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Background and purpose: Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of "body‐first" and "brain‐first" subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body‐first and brain‐first subtypes of PD using urodynamic studies (UDS). Methods: We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body‐first or brain‐first PD based on cardiac sympathetic denervation (CSD) using cardiac meta‐iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body‐first subtype). Results: A total of 55 patients with PD were categorized into body‐first PD (n = 37) and brain‐first PD (n = 18) groups. The body‐first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain‐first PD group (p < 0.05 in both). Also, the body‐first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain‐first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume and negatively correlated with OABSS and IPSS (p < 0.05 in all). Conclusions: Patients with the body‐first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction. [ABSTRACT FROM AUTHOR]

The presence of zooplankton in marine ecosystems is an important factor affecting toxin production in dinoflagellates. However, whether the production of paralytic shellfish toxins (PSTs) by Gymnodinium catenatum and Alexandrium pacificum is affected by substances produced by zooplankton is not yet fully understood. This study assessed the effects of zooplankton extracts on cell abundance, pigment concentration and composition, chlorophyll-a-specific primary production (Chl-a SP), and PST production in G. catenatum and A. pacificum, isolated from Korean coastal waters. In addition, a novel group of hydroxybenzoate PSTs known as GC toxins, which lack commercial reference standards, was evaluated. No significant differences were observed in cell abundance, pigment composition, or Chl-a SP in the experimental group of G. catenatum strains exposed to zooplankton extracts compared to the control group. However, the production of PSTs, including GC toxins, was significantly enhanced when the strain was exposed to extracts of Calanus finmarchicus. Meanwhile, in the A. pacificum strain, some experimental groups showed significant differences in cell abundance and pigment composition, while Chl-a SP significantly decreased in all experimental groups. In addition, PST production was stimulated by the addition of C. finmarchicus extracts. No GC toxins were detected in the A. pacificum strain. This study demonstrated that substances derived from C. finmarchicus enhance the production of PSTs in G. catenatum and A. pacificum. Our findings will improve the current understanding of the occurrence and development mechanisms of PSTs in marine ecosystems and contribute to developing strategies to efficiently secure standard reference toxin products using toxic dinoflagellates. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) is a widely used pharmaceutical for various purposes, including as an anticonvulsant, antibiotic, and antiepileptic agent, and it undergoes diverse metabolic pathways in both the environment and the human body. Therefore, this study aimed to explore the distribution of CBZ, the presence of its transformation products (TPs), and the transformation pathways in the Mangyeong and Dongjin Rivers in the Saemangeum watershed of Korea using non-targeted screening. The concentration distribution results for CBZ and its TPs showed that the average concentrations in the Mangyeong and Dongjin Rivers were 128.8 ng/L and 89.0 ng/L, respectively. The Mangyeong River exhibited a higher CBZ concentration than the Dongjin River, which was similar to those of the reported CBZ concentrations in other major domestic and international rivers. The types and detection frequencies of the identified TPs exhibited similar trends. The detection frequencies of the TPs decreased in the following order: CBZ-EP > DiOH-CBZ > 10OH-CBZ > 2OH-CBZ > 9-carboxyacridine > 9-acridinecarboxaldehyde. The detection frequency of the main TPs was high, and some were believed to be generated during the water treatment process. The presence of additional TPs (CBZ-O-quinone, acridine, and iminostilbene) was confirmed by the generated molecular networks. This study presents the transformation pathway of the CBZ and provides foundational data for understanding the environmental behavior of TPs, improving wastewater treatment plants, managing water quality, and establishing water environmental policies. [ABSTRACT FROM AUTHOR]

Background: Clinical manifestations and risk factors associated with systemic lupus erythematosus (SLE) flares, including recurrent lupus nephritis (LN), in patients with LN who undergo kidney transplantation have been unclear. Methods: Kidney transplant recipients with LN from January 1995 to December 2021 were included in this study. A disease flare was defined as either an increase in the non‐renal SLE disease activity index score or the presence of biopsy‐proven recurrent LN. Results: Among a total of 93 patients with LN who underwent kidney transplantation, 11 patients (11.8%) experienced SLE flares during a median follow‐up period of 76.9 months (IQR, 43.0–122.4). The most common clinical manifestations of SLE flares were recurrent LN (4/11, 36.4%) and hematologic manifestations (4/11, 36.4%). Patients who had flares had significantly higher anti‐double‐stranded DNA (anti‐dsDNA) antibody titers both before and after transplantation. Furthermore, an increased anti‐dsDNA antibody level before transplantation was associated with a high risk of an SLE flare (HR, 1.030; p =.008). Conversely, preemptive transplantation was associated with a lower risk of a flare (HR, 0.617; p =.026). The rate of patient death‐censored graft survival was found to be considerably lower in patients with recurrent LN than in those without LN. Conclusions: Approximately 10% of patients with LN experienced an SLE flare after transplantation, with recurrent LN being the most frequent manifestation. Anti‐dsDNA antibody titers before transplantation were significantly related to the risk of an SLE flare. Notably, preemptive transplantation was associated with a reduced risk of flares following transplantation. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) following pneumonia involves uncontrolled inflammation and tissue injury, leading to high mortality. We previously confirmed the significantly increased cargo content and extracellular vesicle (EV) production in thrombin-preconditioned human mesenchymal stromal cells (thMSCs) compared to those in naïve and other preconditioning methods. This study aimed to investigate the therapeutic efficacy of EVs derived from thMSCs in protecting against inflammation and tissue injury in an Escherichia coli (E. coli)-induced ALI mouse model. Methods: In vitro, RAW 264.7 cells were stimulated with 0.1 µg/mL liposaccharides (LPS) for 1 h, then were treated with either PBS (LPS Ctrl) or 5 × 107 particles of thMSC-EVs (LPS + thMSC-EVs) for 24 h. Cells and media were harvested for flow cytometry and ELISA. In vivo, ICR mice were anesthetized, intubated, administered 2 × 107 CFU/100 µl of E. coli. 50 min after, mice were then either administered 50 µL saline (ECS) or 1 × 109 particles/50 µL of thMSC-EVs (EME). Three days later, the therapeutic efficacy of thMSC-EVs was assessed using extracted lung tissue, bronchoalveolar lavage fluid (BALF), and in vivo computed tomography scans. One-way analysis of variance with post-hoc TUKEY test was used to compare the experimental groups statistically. Results: In vitro, IL-1β, CCL-2, and MMP-9 levels were significantly lower in the LPS + thMSC-EVs group than in the LPS Ctrl group. The percentages of M1 macrophages in the normal control, LPS Ctrl, and LPS + thMSC-EV groups were 12.5, 98.4, and 65.9%, respectively. In vivo, the EME group exhibited significantly lower histological scores for alveolar congestion, hemorrhage, wall thickening, and leukocyte infiltration than the ECS group. The wet-dry ratio for the lungs was significantly lower in the EME group than in the ECS group. The BALF levels of CCL2, TNF-a, and IL-6 were significantly lower in the EME group than in the ECS group. In vivo CT analysis revealed a significantly lower percentage of damaged lungs in the EME group than in the ECS group. Conclusion: Intratracheal thMSC-EVs administration significantly reduced E. coli-induced inflammation and lung tissue damage. Overall, these results suggest therapeutically enhanced thMSC-EVs as a novel promising therapeutic option for ARDS/ALI. [ABSTRACT FROM AUTHOR]

Paralytic shellfish toxins (PSTs) are potent neurotoxins produced by certain microalgae, particularly dinoflagellates, and they can accumulate in shellfish in coastal seawater and thus pose significant health risks to humans. To explore the relationship between toxicity and PST profiles in seawater and mussels, the spatiotemporal variations in PST concentrations and profiles were investigated along the southern coast of Korea under peak PST levels during spring. Seawater and mussel samples were collected biweekly from multiple stations, and the toxin concentrations in the samples were measured. Moreover, the dinoflagellate community composition was analyzed using next-generation sequencing to identify potential PST-producing species. The PST concentrations and toxin profiles showed substantial spatiotemporal variability, with GTX1 and GTX4 representing the dominant toxins in both samples, and C1/2 tending to be higher in seawater. Alexandrium species were identified as the primary sources of PSTs. Environmental factors such as water temperature and salinity influenced PST production. This study demonstrates that variability in the amount and composition of PSTs is due to intricate ecological interactions. To mitigate shellfish poisoning, continuous monitoring must be conducted to gain a deeper understanding of these interactions. [ABSTRACT FROM AUTHOR]

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1–8 were prepared as potential tyrosinase inhibitors. Four analogs (1–3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders. [ABSTRACT FROM AUTHOR]

We established a protocol for the traditional Korean medicine examination (KME) and methodically gathered data following this protocol. Potential indicators for KME were extracted through a literature review; the first KME protocol was developed based on three rounds of expert opinions. The first KME protocol's feasibility was confirmed, and data were collected over four years from traditional Korean medicine (KM) hospitals, focusing on healthy adults, using the final KME protocol. A literature review identified 175 potential core indicators, condensed into 73 indicators after three rounds of expert consultation. The first KME protocol, which was categorized under questionnaires and medical examinations, was developed after the third round of expert opinions. A pilot study using the first KME protocol was conducted to ensure its validity, leading to modifications resulting in the development of the final KME protocol. Over four years, data were collected from six KM hospitals, focusing on healthy adults; we obtained a dataset comprising 11,036 healthy adults. This is the first protocol incorporating core indicators of KME in a quantitative form and systematically collecting data. Our protocol holds potential merit in evaluating predisposition to diseases or predicting diseases. [ABSTRACT FROM AUTHOR]

Objective We investigated the incidence of and risk factors for myelodysplastic syndrome (MDS) in patients with rheumatologic disease. Methods We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. Results During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY {median age 57.0 years [interquartile range (IQR) 41.0–69.0], median duration to MDS diagnosis 6.5 years (IQR 3.0–9.0)]. In an age-matched analysis, SLE was a significant risk factor for MDS [adjusted hazard ratio 2.61 (CI 1.19, 36.06), P  = 0.01]. Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with a favourable prognosis (54.7%). Compared with matched controls, RA, SLE and AS patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behçet's disease had higher levels of glucocorticoid use in terms of frequency of use and mean dose than control patients. Conclusion SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS. [ABSTRACT FROM AUTHOR]

Background Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. Methods This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. Results Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53–38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%–65%), 64% (95% CI, 49%–75%), and 64% (95% CI, 29%–81%) for 2, 3, and 4 doses, respectively. Conclusions SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed. [ABSTRACT FROM AUTHOR]

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health. Microbiome-secreted proteins act as key modulators of host-microbiome crosstalk. Here, the authors show that Amuc_1409 protein, secreted from Akkermansia muciniphila, plays a key role in intestinal homeostasis by regulating intestinal stem cells through interaction with E-cadherin, indicating its potential as a biomolecule for improving gut health. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that the level of extracellular mtDNA would be increased after hyperoxia-induced lung injury but reduced after lung injury attenuation by MSC therapy in our newborn rat model. In an in vitro study using a rat lung epithelial L2 cell line, we found that the level of extracellular mtDNA was significantly increased with H2O2-induced cell death but reduced after MSC co-incubation. In an in vivo study, we confirmed that the levels of cell death, extracellular mtDNA, and inflammatory cytokines were significantly increased in hyperoxic newborn rat lungs but reduced after MSC transplantation. The levels of extracellular mtDNA were significantly and positively correlated with the levels of the inflammatory cytokines. The TLR9/MyD88/NF-κB pathway, which is activated by binding to mtDNA, was also significantly upregulated but downregulated after MSC transplantation. We found a significant positive correlation between inflammatory cytokines and extracellular mtDNA in intubated neonates. The levels of inflammatory cytokines and extracellular mtDNA changed over time in a similar pattern in transtracheal aspirate samples from intubated neonates. In conclusion, increased levels of extracellular mtDNA are associated with increased inflammation in hyperoxia-induced lung injury, and attenuation of lung inflammation by MSC therapy is associated with reduced levels of extracellular mtDNA. [ABSTRACT FROM AUTHOR]

With the recent acceleration in AI adoption and significant investments being made by many countries, the concern regarding the AI divide is becoming increasingly prevalent. We attempt to determine whether countries that have fallen behind in AI development can catch up to those leading the charge over time. Specifically, this study examines the dynamics of the AI divide on AI investments, robotics, AI start-ups, and AI patents in 34–57 countries, analyzing the data sets from Stanford AI Index Report, World Robotics Report, and the OECD Statistics website. We have used the methods of the relative AI divide (RAID) and absolute AI divide (AAID) for the two categories of income and adoption levels. Also, we have tested both γ convergence for the AI divide and σ convergence for the divide over time. We find that for all four AI categories, the relative AI divide between the leading and lagging countries has narrowed rapidly and the divide between the high- and middle-income subgroups has also narrowed at a slower pace. In terms of the micro convergence analysis of the AI divides for individual countries within the respective income and adoption subgroups, a change in the active ranking among countries was evident in nearly all of the subgroups. This study contributes to the literature by presenting not only the absolute AI divide but also the relative AI divide clarifying the changing trends systematically. [ABSTRACT FROM AUTHOR]

Forsythiaside A (FA) is an active constituent isolated from Forsythia suspensa, a beneficial herb used in traditional medicine known for its antioxidant and anti-inflammatory properties. Although various studies have suggested that FA has the protective effects, its impacts on arachidonic acid (AA) plus iron in vitro models and carbon tetrachloride (CCl₄)-induced mouse liver damage in vivo have not been explored. In this study, HepG2 cells were subjected to AA + iron treatment to induce apoptosis and mitochondrial impairment and determine the molecular mechanisms. FA exhibited protective effects by inhibiting cell damage and reactive oxygen species (ROS) production induced by AA + iron, as assessed via immunoblot and flow cytometry analyses. Further molecular investigations revealed that FA resulted in the activation of extracellular-signal-related protein kinase (ERK), which subsequently triggered the activation of AMP-activated protein kinase (AMPK), a critical regulator of cellular oxidative stress. Additionally, FA modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is a significant antioxidant transcription factor regulated by the AMPK pathway. For in vivo studies, mice were orally administered FA and then subjected to induction of CCl₄-based hepatotoxicity. The protective effect of FA was confirmed via blood biochemistry and immunohistochemical analyses. In conclusion, our findings demonstrated the protective effects of FA against oxidative stress both in vitro and in vivo, thus indicating that FA is a potential candidate for liver protection. Our study sheds light on the mechanistic pathways involved in the antioxidant effects of FA, highlighting the hepatoprotective potential of naturally occurring compounds in traditional herbs, such as FA. [ABSTRACT FROM AUTHOR]

Efficient induction of astaxanthin (AXT) biosynthesis remains a considerable challenge for the industrialization of the biorefinement of the microalga Haematococcus lacustris. In this study, we evaluated the technical feasibility of photosynthetic electrotreatment to enhance AXT accumulation in H. lacustris. The AXT content of H. lacustris electrotreated at an optimal current intensity (10 mA for 4 h) was 21.8% to 34.9% higher than that of the untreated control group, depending on the physiological state of the initial palmella cells. The contents of other carotenoids (i.e., canthaxanthin, zeaxanthin, and β-carotene) were also increased by this electrotreatment. However, when H. lacustris cells were exposed to more intense electric treatments, particularly at 20 and 30 mA, cell viability significantly decreased to 84.2% and 65.6%, respectively, with a concurrent reduction in the contents of both AXT and the three other carotenoids compared to those of the control group. The cumulative effect of electric stimulation is likely related to two opposing functions of reactive oxygen species, which facilitate AXT biosynthesis as signaling molecules while also causing cellular damage as oxidizing radicals. Collectively, our findings indicate that when adequately controlled, electric stimulation can be an effective and eco-friendly strategy for inducing targeted carotenoid pigments in photosynthetic microalgae. [ABSTRACT FROM AUTHOR]

Although it has been suggested that toll-like receptor (TLR) 3 and TLR4 activation alters mesenchymal stromal cells (MSCs)' immunoregulatory function as anti- or pro-inflammatory phenotypes, we have previously confirmed that TLR4-primed hUCB-MSCs alleviate lung inflammation and tissue injury in an E. coli-induced acute lung injury (ALI) mouse model. Therefore, we hypothesized that strong stimulation of TLR3 or TLR4 prompts hUCB-MSCs to exhibit an anti-inflammatory phenotype mediated by extracellular vesicles (EVs). In this study, we compared the anti-inflammatory effect of TLR3-primed and TLR4-primed hUCB-MSCs against an LPS-induced ALI in vitro model by treating MSCs, MSC-derived conditioned medium (CM), and MSC-derived extracellular vesicles (EVs). LPS-induced rat primary alveolar macrophage and RAW 264.7 cells were treated with naïve, TLR3-, and TLR4-primed MSCs and their derived CM and EVs. Flow cytometry and ELISA were used to evaluate M1-M2 polarization of macrophages and pro-inflammatory cytokine levels, respectively. LPS-stimulated macrophages showed significantly increased pro-inflammatory cytokines compared to those of the normal control, and the percentage of M2 macrophage phenotype was predominantly low. In reducing the inflammatory cytokines and enhancing M2 polarization, TLR3- and TLR4-primed MSCs were significantly more effective than the naïve MSCs, and this finding was also observed with the treatment of MSC-derived CMs and EVs. No significant difference between the efficacy of TLR3- and TLR-primed MSCs was observed. Strong stimulation of TLR3- and TLR4-stimulated hUCB-MSCs significantly reduced pro-inflammatory cytokine secretion from LPS-induced macrophages and significantly enhanced the M2 polarization of macrophages. We further confirmed that TLR-primed MSC-derived EVs can exert anti-inflammatory and immunosuppressive effects alone comparable to MSC treatment. We hereby suggest that in the LPS-induced macrophage in vitro model, EVs derived from both TLR3 and TLR4-primed MSCs can be a therapeutic candidate by promoting the M2 phenotype. [ABSTRACT FROM AUTHOR]

Pesticides are beneficial in protecting crops from pests and improving agricultural productivity; however, concerns on pesticide pollution in water have increased due to their indiscriminate use and lack of adequate regulations. Many studies have focused on the risks of pesticides considering the limited number and types of pesticide residues in crops and soils, and duration, and very few have focused on surface water throughout the year. Therefore, this study comprehensively identified 308 pesticides in surface water samples collected monthly over one year in the Saemangeum Basin, Korea. Both targeted and non-targeted analyses were used to identify 171 and 24 pesticides, respectively. Results highlight the extensive extent of pesticide contamination. Among the quantified pesticides, bromobutide and pretilachlor consistently exhibited high concentrations and risk levels, as indicated by their elevated risk quotient (RQ) values. Seasonal variations in pesticide concentrations revealed distinct patterns with intensified herbicide use during summer and increased insecticide concentrations during autumn. This study highlights the presence, distribution, and associated ecological risks of pesticides in surface waters, emphasizing the necessity of comprehensive monitoring and regulatory measures to protect aquatic ecosystems. The high RQ values identified for specific pesticides underscore the urgent need to implement effective strategies to mitigate these environmental risks. [ABSTRACT FROM AUTHOR]

Background Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). Methods This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. Results In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06–1.15; second dose aOR, 1.17; 95% CI, 1.12–1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02–1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35–2.02) and second dose (aHR, 1.10; 95% CI, 1.02–1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. Conclusions mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required. [ABSTRACT FROM AUTHOR]

The TARDBP gene variant is a known major cause of amyotrophic lateral sclerosis (ALS), with limited reports of Korean patients with ALS harboring the variants in TARDBP. This large cohort study introduces four ALS patients who share the p.M337V variant of the TARDBP, allowing for an investigation of clinical characteristics and prognosis by analyzing previously reported cases with the same variant. From November 2014 to August 2022, participants were recruited from two tertiary hospitals in Seoul, Korea. Clinical characteristics of patients diagnosed with ALS carrying the variant in TARDBP were evaluated. Previous articles demonstrating subjects' characteristics were reviewed. Four patients were identified with the pathogenic missense variant (c.1009A>G; p.M337V) in the TARDBP. The mean age of onset was 55 years old, and none of the patients showed severe cognitive impairment. Sixty-three patients carrying the p.M337V variant in TARDBP from this study and previous reports delineated young age of onset (51.6 years), high frequency of bulbar onset patients (61.9%), and low comorbidity of frontotemporal dementia. This study reveals the presence of pathogenic variant of TARDBP in Korea and emphasizes the importance of genetic screening of the TARDBP gene, in diagnosing ALS and evaluating prognosis among familial and simplex ALS patients in Korea. [ABSTRACT FROM AUTHOR]

Nicotine, an abundant molecule in tobacco, has immunomodulatory effects on inflammatory diseases, primarily due to the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR). We aim to evaluate the expression of the α7 nAChR+ cells in joint tissue and the effect of smoking on immune cells and peripheral arthritis in curdlan-administered SKG mice, a murine model of spondyloarthropathy (SpA). The SKG mice were injected with curdlan two times at 2-week intervals and were divided into two groups; one exposed to cigarette smoke and the other not exposed. We found that the α7 nAChR+ cells increased in the joint tissue of curdlan-administered SKG mice compared to in the wild type. Furthermore, the peripheral arthritis scores and histological scores for synovial inflammation were lower in smoke-exposed curdlan-administered SKG mice than in mice not exposed to smoke. Immunofluorescence staining of the α7 nAChR+ and IL-17A+ cells was lower in the synovia of smoke-exposed mice than the control mice. The proportions of α7 nAChR+IL-17A+ and α7 nAChR+IL-17A+FOXP3+ cells also decreased in the synovia of smoke-exposed mice compared with the controls. We observed an increase in the α7 nAChR+ cells within the joint tissue of curdlan-administered SKG mice and that cigarette smoke had an influence on both peripheral arthritis and immune cell population, especially α7 nAChR+ cells. Thus, exposure to cigarette smoke after arthritogenic stimuli may have an anti-arthritogenic effect in curdlan-administered SKG mice. [ABSTRACT FROM AUTHOR]

Electrical impedance tomography (EIT) has been proposed as a noninvasive radiation-free functional imaging modality for bedside monitoring of lung ventilation. Due to the intrinsic low sensitivity of measured boundary voltages with respect to internal conductivity changes, EIT image reconstructions are more challenging for the regions that are located deeper from the attached surface electrodes. Considering the worldwide prevalence of obesity, it is highly desirable for an EIT system to produce high-quality images from obese as well as lean subjects. In EIT, the internal current density distribution and the sensitivity of a boundary voltage to a change of internal conductivity vary with respect to the current injection scheme. We quantified the range of measured boundary voltages subject to a chosen current injection scheme and investigated the influence of various obesity levels on the number of distinguishable boundary voltages given a fixed amount of system noise. We found that the 0-skip current injection scheme, where neighboring electrode pairs are used for current injections, could be most favorable to improve spatial resolution but produces the smallest number of distinguishable boundary voltages. To obtain an enough number of distinguishable boundary voltages from an obese subject, the gap between current injection electrodes should be increased depending on the circumference of a chosen imaging plane. We suggested a guideline for current injection schemes in EIT to produce images with better quality from obese as well as lean subjects. [ABSTRACT FROM AUTHOR]

Microglia plays a key role in determining the progression of amyotrophic lateral sclerosis (ALS), yet their precise role in ALS has not been identified in humans. This study aimed to identify a key factor related to the functional characteristics of microglia in rapidly progressing sporadic ALS patients using the induced microglia model, although it is not identical to brain resident microglia. After confirming that microglia-like cells (iMGs) induced by human monocytes could recapitulate the main signatures of brain microglia, step-by-step comparative studies were conducted to delineate functional differences using iMGs from patients with slowly progressive ALS [ALS(S), n = 14] versus rapidly progressive ALS [ALS(R), n = 15]. Despite an absence of significant differences in the expression of microglial homeostatic genes, ALS(R)-iMGs preferentially showed defective phagocytosis and an exaggerated pro-inflammatory response to LPS stimuli compared to ALS(S)-iMGs. Transcriptome analysis revealed that the perturbed phagocytosis seen in ALS(R)-iMGs was closely associated with decreased NCKAP1 (NCK-associated protein 1)-mediated abnormal actin polymerization. NCKAP1 overexpression was sufficient to rescue impaired phagocytosis in ALS(R)-iMGs. Post-hoc analysis indicated that decreased NCKAP1 expression in iMGs was correlated with the progression of ALS. Our data suggest that microglial NCKAP1 may be an alternative therapeutic target in rapidly progressive sporadic ALS. [ABSTRACT FROM AUTHOR]

We report simultaneous removal of NO and SO2 by Fe(II)EDTA2− absorbent in a wet absorption system. Effects of various operation parameters, such as Fe(II)EDTA2− concentration, solution volume, NO inlet concentration, and pH of absorption solution on NO absorption in a semi-batch reaction, were investigated. NO loading capacity increased with increasing NO inlet concentration since NO loading capacity was highly influenced by NO inlet concentration. NO loading capacity increased in neutral and alkaline environments compared to that in an acidic one. To evaluate NO absorption performance of practical flue gas components, simultaneous absorption of NO and SO2 in the presence of O2 over Fe(II)EDTA2 was carried out. As a result, when all gas emission components (NO, SO2 and O2) were introduced, simultaneous removal of NO and SO2 was obtained with a high NO loading capacity (ca. 88.8%). Antagonistic effects of both SO2 and O2 played an essential role in the regeneration of Fe(III)EDTA and Fe(II)EDTA-NO2 to Fe(II)EDTA2, keeping a neutral pH of absorption solution and resulting in a dramatic improvement in the absorption of NO and SO2. [ABSTRACT FROM AUTHOR]

Mutations in ITM2B have been reported to be associated with several familial dementias, such as Familial British dementia and familial Danish dementia. These are autosomal dominant disorders characterized by progressive dementia with an onset at around the fifth decade of life. We describe a family with cognitive impairment caused by a novel ITM2B p.*267Serext*11 mutation. The probands presented with cognitive impairment and cerebral infarction. MRI revealed diffuse white matter hyperintensity and microbleeds. Amyloid deposition was not observed on amyloid positron emission tomography. Our case suggests that the BRI2 mutation impacts cognition regardless of amyloid-β accumulation. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been studied as novel therapeutic agents because of their immunomodulatory properties in inflammatory diseases. The suppressor of cytokine signaling (SOCS) proteins are key regulators of the immune response and macrophage modulation. In the present study, we hypothesized that SOCS in MCSs might mediate macrophage modulation and tested this in a bacteria-induced acute lung injury (ALI) mouse model. The macrophage phenotype was observed in RAW264.7 alveolar macrophages exposed to lipopolysaccharide (LPS) in an in vitro model, and in the ALI mouse model induced by tracheal administration of Escherichia coli (1 × 107 CFU in 0.05mL PBS). In LPS-exposed RAW264.7 cells, the levels of markers of M1 macrophages, such as CD86 and pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α), significantly increased, but they significantly reduced after MSC treatment. Meanwhile, the levels of markers of M2 macrophages, such as CD204 and anti-inflammatory cytokines (IL-4 and IL-10), increased after LPS exposure, and further significantly increased after MSC treatment. This regulatory effect of MSCs on M1/M2 macrophage polarization was significantly abolished by SOCS3 inhibition. In the E. coli-induced ALI model, tissue injury and inflammation in the mouse lung were significantly attenuated by the transplantation of MSCs, but not by SOCS3-inhibited MSCs. The regulatory effect of MSCs on M1/M2 macrophage polarization was observed in the lung injury model but was significantly abolished by SOCS3 inhibition. Taken together, our findings suggest that SOCS3 is an important mediator for macrophage modulation in anti-inflammatory properties of MSCs. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a global health problem that is closely associated with obesity and metabolic syndrome. Spatholobi caulis (SC) is a herbal medicine with potential hepatoprotective effects; however, its active compounds and underlying mechanisms have not been fully explored. In this study, we combined a multiscale network-level approach with experimental validation to investigate SC's antioxidant properties and their impact on NAFLD. Data collection and network construction were performed, and active compounds and key mechanisms were identified through multi-scale network analysis. Validation was conducted using in vitro steatotic hepatocyte models and in vivo high-fat diet-induced NAFLD models. Our findings revealed that SC treatment improved NAFLD by modulating multiple proteins and signaling pathways, including AMPK signaling pathways. Subsequent experiments showed that SC treatment reduced lipid accumulation and oxidative stress. We also validated SC's effects on AMPK and its crosstalk pathways, emphasizing their role in hepatoprotection. We predicted procyanidin B2 to be an active compound of SC and validated it using a lipogenesis in vitro model. Histological and biochemical analyses confirmed that SC ameliorated liver steatosis and inflammation in mice. This study presents SC's potential use in NAFLD treatment and introduces a novel approach for identifying and validating active compounds in herbal medicine. [ABSTRACT FROM AUTHOR]

Background: Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in bone remodeling has not yet been elucidated in detail. Result: We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin−/− OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1β signaling. The ectopic expression of parkin in Parkin−/− OCPs limited the increase in dentin resorption induced by IL-1β, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity. Conclusion: These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease, with two main pathological features: misfolded α-synuclein protein accumulation and neurodegeneration. Inflammation has recently been identified as a contributor to a cascade of events that may aggravate PD pathology. Inflammasomes, a group of intracellular protein complexes, play an important role in innate immune responses to various diseases, including infection. In PD research, accumulating evidence suggests that α-synuclein aggregations may activate inflammasomes, particularly the nucleotide-binding oligomerization domain-leucine-rich repeat-pyrin domain-containing 3 (NLRP3) type, which exacerbates inflammation in the central nervous system by secreting proinflammatory cytokines like interleukin (IL)-18 and IL-1β. Afterward, activated NLRP3 triggers local microglia and astrocytes to release additional IL-1β. In turn, the activated inflammatory process may contribute to additional α-synuclein aggregation and cell loss. This review summarizes current research evidence on how the NLRP3 inflammasome contributes to PD pathogenesis, as well as potential therapeutic strategies targeting the NLRP3 inflammasome in PD. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the length of stay (LOS) and treatment outcomes based on the application and achievement of a newly developed emergency department (ED) LOS management system for severely ill patients. Methods: Data were retrospectively collected from electronic medical records (EMRs) for the system evaluation and research purpose. The study subjects are severely ill patients whose diagnosis codes are designated by the Ministry of Health and Welfare and who visited the ED of a tertiary hospital from January to December 2019. The control group (Group 1) refers to those who have neither applied nor achieved the goal (5 hours or less) of the ED LOS management system even after it was applied, and the experimental group (Group 2) refers to those who have achieved the 5-hour goal after applying the system. Results: A total of 2034 severely ill patients applied the ED LOS management system. Group 1 included 837 patients and Group 2 included 1197 patients. Thirty days in-hospital mortality corresponded to 10.6% in Group 1 and 6.6% in Group 2 (χ2 = 10.58, p =.001). The total duration of hospitalization was 14.66 ± 18.26 days in Group 1 and 10.19 ± 16.00 days in Group 2 (t = 9.03, p <.001). Six hundred forty-two patients (76.6%) in Group 1 were discharged to their home (normal discharge) and 979 patients (81.7%) were discharged to their home in Group 2, but the discharge-as-death rate was 14.1% in Group 1 and 7.5% in Group 2 (χ2 = 29.80, p <.001). Conclusion: With the application and attainment of the ED LOS management system for severely ill patients, we have concluded the new system produced a lower LOS in the ED, 30 days in-hospital mortality, length of the hospitalization, mortality rate, and a higher rate of normal discharge. [ABSTRACT FROM AUTHOR]

Fire in energy storage systems, such as lithium-ion batteries, has been raised as a serious concern due to the difficulty of suppressing it. Fluorine-based non-flammable agents used as internal substances leaked through the fine pores of the polymer outer shell, leading to a degradation of fire extinguishing performance. To improve the durability of the fire suppression microcapsules and the stability of the ouster shell, a complex coacervation was used, which could be microencapsulated at a lower temperature, and the polymer shell was coated with urea-formaldehyde (UF) resin. The outermost UF resin formed elaborate bonds with the gelatin-based shell, and thus, the structure of the outer shell became denser, thereby improving the loss resistance of the inner substance and thermal stability. The double-layered microcapsules had an average particle diameter of about 309 μm, and a stable outer shell formed with a mass loss of 0.005% during long-term storage for 100 days. This study confirmed that the double-layered microcapsules significantly improved thermal stability, resistance to core material loss, core material content and fire suppression performance compared to single wall microcapsules. These results indicated that the double-layered structure was suitable for the production of microcapsules for initial fire suppression, including highly volatile non-flammable agents with a low boiling point. [ABSTRACT FROM AUTHOR]

Background: Mutations in PTEN-induced putative kinase 1 (PINK1) cause autosomal recessive Parkinson's disease (PD) and contribute to the risk of sporadic PD. However, the relationship between PD-related PINK1 mutations and alpha-synuclein (α-syn) aggregation—a main pathological component of PD—remains unexplored. Objective: To investigate whether α-syn pathology is exacerbated in the absence of PINK1 after α-syn preformed fibril (PFF) injection in a PD mouse model and its effects on neurodegeneration. Methods: In this study, 10-week-old Pink1 knockout (KO) and wildtype (WT) mice received stereotaxic unilateral striatal injection of recombinant mouse α-syn PFF. Then, α-syn pathology progression, inflammatory responses, and neurodegeneration were analyzed via immunohistochemistry, western blot analysis, and behavioral testing. Results: After PFF injection, the total α-syn levels significantly increased, and pathological α-syn was markedly aggregated in Pink1 KO mice compared with Pink1 WT mice. Then, earlier and more severe neuronal loss and motor deficits occurred. Moreover, compared with WT mice, Pink1 KO mice had evident microglial/astrocytic immunoreactivity and prolonged astrocytic activation, and a higher rate of protein phosphatase 2A phosphorylation, which might explain the greater α-syn aggravation and neuronal death. Conclusion: The loss of Pink1 function accelerated α-syn aggregation, accumulation and glial activation, thereby leading to early and significant neurodegeneration and behavioral impairment in the PD mouse model. Therefore, our findings support the notion that PINK1 dysfunction increases the risk of synucleinopathy. [ABSTRACT FROM AUTHOR]

Formyl peptide receptor (FPR) 2 is known to play a critical role in regulating inflammation, including either the pro-inflammatory or pro-resolving effects. However, its role in neonatal hyperoxia-induced lung injury has not been delineated. In this study, we investigate whether mesenchymal stem cells (MSCs) attenuate hyperoxia-induced neonatal lung injury by regulating FPR2 activity. We observed a significant increase in FPR2 levels in alveolar macrophages (RAW264.7 cells) after H2O2-induced stress, which decreased after MSC treatment. In the H2O2-induction model, increased levels of inflammatory cytokines (IL-1α and TNF-α) were significantly reduced in RAW264.7 cells after treatment with WRW4, an inhibitor of FPR2, or MSCs. Viability of lung epithelial cells and endothelial cells was significantly improved when cultured in the conditioned media of RAW264.7 cells treated with WRW4 or MSCs, compared to when cultured in the conditioned media of control RAW265.7 cells exposed to H2O2. For the in vivo study, wild-type and FPR2 knockout (FPR2−/−) C57/BL6 mouse pups were randomly exposed to 80% oxygen or room air from postnatal day (P) 1 to P14. At P5, 2 × 105 MSCs were transplanted intratracheally. MSCs reduced the elevated FPR2 activity at P7 and improved the decreased FPR2 activity as well as the increased immuno-stained FPR2 activity in alveolar macrophages in hyperoxic lungs at P14. Both FPR2−/− and MSCs similarly attenuated impaired alveolarization and angiogenesis, and increased apoptosis and inflammation of hyperoxic lungs without synergistic effects. Our findings suggest that the protective effects of MSCs in hyperoxic lung injury might be related to indirect modulation of FPR2 activity, at least of alveolar macrophages in neonatal mice. [ABSTRACT FROM AUTHOR]

The lifetime prevalence of mental disorders in South Korea was 25.4% in 2016. The Act on Mental Health enabled the expansion of psychiatric facilities; however, resources were allocated without considering the population structure or the characteristics of mental health problems. This paper investigates the status and trends of disease burden and the government budget for Korean mental health. The burden of mental and behavioral disorders (MBDs) was measured using the incidence-based disability-adjusted life years (DALYs), and the mental health budget data was from the Ministry of Health and Welfare of South Korea. We estimated that the disease burden of MBDs accounted for 6.4% of the total disease burden, ranking as the seventh leading cause of Korean DALYs. The mental health budget in South Korea was USD 253.4 million in 2019 (USD 90.3 million from the general account, USD 65.8 million from the National Health Promotion Fund, and USD 97.3 million from the special account for the national mental hospitals). Challenges are created by the MBD burden on the Korean healthcare system, and the budget is insufficient to address this disease burden, suggesting that resource allocation systems should be improved. [ABSTRACT FROM AUTHOR]

We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against brain injury in a paracrine manner, this study was designed to estimate the efficacy of MSC-derived extracellular vesicles (MSC-EVs) in E. coli meningitis in newborn rats. E. coli meningitis was induced without concomitant bacteremia by the intra-cerebroventricular injection of 5 × 102 colony-forming units of K1 (-) E. coli in rats, at postnatal day 11. MSC-EVs were intra-cerebroventricularly transplanted 6 h after the induction of meningitis, and antibiotics were administered for three consecutive days starting at 24 h after the induction of meningitis. The increase in bacterial growth in the cerebrospinal fluid measured at 24 h after the meningitis induction was not significantly reduced following MSC-EV transplantation. However, an increase in brain cell death, reactive gliosis, and inflammation following meningitis were significantly attenuated after MSC-EV transplantation. Taken together, our results indicate that MSCs show anti-apoptotic, anti-gliosis, and anti-inflammatory, but not antibacterial effects, in an EV-mediated paracrine manner in E. coli-induced neonatal meningitis. [ABSTRACT FROM AUTHOR]

Preterm births are often associated with neurodevelopmental impairment. In the critical developmental period of the fetal brain, preterm birth disrupts cortical maturation. Notably, preterm birth leads to alterations in the fronto-striatal and temporal lobes and the limbic region. Recent advances in MRI acquisition and analysis methods have revealed an integrated approach to the genetic influence on brain structure. Based on imaging studies, we hypothesized that the altered cortical structure observed after preterm birth is associated with common genetic variations. We found that the presence of the minor allele at rs1042778 in OXTR was associated with reduced curvature in the right medial orbitofrontal gyrus (p < 0.001). The presence of the minor allele at rs174576 in FADS2 (p < 0.001) or rs740603 in COMT (p < 0.001) was related to reduced curvature in the left posterior cingulate gyrus. This study provides biological insight into altered cortical curvature at term-equivalent age, suggesting that the common genetic variations related to autism spectrum disorder (ASD) and lipid metabolism may mediate vulnerability to early cortical dysmaturation in preterm infants. [ABSTRACT FROM AUTHOR]

Objectives: To examine the long-term renal outcomes of systemic lupus erythematosus (SLE) patients with transient proteinuria. Methods: The medical records of SLE patients who showed improvement in proteinuria (urine protein/creatinine ratio < 500 mg/g) after receiving corticosteroid therapy without immunosuppressants were reviewed. Results: A total of 38 patients (mean creatinine: 0.74 ± 0.33 mg/dl) showed an improvement of proteinuria (1361 ± 1053 mg/g to 289 ± 125 mg/g) after receiving corticosteroid therapy alone for a median of 25 days (IQR, 10–55). After follow-up (median, 23 months [IQR, 15–121]), 25 (65%) patients maintained the resolution of proteinuria without renal dysfunction. The remaining 13 (34%) patients experienced a relapse of proteinuria during a median follow-up of 13.9 months from baseline (IQR, 1.6–25). There was no significant difference in the baseline laboratory data according to the occurrence of proteinuria relapse, but longer SLE disease duration at baseline was associated with the risk of proteinuria relapse (HR, 1.007; p = 0.033). Of the patients who underwent renal biopsy with proteinuria relapse, class II (53%) lupus nephritis was the most common pathology. None progressed to end-stage renal disease during an additional long-term further follow-up of median 33 months (IQR, 22–49) after proteinuria relapse. Conclusion: Two-thirds of SLE patients who showed improvement in proteinuria after corticosteroid alone maintained the non-proteinuric state without renal dysfunction. Thus, performing a kidney biopsy at the first onset of proteinuria could be delayed in patients who show an improvement in proteinuria after treatment with corticosteroids. [ABSTRACT FROM AUTHOR]

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton's jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 μL blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), naïve MSCs or thrombin-preconditioned MSCs (1 × 105/10 μL) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to naïve MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to naïve MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does naïve MSC transplantation. [ABSTRACT FROM AUTHOR]

COVID-19 has quickly propagated throughout the globe and triggered the worst economic crisis the world has experienced in recent history. We estimate mortality rates and associated economic loss of fatalities for different contagion suppression scenarios in a worldwide group of countries. We adjust previous estimates of mortality rates by adjusting for lower healthcare capacity to treat critically ill patients in lower-income countries. Furthermore, we adjust previous estimates of the economic loss from fatalities by controlling for the age profile of victims. The results show significant economic gains in adopting mitigation strategies, but the marginal gains decrease when moving from mitigation to suppression strategies. Moreover, lower-income countries gain less in moving from no intervention to mitigation and still less in moving from mitigation to suppression than higher-income countries do. [ABSTRACT FROM AUTHOR]

Background: The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).Methods: A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.Results: Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104).Conclusions: Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.Trial Registration: The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ). [ABSTRACT FROM AUTHOR]

This study compared the prevalence of depressive symptoms and suicidal ideation in individuals living alone compared with those living with others and assessed the contribution of socio-demographic factors and physical health to these differences. We analyzed 2221 individuals living alone and 19,397 individuals living with others aged 20–80 years, drawn from the Korean National Health and Nutrition Examination Survey dataset in South Korea. The study group divided into three subgroups based on age to determine whether there were differences in mental health according to age. Depressive symptoms and suicidal ideation were evaluated by self-reported questionnaires. The sex- and age-adjusted prevalence rates of depressive symptoms and suicidal ideation were higher in those living alone than those living with others. The proportion of socio-economic status and physical health explaining the differences of depressive mood and suicidal ideation between the two groups was greater in the age group over 35 years old. Considering the difference in factors that explain depressive symptoms and suicidal ideation among individuals living alone in the age group over 35 years of age and younger groups under 34 years of age, policies should be developed that will address the mental health needs of each age group. [ABSTRACT FROM AUTHOR]

A small loading of highly dispersed Ru on Ni/MgAl2O4 catalyst was investigated in the dry reforming of methane (DRM) process. The catalysts were synthesized by impregnation and deposition-precipitation methods; the DRM reaction was performed at CH4/CO2/N2 = 1/1/1 and 600‒750°C. The bimetallic Ni‒Ru catalysts exhibited improved reducibility and metal dispersion compared with that of the Ni catalyst. Among the synthesized catalysts, the Ru(D)/Ni(I)/MgAl2O4 catalyst had the highest metal dispersion (7.23%) and largest amount of CO2 desorption (135 μmol/g). Thus, this catalyst exhibited the highest CH4 conversion (85.6%) at 750°C. Additionally, coke deposition of only 2.69% occurred during the stability test. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) are new green solvents, which are widely used in lignocellulosic and microalgal biorefineries. However, high-temperature operating conditions limit their application in the extraction of heat-labile algal products, such as bioactive astaxanthin. In this study, we report the technical feasibility of room-temperature astaxanthin extraction from Haematococcus lacustris cysts with a thick and complex cell wall structure, by combining ultrathin α-quartz nanoplates (NPLs) with ethyl-3-methylimidazolium ([Emim])-based ILs. When four different [Emim]-based ILs with thiocyanate (SCN), diethylphosphate (DEP), HSO4, and Cl anions were applied to 90-day-old H. lacustris cysts at room temperature (~28 °C), the astaxanthin extraction efficiency was as low as 9.6–14.2%. Under sonication, α-quartz NPLs disrupted the cyst cell wall for a short duration (5 min). The astaxanthin extraction efficacies of a subsequent IL treatment improved significantly to 49.8% for [Emim] SCN, 60.0% for [Emim] DEP, 80.7% for [Emim] HSO4, and 74.3% for [Emim] Cl ions, which were 4.4, 6.1, 8.4, and 5.2 times higher than the extraction efficacy of only ILs, respectively. This finding suggests that α-quartz NPLs can serve as powerful cell-wall-disrupting agents for the room-temperature IL-mediated extraction of astaxanthin from robust algal cyst cells. [ABSTRACT FROM AUTHOR]