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Context: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed.Objectives: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect.Design, Setting, and Patients: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute.Interventions: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI.Main Outcome Measures: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size.Results: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups.Conclusion: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo.Trial Registration: clinicaltrials.gov Identifier: NCT00684021. [ABSTRACT FROM AUTHOR]

Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina.Design, Setting, and Patients: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011.Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group).Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory.Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement.Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT.Trial Registration: clinicaltrials.gov Identifier: NCT00824005. [ABSTRACT FROM AUTHOR]

Context: Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation.Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI.Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011.Interventions: Intracoronary infusion of 150 × 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing.Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size.Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline.Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months.Trial Registration: clinicaltrials.gov Identifier: NCT00684060. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to report our experience with a routine completion angiogram after coronary artery bypass surgery (CABG) and simultaneous (1-stop) percutaneous coronary intervention (PCI) at the time of CABG performed in the hybrid catheterization laboratory/operating room. Background: The value of a routine completion angiogram after CABG and 1-stop hybrid CABG/PCI remains unresolved. Methods: Between April 2005 and July 2007, 366 consecutive patients underwent CABG surgery, with (n = 112) or without (n = 254) concomitant 1-stop PCI (hybrid), all with completion angiography before chest closure. Among the 112 1-stop hybrid CABG/PCI patients, 67 (60%) underwent a planned hybrid procedure based on pre-operative assessment, whereas 45 (40%) underwent open-chest PCI (unplanned hybrid) based on intraoperative findings. Results: Among the 796 CABG grafts (345 left internal mammary artery, 12 right internal mammary artery/radial, and 439 veins), 97 (12%) angiographic defects were identified. Defects were repaired with either a minor adjustment of the graft (n = 22, 2.8%), with intraoperative open-chest PCI (unplanned hybrid, n = 48, 6%) or with traditional surgical revision (n = 27, 3.4%). Hybrid patients had clinical outcomes similar to standard CABG patients. Conclusions: Routine completion angiography detected 12% of grafts with important angiographic defects. One-stop hybrid coronary revascularization is reasonable, safe, and feasible. Combining the tools of the catheterization laboratory and operating room greatly enhances the options available to the surgeon and cardiologist for patients with complex coronary artery disease. [ABSTRACT FROM AUTHOR]

Cardiac remodeling is an end-stage manifestation of multiple cardiovascular diseases, and microRNAs are involved in a variety of posttranscriptional regulatory processes. miR-363-5p targeting Thrombospondin3 (THBS3) has been shown to play an important regulatory role in vascular endothelial cells, but the roles of these two in cardiac remodeling are unknown. Firstly, we established an in vivo model of cardiac remodeling by transverse aortic narrow (TAC), and then we stimulated a human cardiomyocyte cell line (AC16) and a human cardiac fibroblast cell line (HCF) using 1 μmol/L angiotensin II (Ang II) to establish an in vitro model of cardiac hypertrophy and an in vitro model of myocardial fibrosis, respectively. In all three of the above models, we found a significant decreasing trend of miR-363-5p, suggesting that it plays a key regulatory role in the occurrence and development of cardiac remodeling. Subsequently, overexpression of miR-363-5p significantly attenuated myocardial hypertrophy and myocardial fibrosis in vitro as evidenced by reduced the area of AC16, the cell viability of HCFs, the relative expression of the protein of fetal genes (ANP, BNP, β-MHC) and fibrosis marker (collagen I, collagen III, α-SMA), whereas inhibition of miR-363-5p expression showed the opposite trend. In addition, we also confirmed the targeted binding relationship between miR-363-5p and THBS3 by dual luciferase reporter gene assay, and the expression of THBS3 was directly inhibited by miR-363-5p. Moreover, overexpression of miR-363-5p with THBS3 simultaneously partially eliminated the delaying effect of miR-363-5p on myocardial hypertrophy and myocardial fibrosis in vitro. In conclusion, Overexpression of miR-363-5p attenuated the prohypertrophic and profibrotic effects of Ang II on AC16 and HCF by a mechanism related to the inhibition of THBS3 expression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variation in determining death by neurologic criteria (DNC). We aim to describe the diagnostic criteria and barriers for DNC in adults on ECMO in a tertiary care center., Methods: A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016 to March 2022. Brain death was defined according to the 2010 American Academy of Neurology guidelines and following the 2020 World Brain Death Project recommendations for performing AT in ECMO patients., Results: Eight (2.7%) ECMO patients (median age = 44 years, 75% male, 50% VA-ECMO) met criteria for DNC, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (transcranial doppler and electroencephalography) were consistent with DNC. An additional seven (2.3%) patients (median age = 55 years, 71% male, 86% VA-ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment (WLST) before a full evaluation was completed. In these patients, AT was never performed, and ancillary tests were inconsistent with either neurological exam findings and/or neuroimaging supporting DNC, or with each other., Conclusion: AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with DNC and was always consistent with the neurological exam and imaging findings, as opposed to ancillary tests alone., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Water pollution is one of serious environmental issues due to the rapid development of industrial and agricultural sectors, and clean water resources have been receiving increasing attention. Recently, more and more studies have witnessed significant development of catalysts (metal oxides, metal sulfides, metal-organic frameworks, zero-valent metal, etc.) for wastewater treatment and water purification. Sustainable and clean catalysts immobilized into chitosan-based materials (Cat@CSbMs) are considered one of the most appealing subclasses of functional materials due to their high catalytic activity, high adsorption capacities, non-toxicity and relative stability. This review provides a summary of various upgrading renewable Cat@CSbMs (such as cocatalyst, photocatalyst, and Fenton-like reagent, etc.). As for engineering applications, further researches of Cat@CSbMs should focus on treating complex wastewater containing both heavy metals and organic pollutants, as well as developing continuous flow treatment methods for industrial wastewater using Cat@CSbMs. In conclusion, this review abridges the gap between different approaches for upgrading renewable and clean Cat@CSbMs and their future applications. This will contribute to the development of cleaner and sustainable Cat@CSbMs for wastewater treatment and water purification., 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 Elsevier B.V. All rights reserved.)

Species of the basidiomycetous genus Tomentella are widely distributed throughout temperate forests. Numerous studies on the taxonomy and phylogeny of Tomentella have been conducted from the temperate zone in the Northern hemisphere, but few have been from subtropical forests. In this study, four new species, T. casiae , T. guiyangensis , T. olivaceomarginata and T. rotundata from the subtropical mixed forests of Southwestern China, are described and illustrated based on morphological characteristics and phylogenetic analyses of the internal transcribed spacer regions (ITS) and the large subunit of the nuclear ribosomal RNA gene (LSU). Molecular analyses using Maximum Likelihood and Bayesian analysis confirmed the phylogenetic positions of these four new species. Anatomical comparisons among the closely related species in phylogenetic and morphological features are discussed. Four new species could be distinguished by the characteristics of basidiocarps, the color of the hymenophoral surface, the size of the basidia, the shape of the basidiospores and some other features.

The origin of highly efficient asymmetric aminohydroxylation of styrene catalyzed by engineered cytochrome c is investigated by the developed Atom-Bond Electronegativity Equalization Method polarizable force field (ABEEM PFF), which is a combined outcome of electronic and steric effects. Model molecules were used to establish the charge parameters of the ABEEM PFF, for which the bond-stretching and angle-bending parameters were obtained by using a combination of modified Seminario and scan methods. The interactions between carbon-radical Fe-porphyrin (FePP) and waters are simulated by molecular dynamics, which shows a clear preference for the pre- R over the pre- S . This preference is attributed to the hydrogen-bond between the mutated 100S and 101P residues as well as van der Waals interactions, enforcing a specific conformation of the carbon-radical FePP complex within the binding pocket. Meanwhile, the hydrogen-bond between water and the nitrogen atom in the active intermediate dictates the stereochemical outcome. Quantum mechanics/molecular mechanics (QM/MM (ABEEM PFF)) and free-energy perturbation calculations elucidate that the 3RTS is characterized by sandwich-like structure among adjacent amino acid residues, which exhibits greater stability than crowed arrangement in 3STS and enables the R enantiomer to form more favorably. Thus, this study provides mechanistic insight into the catalytic reaction of hemoproteins.

Purpose: During the induction of general anesthesia, opioids and endotracheal intubation may cause coughing. This study aimed to investigate the safety and effectiveness of an optimized drug induction scheme for general anesthesia to prevent coughing in patients., Methods: A total of 220 patients aged 18 to 65 years who underwent surgery under general anesthesia with endotracheal intubation were randomly assigned to two groups, each with 110 patients. One group was administered a divided sufentanil bolus (group A) and the other with a single sufentanil bolus (group B). Anesthesia induction was performed according to the drug induction scheme of 1st, 2nd, and 3rd minutes. The primary outcome was a coughing episode associated with the administration of opioids during anesthesia induction. We also recorded the pain associated with drug injection, hemodynamics, and blood oxygen saturation during the induction of anesthesia., Findings: All patients were included in the final statistical analysis. Compared with group B, the incidence of opioid induced cough (OIC) was significantly higher in group A (9.1% vs. 0, P = 0.001). There was no cough reaction of tracheal intubation in either group. There was no severe pain due to propofol and rocuronium injection in either group (P > 0.05). The mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO 2 ) values were within the normal range at each time point during the induction period in both groups., Implications: According to the optimized 1st, 2nd, and 3rd minutes anesthesia induction regimen, with a single final intravenous bolus of sufentanil after the diluted rocuronium bromide administration, no sufentanil and tracheal intubation induced coughing reactions were observed., Trial Registration: The study protocol was registered in the Chinese Clinical Trial Registry (ChiCTR2200062749, http://www.chictr.org.cn/showproj.aspx?proj=175018) on August 17, 2022., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects., Methods: Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p < 0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions., Results: Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD = 14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR = 15.0, 95% CI = 6.3-35.7) and spots in vision (OR = 2.8, 95% CI = 1.2-6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR = 9.2, 95% CI = 2.0-41.7), but less frequent poor peripheral vision (OR = 0.2, 95% CI = 0.06-0.7), difference in vision between eyes (OR = 0.09, 95% CI = 0.01-0.7), and missing patches of vision (OR = 0.06, 95% CI = 0.009-0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR = 4.5, 95% CI = 1.5-13.4) and vision variability across the week (OR = 4.7, 95% CI = 1.2-17.7) and were less likely to report worsening vision (OR = 0.1, 95% CI = 0.03-0.4) and blindness (OR = 0.1, 95% CI = 0.02-0.8)., Conclusion: Visual symptoms may serve as a complementary tool to distinguish dry eye from various ocular conditions, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions., (© 2024. The Author(s).)

Background: There are limited data on in-hospital cardiac arrest (IHCA) complicating non-ST-segment-elevation myocardial infarction (NSTEMI) based on management strategy., Methods: We used National Inpatient Sample (2000-2017) to identify adults with NSTEMI (not undergoing coronary artery bypass grafting) and concomitant IHCA. The cohort was stratified based on use of early (hospital day 0) or delayed (≥hospital day 1) coronary angiography (CAG), percutaneous coronary intervention (PCI), and medical management. Outcomes included incidence of IHCA, in-hospital mortality, adverse events, length of stay, and hospitalization costs., Results: Of 6,583,662 NSTEMI admissions, 375,873 (5.7 %) underwent early CAG, 1,133,143 (17.2 %) received delayed CAG, 2,326,391 (35.3 %) underwent PCI, and 2,748,255 (41.7 %) admissions were managed medically. The medical management cohort was older, predominantly female, and with higher comorbidities. Overall, 63,085 (1.0 %) admissions had IHCA, and incidence of IHCA was highest in the medical management group (1.4 % vs 1.1 % vs 0.7 % vs 0.6 %, p < 0.001) compared to early CAG, delayed CAG and PCI groups, respectively. In adjusted analysis, early CAG (adjusted OR [aOR] 0.67 [95 % confidence interval {CI} 0.65-0.69]; p < 0.001), delayed CAG (aOR 0.49 [95 % CI 0.48-0.50]; p < 0.001), and PCI (aOR 0.42 [95 % CI 0.41-0.43]; p < 0.001) were associated with lower incidence of IHCA compared to medical management. Compared to medical management, early CAG (adjusted OR 0.53, CI: 0.49-0.58), delayed CAG (adjusted OR 0.34, CI: 0.32-0.36) and PCI (adjusted OR 0.19, CI: 0.18-0.20) were associated with lower in-hospital mortality (all p < 0.001)., Conclusion: Early CAG and PCI in NSTEMI was associated with lower incidence of IHCA and lower mortality among NSTEMI-IHCA admissions., 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 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: There are limited national-level data on the contemporary practices of mechanical circulatory support (MCS) use in acute myocardial infarction-cardiogenic shock (AMI-CS)., Methods: We utilized the Healthcare Cost and Utilization Project-National/Nationwide Inpatient Sample data (2005-2017) to identify adult admissions (>18 years) with AMI-CS. MCS devices were classified as intra-aortic balloon pump (IABP), percutaneous left ventricular assist devices (pLVAD), or extracorporeal membrane oxygenation (ECMO). We evaluated trends in the initial device used (IABP alone, pLVAD alone or ≥2 MCS devices), device escalation, bridging to durable LVAD/heart transplantation, and predictors of in-hospital mortality and device escalation., Results: Among 327,283 AMI-CS admissions, 131,435 (40.2%) had an MCS device placed with available information on timing of placement. IABP, pLVAD, and ≥2 MCS devices were used as initial device in 120,928 (92.0%), 8202 (6.2%), and 2305 (1.7%) admissions, respectively. Most admissions were maintained on the initial MCS device with 1%-1.5% being escalated (IABP to pLVAD/ECMO, pLVAD to ECMO). Urban, medium, and large-sized hospitals and acute multiorgan failure were significant independent predictors of MCS escalation. In admissions receiving MCS, escalation of MCS device was associated with higher in-hospital mortality (adjusted odds ratio: 1.56, 95% confidence interval:  1.38-1.75; p < 0.001). Admissions receiving durable LVAD/heart transplantation increased over time in those initiated on pLVAD and ≥2 MCS devices, resulting in lower in-hospital mortality., Conclusions: In this 13-year study, escalation of MCS in AMI-CS was associated with higher in-hospital mortality suggestive of higher acuity of illness. The increase in number of durable LVAD/heart transplantations alludes to the role of MCS as successful bridge strategies., (© 2023 Wiley Periodicals LLC.)

Intracoronary imaging (ICI) facilitates stent implant by characterizing the lesion calcification, providing accurate vessel dimensions, and optimizing the stent results. We sought to investigate the outcomes of routine ICI versus coronary angiography (CA) to guide percutaneous coronary intervention (PCI) with second- and third-generation drug-eluting stents. A systematic search of PubMed, Medline, and Cochrane databases was conducted from their inception to July 16, 2022 for randomized controlled trials comparing routine ICI with CA. The primary outcome was major adverse cardiovascular events. The secondary outcomes of interest were target lesion revascularization, target vessel revascularization, myocardial infarction, stent thrombosis, and cardiac and all-cause mortality. A random-effects model was used to calculate the pooled incidence and relative risk (RR) with 95% confidence intervals (CIs). A total of 9 randomized controlled trials with 5,879 patients (2,870 ICI-guided and 3,009 CA-guided PCI) met the inclusion criteria. The ICI and CA groups were similar in demographic characteristics and co-morbidity profiles. Compared with CA, patients in the routine ICI-guided PCI group had lower rates of major adverse cardiovascular events (RR 0.61, 95% CI 0.48 to 0.78, p <0.0001), target lesion revascularization (RR 0.60, 95% CI 0.43 to 0.83, p = 0.002), target vessel revascularization (RR 0.72, 95% CI 0.51 to 1.00, p = 0.05), and myocardial infarction (RR 0.48, 95% CI 0.25 to 0.95, p = 0.03). There were no significant differences in stent thrombosis or cardiac/all-cause mortality between the 2 strategies. In conclusion, routine ICI-guided PCI strategy, compared with CA guidance alone, is associated with improved clinical outcomes, largely driven by lower repeat revascularization., Competing Interests: Declaration of Competing Interest Dr. Vallabhajosyula is supported, in part, by the Wake Forest CTSI, funded by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Award Number UL1TR001420. Dr. Vallabhajosyula is supported by intramural funding from the Wake Forest University School of Medicine. Dr. Goldsweig reports support from the National Institute of General Medical Sciences, 1U54GM115458, and the UNMC Center for Heart and Vascular Research. Dr. Goldsweig is a consultant at Inari Medical. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Society of Cardiovascular Angiography and Intervention (SCAI) classified cardiogenic shock (CS) into five stages ranging from A-E. There remains significant ambiguity regarding the assessment and management of SCAI Stage B. Given its nebulous nature that can rapidly escalate, prompt interventions are needed. Here, we describe the trajectory of cases that presented with SCAI Stage B CS., Competing Interests: Declaration of competing interest None.

Implantation of electrodes in the brain can be used to record from or stimulate neural tissues to treat neurological disease and injury. However, the tissue response to implanted devices can limit their functional longevity. Recent RNA-seq datasets identify hundreds of genes associated with gliosis, neuronal function, myelination, and cellular metabolism that are spatiotemporally expressed in neural tissues following the insertion of microelectrodes. To validate mRNA as a predictor of protein expression, this study evaluates a sub-set of RNA-seq identified proteins (RSIP) at 24-hours, 1-week, and 6-weeks post-implantation using quantitative immunofluorescence methods. This study found that expression of RSIPs associated with glial activation (Glial fibrillary acidic protein (GFAP), Polypyrimidine tract binding protein-1 (Ptbp1)), neuronal structure (Neurofilament heavy chain (Nefh), Proteolipid protein-1 (Plp1), Myelin Basic Protein (MBP)), and iron metabolism (Transferrin (TF), Ferritin heavy chain-1 (Fth1)) reinforce transcriptional data. This study also provides additional context to the cellular distribution of RSIPs using a MATLAB-based approach to quantify immunofluorescence intensity within specific cell types. Ptbp1, TF, and Fth1 were found to be spatiotemporally distributed within neurons, astrocytes, microglia, and oligodendrocytes at the device interface relative to distal and contralateral tissues. The altered distribution of RSIPs relative to distal tissue is largely localized within 100µm of the device injury, which approaches the functional recording range of implanted electrodes. This study provides evidence that RNA-sequencing can be used to predict protein-level changes in cortical tissues and that RSIPs can be further investigated to identify new biomarkers of the tissue response that influence signal quality. STATEMENT OF SIGNIFICANCE: Microelectrode arrays implanted into the brain are useful tools that can be used to study neuroscience and to treat pathological conditions in a clinical setting. The tissue response to these devices, however, can severely limit their functional longevity. Transcriptomics has deepened the understandings of the tissue response by revealing numerous genes which are differentially expressed following device insertion. This manuscript provides validation for the use of transcriptomics to characterize the tissue response by evaluating a subset of known differentially expressed genes at the protein level around implanted electrodes over time. In additional to validating mRNA-to-protein relationships at the device interface, this study has identified emerging trends in the spatiotemporal distribution of proteins involved with glial activation, neuronal remodeling, and essential iron binding proteins around implanted silicon devices. This study additionally provides a new MATLAB based methodology to quantify protein distribution within discrete cell types at the device interface which may be used as biomarkers for further study or therapeutic intervention in the future., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest with the work conducted in this study. The authors have no commercial or associative interest connected to the work of this study., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A patient presented with acute respiratory failure and shock due to severe prosthetic mitral valve stenosis. A valve-in-valve transcatheter mitral valve replacement procedure was performed via the transeptal approach due to his high-risk presentation with good results., Competing Interests: Declaration of competing interest None.

Introduction and Methods: We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO 2 ) and arterial carbon dioxide tension (PaCO 2 ) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring., Results: Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO 2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO 2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO 2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01)., Conclusion: In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to identify the immune and Toll-like receptor (TLR) signaling pathway related feature lncRNAs to construct the diagnostic nomograms for acute ischemic stroke (AIS). Two AIS-associated expression profiles GSE16561 and GSE22255 were downloaded from NCBI Gene Expression Omnibus, the former was the training set and the latter was the validation set. The differential expression genes (DEGs) and lncRNAs (DElncRNAs) related to TLR signaling pathway were identified between AIS and control groups. The single sample gene set enrichment analysis (ssGSEA) was applied to evaluate the immune infiltration. The immune and TLR signaling pathway related DElncRNAs were determined. Three optimization algorithms were utilized to select the immune and TLR signaling pathway related feature lncRNAs to construct the diagnostic nomograms of AIS. Based on the lncRNA signature, a ceRNA network was constructed. 37 DEGs and 28 DElncRNAs related to TLR signaling pathway were identified in GSE16561. 16 immune cell types exhibited significant differences in distribution between AIS and control groups. 28 immune and TLR signaling pathway related DElncRNAs were determined. 8 immune and TLR signaling pathway related feature lncRNAs were selected. The diagnostic nomograms of AIS performed well in both datasets. A ceRNA network was constructed consisting of 7 immune and TLR signaling pathway related feature lncRNAs as well as 19 AIS related miRNAs and 21 TLR signaling pathway related genes. LINC00173, LINC01089, LINC02210, MIR600HG, SNHG14, TP73-AS1, LINC00680 and CASC2 may be the potential biomarkers of AIS diagnosis, and TLR signaling pathway may be a promising immune related therapeutic target for AIS., (© 2023. The Author(s).)

Competing Interests: Disclosures The authors have no conflicts of interest to declare.

Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. In recent times, there is increasing interest in the role of angiotensin II in CS. We sought to systematically review the current literature on the use of angiotensin II in CS., Methods: PubMed, EMBASE, Medline, Web of Science, PubMed Central, and CINAHL databases were systematically searched for studies that evaluated the efficacy of angiotensin II in patients with CS during 01/01/2010-07/07/2022. Outcomes of interest included change in mean arterial pressure (MAP), vasoactive medication requirements (percent change in norepinephrine equivalent [NEE] dose), all-cause mortality, and adverse events., Results: Of the total 2,402 search results, 15 studies comprising 195 patients were included of which 156 (80%) received angiotensin II. Eleven patients (84.6%) in case reports and case series with reported MAP data at hour 12 noted an increase in MAP. Two studies noted a positive hemodynamic response (defined a priori) in eight (88.9%) and five (35.7%) patients. Eight studies reported a reduction in NEE dose at hour 12 after angiotensin II administration and one study noted a 100% reduction in NEE dose. Out of 47 patients with documented information, 13 patients had adverse outcomes which included hepatic injury (2), digital ischemia (1), ischemic optic neuropathy (1), ischemic colitis (2), agitated delirium (1), and thrombotic events (2)., Conclusions: In this first systematic review of angiotensin II in CS, we note the early clinical experience. Angiotensin II was associated with improvements in MAP, decrease in vasopressor requirements, and minimal reported adverse events., Competing Interests: Declaration of Competing Interest PMW previously served as a consultant for La Jolla Pharmaceutical Company., (Copyright © 2023. Published by Elsevier Inc.)

Context: To date, researchers have found that poor mental health was common during the COVID-19 epidemic. Even if they had been relatively resistant to suicidal ideation during the first three waves of the pandemic, university students may experience a delayed impact on their mental health., Objective: The study intended to measure mental health among university students in Wuhu City, China and to identify an effective approach to universities can use to prevent mental-health issues., Design: The research team performed a cross-sectional study., Setting: The study took place at Anhui polytechnic university, Wuhu, China., Participants: Participants were 2371 students at Anhui polytechnic university in Wuhu city, China., Outcome Measures: The research team used the two-item General Health Questionnaire-12 (GHQ-12) to measure participants' mental health., Results: Among the 2371 participants, 1727 had poor mental health (72.84%), including 843 males (48.81%) and 884 females (51.19%). Poor mental health was significantly associated with an urban residential location (P > .01), the female gender (p>0.01), the second school year (P > .01), and the parents' education level of junior high school or below (both P > .01)., Conclusions: The current study suggests that poor mental health among university students is common. Being female, from an urban area, and in the second year of school and having parents with an education of junior high school or below had poorer mental health than those who were male, from the countryside, and in the first year of school and who had parents with a higher level of education.

Atomic charge (AC), which is the charge distribution of a molecule, is an important property that is closely associated with structures, reactivities, and intra- and inter-molecular interactions among molecules. Several theoretical models or methods can be used to obtain the magnitudes of AC with different characteristics. These models can be classified into fuzzy-atoms models and models partitioning a molecule into individual atoms with sharp boundaries. The first category includes Mulliken, natural population analysis (NPA), Hirshfeld, Merz-Kollman-Singh (MK), CHELPG, the electronegativity equalization method (EEM), the atom-bond electronegativity equalization method (ABEEM), and atomic polar tensor (APT). The second category is derived from quantum chemical topology (QCT) and includes the quantum theory of atoms in molecules (QTAIM) and QCT analysis based on the potential acting on one electron in a molecule (PAEMQCT). Herein, after giving a bird's-eye view of the population methods of the first category, we specifically describe some features of the second category. We only present the basic framework of QCT for obtaining ACs from QTAIM and PAEMQCT and show their important characteristics. QCT establishes the basis of the following chemical concept: a molecule is spatially partitioned into individual atoms with sharp boundaries. The ACs from QTAIM are close to the atomic valence in chemistry, and ACs from PAEMQCT may be practically suitable for modeling intra- and inter-molecular interactions.

The established benefits of cooling along with development of sophisticated methods to safely and precisely induce, maintain, monitor, and reverse hypothermia have led to the development of targeted temperature management (TTM). Early trials in human subjects showed that hypothermia conferred better neurological outcomes when compared to normothermia among survivors of cardiac arrest, leading to guidelines recommending targeted hypothermia in this patient population. Multiple studies have sought to explore and compare the benefit of hypothermia in various subgroups of patients, such as survivors of out-of-hospital cardiac arrest versus in-hospital cardiac arrest, and survivors of an initial shockable versus non-shockable rhythm. Larger and more recent trials have shown no statistically significant difference in neurological outcomes between patients with targeted hypothermia and targeted normothermia; further, aggressive cooling is associated with a higher incidence of multiple systemic complications. Based on this data, temporal trends have leaned towards using a lenient temperature target in more recent times. Current guidelines recommend selecting and maintaining a constant target temperature between 32 and 36 °C for those patients in whom TTM is used (strong recommendation, moderate-quality evidence), as soon as possible after return of spontaneous circulation is achieved and airway, breathing (including mechanical ventilation), and circulation are stabilized. The comparative benefit of lower (32-34 °C) versus higher (36 °C) temperatures remains unknown, and further research may help elucidate this. Any survivor of cardiac arrest who is comatose (defined as unarousable unresponsiveness to external stimuli) should be considered as a candidate for TTM regardless of the initial presenting rhythm, and the decision to opt for targeted hypothermia versus targeted normothermia should be made on a case-by-case basis., (© 2022. The Author(s).)

A macrocyclic tetra-imidazolium salt ( 2 ) based on quinoxaline was prepared and characterized. The recognition of 2 to nitro compounds was investigated by fluorescence spectroscopy, 1 H NMR titrations, MS, IR spectroscopy, and UV/vis spectroscopy. The results displayed that 2 was able to effectively differentiate p -dinitrobenzene from other nitro compounds via the fluorescence method., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Measuring the Hounsfield units (HU) of the vertebrae may yield diagnostic information for fracture risk. This study aimed to measure HU of vertebrae in percutaneous kyphoplasty (PKP) patients using computed tomography (CT) imaging to determine the HU measurements threshold for adjacent vertebral fracture and to assess the relationship between HU measurements and the risk of adjacent vertebral fracture., Methods: A retrospective study was conducted on consecutive patients who underwent PKP between January 2019 and October 2021 in the China-Japan Union Hospital of Jilin University. The HU of the vertebra was measured on the reconstructed CT images by 2 independent spine surgeons. The HU measurements of adjacent vertebrae and the ratio of HU measurements between the surgical vertebra and adjacent vertebrae were statistically analyzed to determine the best critical value and evaluate the prediction effectiveness and accuracy of the best critical value., Results: A total of 105 patients were identified with complete imaging and follow-up information. Of these, 47 patients (44.8%) had evidence of an adjacent vertebral fracture on follow-up imaging. The mean HU measurements of the fractured adjacent vertebra were significantly different from the mean HU measurements of the unfractured adjacent vertebra (50.94±20.59 vs. 81.74±18.97 HU; P<0.001). There was a significant difference in the ratio of HU measurements between the surgical vertebra and the fractured adjacent vertebra and between the surgical vertebra and the unfractured adjacent vertebra (26.34±17.52 vs. 14.53±9.40; P<0.001). Interactive scatter plots and receiver operating characteristic (ROC) curve showed that a HU measurement of 66.9 and a HU measurements ratio of 15.18 were the best thresholds for predicting the risk of fracture of adjacent vertebrae after PKP surgery, with an area under the curve (AUC) of 0.901 [95% confidence interval (CI): 0.822-0.953; P<0.001] and 0.874 (95% CI: 0.790-0.934; P<0.001), respectively. The prediction accuracy was 90.4% and 84.0%, respectively., Conclusions: A low mean HU measurements of adjacent vertebrae or a high ratio of the mean HU measurements of the operated vertebrae to the adjacent vertebrae are risk factors for the vulnerability of adjacent vertebrae to fracture. The risk of fracture in the adjacent vertebrae after PKP can be predicted by measuring HU., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-588/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aim: To identify risk factors of recurrence of this disorder after intravitreal ranibizumab (IVR) monotherapy., Methods: Totally 33 eyes of 19 patients who underwent initial IVR treatments for type 1 retinopathy of prematurity (ROP) at our center were retrospectively reviewed between April 1, 2016 and December 31, 2017. Patient demographics, the side of ROP, multiple gestations, Apgar scores, zone, stage, plus disease, postmenstrual age at injection, surfactant therapy, blood transfusion therapy, hemorrhage before IVR, hemorrhage after IVR, gestational diabetes mellitus, pregnancy-induced hypertension, anemia, intraventricular hemorrhage, sepsis, respiratory distress syndrome, carbohemia, and congenital heart defects were recorded. Adjusted hazard ratios (HRs) and 95% confidence intervals were determined after adjusting for potential confounders using multivariate proportional Cox regression., Results: Of the 33 eyes, 12 (36.4%) had ROP recurrences 45.3 (5.1, 50.9)mo after initial IVR treatments. The independent risk factors for ROP recurrences were zone (II vs I, HR: 0.056, P =0.003) and gestational diabetes mellitus (no vs yes, HR: 0.095, P <0.001). The mean uncorrected visual acuity for four recurrence eyes was 0.46 logMAR (0.13, 0.70) at 55.0 (51.0, 58.9) mo after the initial IVR treatment. The mean uncorrected visual acuity for 10 eyes without recurrence was 0.46 logMAR (0.19, 0.63) at 48.0 (43.8, 58.4) mo after the initial IVR treatment., Conclusion: Two independent risk factors for type 1 ROP recurrence after IVR treatment involving zone I and gestational diabetes mellitus are identified, and the mean uncorrected visual acuity is 0.46 logMAR at 51.0 (44.0, 58.9)mo. The findings of this study are important for follow-up management and for improving the visual function of ROP patients., (International Journal of Ophthalmology Press.)

Background: There has been conflicting reports on the effect of new trainees on clinical outcomes at teaching hospitals in the first training month (July in the United States of America). We sought to assess this "July effect" in a contemporary acute myocardial infarction (AMI) population., Methods: Adult (>18 years) AMI hospitalizations in May and July in urban teaching and urban nonteaching hospitals in the United States were identified from the HCUP-NIS database (2000-2017). In-hospital mortality was compared between May and July admissions. A difference-in-difference analysis comparing a change in outcome from May to July in teaching hospitals to a change in outcome from May to July in nonteaching hospitals was also performed., Results: A total of 1,312,006 AMI hospitalizations from urban teaching (n = 710,593; 54.2%) or nonteaching (n = 601,413; 45.8%) hospitals in the months of May and July were evaluated. May admissions in teaching hospitals, had greater comorbidity, higher rates of acute multiorgan failure (10.6% vs. 10.2%, p < 0.001) and lower rates of cardiac arrest when compared to July admissions. July AMI admissions had lower in-hospital mortality compared to May (5.6% vs. 5.8%; adjusted odds ratio 0.94 [95% confidence interval 0.92-0.97]; p < 0.001) in teaching hospitals. Using the difference-in-difference model, there was no evidence of a July effect for in-hospital mortality (p = 0.19)., Conclusions: There was no July effect for in-hospital mortality in this contemporary AMI population., (© 2023 Wiley Periodicals LLC.)

This study sought to compare the impact of additional anticoagulation or thrombolytic therapy in patients with cardiac arrest without ST-segment-elevation on electrocardiography and not receiving percutaneous coronary intervention. Three studies (two randomized controlled studies and one observational study) were included, which demonstrated that use of anticoagulation or thrombolytic therapy was associated with higher risk of bleeding, without improvements in time to return of spontaneous circulation or in-hospital mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The effect of prior coronary artery bypass graft (CABG) on the outcomes of transcatheter aortic valve replacement (TAVR) remains incompletely characterized. In this meta-analysis, we investigated the impact of prior CABG on TAVR outcomes., Methods: A systematic search was conducted in PubMed, Google Scholar, and Cochrane databases from inception to 24 July 2022, using the search terms 'TAVR', 'CABG', 'peri-procedural complications', and 'mortality'. The major outcomes were peri-procedural complications, intraprocedural mortality, 30-day mortality, and 30-day cardiac mortality. We used random-effects models to aggregate data and to calculate pooled incidence and risk ratios with 95% confidence intervals (CIs)., Results: Among 116 results from the systematic search, a total of 8 studies (5952 patients) were included. Compared to patients without previous CABG, patients with prior CABG undergoing TAVR were younger, predominantly male sex, had more comorbidities, higher rates of peri-procedural myocardial infarction (MI) [relative risk (RR) 1.93; 95% CI, 1.09-3.43; P  = 0.03], but lower rates of stroke (RR 0.71; 95% CI, 0.51-0.99; P  = 0.04), major vascular complications (RR 0.70; 95% CI, 0.51-0.95; P  = 0.02), and major bleeding (RR 0.70; 95% CI, 0.56-0.88; P  = 0.002). There were no significant differences between the two cohorts in rates of pacemaker implantation, cardiac tamponade, acute kidney injury, intra-procedural mortality, 30-day mortality, and 30-day cardiac mortality., Conclusion: Among patients undergoing TAVR, a history of prior CABG was not associated with an increased risk of periprocedural complications (except for acute MI) or short-term mortality compared to those without CABG., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and objectives: Primary percutaneous coronary intervention (PCI)-related outcomes in acute myocardial infarction (AMI) have improved over time, but there are limited data on the length of stay (LOS) in relation to in-hospital mortality. Materials and Methods: A retrospective cohort of adult AMI admissions was identified from the National Inpatient Sample (2000−2017) and stratified into short (≤3 days) and long (>3 days) LOS. Outcomes of interest included temporal trends in LOS and associated in-hospital mortality, further sub-stratified based on demographics and comorbidities. Results: A total 11,622,528 admissions with AMI were identified, with a median LOS of 3 (interquartile range [IQR] 2−6) days with 49.9% short and 47.3% long LOS, respectively. In 2017, compared to 2000, temporal trends in LOS declined in all AMI, with marginal increases in LOS >3 days and decreases for ≤3 days (median 2 [IQR 1−3]) vs. long LOS (median 6 [IQR 5−9]). Patients with long LOS had lower rates of coronary angiography and PCI, but higher rates of non-cardiac organ support (respiratory and renal) and use of coronary artery bypass grafting. Unadjusted in-hospital mortality declined over time. Short LOS had comparable mortality to long LOS (51.3% vs. 48.6%) (p = 0.13); however, adjusted in-hospital mortality was higher in LOS >3 days when compared to LOS ≤ 3 days (adjusted OR 3.00, 95% CI 2.98−3.02, p < 0.001), with higher hospitalization (p < 0.001) when compared to long LOS. Conclusions: Median LOS in AMI, particularly in STEMI, has declined over the last two decades with a consistent trend in subgroup analysis. Longer LOS is associated with higher in-hospital mortality, higher hospitalization costs, and less frequent discharges to home compared to those with shorter LOS.

Objective: To evaluate the prevalence, management and outcomes of concomitant aortic stenosis (AS) in admissions with acute myocardial infarction (AMI)., Methods: We used the HCUP-NIS database (2000-2017) to identify adult AMI admissions with concomitant AS. Outcomes of interest included prevalence of AS, in-hospital mortality, use of cardiac procedures, hospitalization costs, length of stay, and discharge disposition., Results: Among a total of 11,622,528 AMI admissions, 513,688 (4.4 %) were identified with concomitant AS. Adjusted temporal trends revealed an increase in STEMI and NSTEMI hospitalizations with concomitant AS. Compared to admissions without AS, those with AS were on average older, of female sex, had higher comorbidity, higher rates of NSTEMI (78.9 % vs 62.1 %), acute non-cardiac organ failure, and cardiogenic shock. Concomitant AS was associated with significantly lower use of coronary angiography (45.5 % vs 64.4 %), percutaneous coronary intervention (20.1 % vs 42.5 %), coronary atherectomy (1.7 % vs. 2.8 %) and mechanical circulatory support (3.5 % vs 4.8 %) (all p < 0.001). Admissions with AS had higher rates of coronary artery bypass surgery and surgical aortic valve replacement (5.9 % vs 0.1 %) compared to those without AS. Admissions with AMI and AS had higher in-hospital mortality (9.2 % vs. 6.0 %; adjusted OR 1.12 [95 % CI 1.10-1.13]; p <0.001). Concomitant AS was associated with longer hospital stay, more frequent palliative care consultations and less frequent discharges to home., Conclusions: In this 18-year study, an increase in prevalence of AS in AMI hospitalization was noted. Concomitant AS was associated with lower use of guideline-directed therapies and worse clinical outcomes among AMI admissions., 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.

Background and Objective: Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS., Methods: First, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes., Results: Twelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets., Conclusions: ICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS., (© 2022. The Author(s).)

Objective: Cerebral microbleeds (CMB) are small accumulations of hemosiderin associated with cerebrovascular risk factors, but whether they are associated with atrial cardiopathy is not known. The goal of this study is to determine, among ischemic stroke patients, the association between study-defined atrial cardiopathy and CMB presence, location, and number., Methods: Ischemic stroke patients admitted to Johns Hopkins (2015-2019) with transthoracic echocardiography and electrocardiography were included. Cerebral microbleeds were defined as small, round hypo-intensities on T2 * susceptibility weighted imaging or gradient recalled echo magnetic resonance imaging sequences. Atrial cardiopathy was defined as the presence of ≥1: left atrium diameter >4.0 cm (males) or >3.8 cm (females), PR interval >200 ms, or N-terminal pro-B-type natriuretic peptide >250 pg/ml. Binary/Ordinal logistic regression models were used to determine the association between atrial cardiopathy, and cerebral microbleed presence, location (lobar/deep), or number, each, adjusted for potential confounders., Results: Patients ( N = 120) were mean age 60 years (range 22-98), 46% female, 62% black, and 39% were on anti-thrombotic medication at time of admission. 39 (32%) participants had ≥1 cerebral microbleeds. Forty-six (38%) patients had atrial cardiopathy. Atrial cardiopathy was associated with higher odds of having cerebral microbleeds (OR 2.50, 95% CI 1.02-6.15). Atrial cardiopathy was associated with lobar cerebral microbleeds (OR 2.33, 95% CI 1.01-5.37) in univariate analysis but not with deep cerebral microbleeds (OR 0.45, 95% CI 0.13-1.54), with neither association significant after adjustment. There was no difference in risk of having 1 vs. no cerebral microbleeds (RRR 2.51, 95% CI 0.75-8.37) and >1 cerebral microbleed vs none (RRR 2.57, 95% CI 0.87-7.60) among those with atrial cardiopathy., Conclusions: Atrial cardiopathy is associated with the presence, but not burden, of cerebral microbleeds in ischemic stroke patients. We cautiously suggest that atrial cardiopathy, either directly or through shared vascular risk, may contribute to the presence of CMB., 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 © 2022 Zhao, Gootee and Johansen.)

Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated with high mortality and requires careful risk stratification for individualized management. PE is divided into three risk categories: low risk, intermediate-risk, and high risk. In terms of initial therapeutic choice and long-term management, intermediate-risk (or submassive) PE remains the most challenging subtype. The definitions, classifications, risk stratification, and management options of intermediate-risk PE are discussed in this review.

The impact of socioeconomic status on care and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains understudied. Hence, adult admissions with AMI-CS were identified from the National Inpatient Sample database (2005 to 2017) and were divided into quartiles on the basis of median household income for zip code (0 to 25th, 26th to 50th, 51st to 75th, and 76th to 100th). In-hospital mortality, use of cardiac and noncardiac procedures, and resource utilization were compared between all 4 income quartiles. Among a total of 7,805,681 AMI admissions, cardiogenic shock was identified in 409,294 admissions (5.2%) with comparable prevalence of cardiogenic shock across all 4 income quartiles. AMI-CS admissions belonging to the lowest income quartile presented more often with non-ST-elevation myocardial infarction and had comparable use of coronary angiography and percutaneous coronary intervention but lower use of early coronary angiography, early percutaneous coronary intervention, mechanical circulatory support devices, and pulmonary artery catheterization than higher income quartiles. In the adjusted analysis, admissions belonging to the 0 to 25th income quartile (odds ratio [OR] 1.17 [95% confidence interval [CI] 1.15 to 1.20], p <0.001), 26th to 50th quartile (OR 1.11 [95% CI 1.09 to 1.14], p <0.001), and 51st to 75th income quartile (OR 1.06 [95% CI 1.04 to 1.09], p <0.001) had higher adjusted in-hospital mortality than the highest income quartile (76th to 100th). Lowest income quartile admissions had lower rates of palliative care consultations and higher rates of do-not-resuscitate status than the higher income quartiles. Hospitalization charges and length of stay were higher for admissions belonging to the highest income quartile. In conclusion, lowest income quartile AMI-CS admissions were associated with higher rates of non-ST-elevation myocardial infarction, lower use of mechanical circulatory support devices, and higher in-hospital mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

MF X (AlF 3 0 , AlF 4 - and MgF 3 - ) as transition state analogues of phosphoryl transfer enzymes (enzyme-MF X -TSAs) is of great significance for study of the catalytic mechanism of phosphoryl transfer enzymes. Bonded model and non-bonded model based on the ABEEM polarizable force field (ABEEM PFF) are developed and applied to study the coordination of enzyme-MF X -TSAs. The bond stretching of the bond containing metal is simulated by Morse potential energy function, because the change of chemical bond is described more accurately in a large range. The charge distribution of the system is distributed to multiple-charge-sites, including atomic site, σ bond site, π bond site and lone pair electron site. Partial charge can fluctuate according to the surrounding environment and molecular conformation. The reasonable charge distribution of 68 model molecules can be obtained, and the energy minimizations are performed in vacuum. Then, with the same parameters the charge distribution and the charge transfer of four complexes are obtained, and the energy minimization and molecular dynamics simulation in NVT ensemble are carried out in vacuum and explicit water solution. The results verify the correctness, rationality and transferability of the new parameters of ABEEM PFF, and the bonded model simulates more reasonable charge distribution and geometry. The parameters determined in this paper make up the blank of the parameters of MF X and phosophoryl transfer enzymes containing Mg 2+ . The development of ABEEM PFF provides a refined tool for MF X -TSAs to study the catalytic mechanism of phosphoryl transfer enzymes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y 12 inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS)., Patients and Methods: MEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y 12 inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y 12 inhibitors and clopidogrel in patients with AMI-CA/CS., Results: Eight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y 12 cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies)., Conclusion: In patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y 12 inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China., Methods: A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator., Results: A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels., Conclusions: Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535)., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: A quasi-dynamic food chain model (Chi-FDMT) was developed to predict the consequences of nuclear accidents on the food chain through the ingestion pathway in Chinese agricultural conditions. The Chi-FDMT structure is based on ECOSYS-87, with some revised calculation processes and the adoption of new parameters; herein, it was applied to two regions in China. The model was used to estimate the spatial and temporal patterns of crop plant activity and ingestion dose in the Chinese agricultural environment at the scale of the Fukushima nuclear disaster. A comparative study between Chi-FDMT and an equilibrium model demonstrated good agreement for depositions occurring during the growth season. The parameter sensitivity analysis of Chi-FDMT indicated that the parameters of food intake and processing factor are sensitive, and the sensitivity of the transfer factors within plant and soil-plant systems are dependent on the deposition scenario., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Health Physics Society.)

Abstract: Despite advances in early revascularization, percutaneous hemodynamic support platforms, and systems of care, cardiogenic shock (CS) remains associated with a mortality rate higher than 50%. Several risk stratification models have been derived since the 1990 s to identify patients at high risk of adverse outcomes. Still, limited information is available on the differences between scoring systems and their relative applicability to both acute myocardial infarction and advanced decompensated heart failure CS. Thus, we reviewed the similarities, differences, and limitations of published CS risk prediction models and herein discuss their suitability to the contemporary management of CS care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Liquid chromatography/mass spectrometry (LC/MS) is extensively applied for the untargeted/targeted analyses of the herbal components, utilizing data-dependent acquisition (DDA) or data-independent acquisition (DIA) to record the fragmentation information useful for the structural elucidation. A new trend recently has emerged by integrating DDA and DIA to render the hybrid scan, which, unfortunately, has rarely been reported. Herein, by using the Vion™ ion-mobility quadrupole time-of-flight mass spectrometer, a hybrid scan strategy (HDMS E -HDDDA) was presented and validated by the untargeted characterization of the multicomponents from Carthamus tinctorius (safflower), in combination with reversed-phase ultra-high performance liquid chromatography (RP-UHPLC). Good chromatographic separation was achieved on an HSS T3 column within 26 min, while HDMS E -MS/MS was used to acquire the collision-induced dissociation MS 2 data in the negative mode. Automatic workflows (e.g., data correction, precursors/product ions matching, and peak annotation) were well established on UNIFI™ (incorporating an in-house library recording 261 known compounds) to process the obtained MS 2 data. Compared with single DDA or DIA, the hybrid approach of HDMS E -HDDDA better balanced between the coverage and reliability, led to high-definition MS spectra, offered useful collision cross section (CCS) information, and showed satisfactory identification performance comparable to MS E . A total of 141 components (involving 41 quinochalcones, 66 flavanols/flavones, 11 flavanones, 6 organic acids, 1 polyacetylene, and 16 others) were characterized from safflower. Moreover, CCS prediction could assist isomers characterization, to some extent. Conclusively, this hybrid scan approach enables a dimension-enhanced MS data acquisition strategy providing the complementary structural information, which more suits the chemical characterization of complex samples., Competing Interests: Declaration of Competing Interest We declare that, we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, "An ion mobility-enabled and high-efficiency hybrid scan approach in combination with ultra-high performance liquid chromatography enabling the comprehensive characterization of the multicomponents from Carthamus tinctorius"., (Copyright © 2022. Published by Elsevier B.V.)

The development of an atom-bond electronegativity equalisation method at the σπ-level (ABEEM) polarisable force field (PFF) for peptides is presented. ABEEM PFF utilises a fluctuating charge model to explicitly describe the polarisation effects in an extensive environment. The partial charge of any individual site changes in response to changes in its surroundings. The peptide parameters are derived from ab initio methods in vacuum using a consistent and automatic protocol. By including explicit σ- and π-bond sites and lone pair sites, the anisotropy around an atom has been characterised. The fluctuating charge at each site ensures the distinction between the intrinsic behaviour observed among the various conformations of peptides, as corroborated by the agreement between quantum mechanics (QM) and ABEEM PFF concerning the calculated energy order, charge distribution, locations of minima, and potential energy surface (PES) in vacuo . The energy barriers in the PES have been clearly described using ABEEM PFF, in which a good charge distribution plays a vital role. Molecular dynamic simulations have been performed for short peptides in explicit ABEEM 7P-water boxes to examine their conformational properties in solution. The J -coupling constants obtained using ABEEM PFF are consistent with the experimental nuclear magnetic resonance (NMR) spectra and the influence of the chain length and temperature also investigated. The results demonstrate that the ABEEM PFF method is capable of locating conformations and describing the energetics of peptides with high accuracy and efficiency both in vacuo and an aqueous solution.

Objectives: Mixed cardiogenic-septic shock is common and associated with high mortality. There are limited contemporary data on concomitant sepsis in acute myocardial infarction complicated by cardiogenic shock (AMI-CS)., Design: Observational study., Setting: Twenty percent stratified sample of all community hospitals (2000-2014) in the United States., Participants: Adults (> 18 yr) with AMI-CS with and without concomitant sepsis., Interventions: None., Measurements and Main Results: Outcomes of interest included inhospital mortality, development of noncardiac organ failure, complications, utilization of guideline-directed procedures, length of stay, and hospitalization costs. Over 15 years, 444,253 AMI-CS admissions were identified, of which 27,057 (6%) included sepsis. The sepsis cohort had more comorbidities and had higher rates of noncardiac multiple organ failure (92% vs 69%) (all p < 0.001). In 2014, compared with 2000, the prevalence of sepsis increased from 0.5% versus 11.5% with an adjusted odds ratio (aOR) 11.71 (95% CI, 9.7-14.0) in ST-segment elevation myocardial infarction and 24.6 (CI, 16.4-36.7) (all p < 0.001) in non-ST segment elevation myocardial infarction. The sepsis cohort received fewer cardiac interventions (coronary angiography [65% vs 68%], percutaneous coronary intervention [43% vs 48%]) and had greater use of mechanical circulatory support (48% vs 45%) and noncardiac support (invasive mechanical ventilation [65% vs 41%] and acute hemodialysis [12% vs 3%]) ( p < 0.001). The sepsis cohort had higher inhospital mortality (44.3% vs 38.1%; aOR, 1.21; 95% CI, 1.18-1.25; p < 0.001), longer length of stay (14.0 d [7-24 d] vs 7.0 d [3-12 d]), greater hospitalization costs (×1,000 U.S. dollars) ($176.0 [$85-$331] vs $77.0 [$36-$147]), fewer discharges to home (22% vs 44%) and more discharges to skilled nursing facilities (51% vs 28%) (all p < 0.001)., Conclusions: In AMI-CS, concomitant sepsis is associated with higher mortality and morbidity highlighting the need for early recognition and integrated management of mixed shock., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)