The alternative coproporphyrinogen III oxidase (CgoN) catalyzes the oxygen-independent conversion of coproporphyrinogen III into coproporphyrin III.

Nature utilizes three distinct pathways to synthesize the essential enzyme cofactor heme. The coproporphyrin III-dependent pathway, predominantly present in Bacillaceae, employs an oxygen-dependent coproporphyrinogen III oxidase (CgoX) that converts coproporphyrinogen III into coproporphyrin III. In this study, we report the bioinformatic-based identification of a gene called ytpQ, encoding a putative oxygen-independent counterpart, which we propose to term CgoN, from Priestia (Bacillus) megaterium. The recombinantly produced, purified, and monomeric YtpQ (CgoN) protein is shown to catalyze the oxygen-independent conversion of coproporphyrinogen III into coproporphyrin III. Minimal non-enzymatic conversion of coproporphyrinogen III was observed under the anaerobic test conditions employed in this study. FAD was identified as a cofactor, and menadione served as an artificial acceptor for the six abstracted electrons, with a KM value of 3.95 µmol/L and a kcat of 0.63 per min for the substrate. The resulting coproporphyrin III, in turn, acts as an effective substrate for the subsequent enzyme of the pathway, the coproporphyrin III ferrochelatase (CpfC). Under aerobic conditions, oxygen directly serves as an electron acceptor, but is replaced by the more efficient action of menadione. An AlphaFold2 model of the enzyme suggests that YtpQ adopts a compact triangular shape consisting of three domains. The N-terminal domain appears to be flexible with respect to the rest of the structure, potentially creating a ligand binding site that opens and closes during the catalytic cycle. A catalytic mechanism similar to the oxygen-independent protoporphyrinogen IX oxidase PgoH1 (HemG), based on the flavin-dependent abstraction of six electrons from coproporphyrinogen III and their potential quinone-dependent transfer to a membrane-localized electron transport chain, is proposed.

Prognostic Utility of Society for Cardiovascular Angiography and Interventions Shock Stage Approach for Classifying Cardiogenic Shock Severity in Takotsubo Syndrome.

BACKGROUND: Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. METHODS AND RESULTS: From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all-cause in-hospital mortality; secondary end points were TTS-related in-hospital complications and 1-year all-cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in-hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in-hospital mortality (adjusted odds ratio: 1.77-29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1-year mortality. CONCLUSIONS: In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in-hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS-related CS.

Isolation, Quantification, and Visualization of Extracellular Membrane Vesicles in Rhizobia Under Free-Living Conditions.

Rhizobia are a group of soil proteobacteria that are able to establish a symbiotic interaction with legumes. These bacteria are capable to fix atmospheric nitrogen into ammonia within specific plant root organs called nodules. The rhizobia-legume interaction is established by a complex molecular dialogue that starts with flavonoids exudated by the plant roots. In response, signaling molecules known as Nod factors (NFs) are secreted by the bacteria. These factors are sensed by specific plant receptors that trigger a downstream signaling cascade leading to rhizobium-specific intracellular colonization of the root hair via the formation of infection threads and the eventual development of nodules on roots. In these organs, rhizobia can fix nitrogen from the atmosphere for the plant in exchange for photosynthates and the appropriate environment for nitrogen fixation. Recently, it has been demonstrated that extracellular membrane vesicles (EMVs) produced by some rhizobia carry NFs. EMVs are proteolipidic structures that are secreted to the milieu from the bacterial membranes and are involved in several important biological processes, including intercellular communication. Thus far, little is known about rhizobia vesicles, and further studies are needed to understand their functions, including their role as transporting vessels of signaling molecules during the process of symbiosis. Here, we present a detailed protocol to isolate high-purity EMVs from free-living cultured rhizobia, test their integrity, and quantify their abundance.

Isolation of Rhizobial Extracellular Membrane Vesicles from Bacteroids.

Extracellular-membrane vesicles (EMVs) are spherical buds of the extracellular membrane, commonly produced by Gram-negative bacteria, known to mediate intricate inter-kingdom communication. In this context, comprehensive research dissecting the role of EMVs in one of the most complex nature-occurring molecular dialogues, rhizobium-legume symbiosis, has been so far neglected. During the different stages of the symbiotic process, rhizobia and their host plants establish a very specific and controlled intercellular trafficking of signal molecules. Thus, as conveyors of a broad range of molecules into the target cell, EMVs are gaining weight in the field. Here, we describe a detailed protocol to isolate EMVs from bacteroids of legume nodules, opening a new door for discovering new authors of the symbiotic process.

Spatial and seasonal variability of picoplankton abundance and growth rates in the southern Bay of Biscay.

Autotrophic and heterotrophic picoplankton play fundamental roles in marine food webs and biogeochemical cycles. However, their growth responses have seldom been jointly assessed, including many temperate regions such as the Bay of Biscay. There, previous studies have shown their relevance in carbon fluxes. We describe here the spatio-temporal variability of the abundances and growth rates of the picoplanktonic groups routinely distinguished by flow cytometry (Synechococcus and Prochlorococcus cyanobacteria, two groups of differently sized picoeukaryotes and two groups of heterotrophic bacteria distinguished by their relative nucleic acid content) in the central Cantabrian Sea (S Bay of Biscay). To that end, from February to December 2021 we collected surface water on 5 occasions from 6 stations distributed along the S Bay of Biscay (6-3°W) and incubated it after removing protistan grazers in order to determine their dynamics along the seasonal cycle as well as the inshore-offshore and the west-east gradients. Seasonal variations in initial and maximum abundances generally matched previous knowledge of the region but growth rates were more variable, with Prochlorococcus and high nucleic acid (HNA) bacteria showing the maximum values (up to 2 d-1) while negative growth was observed in one third of Synechococcus incubations. Temporal differences generally overrode differences along the inshore-offshore gradient in trophic status while in situ and maximum abundances of most of the groups generally decreased towards the east following the increase in stratification and lower nutrient availability. Responses to stratification suggest Prochlorococcus and low nucleic acid (LNA) cells may prevail among autotrophic and heterotrophic bacteria, respectively, in a warmer ocean.

Rashba Spin Splitting Limiting the Application of 2D Halide Perovskites for UV-Emitting Devices.

Layered lead halide perovskites have attracted much attention as promising materials for a new generation of optoelectronic devices. To make progress in applications, a full understanding of the basic properties is essential. Here, we study 2D-layered (BA)2PbX4 by using different halide anions (X = I, Br, and Cl) along with quantum confinement. The obtained cell parameter evolution, supported by experimental measurements and theoretical calculations, indicates strong lattice distortions of the metal halide octahedra, breaking the local inversion symmetry in (BA)2PbCl4, which strongly correlates with a pronounced Rashba spin-splitting effect. Optical measurements reveal strong photoluminescence quenching and a drastic reduction in the PL quantum yield in this larger band gap compound. We suggest that these optical results are closely related to the appearance of the Rashba effect due to the existence of a local electric dipole. The results obtained in ab initio calculations showed that the (BA)2PbCl4 possesses electrical polarization of 0.13 µC/cm2 and spin-splitting energy of about 40 meV. Our work establishes that local octahedra distortions induce Rashba spin splitting, which explains why obtaining UV-emitting materials with high PLQY is a big challenge.

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures.

Bacterial membrane vesicles (BMVs) are produced by most bacteria and participate in various cellular processes, such as intercellular communication, nutrient exchange, and pathogenesis. Notably, these vesicles can contain virulence factors, including toxic proteins, DNA, and RNA. Such factors can contribute to the harmful effects of bacterial pathogens on host cells and tissues. Although the general effects of BMVs on host cellular physiology are well known, the underlying molecular mechanisms are less understood. In this study, we introduce a vesicle quantification method, leveraging the membrane dye FM4-64. We utilize a linear regression model to analyze the fluorescence emitted by stained vesicle membranes to ensure consistent and reproducible vesicle-host interaction studies using cultured cells. This method is particularly valuable for identifying host cellular processes impacted by vesicles and their specific cargo. Moreover, it outcompetes unreliable protein concentration-based methods. We (1) show a linear correlation between the number of vesicles and the fluorescence signal emitted from the FM4-64 dye; (2) introduce the "vesicle load" as a new semi-quantitative unit, facilitating more reproducible vesicle-cell culture interaction experiments; (3) show that a stable vesicle load yields consistent host responses when studying vesicles from Pseudomonas aeruginosa mutants; (4) demonstrate that typical vesicle isolation contaminants, such as flagella, do not significantly skew the metabolic response of lung epithelial cells to P. aeruginosa vesicles; and (5) identify inositol monophosphatase 1 (SuhB) as a pivotal regulator in the vesicle-mediated pathogenesis of P. aeruginosa.

Datasets describing optimization of the cutting regime in the turning of AISI 316L steel for biomedical purposes based on the NSGA-II and NSGA-III multi-criteria algorithms.

There are several methods of analysis used in the metalworking industry for dry machining processes and with Minimum Quantity Lubrication (MQL). Evolutionary methods [1] have been used in the decision-making process in the machining process to select the optimal data and to analyze the behavior of variables such as cutting speed (V), feed rate (f) and cutting depth (ap). This work addresses the use of evolutionary algorithms of low dominance class II and III (NSGA-II and NSGA-III) to analyze from the multicriteria approach the initial wear of the cutting tool (VB), the energy consumption (E) and the machining time (t) in the turning process of the AISI 316L steel workpiece for biomedical purposes. As input variables to the algorithm with 54 records, there are: cutting speed (V: 200, 300, 400 m/min) and feed rate (f: 0.1, 0.15, 0.2 mm/rev). The experiment was developed for a dry (1) turning operation and with the use of MQL (-1). For the MQL lubrication regime, a TRI-COOL MD-1 lubricant was employed, a vegetable type used in ferrous and non-ferrous metal cutting operations. A BIDEMICS JX1 ceramic cutting tool was used.

Systematic influenza screening in cardiac intensive care units during the influenza season: A prospective study in Spain.

BACKGROUND: Little is known about the incidence of influenza among admissions to the cardiac intensive care unit (C-ICU), accuracy of clinical suspicion, and influenza vaccination uptake. We evaluated the incidence of influenza at C-ICU admission during the influenza season, potential underdiagnosis, and vaccination uptake. METHODS: Prospective study at five C-ICUs during the 2017-2020 influenza seasons. A nasopharyngeal swab was collected at admission from patients who consented (n = 788). Testing was with Xpert®XpressFlu/RSV. RESULTS: Influenza was detected in 43 patients (5.5%) (40 FluA; 3 FluB) and clinically suspected in 27 (62.8%). Compared to patients without influenza, patients with influenza more frequently had heart failure (37.2% vs 22.8%, P = 0.031), previous contact with relatives with influenza-like illnesses (23.3% vs 12.5%, P = 0.042), antimicrobial use (67.4% vs 23.2%, P <0.01), and need for mechanical ventilation (25.6% vs 14.5%, P = 0.048). Patients received oseltamivir promptly. We found no differences in mortality (11.6% vs 5.2%, P = 0.076). Patients with influenza more frequently had myocarditis (9.3% vs 0.9%, P <0.01) and pericarditis (7.0% vs 0.8%, P = 0.01). Overall, 43.0% of patients (339/788) were vaccinated (51.9% of those with a clear indication [303/584]). CONCLUSION: Influenza seems to be a frequently underdiagnosed underlying condition in admissions to the C-ICU. Influenza should be screened for at C-ICU admission during influenza epidemics.

Membrane vesicle engineering with "à la carte" bacterial-immunogenic molecules for organism-free plant vaccination.

The United Nations heralds a world population exponential increase exceeding 9.7 billion by 2050. This poses the challenge of covering the nutritional needs of an overpopulated world by the hand of preserving the environment. Extensive agriculture practices harnessed the employment of fertilizers and pesticides to boost crop productivity and prevent economic and harvest yield losses attributed to plagues and diseases. Unfortunately, the concomitant hazardous effects stemmed from such agriculture techniques are cumbersome, that is, biodiversity loss, soils and waters contaminations, and human and animal poisoning. Hence, the so-called 'green agriculture' research revolves around designing novel biopesticides and plant growth-promoting bio-agents to the end of curbing the detrimental effects. In this field, microbe-plant interactions studies offer multiple possibilities for reshaping the plant holobiont physiology to its benefit. Along these lines, bacterial extracellular membrane vesicles emerge as an appealing molecular tool to capitalize on. These nanoparticles convey a manifold of molecules that mediate intricate bacteria-plant interactions including plant immunomodulation. Herein, we bring into the spotlight bacterial extracellular membrane vesicle engineering to encase immunomodulatory effectors into their cargo for their application as biocontrol agents. The overarching goal is achieving plant priming by deploying its innate immune responses thereby preventing upcoming infections.

Calibration and Uncertainty Quantification for Single-Ended Raman-Based Distributed Temperature Sensing: Case Study in a 800 m Deep Coaxial Borehole Heat Exchanger.

Raman-based distributed temperature sensing (DTS) is a valuable tool for field testing and validating heat transfer models in borehole heat exchanger (BHE) and ground source heat pump (GSHP) applications. However, temperature uncertainty is rarely reported in the literature. In this paper, a new calibration method was proposed for single-ended DTS configurations, along with a method to remove fictitious temperature drifts due to ambient air variations. The methods were implemented for a distributed thermal response test (DTRT) case study in an 800 m deep coaxial BHE. The results show that the calibration method and temperature drift correction are robust and give adequate results, with a temperature uncertainty increasing non-linearly from about 0.4 K near the surface to about 1.7 K at 800 m. The temperature uncertainty is dominated by the uncertainty in the calibrated parameters for depths larger than 200 m. The paper also offers insights into thermal features observed during the DTRT, including a heat flux inversion along the borehole depth and the slow temperature homogenization under circulation.

Identifying sustainability priorities among value chain actors in artisanal common octopus fisheries.

The United Nations (UN) Decade of Ocean Science highlights a need to improve the way in which scientific results effectively inform action and policies regarding the ocean. Our research contributes to achieving this goal by identifying practical actions, barriers, stakeholder contributions and resources required to increase the sustainability of activities carried out in the context of artisanal fisheries to meet UN Sustainable Development Goals (SDG) and International Year of Artisanal Fisheries and Aquaculture (IYAFA) Global Action Plan (GAP) Pillar targets. We conducted a novel 'social value chain analysis' via a participatory workshop to elicit perspectives of value chain actors and fisheries stakeholders associated with two Spanish artisanal common octopus (Octopus vulgaris) fisheries (western Asturias-Marine Stewardship Council [MSC] certified, and Galicia-non-MSC certified) about their priorities regarding sustainable octopus production and commercialization. Our adapted Rapfish sustainability framework emphasised the importance of economic, environmental, ethical, institutional, social, and technological indicators to different actors across the value chain. We mapped participants' shared sustainability priorities (e.g. integrated fisheries management, knowledge-based management, product traceability) to six Rapfish indicators, seven IYAFA Pillars and twelve SDGs to reveal how our results can inform ocean policy and actions. This identified how certification incentives and other cooperative approaches can facilitate environmental, economic and social sustainability (e.g. value-added products, price premiums for producers, gender inclusive organisations); support IYAFA priority outcomes (raised awareness, strengthened science-policy interface, empowered stakeholders, partnerships); and help to achieve UN SDG targets (e.g. SDG 14.b, SDG 17.17). The results can inform actors, stakeholders and policymakers about how different actors contribute to efforts to achieve the SDGs and how to manage priorities for sustainable actions within artisanal fisheries and their value chains. We recommend inclusive and equitable participatory knowledge transfer and governance platforms as part of the UN Decade of Ocean Science and beyond where participants can create theories of change towards sustainability involving the development of multi-sectoral ocean policies framed at the level of the value chain and supported by appropriate governance structures. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-023-09768-5.

Differential prognosis of patients that are candidates for standard, short or prolonged dual antiplatelet treatment discharged after an acute coronary syndrome.

BACKGROUND: Current evidence supports the efficacy of prolonged dual antiplatelet treatment (DAPT) for patients at high-ischemic risk and low bleeding risk as well as the efficacy and safety of short DAPT in high-bleeding risk (HBR) patients. METHODS: We evaluated patterns of DAPT candidates in all patients discharged in 2 hospitals after an acute coronary syndrome (ACS). Patients categorized in 3 groups: 1) short-DAPT candidates if they met 1 major o 2 minor criteria for HBR, by the 2019 ARC-HBR criteria; 2) prolonged-DAPT candidates if were not HBR and had recurrent ACS, complex percutaneous coronary interventions or diabetes; 3) standard 12 months DAPT if were not include in the previous 2 groups. Major bleeding (MB) was registered according to 3 or 5 of the BARC consortium definitions. RESULTS: We included 8252 patients and 3215 (39 %) were candidates for abbreviated DAPT, 3119 (37.8 %) for prolonged DAPT, and 1918 (23.2 %) for 12 m DAPT. Relevant differences were observed between the 3 categories beyond the bleeding risk. Median follow-up was 57 months. Multivariate analysis identified higher risk of all-cause mortality (HR: 1.96 95 % CI 1.45-2.67; p < 0.001), cardiovascular mortality (HR: 2.10 95 % CI 1.39-3.19; p < 0.011), MACE (HR: 1.69 95 % 1.50-2.02; p < 0.001) and MB (sHR: 3.41 95 % CI 1.45-8.02; p = 0.005) in candidates to short DAPT. Candidates to prolonged DAPT had higher risk of MACE (HR: 1.17 95 % CI 1.02-1.35; p = 0.027). CONCLUSIONS: Almost two thirds of patients discharged after an ACS would be candidates for short or prolonged DAPT and these patients are at higher risk of MACE and mortality.

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle.

Pseudomonas aeruginosa (PA) is an opportunistic human pathogen, which is involved in a wide range of dangerous infections. It develops alarming resistances toward antibiotic treatment. Therefore, alternative strategies, which suppress pathogenicity or synergize with antibiotic treatments are in great need to combat these infections more effectively. One promising approach is to disarm the bacteria by interfering with their quorum sensing (QS) system, which regulates the release of various virulence factors as well as biofilm formation. Herein, this work reports the rational design, optimization, and in-depth profiling of a new class of Pseudomonas quinolone signaling receptor (PqsR) inverse agonists. The resulting frontrunner compound features a pyrimidine-based scaffold, high in vitro and in vivo efficacy, favorable pharmacokinetics as well as clean safety pharmacology characteristics, which provide the basis for potential pulmonary as well as systemic routes of administration. An X-ray crystal structure in complex with PqsR facilitated further structure-guided lead optimization. The compound demonstrates potent pyocyanin suppression, synergizes with aminoglycoside antibiotic tobramycin against PA biofilms, and is active against a panel of clinical isolates from bronchiectasis patients. Importantly, this in vitro effect translated into in vivo efficacy in a neutropenic thigh infection model in mice providing a proof-of-principle for adjunctive treatment scenarios.

Remnant cholesterol in patients admitted for acute coronary syndromes.

BACKGROUND: Remnant cholesterol has been identified as one of leading lipid values associated with the incidence of coronary heart disease. There is scarce evidence on its distribution and prognostic value in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We included all consecutive patients admitted for ACS in two different centres. Remnant cholesterol was calculated by the equation: total cholesterol minus LDL cholesterol minus HDL cholesterol, and values ≥30 were considered high. Among the 7479 patients, median remnant cholesterol level was 28 mg/dL (21-39), and 3429 (45.85%) patients had levels ≥30 mg/dL. Age (r: -0.29) and body mass index (r: 0.44) were the variables more strongly correlated. At any given age, patients with overweigh or obesity had higher levels. In-hospital mortality was 3.75% (280 patients). Remnant cholesterol was not associated to higher in-hospital mortality risk (odds ratio: 0.89; P = 0.21). After discharge (median follow-up of 57 months), an independent and linear risk of all-cause mortality and heart failure (HF) associated to cholesterol remnant levels was observed. Remnant cholesterol levels >60 mg/dL were associated to higher risk of mortality [hazard ratio (HR): 1.49 95% CI 1.08-2.06; P = 0.016], cardiovascular mortality (HR: 1.49 95% CI 1.08-2.06; P = 0.016), and HF re-admission (sub-HR: 1.55 95% CI 1.14-2.11; P = 0.005). CONCLUSIONS: Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is inversely correlated with age and positively with body mass index. Remnant cholesterol levels were not associated to higher in-hospital mortality risk, but they were associated with higher long-term risk of mortality and HF.

Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is related to body mass index and negatively with age. Remnant cholesterol it is not associated to higher in-hospital mortality risk, but it confers higher long-term risk of mortality and heart failure.

Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial.

INTRODUCTION AND OBJECTIVES: The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. METHODS: In this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. RESULTS: A total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). CONCLUSIONS: In this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG. CLINICALTRIALS: gov Identifier: NCT02641626.

Rational engineering of natural polyhydroxyalkanoates producing microorganisms for improved synthesis and recovery.

Microbial production of biopolymers derived from renewable substrates and waste streams reduces our heavy reliance on petrochemical plastics. One of the most important biodegradable polymers is the family of polyhydroxyalkanoates (PHAs), naturally occurring intracellular polyoxoesters produced for decades by bacterial fermentation of sugars and fatty acids at the industrial scale. Despite the advances, PHA production still suffers from heavy costs associated with carbon substrates and downstream processing to recover the intracellular product, thus restricting market positioning. In recent years, model-aided metabolic engineering and novel synthetic biology approaches have spurred our understanding of carbon flux partitioning through competing pathways and cellular resource allocation during PHA synthesis, enabling the rational design of superior biopolymer producers and programmable cellular lytic systems. This review describes these attempts to rationally engineering the cellular operation of several microbes to elevate PHA production on specific substrates and waste products. We also delve into genome reduction, morphology, and redox cofactor engineering to boost PHA biosynthesis. Besides, we critically evaluate engineered bacterial strains in various fermentation modes in terms of PHA productivity and the period required for product recovery.

Applicability of the Zwolle score for selection of very high-risk ST-elevation myocardial infarction patients treated with primary angioplasty.

The Zwolle risk score was designed to stratify in-hospital mortality risk of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI) and for decision-making in the unit where patients are admitted. We assessed the accuracy of Zwolle risk score for in-hospital mortality estimation compared with the GRACE score in all patients (n = 4446) admitted for STEMI in 3 university hospitals. Only one fourth of the patients were classified as high-risk by the Zwolle risk score vs 60% by the GRACE score. In-hospital mortality was 10.6%. A statistically significant increase in in-hospital mortality, adjusted by age, gender, and revascularization, was observed with both scores. The assessment of the optimal cut-off points verified the accuracy of Zwolle score ≥4 as optimal threshold for high-risk categorization. In contrast, GRACE score ≥140 had very low specificity as well as percentage of patients correctly classified; GRACE score ≥175 was fairly better. The reclassification index of the Zwolle score after applying the GRACE score was 35.5%. Selection of high-risk STEMI patients treated with pPCI based on the Zwolle risk score has higher specificity than the GRACE score and might be useful in clinical practice.

Predictive Model and Risk Score for In-Hospital Mortality in Patients with All-Cause Cardiogenic Shock.

Cardiogenic shock (CS) is a condition associated with high morbidity and mortality. Our study aimed to perform a risk score for in-hospital mortality that allows for stratifying the risk of death in patients with CS.This is a retrospective analysis, which included 135 patients from a Spanish university hospital between 2011 and 2020. The Santiago Shock Score (S3) was created using clinical, analytical, and echocardiographic variables obtained at the time of admission.The in-hospital mortality rate was 41.5%, and acute coronary syndrome (ACS) was the responsible cause of shock in 60.7% of patients. Mitral regurgitation grade III-IV, age, ACS etiology, NT-proBNP, blood hemoglobin, and lactate at admission were included in the score. The S3 had good accuracy for predicting in-hospital mortality area under the receiver operating characteristic curve (AUC) 0.85 (95% confidence interval (CI) 0.78-0.90), higher than the AUC of the CardShock score, which was 0.74 (95% CI 0.66-0.83). Predictive power in a cohort of 131 patients with profound CS was similar to that of CardShock with an AUC of 0.601 (95% CI 0.496-0.706) versus an AUC of 0.558 (95% CI 0.453-0.664). Three risk categories were created according to the S3: low (scores 0-6), intermediate (scores 7-10), and high (scores 11-16) risks, with an observed mortality of 12.9%, 49.1%, and 87.5% respectively (P < 0.001).The S3 score had excellent predictive power for in-hospital mortality in patients with nonprofound CS. It could aid the initial risk stratification of patients and thus, guide treatment and clinical decision making in patients with CS.