method for assessing sagittal cervical alignment, it is frequently determined, or reported, based on MRI performed on the subject in a supine position. (2) Methods: Cervical alignment observed in both imaging modalities was assessed using four methods: the C2-7 Cobb angle, the absolute rotation angle (ARA), Borden&rsquo;s method, and the sagittal vertical axis (SVA). Cervical alignment was determined (lordosis, kyphosis, and straight) based on radiography. Then, the diagnostic cut-off values for the MRI images and their corresponding diagnostic accuracies were assessed. (3) Results: The analysis included 142 outpatients. The determined diagnostic cut-off values for lordosis, using three measurements (Cobb angle, ARA, and Borden&rsquo;s method), were &minus;8.5&deg;, &minus;12.5&deg;, and 3.5 mm, respectively, and the cut-off values for kyphosis were &minus;4.5&deg;, 0.5&deg;, and &minus;1.5 mm, respectively. The cut-off value for SVA &gt; 40 mm was 19.5 mm. The Cobb angle, ARA, and Borden&rsquo;s method, on MRI, showed high negative predictive values for determining kyphosis. The SVA on MRI measurements also showed high negative predictive values for determining &gt;40 mm. (4) Conclusions: MRI measurements may be predictive of cervical alignment, especially for the exclusion of kyphosis and SVA &gt; 40 mm. However, caution is needed in the other determinations using MRI, as their accuracies are limited

Association between Sagittal Cervical Spinal Alignment and Degenerative Cervical Spondylosis: A Retrospective Study Using a New Scoring System

(1) Background: Prolonged neck flexion is thought to cause harmful loading on the cervical spine. Along with the degenerative process, cervical alignment tends to change toward lordotic curvature. The association between cervical alignment and cervical spondylosis remains unclear. (2) Methods: Three raters retrospectively assessed cervical radiographies of outpatients at a tertiary center in 2019 using degenerative cervical spondylosis score (DCS score; a newly developed scoring system), C2-7 absolute rotational angle (ARA), and C2-7 sagittal vertical axis (SVA). (3) Results: A total of 561 patients were included in the analysis. Multiple regression analysis with adjustments for age and sex revealed that C2-7 ARA, rather than SVA, was a significant parameter for degenerative spondylosis. The interaction between age and C2-7 ARA was significant, indicating that the increase in DCS score with increasing age was more pronounced in patients with kyphotic cervical alignment. The direct effect of age on DCS score was 0.349 (95% CI 0.319 to 0.380, p p < 0.001). (4) Conclusions: C2-7 ARA was significantly associated with DCS after adjustment for both age and sex. Subjects with more kyphotic cervical alignment showed a greater correlation between increased DCS score and older age

Association between Sagittal Cervical Spinal Alignment and Degenerative Cervical Spondylosis: A Retrospective Study Using a New Scoring System

(1) Background: Prolonged neck flexion is thought to cause harmful loading on the cervical spine. Along with the degenerative process, cervical alignment tends to change toward lordotic curvature. The association between cervical alignment and cervical spondylosis remains unclear. (2) Methods: Three raters retrospectively assessed cervical radiographies of outpatients at a tertiary center in 2019 using degenerative cervical spondylosis score (DCS score; a newly developed scoring system), C2-7 absolute rotational angle (ARA), and C2-7 sagittal vertical axis (SVA). (3) Results: A total of 561 patients were included in the analysis. Multiple regression analysis with adjustments for age and sex revealed that C2-7 ARA, rather than SVA, was a significant parameter for degenerative spondylosis. The interaction between age and C2-7 ARA was significant, indicating that the increase in DCS score with increasing age was more pronounced in patients with kyphotic cervical alignment. The direct effect of age on DCS score was 0.349 (95% CI 0.319 to 0.380, p &lt; 0.001) and the proportion of the mediation effect of C2-7 ARA was &minus;0.125 (p &lt; 0.001). (4) Conclusions: C2-7 ARA was significantly associated with DCS after adjustment for both age and sex. Subjects with more kyphotic cervical alignment showed a greater correlation between increased DCS score and older age