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Introduction: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke., Methods: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI)., Results: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic stroke exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43-0.50, P < 0.001) across all stroke subtypes., Conclusion: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke., (S. Karger AG, Basel.)

Background: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients., Methods: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months., Results: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (P interaction =0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes., Conclusion: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes., (Copyright © 2023. Published by Elsevier Inc.)

Background: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend., Methods: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders., Results: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome., Conclusions: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population., Competing Interests: Disclosures Dr Bae reports grants from Astrazeneca, Bayer Korea, Bristol Myers Squibb, Bristol Myers Squibb Korea, Chong Gun Dang Pharmaceutical Corp, Dong-A ST, Jeil Pharmaceutical Co, Ltd, Korean Drug Co, Ltd, SAMJIN Pharm, Takeda Pharmaceuticals Korea Co, Ltd, and Yuhan Corporation, and personal fees from Amgen Korea, Hanmi Pharmaceutical Co, Ltd, Otsuka Korea, SK Chemicals, and Viatris Korea outside the submitted work. Dr Gorelick received consultative fees for an expert opinion in a medical-legal matter related to stroke in atrial fibrillation.

Redox chemistry involving the quinone/phenol cycling of natural organic matter (NOM) is known to modulate microbial respiration. Complexation with metals or minerals can also affect NOM solubilization and stability. Inspired by these natural phenomena, a new soil amendment approach was suggested to effectively decrease methane emissions in flooded rice paddies. Structurally stable forms of NOM such as lignin and humic acids (HAs) were shown to decrease methane gas emissions in a vial experiment using different soil types and rice straw as a methanogenic substrate, and this inhibitory behavior was likely enhanced by ferric ion-NOM complexation. A mechanistic study using HAs revealed that complexation facilitated the slow release of the humic components. Interestingly, borohydride-based reduction, which transformed quinone moieties into phenols, caused the HAs to lose their inhibitory capacity, suggesting that the electron-accepting ability of HAs is vital for their inhibitory effect. In rice field tests, the humic-metal complexes were shown to successfully mitigate methane generation, while carbon dioxide emissions were relatively unchanged. Microbial community analysis of the rice fields by season revealed a decrease in specific cellulose-metabolizing and methanogenic genera associated with methane emissions. In contrast, the relative abundance of Thaumarchaeota and Actinomycetota, which are associated with NOM and recalcitrant organics, was higher in the presence of Fe-stabilized HAs. These microbial dynamics suggest that the slow release of humic components is effective in modulating the anoxic soil microbiome, possibly due to their electron-accepting ability. Given the simplicity, cost-effectiveness, and soil-friendly nature of complexation processes, Fe-stabilized NOM represents a promising approach for the mitigation of methane emissions from flooded rice paddies., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

The aim of this study was to investigate the prevalence of shoulder pain and analyze its association with socio-demographic factors, agricultural work-related conditions, and biomechanical factors among farmers on Jeju Island. We utilized initial survey data from the Safety for Agricultural Injury of Farmers' cohort study involving adult farmers on Jeju Island. The presence and characteristics of shoulder pain, socio-demographics, agricultural work-related conditions, and biomechanical factors were assessed using semi-structured questionnaires. A total of 1206 participants were analyzed for prevalence and associated risk factors using frequency and multivariate logistic regression analyses. The overall prevalence of shoulder pain was 17%. Multivariate logistic regression analysis, adjusted for significant socio-demographic and agricultural work-related condition variables, revealed that stress level, type of farming, and experiencing an agricultural injury within the preceding year were significantly associated with shoulder pain (stress level: "occasional," adjusted odds ratio [aOR], 1.581; 95% confidence interval [CI], 1.079-2.318; "frequent," aOR, 1.964; 95% CI, 1.205-3.200; and "extreme," aOR, 2.999; 95% CI, 1.480-6.074 vs "rarely"; type of farming: "orchard," aOR, 0.82; 95% CI, 0.597-1.124; "livestock," aOR, 0.225; 95% CI, 0.079-0.641 vs "field"; and experienced an agricultural injury within the past year: "yes," aOR, 2.078; 95% CI, 1.269-3.405). In addition, 3 biomechanical factors significantly contributed to shoulder pain: activities requiring significant power such as shoveling, pickaxing, and hammering; repetitive use of a particular body part; and constant elevation of the arm above the head. The findings highlight the importance of postural education, injury prevention, and psychological support in managing shoulder pain among farmers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The purpose of this study was to evaluate surgeons' ability to perform or supervise a standard operation with agreed-upon radiologic parameters after being on call., Methods: We reviewed a consecutive series of patients with intertrochanteric hip fractures treated with a fixed angle device at 9 centers and compared corrected tip-apex distance and reduction quality for post-call surgeons versus those who were not. Subgroup analyses included surgeons who operated the night before versus not and attending-only versus resident involved cases. Secondary outcomes included union and perioperative complications., Results: One thousand seven hundred fourteen patients were of average age 77 years. Post-call surgeons treated 823 patients and control surgeons treated 891. Surgical corrected tip-apex distance did not differ between groups: on-call 18 mm versus control 18 mm (P = 0.59). The Garden indices were 160° on the AP and 179° on the lateral in both groups. In 66 cases performed by surgeons who operated the night before, the TAD was 17 mm. No difference was noted in corrected tip-apex distance with and without resident involvement (P = 0.101). No difference was observed in pooled fracture-related complications (P = 0.23)., Conclusion: Post-call surgeons demonstrated no difference in quality and no increase in complications when performing hip fracture repair the next day compared with surgeons who were not on call., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Antibody-based therapeutics (ABTs), including monoclonal/polyclonal antibodies and fragment crystallizable region (Fc)-fusion proteins, are increasingly used in disease treatment, driving the global market growth. Understanding the pharmacokinetic (PK) properties of ABTs is crucial for their clinical effectiveness. This study investigated the PK profile and tissue distribution of efineptakin alfa, a long-acting recombinant human interleukin-7 (rhIL-7-hyFc), using enzyme-linked immunosorbent assay (ELISA) and accelerator mass spectrometry (AMS). Totally, four rats were injected intramuscularly with 1 mg/kg of rhIL-7-hyFc containing 14 C-rhIL-7-hyFc, which was prepared via reductive methylation. Serum total radioactivity (TRA) and serum rhIL-7-hyFc concentrations were quantified using AMS and ELISA, respectively. The TRA concentrations in organs were determined by AMS. Serum TRA peaked at 10 hours with a terminal half-life of 40 hours. The rhIL-7-hyFc exhibited a mean peak concentration at around 17 hours and a rapid elimination with a half-life of 12.3 hours. Peak concentration and area under the curve of TRA were higher than those of rhIL-7-hyFc. Tissue distribution analysis showed an elevated TRA concentrations in lymph nodes, kidneys, and spleen, indicating rhIL-7-hyFc's affinity for these organs. The study also simulated the positions of 14C labeling in rhIL-7-hyFc, identifying specific residues in the fragment of rhIL-7 portion, and provided the explanation of distinct analytes targeted by each method. Combining ELISA and AMS provided advantages by offering sensitivity and specificity for quantification as well as enabling the identification of analyte forms. The integrated use of ELISA and AMS offers valuable insights for the development and optimization of ABT., Competing Interests: Mi-sun Byun and Donghoon Choi are employees of Genexine, Inc. and NeoImmuneTech, Inc., respectively. All other authors declared no competing interests for this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of Antibody Therapeutics.)

Background: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications., Methods: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021)., Results: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% ( P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation ( P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality ( P < 0.001)., Conclusion: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Although urine drug testing can have vast legal and social ramifications, its interpretation during pregnancy and after birth remains not well understood. Fentanyl metabolism is altered by an individual's genetics, history of opioid use, and liver function. However, little is known about the clearance of fentanyl or its primary metabolite, norfentanyl, in the peripartum period., Objective: We sought to identify and describe cases of delayed urine norfentanyl clearance in the pregnancy and postpartum period within our institution., Study Design: This study described 3 cases of delayed urine norfentanyl clearance in pregnant and postpartum individuals in a colocated obstetrics, postpartum, and addiction medicine program. This program included prescriptions for medication for opioid use disorder and weekly urine drug testing with fentanyl immunoassay with reflex confirmation testing with liquid chromatography-tandem mass spectrometry for positive results with a limit of detection of 2.5 ng/mL., Results: Low levels of norfentanyl (<16.3 ng/mL) were detected in urine 294 days, 126 days, and 231 days after the last fentanyl use. Patient self-reported abstinence was supported by consistently negative urine fentanyl levels throughout the collection period, compliant weekly urine drug tests that were otherwise only positive for buprenorphine, and negative fentanyl and norfentanyl in umbilical cord toxicology., Conclusion: Despite compliance in a medication for opioid use disorder program, the presence of norfentanyl in urine has significant consequences on the maternal-child dyad in the postpartum period. Caution should be used when using low levels of norfentanyl to determine an individual's abstinence, as it can lead to further discrimination against women in medication for opioid use disorder programs., (© 2024 The Authors.)

Background: Cerebral small vessel disease is characterized by white matter hyperintensities (WMH) and acute small vessel occlusion (SVO) stroke. We investigated the effect of prior antiplatelet use (APU) on stroke outcome in 1151 patients with acute SVO stroke patients and moderate to severe WMH., Methods: Using a multicenter database, this retrospective study used quantitative WMH volume measurements and propensity score matching (PSM) for comparisons between patients with prior APU and without APU. Primary outcomes were stroke progression and poor functional outcome (modified Rankin Scale>2) at 3 months. Logistic regression analyses assessed associations between prior APU, WMH burden, and stroke outcomes., Results: Stroke progression was lower in the prior APU group in both the total cohort (14.8% vs. 6.9%, p < 0.001) and the PSM cohort (16.3% vs. 6.9%, p < 0.001). The proportion of poor functional outcomes at 3 months was not significantly different in the total cohort, but the PSM cohort showed a lower proportion in the prior APU group (30.8% vs. 20.2%, p = 0.002). Logistic regression analysis confirmed that prior APU was associated with a reduced risk of stroke progression (OR, 0.39; 95% CI, 0.22-0.70; p = 0.001) and poor functional outcome at 3 months (OR, 0.37; 95% CI, 0.23-0.59; p < 0.001)., Conclusion: Prior APU is associated with reduced stroke progression and improved functional outcome at 3 months in acute SVO stroke patients with moderate to severe WMH. Early treatment of WMH and acute SVO stroke may have potential benefits in improving stroke outcomes., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Alzheimer's disease (AD), the most common form of dementia, is characterized by memory loss and the abnormal accumulation of senile plaques composed of amyloid-β (Aβ) protein. Trichosanthis Semen (TS) is a traditional herbal medicine used to treat phlegm-related conditions. While TS is recognized for various bioactivities, including anti-neuroinflammatory effects, its ability to attenuate AD remains unknown., Objective: To evaluate the effects of TS extract (TSE) on neuronal damage, Aβ accumulation, and neuroinflammation in AD models., Methods: Thioflavin T and western blot assays were used to assess effects on Aβ aggregation in vitro. TS was treated to PC12 cells with Aβ to assess the neuroprotective effects. Memory functions and histological brain features were investigated in TSE-treated 5×FAD transgenic mice and mice with intracerebroventricularly injected Aβ., Results: TSE disrupted Aβ aggregation and increased the viability of cells and phosphorylation of both protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) in vitro. TSE treatment also suppressed the accumulation of Aβ plaques in the brain of 5×FAD mice, protected neuronal cells in both the subiculum and medial septum, and upregulated Akt/ERK phosphorylation in the hippocampus. Moreover, TSE ameliorated the memory decline and glial overactivation observed in 5×FAD mice. As assessing whether TS affect Aβ-induced neurotoxicity in the Aβ-injected mice, the effects of TS on memory improvement and neuroinflammatory inhibition were confirmed., Conclusions: TSE disrupted Aβ aggregation, protected neurons against Aβ-induced toxicity, and suppressed neuroinflammation, suggesting that it can suppress the development of AD.

The objective of this study was to investigate the effect of a removable physical barrier on the air sparging performance using a lab-scale aquifer model was investigated. The barrier was installed in water-saturated porous media, prior to the air sparging, by injecting calcium chloride aqueous solution into the aquifer with pre-applied alginate solution. Changes in the air flow direction and air flux at the media surface during air sparging were evaluated. With a hydrogel barrier set at the center of the media, the airflow detoured the barrier resulting in a bimodal air flux distribution at the media surface. While employing two gel-formed barriers positioned away from the media's center, the airflow concentrated specifically on the gap between the barriers. The hydrogel was successfully removed using a sodium bicarbonate solution (1.0 mol/L). Using the hydrogel barrier, the performance of air sparging was significantly enhanced for removing contaminants [tetrachloroethene (PCE) and n-hexane mixture] due to increased air flux; 9.8% of PCE applied (7.8 g) was removed during 120 min air sprging for the gel barrier system whereas no PCE was removed for the control. Alginate gel did not show significant sorption capacity for PCE. It was stable in the contaminant up to 68 days with reasonable loss of its mass. Findings of this study present a promising option for air sparging process specifically targeting the contaminant source zone in the aquifer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain., Methods: We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro., Findings: The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells., Interpretation: Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis., Funding: This study was supported by a grant from the National Research Foundation of Korea., Competing Interests: Declaration of interests EH, JGC, DHK and MSO are inventors with a provisional patent, “Method for diagnosing neurodegenerative disease using HpmA” that is licensed to MetaCen Therapeutics. MGP is a co-founder of MetaCen Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Dr. Alfonso has a consultant agreement with Cochlear Americas. Drs. Oh, Govil, and Todd disclose no conflicts of interest.

Neuroinflammation and synaptic damage are important etiologies associated with the progression of Alzheimer's disease (AD). Linderae Radix (LR) has antioxidant and anti-inflammatory properties. This study investigated whether LR attenuates microglia activation-mediated neuroinflammation and synaptic degeneration and improves AD pathological phenotypes induced by amyloid beta oligomers (AβO) or lipopolysaccharide (LPS) toxicity. For in vitro studies, we treated LR to AβO-stimulated HT22 cells or LR LPS-stimulated BV2 cells. For in vivo studies, we administered LR to mice and AβO was injected by stereotaxic to induce cognitive impairment, neuroinflammation, and synaptic loss. We found that LR increased the cell viability reduced by AβO. Moreover, LR inhibited pro-inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), and downregulated p38 mitogen-activated protein kinase (MAPK) signaling in BV2 cells. Behavioral assessments demonstrated that LR administration significantly improved cognitive decline induced by AβO-injection. Furthermore, we found that microglia activation increased, and the expression of synaptic proteins decreased in the hippocampus of the AβO-injected group, which was alleviated in the LR-treated group. These findings suggest that LR may be a potential candidate for protection against neuroinflammation and synaptic loss, and may prevent or delay AD progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population., Methods: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed., Results: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years ( P trend =0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; P trend <0.01). Door-to-needle time improved ( P trend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased ( P trend <0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; P trend =0.04), although the difference was not significant after adjusting for sex and age., Conclusions: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress., Competing Interests: Disclosures Dr Gorelick reports grants from Amerian Telephysicians, AbbVie, and Pickus Law, outside the submitted work. Dr Bae reports grants from AstraZeneca, Bayer Korea, Bristol Myers Squibb Korea, Dong-A ST, Jeil Pharmaceutical Co, Ltd, Korean Drug Co, Ltd, Samjin Pharm, Takeda Pharmaceuticals Korea Co, Ltd, and Yuhan Corporation and people fees from Amgen Korea, Bayer, Daiichi Sankyo, JW Pharmaceutical, Hanmi Pharmaceutical Co, Ltd, Otsuka Korea, SK Chemicals, and Viatris Korea, outside the submitted work. The other authors report no conflicts.

Aim: While the relationship between impaired kidney function and non-vitamin K antagonist oral anticoagulants (NOACs) is well established, there is limited research exploring the association between an elevated estimated glomerular filtration rate (eGFR) and the efficacy of NOACs, especially concerning the outcomes of acute ischemic stroke (AIS). This study aimed to examine the association between higher-than-normal eGFR and the severity of AIS during the use of NOACs using a nationwide multicenter stroke registry in Korea., Material and Methods: This study utilized data from the Korean Stroke Registry (KSR) database, examining information from 2,379 patients with AIS, who had atrial fibrillation (AF) and a history of utilizing NOACs prior to hospitalization due to incident stroke occurring between 2016 and 2021. Patients with a history involving two or more types of anticoagulants or one or more forms of antiplatelet agents were excluded. Baseline characteristics, medical history, medication usage, CHADS 2 -VASc score, and the anticoagulation and risk factors in atrial fibrillation (ATRIA) score were evaluated. Renal function was assessed using eGFR levels and calculated with the Cockcroft-Gault equation. The severity of stroke was measured by the National Institutes of Health Stroke Scale as an outcome. For sensitivity analysis, further evaluation was performed using eGFR levels according to the modification of diet in renal disease (MDRD) study equation., Results: The mean age of subjects was 76.1 ± 8.9 years. The moderate-to-severe stroke severity group exhibited an elevation in creatinine levels. The eGFR of 60 to 89 mL/min/1.73 m 2 group was associated with a decreased risk of moderate-to-severe stroke severity [hazard ratio (HR)] (0.77, 95% confidence interval (CI) [0.61, 0.98], p = 0.031) compared to the eGFR≥90 mL/min/1.73 m 2 group. An increment of 10 units in eGFR was marginally associated with an increased risk of moderate-to-severe stroke severity (HR: 1.03, 95% CI [1.00, 1.07], p = 0.054)., Conclusion: The study revealed that individuals with eGFR ≥ 90 mL/min/1.73 m 2 had an association linked to an increased risk of moderate-to-severe stroke severity. Our study suggests that patients taking NOACs with higher-than-normal eGFR levels may have an increased severity of AIS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Lee, Oh, Lee, Jeong, Shin, Yoon and Park.)

The dysfunction of natural killer (NK) cells, mediated by transforming growth factor β1 (TGFβ1) within the tumor microenvironment, impedes antitumor therapy and contributes to poor clinical outcomes. Our study introduces self-activating chimeric antigen receptor (CAR)-NK cells that block TGFβ1 signaling by releasing a specifically designed peptide, P6, which targets mesothelin in pancreatic tumors. P6 originates from the interaction sites between TGFβ1 and TGFβ receptor 1 and effectively disrupts TGFβ1's inhibitory signaling in NK cells. Our analysis demonstrates that P6 treatment interrupts the SMAD2/3 pathway in NK cells, mitigating TGFβ1-mediated suppression of NK cell activity, thereby enhancing their metabolic function and cytotoxic response against pancreatic tumors. These CAR-NK cells exhibit potent antitumor capabilities, as evidenced in spheroid cultures with cancer-associated fibroblasts and in vivo mouse models. Our approach marks a substantial advancement in overcoming TGFβ1-mediated immune evasion, offering a promising avenue for revolutionizing cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown., Methods: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age., Results: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib -/- mice., Conclusion: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications., (© 2023. The Author(s).)

Background: We aimed to investigate the association between the ApoB/ApoA-I ratio and post-stroke cognitive impairment (PSCI) in patients with acute stroke of large artery atherosclerosis etiology., Methods: Prospective stroke registry data were used to consecutively enroll patients with acute ischemic stroke due to large artery atherosclerosis. Cognitive function assessments were conducted 3 to 6 months after stroke. PSCI was defined as a z-score of less than -2 standard deviations from age, sex, and education-adjusted means in at least one cognitive domain. The ApoB/ApoA-I ratio was calculated, and patients were categorized into five groups according to quintiles of the ratio. Logistic regression analyses were performed to assess the association between quintiles of the ApoB/ApoA-I ratio and PSCI., Results: A total of 263 patients were included, with a mean age of 65.9 ± 11.6 years. The median NIHSS score and ApoB/ApoA-I ratio upon admission were 2 (IQR, 1-5) and 0.81 (IQR, 0.76-0.88), respectively. PSCI was observed in 91 (34.6%) patients. The highest quintile (Q5) of the ApoB/ApoA-I ratio was a significant predictor of PSCI compared to the lowest quintile (Q1) (adjusted OR, 3.16; 95% CI, 1.19-8.41; p -value = 0.021) after adjusting for relevant confounders. Patients in the Q5 group exhibited significantly worse performance in the frontal domain., Conclusions: The ApoB/ApoA-I ratio in the acute stage of stroke independently predicted the development of PSCI at 3-6 months after stroke due to large artery atherosclerosis. Further, a high ApoB/ApoA-I ratio was specifically associated with frontal domain dysfunction.

Non-small-cell lung cancer (NSCLC) remains one of the leading causes of death worldwide. While NSCLCs possess antigens that can potentially elicit T cell responses, defective tumor antigen presentation and T cell activation hinder host anti-tumor immune responses. The NSCLC tumor microenvironment (TME) is composed of cellular and soluble mediators that can promote or combat tumor growth. The composition of the TME plays a critical role in promoting tumorigenesis and dictating anti-tumor immune responses to immunotherapy. Dendritic cells (DCs) are critical immune cells that activate anti-tumor T cell responses and sustain effector responses. DC vaccination is a promising cellular immunotherapy that has the potential to facilitate anti-tumor immune responses and transform the composition of the NSCLC TME via tumor antigen presentation and cell-cell communication. Here, we will review the features of the NSCLC TME with an emphasis on the immune cell phenotypes that directly interact with DCs. Additionally, we will summarize the major preclinical and clinical approaches for DC vaccine generation and examine how effective DC vaccination can transform the NSCLC TME toward a state of sustained anti-tumor immune signaling.

As the potential of pluripotent stem cell-derived differentiated cells has been demonstrated in regenerative medicine, differentiated vascular endothelial cells (ECs) are emerging as a therapeutic agent for the cardiovascular system. To verify the therapeutic efficacy of differentiated ECs in an ischemic model, human embryonic stem cells (hESCs) are induced as EC lineage and produce high-purity ECs through fluorescence-activated cell sorting (FACS). When hESC-ECs are transplanted into a hindlimb ischemic model, it is confirmed that blood flow and muscle regeneration are further improved by creating new blood vessels together with autologous ECs than the primary cell as cord blood endothelial progenitor cells (CB-EPCs). In addition, previously reported studies show the detection of transplanted cells engrafted in blood vessels through various tracking methods, but fail to provide accurate quantitative values over time. In this study, it is demonstrated that hESC-ECs are engrafted approximately sevenfold more than CB-EPCs by using an accelerator mass spectrometry (AMS)-based cell tracking technology that can perform quantification at the single cell level. An accurate quantification index is suggested. It has never been reported in in vivo kinetics of hESC-ECs that can act as therapeutic agents., (© 2023 Wiley-VCH GmbH.)

Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated., Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype., Methods and Study Design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months., Study Outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding., Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype., Trial Registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Objectives: More than half of patients with acute ischemic stroke develop post-stroke cognitive impairment (PSCI), a significant barrier to future neurological recovery. Thus, predicting cognitive trajectories post-AIS is crucial. Our primary objective is to determine whether brain network properties from electroencephalography (EEG) can predict post-stroke cognitive function using machine learning approach., Methods: We enrolled consecutive stroke patients who underwent both EEG during the acute stroke phase and cognitive assessments 3 months post-stroke. We preprocessed acute stroke EEG data to eliminate low-quality epochs, then performed independent component analysis and quantified network characteristics using iSyncBrain®. Cognitive function was evaluated using the Montreal cognitive assessment (MoCA). We initially categorized participants based on the lateralization of their lesions and then developed machine learning models to predict cognitive status in the left and right hemisphere lesion groups., Results: Eighty-seven patients were included, and the accuracy of lesion laterality prediction using EEG attributes was 97.0%. In the left hemispheric lesion group, the network attributes of the theta band were significantly correlated with MoCA scores, and higher global efficiency, clustering coefficient, and lower characteristic path length were associated with higher MoCA scores. Most features related to cognitive scores were selected from the frontal lobe. The predictive powers ( R -squared) were 0.76 and 0.65 for the left and right stroke groups, respectively., Conclusion: Estimating EEG-based network properties in the acute phase of ischemic stroke through a machine learning model has a potential to predict cognitive outcomes after ischemic stroke., Competing Interests: YH, UP, JS and SK were employed by iMedisync, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Hong, An, Park, Shin, Lee, Oh, Lee, Yu, Lim and Kang.)

Background: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT., Methods: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding., Results: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001)., Conclusion: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group ( P <0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). Conclusions Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.

Background: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission., Objective: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes., Patients and Methods: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored., Results: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (P non-linearity <0.001), with substantial relationships in the no pretreatment subgroup., Conclusions: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background and Objectives: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of patients with acute ischemic stroke (AIS). Thus, the prediction of cognitive outcomes in AIS may be useful for treatment decisions. This PSCI cohort study aimed to determine the applicability of a machine learning approach for predicting PSCI after stroke., Methods: This retrospective study used a prospective PSCI cohort of patients with AIS. Demographic features, clinical characteristics, and brain imaging variables previously known to be associated with PSCI were included in the analysis. The primary outcome was PSCI at 3-6 months, defined as an adjusted z-score of less than - 2.0 standard deviation in at least one of the four cognitive domains (memory, executive/frontal, visuospatial, and language), using the Korean version of the Vascular Cognitive Impairment Harmonization Standards-Neuropsychological Protocol (VCIHS-NP). We developed four machine learning models (logistic regression, support vector machine, extreme gradient boost, and artificial neural network) and compared their accuracies for outcome variables., Results: A total of 951 patients (mean age 65.7 ± 11.9; male 61.5%) with AIS were included in this study. The area under the curve for the extreme gradient boost and the artificial neural network was the highest (0.7919 and 0.7365, respectively) among the four models for predicting PSCI according to the VCIHS-NP definition. The most important features for predicting PSCI include the presence of cortical infarcts, mesial temporal lobe atrophy, initial stroke severity, stroke history, and strategic lesion infarcts., Conclusion: Our findings indicate that machine-learning algorithms, particularly the extreme gradient boost and the artificial neural network models, can best predict cognitive outcomes after ischemic stroke., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Hot-dip Al-Si alloy coatings with excellent resistance to corrosion and high-temperature oxidation have emerged as promising lightweight substitutes for conventional corrosion-resistant coatings. The introduction of Mg can be an effective strategy for enhancing the sacrificial protection capability of Al-Si coatings. In this study, the effects of Mg addition on the morphology, electrochemical behavior, and mechanical properties of Al-Si coatings were investigated, along with the Mg-content optimization of the coating layer. Adding Mg promoted the formation of finely distributed eutectic intermetallic phases, such as Al/Mg 2 Si and the primary Mg 2 Si phase. Notably, the Mg 2 Si phase coarsened significantly when ≥15 wt.% of Mg was added. In addition, an Al 3 Mg 2 intermetallic compound was observed in coating layers containing >20 wt.% of Mg, reducing the adhesion of the coating layers. Samples containing 5-10 wt.% of Mg exhibited excellent corrosion resistance (owing to a uniform distribution of the fine eutectic Al/Mg 2 Si phase and the formation of stable corrosion products), whereas those containing 20 wt.% of Mg exhibited unremarkable corrosion resistance (owing to the formation of an Al 3 Mg 2 phase that is susceptible to intergranular corrosion).

Introduction: Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis ( P. mirabilis )-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis., Methods: We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis -induced disease progression and pathology., Results and Discussion: Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis -induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis -mediated pathology of brain neurodegeneration., Competing Interests: MP was employed by MetaCen Therapeutics Inc. R&D Center. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huh, Choi, Lee, Kim, Choi, Ju, Eo, Park, Kim, Park, Lee and Oh.)

Hypothesis: Surface nanodroplets have recently been employed for in situ chemical analysis leveraging their low volume, e.g. O(10 -15 L), that enables rapid analyte extraction and pre-concentration. So far, most surface nanodroplets have been formed using single organic solvents such as 1-octanol, toluene, among others. Designing multicomponent surface nanodroplet with controllable composition is highly desirable for extending their application as extractant., Experiment: Here, we formed surface nanodroplets using green deep eutectic solvent (gDES) composed of thymol and decanoic acid, both of which are naturally occurring chemicals. The influence of parameters such as flowrate and the composition of deep eutectic solvent on the surface nanodroplet formation were studied. As proof-of-concept, the gDES surface nanodroplets were further used to extract and detect trace amounts of fluorescent rhodamine 6G dye and copper ions from water., Findings: The formation of gDES surface nanodroplets follows the theoretical model which states that the final droplet volume (V f ) scales with the Peclét number (Pe) of the flow during formation by the solvent exchange process, that is V f  ∼ Pe 3/4 , and the nanodroplets demonstrate excellent ability as extractant for rhodamine 6G and copper ions from water. Surprisingly, the confined volume of gDES surface nanodroplets enables fast and controlled formation of Cu (II)-decanoate crystal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown., Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes., Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores., Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups., Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Background: Previous studies have suggested that acute mood states may influence levels of fetal activity. Because the fetal nonstress test relies on markers of fetal activity to suggest fetal wellbeing, its interpretation may be affected by maternal mood., Objective: This study sought to determine if there are differences in nonstress test characteristics between pregnant individuals with and without symptoms of mood disorder., Study Design: In this prospective cohort study, we recruited pregnant individuals undergoing nonstress test in the third trimester and compared the results of the nonstress test between pregnant individuals with scores above and below the cutoff values on validated screening questionnaires for depression and anxiety symptoms, the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic information was collected from each participant at the time of recruitment, and medical information was extracted from the electronic medical record., Results: A total of 68 pregnant individuals were enrolled, 10 (15%) of which screened positive for perinatal mood disorders. There was no significant difference in means of time to reactivity (15.6 [4.8] minutes vs 15.0 [8.0] minutes, P=.77), number of accelerations (0.16/min [0.08] vs 0.16/min [0.10], P>.95), number of fetal movements (17.0 [14.7] vs 19.7 [20.4], P=.62), heart rate baseline (138.0 [7.5] bpm vs 139.2 [9.0] bpm, P=.67) or variability (8.5 [2.5] bpm vs 9.1 (4.3) bpm, P=.51) between pregnant individuals who screen positive for mood disorders and those who did not., Conclusion: Fetal heart rate patterns are similar in pregnant individuals with and without symptoms of mood disorder. The results provide reassurance that acute symptoms of anxiety and depression do not have significant effects on the fetal nonstress test., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke., Methods: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed., Results: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures., Conclusions: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke., Competing Interests: Disclosures None.

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis ( P. mirabilis ) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis -induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by amyloid-β (Aβ) deposition, accompanied by neuroinflammation and memory dysfunction. Houttuyniae Herba (aerial parts of Houttuynia cordata, also known as fish mint; HH), an herbal medicine traditionally used to treat fever, urinary disorders, and pus, is revealed to protect neurons from Aβ toxicity and regulate cholinergic dysfunction in AD models. In this study, we aimed to investigate the effects of HH on excessive accumulation of Aβ followed by neuroinflammation, synaptic degeneration, and memory impairment. Two-month-old 5xFAD transgenic mice were administered HH at 100 mg/kg for 4 months. We observed that HH treatment ameliorated memory impairment and reduced Aβ deposits in the brains of the mice. HH directly inhibited Aβ aggregation in vitro using the Thioflavin T assay and indirectly suppressed the amyloidogenic pathway by increasing alpha-secretase expression in the mice brain. In addition, HH exerted antineuroinflammatory effects by reducing of glial activation and p38 phosphorylation. Moreover, HH treatment increased the expression of synaptophysin, a presynaptic marker protein. Overall, HH alleviates memory impairment in AD by facilitating nonamyloidogenic pathway and inhibiting neuroinflammation. Therefore, we suggest that HH can be a promising herbal drug for patients with AD requiring multifaceted improvement., (© 2023 John Wiley & Sons Ltd.)

Background: Recent literature indicates that adverse childhood experiences have been associated with poor obstetrical outcomes, including pregnancy loss, preterm birth, and low birthweight. Several studies have been conducted in primarily self-identified White individuals who report middle to high income levels. Less is known about the impact of adverse childhood experiences on obstetrical outcomes in minority-identifying and low-income populations, who are known to experience a greater number of adverse childhood experiences and are at higher risk of maternal morbidity., Objective: This study aimed to examine associations between adverse childhood experiences and a broad range of obstetrical outcomes among predominantly Black-identifying pregnant persons who have low income and live in an urban area., Study Design: This is a single-center retrospective cohort study of pregnant persons referred to a mental healthcare manager because of elevated psychosocial risks identified by screening tools or provider concerns during the study period from April 2018 to May 2021. Pregnant persons aged <18 years and those who did not speak English were excluded. Patients completed validated mental and behavioral health screening tools including the Adverse Childhood Experiences Questionnaire. Medical charts were reviewed for obstetrical outcomes, including preterm birth, low birthweight, hypertensive disorders of pregnancy, gestational diabetes mellitus, chorioamnionitis, sexually transmitted infection, maternal group B streptococcus carrier status, type of delivery, and attendance of a postpartum visit. Associations between high (≥4) and very high (≥6) of 10 adverse childhood experience score and obstetrical outcomes were analyzed using bivariate analysis and multivariate logistic regression, adjusting for confounding factors (significant at P<.05 in bivariate analysis)., Results: Our cohort included 192 pregnant persons, of whom 176 (91.7%) self-identified as Black or African American and 181 (94.8%) had public insurance (used as a proxy for low income). Adverse childhood experience score ≥4 was reported by 91 (47.4%) individuals and score ≥6 by 50 (26%). On univariate analysis, adverse childhood experience score ≥4 was associated with preterm birth (odds ratio, 2.17; 95% confidence interval, 1.02-4.61). Adverse childhood experience score ≥6 was associated with hypertensive disorders of pregnancy (odds ratio, 2.09; 95% confidence interval, 1.05-4.15) and preterm birth (odds ratio, 2.29; 95% confidence interval, 1.05-4.96). After accounting for chronic hypertension, associations between adverse childhood experience score and obstetrical outcomes were no longer significant., Conclusion: Approximately half of the pregnant persons referred to a mental healthcare manager had a high adverse childhood experience score, underscoring the high burden of childhood trauma on populations facing long-standing systemic racism and barriers to healthcare access. High and very high adverse childhood experience score may be associated with chronic health conditions that predate pregnancy and can alter obstetrical outcomes. Obstetrical care providers have a unique opportunity to mitigate risk of associated poor health outcomes during preconception and prenatal care by screening for adverse childhood experiences., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Long-term administration of levodopa (L-DOPA) to patients with Parkinson's disease (PD) commonly results in involuntary dyskinetic movements, as is known for L-DOPA-induced dyskinesia (LID). 5-Hydroxytryptophan (5-HTP) has recently been shown to alleviate LID; however, no biochemical alterations to aberrant excitatory conditions have been revealed yet. In the present study, we aimed to confirm its anti-dyskinetic effect and to discover the unknown molecular mechanisms of action of 5-HTP in LID. We made an LID-induced mouse model through chronic L-DOPA treatment to 6-hydroxydopamine-induced hemi-parkinsonian mice and then administered 5-HTP 60 mg/kg for 15 days orally to LID-induced mice. In addition, we performed behavioral tests and analyzed the histological alterations in the lesioned part of the striatum (ST). Our results showed that 5-HTP significantly suppressed all types of dyskinetic movements (axial, limb, orolingual and locomotive) and its effects were similar to those of amantadine, the only approved drug by Food and Drug Administration. Moreover, 5-HTP did not affect the efficacy of L-DOPA on PD motor manifestations. From a molecular perspective, 5-HTP treatment significantly decreased phosphorylated CREB and ΔFosB expression, commonly known as downstream factors, increased in LID conditions. Furthermore, we found that the effects of 5-HTP were not mediated by dopamine1 receptor (D1)/DARPP32/ERK signaling, but regulated by AKT/mTOR/S6K signaling, which showed different mechanisms with amantadine in the denervated ST. Taken together, 5-HTP alleviates LID by regulating the hyperactivated striatal AKT/mTOR/S6K and CREB/ΔFosB signaling.

Type 2 diabetes mellitus (T2DM) is one of the biggest public health issues worldwide and closely related to development of other chronic diseases such as cardiovascular diseases, cancer and neurodegenerative diseases. Considerable percentage of T2DM patients undergo have suffered from binge eating disorder which exacerbates insulin resistance and metabolic challenges. Longan ( Dimocarpus longan L. ) and its constituents are reported for their various health benefits. However, it is still unknown whether longan fruit supplementation can ameliorate glucose homeostasis and binge eating disorder found in T2DM. The current study aimed to investigate whether longan fruit extract (LE) supplementation can improve diabetic hyperglycemia through modulation of feeding center located in hypothalamus of db/db T2DM mice. As a result, LE supplementation ameliorated fasting blood glucose levels and reduced excessive epididymal fat accumulation. In addition, LE administration improved glucose tolerance and insulin sensitivity in db/db mice. Especially, LE supplemented mice showed less food consumption which was in line with increase of pro-opiomelanocortin (POMC) neuronal activities and decrease of agouti-related peptide (AgRP) neuronal activities. Furthermore, LE supplementation reduced hypothalamic endoplasmic reticulum (ER) stress which was stimulated in db/db mice. As ER stress is a crucial factor involving in appetite control and glucose homeostasis, the effect of LE supplementation on circulating glucose levels and feeding behavior might be mediated by suppression of hypothalamic ER stress. Collectively, these findings suggest that LE could be a potential nutraceutical for improvement of T2DM as well as patients with satiety issues., Competing Interests: SK, JC, SWK, and MS are employed by MThera Pharma Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Eo, Kim, Ju, Huh, Kim, Choi, Kim, Son and Oh.)

Background and Objectives: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location., Methods: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations., Results: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001)., Discussion: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Developing a methodology to enhance long-term stability is one of the most important issues in MXene research, since they are prone to oxidation in the ambient environment. Although various approaches have been suggested to improve the stability of MXene, they have suffered from complicated processes and limited applicability to various types of MXene nanostructures. Herein, we report a simple and versatile technique to enhance the environmental stability of MXenes. Ti 3 C 2 T x MXene films were decorated with a highly hydrophobic polymer, 1H,1H,2H,2H-perfluorodecyl methacrylate (PFDMA), using initiated chemical vapor deposition (iCVD) where iCVD allows the facile postdeposition of polymer films of desired thickness on MXene films. The oxidation resistance was evaluated by fabricating MXene gas sensors and measuring the change in signal-to-noise ratio (SNR) of volatile organic compound (VOC) gases under harsh conditions (RH 100% at 50 °C) for several weeks where the performance in the absence and presence of PFDMA was compared. The results show that while the SNR of PFDMA-Ti 3 C 2 T x sensors was retained, a dramatic increase of the noise level and a decrease in the SNR were observed in pristine Ti 3 C 2 T x . We believe that this simple and nondestructive method will offer great potential to enhance the stability of a wide range of MXenes.

Background/objectives: Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization., Materials/methods: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks., Results: Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysin-treated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice., Conclusion: Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosis-associated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2023 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Background: Hypertensive disorders of pregnancy are a leading cause of severe maternal morbidity and mortality, and studies have shown that more than 60% of cases are preventable. As part of a statewide quality Maternal Safety Quality Improvement Project, we adapted the Alliance for Innovation on Maternal Health Severe Hypertension in Pregnancy bundle in a consortium of maternity hospitals in Ohio to improve care processes and outcomes for patients with a severe hypertensive event during pregnancy or the postpartum period., Objective: This study aimed to report the first year of data from this Maternal Safety Quality Improvement Project, including an assessment of the process measures by hospital level of maternal care designation, and provide perspective on the unique challenges of implementing a large-scale Maternal Safety Quality Improvement Project during a global pandemic., Study Design: This Maternal Safety Quality Improvement Project engaged Ohio level 1 to 4 maternity hospitals and provided multimodal quality improvement support. Participating hospitals submitted monthly patient-level data, which included all cases of new-onset sustained severe hypertension. The primary process measure was the proportion of birthing people in Ohio with sustained severe hypertension who received treatment with appropriate acute antihypertensive therapy within 60 minutes. The secondary process measures included receipt of a follow-up appointment after hospital discharge within 72 hours (if discharged on medication) or 10 days (if discharged without medication), a blood pressure cuff on hospital discharge, and education about urgent maternal warning signs. Data for primary and secondary process measures were plotted on a biweekly basis, and statistical process control methods were used to identify special cause variation over time. Data were stratified by various demographic variables, including race or ethnicity, insurance status, and maternal level of care. To assess the effect of the COVID-19 pandemic on this Maternal Safety Quality Improvement Project, process measure data were compared with COVID-19 case volume in Ohio across the study epoch., Results: A total of 29 hospitals participated in the project from July 2020 to September 2021. Data were collected on 4948 hypertensive events representing 4678 unique patients. In aggregate, the primary process measure (timely and appropriate treatment) demonstrated a 19.3% increase (from a baseline of 56.5% to 67.4%; P<.001). The secondary process measures demonstrated significant increases ranging from 26.1% to 166.8% (all P<.001). Both non-Hispanic Black and White pregnant or postpartum people demonstrated shifts and sustained improvements in the treatment of severe hypertension, which did not differ by race across the study period. Process measure improvements were achieved and sustained across peaks in the COVID-19 pandemic., Conclusion: This Ohio Maternal Safety Quality Improvement Project demonstrated meaningful changes in project process measures in the identification and treatment of severe hypertension in pregnancy and the postpartum period. Process measures improvements were achieved across all hospital levels of maternal care, and differences were not observed by race or ethnicity. Our findings suggest that a robust and comprehensive quality improvement initiative with appropriate support and resources can achieve meaningful gains in the setting of a global pandemic., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: No guidelines exist for recommending return to driving. This study will examine time to brake (TTB) after lower extremity injuries versus in uninjured people. The potential effect of various types of lower extremity injuries on TTB will be measured., Methods: Patients with injuries to the pelvis, hip, femur, knee, tibia, ankle, and foot underwent testing using a driving simulator to assess TTB. Comparison was with a control group of uninjured people., Results: Two-hundred thirty-two patients with lower extremity injuries participated. The majority were in the tibia and ankle regions (47%). Mean TTB for control subjects was 0.74 seconds, compared with 0.83 for injured patients, noting a 0.09-second difference (P = 0.017). Left-sided injuries averaged TTB of 0.80 seconds, right-sided injuries averaged TTB of 0.86 seconds, and bilateral injuries averaged TTB of 0.83 seconds, all prolonged versus control subjects. The longest TTB was exhibited after ankle and foot injuries (0.89 seconds) while the shortest was after tibial shaft fractures (0.76 seconds)., Discussion: Any lower extremity injury caused a prolonged TTB compared with control patients. Left, right, and bilateral injuries all had longer TTB. Ankle and foot injuries experienced the longest TTB. Additional investigation is warranted to develop safe guidelines for return to driving., Competing Interests: This research was supported by a grant from the Orthopaedic Trauma Association. Each author certifies that he or she has no other commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) or other financial or non-financial concerns that might pose a conflict of interest in connection with the submitted article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

This study presents the use of organic gel-forming material for the construction of hydraulic barriers in aquifer, which can be easily removed after use. Experiments on the performance of the temporary hydraulic barrier during NAPL removal (aquifer flushing) were also conducted. An aqueous solution of sodium alginate was injected into the horizontally oriented, 2-dimensional flow chamber packed with sand, followed by gelation using a calcium solution. The alginate gel formed in the porous media produced a circular shape barrier (24 cm diameter, 1.3 cm thickness) that was successfully removed using sodium bicarbonate solution (1.0 M) in 72 h, whereas the gel was stable for 7 days during simulated groundwater flushing at the same flow rate as the sodium bicarbonate solution. When circular hydraulic barriers (12 cm diameter each, 14 cm apart) were set on either side of the NAPL (n-hexane and PCE mixture)-contaminated zone, the increased water flux during water flushing resulted in significantly increased PCE removal by almost 108%. When a surfactant solution (sodium dodecyl sulfate, 0.037%) was applied, the influenced groundwater flow controlled by hydraulic barriers on the NAPL removal was amplified by 196% removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Hypertension is estimated at a prevalence of 30 to 50% in the United States. Only 54% of patients with hypertension have their condition adequately controlled. This study aimed to use academic detailing (AD) to improve practice team knowledge and confidence in blood pressure (BP) management, specifically in low-income, underresourced patient populations., Methods: AD was developed for five practices that care for high percentages of Medicaid-eligible patients. A needs assessment was administered to each site's practice champion to determine high-yield AD sessions for their team. Presession and postsession evaluations were completed by practice team members., Results: Fifty providers and eight staff member participants completed evaluations over nine sessions for two AD topics at four practice sites. Statistical significance was found for several items within sessions including accurately choosing cuff sizes and identifying barriers to home BP monitoring., Discussion: AD is a potentially financially efficient model to improve knowledge and confidence in hypertension care at the practice level. Tailoring session content to specific needs of a practice site, along with an identified practice champion, facilitated implementation of the program. This replicable model is one way to deliver evidence-based information to those who serve Medicaid-eligible patients., Competing Interests: Disclosures: The authors declare no conflict of interest., (Copyright © 2022 The Alliance for Continuing Education in the Health Professions, the Association for Hospital Medical Education, and the Society for Academic Continuing Medical Education.)

Objective: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population., Methods: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel., Results: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients., Interpretation: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782., (© 2022 American Neurological Association.)

We aimed to investigate the effects of exercise habit changes on the risk of incident dementia after ischemic stroke using the Korean National Health Insurance Services Database. This study included 223,426 patients with a new diagnosis of ischemic stroke between 2010 and 2016 who underwent two serial ambulatory health checkups. The participants were divided into four categories according to their habit change or regular exercise: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was new diagnosis of dementia. Multivariate Cox proportional models were used to assess the effects of changes in exercise habits on the risk of incident dementia. After a median of 4.02 years of follow-up, 22,554 (10.09%) dementia cases were observed. After adjusting for covariates, exercise dropouts, new exercisers, and exercise maintainers were significantly associated with a lower risk of incident dementia than persistent non-exercisers (adjusted hazard ratio [aHR] 0.937; 95% confidence interval [CI] 0.905-0.970, aHR 0.876; 95% CI 0.843-0.909, aHR 0.705; 95% CI 0.677-0.734, respectively). The impact of changes in exercise habit was more prominent in the 40-65 years age group. An energy expenditure ≥ 1000 metabolic equivalents of task-min/wk post-stroke, regardless of pre-stroke physical activity status, was mostly associated with a lower risk of each outcome. In this retrospective cohort study, initiating or continuing moderate-to-vigorous exercise after ischemic stroke was associated with a lower risk of dementia development. Further, pre-stroke regular physical activity also reduced the risk of incident dementia. The promotion of exercise in ambulatory stroke patients may reduce their future risk of incident dementia., (© 2023. The Author(s).)