Treatment Outcome After Switching From Galcanezumab to Fremanezumab in Patients With Migraine.

BACKGROUND AND PURPOSE: Monoclonal antibodies (mAbs) targeting calcitonin-gene-related peptide (CGRP) or its receptor (anti-CGRP-R) have been widely administered to patients with migraine who show inadequate responses to preventive medications. Among patients in whom a particular anti-CGRP-R mAb is ineffective, switching between different anti-CGRP-R mAbs can be the next option. Few studies have investigated treatment outcomes for antibody switching, especially between mAbs with the same target of the CGRP ligand. We aimed to determine the treatment outcome after switching between two anti-CGRP mAbs (galcanezumab to fremanezumab). METHODS: We identified migraine patients in a prospective headache clinic registry who received galcanezumab for ≥3 months and were switched to fremanezumab for a further ≥3 months at a single university hospital. We defined a treatment response as a ≥50% reduction in the number of days with a moderate or severe headache at the third month of treatment relative to baseline. The treatment response after switching to fremanezumab was compared with the initial treatment response to galcanezumab. RESULTS: Among 21 patients identified in the registry, 7 (33.3%) were initial responders to galcanezumab. After switching to fremanezumab, 7 (33.3%) showed a treatment response. The treatment response rate was 28.6% in the initial responders and 71.4% in the nonresponders to galcanezumab (p>0.999). CONCLUSIONS: Switching between anti-CGRP mAbs (galcanezumab to fremanezumab) yielded a treatment outcome comparable to that reported previously when switching from an anti-CGRP-R mAb (erenumab) to an anti-CGRP mAb (galcanezumab or fremanezumab). The treatment response to fremanezumab seems to be independent of the prior treatment response to galcanezumab. Our findings suggest that switching to another anti-CGRP mAb can be considered when a particular anti-CGRP mAb is ineffective or intolerable.

Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia.

Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when co-administered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).

Gemigliptin, a potent selective dipeptidyl peptidase 4 inhibitor, protects endothelial progenitor cells by oxidative stress via caspase-3 dependent pathway.

Endothelial progenitor cells (EPCs) are exclusive players in vasculogenesis and endothelial regeneration. EPCs are of two types and their differentiation is mediated by different growth factors. A decrease in EPC number and function causes cardiovascular abnormalities and reduced angiogenesis. Various studies has documented a role of EPCs in diabetes. EPCs treatment with different drugs improve insulin secretion but causes other abnormalities. In vivo and in vitro studies have reported anti glycation effect of gemigliptin but no data is available on in vitro effect of gemigliptin on EPC number and functional credibility. The current study was aimed to find an in vitro effect of gemigliptin on EPC number and function along with an effective treatment dose of gemigliptin. EPCs were isolated, cultured and phenotypically characterized using Dil- AcLDL and ulex-lectin fluorescence staining. EPCs were then treated with different doses of Zemiglo and their viability analyzed with viability assay using water-soluble tetrazolium salt (WST-1), by Annexin V and Propidium Iodide (PI) staining, senescence-associated beta-galactosidase (SA-ß-gal) staining, western blot and Flow cytometric analysis of apoptotic signals. The results demonstrated that the isolated EPCs has typical endothelial phenotypes. And these EPCs were of two types based on morphology i.e., early and late EPCs. Gemigliptin dose dependently improved the EPCs morphology and increased EPCs viability, the most effective dose being the 20 µM. Gemigliptin at 10 µM, 20 µM and 50 µM significantly increased the BCL-2 levels and at 20 µM significantly decreased the Caspase-3 levels in EPCs. In conclusion, gemigliptin dose dependently effects the EPCs viability and morphology through Caspase-3 signaling. Our results are the first report of gemigliptin effect on EPC viability and morphology.

Biocidal products: Opportunities in risk assessment, management, and communication.

In the coronavirus disease 2019 era, biocidal products are increasingly used for controlling harmful organisms, including microorganisms. However, assuring safety against adverse health effects is a critical issue from a public health standpoint. This study aimed to provide an overview of key aspects of risk assessment, management, and communication that ensure the safety of biocidal active ingredients and products. The inherent characteristics of biocidal products make them effective against pests and pathogens; however, they also possess potential toxicities. Therefore, public awareness regarding both the beneficial and potential adverse effects of biocidal products needs to be increased. Biocidal active ingredients and products are regulated under specific laws: the Federal Insecticide, Fungicide, and Rodenticide Act for the United States; the European Union (EU) Biocidal Products Regulation for the EU; and the Consumer Chemical Products and Biocide Safety Management Act for the Republic of Korea. Risk management also needs to consider the evidence of enhanced sensitivity to toxicities in individuals with chronic diseases, given the increased prevalence of these conditions in the population. This is particularly important for post-marketing safety assessments of biocidal products. Risk communication conveys information, including potential risks and risk-reduction measures, aimed at managing or controlling health or environmental risks. Taken together, the collaborative effort of stakeholders in risk assessment, management, and communication strategies is critical to ensuring the safety of biocidal products sold in the market as these strategies are constantly evolving.

Caregiver Burden of Patients With Huntington's Disease in South Korea.

OBJECTIVE: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers. METHODS: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups. RESULTS: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly. CONCLUSION: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Exosomes: Membrane-associated proteins, challenges and perspectives.

Membrane proteins determine the precise function of each membrane and, therefore, the function of each cell type. These proteins essential roles in cell physiology, participating in the maintenance of the cell metabolism, its homeostasis or promoting proper cell growth. Membrane proteins, as has long been described, are located both in the plasma membrane and in complex subcellular structures. However, they can also be released into the extracellular environment associated with extracellular vesicles (EVs). To date, most of the research have been focused on understanding the role of exosomal RNA in several processes. Recently, there has been increasing interest in studying the function of exosome membrane proteins for exosome-based therapy, but not much research has been done yet on the function of exosome membrane proteins. One of the major limitations of studying exosome membrane proteins and their application to translational research of exosome-based therapeutics is the low yield of exosome isolation. Here, we have introduced a new perspective on exosome membrane protein research by reviewing studies showing the important role of exosome membrane proteins in exosome-based therapies. Furthermore, we have proposed a new strategy to boost the yield of exosome isolation: hybridization of liposomes with exosome-derived membrane. Liposomes have already been reported to affect the cell excitation to increase exosome production in tumor cells. Therefore, increasing cellular uptake of these liposomes would enhance exosome release by increasing cellular excitation. This new perspective could be a breakthrough in exosome-based therapeutic research.

Cognitive function improvement effects of gintonin-enriched fraction in subjective memory impairment: An assessor- and participant-blinded placebo-controlled study.

Background: Gintonin is a new material of ginseng that acts through the ginseng-derived lysophosphatidic acid (LPA) receptor ligand. The gintonin-enriched fraction (GEF) inhibits amyloid plaque accumulation in the cortex and hippocampus, improves cognitive dysfunction by increasing acetylcholine levels, and promoted hippocampal neurogenesis in an animal model of Alzheimer's disease. We evaluated the effect of the GEF on the cognitive performance of subjects with subjective memory impairment (SMI). Methods: In this eight-week, randomized, assessor- and participant-blinded, placebo-controlled study, participants with SMI were assigned to three groups receiving placebo, GEF 300 mg/day or GEF 600 mg/day. The Korean versions of the Alzheimer's Disease Assessment Scale (K-ADAS), Mini-Mental State Examination (K-MMSE), and Stroop color-word test (K-SCWT) were also evaluated along with the safety profiles. Results: One hundred thirty-six participants completed the study. After eight weeks, we analyzed intergroup differences in primary or secondary outcome score changes. When we compared the GEF group with the placebo group, we observed significant improvements in the K-ADAS and K-SCWT scores. The GEF group did not show a significant improvement in K-MMSE and BDI scores compared to the placebo group. No adverse events were observed in the gintonin and placebo groups for eight weeks. Conclusion: The GEF is safe and effective in improving subjective cognitive impairment related to both the K-ADAS and K-SCWT in this study. However, further large-scale and randomized controlled studies are warranted to secure other cognitive function tests besides the K-ADAS and K-SCWT, and to confirm the findings of the current study.

Endothelial Progenitor Cells: A Brief Update.

An enormous amount of current data has suggested involvement of endothelial progenitor cells (EPCs) in neovasculogenesis in both human and animal models. EPC level is an indicator of possible cardiovascular risk such as Alzheimer disease. EPC therapeutics requires its identification, isolation, differentiation and thus expansion. We approach here the peculiar techniques through current and previous reports available to find the most plausible and fast way of their expansion to be used in therapeutics. We discuss here the techniques for EPCs isolation from different resources like bone marrow and peripheral blood circulation. EPCs have been isolated by methods which used fibronectin plating and addition of various growth factors to culture media. Particularly, the investigations which tried to enhance EPC differentiation while inducing with growth factors and endothelial nitric oxide synthase are shared. We also include the cryopreservation and other storage methods of EPCs for a longer time. Sufficient amount of EPCs are required in transplantation and other therapeutics which signifies their in vitro expansion. We highlight the role of EPCs in transplantation which improved neurogenesis in animal models of ischemic stroke and human with acute cerebral infarct in the brain. Accumulatively, these data suggest the exhilarating route for enhancing EPC number to make their use in the clinic. Finally, we identify the expression of specific biomarkers in EPCs under the influence of growth factors. This review provides a brief overview of factors involved in EPC expansion and transplantation and raises interesting questions at every stage with constructive suggestions.

Plasma neurofilament light-chain and phosphorylated tau as biomarkers of disease severity in Huntington's disease: Korean cohort data.

OBJECTIVE: To investigate neurofilament light chain (NfL), phosphorylated tau (p-Tau) and total tau (t-Tau) as plasma markers for clinical severity in Korean Huntington's disease (HD) cohort. METHODS: Genetically-confirmed 67 HD patients participated from 13 referral hospitals in South Korea. The subjects were evaluated with the Unified Huntington's Disease Rating Scale (UHDRS), total motor score (TMS) and total functional capacity (TFC), Mini-Mental Status Examination (K-MMSE), Montreal Cognitive Assessment (MoCA-K), and Beck's depression inventory (K-BDI). We measured plasma NfL, p-Tau and t-Tau concentrations using single-molecule array (SIMOA) assays. Stages of HD were classified based on UHDRS-TFC score and plasma markers were analyzed for correlation with clinical severity scales. RESULTS: Plasma NfL was elevated in both 6 premanifest and 61 full manifest HD patients compared to the reference value, which increased further from premanifest to manifest HD groups. The NfL level was not significantly correlated with UHDRS TMS or TFC scores in manifest HD patients. Plasma p-Tau was also elevated in HD patients (p = 0.038). The level was the highest in stage III-V HD (n = 30) group (post-hoc p < 0.05). The p-Tau was correlated with UHDRS TFC scores (adjusted p = 0.002). Plasma t-Tau neither differed among the groups nor associated with any clinical variables. CONCLUSIONS: This study supports plasma NfL being a biomarker for initial HD manifestation in Korean cohort, and a novel suggestion of plasma p-Tau as a potential biomarker reflecting the clinical severity in full-manifest HD.

Efficacy and Safety of Galcanezumab as a Preventive Treatment for Episodic Migraine in South Korean Patients: A Post-Hoc Analysis of a Phase 3 Clinical Trial.

BACKGROUND AND PURPOSE: The estimated prevalence of migraines in South Korea is 6.0%, with affected patients having unmet needs. The efficacy, safety, and tolerability of galcanezumab, a humanized monoclonal antibody, for episodic migraine (EM) prevention was evaluated in South Korean patients. METHODS: During the double-blind period of the EVOLVE-2 phase 3 trial, patients with EM were randomized into placebo, 120 mg-galcanezumab, and 240-mg galcanezumab treatment groups. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days during the 6-month double-blind period. We conducted a post-hoc analysis of the South Korean cohort in EVOLVE-2. RESULTS: Among 98 South Korean patients in the intent-to-treat population, significant changes from baseline were observed in the number of monthly migraine headache days in the 240-mg galcanezumab group compared with the placebo group (-2.64, p=0.013), in the percentage of patients with ≥50% reduction in the number of monthly migraine headache days (120 mg: odds ratio=2.43, p=0.030; 240 mg: odds ratio=2.60, p=0.019), in the number of monthly migraine headache days with acute medication use (120 mg: -2.22, p=0.006; 240 mg: -2.23, p=0.005), and in the Migraine-Specific Quality-of-Life Role Function-Restrictive (120 mg: 8.34, p=0.040). Numerical improvements from baseline were observed relative to the placebo group in at least one galcanezumab group for: the percentage of patients with ≥75% reduction in the number of monthly migraine headache days functional impairment, and disease severity. The most common treatment-emergent adverse event in the combined galcanezumab group was injection site reaction, which led to treatment discontinuation for one patient. CONCLUSIONS: Galcanezumab treatment demonstrated efficacy and a favorable safety and tolerability profile in South Korean patients with EM.

Enhanced osteogenesis of human urine-derived stem cells by direct delivery of 30Kc19α-Lin28A protein.

Urine-derived stem cells (USCs) are a promising source for regenerative medicine because of their advantages such as easy and non-invasive collection from the human body, stable expansion, and the potential to differentiate into multiple lineages, including osteoblasts. In this study, we propose a strategy to enhance the osteogenic potential of human USCs using Lin28A, a transcription factor that inhibits let-7 miRNA processing. To address concerns regarding the safety of foreign gene integration and potential risk of tumorigenicity, we intracellularly delivered Lin28A as a recombinant protein fused with a cell-penetrating and protein-stabilizing protein, 30Kc19α. 30Kc19α-Lin28A fusion protein exhibited improved thermal stability and was delivered into USCs without significant cytotoxicity. 30Kc19α-Lin28A treatment elevated calcium deposition and upregulated several osteoblast-specific gene expressions in USCs derived from multiple donors. Our results indicate that intracellularly delivered 30Kc19α-Lin28A enhances the osteoblastic differentiation of human USCs by affecting the transcriptional regulatory network involved in metabolic reprogramming and stem cell potency. Therefore, 30Kc19α-Lin28A may provide a technical advancement toward developing clinically feasible strategies for bone regeneration.

Balloon Flower Root-Derived Extracellular Vesicles: In Vitro Assessment of Anti-Inflammatory, Proliferative, and Antioxidant Effects for Chronic Wound Healing.

Excessive reactive oxygen species (ROS) in wound lesions can lead to oxidative stress and failure of normal wound healing processes, eventually resulting in chronic skin wounds. A multitude of researchers have investigated various natural products with physiological activities, including antioxidant effects, for healing chronic skin wounds. Balloon flower root (BFR), which contains bioactive components such as platycodins, is known for its anti-inflammatory and antioxidant effects. In this study, we isolated BFR-derived extracellular vesicles (BFR-EVs) that possess anti-inflammatory, proliferative, and antioxidant activities via a combination of polyethylene glycol-based precipitation and ultracentrifugation. Our objective was to investigate the potential of BFR-EVs in treating chronic wounds caused by ROS. Despite efficient intracellular delivery, BFR-EVs showed no significant cytotoxicity. In addition, BFR-EVs inhibited the expression of pro-inflammatory cytokine genes in lipopolysaccharide-stimulated RAW 264.7 cells. Furthermore, water-soluble tetrazolium salt-8 assay showed that BFR-EVs had a proliferation-promoting effect on human dermal fibroblasts (HDFs). Scratch closure and transwell migration assays indicated that BFR-EVs could promote the migration of HDFs. When the antioxidant effect of BFR-EVs was evaluated through 2',7'-dichlorodihydrofluorescein diacetate staining and quantitative real-time polymerase chain reaction, the results revealed that BFR-EVs significantly suppressed ROS generation and oxidative stress induced by H2O2 and ultraviolet irradiation. Our findings suggest that BFR-EVs hold the potential as a natural candidate for healing chronic skin wounds.

Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases.

Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as nucleic acids, lipids, and proteins, and can also be utilized as carriers for drug delivery. However, the low productivity and high cost of mammalian-derived EVs (MDEVs) are major barriers to their practical clinical application where large-scale production is essential. Recently, there has been growing interest in plant-derived EVs (PDEVs) that can produce large amounts of electricity at a low cost. In particular, PDEVs contain plant-derived bioactive molecules such as antioxidants, which are used as therapeutic agents to treat various diseases. In this review, we discuss the composition and characteristics of PDEVs and the appropriate methods for their isolation. We also discuss the potential use of PDEVs containing various plant-derived antioxidants as replacements for conventional antioxidants.

Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial.

BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.

Epicranial headache part 1: Primary stabbing headache.

BACKGROUND/OBJECTIVE: Primary stabbing headache is a common but under-recognized primary headache disorder. The objectives of this review were to provide practical information for better understanding and identification of the disease, suggest an algorithm for differential diagnosis, and provide an insight into the pathophysiology of primary stabbing headache hypothesized from its clinical course. METHODS: This narrative review of primary stabbing headache is based on a literature search and the authors' clinical reasoning. RESULT: The phenotype of each stab is typically abrupt, ultrashort-lasting (<3 s), focal or multifocal, paroxysms of pain occurring sporadically or in clusters. The diagnosis of primary stabbing headache is clinical; fixed or migrating stabs without background pain or sensory abnormalities and the absence of features suggestive of other disorders (e.g., cranial autonomic symptoms or signs) can aid in the diagnosis of primary stabbing headache. The clinical patterns include monophasic, intermittent, and chronic primary stabbing headache, of which the first two are considered typical. The pathophysiology of primary stabbing headache has not yet been elucidated. In this review, we postulated the mechanism of stabbing headache, based on the pain phenotype and clinical course, and provide a clinical algorithm for the differential diagnosis of primary stabbing headache. CONCLUSION: Knowledge about the typical manifestations and clinical patterns of primary stabbing headache will aid in the proper diagnosis and differential diagnosis. Treatment should be tailored by considering the clinical patterns. Further research is needed to elucidate the pathophysiological mechanisms and optimal treatment of primary stabbing headache.

Increased 10-Year Prevalence of Huntington's Disease in South Korea: An Analysis of Medical Expenditure Through the National Healthcare System.

BACKGROUND AND PURPOSE: This study aimed to determine the updated 10-year prevalence of Huntington's disease (HD) in South Korea and the medical and economic burdens across the duration of the disease. METHODS: Data from the National Health Insurance database during 2010-2019 were analyzed. We identified HD cases using predefined criteria. Information on age at diagnosis, sex, and common nonneurological comorbidities were collected. We analyzed individual patterns of the use of medical services and yearly medical expenditure. Incidence rates, 10-year prevalence rates, and longitudinal medical expenditure changes were assessed. RESULTS: New patients with HD (average=152.10) were detected every year, with an annual incidence of 0.29 per 100,000. The estimated 10-year prevalence of HD was 2.2 per 100,000. The most common ages at the time of diagnosis were 50-59 years (23.3%). In 2019, 56.4% of patients with HD were followed-up at referral or general hospitals, and 32.2% were managed at long-term-care hospitals. The annual medical cost for an individual was KRW 6,569,341±895,097 (mean±SD) (mean≈USD 5,653). Medical expenditure was the highest in those aged 60-79 years, and lowest in those younger than 30 years. However, in all age groups, the annual medical expenditure was highest during the 9 years following a diagnosis. CONCLUSIONS: This study found that the actual prevalence of HD in South Korea was higher than previously thought and that patients are in a situation with high medical expenditure that persists over time.

Isolation of Aloe saponaria-Derived Extracellular Vesicles and Investigation of Their Potential for Chronic Wound Healing.

A chronic wound is caused by a failure to progress through the normal phases of wound repair in an orderly and timely manner. To induce skin regeneration while inhibiting chronic inflammation, numerous natural products, and in particular, plant-derived biomaterials, have been developed. Aloe saponaria, is known to contain flavonoid and phenolic acid compounds with anti-oxidative and anti-inflammatory properties. Here, we isolated extracellular vesicles (EVs) from Aloe saponaria by polyethylene glycol (PEG)-based precipitation and investigated their potential as a therapeutic for chronic wound healing. The Aloe saponaria-derived EVs (AS-EVs) showed no significant cytotoxicity on several cell types, despite a high level of intracellular uptake. When lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were treated with AS-EVs, significant reductions in the expression of pro-inflammatory genes, such as interleukin-6 and interleukin-1ß, were observed. Proliferation and migration of human dermal fibroblasts, as determined by the water-soluble tetrazolium salt-8 and transwell migration assay, respectively, were shown to be promoted by treatment with AS-EVs. It was also demonstrated that AS-EVs enhanced tube formation in human umbilical vein endothelial cells, indicating a stimulatory activity on angiogenesis; one of the crucial steps for effective wound healing. Collectively, our results suggest the potential of AS-EVs as a natural therapeutic for chronic wound healing.

Effect of Lactobacillus dominance modified by Korean Red Ginseng on the improvement of Alzheimer's disease in mice.

Background: Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain. Methods: Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aß) accumulation demonstrated through Aß 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test. Results: KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aß 42/40 ratio (p < 0.01) indicating reduced Aß accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%). Conclusions: KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.

Isolated rapid eye movement sleep behavior disorder combined with obstructive sleep apnea: response to treatment and its associated factors.

OBJECTIVE/BACKGROUND: When isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is combined with obstructive sleep apnea (OSA), the pattern of temporal association between REM without atonia (RWA) and apnea-hypopnea events may be related to improvements in RBD symptoms after positive airway pressure (PAP) treatment. We evaluated the frequency of improvement in RBD symptoms after PAP and the relationship of the degree of co-occurrence between RWA and apnea-hypopnea events to RBD symptom improvement after PAP treatment. PATIENTS/METHODS: In an institutional cohort with sleep disorders, 31 patients with video-polysomnography confirmed iRBD and concomitant OSA with an apnea-hypopnea index (AHI) of ≥15/h who received PAP treatment were included. Along with gross video-polysomnography parameters such as AHI and electromyography activity index during REM sleep, a mini-epoch-based parameter apnea-hypopnea-electromyography activity ratio (AH EMG activity ratio) was used to evaluate the co-occurrence between RWA and apnea-hypopnea events. Improvement in RBD symptoms after PAP treatment was designated as a clinical global impression-improvement (CGI-I) score of 0-3 at three-month. RESULTS: Twenty-three (74.2%) patients exhibited improvement in RBD symptoms after PAP treatment. No patient was taking an antidepressant medication. An AH EMG activity ratio of ≥15% (Odds ratio [OR] 10.146, 95% CI 1.302-79.032, P = 0.027) was significantly associated with clinical improvement after PAP treatment in a regression model adjusted for age, sex, AHI, and electromyography activity index during REM. CONCLUSIONS: Treatment of concomitant OSA with PAP can improve symptoms of iRBD. Respiratory events that co-occur with RWA may predict improvement in RBD symptoms after PAP treatment.