The RNA chaperone Hfq has a multifaceted role in Edwardsiella ictaluri.

Edwardsiella ictaluri is a Gram-negative, facultative intracellular bacterium that causes enteric septicemia in catfish (ESC). The RNA chaperone Hfq (host factor for phage Qß replication) facilitates gene regulation via small RNAs (sRNAs) in various pathogenic bacteria. Despite its significance in other bacterial species, the role of hfq in E. ictaluri remains unexplored. This study aimed to elucidate the role of hfq in E. ictaluri by creating an hfq mutant (EiΔhfq) through in-frame gene deletion and characterization. Our findings revealed that the Hfq protein is highly conserved within the genus Edwardsiella. The deletion of hfq resulted in a significantly reduced growth rate during the late exponential phase. Additionally, EiΔhfq displayed a diminished capacity for biofilm formation and exhibited increased motility. Under acidic and oxidative stress conditions, EiΔhfq demonstrated impaired growth, and we observed elevated hfq expression when subjected to in vitro and in vivo stress conditions. EiΔhfq exhibited reduced survival within catfish peritoneal macrophages, although it had no discernible effect on the adherence and invasion of epithelial cells. The infection model revealed that hfq is needed for bacterial persistence in catfish, and its absence caused significant virulence attenuation in catfish. Finally, the EiΔhfq vaccination completely protected catfish against subsequent EiWT infection. In summary, these results underscore the pivotal role of hfq in E. ictaluri, affecting its growth, motility, biofilm formation, stress response, and virulence in macrophages and within catfish host.

Clinical Guidelines on Compression Therapy in Venous Diseases.

BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (Grade I), moderate (Grade IIa and IIb), and weak (Grade III) recommendations based on high quality (Class A), moderate quality (Class B), and low quality (Class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on seven fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome, chronic venous insufficiency, varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (Grade I) and 17 were based on high quality (Class A) evidence, highlighting the need for further research of the use of compression therapy for .

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

AIMS: Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. METHODS: Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6-12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6-12 months using two established methods: reference change value (RCV) and minimal important difference (MID). RESULTS: Median baseline hs-cTnT concentrations were 34.4 ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6 months (IQR: 6-7). Median concentration change was 1.9 ng/L (IQR: 0.7-3.2) and 0.8 ng/L (IQR: 0-7.0) at 60 min and 6-9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT ≥ 52 ng/L. Biological variabilities at 6-12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. CONCLUSIONS: The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Stem cell-derived extracellular vesicles as senotherapeutics.

Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells can promote a pro-inflammatory and pro-cancerogenic microenvironment. Among potential senotherapeutics are extracellular vesicles (EVs) (40-1000 nm), including exosomes (40-150 nm), that play an important role in cell-cell communications. Here, we review the most recent studies on the impact of EVs derived from stem cells (MSCs, ESCs, iPSCs) as well as non-stem cells of various types on CS and discuss potential mechanisms responsible for the senotherapeutic effects of EVs. The analysis revealed that (i) EVs derived from stem cells, pluripotent (ESCs, iPSCs) or multipotent (MSCs of various origin), can mitigate the cellular senescence phenotype both in vitro and in vivo; (ii) this effect is presumably senomorphic; (iii) EVs display cross-species activity, without apparent immunogenic responses. In summary, stem cell-derived EVs appear to be promising senotherapeutics, with a feasible application in humans.

Variations in sexual and reproductive health services for the provision of comprehensive contraceptive and abortion services across Europe: A questionnaire-based study commissioned by the European Board and College of Obstetrics & Gynaecology (EBCOG) and European Society of Contraception (ESC).

A questionnaire-based study was jointly organised by European Board and College of Obstetrics and Gynaecology and European Society of Contraception to evaluate the current status as regards access and quality of care regarding contraception, abortion care, and pre-conceptional counselling and care among the 26 European countries. There are considerable variations among these countries as regards the provision of contraceptive services and abortion care. There is ample room for improvement through European training and education programs. However, the most important difference is the absence of a comprehensive network of healthcare providers in various countries to deliver these services at different points of access. There is notable absence of educational programs and instructional materials tailored specifically for nurses and midwives in several countries. This deficiency impedes the professional development and skills enhancement of these healthcare professionals, potentially compromising the quality of healthcare services provided to women in these countries.

Using machine learning to improve the diagnostic accuracy of the modified Duke/ESC 2015 criteria in patients with suspected prosthetic valve endocarditis - a proof of concept study.

INTRODUCTION: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [18F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms. METHODS: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard. RESULTS: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively. DISCUSSION: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [18F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE.

Eosinophilic Solid and Cystic Renal Cell Carcinoma-A Systematic Review and Meta-Analysis.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a distinct entity in the WHO 2022 kidney tumor classification. Previously known as "unclassified RCC", followed by "tuberous sclerosis complex (TSC)-associated RCC", ESC-RCC is now a distinct category of kidney tumor, with its own name, with specific clinical manifestations, and a unique morphological, immunohistochemical and molecular profile. Due to its recent introduction and the limited available data, the diagnosis of ESC-RCC is still a complex challenge, and it is probably frequently misdiagnosed. The secret of diagnosing this tumor lies in the pathologists' knowledge, and keeping it up to date through research, thereby limiting the use of outdated nomenclature. The aim of our case-based review is to provide a better understanding of this pathology and to enrich the literature with a new case report, which has some particularities compared to the existing cases.

Head-to-Head Comparison and Temporal Trends of Cardiac MRI Recommendations in ESC versus ACC/AHA Guidelines: A Systematic Review and Meta-Analysis.

Purpose To provide a comprehensive head-to-head comparison and temporal analysis of cardiac MRI indications between the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines to identify areas of consensus and divergence. Materials and Methods A systematic review and meta-analysis was conducted. ESC and ACC/AHA guidelines published until May 2023 were systematically screened for recommendations related to cardiac MRI. The class of recommendation (COR) and level of evidence (LOE) for cardiac MRI recommendations were compared between the two guidelines and between newer versus older versions of each guideline using χ2 or Fisher exact tests. Results ESC guidelines included 109 recommendations regarding cardiac MRI, and ACC/AHA guidelines included 90 recommendations. The proportion of COR I and LOE B was higher in ACC/AHA versus ESC guidelines (60% [54 of 90] vs 46.8% [51 of 109]; P = .06 and 53% [48 of 90] vs 35.8% [39 of 109], respectively; P = .01). The increase in the number of cardiac MRI recommendations over time was significantly higher in ESC guidelines (from 63 to 109 for ESC vs from 65 to 90 for ACC/AHA; P = .03). The main areas of consensus were found in heart failure and hypertrophic cardiomyopathy, while the main divergences were in valvular heart disease, arrhythmias, and aortic disease. Conclusion ESC guidelines included more recommendations related to cardiac MRI use, whereas the ACC/AHA recommendations had higher COR and LOE. The number of cardiac MRI recommendations increased significantly over time in both guidelines, indicating the increasing role of cardiac MRI evaluation and management of cardiovascular disease. Keywords: Cardiovascular Magnetic Resonance, Guideline, European Society of Cardiology, ESC, American College of Cardiology/American Heart Association, ACC/AHA Supplemental material is available for this article. © RSNA, 2024.

Chemical resistance testing of plastics: material compatibility of detergent and disinfectant products.

BACKGROUND: Surface cleaning and disinfection is a key part of breaking the chain of transmission and reducing the risk of healthcare associated infections. However, if cleaning and disinfectant formulations are incompatible with surface materials, frequent application can cause premature failure of plastics due to environmental stress cracking (ESC). Material compatibility should be considered when selecting cleaning and disinfecting products. AIM: This study evaluated the tendency of 2-in-1 wet wipes to cause ESC in commonly found healthcare plastics. METHODS: Eight ready-to-use 2-in-1 wet wipes were evaluated for their ability to cause ESC in 13 plastic surfaces in accordance with BS EN ISO-22088-3. Polymers were exposed to fluid extracted from wipes at a fixed strain of 0.5% for seven days and assessed for cracking, crazing, and tensile strength in accordance with ISO 527-2:2012. FINDINGS: All 2-in-1 wet wipes tested contained ESC agents, although the severity of ESC varied. Products with higher pH (>8.0) were responsible for 74% of failures, with 22 of the 39 tested plastics visibly cracking. Although the primary active in all tested wipe formulations were quaternary ammonium compounds, formulations that included small/medium amines or alcohol demonstrated a greater propensity for plastic cracking. CONCLUSION: Each disinfectant formulation exhibits a unique spectrum of microbial efficacy and unique potential to cause surface damage. This may result in device failures and recalls that could compromise patient and staff safety. BS EN ISO-22088-3 can support material compatibility assessments of disinfectant and detergent products before they come to market.

Therapeutic potential of esculetin in various cancer types (Review).

Esculetin (Esc), a coumarin derivative and herbal medicinal compound used in traditional Chinese medicine, is extracted from Fraxinus chinensis. Esc has shown notable potential in the inhibition of proliferation, metastasis and cell cycle arrest in various cancer cell lines. The present review is based on research articles regarding Esc in the field of carcinoma, published between 2009 and 2023. These studies have unanimously demonstrated that Esc can effectively inhibit cancer cell proliferation through diverse mechanisms and modulate multiple signaling pathways, such as Wnt/ß-catenin, PI3K/Akt, MAPK and janus kinase/signal transducer and activator of transcription-3. In addition, the safety profile of Esc has been demonstrated in credible animal experiments, which has indicated Esc as an effective compound. Furthermore, the combination therapy of Esc with commonly used chemotherapeutic drugs holds great promise. The aim of the present review was to encourage further studies and applications of Esc in cancer therapy.

25 years of lipid-lowering therapy: secular trends in therapy of coronary patients.

BACKGROUND AND AIM: Guidelines on dyslipidemia and lipid-lowering therapy (LLT) over the years recommend lower low-density lipoprotein cholesterol (LDL-C) goals by more intense therapy. Nevertheless, LDL­C has increased in the general population. Real-world trends of LLT medication as well as of LDL­C levels in cardiovascular high-risk patients are unclear. METHODS: From 2158 patients who were referred for elective coronary angiography, lipid medication was analyzed at admission in three cardiovascular observational studies (OS) over the last 25 years: OS1: 1999-2000, OS2: 2005-2008 and OS3: 2022-2023. The three studies were performed at the same cardiology unit of a tertiary care hospital in Austria. RESULTS: The proportion of patients without LLT significantly decreased from OS1 through OS2 to OS3 (49.4%, 45.6%, and 18.5%, respectively, ptrend < 0.001). Moreover, the percentage of patients under high-intensity statin treatment significantly increased from 0% to 5.1%, and 56.5% (ptrend < 0.001). Significantly more patients became treated by more than one compound (OS1: 1.8%, OS2: 1.6%, OS3: 31.2%; ptrend < 0.001). In the latest OS3, a trend to fixed-dose combination of statins with ezetimibe was observed. Mean LDL­C levels decreased from 129 mg/dL over 127 mg/dL to 83 mg/dL, respectively (ptrend < 0.001). Of the patients on high-intensity therapy 34% met the recent ESC/EAS goals (LDL-C < 55 mg/dL), but only 3% on non-intense therapy. CONCLUSION: We conclude that during the observational period of a quarter of a century, treatment intensity increased and LDL­C levels improved considerably. Guidelines apparently matter in this high-risk population and are considered by primary care physicians.

Physiological dynamics dominate the relationship between solar-induced chlorophyll fluorescence and gross primary productivity along the nitrogen gradient in cropland.

Solar-induced chlorophyll fluorescence (SIF) has been found to be robustly correlated with gross primary productivity (GPP) based on satellite datasets. However, it is unclear whether nitrogen affects the relationship between SIF and GPP at the canopy scale. Here, seasonal dynamics of SIF, GPP, vegetation physiology and canopy structure were measured synchronously throughout growing season along the nitrogen gradient in a rice paddy of China's subtropical region. Our results found that the slope of SIF against GPP was not constant, showing an increasing trend from low to high nitrogen levels. The sensitivity of SIF to nitrogen was larger than that of GPP. Nitrogen enrichment versus deficiency had asymmetrical effects on the SIF-GPP relationship. The steeper slope of SIF against GPP under high nitrogen level was mainly attributed to the promotion of canopy fluorescence efficiency (ΦF) rather than the variation of canopy fluorescence escape probability (Fesc). These results emphasize the vital role of nitrogen in exploring mechanisms underlying SIF dynamics and decoding GPP from SIF.

Pax6 isoforms shape eye development: Insights from developmental stages and organoid models.

Pax6 is a critical transcription factor involved in the development of the central nervous system. However, in humans, mutations in Pax6 predominantly result in iris deficiency rather than neurological phenotypes. This may be attributed to the distinct functions of Pax6 isoforms, Pax6a and Pax6b. In this study, we investigated the spatial and temporal expression patterns of Pax6 isoforms during different stages of mouse eye development. We observed a strong correlation between Pax6a expression and the neuroretina gene Sox2, while Pax6b showed a high correlation with iris-component genes, including the mesenchymal gene Foxc1. During early patterning from E10.5, Pax6b was expressed in the hinge of the optic cup and neighboring mesenchymal cells, whereas Pax6a was absent in these regions. At E14.5, both Pax6a and Pax6b were expressed in the future iris and ciliary body, coinciding with the integration of mesenchymal cells and Mitf-positive cells in the outer region. From E18.5, Pax6 isoforms exhibited distinct expression patterns as lineage genes became more restricted. To further validate these findings, we utilized ESC-derived eye organoids, which recapitulated the temporal and spatial expression patterns of lineage genes and Pax6 isoforms. Additionally, we found that the spatial expression patterns of Foxc1 and Mitf were impaired in Pax6b-mutant ESC-derived eye organoids. This in vitro eye organoids model suggested the involvement of Pax6b-positive local mesodermal cells in iris development. These results provide valuable insights into the regulatory roles of Pax6 isoforms during iris and neuroretina development and highlight the potential of ESC-derived eye organoids as a tool for studying normal and pathological eye development.

Comparison of IncK-blaCMY-2 Plasmids in Extended-Spectrum Cephalosporin-Resistant Escherichia coli Isolated from Poultry and Humans in Denmark, Finland, and Germany.

Escherichia coli carrying IncK-blaCMY-2 plasmids mediating resistance to extended-spectrum cephalosporins (ESC) has been frequently described in food-producing animals and in humans. This study aimed to characterize IncK-blaCMY-2-positive ESC-resistant E. coli isolates from poultry production systems in Denmark, Finland, and Germany, as well as from Danish human blood infections, and further compare their plasmids. Whole-genome sequencing (Illumina) of all isolates (n = 46) confirmed the presence of the blaCMY-2 gene. Minimum inhibitory concentration (MIC) testing revealed a resistant phenotype to cefotaxime as well as resistance to ≥3 antibiotic classes. Conjugative transfer of the blaCMY-2 gene confirmed the resistance being on mobile plasmids. Pangenome analysis showed only one-third of the genes being in the core with the remainder being in the large accessory gene pool. Single nucleotide polymorphism (SNP) analysis on sequence type (ST) 429 and 1286 isolates showed between 0-60 and 13-90 SNP differences, respectively, indicating vertical transmission of closely related clones in the poultry production, including among Danish, Finnish, and German ST429 isolates. A comparison of 22 ST429 isolates from this study with 80 ST429 isolates in Enterobase revealed the widespread geographical occurrence of related isolates associated with poultry production. Long-read sequencing of a representative subset of isolates (n = 28) allowed further characterization and comparison of the IncK-blaCMY-2 plasmids with publicly available plasmid sequences. This analysis revealed the presence of highly similar plasmids in ESC-resistant E. coli from Denmark, Finland, and Germany pointing to the existence of common sources. Moreover, the analysis presented evidence of global plasmid transmission and evolution. Lastly, our results indicate that IncK-blaCMY-2 plasmids and their carriers had been circulating in the Danish production chain with an associated risk of spreading to humans, as exemplified by the similarity of the clinical ST429 isolate to poultry isolates. Its persistence may be driven by co-selection since most IncK-blaCMY-2 plasmids harbor resistance factors to drugs used in veterinary medicine.

Unlocking trophectoderm mysteries: In vivo and in vitro perspectives on human and mouse trophoblast fate induction.

In recent years, the pursuit of inducing the trophoblast stem cell (TSC) state has gained prominence as a compelling research objective, illuminating the establishment of the trophoblast lineage and unlocking insights into early embryogenesis. In this review, we examine how advancements in diverse technologies, including in vivo time course transcriptomics, cellular reprogramming to TSC state, chemical induction of totipotent stem-cell-like state, and stem-cell-based embryo-like structures, have enriched our insights into the intricate molecular mechanisms and signaling pathways that define the mouse and human trophectoderm/TSC states. We delve into disparities between mouse and human trophectoderm/TSC fate establishment, with a special emphasis on the intriguing role of pluripotency in this context. Additionally, we re-evaluate recent findings concerning the potential of totipotent-stem-like cells and embryo-like structures to fully manifest the trophectoderm/trophoblast lineage's capabilities. Lastly, we briefly discuss the potential applications of induced TSCs in pregnancy-related disease modeling.

Timing of coronary angiography and use of antiplatelet pretreatment in patients with NSTEACS in Spain.

INTRODUCTION AND OBJECTIVES: The optimal timing of coronary angiography in patients admitted with non-ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. METHODS: This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. RESULTS: Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67±12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score>140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). CONCLUSIONS: In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low.

Mitochondria-targeted esculetin and metformin delay endothelial senescence by promoting fatty acid ß-oxidation: Relevance in age-associated atherosclerosis.

Impaired mitochondrial fatty acid ß-oxidation (FAO) plays a role in the onset of several age-associated diseases, including atherosclerosis. In the current work, we investigated the efficacies of mitochondria-targeted esculetin (Mito-Esc) and metformin in enhancing FAO in human aortic endothelial cells (HAECs), and its relevance in the delay of cellular senescence and age-associated atherosclerotic plaque formation in Apoe-/- mice. Chronic culturing of HAECs with either Mito-Esc or metformin increased oxygen consumption rates (OCR), and caused delay in senescence features. Conversely, etomoxir (CPT1 inhibitor) reversed Mito-Esc- and metformin-induced OCR, and caused premature endothelial senescence. Interestingly, Mito-Esc, unlike metformin, in the presence of etomoxir failed to preserve OCR. Thereby, underscoring Mito-Esc's exclusive reliance on FAO as an energy source. Mechanistically, chronic culturing of HAECs with either Mito-Esc or metformin led to AMPK activation, increased CPT1 activity, and acetyl-CoA levels along with a concomitant reduction in malonyl-CoA levels, and lipid accumulation. Similar results were observed in Apoe-/- mice aorta and liver tissue with a parallel reduction in age-associated atherosclerotic plaque formation and degeneration of liver with either Mito-Esc or metformin administration. Together, Mito-Esc and metformin by potentiating FAO, may have a role in the delay of cellular senescence by modulating mitochondrial function.

Tiempos de cateterismo y uso de pretratamiento antiagregante plaquetario en pacientes con SCASEST en España / Timing of coronary angiography and use of antiplatelet pretreatment in patients with NSTEACS in Spain

Introducción y objetivos El momento óptimo para un cateterismo en el síndrome coronario agudo sin elevación del segmento ST (SCASEST) y la necesidad de pretratamiento son motivo de controversia. El objetivo principal del registro IMPACT-TIMING-GO es conocer el porcentaje de pacientes examinados con una coronariografía precoz (0-24 h) y que no recibieron doble antiagregación plaquetaria antes del cateterismo (estrategia sin pretratamiento) en España. Métodos Estudio observacional, prospectivo y multicéntrico, que incluyó a pacientes consecutivos con diagnóstico de SCASEST sometidos a cateterismo en los que se evidenció enfermedad coronaria ateroesclerótica causal. Resultados Entre abril y mayo de 2022 se incluyó a 1.021 pacientes (media de edad, 67±12 años; el 23,6% mujeres). El 86,8% de los pacientes cumplían criterios de alto riesgo (elevación de troponina, cambios electrocardiográficos o puntuación GRACE>140); sin embargo, únicamente el 37,8% se sometió a una estrategia invasiva precoz, y el 30,3% no recibió pretratamiento. Globalmente, solo el 13,6% de los pacientes se sometieron a una estrategia invasiva precoz sin un segundo antiagregante plaquetario, y la estrategia diferida con pretratamiento fue la más utilizada (46%). Durante el ingreso, 9 pacientes (0,9%) fallecieron y 34 (3,3%) presentaron una hemorragia grave. Conclusiones En España, solo el 13,6% de los pacientes con SCASEST sometidos a cateterismo reciben una estrategia invasiva precoz sin pretratamiento. La incidencia de eventos cardiovasculares y hemorragias graves en el ingreso es baja. (AU)

Introduction and objectives The optimal timing of coronary angiography in patients admitted with non–ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. Methods This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. Results Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67±12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score>140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). Conclusions In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low. (AU)

The effects of Electronic Stability Control (ESC) on fatal crash rates in the United States.

PROBLEM: Electronic Stability Control (ESC) is believed to be among the most efficient vehicle safety interventions with reported effects around 50% for fatal single and rollover crashes. However, such estimates have used sample data, which have not controlled for the possibilities of self-selection, behavioral adaptation, increased access to the technology by less safe drivers, and the calculation of effects on very specific categories of crashes. Effects of ESC in the population can therefore be expected to be smaller than is currently believed. METHOD: National U.S. data for fatal crashes, driving exposure and other control factors, and market penetration of ESC over 1991-2021 were used to calculate whether the trends in fatalities over time in crash rates for singles, rollovers, and fatal crashes in general matched projections from estimates of effectiveness. RESULTS: It was found that downward trends in the relevant crash types were generally present before ESC was introduced, and that the trends thereafter were weaker. Although some trends were consistent with effects of ESC, they were markedly smaller than the projected ones, and could be explained by other factors such as the number of vehicles per capita. At best, the effect for rollovers could be up to two-thirds of previous estimates, no effect was detected for singles, while for all fatal crashes results depended upon the type of analysis performed. These results conflict with conclusions in all published ESC crash sample studies, which have compared vehicles with and without ESC. This discrepancy can be explained by methodological errors in the previous studies using induced exposure methods and self-selected samples. PRACTICAL APPLICATIONS: Traffic safety may not be as much improved by technological interventions as believed. Alternative approaches to traffic safety are needed, which do not rely on technology that interferes with driver behavior.