TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.

BACKGROUND: The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification. METHODS: The atherosclerotic phenotypes of Txnip-/- mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of Tagln-Cre; Txnipflox/flox mice (smooth muscle cell-specific Txnip ablation model), and the mice transplanted with the bone marrow of Txnip-/- mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed. RESULTS: Atherosclerotic lesions of Txnip-/- mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in Txnip-/- mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation-related pathways and bone morphogenetic protein signaling in Txnip-/- mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions. Tagln-Cre; Txnipflox/flox mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of Txnip-/- mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation. CONCLUSIONS: Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.

Investigation of Neuromodulatory Effect of Anodal Cerebellar Transcranial Direct Current Stimulation on the Primary Motor Cortex Using Functional Near-Infrared Spectroscopy.

Cerebellar brain inhibition (CBI), a neural connection between the cerebellum and primary motor cortex (M1), has been researched as a target pathway for neuromodulation to improve clinical outcomes in various neurological diseases. However, conflicting results of anodal cerebellar transcranial direct current stimulation (acb-tDCS) on M1 excitability indicate that additional investigation is required to examine its precise effect. This study aimed to gather evidence of the neuromodulatory effect of acb-tDCS on the M1 using functional near-infrared spectroscopy (fNIRS). Sixteen healthy participants were included in this cross-over study. Participants received real and sham acb-tDCS randomly, with a minimum 1-week washout period between them. The anode and cathode were placed on the right cerebellum and the right buccinator muscle, respectively. Stimulation lasted 20 min at an intensity of 2 mA, and fNIRS data were recorded for 42 min (including a 4-min baseline before stimulation and an 18-min post-stimulation duration) using eight channels attached bilaterally on the M1. acb-tDCS induced a significant decrease in oxyhemoglobin (HbO) concentration (inhibitory effect) in the left (contralateral) M1, whereas it induced a significant increase in HbO concentration (excitatory effect) in the right (ipsilateral) M1 compared to sham tDCS during (p < 0.05) and after stimulation (p < 0.01) in a group level analysis. At the individual level, variations in response to acb-tDCS were observed. Our findings demonstrate the neuromodulatory effects of acb-tDCS on the bilateral M1 in terms of neuronal hemodynamics.

Factors to predict recurrence after epidural blood patch in patients with spontaneous intracranial hypotension.

OBJECTIVES: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). BACKGROUND: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. METHODS: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. RESULTS: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). CONCLUSION: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.

PREVALENCE AND RISK FACTORS OF AGE-RELATED MACULAR DEGENERATION FEATURES AMONG PILOTS.

PURPOSE: To investigate the prevalence and risk factors of age-related macular degeneration features among pilots of Republic of Korea Air Force. METHODS: This retrospective, cross-sectional study was performed with a total of 2781 Republic of Korea Air Force pilots who underwent regular medical examinations between 2020 and 2021. Age-related macular degeneration features were determined and graded by fundus photographs. Risk factors were identified with logistic regression analysis in odds ratio (OR) and 95% confidence interval (CI). RESULTS: The prevalence was 12.9% in the Republic of Korea Air Force pilots and 35.2% in those older than 50 years. Pilots with age-related macular degeneration features were positively associated with age (OR: 1.082, CI: 1.067-1.096, P < 0.001), male sex (OR: 0.229, CI: 0.056-0.939, P = 0.041), smoking (OR: 1.027, CI: 1.008-1.047, P = 0.006), flight time (OR: 1.004, CI: 1.003-1.005, P < 0.001), total cholesterol (OR: 1.004, CI: 1.000-1.007, P = 0.033), and low-density lipoprotein (OR: 1.005, CI: 1.001-1.008, P = 0.011). Aircraft type was also identified as a risk factor (OR: 0.617, CI: 0.460-0.827 for carrier, OR: 0.572, CI: 0.348-0.940 for helicopter, P = 0.002), with fighter pilots having a higher risk than carrier and helicopter pilots. The results were similar for pilots older than 50 years. CONCLUSION: The prevalence of age-related macular degeneration features in Republic of Korea Air Force pilots was higher than in other general populations studied. Identified risk factors such as flight time and aircraft type suggest potential occupational risk of age-related macular degeneration in aviators.

Recent Outcomes of Surgical Redo Aortic Valve Replacement in Prosthetic Valve Failure.

BACKGROUND: As redo surgical aortic valve replacement (AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. METHODS AND RESULTS: This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (hazard ratio [HR]: 3.990, p = 0.014), longer cardiopulmonary bypass time (HR: 1.006, p = 0.037), and lower left ventricular ejection fraction (LVEF) (HR: 0.956, p = 0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. CONCLUSION: The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for nonendocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

A Network Meta-Analysis of Randomized Controlled Trials Assessing Intraoperative Anesthetic Therapies for Analgesic Efficacy and Morphine Consumption Following Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to compare intraoperative anesthetic therapies for total knee arthroplasty (TKA) regarding postoperative analgesic efficacy and morphine consumption by conducting a systematic literature search. METHODS: Randomized controlled trials of TKA using various anesthetic therapies were identified from various databases from conception through December 31, 2021. A network meta-analysis of relevant literature was performed to investigate which treatment showed better outcomes. In total, 40 trials were included in this study. RESULTS: Surface under the cumulative ranking curve showed local infiltration anesthesia (LIA) with saphenous nerve block (SNB) to produce the best pain relief on postoperative days (PODs) 1 and 2 and the best reduction of morphine consumption on PODs 1 and 3. However, femoral nerve block showed the largest effect on pain relief on POD 3, and liposomal bupivacaine showed the largest effect on reduction of morphine consumption on POD 2. CONCLUSIONS: According to this network meta-analysis, surface under the cumulative ranking curve percentage showed that LIA with SNB provided the best analgesic effect after TKA. Furthermore, patients receiving LIA with SNB had the lowest consumption of morphine. Although femoral nerve block resulted in better pain relief on POD 3, LIA with SNB could be selected first when trying to reduce morphine consumption or increase early ambulation.

Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.

Deep learning reconstruction in pediatric brain MRI: comparison of image quality with conventional T2-weighted MRI.

INTRODUCTION: Deep learning-based MRI reconstruction has recently been introduced to improve image quality. This study aimed to evaluate the performance of deep learning reconstruction in pediatric brain MRI. METHODS: A total of 107 consecutive children who underwent 3.0 T brain MRI were included in this study. T2-weighted brain MRI was reconstructed using the three different reconstruction modes: deep learning reconstruction, conventional reconstruction with an intensity filter, and original T2 image without a filter. Two pediatric radiologists independently evaluated the following image quality parameters of three reconstructed images on a 5-point scale: overall image quality, image noisiness, sharpness of gray-white matter differentiation, truncation artifact, motion artifact, cerebrospinal fluid and vascular pulsation artifacts, and lesion conspicuity. The subjective image quality parameters were compared among the three reconstruction modes. Quantitative analysis of the signal uniformity using the coefficient of variation was performed for each reconstruction. RESULTS: The overall image quality, noisiness, and gray-white matter sharpness were significantly better with deep learning reconstruction than with conventional or original reconstruction (all P < 0.001). Deep learning reconstruction had significantly fewer truncation artifacts than the other two reconstructions (all P < 0.001). Motion and pulsation artifacts showed no significant differences among the three reconstruction modes. For 36 lesions in 107 patients, lesion conspicuity was better with deep learning reconstruction than original reconstruction. Deep learning reconstruction showed lower signal variation compared to conventional and original reconstructions. CONCLUSION: Deep learning reconstruction can reduce noise and truncation artifacts and improve lesion conspicuity and overall image quality in pediatric T2-weighted brain MRI.

Exogenous Lipoxin A4 attenuates IL4-induced Mucin Expression in Human Airway Epithelial Cells.

Introduction: The proinflammatory cytokine interleukin-4 (IL-4) induces mucus hypersecretion by human airway epithelial cells and the MAP kinase signalling pathway may be important in terms of IL-4-induced MUC5AC gene expression. Lipoxin A4 (LXA4) is an arachidonic acid-derived mediator that promotes inflammation by binding to the anti-inflammatory receptors (ALXs) or the formyl-peptide receptor like-1 (FPRL1) protein expressed by airway epithelial cells. Here, we explore the effects of LXA4 on IL-4-induced mucin gene expression in, and secretion from, human airway epithelial cells. Methods: We co-treated cells with IL-4 (20 ng/mL) and LXA4 (1 nM) and measured the expression levels of mRNAs encoding MUC5AC and 5B via real-time polymerase chain reaction; protein expression levels were determined by Western blotting and immunocytofluorescence. The ability of IL-4 and LXA4 to suppress protein expression was determined by Western blotting. Results: IL-4 increased MUC5AC and 5B gene and protein expression. LXA4 suppressed IL-4-induced MUC5AC and 5B gene and protein expression by interacting with the IL4 receptor and mitogen-activated protein kinase (MAPK) pathway, including both phospho-p38 MAPK and phospho-extracellular signal-regulated kinase (phospho-ERK). IL-4 and LXA4 increased and decreased, respectively, the number of cells that stained with anti-MUC5AC and 5B antibodies. Conclusions: LXA4 may regulate mucus hypersecretion induced by IL4 in human airway epithelial cells.

Soluble Programmed Cell Death Ligand-1 (sPD-L1) Levels in Various Cancer Types and Normal Populations.

BACKGROUND: To date, PD-L1 expression in tumor tissue, assessed by immunohistochemical stain, is clinically applicable as a predictive companion biomarker for PD-1/PD-L1 inhibitor which has been highlighted over the past several years. Before blood-based sPD-L1 enters clinical use, it is critical to establish the reference range. This study was designed to investigate soluble sPD-L1 levels in various cancer patients and normal population. METHODS: For the detection of sPD-L1, 4 cancer groups (hepatocellular carcinoma, lung cancer, bladder cancer, gastric cancer) and healthy volunteers' samples were analyzed using an ELISA kit. Using a receiver operating characteristic curve, optimal sPD-L1 cutoff levels were determined. RESULTS: The mean serum sPD-L1 level of the normal population was 59.97 pg/mL (range; 23.780 - 115.2 pg/mL). In various cancer types, serum sPD-L1 levels ranged from 38.696 pg/mL to 228.77 pg/mL, and cutoff values under AUC ranged from 60.307 pg/mL to 64.371 pg/mL. CONCLUSIONS: sPD-L1 can be used as a screening biomarker in various cancer patients referring to optimal cutoff levels suggested.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Differences in time-to-fusion based on "absence of peri-graft radiolucency" and "trabecular bone bridging" criteria after transforaminal lumbar interbody fusion in patients with low and normal bone density.

OBJECTIVE: To investigate the difference in time-to-fusion between two sets of interbody fusion criteria (absence of peri-graft radiolucency vs. trabecular bone bridging), and to determine the effect of osteoporosis on time-to-fusion. MATERIALS AND METHODS: This retrospective study enrolled 79 patients treated for degenerative disease with one-level transforaminal lumbar interbody fusion from February 2012 to December 2018, and who had both pre- and post-operative CTs. Patients were divided into osteoporosis, osteopenia, and normal groups based on L1 vertebral body attenuation values in pre-operative CT with cutoff of 90 Hounsfield units (HU) and 120 HU. The osteoporosis, osteopenia, and normal groups included 36 patients (mean age: 69.9 years; 8 men and 28 women), 18 patients (mean age: 62.6 years; 7 men and 11 women), and 25 patients (mean age: 56.6 years; 15 men and 10 women), respectively. Fusion was assessed annually on post-operative CT images using absence of peri-graft radiolucency and trabecular bone bridging criteria. Time-to-fusion was estimated using the Kaplan-Meier method, and differences between the groups were examined using the log-rank test. Cox proportional hazards regression was performed. RESULTS: Time-to-fusion took significantly longer in the osteoporosis group in both fusion criteria (0.5 years in normal vs. 2 years in osteopenia vs. 3 years in osteoporosis for absence of peri-graft radiolucency; p = 0.003, and 3 years vs. 4 years vs. 5 years for trabecular bone bridging; p = 0.001). Only osteoporosis grouping was independent risk factor for slow trabecular bone fusion (hazard ratio:0.339; p = 0.003). CONCLUSION: The median time to fusion was significantly longer when using trabecular bone bridging criteria than absence of peri-graft radiolucency criteria.

Aortic Valve Replacement in the Era of Transcatheter Aortic Valve Implantation: Current Status in Korea.

BACKGROUND: In the era of transcatheter aortic valve implantation, this study was conducted to investigate the current trend of aortic valve procedures in Korea and to evaluate the early and mid-term outcomes of isolated surgical aortic valve replacement (SAVR) using bioprosthetic valves in contemporary Korea. METHODS: Contemporary outcomes of isolated bioprosthetic SAVR in Korea were analyzed using the datasets on a multicenter basis. Patients who underwent isolated SAVR using bioprostheses from June 2015 to May 2019 were included, and those with concomitant cardiac procedures, SAVR with mechanical valve, or SAVR for infective endocarditis were excluded. A total of 456 patients from 4 large-volume centers were enrolled in this study. Median follow-up duration was 43.4 months. Early postoperative outcomes, mid-term clinical outcomes, and echocardiographic outcomes were evaluated. RESULTS: Mean age of the patients was 73.1 ± 7.3 years, and EuroSCORE II was 2.23 ± 2.09. The cardiopulmonary bypass time and aortic cross-clamp times were median 106 and 76 minutes, respectively. SAVR was performed with full median sternotomy (81.8%), right thoracotomy (14.7%), or partial sternotomy (3.5%). Operative mortality was 1.8%. The incidences of stroke and permanent pacemaker implantation were 1.1% and 1.1%, respectively. Paravalvular regurgitation ≥ mild was detected in 2.6% of the patients. Cumulative incidence of all-cause mortality at 5 years was 13.0%. Cumulative incidences of cardiovascular mortality and bioprosthetic valve dysfunction at 5 years were 7.6% and 6.8%, respectively. CONCLUSION: The most recent data for isolated SAVR using bioprostheses in Korea resulted in excellent early and mid-term outcomes in a multicenter study.

A Novel Early Life Stress Model Affects Brain Development and Behavior in Mice.

Early life stress (ELS) in developing children has been linked to physical and psychological sequelae in adulthood. In the present study, we investigated the effects of ELS on brain and behavioral development by establishing a novel ELS model that combined the maternal separation paradigm and mesh platform condition. We found that the novel ELS model caused anxiety- and depression-like behaviors and induced social deficits and memory impairment in the offspring of mice. In particular, the novel ELS model induced more enhanced depression-like behavior and memory impairment than the maternal separation model, which is the established ELS model. Furthermore, the novel ELS caused upregulation of arginine vasopressin expression and downregulation of GABAergic interneuron markers, such as parvalbumin (PV), vasoactive intestinal peptide, and calbindin-D28k (CaBP-28k), in the brains of the mice. Finally, the offspring in the novel ELS model showed a decreased number of cortical PV-, CaBP-28k-positive cells and an increased number of cortical ionized calcium-binding adaptors-positive cells in their brains compared to mice in the established ELS model. Collectively, these results indicated that the novel ELS model induced more negative effects on brain and behavioral development than the established ELS model.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Effect of Home-Based Self-Management Intervention for Community-Dwelling Patients with Early Parkinson's Disease: A Feasibility Study.

PURPOSE: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). DESIGN: A randomized-controlled design. METHODS: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. FINDINGS: Physical activity and non-motor symptoms improved more in the intervention group than in the control group. CONCLUSION: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. CLINICAL EVIDENCE: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.

Effect of Perioperative Intravenous Iron Supplementation for Complex Cardiac Surgery on Transfusion Requirements: A Randomized, Double-blinded Placebo-controlled Trial.

OBJECTIVES: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY OF BACKGROUND DATA: Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS: Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS: pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dL vs 10.9 ± 1.4 g/dL, P < 0.001). The iron group showed higher reticulocyte count [205 (150-267)×103/µL vs 164 (122-207)×103/µL, P = 0.003] at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 [106.3 (42.9-115.9) ng/mL vs 39.3 (33.3-43.6) ng/mL, P < 0.001]. Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS: Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

True holographic ghost illusion.

Pepper's ghost optical illusion, used in amusement parks, theaters, movies, museums, and other venues since 1862, is produced by reflected light and is often wrongly described as holographic. This paper presents an alternative illusion technique based on the use of full-color analog Denisyuk holograms mixed with real elements with the help of special lighting. The result is a stunning applied-science experiment that arouses the curiosity of even the most discerning observer, first by combining the real-world and holography on a level never before achieved, and then by creating an unexpected final effect of disappearance.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Occurrence and characteristics of microplastics in fish of the Han River, South Korea: Factors affecting microplastic abundance in fish.

This study examined the abundance of microplastics (MPs) in 106 fish from 22 species inhabiting three sites of the Han River, South Korea. In total, 1753 MPs from 106 fish samples were identified with an average abundance of 15.60 ± 13.45 MPs per individual fish (MPs indiv-1) in the North Han River, 16.35 ± 12.32 MPs indiv-1 in the South Han River, and 20.14 ± 10.01 MPs indiv-1 in downstream of the Han River, indicating that the fish in the downstream of the Han River was the most contaminated by MPs. The dominant size of MPs detected in fish ranged between 0.1 and 0.2 mm, and the most common polymer types found in fish were polypropylene (PP) (≥40%) and polyethylene (PE) (≥23%), followed by polytetrafluoroethylene (PTFE) (≥16%) at all sampling locations. A significant correlation was observed between the log-transformed number of MPs with log-transformed fish length (p < 0.01) and with log-transformed fish weight (p < 0.01). The Kruskal-Wallis test disclosed a significant difference in the number of MPs among the feeding habits (p < 0.01), indicating that omnivorous and insectivorous fish contained more MPs than carnivorous and herbivorous fish. In addition, fish habitat result showed that pelagic fish contained a higher level of MPs than demersal fish, but no significant differences in the number of MPs among fish habitats were observed (p > 0.05).