Novel Cosmetic Ingredient CS-AA Polyion Complex and Skin Moisturizing Effect.

PURPOSE: The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS-AA complex was examined. METHODS: After analyzing the CS-AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS-AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. RESULTS: Validating a systematic reduction in particle size, the following order was observed: CS > CS/AA simple mixture > CS-AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS-AA complex exhibits negligible surface charge. Additionally, Fourier-transform infrared spectroscopy (FT-IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS-AA complex. Subsequently, the water-holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS-Q complex: 40.6% (1 h), 20.5% (2 h), and 18.7% (4 h) compared to glycerin. Similarly, the CS-R complex demonstrated enhancements of 50.2% (1 h), 37.5% (2 h), and 33% (4 h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS-Q complex and CS-R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS-Q complex and CS-R complex showed a significant increase in moisture levels after 4 weeks of application. CONCLUSION: In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well-known moisturizing agent, confirmed that the CS-AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS-AA complex is a more effective ingredient than CS or AA alone in terms of efficacy.

Percutaneous radiofrequency ablation of liver metastases from colorectal cancer: Development of a prognostic score to predict overall survival.

PURPOSE: To develop a model for pretreatment prediction of overall survival (OS) after radiofrequency ablation (RFA) for colorectal liver metastasis (CRLM). METHOD: This retrospective study included 491 patients (median age, 61 years; 348 men) who underwent percutaneous RFA for CRLM between 2000 and 2021. The Kaplan-Meier method was used to estimate OS rates. Independent factors affecting OS were investigated using multivariable Cox regression analysis. Risk scores were assigned to the risk factors and pretreatment prediction models were created using the risk factors. RESULTS: After RFA, the 5-, 10-, and 20-year OS rates were 44 %, 31 %, and 24 %, respectively, and the median OS was 46 months. Multivariate Cox regression analysis showed that a largest tumor size ≥ 2 cm (P<0.001), positive nodal status of primary tumor (P<0.001), carcinoembryonic antigen level > 30 ng/mL (P=0.049), multiple tumors (P=0.008), and T4 stage of the primary tumor (P=0.029) were independently associated with OS. In patients with a single CRLM, tumor diameter (P<0.001), positive nodal status of primary tumor (P=0.001), disease-free interval <12 months (P=0.045), and subcapsular location (P=0.03) were risk factors affecting OS. According to our prediction models, which included the aforementioned risk factors, OS rates progressively decreased as the risk scores increased, with significantly different OS rates between contiguous groups (P<0.001). CONCLUSIONS: Our prediction models can be used as a prognostic stratification tool in patients with CRLM, and can help select those candidates who will benefit most from RFA.

Small Molecule Detection with Ligation-Dependent Light-Up Aptamer Transcriptional Amplification.

ATP and NAD+ are small biomolecules that participate in a variety of physiological functions and are considered as potential biomarkers for disease diagnosis. In this study, we developed a ligation-dependent light-up aptamer transcriptional amplification assay for the sensitive and selective detection of ATP and NAD+. This assay relies on a specific DNA ligase that catalyzes the ligation of a nicked DNA template in the presence of a specific small molecule. We prepared a nicked template consisting of a duplex fragment with an overhang for the T7 promoter region and a single-stranded DNA with a complementary overhang sequence for the Broccoli aptamer. The nicked template was connected using a DNA ligase in the presence of a specific small molecule. The ligation product was subjected to in vitro transcription to amplify the light-up aptamer-mediated fluorescence signals. By integrating the target-dependent ligation and transcription amplification, significant signal amplification was achieved with 5.9 and 142 pM detection limits for ATP and NAD+, respectively. Moreover, good selectivity to discriminate between the target and its analogues was also realized. The application of this method to biological samples was evaluated using human serum and exhibited excellent recovery values.

MicroRNA Regulation for Inflammasomes in High Glucose-Treated ARPE-19 Cells.

Purpose: This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods: To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells. Results: In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased. Conclusions: This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

Analyzing Mental Health Shifts Among Migrant Workers in Korea: A Comparative Study During and Post the COVID-19 Era.

In the midst of a pandemic like COVID-19, migrant workers are highly vulnerable to the risk of mental health challenges and disorders. This study aimed to examine the variations in mental health and associated factors among migrant workers in Korea during and after the COVID-19 pandemic. A total of 830 migrant workers were included in this quantitative population-based study across two distinct COVID-19 periods: 415 from August 15, 2020 to January 20, 2021 (termed "during COVID-19" post-WHO pandemic declaration) and 415 from June 10 to September 18, 2023 (termed "after COVID-19" post-WHO and Korean Government announcement of the end COVID-19 as a global health emergency). The mental health of migrants was assessed using Patient Health Questionnaire-9 for depression and Generalized Anxiety Disorder-7 for anxiety, and compared between the two defined COVID-19 periods. Migrant workers exhibited higher means of depression (15.99 ± 5.16 vs. 8.78 ± 5.77) and anxiety (11.02 ± 4.45 vs. 6.97 ± 4.42) during the COVID-19 compared to after the COVID-19. The prevalence of severe depression (30.4% vs. 8.2%, p = .038) and severe anxiety (24.1% vs. 5.3%, p = .047) was significantly higher during the COVID-19 than after the pandemic. Changes in the mean depression scores among migrants were significantly influenced by living status (0.12 ± 11.10, p = .030) and employment status (0.44 ± 10.33, p = .043), while changes in mean anxiety scores were influenced by social relief funds (2.88 ± 8.61, p = .046) and employment status (1.13 ± 8.39, p = .012). This study highlights the increased susceptibility of migrant workers to depression and anxiety during COVID-19 compared to after the pandemic. Thus, it is imperative to prioritize the expansion of social support funds, ensure employment stability, and implement regular health check-up services to reduce mental health disorders among migrants.

Incidence and risk factor analysis of neovascular glaucoma following vitrectomy in patients with proliferative diabetic retinopathy.

To investigate the incidence and risk factors for neovascular glaucoma (NVG) after vitrectomy in patients with proliferative diabetic retinopathy (PDR). Patients were categorized into two subgroups based on their treatment regimen: one group received vitrectomy only (Group 1), while the other received combined phacovitrectomy (Group 2). A comparative analysis was conducted to evaluate the distinguishing characteristics of the two groups. Kaplan-Meier survival analysis was used to determine the incidence of NVG following surgery. Furthermore, multivariate analysis using the Cox proportional hazards model was conducted to identify the risk factors associated with the development of NVG after surgery. A total of 484 eyes of 484 patients were included in the study. When comparing Group 1 with Group 2, a significant difference was observed in the occurrence of NVG. In Group 1, there were 10 cases of NVG (3.9%), whereas 29 cases of NVG occurred in Group 2 (12.71%). Male sex, high preoperative intraocular pressure (IOP), and combined phacovitrectomy were found to be associated with the occurrence of NVG following phacovitrectomy. Higher creatinine levels had a protective effect in preventing the development of NVG. Male sex, high preoperative IOP, and combined phacovitrectomy were associated with a high incidence of NVG. Explore strategies to prevent NVG is important when performing combined phacovitrectomy in patients with PDR.

Reproducibility for carotid wall segmentation using T1-weighted DANTE-SPACE sequence on high-resolution 3-T carotid MRI.

BACKGROUND: T1-weighted (T1W) magnetic resonance imaging (MRI) using the delay alternating with nutation for excitation-sampling perfection with application-optimized contrasts using different flip angle evolution (DANTE-SPACE) is the preferred imaging technique for evaluation of the vessel wall. PURPOSE: To evaluate the intra- and inter-rater reproducibility of carotid wall segmentation on T1W DANTE-SPACE in patients with symptomatic (acute stroke or transient ischemic attack) internal carotid artery (ICA) stenosis. MATERIAL AND METHODS: This prospective study included 25 patients with acute (≤3 months) stroke or transient ischemic attack and 50%-99% stenosis of the ICA. All patients underwent 3.0-T high-resolution carotid MRI. Two radiologists independently performed the manual segmentation of the vessel wall and inner lumen of the bilateral carotid artery on DANTE-SPACE. The intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and Hausdorff distance (HD) were calculated. RESULTS: The ICCs for intra-rater reproducibility of carotid wall volume, inner lumen volume, and normalized wall index were 0.965, 0.990, and 0.962, respectively. The ICCs for inter-rater reproducibility of carotid wall volume, inner lumen, and normalized wall index were 0.856, 0.981, and 0.904. DSC and HD for intra- and inter-rater reproducibility of carotid wall segmentation were as follows: 0.873 and 0.809 (DSC); and 0.079 and 0.118 (HD), respectively. For evaluation of reproducibility only in the carotid artery with symptomatic stenosis, the ICCs for intra- and inter-rater reproducibility indicated all perfect agreement. CONCLUSION: T1W DANTE-SPACE is a reproducible sequence for evaluation of the carotid wall using carotid MRI in patients with symptomatic ICA stenosis.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

STUDY OBJECTIVES: Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. METHODS: This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. RESULTS: In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). CONCLUSIONS: Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.

Photobiomodulation Mitigates PM2.5-Exacerbated Pathologies in a Mouse Model of Allergic Asthma.

Exposure to particulate matter (PM), especially PM2.5, is known to exacerbate asthma, posing a significant public health risk. This study investigated the asthma-reducing effects of photobiomodulation (PBM) in a mice model mimicking allergic airway inflammation exacerbated by PM2.5 exposure. The mice received sensitization with ovalbumin (OVA) and were subsequently treated with PM2.5 at a dose of 0.1 mg/kg every 3 days, for 9 times over 3 weeks during the challenge. PBM, using a 610 nm wavelength LED, was applied at 1.7 mW/cm2 to the respiratory tract via direct skin contact for 20 min daily for 19 days. Results showed that PBM significantly reduced airway hyperresponsiveness, plasma immunoglobulin E (IgE) and OVA-specific IgE, airway inflammation, T-helper type 2 cytokine, histamine and tryptase in bronchoalveolar lavage fluid (BALF), and goblet cell hyperplasia in PM2.5-exposed asthmatic mice. Moreover, PBM alleviated subepithelial fibrosis by reducing collagen deposition, airway smooth muscle mass, and expression of fibrosis-related genes. It mitigated reactive oxygen species generation, oxidative stress, endoplasmic reticulum stress, apoptotic cell death, ferroptosis, and modulated autophagic signals in the asthmatic mice exposed to PM2.5. These findings suggest that PBM could be a promising intervention for PM2.5-induced respiratory complications in patients with allergic asthma.

Incidence of Panic Disorder Diagnoses After Celebrity Disclosures of Panic Disorder in South Korea.

Importance: The persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions. Objective: To evaluate the impact of celebrity mental health disclosures on the incidence and prevalence of panic disorder diagnosis in South Korea. Design, Setting, and Participants: This cohort study included the entire South Korean population from January 2004 to December 2021, as reflected in the National Health Insurance Service data. Analysis was conducted from May 2022 through January 2024. Exposure: Time periods analyzed included the timeframe before (from January 2004 to December 2010) and after the public disclosures of panic disorder by 3 high-profile Korean celebrities between December 2010 and January 2012 (from January 2011 to December 2021). Main Outcomes and Measures: Monthly incidence and prevalence of panic disorder, defined by the presence of a clinical diagnosis of the condition. Trends were assessed using interrupted time series analysis with autoregressive integrated moving average models. To assess public interest in panic disorder, trends in search data were analyzed, examining the association between the timing of increased searches and changes in the incidence and prevalence of panic disorder. Data on obsessive-compulsive disorder (OCD) were included as a control. Results: The study covered the entire population of South Korea, including 48 559 946 individuals in January 2004 and 52 593 886 individuals in December 2021. Before 2011, the mean (SD) annual prevalence of panic disorder was stable at 560 (140) persons per 100 000 persons per year. The celebrity disclosure in December 2010 was associated with higher monthly incidence rates of panic disorder, as measured by insurance claims data, changes that were observed in both the level (5.8 persons; 95% CI, 2.2-9.5 persons) and slope (0.78 persons per month; 95% CI, 0.19-1.40 persons per month) per 100 000 persons. By 2021, the observed annual prevalence per 100 000 persons reached 7530 persons, an increase of 775.6% compared with the 860 persons (95% CI, 330-1400 persons) estimated if the disclosures had not occurred. Internet searches anticipated changes in monthly prevalence with a lag of 2 or 3 months (F = 4.26, P = .02 and F = 3.11, P = .03, respectively). The celebrity disclosures had no significant association with the incidence or prevalence of OCD. Conclusions and Relevance: In this observational cohort study, celebrity disclosure of mental health conditions was associated with a sustained reduction in stigma, as reflected in increased help-seeking behavior for the condition over more than a decade. This underscores the influential role celebrities can play in shaping public health perceptions and behaviors, offering valuable insights for the development of future mental health policies and public awareness campaigns.

Broadening the scope of multigene panel analysis for adult epilepsy patients.

OBJECTIVE: Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients. METHODS: We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti-seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains. RESULTS: A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12-q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood-onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies. SIGNIFICANCE: Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early-onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background. PLAIN LANGUAGE SUMMARY: This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood-onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.

Dual Volume Image Fusion Technique for Anatomical Evaluation of Cavernous Sinus Dural Arteriovenous Fistula: Usefulness for Transvenous Target Segment Embolization.

OBJECTIVE: In this preliminary study, we investigated the value of fusion techniques by flat detector computed tomography based dual volume rotational angiography (DVRA) for the evaluation of the anatomical relationship of cavernous sinus dural arteriovenous fistula (CSDAVF) and assessed the possibility of transvenous target segment embolization. METHODS: Twenty-six patients with CSDAVF supplied by multiple feeders underwent DVRA for each feeding large vessel separately. We assessed the anatomical relationship of feeders, fistula points, and venous drainage with 3 dual volume image fusion techniques. Transvenous embolization was targeted to the segment of fistulous point for preserving those not involved and reducing coil mass effect. RESULTS: Dual vessel multi-planar reconstruction fusion technique could show which segment of the cavernous sinus supplied by feeding arteries. In the dual vessel volume rendering fusion technique, the association between feeding arteries, fistula points, and draining veins of 2 different vessels could be accurately identified in 3 dimensions. In addition, we could visualize the exact anatomical relationship between the components of CSDAVF and skull anatomy with the single vessel fusion technique. Based on various fusion images, target segment embolization was successfully performed in 8 patients. In this group, we achieved complete or near complete occlusion without complications, including cranial nerve palsy. CONCLUSIONS: Detailed anatomical information including accurate fistula point, specific feeding arteries, and draining veins could be obtained with various dual volume image fusion techniques. In addition, the target segment embolization of CSDAVF could be possible with understanding of the precise CSDAVF architectures.

Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling.

Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.

The Relationship Between Brain Activation for Taking Others' Perspective and Interoceptive Abilities in Autism Spectrum Disorder: An fMRI Study.

Objectives: In this functional magnetic resonance imaging study, we aimed to investigate the differences in brain activation between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals during perspective taking. We also examined the association between brain activation and empathic and interoceptive abilities. Methods: During scanning, participants from the ASD (n=17) and TD (n=22) groups were shown pain stimuli and asked to rate the level of the observed pain from both self- and other-perspectives. Empathic abilities, including perspective taking, were measured using an empathic questionnaire, and three dimensions of interoception were assessed: interoceptive accuracy, interoceptive sensibility, and interoceptive trait prediction errors. Results: During self-perspective taking, the ASD group exhibited greater activation in the left precuneus than the TD group. During other-perspective taking, relative hyperactivation extended to areas including the right precuneus, right superior frontal gyrus, left caudate nucleus, and left amygdala. Brain activation levels in the right superior frontal gyrus while taking other-perspective were negatively correlated with interoceptive accuracy, and those in the left caudate were negatively correlated with perspective taking ability in the ASD group. Conclusion: Individuals with ASD show atypical brain activation during perspective taking. Notably, their brain regions associated with stress reactions and escape responses are overactivated when taking other-perspective. This overactivity is related to poor interoceptive accuracy, suggesting that individuals with ASD may experience difficulties with the self-other distinction or atypical embodiment when considering another person's perspective.

CRISPR/Cas12a Collateral Cleavage-Driven Transcription Amplification for Direct Nucleic Acid Detection.

The clustered regularly interspaced short palindromic repeat/Cas (CRISPR/Cas) system is a powerful tool for nucleic acid detection owing to specific recognition as well as cis- and trans-cleavage capabilities. However, the sensitivity of CRISPR/Cas-based diagnostic approaches is determined by nucleic acid preamplification, which has several limitations. Here, we present a method for direct nucleic acid detection without preamplification, by combining the CRISPR/Cas12a system with signal enhancement based on light-up RNA aptamer transcription. We first designed two DNA templates to transcribe the light-up RNA aptamer and kleptamer (Kb) RNA: the first DNA template encodes a Broccoli RNA aptamer for fluorescence signal generation, and the Kb DNA template comprises a dsDNA T7 promoter sequence and an ssDNA sequence that encodes an antisense strand for the Broccoli RNA aptamer. Hepatitis B virus (HBV) target recognition activates a CRISPR/Cas12a complex, leading to the catalytic cleavage of the ssDNA sequence. Transcription of the added Broccoli DNA template can then produce several Broccoli RNA aptamer transcripts for fluorescence enhancement. The proposed strategy exhibited excellent sensitivity and specificity with 22.4 fM detection limit, good accuracy, and stability for determining the target HBV dsDNA in human serum samples. Overall, this newly designed signal enhancement strategy can be employed as a universal sensing platform for ultrasensitive nucleic acid detection.

Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year.

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150-300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized 'responsive' when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30-49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).

Hemodialysis-induced positional changes in lamina cribrosa.

This study is aimed to investigate the effect of hemodialysis (HD) on the lamina cribrosa (LC) of the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT) and other ophthalmological parameters in patients with end-stage kidney disease (ESKD). This prospective observational study included 29 patients who underwent HD for ESKD. ONH parameters including neural canal diameter (NCD), peripapillary vertical height (PVH), and anterior LC depth (LCD), were assessed using SS-OCT. Changes in the ONH parameters before and after HD were statistically analysed. Correlations between changes in the LCD and other ocular and systemic measurements were identified using Pearson's correlation analyses. The mean anterior LCD significantly decreased from 441.6 ± 139.8 µm before HD to 413.5 ± 141.7 µm after HD (P = 0.001). Mean NCD and PVH did not show significant changes after HD (P = 0.841 and P = 0.574, respectively). A significant correlation was found between changes in the anterior LCD and the mean ocular perfusion pressure (r = 0.397, P = 0.036). We observed a significant decrease in anterior LCD after HD. Our study suggests that HD can influence the ONH, especially in the LC.

Liquid collagen from freshwater fish skin ameliorates hydration, roughness and elasticity in photo-aged skin: a randomized, controlled, clinical study.

BACKGROUND/OBJECTIVES: Collagen is commonly used in diverse forms as a functional component in skincare products. On the other hand, the effects of collagen on human skin are controversial. Dietary collagen hydrolysates from freshwater Pangasius hypophthalmus fish skin ameliorated photo-aged skin of hairless mice. This study conducted a randomized, double-blind, placebo-controlled clinical trial to determine if liquid fish collagen (Collagen-Tripep20™, Tripep20) as a drink strengthens skin health and quality. SUBJECTS/METHODS: In this clinical trial, 85 subjects aged 35-60 yrs were diagnosed with photo-aged skin. Eighty-five subjects were randomized to receive either Tripep20 (n = 44) or placebo (n = 41). Seventy-eight subjects fully participating for a 12-week period consumed 1,000 mg of Tripep20 (n = 41) or placebo (n = 37) in a 50-mL bottle as a daily drink. The intend-to-treat and per-protocol populations were 85 and 78, respectively. Skin hydration, wrinkles, and elasticity were assessed at 0 (baseline), 6, and 12 weeks during the study period. RESULTS: Skin hydration in the Tripep20 group was significantly higher from 6 weeks (P < 0.001) than the baseline. After 12 weeks, the Crow's-feet visual score and skin roughness (Ra, Rq, and Rmax) were significantly improved in the Tripep20 group than in the placebo group (P < 0.05). Consuming liquid collagen Tripep20 greatly enhanced skin elasticity (Gross R2, Net R5, and Biological elasticity R7) in 6 weeks compared to the placebo group. The Tripep20 group showed a significant increase in skin elasticity from the baseline after 6 and 12 weeks (P < 0.001). Neither abnormal symptoms nor adverse events were encountered during the study period in subjects ingesting Tripep20 or placebo. The changes in parameters related to hematology and clinical chemistry were within the normal ranges. CONCLUSION: Oral consumption of liquid collagen Tripep20 was safe and well-tolerated. The results of this study show that freshwater fish-derived liquid collagen Tripep20 can be used as a healthy functional food ingredient to improve skin moisturizing, anti-wrinkling, and elasticity in an aging population.

Improvement in functional motor scores in patients with non-ambulatory spinal muscle atrophy during Nusinersen treatment in South Korea: a single center study.

We analyzed the changes in various motor function scores over a four-year period in patients with non-ambulatory spinal muscular atrophy (SMA) during Nusinersen treatment. Patients underwent Hammersmith Infant Neurological Examination (HINE) or Hammersmith Functional Motor Scale Expanded (HFMSE) before treatment, and approximately every 4 months thereafter. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) or Children's Hospital of Philadelphia - Adult Test of Neuromuscular Disorders (CHOP ATEND), Revised Upper Limb Module (RULM), and Motor Function Measure (MFM) were performed based on baseline functional status. Narrative interviews were conducted to explore post-treatment physical improvement regarding activities of daily living (ADLs) and fatigue after ADLs. Based on HFMSE results, 9 patients achieved minimum clinically important differences. Average rates of change (slopes) with corresponding 95% confidence intervals for all assessment tools were in a positive direction. CHOP-INTEND showed the most prominent improvement in children and adolescents followed by HFMSE. Improvements in CHOP-ATEND were most noticeable in adults. Improvements were accompanied by changes in ADLs as observed in the narrative interviews. It is necessary to consider various functional aspects to determine the effectiveness of Nusinersen therapy. The objective assessment of the therapeutic effect of Nusinersen in non-ambulatory SMA requires consideration of functional aspects and the related ADLs.