As the volume of plastic waste from electrical and electronic equipment (WEEE) continues to rise, a significant portion is disposed of in the environment, with only a small fraction being recycled. Both disposal and recycling pose unknown health risks that require immediate attention. Existing knowledge of WEEE plastic toxicity is limited and mostly relies on epidemiological data and association studies, with few insights into the underlying toxicity mechanisms. Therefore, this study aimed to perform comprehensive chemical screening and mechanistic toxicological assessment of WEEE plastic-associated chemicals. Chemical analysis, utilizing suspect screening based on high-resolution mass spectrometry, along with quantitative target chemical analysis, unveiled numerous hazardous compounds including polyaromatic compounds, organophosphate flame retardants, phthalates, benzotriazoles, etc. Toxicity endpoints included perturbation of morphological phenotypes using the Cell Painting approach, inflammatory response, oxidative stress, and endocrine disruption. Results demonstrated that WEEE plastic chemicals altered the phenotypes of the cytoskeleton, endoplasmic reticulum, and mitochondria in a dose-dependent manner. In addition, WEEE chemicals induced inflammatory responses in resting macrophages and altered inflammatory responses in lipopolysaccharide-primed macrophages. Furthermore, WEEE chemicals activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, indicating oxidative stress, and the aryl hydrocarbon receptor (AhR). Endocrine disruption was also observed through the activation of estrogenic receptor-α (ER-α) and the induction of anti-androgenic activity. The findings show that WEEE plastic-associated chemicals exert effects in multiple subcellular sites, via different receptors and mechanisms. Thus, an integrated approach employing both chemical and toxicological methods is essential for comprehensive assessment of the toxicity mechanisms and cumulative chemical burden of WEEE plastic-associated chemicals.

Background: Rescue stenting (RS) is a bailout strategy for failed thrombectomy. Optimal platelet inhibition strategy after RS remains unclear. Objectives: We aimed to describe and compare different platelet inhibition strategies during/after RS. Design: Retrospective cohort study across 34 international centers. Methods: Patients with large vessel occlusion and RS after failed thrombectomy (2019–2023) were included. Periprocedural and postprocedural platelet inhibition strategies were described and compared, focusing on glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, single antiplatelet therapy (SAPT), and dual antiplatelet therapy (DAPT). We assessed the effects of platelet inhibition strategy and potentially covariates on the primary outcome of 90-day modified Rankin Scale (mRS) using ordinal shift analysis with proportional odds models. Results: RS was performed in 589 patients (mean age 67.9 years, 60.8% male). Numerous combinations of platelet inhibitors were administered. Periprocedural GPIIb/IIIa inhibitors were used in 61.5% of patients. Postprocedural DAPT was administered to 80.5% and SAPT to 13.3%. Functional independence (mRS 0–2) was achieved in 40.7%, while 26.3% died within 90 days. Stent occlusion occurred in 20.5%, with 67.6% of these occlusions within 24 h. Postprocedural stent-occlusion was independently associated with worse functional outcome at 90 days (OR 4.1, 95% CI 2.3–7.2, p < 0.001). No significant association between periprocedural GPIIb/IIIa inhibitors, and 90-day mRS or stent occlusion was found. Postprocedural SAPT was associated with worse functional outcomes (adjusted odds ratio (aOR) 2.4, 95% CI 1.1–5.0, p = 0.02), higher mortality (aOR 2.1, 95% CI 1.05–4.0, p = 0.03), and increased stent occlusion rates (aOR 4.8, 95% CI 2.3–9.7, p < 0.001) compared to postprocedural DAPT. Symptomatic intracranial hemorrhage occurred in 6.8% of patients, with no significant difference between antiplatelet regimens. Conclusion: Extensive heterogeneity exists in platelet inhibition strategies following RS. Stent occlusion is associated with worse clinical outcomes, and the first 24 h post-RS are critical for stent patency. Compared to SAPT, DAPT was associated with better functional outcome, lower mortality, and lower stent occlusion rates. Plain language summary When clot removal for stroke fails and a stent is placed, different blood thinner treatments affect risk of stent blockage and outcomes When doctors try to remove a blood clot during a stroke but are unsuccessful, they sometimes place a stent to reopen the blocked artery—a procedure called “rescue stenting.” After placing a stent, patients need blood-thinning medications to prevent the stent from becoming blocked again. However, the best way to manage these medications is unclear. In this study, we looked at 589 patients from 34 hospitals around the world who had rescue stenting between 2019 and 2023. We compared different strategies for using blood thinners, including strong drugs given during the procedure and either one (“single”) or two (“dual”) blood thinners given afterward. We found a lot of variation in how doctors used these medications. Using a strong blood thinner during the procedure didn’t seem to change long-term recovery or the risk of the stent blocking. However, after the procedure, patients who were treated with two blood thinners did better than those who got only one. Patients on dual therapy were more likely to recover well, less likely to die, and less likely to have their stent block again. Importantly, most stent blockages happened within the first 24 hours after the procedure, and patients with stent blockages did worse, highlighting the 24h period as critical for blood thinner treatment.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity including patients with different phenotypes of near normal, normal, and supernormal left ventricular (LV) function. OBJECTIVES To assess the value of resting LV elastance (also known as force) with transthoracic echocardiography (TTE) to identify HFpEF phenotypes. METHODS In a prospective, observational, multicenter study, 2380 HFpEF patients were recruited from July 2016 to May 2024. Systolic blood pressure (SBP) was measured. We assessed LV end-diastolic volume (EDV), end-systolic volume (ESV), EF, force (SBP/ESV), stroke volume (SV), arterial elastance (AE), ventricular-arterial coupling (VAC), and left atrial volume index (LAVI). Global longitudinal strain (GLS) was available in 1164 (48.9%) patients. 680 patients finished follow-up with a composite end-point of major adverse cardiac events (MACEs). Patients were divided into three groups: low force (< 25th percentile, Group 1, < 3.24 mmHg/ml), intermediate force (≥ 25th percentile and ≤ 75 th percentile, Group 2, 3.24-5.48 mmHg/ml), and high force (> 75 th percentile, Group 3, >5.48 mmHg/ml). RESULTS The 3 groups showed a gradient with descending values (Group 3>2>1) for SBP, EF, GLS, AE, and VAC, with the opposite gradient (Group 1> 2> 3) for EDV, ESV, SV, and LAVI values (all P<0.01). After a median follow-up of 16 months, 205 MACEs occurred in 138 patients. Cumulative MACEs rate was lowest in group 2 (14.7% person-year), higher in group 1 (16.1% person-year) and 3 (22.9% person-year, log rank p = 0.036). CONCLUSIONS HFpEF patients present with different LV contractile phenotypes, easily identified with resting LV force and volumetric TTE. The dominant hemodynamic feature of hypocontractile phenotype is a preload recruitment with larger LV EDV and normal SV, while the hypercontractile phenotype is characterized by a small LV with reduced SV. The hypercontractile and hypocontractile phenotypes are associated with a higher risk of subsequent events.

Lung ultrasound (LUS) is a valuable, non-invasive tool for detecting pulmonary congestion in patients with acute heart failure (AHF), with a higher sensitivity relative to physical examination. However, the association between LUS-detected pulmonary congestion and cardiovascular outcomes in patients with ST-segment elevation (STEMI) is not well established. This systematic review and meta-analysis evaluated cardiovascular outcomes in patients with STEMI and congested (wet) or non-congested (dry) lungs by LUS. We searched PubMed, Embase, and Cochrane databases, and conference abstracts for clinical trials evaluating LUS-congestion (LUS+) versus non-LUS-congestion (LUS-) in patients with STEMI. Risk ratios (RRs) and hazard ratios (HR) with 95%CIs were pooled using R software under random-effects models. We also calculated LUS sensitivity, specificity, and area under the curves (AUCs) for the prediction of in-hospital mortality and cardiogenic shock. We included five studies with 1,454 patients. The mean age was 60 to 65 years; 1,066 (73.3%) were male, and 451 (31%) had congested lungs (LUS+). Patients with congestion on LUS had a significantly higher risk of the composite endpoint of death, heart failure, acute coronary syndrome, and cardiogenic shock (HR 4.00; 95%CI 2.12-7.54; p<0.01; Figure 1A). There was also a higher risk of in-hospital mortality (RR 5.09; 95%CI 2.25-11.49; p<0.001; Figure 1B) and cardiogenic shock (RR 5.01; 95%CI 2.47-10.17; p<0.001; Figure 1C) compared to patients with non-congested lungs. Reinfarction was similar between groups (p=0.08; Figure 1D). LUS had high diagnostic accuracy for in-hospital mortality (SROC-AUC: 0.82) and cardiogenic shock (SROC-AUC: 0.77); a high sensitivity (0.84; 95%CI 0.49-0.97; Figure 2A), and moderate specificity (0.78; 95%CI 0.67-0.87; Figure 2A) for in-hospital mortality; and moderate sensitivity (0.75; 95%CI 0.42-0.93; Figure 2B) and specificity (0.76; 95% CI 0.61-0.87; Figure 2B) for cardiogenic shock. Congested lungs on LUS are significantly associated with a higher risk of in-hospital mortality and cardiogenic shock in patients with STEMI. Moreover, LUS has a high AUC for identifying in-hospital mortality and cardiogenic shock in this patient population. Figure 1 Figure 2

Over the past decade, stress echocardiography has evolved from a test for assessing epicardial artery stenosis to a comprehensive functional test, targeting multiple cardiovascular parameters. The new approach includes several structured steps: (a) evaluating regional wall motion abnormalities to detect epicardial artery stenosis or vasospasm; (b) assessing pulmonary congestion and diastolic function via B-lines with lung ultrasound; (c) gauging preload and contractile reserve with volumetric echocardiography; (d) measuring coronary microvascular reserve using Doppler-based coronary flow velocity in the middistal left anterior descending artery; and (e) determining cardiac sympathetic reserve by tracking heart rate reserve on an ECG. This evolution was supported extensively by the Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI), which played a key role in five areas: (1) developing the initial, curiosity-driven project; (2) disseminating protocols and results at national and international conferences, supporting logistic infrastructure and publication expenses; (3) establishing a digital platform (customized Redcap) for data entry and storage; (4) facilitating patient recruitment across 19 Italian centers; and (5) offering formal endorsement through six presidencies, adding credibility and reach beyond any single institution. The protocol quickly advanced from concept to high-impact publications, earning inclusion in 2024 specialty guidelines. Initially Italian-led, the study now includes 50 centers across 20 countries (e.g. USA and China). Beyond the 50 peer-reviewed papers published in 2016–2024, this study offers a novel, sustainable approach to cardiac stress testing, providing more information at lower costs, with zero radiation and minimal environmental impact. SIECVI’s endorsement was instrumental in amplifying the study’s rigor and outreach.

Abstract Human activities cause a global loss of soil microbiome diversity and functionality. One way to reverse this trend is through microbiota transplants, but the processes determining merger outcomes are not well understood. Here, we investigated the roles of habitat filtering and microbiota origin on microbiome development upon mergers, with the hypothesis that native strains are better adapted to their own habitat and will outcompete non-native ones in niche colonization. To test this, we contrasted community development in soil microcosms between two taxa-diverse microbiota originating from either topsoil [SoilCom (SC)] or freshwater lake [LakeCom (LC)], and a defined mixture of 21 soil bacteria (SynCom). When inoculated separately, SC and LC showed similar taxa and colonization patterns contributing to community growth and decline within the soil microcosms. SynCom transplants to either SC or LC under renewed growth conditions permanently altered their community trajectories, and slightly further converged their taxa compositions. Levels of SynCom members in both resident backgrounds decreased from initial 50–80% to below 1% within 2 months. Merged as well as non-merged communities resembled natural soils in comparison to over 81 000 publicly available soil, sediment, and lake microbiomes. Our results show that habitat filtering is dominant over microbiota taxa origin in determining transplant outcomes. Even though the proliferation of SynCom transplants remained limited, their capacity to influence community merger trajectories long term opens new paths for soil microbiome engineering.

Considering our previous experience in the design of new cholinesterase inhibitors, especially resveratrol analogs, in this research, the basic stilbene skeleton was used as a structural unit for new carbamates designed as potentially highly selective butyrylcholinesterase (BChE) inhibitors with excellent absorption, distribution, metabolism, excretion and toxicity ADMET properties. The inhibitory activity of newly prepared carbamates 1–13 was tested toward the enzymes acetylcholinesterase (AChE) and BChE. In the tested group of compounds, the leading inhibitors were 1 and 7, which achieved excellent selective inhibitory activity for BChE with IC50 values of 0.12 ± 0.09 μM and 0.38 ± 0.01 μM, respectively. Both were much more active than the standard inhibitor galantamine against BChE. Molecular docking of the most promising inhibitor candidates, compounds 1 and 7, revealed that stabilizing interactions between the active site residues of BChE and the ligands involve π-stacking, alkyl-π interactions, and, when the carbamate orientation allows, H-bond formation. MD analysis confirmed the stability of the obtained complexes. Some bioactive resveratrol-based carbamates displayed complex-forming capabilities with Fe3+ ions as metal centers. Spectrophotometric investigation indicated that they coordinate one or two metal ions, which is in accordance with their chemical structure, offering two binding sites: an amine and a carboxylic group in the carbamate moiety. Based on the obtained in silico, experimental and computational results on biological activity in the present work, new carbamates 1 and 7 represent potential selective BChE inhibitors as new therapeutics for neurological disorders.

OBJECTIVE Brainstem cavernous malformations (BSCMs) were once considered inoperable. Microsurgical resection now represents a valuable option for treating patients with hemorrhagic or symptomatic lesions. The aim of this study was to provide a practical guide for surgical planning by analyzing postoperative neurological and functional outcomes. METHODS The early- and long-term neurological (National Institutes of Health Stroke Scale [NIHSS] score) and functional (modified Rankin Scale [mRS] and Glasgow Outcome Scale [GOS] scores) outcomes of 32 patients who underwent surgery for hemorrhagic BSCM were reviewed. The three-step surgical planning was based on an anatomosurgical algorithm. RESULTS Nine lesions (28.1%) were located in the mesencephalon, 19 (59.4%) in the pons, and 4 (12.5%) in the medulla. A fronto-temporo-orbito-zygomatic approach was selected to reach anterior mesencephalic BSCMs (2, 6.3%). A retrosigmoid approach and its extended variant were selected for lateral mesencephalic (6, 18.8%), anterior (2, 6.3%) and lateral (13, 40.6%) pontine, and anterior (1, 3.1%) and lateral (1, 3.1%) medullary BSCMs. A supracerebellar infratentorial approach was selected for posterior mesencephalic BSCMs (1, 3.1%). A telovelar approach was selected for posterior pontine (4, 12.5%) and medullary (2, 6.3%) BSCMs. Total resection was achieved in 29 cases (90.6%), with a 12.5% rate of surgical complications. The NIHSS score progressively improved at both the early (5.16 ± 3.70 vs 4.63 ± 2.78, p = 0.446) and late (4.63 ± 2.78 vs 2.41 ± 2.39, p < 0.001) postoperative evaluations. Functional outcomes showed an initial deterioration followed by a long-term improvement (mRS score: 2.66 ± 1.07 vs 3.06 ± 1.11 vs 2.13 ± 1.29, GOS score: 3.78 ± 0.61 vs 3.59 ± 0.62 vs 4.19 ± 0.78). Time to surgery significantly correlated with early- and long-term NIHSS, mRS, and GOS scores, while the number of hemorrhages before surgery correlated with early- and long-term mRS and GOS scores. CONCLUSIONS Early surgery after the first bleed following systematic surgical planning may be considered as an effective option for managing hemorrhagic BSCMs with acceptable operative morbidity and relatively favorable early- and long-term neurological and functional outcomes.

Network emulators play an important role in testing network systems, applications, and protocols. Emulators bridge the gap between simulation setups that lack realism in results and real-world trials that are accurate but often expensive, non-reproducible, and uncontrollable. This article presents an extended model of the Quantum Key Distribution Network Simulation Module (QKDNetSim) with a model catalog of QKD components and functionalities. We explore emulations of point-to-point connections in QKD networks and the interaction of essential components within QKD nodes. The presented tool will undoubtedly spur future development and teaching, and it is critical for testing novel applications and protocols applied to QKD networks.