Inhibition of late sodium current via PI3K/Akt signaling prevents cellular remodeling in tachypacing-induced HL-1 atrial myocytes.

An aberrant late sodium current (INa,Late) caused by a mutation in the cardiac sodium channel (Nav1.5) has emerged as a contributor to electrical remodeling that causes susceptibility to atrial fibrillation (AF). Although downregulation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with AF, the molecular mechanisms underlying the negative regulation of INa,Late in AF remain unclear, and potential therapeutic approaches are needed. In this work, we constructed a tachypacing-induced cellular model of AF by exposing HL-1 myocytes to rapid electrical stimulation (1.5 V/cm, 4 ms, 10 Hz) for 6 h. Then, we gathered data using confocal Ca2+ imaging, immunofluorescence, patch-clamp recordings, and immunoblots. The tachypacing cells displayed irregular Ca2+ release, delayed afterdepolarization, prolonged action potential duration, and reduced PI3K/Akt signaling compared with controls. Those detrimental effects were related to increased INa,Late and were significantly mediated by treatment with the INa,Late blocker ranolazine. Furthermore, decreased PI3K/Akt signaling via PI3K inhibition increased INa,Late and subsequent aberrant myocyte excitability, which were abolished by INa,Late inhibition, suggesting that PI3K/Akt signaling is responsible for regulating pathogenic INa,Late. These results indicate that PI3K/Akt signaling is critical for regulating INa,Late and electrical remodeling, supporting the use of PI3K/Akt-mediated INa,Late as a therapeutic target for AF.

Production of Tyrian purple indigoid dye from tryptophan in Escherichia coli.

Tyrian purple, mainly composed of 6,6'-dibromoindigo (6BrIG), is an ancient dye extracted from sea snails and was recently demonstrated as a biocompatible semiconductor material. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and the difficulty of regiospecific bromination. Here, we introduce an effective 6BrIG production strategy in Escherichia coli using tryptophan 6-halogenase SttH, tryptophanase TnaA and flavin-containing monooxygenase MaFMO. Since tryptophan halogenases are expressed in highly insoluble forms in E. coli, a flavin reductase (Fre) that regenerates FADH2 for the halogenase reaction was used as an N-terminal soluble tag of SttH. A consecutive two-cell reaction system was designed to overproduce regiospecifically brominated precursors of 6BrIG by spatiotemporal separation of bromination and bromotryptophan degradation. These approaches led to 315.0 mg l-1 6BrIG production from tryptophan and successful synthesis of regiospecifically dihalogenated indigos. Furthermore, it was demonstrated that 6BrIG overproducing cells can be directly used as a bacterial dye.

Multi-MicroRNA Analysis Can Improve the Diagnostic Performance of Mammography in Determining Breast Cancer Risk.

The objective of this study was to determine whether multi-microRNA analysis using a combination of four microRNA biomarkers (miR-1246, 202, 21, and 219B) could improve the diagnostic performance of mammography in determining breast cancer risk by age group (under 50 vs. over 50) and distinguish breast cancer from benign breast diseases and other cancers (thyroid, colon, stomach, lung, liver, and cervix cancers). To verify breast cancer classification performance of the four miRNA biomarkers and whether the model providing breast cancer risk score could distinguish between benign breast disease and other cancers, the model was verified using nonlinear support vector machine (SVM) and generalized linear model (GLM) and age and four miRNA qRT-PCR analysis values (dCt) were input to these models. Breast cancer risk scores for each Breast Imaging-Reporting and Data System (BI-RADS) category in multi-microRNA analysis were analyzed to examine the correlation between breast cancer risk scores and mammography categories. We generated two models using two classification algorithms, SVM and GLM, with a combination of four miRNA biomarkers showing high performance and sensitivities of 84.5% and 82.1%, a specificity of 85%, and areas under the curve (AUCs) of 0.967 and 0.965, respectively, which showed consistent performance across all stages of breast cancer and patient ages. The results of this study showed that this multi-microRNA analysis using the four miRNA biomarkers was effective in classifying breast cancer in patients under the age of 50, which is challenging to accurately diagnose. In addition, breast cancer and benign breast diseases can be classified, showing the possibility of helping with diagnosis by mammography. Verification of the performance of the four miRNA biomarkers confirmed that multi-microRNA analysis could be used as a new breast cancer screening aid to improve the accuracy of mammography. However, many factors must be considered for clinical use. Further validation with an appropriate screening population in large clinical trials is required. This trial is registered with (KNUCH 2022-04-036).

Risk of Subsequent Events in Patients With Minor Ischemic Stroke or High-Risk Transient Ischemic Attack.

This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.

Risk of Periprosthetic Joint Infection in Patients With Total Knee Arthroplasty Undergoing Colonoscopy: A Nationwide Propensity Score Matched Study.

BACKGROUND: The post-colonoscopy periprosthetic joint infection (PJI) risk in patients with total prosthetic knee joints has limited research. The present study investigated the PJI risk and determined the risk factors for post-colonoscopy PJI in total knee arthroplasty (TKA) recipients. The hypothesis was that colonoscopy is associated with an increased PJI risk in patients with total prosthetic knee joints. This study can potentially help guide the decision making for prophylactic antibiotic use for colonoscopy. METHODS: This nationwide matched cohort study used claims data from the Health Insurance Review and Assessment Service database and enrolled patients who underwent unilateral TKA between 2008 and 2016. The history of diagnostic colonoscopy was investigated at least 1 year postoperatively. The propensity score was matched between colonoscopy and non-colonoscopy cohorts, and the post-colonoscopy PJI risk was compared. The PJI risk following invasive colonoscopic procedures, including biopsy, polypectomy, and mucosal or submucosal resection, was investigated, and the risk factors for post-colonoscopy PJI were determined. RESULTS: In total, 45,612 and 211,841 patients were matched in the colonoscopy and control cohorts, respectively. The colonoscopy cohort had greater 9-month and 1-year PJI risks from the index colonoscopy date than the matched controls (9 months: hazard ratio [HR] 1.836, P = .006; 1 year: HR 1.822, P = .031). Invasive colonoscopic procedures did not increase the PJI risk at any time point post-colonoscopy. The only significant risk factor for PJI was post-traumatic arthritis (adjusted HR 4.034, P = .023). CONCLUSION: Colonoscopy was associated with an increased PJI risk in TKA recipients, regardless of concomitant invasive colonoscopic procedures. LEVEL OF EVIDENCE: III, Prognostic.

Whole blood RNA sequencing reveals a differential transcriptomic profile associated with cervical insufficiency: a pilot study.

BACKGROUND: The uterine cervix is a mechanical and immunological barrier against ascending infection during pregnancy. Cervical insufficiency (CI), a painless cervical dilation that occurs in the mid-trimester, is an important cause of extremely preterm birth. We hypothesized that women with CI have a differential transcriptomic profile. Therefore, we compared the transcriptomic profile of peripheral blood in women with CI and that of controls. METHODS: RNA sequencing was used to generate the global gene expression profiles of 11 women with CI and 4 controls, and differential expression analysis was performed to identify genes showing significant expression changes between the CI (n = 11) and control (n = 4) groups as well as between the CI-preterm (n = 7) and CI-term (n = 4) groups. Gene set enrichment was assessed in terms of Gene Ontology processes, and a subset of differentially expressed genes in CI was validated in a different sample-set by qRT-PCR and ELISA. RESULTS: Thirty genes were differentially expressed between the CI and control groups. Differentially upregulated genes in the CI group included neutrophil-mediated immunity-associated (DEFA3 and ELANE) and bicarbonate transport-related genes. The serum concentration of alpha defensin 3 was significantly higher in women with CI than in controls (P = 0.014). Analysis of differential gene expression according to pregnancy outcomes revealed 338 differentially expressed genes between the CI-term and CI-preterm groups. Immune and defense response to organism-associated genes and influenza A and NOD-like receptor signaling pathways were upregulated in the CI-term group. CONCLUSIONS: Our results revealed significant differences in the whole blood transcriptomic profiles of women with CI compared to those of controls. Different immune responses in women with CI may affect pregnancy outcomes.

Comparison of refractive outcomes after photorefractive keratectomy with different optical zones using Mel 90 excimer laser.

BACKGROUND: A larger optical zone for photorefractive keratectomy may improve optical quality and stability. However, there is need for limiting ablation diameter in that a larger ablation diameter requires greater ablation depth, and minimizing ablation depth may reduce adverse effects on postoperative wound healing, haze and keratoectasia. In this study, we compared the changes in clinical outcomes and the degree of regression between a 6.0 mm optical zone and 6.5 mm optical zone following PRK. METHODS: The records of 95 eyes that had undergone PRK with a 6.0 OZ (n = 40) and a 6.5 OZ (n = 55) were retrospectively reviewed. We compared data including the spherical equivalent of manifest refraction (SE of MR), simulated K (Sim K), thinnest corneal thickness, change in thinnest corneal thickness (the initial value divided by corrected diopter [ΔTCT/CD]), Q value, corneal higher order aberrations (HOAs) and spherical aberration (SA) pre-operation, at 3 and 6 months postoperative and at the last follow-up visit (Mean; 20.71 ± 10.52, 17.47 ± 6.57 months in the 6.0 and 6.5 OZ group, respectively). RESULTS: There were no significant differences in the SE of MR, Sim K and UDVA between the 6.0 OZ group and the 6.5 OZ group over 1 year of follow-up after PRK, and the 6.0 OZ group required less ΔTCT/CD than the 6.5 OZ group. The 6.5 OZ group showed better results in terms of post-operative HOAs of RMS, SA and Q value. When comparing that pattern of change in Sim K, there was no significant difference between the 6.0 OZ group and the 6.5 OZ group. CONCLUSIONS: The clinical refractive outcomes and regression after PRK using Mel 90 excimer laser with a 6.0 OZ were comparable to those with a 6.5 OZ.

Flow Behaviors of Polymer Colloids and Curing Resins Affect Pore Diameters and Heights of Periodic Porous Polymer Films to Direct Their Surface and Optical Characteristics.

Manipulation of both pore diameters and heights of two-dimensional periodic porous polymer films is important to extensively control their characteristics. However, except for using different sized colloid templates in replication methods, an effective method that tunes these factors has rarely been reported. We found that both parameters are controllable by adjusting the flow behaviors of polystyrene colloids and curing resin precursors during the preparation of phenolic resin and poly(dimethylsiloxane) periodic porous films by embedding their precursors into colloidal crystal monolayers. We adjust the flow behaviors by either varying film preparation temperatures (≥glass transition temperature of polystyrene) or using the precursors mixed with different amounts of solvents that renders the colloids viscous. Consequently, the pore diameters and film heights change by 36-56 and 56-84%, respectively. Such modulation results in the change in height to diameter ratios and the areal fractions of resins at air-film interfaces, thereby significantly changing the water contact angles on these surfaces and their photonic characteristics. This straightforward method does not require additional steps, differently sized colloids, or different amounts of precursors for these parameter controls.

Predictors of Left Ventricular Functional Recovery and Their Impact on Clinical Outcomes in Patients With Newly Diagnosed Dilated Cardiomyopathy and Heart Failure.

BACKGROUND: To identify the predictors of left ventricular functional recovery (LVFR) and its impacts on clinical outcomes in acute heart failure (AHF) patients with newly diagnosed dilated cardiomyopathy (DCM). METHODS: A total of 175 consecutive patients with newly diagnosed DCM and AHF were divided into two groups according to LVFR on FU echocardiography; the recovered group (n=54, 54.3±18.5years, 31 males) vs. the non-recovered group (n=121, 60.5±15.1years, 79 males). Clinical, laboratory, and echocardiographic findings were compared, and major adverse cardiac and cerebrovascular events (MACCE) including death, rehospitalisation, and stroke were analysed. RESULTS: Left ventricular function (LV) was normalised in 54 patients (30.8%) on follow-up echocardiography. The change in the level of N-terminal pro-B-type natriuretic peptide (ΔNT-proBNP) between initial presentation and discharge >1633.5pg/mL was an independent predictor of LVFR, whereas diabetes and LV end-systolic diameter >50mm were negative predictors of LVFR on multivariate analysis. During five years of clinical follow-up, MACCE developed in 91 patients: 58 deaths, 29 rehospitalisations, and 4 strokes. On multivariate analysis, baseline LVEF <30% and no LVFR were independent predictors of MACCE. CONCLUSION: Left ventricular functional recovery was not uncommon in newly diagnosed DCM with AHF. The changes in NT-proBNP level during hospitalisation, diabetes, and larger initial LV size were independent predictors of LVFR, and LVFR was an independent predictor of future MACCE. Serial monitoring of NT-proBNP and LV function would be useful in the risk stratification of newly diagnosed DCM with AHF.

Nanoscale Structural Switching of Plasmonic Nanograin Layers on Hydrogel Colloidal Monolayers for Highly Sensitive and Dynamic SERS in Water with Areal Signal Reproducibility.

Developing substrates that enable both reproducible and highly sensitive Raman detection of trace amounts of molecules in aqueous systems remains a challenge, although these substrates are crucial in biomedicine and environmental sciences. To address this issue, we report spatially uniform plasmonic nanowrinkles formed by intimate contact between plasmonic nanograins on the surface of colloidal crystal monolayers. The Au or Ag nanograin layers coated on hydrogel colloidal crystal monolayers can reversibly wrinkle and unwrinkle according to changes in the water temperature. The reversible switches are directed by surface structural changes in the colloidal crystal monolayers, while the colloids repeat the hydration-dehydration process. The Au and Ag nanowrinkles are obtained upon hydration, thus enabling the highly reproducible detection of Raman probes in water at the nano- and picomolar levels, respectively, throughout the entire substrate area. Additionally, the reversible switching of the nanostructures in the plasmonic nanograin layers causes reversible dynamic changes in the corresponding Raman signals upon varying the water temperature.

A Surfactant-Free and Shape-Controlled Synthesis of Nonspherical Janus Particles with Thermally Tunable Amphiphilicity.

A surfactant-free approach is proposed to synthesize nonspherical Janus particles with temperature-dependent wettability on hydrophobic surfaces. Sub-micrometer-sized particles comprising poly(styrene-co-divinylbenzene) core and a thermally responsive poly(N-isopropylacrylamide-co-methacrylic acid) shell are first synthesized to stabilize styrene droplets in water, producing a Pickering emulsion. Upon heating to 80 °C and subsequent addition of initiators to the aqueous phase, styrene droplets are polymerized and combine with the core-shell particles to construct dumbbell-shaped nonspherical particles. The shape of the nonspherical particles is controllable by adjusting the equilibrium time of the Pickering emulsion at 80 °C, which is conducted prior to polymerization. The mechanism of formation is discussed in more detail. Since molecular surfactants or stabilizers are not used during the synthesis, the present nonspherical particles well exhibit their own temperature-dependent amphiphilic characteristics. The aqueous dispersion containing the dumbbell-shaped particles alters its wettability on hydrophobic polymer surfaces according to temperature changes, demonstrating its temperature-dependent amphiphilicity change.

NOX1/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis.

Periodontal diseases are infectious polymicrobial inflammatory diseases that lead to destruction of the periodontal ligament, gingiva, and alveolar bone. Sequential colonization of a broad range of bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, is an important phenomenon in this disease model. F. nucleatum is a facultative anaerobic species thought to be a key mediator of dental plaque maturation due to its extensive coaggregation with other oral bacteria, while P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting various virulence factors. The formation of a bacterial complex by these two species is central to the pathogenesis of periodontal disease. Reactive oxygen species (ROS) are produced during bacterial infections and are involved in intracellular signaling. However, the impact of oral bacteria-induced ROS on the ecology of F. nucleatum and P. gingivalis has yet to be clarified. In the present study, we investigated ROS production induced in primary human oral cells by F. nucleatum and P. gingivalis and its effect on the formation of their bacterial complexes and further host cell apoptosis. We found that in primary human gingival fibroblasts (GFs), two NADPH oxidase isoforms, NOX1 and NOX2, were activated in response to F. nucleatum infection but not P. gingivalis infection. Accordingly, increased NADPH oxidase activity and production of superoxide anion were observed in GFs after F. nucleatum infection, but not after P. gingivalis infection. Interestingly, in NOX1, NOX2, or NOX1/NOX2 knockdown cells, the number of P. gingivalis decreased when the cells were coinfected with F. nucleatum. A similar pattern of host cell apoptosis was observed. This implies that F. nucleatum contributes to attachment of P. gingivalis by triggering activation of NADPH oxidase in host cells, which may provide an environment more favorable to strict anaerobic bacteria and have a subsequent effect on apoptosis of host cells.

Use of fluorescence signals generated by elastic scattering under monochromatic incident light for determining the scattering efficiencies of various plasmonic nanoparticles.

We present a route that estimates the scattering/absorption characteristics of plasmonic nanoparticles by using fluorescence and UV-visible spectroscopy. Because elastic scattering of nanoparticles caused by a monochromatic incident light is reflected in fluorescence emission spectra when recording at the excitation wavelength, the scattering intensities at the excitation wavelength during fluorescence emission scans are used to compare the scattering characteristics of various plasmonic nanoparticles under conditions where the extinction values of all of the nanoparticles are kept constant at this wavelength. For the two excitation wavelengths (519 and 560 nm) we investigated, the scattering intensities of spherical gold nanoparticles increase with increasing size (15, 33, 51, 73, and 103 nm in diameter). These results are correlated with the nanoparticles' scattering efficiencies (the ratios of scattering to the extinction cross-sections), which are theoretically calculated in the literature using Mie theory. Then, linear calibration equations at each wavelength are derived to estimate the scattering efficiencies of two Au nanorods, Au nanocages, and spherical Ag nanoparticles (15, 25, 37, and 62 nm). The values are very comparable with literature values. For various purposes such as biomedicine and optoelectronics, the present method could be beneficial to those who wish to easily compare and determine the scattering characteristics of various plasmonic nanoparticles at a certain wavelength by using commercially-available spectroscopic techniques.

Use of a uniconcave balloon in emergency cerclage.

Pushing bulging fetal membranes back into the uterine cavity effectively without rupture of fetal membranes during emergency cerclage is a concern to obstetricians. We have developed a new uniconcave balloon device for repositioning fetal membranes into the uterus during emergency cerclage. Our technique can be accomplished easily with few complications.

Rapid Retinal Nerve Fiber Layer Thinning in the Unaffected Contralateral Eyes of Patients with Unilateral Normal-Tension Glaucoma: A Retrospective Observational Study.

PURPOSE: To observe the rate of progressive retinal nerve fiber layer (RNFL) thinning in the unaffected eyes of patients with unilateral normal-tension glaucoma (NTG), in comparison with that of healthy subjects, and to identify the factors associated with progressive RNFL thinning. DESIGN: Retrospective, longitudinal, observational study. PARTICIPANTS: Ninety-five patients with unilateral NTG and 61 healthy controls. METHODS: This study included unilateral NTG and healthy control subjects who were followed up for longer than 4 years and in whom at least 5 reliable retinal nerve fiber layer thickness (RNFLT) measurements were performed using OCT. Factors associated with the rate of thinning of the unaffected eyes of unilateral patients with NTG were identified using regression analysis. MAIN OUTCOME MEASURES: The rate of progressive RNFL thinning and the associated factors. RESULTS: Retinal nerve fiber layer thickness decreased significantly in both the unaffected eyes of unilateral patients with NTG and the healthy eyes (both P < 0.001). The RNFL thinning was significantly faster in the unaffected eyes of unilateral patients with NTG than in the healthy eyes (P < 0.001), specifically in the temporal-inferior (TI) sector (P = 0.003). Factors associated with faster RNFL thinning in the unaffected eyes of unilateral patients with NTG were thicker baseline RNFL of the unaffected eyes (P = 0.002) and a worse visual field (VF) mean deviation (MD) in the NTG eyes (P = 0.040). In the healthy controls, the rate of RNFL thinning in the contralateral eyes was the only factor associated with faster thinning (P = 0.007). CONCLUSIONS: The unaffected eyes of unilateral patients with NTG showed faster RNFL thinning than healthy control eyes, more obviously in the TI sector, and were likely to progress faster when they had a thicker baseline RNFL, and when the NTG eyes had a worse VF MD. In unilateral patients with NTG, initiation of prophylactic treatment could be considered for the unaffected eyes when they are accompanied by a risk of developing glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice.

Purpose: Anti-obesity medications (AOMs), along with lifestyle interventions, are effective means of inducing and maintaining weight loss in patients with obesity. Although the efficacy of AOMs has been reported, there have been no direct comparisons of these drugs. Therefore, in the present study, we aimed to compare the efficacy of all the AOMs available in Korea in a real-world setting. Patients and Methods: The body weight and composition of 205 adults treated with phentermine, phentermine/topiramate, liraglutide, naltrexone/bupropion, lorcaserin, or orlistat for at least 6 months were analyzed at 2 month intervals. The prevalence of the achievement of a ≥5% weight loss and the changes in body composition were compared between participants using each AOM at each visit. Results: A total of 132 (64.4%) participants achieved ≥5% weight loss within 6 months (prevalence of ≥5% weight loss after 6 months: phentermine, 87.2%; phentermine/topiramate, 67.7%; liraglutide, 58.1%; naltrexone/bupropion, 35.3%; lorcaserin, 75%; orlistat, 50%). At each visit, after adjustment for age, sex, and baseline body weight, phentermine use was associated with a significantly higher prevalence of ≥5% weight loss than the use of the other AOMs, except for liraglutide. There were significant differences in the body weight, body mass index and body fat mass among the AOM groups by visit (P for interaction <0.05), but not in their waist circumference, skeletal muscle mass, percentage body fat, or visceral fat area. Conclusion: All the AOMs were effective at inducing and maintaining weight loss, in the absence of significant changes in muscle mass, over a 6 month period, and the short-term use of phentermine and the long-term use of phentermine/topiramate or liraglutide would be practical choices for the treatment of obesity. However, further, large-scale studies are necessary to confirm these findings.

Prevalence, Risk Factors, and Postoperative Infection Rates of Blood Transfusion in Lumbar Spinal Fusion Surgery: A Nationwide Population-Based Study.

Study Design: Retrospective cohort study. Objectives: Effects of blood loss that requires blood transfusion after lumbar spinal fusion remain an important issue. Blood transfusions are used commonly in cases of significant blood loss in lumbar spinal fusion but are associated with adverse effects. The objective was to assess the rate of blood transfusion and the associated risk after lumbar spinal fusion from 2013 to 2018. Methods: In this nationwide population-based cohort study, the Korean Health Insurance Review and Assessment Service database was reviewed retrospectively from 2013 to 2018. Data were extracted from patients who underwent lumbar spinal fusion without history of lumbar spinal surgery in the preceding year. The primary outcome was the rate of blood transfusion within 1 week of surgery. In addition, the risk factors for blood transfusion and the rate of postoperative infection were evaluated. Results: A total of 188,581 patients underwent lumbar spinal fusion between 2013 and 2018. A significant decline in blood transfusions was observed during the study period (56.38-47.51%). The presence of comorbidities was associated with an increased risk of blood transfusion. Patients who underwent the posterior approach were more likely to receive blood transfusion than patients who underwent the anterior or anterior and posterior approach. Receiving blood transfusion was associated with postoperative infection. Conclusions: In the present study, the prevalence, risk factors, and postoperative infection rates associated with blood transfusion in lumbar spinal fusion were identified. Spine surgeons should consider these risk factors in patients at high risk of blood transfusion.

Formulation of Ascorbic Acid and Betaine-based Therapeutic Deep Eutectic System for Enhanced Transdermal Delivery of Ascorbic Acid.

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.

The Role of Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Ratio in Synovial Fluid as a Potential Marker for Periprosthetic Osteolysis Following Total Ankle Arthroplasty.

Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA. Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines. Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group (p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls (p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group. Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA.

Exploring the Correlation between Systemic Inflammatory Markers and Carotid Atherosclerosis Indices in Middle-Aged Adults: A Cross-Sectional Study.

BACKGROUND: This study investigated the association between atherosclerosis and systemic inflammation markers, specifically the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in healthy middle-aged adults. METHODS: A retrospective cross-sectional study was conducted on a total of 1264 Korean adults aged 40-65. We assessed these inflammatory markers and carotid metrics, such as carotid intima-media thickness (cIMT), plaque number (PN), plaque stenosis score (PSS), and plaque score (PS), using linear regression, logistic regression, and receiver operating characteristic analysis. RESULTS: In males, the ESR and CRP were significantly correlated with the PN (p < 0.001 and p = 0.048, respectively). The ESR was correlated with the PN in females (p = 0.004). The NLR and PLR both correlated with the PS in males (p < 0.001 and p = 0.015, respectively) and females (p = 0.015 and p = 0.023, respectively). The odds ratio for the NLR as a risk factor for increased cIMT was 1.15 (95% confidence interval [CI], 1.03-2.15) for males and 1.05 (95% CI, 1.01-1.29) for females. The AUC for the NLR and PLR as a predictor for the PS showed significance in both men and women. CONCLUSIONS: Inflammatory markers, particularly the NLR and PLR, demonstrate a correlation with carotid atherosclerosis. Both the NLR and PLR hold potential as valuable surrogate markers for carotid atherosclerosis. To further substantiate their predictive efficacy, further prospective studies are needed.