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1.
Nature ; 630(8015): 59-63, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750357

ABSTRACT

Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.

2.
Nature ; 618(7966): 790-798, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37316665

ABSTRACT

Psychedelics are a broad class of drugs defined by their ability to induce an altered state of consciousness1,2. These drugs have been used for millennia in both spiritual and medicinal contexts, and a number of recent clinical successes have spurred a renewed interest in developing psychedelic therapies3-9. Nevertheless, a unifying mechanism that can account for these shared phenomenological and therapeutic properties remains unknown. Here we demonstrate in mice that the ability to reopen the social reward learning critical period is a shared property across psychedelic drugs. Notably, the time course of critical period reopening is proportional to the duration of acute subjective effects reported in humans. Furthermore, the ability to reinstate social reward learning in adulthood is paralleled by metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Finally, identification of differentially expressed genes in the 'open state' versus the 'closed state' provides evidence that reorganization of the extracellular matrix is a common downstream mechanism underlying psychedelic drug-mediated critical period reopening. Together these results have important implications for the implementation of psychedelics in clinical practice, as well as the design of novel compounds for the treatment of neuropsychiatric disease.


Subject(s)
Critical Period, Psychological , Hallucinogens , Learning , Reward , Animals , Humans , Mice , Consciousness/drug effects , Hallucinogens/pharmacology , Hallucinogens/therapeutic use , Learning/drug effects , Time Factors , Oxytocin/metabolism , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Long-Term Synaptic Depression/drug effects , Extracellular Matrix/drug effects
3.
Nature ; 605(7909): 268-273, 2022 05.
Article in English | MEDLINE | ID: mdl-35292753

ABSTRACT

Optoelectronic devices consist of heterointerfaces formed between dissimilar semiconducting materials. The relative energy-level alignment between contacting semiconductors determinately affects the heterointerface charge injection and extraction dynamics. For perovskite solar cells (PSCs), the heterointerface between the top perovskite surface and a charge-transporting material is often treated for defect passivation1-4 to improve the PSC stability and performance. However, such surface treatments can also affect the heterointerface energetics1. Here we show that surface treatments may induce a negative work function shift (that is, more n-type), which activates halide migration to aggravate PSC instability. Therefore, despite the beneficial effects of surface passivation, this detrimental side effect limits the maximum stability improvement attainable for PSCs treated in this way. This trade-off between the beneficial and detrimental effects should guide further work on improving PSC stability via surface treatments.

4.
N Engl J Med ; 388(18): 1668-1679, 2023 May 04.
Article in English | MEDLINE | ID: mdl-36876735

ABSTRACT

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Coronary Angiography/adverse effects , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/etiology , Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Prospective Studies , Treatment Outcome , Ultrasonography, Interventional/methods
5.
Chem Rev ; 124(3): 768-859, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38241488

ABSTRACT

Optoelectronic devices with unconventional form factors, such as flexible and stretchable light-emitting or photoresponsive devices, are core elements for the next-generation human-centric optoelectronics. For instance, these deformable devices can be utilized as closely fitted wearable sensors to acquire precise biosignals that are subsequently uploaded to the cloud for immediate examination and diagnosis, and also can be used for vision systems for human-interactive robotics. Their inception was propelled by breakthroughs in novel optoelectronic material technologies and device blueprinting methodologies, endowing flexibility and mechanical resilience to conventional rigid optoelectronic devices. This paper reviews the advancements in such soft optoelectronic device technologies, honing in on various materials, manufacturing techniques, and device design strategies. We will first highlight the general approaches for flexible and stretchable device fabrication, including the appropriate material selection for the substrate, electrodes, and insulation layers. We will then focus on the materials for flexible and stretchable light-emitting diodes, their device integration strategies, and representative application examples. Next, we will move on to the materials for flexible and stretchable photodetectors, highlighting the state-of-the-art materials and device fabrication methods, followed by their representative application examples. At the end, a brief summary will be given, and the potential challenges for further development of functional devices will be discussed as a conclusion.

6.
Plant J ; 117(2): 599-615, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37902786

ABSTRACT

Chloroplasts are essential organelles in plants that contain chlorophylls and facilitate photosynthesis for growth and development. As photosynthetic efficiency significantly impacts crop productivity, understanding the regulatory mechanisms of chloroplast development has been crucial in increasing grain and biomass production. This study demonstrates the involvement of OsGATA16, an ortholog of Arabidopsis GATA, NITRATE INDUCIBLE, CARBON-METABOLISM INVOLVED (GNC), and GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR 1 (GNL/CGA1), in chlorophyll biosynthesis and chloroplast development in rice (Oryza sativa). The osgata16-1 knockdown mutants produced pale-green leaves, while OsGATA16-overexpressed plants (OsGATA16-OE1) generated dark-green leaves, compared to their parental japonica rice. Reverse transcription and quantitative PCR analysis revealed downregulation of genes related to chloroplast division, chlorophyll biosynthesis, and photosynthesis in the leaves of osgata16-1 and upregulation in those of OsGATA16-OE1. Additionally, in vivo binding assays showed that OsGATA16 directly binds to the promoter regions of OsHEMA, OsCHLH, OsPORA, OsPORB, and OsFtsZ, and upregulates their expression. These findings indicate that OsGATA16 serves as a positive regulator controlling chlorophyll biosynthesis and chloroplast development in rice.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Oryza , Oryza/metabolism , Chloroplasts/metabolism , Photosynthesis/genetics , Chlorophyll/metabolism , Arabidopsis/genetics , Plant Leaves/metabolism , Gene Expression Regulation, Plant , Transcription Factors/metabolism , Arabidopsis Proteins/metabolism
7.
Lancet ; 404(10456): 937-948, 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39226909

ABSTRACT

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.


Subject(s)
Acute Coronary Syndrome , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Randomized Controlled Trials as Topic , Ticagrelor , Humans , Ticagrelor/therapeutic use , Ticagrelor/administration & dosage , Acute Coronary Syndrome/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Dual Anti-Platelet Therapy/methods , Hemorrhage/chemically induced , Drug-Eluting Stents , Treatment Outcome
8.
Plant Physiol ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240752

ABSTRACT

Heat stress is a substantial and imminent threat to plant growth and development. Understanding its adverse effects on plant development at the molecular level is crucial for sustainable agriculture. However, the molecular mechanism underlying how heat stress causes developmental defects in flowers remains poorly understood. Here, we identified Indole-3-Acetic Acid 8 (IAA8), a repressor of auxin signaling, as a substrate of mitogen-activated protein kinases (MPKs) in Arabidopsis thaliana, and found that MPK-mediated phosphorylation of IAA8 inhibits flower development. MPKs phosphorylated three residues of IAA8: S74, T77, and S135. Interestingly, transgenic plants overexpressing a phospho-mimicking mutant of IAA8 (IAA8DDD OX) exhibited defective flower development due to high IAA8 levels. Furthermore, MPK-mediated phosphorylation inhibited IAA8 polyubiquitination, thereby significantly increasing its stability. Additionally, the expression of key transcription factors involved in flower development, such as bZIP and MYB genes, was significantly perturbed in the IAA8DDD OX plants. Collectively, our study demonstrates that heat stress inhibits flower development by perturbing the expression of flower development genes through the MPK-mediated phosphorylation of IAA8, suggesting that Aux/IAA phosphorylation enables plants to fine-tune their development in response to environmental stress.

9.
Plant Physiol ; 2024 Oct 17.
Article in English | MEDLINE | ID: mdl-39418078

ABSTRACT

In plants, balancing growth and environmental responses is crucial for maximizing fitness. Close proximity among plants and canopy shade, which negatively impacts reproduction, elicits morphological adjustments such as hypocotyl growth and leaf hyponasty, mainly through changes in light quality and auxin levels. However, how auxin, synthesized from a shaded leaf blade, distally induces elongation of hypocotyl and petiole cells remains to be elucidated. We demonstrated that ASYMMETRIC LEAVES1 (AS1) promotes leaf hyponasty through the regulation of auxin biosynthesis, polar auxin transport, and auxin signaling genes in Arabidopsis (Arabidopsis thaliana). AS1 overexpression leads to elongation of the abaxial petiole cells with auxin accumulation in the petiole, resulting in hyponastic growth, which is abolished by the application of an auxin transport inhibitor to the leaf blade. In addition, the as1 mutant exhibits reduced hypocotyl growth under shade conditions. We observed that AS1 protein accumulates in the nucleus in response to shade or far-red light. Chromatin immunoprecipitation analysis identified the association of AS1 with the promoters of YUCCA8 (YUC8) and INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19). In addition, AS1 forms complexes with PHYTOCHROME INTERACTING FACTORs in the nucleus and synergistically induces YUC8 and IAA19 expression. Our findings suggest that AS1 plays a crucial role in facilitating phenotypic plasticity to the surroundings by connecting light and phytohormone action.

10.
Proc Natl Acad Sci U S A ; 119(16): e2200545119, 2022 04 19.
Article in English | MEDLINE | ID: mdl-35412917

ABSTRACT

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.


Subject(s)
Calmodulin-Binding Proteins , Carrier Proteins , Cocaine , Cytoskeletal Proteins , Nerve Tissue Proteins , Receptors, Drug , Animals , Binding Sites , Calmodulin-Binding Proteins/genetics , Calmodulin-Binding Proteins/metabolism , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cocaine/metabolism , Cocaine/pharmacology , Corpus Striatum/metabolism , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors , Gene Knock-In Techniques , Humans , Mice , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Rats , Receptors, Drug/genetics , Receptors, Drug/metabolism
11.
Eur Heart J ; 2024 Oct 21.
Article in English | MEDLINE | ID: mdl-39429032

ABSTRACT

BACKGROUND AND AIMS: Despite the increasing popularity of electronic cigarettes (E-cigarettes), the prognostic impact of switching to E-cigarettes in smokers with coronary artery disease who have undergone percutaneous coronary intervention (PCI) remains unclear. METHODS: Using a nationwide cohort from the Korean National Health Insurance database, 17 973 adults (≥20 years) identified as smokers (based on a health screening examination within 3 years before PCI) who underwent health screening within 3 years after PCI were enrolled to determine changes in smoking habits. Patients were classified as continued combustible cigarette users, successful quitters, or switchers to E-cigarettes. The group switching to E-cigarettes was further divided into dual users (using both combustible and E-cigarettes) and those exclusively using E-cigarettes. Primary outcomes included major adverse cardiac events (MACEs), a composite of all-cause death, spontaneous myocardial infarction, and repeat revascularization. RESULTS: Among the total population, 8951 patients (49.8%) continued using combustible cigarettes, 1694 (9.4%) were switched to E-cigarettes, and 7328 (40.7%) successfully quit smoking after PCI. During a median follow-up of 2.4 years, the cumulative incidence of MACE was lower among E-cigarette switchers (10%) or quitters (13.4%) than among continued combustible cigarette users (17%). When continued combustible cigarette users were used as the reference, the multivariable-adjusted hazard ratios with 95% confidence intervals for MACE were 0.82 (0.69-0.98) for switchers to E-cigarettes and 0.87 (0.79-0.96) for successful quitters. Compared with dual users, entirely switching to E-cigarettes was associated with a significantly lower MACE risk (hazard ratio 0.71; 95% confidence interval 0.51-0.99). CONCLUSIONS: Among smokers who underwent PCI for coronary artery disease, switching to E-cigarette use (particularly complete transition) or quitting smoking was associated with reduced MACE risk than with continued combustible cigarette use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT06338761.

12.
Clin Gastroenterol Hepatol ; 22(9): 1953-1955.e1, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38484945

ABSTRACT

Hepatocellular carcinoma (HCC) represents a significant global health burden, with its incidence and mortality rates varying significantly across different geographic regions. This variance is largely attributed to differences in the prevalence of risk factors such as hepatitis B and C infections, and alcohol consumption, as well as genetic predispositions that are distinct between Eastern and Western populations. Moreover, the impact of racial and ethnic diversity on the disease's epidemiology further complicates the global understanding and prediction of HCC. Such disparities highlight the critical need to evaluate the applicability of predictive models across diverse populations, acknowledging that a model developed in one region may not necessarily translate with the same accuracy or effectiveness when applied to another, because of these underlying epidemiologic and genetic differences. In this study, we aimed to assess the cross-regional applicability and accuracy of an HCC prediction model (Texas hepatocellular carcinoma risk index [THCC-RI] predictive model) originally developed in Western populations, within an Eastern context.1,2.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Aged , Female , Humans , Male , Middle Aged , Asian People/statistics & numerical data , Carcinoma, Hepatocellular/epidemiology , Cohort Studies , Liver Neoplasms/epidemiology , Risk Assessment/methods , Risk Factors
13.
BMC Med ; 22(1): 251, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886720

ABSTRACT

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.


Subject(s)
Diabetes Mellitus, Type 2 , Exercise , Thyroid Neoplasms , Thyroidectomy , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications , Male , Female , Middle Aged , Exercise/physiology , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Incidence , Adult , Republic of Korea/epidemiology , Thyroidectomy/adverse effects , Aged , Cohort Studies
14.
BMC Med ; 22(1): 335, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39148087

ABSTRACT

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.


Subject(s)
Clopidogrel , Cytochrome P-450 CYP2C19 , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Proton Pump Inhibitors , Humans , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Clopidogrel/administration & dosage , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Male , Female , Drug-Eluting Stents/adverse effects , Aged , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Percutaneous Coronary Intervention/adverse effects , Cytochrome P-450 CYP2C19/genetics , Treatment Outcome , Registries , East Asian People
15.
Microvasc Res ; 155: 104713, 2024 09.
Article in English | MEDLINE | ID: mdl-38914307

ABSTRACT

Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.


Subject(s)
Antioxidants , Muscle, Skeletal , Oxidative Stress , Peripheral Arterial Disease , Reactive Oxygen Species , Signal Transduction , Humans , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/metabolism , Peripheral Arterial Disease/drug therapy , Peripheral Arterial Disease/therapy , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Antioxidants/therapeutic use , Animals , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiopathology , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism
16.
Langmuir ; 2024 Oct 18.
Article in English | MEDLINE | ID: mdl-39420794

ABSTRACT

Lithium nickel manganese oxide (LiNi0.5Mn1.5O4, LNMO) provides an elevated operating potential of 4.7 V and a theoretical capacity of 147 mAh g-1, without the need for expensive cobalt. Zr-doped LNMO was synthesized using the coprecipitation technique with Couette-Taylor flow. FE-SEM images and TEM SAED patterns revealed that Zr-doped LNMO formed truncated octahedral structures with exposed (100) crystal facets. When compared to undoped LNMO, Zr-doped LNMO exhibited superior electrochemical performance. Electrochemical evaluations showed that Zr0.1-LNMO achieved 85.9% rate capability at 10 C, significantly outperforming the 69.1% of bare LNMO. In addition, Zr0.1-LNMO exhibited high stability, maintaining 76.8% of the discharge capacity even after 100 cycles.

17.
Anesthesiology ; 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39388595

ABSTRACT

BACKGROUND: Electroencephalogram burst suppression can be associated with postoperative delirium; however, the results of relevant studies are discrepant. This systematic review and meta-analysis aimed to assess the association between intraoperative burst suppression and postoperative delirium in adult surgical patients. METHODS: PubMed, MEDLINE, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were systematically searched and updated in May 2023. We included cohort studies, case-control studies, and randomized-controlled studies reporting on postoperative delirium incidence with documented intraoperative burst suppression in adults receiving general anesthesia for any surgery. The primary outcome was the pooled odds ratio (OR) for postoperative delirium in cases with intraoperative burst suppression compared to those without burst suppression, calculated using a random-effects model. Two independent investigators extracted the data. The protocol was prospectively registered in PROSPERO (registration number: CRD42022326479); the results were reported according to PRISMA guidelines. RESULTS: Fourteen studies (6435 patients) were included in the analysis. The overall incidence of postoperative delirium was 21.1% (1358/6435). Patients with intraoperative burst suppression had a higher incidence of postoperative delirium than those without burst suppression (pooled OR, 1.492; 95% confidence interval (CI) [1.022-2.178]; I2 =44%; 95% CI [0%-75%]; τ2 = 0.110). The intraoperative duration of burst suppression was significantly longer in patients who developed postoperative delirium (standardized mean difference [SMD] 0.462 [95% CI, 0.293-0.632]; I2 = 63%; 95% CI [16%-84%]; τ2 = 0.027). The burst suppression ratio was significantly higher in the delirium group (SMD 0.150; 95% CI [0.055-0.245]; I2 = 0%; 95% CI [0%-85%]; τ2 = 0.00). CONCLUSION: Our meta-analysis suggests an association between intraoperative burst suppression and postoperative delirium; however, the quality of evidence was very low. The limited number of studies and substantial heterogeneity across them emphasize the need for further high-quality studies to establish a more robust conclusion.

18.
Circ J ; 88(8): 1237-1245, 2024 07 25.
Article in English | MEDLINE | ID: mdl-38599833

ABSTRACT

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.


Subject(s)
Natriuretic Peptide, Brain , Non-ST Elevated Myocardial Infarction , Peptide Fragments , Percutaneous Coronary Intervention , Registries , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Aged , Male , Female , Middle Aged , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/diagnosis , Republic of Korea/epidemiology , Prognosis , Heart Failure/blood , Heart Failure/mortality , Biomarkers/blood
19.
Crit Care ; 28(1): 99, 2024 03 25.
Article in English | MEDLINE | ID: mdl-38523296

ABSTRACT

BACKGROUND: Despite the high workload of cardiac intensive care unit (ICU), there is a paucity of evidence on the association between nurse workforce and mortality in patients with cardiogenic shock (CS). This study aimed to evaluate the prognostic impact of the ICU nursing grade on mortality and cost-effectiveness in CS. METHODS: A nationwide analysis was performed using the K-NHIS database. Patients diagnosed with CS and admitted to the ICU at tertiary hospitals were enrolled. ICU nursing grade was defined according to the bed-to-nurse ratio: grade1 (bed-to-nurse ratio < 0.5), grade2 (0.5 ≤ bed-to-nurse ratio < 0.63), and grade3 (0.63 ≤ bed-to-nurse ratio < 0.77) or above. The primary endpoint was in-hospital mortality. Cost-effective analysis was also performed. RESULTS: Of the 72,950 patients with CS, 27,216 (37.3%) were in ICU nursing grade 1, 29,710 (40.7%) in grade 2, and 16,024 (22.0%) in grade ≥ 3. The adjusted-OR for in-hospital mortality was significantly higher in patients with grade 2 (grade 1 vs. grade 2, 30.6% vs. 37.5%, adjusted-OR 1.14, 95% CI1.09-1.19) and grade ≥ 3 (40.6%) with an adjusted-OR of 1.29 (95% CI 1.23-1.36) than those with grade 1. The incremental cost-effectiveness ratio of grade1 compared with grade 2 and ≥ 3 was $25,047/year and $42,888/year for hospitalization and $5151/year and $5269/year for 1-year follow-up, suggesting that grade 1 was cost-effective. In subgroup analysis, the beneficial effects of the high-intensity nursing grade on mortality were more prominent in patients who received CPR or multiple vasopressors usage. CONCLUSIONS: For patients with CS, ICU grade 1 with a high-intensity nursing staff was associated with reduced mortality and more cost-effectiveness during hospitalization compared to grade 2 and grade ≥ 3, and its beneficial effects were more pronounced in subjects at high risk of CS.


Subject(s)
Nursing Staff, Hospital , Shock, Cardiogenic , Humans , Cost-Benefit Analysis , Intensive Care Units , Workload , Hospital Mortality
20.
Phys Chem Chem Phys ; 26(41): 26370-26376, 2024 Oct 23.
Article in English | MEDLINE | ID: mdl-39387114

ABSTRACT

Although iron-based single atom catalysts are regarded as a promising alternative to precious metal catalysts, their precise electronic structures during catalysis still pose challenges for computational descriptions. A particularly urgent issue to be addressed is the influence of the environment on the electronic structure, and how to describe this accurately using computational methods. Here, we study an iron porphyrin chloride complex adsorbed on a graphene sheet using density functional theory calculations to probe how much the electronic structure is influenced by the presence of a graphene layer. Our results indicate that weak interactions due to van der Waals forces dominate between the porphyrin complex and graphene, and only a small amount of charge is transferred between the two entities. Furthermore, the interplay of the ligand field environment, strong p-d hybridization, and correlation effects within the complex are strongly involved in determining the spin state of the iron ion. By bridging molecular chemistry and solid state physics, this study provides first steps towards a joint analysis of the properties of iron-based catalysts from first principles.

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