Binding of IscU and TusA to different but competing sites of IscS influences the activity of IscS and directs sulfur to the respective biomolecular synthesis pathway.

All sulfur transfer pathways generally have in common an l-cysteine desulfurase as the initial sulfur-mobilizing enzyme, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In Escherichia coli, the housekeeping l-cysteine desulfurase IscS functions as a hub for sulfur transfer through interactions with several partner proteins, which bind at different sites on IscS. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron sulfur (Fe-S) cluster assembly, TusA, required for molybdenum cofactor biosynthesis and mnm5s2U34 transfer RNA (tRNA) modifications, and ThiI, involved in both the biosynthesis of thiamine and s4U8 tRNA modifications, have been mapped. Previous studies have suggested that IscS partner proteins bind only one at a time, with the exception of Fe-S cluster assembly, which involves the formation of a ternary complex involving IscS, IscU, and one of CyaY, Fdx, or IscX. Here, we show that the affinity of TusA for IscS is similar to but lower than that of IscU and that these proteins compete for binding to IscS. We show that heterocomplexes involving the IscS dimer and single IscU and TusA molecules are readily formed and that binding of both TusA and IscU to IscS affects its l-cysteine desulfurase activity. A model is proposed in which the delivery of sulfur to different sulfur-requiring pathways is controlled by sulfur acceptor protein levels, IscS-binding affinities, and acceptor protein-modulated IscS desulfurase activity.IMPORTANCEIron-sulfur clusters are evolutionarily ancient prosthetic groups. The housekeeping l-cysteine desulfurase IscS functions as a central core for sulfur transfer through interactions with several partner proteins, which bind at different sites on each IscS monomer with different affinities and partially overlapping binding sites. We show that heterocomplexes involving the IscS dimer and single IscU and TusA molecules at each site of the dimer are formed, thereby influencing the activity of IscS.

Molecular behavior of silicone adhesive at buried polymer interface studied by molecular dynamics simulation and sum frequency generation vibrational spectroscopy.

Silicones have excellent material properties and are used extensively in many applications, ranging from adhesives and lubricants to electrical insulation. To ensure strong adhesion of silicone adhesives to a wide variety of substrates, silane-based adhesion promotors are typically blended into the silicone adhesive formulation. However, little is known at the molecular level about the true silane adhesion promotion mechanism, which limits the ability to develop even more effective adhesion promoters. To understand the adhesion promotion mechanism of silane molecules at the molecular level, this study has used sum frequency generation vibrational spectroscopy (SFG) to determine the behavior of (3-glycidoxypropyl)trimethoxy silane (γ-GPS) at the buried interface between poly(ethylene terephthalate) (PET) and a bulk silicone adhesive. To complement and extend the SFG results, atomistic molecular dynamics (MD) simulations were applied to investigate molecular behavior and interfacial interaction of γ-GPS at the silicone/PET interface. Free energy computations were used to study the γ-GPS interaction in the sample system and determine the γ-GPS interfacial segregation mechanism. Both experiments and simulations consistently show that γ-GPS molecules prefer to segregate at the interface between PET and PDMS. The methoxy groups on γ-GPS molecules orient toward the PDMS polymer phase. The consistent picture of interfacial structure emerging from both simulation and experiment provides enhanced insight on how γ-GPS behaves in the silicone - PET system and illustrates why γ-GPS could improve the adhesion of silicone adhesive, leading to further understanding of silicone adhesion mechanisms useful in the design of silicone adhesives with improved performance.

Inter-subject correlation of audience facial expressions predicts audience engagement during theatrical performances.

During performances, audiences experience various emotional states, and these are reflected in their ongoing facial expressions. We investigated if audience engagement could be determined by measuring the inter-subject correlation (ISC) of non-invasively recorded audience facial expressions. We filmed the faces of multiple audience members at theatrical performances and determined the intensity of their different facial expressions throughout the performances. Neutral, happy, anger, and disgust expression ISCs accounted for up to 24% of the performance dramaturge's predictions of audience engagement. Expression synchrony was greater between individuals in close proximity, suggesting effects of emotional contagion or cognitive similarities between neighboring individuals, whereas expression synchrony was greatest between individuals who were younger, female, and with greater levels of empathy, showing that individual characteristics impact shared audience experiences. Together, our results show that facial expression synchronization could be used as a real-time non-invasive indicator of engagement in audiences larger than achieved using previous approaches.

Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Variability in research culture across busy catheterisation labs in the Asia-Pacific region.

Background: Information related to research culture in the busy catheterisation (cath) labs across the Asia-Pacific (APAC) region is sparse. Aims: The aims of this study were to examine the variability in research culture in busy cath labs in the APAC region and to propose a roadmap for hospitals to develop in-house research capabilities in conjunction with industry and academia. Methods: Data related to research practices in the APAC region were collected from busy cath labs (at least 250 angioplasty/year) and analysed. Results were shared with research experts to understand the challenges in institutional research and create a roadmap for hospitals to develop research capabilities. Results: A total of 220 respondents from 62 cath labs (88.6%) across 13 APAC countries participated in the survey. A wide variation was noted in research culture across APAC countries. Well-established infrastructure was reported in Australia, New Zealand, South Korea, Singapore, and Japan. Large multicentre trials were common in South Korea, while routine follow-ups were common in Japan. Linking medical records across hospitals/states was considered challenging. Research exposure and training were limited in the APAC region. The experts suggested a roadmap, including creating a conducive regulatory environment, forming synergistic goals, training programs for the professionals involved in research, and leveraging best practices, for improving the research culture in APAC. Conclusions: Clinical research in cardiology has grown significantly in the APAC region, with a huge research potential in China and India. Implementing measures to improve research training and involvement of the industry will boost the research culture in the APAC region.

Fractional flow reserve measurements and long-term mortality-results from the FLORIDA study.

Background: Randomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown. Aims: The FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort. Methods: This study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality. Results: In the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients aged ≥75 years (14.9% vs. 20.1%, p < 0.01) and those presenting with ACS (10.2% vs. 14.0%, p = 0.04). Conclusions: FFR-based revascularization strategy was associated with reduced mortality at 3 years. These findings further support the use of FFR in everyday clinical practice.

The Ferroxidase Centre of Escherichia coli Bacterioferritin Plays a Key Role in the Reductive Mobilisation of the Mineral Iron Core.

Ferritins are multimeric cage-forming proteins that play a crucial role in cellular iron homeostasis. All H-chain-type ferritins harbour a diiron site, the ferroxidase centre, at the centre of a 4 α-helical bundle, but bacterioferritins are unique in also binding 12 hemes per 24 meric assembly. The ferroxidase centre is known to be required for the rapid oxidation of Fe2+ during deposition of an immobilised ferric mineral core within the protein's hollow interior. In contrast, the heme of bacterioferritin is required for the efficient reduction of the mineral core during iron release, but has little effect on the rate of either oxidation or mineralisation of iron. Thus, the current view is that these two cofactors function in iron uptake and release, respectively, with no functional overlap. However, rapid electron transfer between the heme and ferroxidase centre of bacterioferritin from Escherichia coli was recently demonstrated, suggesting that the two cofactors may be functionally connected. Here we report absorbance and (magnetic) circular dichroism spectroscopies, together with in vitro assays of iron-release kinetics, which demonstrate that the ferroxidase centre plays an important role in the reductive mobilisation of the bacterioferritin mineral core, which is dependent on the heme-ferroxidase centre electron transfer pathway.

Probing the mechanism of the dedicated NO sensor [4Fe-4S] NsrR: the effect of cluster ligand environment.

NsrR from Streptomyces coelicolor is a bacterial nitric oxide (NO) sensor/nitrosative stress regulator as its primary function, and has been shown to have differential response at low, mid, and high levels of NO. These must correspond to discrete structural changes at the protein-bound [4Fe-4S] cluster in response to stepwise nitrosylation of the cluster. We have investigated the effect of the monohapto carboxylate ligand in the site differentiated [4Fe-4S] cluster cofactor of the protein NsrR on modulating its reactivity to NO with a focus on indentifying mechanistic intermediates. We have prepared a synthetic model [4Fe-4S] cluster complex with tripodal ligand and one single site differentiated site occupied by either thiolate or carboxylate ligand. We report here the mechanistic details of sequential steps of nitrosylation as observed by ESI MS and IR spectroscopy. Parallel non-denaturing mass spectrometry analyses were performed using site-differentiated variants of NsrR with the native aspartic acid, cysteine, or alanine in the position of the forth ligand to the cluster. A mono-nitrosylated synthetic [4Fe-4S] cluster was observed for the first time in a biologically-relevant thiolate-based coordination environment. Combined synthetic and protein data give unprecedented clarity in the modulation of nitrosylation of a [4Fe-4S] cluster.

Four fundamental dimensions underlie the perception of human actions.

We evaluate the actions of other individuals based upon a variety of movements that reveal critical information to guide decision making and behavioural responses. These signals convey a range of information about the actor, including their goals, intentions and internal mental states. Although progress has been made to identify cortical regions involved in action processing, the organising principles underlying our representation of actions still remains unclear. In this paper we investigated the conceptual space that underlies action perception by assessing which qualities are fundamental to the perception of human actions. We recorded 240 different actions using motion-capture and used these data to animate a volumetric avatar that performed the different actions. 230 participants then viewed these actions and rated the extent to which each action demonstrated 23 different action characteristics (e.g., avoiding-approaching, pulling-pushing, weak-powerful). We analysed these data using Exploratory Factor Analysis to examine the latent factors underlying visual action perception. The best fitting model was a four-dimensional model with oblique rotation. We named the factors: friendly-unfriendly, formidable-feeble, planned-unplanned, and abduction-adduction. The first two factors of friendliness and formidableness explained approximately 22% of the variance each, compared to planned and abduction, which explained approximately 7-8% of the variance each; as such we interpret this representation of action space as having 2 + 2 dimensions. A closer examination of the first two factors suggests a similarity to the principal factors underlying our evaluation of facial traits and emotions, whilst the last two factors of planning and abduction appear unique to actions.

Impact of Intensity of Vascular Care Preceding Major Amputation Among Patients With Chronic Limb-Threatening Ischemia.

BACKGROUND: Lower-limb amputation rates in patients with chronic limb-threatening ischemia vary across the United States, with marked disparities in amputation rates by gender, race, and income status. We evaluated the association of patient, hospital, and geographic characteristics with the intensity of vascular care received the year before a major lower-limb amputation and how intensity of care associates with outcomes after amputation. METHODS: Using Medicare claims data (2016-2019), beneficiaries diagnosed with chronic limb-threatening ischemia who underwent a major lower-limb amputation were identified. We examined patient, hospital, and geographic characteristics associated with the intensity of vascular care received the year before amputation. Secondary objectives evaluated all-cause mortality and adverse events following amputation. RESULTS: Of 33 036 total Medicare beneficiaries undergoing major amputation, 7885 (23.9%) were due to chronic limb-threatening ischemia; of these, 4988 (63.3%) received low-intensity and 2897 (36.7%) received high-intensity vascular care. Mean age, 76.6 years; women, 38.9%; Black adults, 24.5%; and of low income, 35.2%. After multivariable adjustment, those of low income (odds ratio, 0.65 [95% CI, 0.58-0.72]; P<0.001), and to a lesser extent, men (odds ratio, 0.89 [95% CI, 0.81-0.98]; P=0.019), and those who received care at a safety-net hospital (odds ratio, 0.87 [95% CI, 0.78-0.97]; P=0.012) were most likely to receive low intensity of care before amputation. High-intensity care was associated with a lower risk of all-cause mortality 2 years following amputation (hazard ratio, 0.79 [95% CI, 0.74-0.85]; P<0.001). CONCLUSIONS: Patients who were of low-income status, and to a lesser extent, men, or those cared for at safety-net hospitals were most likely to receive low-intensity vascular care. Low-intensity care was associated with worse long-term event-free survival. These data emphasize the continued disparities that exist in contemporary vascular practice.

From cultivation to cancer: formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications.

Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.

Whole-cell studies of substrate and inhibitor specificity of isoprene monooxygenase and related enzymes.

Co-oxidation of a range of alkenes, dienes, and aromatic compounds by whole cells of the isoprene-degrading bacterium Rhodococcus sp. AD45 expressing isoprene monooxygenase was investigated, revealing a relatively broad substrate specificity for this soluble diiron centre monooxygenase. A range of 1-alkynes (C2 -C8 ) were tested as potential inhibitors. Acetylene, a potent inhibitor of the related enzyme soluble methane monooxygenase, had little inhibitory effect, whereas 1-octyne was a potent inhibitor of isoprene monooxygenase, indicating that 1-octyne could potentially be used as a specific inhibitor to differentiate between isoprene consumption by bona fide isoprene degraders and co-oxidation of isoprene by other oxygenase-containing bacteria, such as methanotrophs, in environmental samples. The isoprene oxidation kinetics of a variety of monooxygenase-expressing bacteria were also investigated, revealing that alkene monooxygenase from Xanthobacter and soluble methane monooxygenases from Methylococcus and Methylocella, but not particulate methane monooxygenases from Methylococcus or Methylomicrobium, could co-oxidise isoprene at appreciable rates. Interestingly the ammonia monooxygenase from the nitrifier Nitrosomonas europaea could also co-oxidise isoprene at relatively high rates, suggesting that co-oxidation of isoprene by additional groups of bacteria, under the right conditions, might occur in the environment.

Artificial Intelligence, Computational Simulations, and Extended Reality in Cardiovascular Interventions.

Artificial intelligence, computational simulations, and extended reality, among other 21st century computational technologies, are changing the health care system. To collectively highlight the most recent advances and benefits of artificial intelligence, computational simulations, and extended reality in cardiovascular therapies, we coined the abbreviation AISER. The review particularly focuses on the following applications of AISER: 1) preprocedural planning and clinical decision making; 2) virtual clinical trials, and cardiovascular device research, development, and regulatory approval; and 3) education and training of interventional health care professionals and medical technology innovators. We also discuss the obstacles and constraints associated with the application of AISER technologies, as well as the proposed solutions. Interventional health care professionals, computer scientists, biomedical engineers, experts in bioinformatics and visualization, the device industry, ethics committees, and regulatory agencies are expected to streamline the use of AISER technologies in cardiovascular interventions and medicine in general.

Impact of Post-PCI FFR Stratified by Coronary Artery.

BACKGROUND: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated. OBJECTIVES: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. METHODS: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. RESULTS: Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005). CONCLUSIONS: The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels.

Standardized Definitions for Cardiogenic Shock Research and Mechanical Circulatory Support Devices: Scientific Expert Panel From the Shock Academic Research Consortium (SHARC).

The Shock Academic Research Consortium is a multi-stakeholder group, including representatives from the US Food and Drug Administration and other government agencies, industry, and payers, convened to develop pragmatic consensus definitions useful for the evaluation of clinical trials enrolling patients with cardiogenic shock, including trials evaluating mechanical circulatory support devices. Several in-person and virtual meetings were convened between 2020 and 2022 to discuss the need for developing the standardized definitions required for evaluation of mechanical circulatory support devices in clinical trials for cardiogenic shock patients. The expert panel identified key concepts and topics by performing literature reviews, including previous clinical trials, while recognizing current challenges and the need to advance evidence-based practice and statistical analysis to support future clinical trials. For each category, a lead (primary) author was assigned to perform a literature search and draft a proposed definition, which was presented to the subgroup. These definitions were further modified after feedback from the expert panel meetings until a consensus was reached. This manuscript summarizes the expert panel recommendations focused on outcome definitions, including efficacy and safety.

Stabilisation of the RirA [4Fe-4S] cluster results in loss of iron-sensing function.

RirA is a global iron regulator in diverse Alphaproteobacteria that belongs to the Rrf2 superfamily of transcriptional regulators, which can contain an iron-sulfur (Fe-S) cluster. Under iron-replete conditions, RirA contains a [4Fe-4S] cluster, enabling high-affinity binding to RirA-regulated operator sequences, thereby causing the repression of cellular iron uptake. Under iron deficiency, one of the cluster irons dissociates, generating an unstable [3Fe-4S] form that subsequently degrades to a [2Fe-2S] form and then to apo RirA, resulting in loss of high-affinity DNA-binding. The cluster is coordinated by three conserved cysteine residues and an unknown fourth ligand. Considering the lability of one of the irons and the resulting cluster fragility, we hypothesized that the fourth ligand may not be an amino acid residue. To investigate this, we considered that the introduction of an amino acid residue that could coordinate the cluster might stabilize it. A structural model of RirA, based on the Rrf2 family nitrosative stress response regulator NsrR, highlighted residue 8, an Asn in the RirA sequence, as being appropriately positioned to coordinate the cluster. Substitution of Asn8 with Asp, the equivalent, cluster-coordinating residue of NsrR, or with Cys, resulted in proteins that contained a [4Fe-4S] cluster, with N8D RirA exhibiting spectroscopic properties very similar to NsrR. The variant proteins retained the ability to bind RirA-regulated DNA, and could still act as repressors of RirA-regulated genes in vivo. However, they were significantly more stable than wild-type RirA when exposed to O2 and/or low iron. Importantly, they exhibited reduced capacity to respond to cellular iron levels, even abolished in the case of the N8D version, and thus were no longer iron sensing. This work demonstrates the importance of cluster fragility for the iron-sensing function of RirA, and more broadly, how a single residue substitution can alter cluster coordination and functional properties in the Rrf2 superfamily of regulators.

Optical Coherence Tomography-Guided versus Angiography-Guided PCI.

BACKGROUND: Data regarding clinical outcomes after optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) as compared with angiography-guided PCI are limited. METHODS: In this prospective, randomized, single-blind trial, we randomly assigned patients with medication-treated diabetes or complex coronary-artery lesions to undergo OCT-guided PCI or angiography-guided PCI. A final blinded OCT procedure was performed in patients in the angiography group. The two primary efficacy end points were the minimum stent area after PCI as assessed with OCT and target-vessel failure at 2 years, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization. Safety was also assessed. RESULTS: The trial was conducted at 80 sites in 18 countries. A total of 2487 patients underwent randomization: 1233 patients were assigned to undergo OCT-guided PCI, and 1254 to undergo angiography-guided PCI. The minimum stent area after PCI was 5.72±2.04 mm2 in the OCT group and 5.36±1.87 mm2 in the angiography group (mean difference, 0.36 mm2; 95% confidence interval [CI], 0.21 to 0.51; P<0.001). Target-vessel failure within 2 years occurred in 88 patients in the OCT group and in 99 patients in the angiography group (Kaplan-Meier estimates, 7.4% and 8.2%, respectively; hazard ratio, 0.90; 95% CI, 0.67 to 1.19; P = 0.45). OCT-related adverse events occurred in 1 patient in the OCT group and in 2 patients in the angiography group. Stent thrombosis within 2 years occurred in 6 patients (0.5%) in the OCT group and in 17 patients (1.4%) in the angiography group. CONCLUSIONS: Among patients undergoing PCI, OCT guidance resulted in a larger minimum stent area than angiography guidance, but there was no apparent between-group difference in the percentage of patients with target-vessel failure at 2 years. (Funded by Abbott; ILUMIEN IV: OPTIMAL PCI ClinicalTrials.gov number, NCT03507777.).

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Holocynips illinoiensis, sp. nov., a new species of oak gall wasp (Hymenoptera: Cynipidae) from the USA.

A new species, Holocynips illinoiensis Melika & Nicholls, sp. nov. is described from the Nearctic (America north of Mexico). Description, diagnoses, information on biology and host association is given for the new species, as well as preliminary discussion on the coherence of the genus Holocynips.

5-Year Outcomes After Bioresorbable Coronary Scaffolds Implanted With Improved Technique.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated noninferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES). OBJECTIVES: This study sought to evaluate the long-term outcomes from the ABSORB IV trial. METHODS: We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs CoCr-EES. Patients, clinical assessors, and event adjudicators were blinded to randomization. Five-year follow-up was completed. RESULTS: Target lesion failure at 5 years occurred in 216 (17.5%) patients assigned to BVS and 180 (14.5%) patients assigned to CoCr-EES (P = 0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P = 0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and were similar between 3 and 5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 (53.3%) patients assigned to CoCr-EES (P = 0.63). CONCLUSIONS: In this large-scale, blinded randomized trial, despite the improved implantation technique, the absolute 5-year rate of target lesion failure was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was limited to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.(Absorb IV Randomized Controlled Trial; NCT02173379).